FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Sher, L
Holmes, K
Flory, JD
Bierer, LM
Yehuda, R
AF Sher, Leo
Holmes, Kristin
Flory, Janine D.
Bierer, Linda M.
Yehuda, Rachel
TI Clinical features of military veterans with or without a history of
suicide attempt
SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY
LA English
DT Meeting Abstract
DE suicide; veterans; substance dependence; psychosis; bipolar disorder
C1 James J Peters Vet Adm Med Ctr, New York, NY USA.
Mt Sinai Sch Med, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CO-ACTION PUBLISHING
PI JARFALLA
PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN
SN 2000-8066
J9 EUR J PSYCHOTRAUMATO
JI Eur. J. Psychotraumatol.
PY 2012
VL 3
SU 1
DI 10.3402/ejpt.v3i0.19476
PG 1
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA V31FC
UT WOS:000208868500188
ER
PT J
AU Talbot, L
Richards, A
Inslicht, SS
O'Donovan, A
Neylan, TC
AF Talbot, Lisa
Richards, Anne
Inslicht, Sabra S.
O'Donovan, Aoife
Neylan, Thomas C.
TI Sleep and lipids in posttraumatic stress disorder
SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY
LA English
DT Meeting Abstract
DE sleep; PTSD; lipids; cardiovascular risk; metabolism
C1 [Talbot, Lisa; Richards, Anne; Inslicht, Sabra S.; O'Donovan, Aoife; Neylan, Thomas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Talbot, Lisa; Richards, Anne; Inslicht, Sabra S.; O'Donovan, Aoife; Neylan, Thomas C.] San Francisco VA Med Ctr, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CO-ACTION PUBLISHING
PI JARFALLA
PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN
SN 2000-8066
J9 EUR J PSYCHOTRAUMATO
JI Eur. J. Psychotraumatol.
PY 2012
VL 3
SU 1
DI 10.3402/ejpt.v3i0.19496
PG 2
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA V31FC
UT WOS:000208868500012
ER
PT B
AU Hussain, F
Sprague, S
Rubash, HE
AF Hussain, Farrah
Sprague, Sheila
Rubash, Harry E.
BE Bhandari, M
TI Critical Appraisal Tools for Surgeons
SO EVIDENCE-BASED ORTHOPEDICS
SE Evidence-Based Medicnie
LA English
DT Article; Book Chapter
C1 [Hussain, Farrah; Sprague, Sheila] McMaster Univ, Hamilton, ON, Canada.
[Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
RP Hussain, F (reprint author), McMaster Univ, Hamilton, ON, Canada.
NR 18
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND
BN 978-1-4443-4507-0; 978-1-4051-8476-2
J9 EVIDENCE-BASED MED
PY 2012
BP 12
EP 16
PG 5
WC Orthopedics
SC Orthopedics
GA BA9IT
UT WOS:000339448600005
ER
PT B
AU Doornberg, JN
Ring, D
AF Doornberg, Job N.
Ring, David
BE Bhandari, M
TI Proximal Humerus Fractures
SO EVIDENCE-BASED ORTHOPEDICS
SE Evidence-Based Medicnie
LA English
DT Article; Book Chapter
ID RANDOMIZED CONTROLLED-TRIAL; DISPLACED FRACTURES; COMPUTED-TOMOGRAPHY;
4-PART FRACTURES; 2-PART FRACTURES; ELDERLY-PATIENTS; CLINICAL-TRIAL;
REHABILITATION; NECK; IMMOBILIZATION
C1 [Doornberg, Job N.] Acad Med Ctr Amsterdam, Orthotrauma Res Ctr Amsterdam, Amsterdam, Netherlands.
[Doornberg, Job N.] St Lucas Andreas Hosp, Acad Med Ctr, Amsterdam, Netherlands.
[Ring, David] Harvard Univ, Sch Med, Boston, MA USA.
[Ring, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Doornberg, JN (reprint author), Acad Med Ctr Amsterdam, Orthotrauma Res Ctr Amsterdam, Amsterdam, Netherlands.
NR 28
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND
BN 978-1-4443-4507-0; 978-1-4051-8476-2
J9 EVIDENCE-BASED MED
PY 2012
BP 360
EP 365
PG 6
WC Orthopedics
SC Orthopedics
GA BA9IT
UT WOS:000339448600043
ER
PT B
AU Bauer, AS
Ring, D
AF Bauer, Andrea S.
Ring, David
BE Bhandari, M
TI Radial Head Fractures
SO EVIDENCE-BASED ORTHOPEDICS
SE Evidence-Based Medicnie
LA English
DT Article; Book Chapter
ID MASON TYPE-III; INTERNAL-FIXATION; FOLLOW-UP; OPEN REDUCTION;
ASPIRATION; ELBOW; RESECTION; ADULTS; NECK
C1 [Bauer, Andrea S.; Ring, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Bauer, AS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 21
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND
BN 978-1-4443-4507-0; 978-1-4051-8476-2
J9 EVIDENCE-BASED MED
PY 2012
BP 397
EP 402
PG 6
WC Orthopedics
SC Orthopedics
GA BA9IT
UT WOS:000339448600047
ER
PT B
AU Gillespie, BT
Jupiter, JB
AF Gillespie, Bryce T.
Jupiter, Jesse B.
BE Bhandari, M
TI Monteggia Fracture-Dislocations
SO EVIDENCE-BASED ORTHOPEDICS
SE Evidence-Based Medicnie
LA English
DT Article; Book Chapter
ID PROXIMAL ULNA; ADULTS; LESION
C1 [Gillespie, Bryce T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jupiter, Jesse B.] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA.
RP Gillespie, BT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 21
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND
BN 978-1-4443-4507-0; 978-1-4051-8476-2
J9 EVIDENCE-BASED MED
PY 2012
BP 403
EP 408
PG 6
WC Orthopedics
SC Orthopedics
GA BA9IT
UT WOS:000339448600048
ER
PT B
AU Gillespie, BT
Jupiter, JB
AF Gillespie, Bryce T.
Jupiter, Jesse B.
BE Bhandari, M
TI Olecranon Fractures
SO EVIDENCE-BASED ORTHOPEDICS
SE Evidence-Based Medicnie
LA English
DT Article; Book Chapter
ID 3-DIMENSIONAL COMPUTED-TOMOGRAPHY; DISPLACED FRACTURES; PLATE FIXATION;
SURGICAL-TREATMENT; TENSION; ELBOW; COMPLICATIONS; RELIABILITY;
MANAGEMENT
C1 [Gillespie, Bryce T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jupiter, Jesse B.] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA.
RP Gillespie, BT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 32
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND
BN 978-1-4443-4507-0; 978-1-4051-8476-2
J9 EVIDENCE-BASED MED
PY 2012
BP 409
EP 415
PG 7
WC Orthopedics
SC Orthopedics
GA BA9IT
UT WOS:000339448600049
ER
PT B
AU ten Berg, PWL
Oh, LS
Ring, D
AF ten Berg, Paul W. L.
Oh, Luke S.
Ring, David
BE Bhandari, M
TI Pathology of the Long Head of the Biceps
SO EVIDENCE-BASED ORTHOPEDICS
SE Evidence-Based Medicnie
LA English
DT Article; Book Chapter
ID ROTATOR CUFF TEARS; INDIRECT MR ARTHROGRAPHY; IMPINGEMENT SYNDROME;
INTERFERENCE SCREW; TENDON PATHOLOGY; CLINICAL-TEST; SHOULDER;
TENODESIS; TENOTOMY; RUPTURE
C1 [ten Berg, Paul W. L.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
[Oh, Luke S.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Ring, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP ten Berg, PWL (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
NR 51
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND
BN 978-1-4443-4507-0; 978-1-4051-8476-2
J9 EVIDENCE-BASED MED
PY 2012
BP 772
EP 780
PG 9
WC Orthopedics
SC Orthopedics
GA BA9IT
UT WOS:000339448600092
ER
PT B
AU Monica, JT
Ring, D
AF Monica, James T.
Ring, David
BE Bhandari, M
TI Reconstruction of Malunited Distal Radius Fracture
SO EVIDENCE-BASED ORTHOPEDICS
SE Evidence-Based Medicnie
LA English
DT Article; Book Chapter
ID CLOSING WEDGE OSTEOTOMY; CORRECTIVE OSTEOTOMY; COLLES FRACTURE;
INTERNAL-FIXATION; YOUNG-ADULTS; INTRAARTICULAR FRACTURES; MIDCARPAL
INSTABILITY; JOINT MECHANICS; WRIST FRACTURES; END
C1 [Monica, James T.; Ring, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Monica, James T.; Ring, David] Harvard Univ, Sch Med, Boston, MA USA.
RP Monica, JT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 61
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND
BN 978-1-4443-4507-0; 978-1-4051-8476-2
J9 EVIDENCE-BASED MED
PY 2012
BP 930
EP 937
PG 8
WC Orthopedics
SC Orthopedics
GA BA9IT
UT WOS:000339448600111
ER
PT B
AU de Haseth, KB
Ring, D
AF de Haseth, Kristin B.
Ring, David
BE Bhandari, M
TI Management of Finger Fractures
SO EVIDENCE-BASED ORTHOPEDICS
SE Evidence-Based Medicnie
LA English
DT Article; Book Chapter
ID PROXIMAL INTERPHALANGEAL JOINT; METACARPAL FRACTURES; SCREW FIXATION;
PHALANGEAL FRACTURES; INTERNAL-FIXATION; EXTERNAL FIXATION; PLATE
FIXATION; OPEN REDUCTION; MALLET-FINGER; FUNCTIONAL TREATMENT
C1 [de Haseth, Kristin B.; Ring, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP de Haseth, KB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 45
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND
BN 978-1-4443-4507-0; 978-1-4051-8476-2
J9 EVIDENCE-BASED MED
PY 2012
BP 987
EP 992
PG 6
WC Orthopedics
SC Orthopedics
GA BA9IT
UT WOS:000339448600118
ER
PT B
AU Gee, MS
Harisinghani, MG
AF Gee, Michael S.
Harisinghani, Mukesh G.
BE Ahmed, HU
Arya, M
Carroll, P
Emberton, M
TI The Future of Molecular and Biomolecular Imaging in Prostate Cancer
SO FOCAL THERAPY IN PROSTATE CANCER
LA English
DT Article; Book Chapter
ID PLANAR BONE-SCINTIGRAPHY; PET; LOCALIZATION; METASTASES
C1 [Gee, Michael S.; Harisinghani, Mukesh G.] Harvard Univ, Sch Med, Sect Abdominal Imaging & Intervent Radiol, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Gee, MS (reprint author), Harvard Univ, Sch Med, Sect Abdominal Imaging & Intervent Radiol, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 15
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
BN 978-1-4443-4686-2; 978-1-4051-9649-9
PY 2012
BP 75
EP 84
PG 10
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA BA5TL
UT WOS:000337000300010
ER
PT J
AU Astarita, JL
Acton, SE
Turley, SJ
AF Astarita, Jillian L.
Acton, Sophie E.
Turley, Shannon J.
TI Podoplanin: emerging functions in development the immune system and
cancer
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Review
DE podoplanin; CLEC-2; lymph node stromal cells; lymphatic endothelial
cells; platelets; cancer-associated fibroblasts
AB Podoplanin (PDPN) is a well-conserved, mucin-type transmembrane protein expressed in multiple tissues during ontogeny and in adult animals, including the brain, heart, kidney, lungs, osteoblasts, and lymphoid organs. Studies of PDPN-deficient mice have demonstrated that this molecule plays a critical role in development of the heart, lungs, and lymphatic system. PDPN is widely used as a marker for lymphatic endothelial cells and fibroblastic reticular cells of lymphoid organs and for lymphatics in the skin and tumor microenvironment. Much of the mechanistic insight into PDPN biology has been gleaned from studies of tumor cells; tumor cells often upregulate PDPN as they undergo epithelial-mesenchymal transition and this upregulation is correlated with increased motility and metastasis. The physiological role of PDPN that has been most studied is its ability to aggregate and activate CLEC-2-expressing platelets, as PDPN is the only known endogenous ligand for CLEC-2. However, more recent studies have revealed that PDPN also plays crucial roles in the biology of immune cells, including T cells and dendritic cells. This review will provide a comprehensive overview of the diverse roles of PDPN in development, immunology, and cancer.
C1 [Astarita, Jillian L.; Acton, Sophie E.; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Astarita, Jillian L.] Harvard Univ, Sch Med, Div Med Sci, Boston, MA USA.
[Acton, Sophie E.] UCL, Dept Cell & Dev Biol, London, England.
[Turley, Shannon J.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA USA.
RP Turley, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 450 Brookline Ave,Dana 1440A, Boston, MA 02115 USA.
EM shannon_turley@dfci.harvard.edu
OI Acton, Sophie/0000-0003-2704-716X
FU National Institutes of Health [R01 DK074500, P01 AI045757]; National
Science Foundation; Wellcome Trust
FX This work was supported by National Institutes of Health grants R01
DK074500 and P01 AI045757 (to Shannon J. Turley), a National Science
Foundation Graduate Research Fellowship (to Jillian L. Astarita), and a
Wellcome Trust Henry Wellcome Postdoctoral Fellowship (to Sophie E.
Acton).
NR 93
TC 57
Z9 58
U1 1
U2 8
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PY 2012
VL 3
AR 283
DI 10.3389/fimmu.2012.00283
PG 11
WC Immunology
SC Immunology
GA V40TQ
UT WOS:000209501300278
PM 22988448
ER
PT J
AU Benichou, G
Tonsho, M
Tocco, G
Nadazdin, O
Madsen, JC
AF Benichou, Gilles
Tonsho, Makoto
Tocco, Georges
Nadazdin, Ognjenka
Madsen, Joren C.
TI Innate immunity and resistance to tolerogenesis in allotransplantation
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Review
DE innate immunity; tolerance; transplantation; allografts; rejection
AB The development of immunosuppressive drugs to control adaptive immune responses has led to the success of transplantation as a therapy for end-stage organ failure. However, these agents are largely ineffective in suppressing components of the innate immune system. This distinction has gained in clinical significance as mounting evidence now indicates that innate immune responses play important roles in the acute and chronic rejection of whole organ allografts. For instance, whereas clinical interest in natural killer (NK) cells was once largely confined to the field of bone marrow transplantation, recent findings suggest that these cells can also participate in the acute rejection of cardiac allografts and prevent tolerance induction. Stimulation of Toll-like receptors (TLRs), another important component of innate immunity, by endogenous ligands released in response to ischemia/reperfusion is now known to cause an inflammatory milieu favorable to graft rejection and abrogation of tolerance. Emerging data suggest that activation of complement is linked to acute rejection and interferes with tolerance. In summary, the conventional wisdom that the innate immune system is of little importance in whole organ transplantation is no longer tenable. The addition of strategies that target TLRs, NK cells, complement, and other components of the innate immune system will be necessary to eventually achieve long-term tolerance to human allograft recipients.
C1 [Benichou, Gilles; Tonsho, Makoto; Tocco, Georges; Nadazdin, Ognjenka; Madsen, Joren C.] Massachusetts Gen Hosp, Transplant Res Ctr, Boston, MA 02114 USA.
[Benichou, Gilles; Tonsho, Makoto; Tocco, Georges; Nadazdin, Ognjenka; Madsen, Joren C.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Benichou, Gilles; Tonsho, Makoto; Tocco, Georges; Nadazdin, Ognjenka; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Cox 654,55 Fruit St, Boston, MA 02114 USA.
EM jcmadsen@partners.org
FU MGH ECOR; NIAID [AI066705]; NIH [U191066705, PO1HL18646, ROTRF
313867044]
FX This work was supported by grants from the MGH ECOR and NIAID AI066705
grants to Gilles Benichou and NIH U191066705, PO1HL18646, and ROTRF
313867044 to Joren C. Madsen.
NR 316
TC 11
Z9 14
U1 1
U2 1
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PY 2012
VL 3
AR 73
DI 10.3389/fimmu.2012.00073
PG 16
WC Immunology
SC Immunology
GA V40TQ
UT WOS:000209501300071
PM 22566954
ER
PT J
AU Edwards, CK
Green, JS
Volk, HD
Schiff, M
Kotzin, BL
Mitsuya, H
Kawaguchi, T
Sakata, KM
Cheronis, J
Trollinger, D
Bankaitis-Davis, D
Dinarello, CA
Norris, DA
Bevilacqua, MP
Fujita, M
Burmester, GR
AF Edwards, Carl K., III
Green, Julie S.
Volk, Hans-Dieter
Schiff, Michael
Kotzin, Brian L.
Mitsuya, Hiroaki
Kawaguchi, Tatsuya
Sakata, Ken-Mei
Cheronis, John
Trollinger, David
Bankaitis-Davis, Danute
Dinarello, Charles A.
Norris, David A.
Bevilacqua, Michael P.
Fujita, Mayumi
Burmester, Gerd-Rudiger
TI Combined anti-tumor necrosis factor-alpha therapy and DMARD therapy in
rheumatoid arthritis patients reduces inflammatory gene expression in
whole blood compared to DMARD therapy alone
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE gene expression; rheumatoid arthritis; anti-TNF-alpha; whole blood;
biomarker
AB Periodic assessment of gene expression for diagnosis and monitoring in rheumatoid arthritis (RA) may provide a readily available and useful method to detect subclinical disease progression and follow responses to therapy with disease modifying anti-rheumatic agents (DMARDs) or anti-INF-a therapy. We used quantitative real-time PCR to compare peripheral blood gene expression profiles in active ("unstable") RA patients on DMARDs, stable RA patients on DMARDs, and stable RA patients treated with a combination of a disease-modifying anti-rheumatoid drug (DMARD) and an anti-TNF-e agent (infliximab or etanercept) to healthy human controls. The expression of 48 inflammatory genes were compared between healthy controls (N = 122), unstable DMARD patients (N = 18), stable DMARD patients (N = 26), and stable patients on combination therapy (N = 20). Expression of 13 genes was very low or undetectable in all study groups. Compared to healthy controls, patients with unstable RA on DMARDs exhibited increased expression of 25 genes, stable DMARD patients exhibited increased expression of 14 genes and decreased expression of five genes, and combined therapy patients exhibited increased expression of six genes and decreased expression of 10 genes. These findings demonstrate that active RA is associated with increased expression of circulating inflammatory markers whereas increases in inflammatory gene expression are diminished in patients with stable disease on either DMARD or anti-INF-a therapy. Furthermore, combination DMARD and anti-INF-a therapy is associated with greater reductions in circulating inflammatory gene expression compared to DMARD therapy alone. These results suggest that assessment of peripheral blood gene expression may prove useful to monitor disease progression and response to therapy.
C1 [Edwards, Carl K., III; Green, Julie S.; Norris, David A.; Bevilacqua, Michael P.; Fujita, Mayumi] Univ Colorado Denver, Dept Dermatol, Aurora, CO 80045 USA.
[Edwards, Carl K., III; Schiff, Michael; Kotzin, Brian L.] Univ Colorado Denver, Dept Rheumatol, Aurora, CO 80045 USA.
[Volk, Hans-Dieter; Burmester, Gerd-Rudiger] Campus Charite Mitte Inst Med Immunol, Berlin, Germany.
[Mitsuya, Hiroaki; Kawaguchi, Tatsuya; Sakata, Ken-Mei] Kumamoto Univ, Sch Med, Kumamoto 860, Japan.
[Cheronis, John; Trollinger, David; Bankaitis-Davis, Danute; Bevilacqua, Michael P.] Source Precis Med, Boulder, CO USA.
[Dinarello, Charles A.] Univ Colorado Denver, Dept Infect Dis, Aurora, CO 80045 USA.
[Norris, David A.; Fujita, Mayumi] Denver Vet Affairs Med Ctr, Denver, CO USA.
RP Fujita, M (reprint author), Univ Colorado Denver, Anschutz Med Campus,12801 East17thAvenue RC-1, Aurora, CO 80045 USA.
EM carl.edwards@ucdenver.edu; mayumi.fujita@ucdenver.edu
NR 53
TC 4
Z9 4
U1 0
U2 0
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PY 2012
VL 3
AR 366
DI 10.3389/fimmu.2012.00366
PG 10
WC Immunology
SC Immunology
GA V40TQ
UT WOS:000209501300361
PM 23264777
ER
PT J
AU Gleimer, M
von Boehmer, H
Kreslavsky, T
AF Gleimer, Michael
von Boehmer, Harald
Kreslavsky, Taras
TI PLZF controls the expression of a limited number of genes essential for
NKT cell function
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE NKT; PLZF; c-Maf; Id2; CXCR6; ICOS; IL12R; IL18R
AB Natural killer (NKT) T cells exhibit tissue distribution, surface phenotype, and functional responses that are strikingly different from those of conventional T cells. The transcription factor PLZF is responsible for most of these properties, as its ectopic expression in conventional T cells is sufficient to confer to them an NKT-like phenotype. The molecular program downstream of PLZF, however, is largely unexplored. Here we report that PLZF regulates the expression of a surprisingly small set of genes, many with known immune functions. This includes several established components of the NKT cell developmental program. Expression of the transcriptional regulators Id2, previously shown to be required for iNKT cell survival in the liver and c-Maf, which shapes the NKT cytokine profile, was compromised in PLZF-deficient cells. Ectopic expression of c-Maf complemented the cells' defect in producing IL-4 and IL-10. PLZF also induced a program of cell surface receptors which shape the NKT cell's response to external stimuli, including the costimulatory receptor lCOS and the cytokine receptors IL12rb1 and IL18r1. As an ensemble, the known functions of the molecules whose expression is affected by PLZF explain many defects observed in PLZF(-/-) NKT cells.
C1 [Gleimer, Michael; von Boehmer, Harald; Kreslavsky, Taras] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lab Lymphocyte Biol Canc Immunol & AIDS, Boston, MA 02215 USA.
[Gleimer, Michael; von Boehmer, Harald; Kreslavsky, Taras] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA.
RP Gleimer, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lab Lymphocyte Biol Canc Immunol & AIDS, 450 Brookline Ave,Smith 736, Boston, MA 02215 USA.
EM michael_gleimer@dfci.harvard.edu
FU National Institutes of Health [R01 A145846, R01 A151378]
FX We thank Drs. H.-J. Kim, S. Schlenner, and C. Daniel for helpful
discussions and Drs. H.-J. Kim and Nadia Cohen for critical reading of
the manuscript. We are grateful to V. Schmidt for technical assistance.
We thank the National Institutes of Health tetramer core facility for
preparation of CD1d tetramer and Dana-Farber Microarray Core Facility
for generation of microarray data. These studies were supported by
National Institutes of Health Grants R01 A145846 and R01 A151378.
NR 52
TC 18
Z9 18
U1 0
U2 2
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PY 2012
VL 3
AR 374
DI 10.3389/fimmu.2012.00374
PG 13
WC Immunology
SC Immunology
GA V40TQ
UT WOS:000209501300369
PM 23267359
ER
PT J
AU Harriff, MJ
Purdy, GE
Lewinsohn, DM
AF Harriff, Melanie J.
Purdy, Georgiana E.
Lewinsohn, David M.
TI Escape from the phagosome: the explanation for MHC-I processing of
mycobacterial antigens?
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Review
DE Mycobacterium tuberculosis; phagosome; MHC-I antigen processing; CD8(+)
T cells
AB Mycobacterium tuberculosis (Mtb) is thought to live in an altered phagosomal environment. In this setting, the mechanisms by which mycobacterial antigens access the major histocompatibility class I (MHC-I) processing machinery remain incompletely understood. There is evidence that Mtb antigens can be processed in both endocytic and cytosolic environments, with different mechanisms being proposed for how Mtb antigens can access the cytosol. Recently, electron microscopy was used to demonstrate that Mtb has the potential to escape the phagosome and reside in the cytosol. This was postulated as the primary mechanism by which Mtb antigens enter the MHC-I processing and presentation pathway. In this commentary, we will review data on the escape of Mtb from the cytosol and whether this escape is required for antigen presentation to CD8(+) T cells.
C1 [Harriff, Melanie J.; Lewinsohn, David M.] Portland VA Med Ctr, Portland, OR USA.
[Harriff, Melanie J.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Pulm & Crit Care Med, Portland, OR 97239 USA.
[Purdy, Georgiana E.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA.
RP Lewinsohn, DM (reprint author), Oregon Hlth & Sci Univ, Pulm & Crit Care Med, 3181 SW Sam Jackson Pk Rd,Mail Code VA R&D11, Portland, OR 97239 USA.
EM lewinsod@ohsu.edu
RI Lewinsohn, David/I-4936-2013
OI Lewinsohn, David/0000-0001-9906-9494
NR 94
TC 16
Z9 16
U1 0
U2 1
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PY 2012
VL 3
AR 40
DI 10.3389/fimmu.2012.00040
PG 11
WC Immunology
SC Immunology
GA V40TQ
UT WOS:000209501300039
PM 22566923
ER
PT J
AU Hasturk, H
Kantarci, A
Van Dyke, TE
AF Hasturk, Hatice
Kantarci, Alpdogan
Van Dyke, Thomas E.
TI Oral inflammatory diseases and systemic inflammation: role of tne
macrophage
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Review
DE innate immune system; macrophage; oral disease; inflammation; resolution
AB Inflammation is a complex reaction to injurious agents and includes vascular responses, migration, and activation of leukocytes. Inflammation starts with an acute reaction, which evolves into a chronic phase if allowed to persist unresolved. Acute inflammation is a rapid process characterized by fluid exudation and emigration of leukocytes, primarily neutrophils, whereas chronic inflammation extends over a longer time and is associated with lymphocyte and macrophage infiltration, blood vessel proliferation, and fibrosis. Inflammation is terminated when the invader is eliminated, and the secreted mediators are removed; however, many factors modify the course and morphologic appearance as well as the termination pattern and duration of inflammation. Chronic inflammatory illnesses such as diabetes, arthritis, and heart disease are now seen as problems that might have an impact on the periodontium. Reciprocal effects of periodontal diseases are potential factors modifying severity in the progression of systemic inflammatory diseases. Macrophages are key cells for the inflammatory processes as regulators directing inflammation to chronic pathological changes or resolution with no damage or scar tissue formation. As such, macrophages are involved in a remarkably diverse array of homeostatic processes of vital importance to the host. In addition to their critical role in immunity, macrophages are also widely recognized as ubiquitous mediators of cellular turnover and maintenance of extracellular matrix homeostasis. In this review, our objective is to identify macrophage-mediated events central to the inflammatory basis of chronic diseases, with an emphasis on how control of macrophage function can be used to prevent or treat harmful outcomes linked to uncontrolled inflammation.
C1 [Hasturk, Hatice; Kantarci, Alpdogan; Van Dyke, Thomas E.] Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA.
RP Hasturk, H (reprint author), Forsyth Inst, Dept Periodontol, 245 First St,17th Floor, Cambridge, MA 02142 USA.
EM hhasturk@forsyth.org
FU USPHS [DE15566, DE16191, DE018917, DE020906]
FX This work was supported by the USPHS grants DE15566, DE16191 (Thomas E.
Van Dyke), DE018917 (Hatice Hasturk), and DE020906 (Alpdogan Kantarci).
NR 241
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U1 2
U2 8
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PY 2012
VL 3
AR UNSP 118
DI 10.3389/fimmu.2012.00118
PG 17
WC Immunology
SC Immunology
GA V40TQ
UT WOS:000209501300115
PM 22623923
ER
PT J
AU Kim, ST
Shin, YD
Brazin, K
Mallis, RJ
Sun, ZYJ
Wagner, G
Lang, MJ
Reinherz, EL
AF Kim, Sun Taek
Shin, Yongdae
Brazin, Kristine
Mallis, Robert J.
Sun, Zhen-Yu J.
Wagner, Gerhard
Lang, Matthew J.
Reinherz, Ellis L.
TI TCR mechanobiology: torques and tunable structures linkec to early T
cell signaling
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Review
DE quaternary change; mechanosensor; T cell signaling; force transduction;
antigen recognition
AB Mechanotransduction is a basis for receptor signaling in many biological systems. Recent data based upon optical tweezer experiments suggest that the TCR is an anisotropic mechanosensor, converting mechanical energy into biochemical signals upon specific peptide-MHC complex (pMHC) ligation. Tangential force applied along the pseudo-twofold symmetry axis of the TCR complex post-ligation results in the alpha beta heterodimer exerting torque on the CD3 heterodimers as a consequence of molecular movement at the T cell APC interface. Accompanying TCR quaternary change likely fosters signaling via the lipid bilayer predicated on the magnitude and direction of the TCR pMHC force. TCR glycans may modulate quaternary change, thereby altering signaling outcome as might the redox state of the CxxC motifs located proximal to the TM segments in the heterodimeric CD3 subunits. Predicted alterations in TCR TM segments and surrounding lipid will convert ectodomain ligation into the earliest intracellular signaling events.
C1 [Kim, Sun Taek; Brazin, Kristine; Mallis, Robert J.; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA.
[Kim, Sun Taek; Brazin, Kristine; Mallis, Robert J.; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Kim, Sun Taek; Brazin, Kristine; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Shin, Yongdae] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
[Mallis, Robert J.; Sun, Zhen-Yu J.; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Lang, Matthew J.] Vanderbilt Univ, Dept Chem & Biomol Engn, Nashville, TN 37235 USA.
RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, 77 Ave Louis Pasteur,HIM 419, Boston, MA 02115 USA.
EM ellis_reinherz@dfci.harvard.edu
FU NIH [AI19807]
FX We thank Dr. Jia-Huai Wang for thoughtful comments. This work was
supported by NIH grant AI19807.
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PY 2012
VL 3
AR 76
DI 10.3389/fimmu.2012.00076
PG 8
WC Immunology
SC Immunology
GA V40TQ
UT WOS:000209501300074
PM 22566957
ER
PT J
AU Korner, C
Altfeld, M
AF Koerner, Christian
Altfeld, Marcus
TI Role of KIR3DS1 in human diseases
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Review
DE KIR3DS1; HLA; HIV-1; killer-immunoglobulin-like receptors; NK cell
AB The function of natural killer (NK) cells is controlled by several activating and inhibitory receptors, including the family of killer-immunoglobulin-like receptors (KIRs). One distinctive feature of KIRs is the extensive number of various haplotypes generated by the gene content within the KIR gene locus as well as by highly polymorphic members of the KIR gene family, namely KIR3DL1/S1. Within the KIR3DL1/S1 gene locus, KIR3DS1 represents a conserved allelic variant and displays other unique features in comparison to the highly polymorphic KIR3DL1 allele. KIR3DS1 is present in all human populations and belongs to the KIR haplotype group B. KIR3DS1 encodes for an activating receptor featuring the characteristic short cytoplasmic tail and a positively charged residue within the transmembrane domain, which allows recruitment of the ITAM-bearing adaptor molecule DAP12. Although HLA class I molecules are thought to represent natural KIR ligands, and HLA-Bw4 molecules serve as ligands for KIR3DL1, the ligand for KIR3DS1 still needs to be identified. Despite the lack of formal evidence for an interaction of KIR3DS1 with HLA-Bw4-180 or any other HLA class 1 subtype to date, a growing number of associations between the presence of KIR3DS1 and the outcome of viral infections have been described. Especially, the potential protective role of KIR3DS1 in combination with HLA-Bw4-180 in the context of HIV-1 infection has been studied intensively. In addition, a number of recent studies have associated the presence or absence of KIR3DS1 with the occurrence and outcome of some malignancies, autoimmune diseases, and graft-versus-host disease (GVHD). In this review, we summarize the present knowledge regarding the characteristics of KIRD3S1 and discuss its role in various human diseases.
C1 [Koerner, Christian; Altfeld, Marcus] Massachusetts Inst Technol & Harvard Univ, Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA 02129 USA.
RP Altfeld, M (reprint author), Massachusetts Inst Technol & Harvard Univ, Massachusetts Gen Hosp, Ragon Inst, 149 13th St,Room 6-003,MGH East, Charlestown, MA 02129 USA.
EM maltfeld@partners.org
OI Korner, Christian/0000-0002-3431-7319
FU NIH [R01 AI066031]; Doris Duke Charitable Foundation; Ragon Institute of
MGH, MIT and Harvard
FX This study was supported by the NIH (R01 AI066031), the Doris Duke
Charitable Foundation, and the Ragon Institute of MGH, MIT and Harvard.
We thank Cormac Cosgrove and Sagar A. Vaidya for critical review of this
manuscript.
NR 124
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PY 2012
VL 3
AR 326
DI 10.3389/fimmu.2012.00326
PG 11
WC Immunology
SC Immunology
GA V40TQ
UT WOS:000209501300321
PM 23125843
ER
PT J
AU van der Merwe, PA
Zhang, H
Cordoba, SP
AF van der Merwe, P. Anton
Zhang, Hao
Cordoba, Shaun-Paul
TI Why do some T cell receptor cytoplasmic domains associate with the
plasma membrane?
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE T cell receptor; membrane association; polybasic motifs; tyrosine
phosphorylation
AB Based on studies in model systems it has been proposed that the cytoplasmic domains of T cell receptor signaling subunits that have polybasic motifs associate with the plasma membrane, and that this regulates their phosphorylation. Recent experiments in more physiological systems have confirmed membrane association but raised questions as to its function.
C1 [van der Merwe, P. Anton; Zhang, Hao; Cordoba, Shaun-Paul] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
[Zhang, Hao] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP van der Merwe, PA (reprint author), Univ Oxford, Sir William Dunn Sch Pathol, S Parks Rd, Oxford OX1 3RE, England.
EM anton.vandermerwe@path.ox.ac.uk
FU Cancer Research UK; UK Medical Research Council; EP Abraham Research
Fund
FX We thank our fellow lab members for productive and stimulating
discussions. P. Anton van der Merwe, Hao Zhang, and Shaun-Paul Cordoba
are supported by Cancer Research UK, the UK Medical Research Council,
and the EP Abraham Research Fund.
NR 16
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PY 2012
VL 3
AR 29
DI 10.3389/fimmu.2012.00029
PG 3
WC Immunology
SC Immunology
GA V40TQ
UT WOS:000209501300029
PM 22566913
ER
PT J
AU Dai, TH
Fuchs, BB
Coleman, JJ
Prates, RA
Astrakas, C
St Denis, TG
Ribeiro, MS
Mylonakis, E
Hamblin, MR
Tegos, GP
AF Dai, Tianhong
Fuchs, Beth B.
Coleman, Jeffrey J.
Prates, Renato A.
Astrakas, Christos
St Denis, Tyler G.
Ribeiro, Martha S.
Mylonakis, Eleftherios
Hamblin, Michael R.
Tegos, George P.
TI Concepts and principles of photodynamic therapy as an alternative
antifungal discovery platform
SO FRONTIERS IN MICROBIOLOGY
LA English
DT Review
DE photodynamic inactivation; photodynamic therapy; photosensitizer;
reactive oxygen species; permeability barrier; multidrug efflux systems;
biofilms; clinical applications
AB Opportunistic fungal pathogens may cause superficial or serious invasive infections, especially in immunocompromised and debilitated patients. Invasive mycoses represent an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. Therefore systemic fungal infections result in high attributable mortality. There is an urgent need to pursue and deploy novel and effective alternative antifungal countermeasures. Photodynamic therapy (PDT) was established as a successful modality for malignancies and age-related macular degeneration but photodynamic inactivation has only recently been intensively investigated as an alternative antimicrobial discovery and development platform. The concept of photodynamic inactivation requires microbial exposure to either exogenous or endogenous photosensitizer molecules, followed by visible light energy, typically wavelengths in the red/near infrared region that cause the excitation of the photosensitizers resulting in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation and death. Antifungal PDT is an area of increasing interest, as research is advancing (i) to identify the photochemical and photophysical mechanisms involved in photoinactivation; (ii) to develop potent and clinically compatible photosensitizers; (iii) to understand how photoinactivation is affected by key microbial phenotypic elements multidrug resistance and efflux, virulence and pathogenesis determinants, and formation of biofilms; (iv) to explore novel photosensitizer delivery platforms; and (v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants.
C1 [Dai, Tianhong; St Denis, Tyler G.; Hamblin, Michael R.; Tegos, George P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Dai, Tianhong; Hamblin, Michael R.; Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Fuchs, Beth B.; Coleman, Jeffrey J.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Prates, Renato A.; Ribeiro, Martha S.] IPEN CNEN SP, Ctr Lasers & Applicat, Sao Paulo, Brazil.
[Astrakas, Christos] Democritus Univ Thrace, Sch Med, Div Internal Med, Alexandroupolis, Greece.
[St Denis, Tyler G.] Columbia Univ, Dept Chem, New York, NY 10027 USA.
[Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Tegos, George P.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA.
[Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA.
RP Tegos, GP (reprint author), Univ New Mexico, Ctr Mol Discovery, UNM Hlth Sci Ctr, Sch Med,Dept Pathol, 2325 Camino Salud,CRF 217A MSC 07-4025, Albuquerque, NM 87131 USA.
EM gtegos@salud.unm.edu
RI Prates, Renato/F-8235-2014; Coleman, Jeffrey/E-2981-2015; Ribeiro,
Martha/G-3517-2012;
OI Ribeiro, Martha/0000-0002-4203-1134; Coleman,
Jeffrey/0000-0001-8579-1996; Hamblin, Michael/0000-0001-6431-4605
FU NIH [5U54M11084690-02, RO1 AI050875]; US Air Force MFEL Program
[FA9550-04-1-0079]; Bullock-Wellman Fellowship Award; Airlift Research
Foundation Extremity Trauma Research Grant [109421]; Columbia University
I. I. Rabi Fellows Program
FX George P. Tegos is supported by the NIH (grant 5U54M11084690-02).
Research conducted in the Hamblin Laboratory was supported by NIH (RO1
AI050875 to MRH) and US Air Force MFEL Program (FA9550-04-1-0079).
Research conducted in the Mylonakis Laboratory was supported by NIH (RO1
AI050875 to Eleftherios Mylonakis) and, Tianhong Dai was partially
supported by a Bullock-Wellman Fellowship Award and an Airlift Research
Foundation Extremity Trauma Research Grant (grant 109421). Research
conducted by Tyler G. St. Denis is supported by the Columbia University
I. I. Rabi Fellows Program.
NR 150
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U1 6
U2 23
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-302X
J9 FRONT MICROBIOL
JI Front. Microbiol.
PY 2012
VL 3
AR 120
DI 10.3389/fmicb.2012.00120
PG 16
WC Microbiology
SC Microbiology
GA V31DF
UT WOS:000208863600172
PM 22514547
ER
PT J
AU Franzosa, EA
Garamszegi, S
Xia, Y
AF Franzosa, Eric A.
Garamszegi, Sara
Xia, Yu
TI Toward a three-dimensional view of protein networks between species
SO FRONTIERS IN MICROBIOLOGY
LA English
DT Review
DE structural systems biology; protein protein interaction; host pathogen
interaction; bioinformatics and computational biology; network biology
AB General principles governing biomolecular interactions between species are expected to differ significantly from known principles governing the interactions within species, yet these principles remain poorly understood at the systems level. A key reason for this knowledge gap is the lack of a detailed three-dimensional (3D), atomistic view of biomolecular interaction networks between species. Recent progress in structural biology, systems biology, and computational biology has enabled accurate and large-scale construction of 3D structural models of nodes and edges for protein protein interaction networks within and between species. The resulting within- and between-species structural interaction networks have provided new biophysical, functional, and evolutionary insights into species interactions and infectious disease. Here, we review the nascent field of between-species structural systems biology, focusing on interactions between host and pathogens such as viruses.
C1 [Franzosa, Eric A.; Garamszegi, Sara; Xia, Yu] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
[Xia, Yu] Boston Univ, Dept Chem, Boston, MA 02215 USA.
[Xia, Yu] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
[Xia, Yu] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
[Xia, Yu] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
RP Xia, Y (reprint author), Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
EM yuxia@bu.edu
OI Xia, Yu/0000-0002-5596-5518
FU National Science Foundation [CCF-1219007]; National Science Foundation
Grad ha te Research Fellowship [DGE-0741448]
FX lfhis work was supported by a grant from the National Science Foundation
(CCF-1219007) to Yu Xia, Sara Garamszegi was supported by a National
Science Foundation Grad ha te Research Fellowship (DGE-0741448).
NR 79
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-302X
J9 FRONT MICROBIOL
JI Front. Microbiol.
PY 2012
VL 3
AR 428
DI 10.3389/fmicb.2012.00428
PG 6
WC Microbiology
SC Microbiology
GA V31DF
UT WOS:000208863600427
PM 23267356
ER
PT J
AU Wang, R
Starkey, M
Hazan, R
Rahme, LG
AF Wang, Rui
Starkey, Melissa
Hazan, Ronen
Rahme, Laurence G.
TI Honey's ability to counter bacterial infections arises from both
bactericidal compounds and QS inhibition
SO FRONTIERS IN MICROBIOLOGY
LA English
DT Article
DE honey; Pseudomonas; quorum-sensing; infection; anti-infective; QS
inhibition; mvfR(pqsR); sugars
AB The ability of honey to kill bacterial pathogens in vitro and quickly clear even chronic or drug-resistant infections has been demonstrated by several studies. Most current research is focused on identifying the bactericidal compounds in honey, but the action of the compounds discovered is not sufficient to explain honey's activity. By diluting honey to sub-inhibitory levels, we were able to study its impact on bacterial coordinated behavior, and discovered that honey inhibits bacterial quorum sensing (QS). Experiments to characterize and quantify honey's effect on the QS networks of Pseudomonas aeruginosa revealed that low concentrations of honey inhibited the expression of MvfR, las, and rhl regulons, including the associated virulence factors. This research also establishes that inhibition of QS is associated with honey's sugar content. Therefore, honey combats infections by two independent mechanisms acting in tandem: bactericidal components, which actively kill cells, and disruption of QS, which weakens bacterial coordination and virulence.
C1 [Wang, Rui; Starkey, Melissa; Hazan, Ronen; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA.
[Starkey, Melissa; Hazan, Ronen; Rahme, Laurence G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hazan, Ronen] Israeli Inst Adv Res, IYAR, Rehovot, Israel.
RP Rahme, LG (reprint author), Harvard Univ, Sch Med, Dept Surg, Mol Surg Lab, 340 Thier Res Bldg,50 Blossom St, Boston, MA 02114 USA.
EM rahme@molbio.mgh.harvard.edu
FU NIAID NIH HHS [R33 AI105902]
NR 40
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-302X
J9 FRONT MICROBIOL
JI Front. Microbiol.
PY 2012
VL 3
AR 144
DI 10.3389/fmicb.2012.00144
PG 8
WC Microbiology
SC Microbiology
GA V31DF
UT WOS:000208863600194
PM 22514552
ER
PT J
AU Poline, JB
Breeze, JL
Ghosh, S
Gorgolewski, K
Halchenko, YO
Hanke, M
Haselgrove, C
Helmer, KG
Keator, DB
Marcus, DS
Poldrack, RA
Schwartz, Y
Ashburner, J
Kennedy, DN
AF Poline, Jean-Baptiste
Breeze, Janis L.
Ghosh, Satrajit
Gorgolewski, Krzysztof
Halchenko, Yaroslav O.
Hanke, Michael
Haselgrove, Christian
Helmer, Karl G.
Keator, David B.
Marcus, Daniel S.
Poldrack, Russell A.
Schwartz, Yannick
Ashburner, John
Kennedy, David N.
TI Data sharing in neuroimaging research
SO FRONTIERS IN NEUROINFORMATICS
LA English
DT Review
DE brain imaging; data sharing; standards; magnetic resonance imaging;
fMRI; EEG-MEG
AB Significant resources around the world have been invested in neuroimaging studies of brain function and disease. Easier access to this large body of work should have profound impact on research in cognitive neuroscience and psychiatry, leading to advances in the diagnosis and treatment of psychiatric and neurological disease. A trend toward increased sharing of neuroimaging data has emerged in recent years. Nevertheless, a number of barriers continue to impede momentum. Many researchers and institutions remain uncertain about how to share data or lack the tools and expertise to participate in data sharing. The use of electronic data capture (EDC) methods for neuroimaging greatly simplifies the task of data collection and has the potential to help standardize many aspects of data sharing. We review here the motivations for sharing neuroimaging data, the current data sharing landscape, and the sociological or technical barriers that still need to be addressed. The INCF Task Force on Neuroimaging Datasharing, in conjunction with several collaborative groups around the world, has started work on several tools to ease and eventually automate the practice of data sharing. It is hoped that such tools will allow researchers to easily share raw, processed, and derived neuroirnaging data, with appropriate metadata and provenance records, and will improve the reproducibility of neuroimaging studies. By providing seamless integration of data sharing and analysis tools within a commodity research environment, the Task Force seeks to identify and minimize barriers to data sharing in the field of neuroimaging
C1 [Poline, Jean-Baptiste; Schwartz, Yannick] Commissariat Energie Atom & Energies, Neurospin, Gif Sur Yvette, France.
[Poline, Jean-Baptiste] Univ Calif Berkeley, Brain Imaging Ctr, Berkeley, CA 94720 USA.
[Breeze, Janis L.] Karolinska Inst, Int Neuroinformat Coordinating Facil, Stockholm, Sweden.
[Ghosh, Satrajit] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
[Gorgolewski, Krzysztof] Univ Edinburgh, Sch Informat, Edinburgh, Midlothian, Scotland.
[Halchenko, Yaroslav O.] Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA.
[Hanke, Michael] Univ Magdeburg, Dept Expt Psychol, D-39106 Magdeburg, Germany.
[Haselgrove, Christian; Kennedy, David N.] Univ Massachusetts, Sch Med, Dept Psychiat, Div Informat, Worcester, MA 01655 USA.
[Helmer, Karl G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Helmer, Karl G.] Harvard Univ, Sch Med, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA.
[Keator, David B.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA.
[Keator, David B.] Univ Calif Irvine, Dept Comp Sci, Irvine, CA 92717 USA.
[Marcus, Daniel S.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Poldrack, Russell A.] Univ Texas Austin, Imaging Res Ctr, Austin, TX 78712 USA.
[Poldrack, Russell A.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA.
[Poldrack, Russell A.] Univ Texas Austin, Dept Neurobiol, Austin, TX 78712 USA.
[Ashburner, John] Wellcome Trust Ctr Neuroimaging, London, England.
RP Poline, JB (reprint author), CEA, Neurospin, Bat 745, F-97791 Gif Sur Yvette, France.
EM jbpoline@gmail.corn
RI Kennedy, David/H-3627-2012; Ashburner, John/I-3757-2013;
OI Ashburner, John/0000-0001-7605-2518; Ghosh,
Satrajit/0000-0002-5312-6729; Hanke, Michael/0000-0001-6398-6370;
Gorgolewski, Krzysztof/0000-0003-3321-7583; Halchenko,
Yaroslav/0000-0003-3456-2493
FU International Neuroinformatics Coordinating Facility
FX The International Neuroinformatics Coordinating Facility provides
financial support for some of the work reported in this article.
NR 66
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5196
J9 FRONT NEUROINFORM
JI Front. Neuroinformatics
PY 2012
VL 6
AR UNSP 9
DI 10.3389/fninf.2012.00009
PG 13
WC Mathematical & Computational Biology; Neurosciences
SC Mathematical & Computational Biology; Neurosciences & Neurology
GA V36IY
UT WOS:000209207100009
PM 22493576
ER
PT J
AU Cooper, RJ
Seib, J
Gagnon, L
Phillip, D
Schytz, HW
Iversen, HK
Ashina, M
Boas, DA
AF Cooper, Robert J.
Seib, Juliette
Gagnon, Louis
Phillip, Dorte
Schytz, Henrik W.
Iversen, Helle K.
Ashina, Messoud
Boas, David A.
TI A systematic comparison of motion artifact correction techniques for
functional near-infrared spectroscopy
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE near-infrared spectroscopy; functional near-infrared spectroscopy; NIRS;
motion artifact; hemodynamic response
AB Near-infrared spectroscopy (NIRS) is susceptible to signal artifacts caused by relative motion between NIRS optical fibers and the scalp. These artifacts can be very damaging to the utility of functional NIRS, particularly in challenging subject groups where motion can be unavoidable. A number of approaches to the removal of motion artifacts from NIRS data have been suggested. In this paper we systematically compare the utility of a variety of published NIRS motion correction techniques using a simulated functional activation signal added to 20 real NIRS datasets which contain motion artifacts. Principle component analysis, spline interpolation, wavelet analysis, and Kalman filtering approaches are compared to one another and to standard approaches using the accuracy of the recovered, simulated hemodynamic response function (HRF). Each of the four motion correction techniques we tested yields a significant reduction in the mean-squared error (MSE) and significant increase in the contrast-to-noise ratio (CNR) of the recovered HRF when compared to no correction and compared to a process of rejecting motion-contaminated trials. Spline interpolation produces the largest average reduction in MSE (55%) while wavelet analysis produces the highest average increase in CNR (39%). On the basis of this analysis, we recommend the routine application of motion correction techniques (particularly spline interpolation or wavelet analysis) to minimize the impact of motion artifacts on functional NI RS data.
C1 [Cooper, Robert J.; Seib, Juliette; Gagnon, Louis; Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA.
[Gagnon, Louis] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA.
[Gagnon, Louis] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Phillip, Dorte; Schytz, Henrik W.; Iversen, Helle K.; Ashina, Messoud] Univ Copenhagen, Fac Hlth Sci, Glostrup Hosp, Danish Headache Ctr,Dept Neurol, Copenhagen, Denmark.
[Iversen, Helle K.] Univ Copenhagen, Fac Hlth Sci, Glostrup Hosp, Stroke Unit,Dept Neurol, Copenhagen, Denmark.
RP Boas, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Room 2301,149,13th St, Charlestown, MA 02129 USA.
EM dboas@nmr.mgh.harvard.edu
OI Cooper, Robert/0000-0001-6696-8020; Schytz, Henrik
Winther/0000-0002-6262-2986; Iversen, Helle
Klingenberg/0000-0002-5880-6352
FU NIH [P41RR14075, R01EB006385]; Fond Quebecois sur la Nature et les
Technologies; Augustinus Foundation
FX We would like to thank Behnam Molavi at the University of British
Columbia for assistance with implementing the process of wavelet
analysis. This work is supported by NIH grants P41RR14075 R01EB006385
(to David A. Boas) the Fond Quebecois sur la Nature et les Technologies
(to Louis Gagnon). The study of stroke patients was supported by the
Augustinus Foundation.
NR 25
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U1 2
U2 8
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PY 2012
VL 6
DI 10.3389/fnins.2012.00147
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA V35RF
UT WOS:000209165300153
PM 23087603
ER
PT J
AU Sohur, US
Arlotta, P
Macklis, JD
AF Sohur, U. Shivraj
Arlotta, Paola
Macklis, Jeffrey D.
TI Developmental controls are re-expressed during induction of neurogenesis
in the neocortex of young adult mice
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE induced adult neocortical neurogenesis; developmental molecular
controls; cortex
AB Whether induction of low-level neurogenesis in normally non-neurogenic regions of the adult brain mimics aspects of developmental neurogenesis is currently unknown. Previously, we and others identified that biophysically induced, neuron subtype-specific apoptosis in mouse neocortex results in induction of neurogenesis of limited numbers of subtype-appropriate projection neurons with axonal projections to either thalamus or spinal cord, depending on the neuron subtype activated to undergo targeted apoptosis. Here, we test the hypothesis that developmental genes from embryonic corticogenesis are re-activated, and that some of these genes might underlie induction of low-level adult neocortical neurogenesis. We directly investigated this hypothesis via microarray analysis of microdissected regions of young adult mouse neocortex undergoing biophysically activated targeted apoptosis of neocortical callosal projection neurons. We compared the microarray results identifying differentially expressed genes with public databases of embryonic developmental genes. We find that, following activation of subtype-specific neuronal apoptosis, three distinct sets of normal developmental genes are selectively re-expressed in neocortical regions of induced neurogenesis in young adult mice: (1) genes expressed by subsets of progenitors and immature neurons in the developing ventricular and/or sub-ventricular zones; (2) genes normally expressed by developmental radial glial progenitors; and (3) genes involved in synaptogenesis. Together with previous results, the data indicate that at least some developmental molecular controls over embryonic neurogenesis can be re-activated in the setting of induction of neurogenesis in the young adult neocortex, and suggest that some of these activate and initiate adult neuronal differentiation from endogenous progenitor populations. Understanding molecular mechanisms contributing to induced adult neurogenesis might enable directed CNS repair.
C1 [Sohur, U. Shivraj; Arlotta, Paola; Macklis, Jeffrey D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Sohur, U. Shivraj; Arlotta, Paola; Macklis, Jeffrey D.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Sohur, U. Shivraj; Arlotta, Paola; Macklis, Jeffrey D.] Harvard Univ, Sch Med, Dept Neurol, MGH HMS Ctr Nervous Syst Repair,Program Neurosci, Boston, MA 02115 USA.
[Sohur, U. Shivraj; Arlotta, Paola; Macklis, Jeffrey D.] Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg, Boston, MA USA.
[Sohur, U. Shivraj; Arlotta, Paola; Macklis, Jeffrey D.] Massachusetts Gen Hosp, Nayef Al Rodhan Labs, Boston, MA 02114 USA.
RP Macklis, JD (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, 7 Divin Ave,Bauer Lab 103, Cambridge, MA 02138 USA.
EM jeffrey_macklis@hms.harvard.edu
FU National Institutes of Health [NS49553, N545523, N541590]; Harvard Stem
Cell Institute; Jane and Lee Seidman Fund for CNS Research; Emily and
Robert Pearlstein Fund for Nervous System Repair; Wills Foundation
Fellowship
FX We thank Vitek Lipski for technicaI assistance. We thank the National
Center for Biotechnology Information's Gene Expression Omnibus (GEO;
http://www.ncbi.nlm.nih.gov/sites/entrez), and the Eurexpress/Genepaint
consortium (http://www.eurexpress.org/ee/intro.html) publicly available
databases for generously providing free access to their important data.
This work was partially supported by the National Institutes of Health
(grants NS49553 and N545523), the Harvard Stem Cell Institute, the Jane
and Lee Seidman Fund for CNS Research, and the Emily and Robert
Pearlstein Fund for Nervous System Repair (Jeffrey D. Macklis), with
additional infrastructure support by National Institutes of Health grant
N541590 (Jeffrey D. Macklis). Paola Arlotta was partially supported by a
Wills Foundation Fellowship. U. Shivraj Sohur was partially supported by
a seed grant from the Harvard Stem Cell Institute.
NR 89
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U1 3
U2 5
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PY 2012
VL 6
AR UNSP 12
DI 10.3389/fnins.2012.00012
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA V35RF
UT WOS:000209165300028
PM 22347158
ER
PT J
AU Stengel, A
Tache, Y
AF Stengel, Andreas
Tache, Yvette
TI Ghrelin a pleiotropic hormone secreted from endocrine X/A-like cells of
the stomach
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Review
DE acyl and desacyl; GOAT; ghrelin; nesfatin-1; NUCB2; endocrine cells;
stress
AB The gastric X/A-like endocrine cell receives growing attention due to its peptide products with ghrelin being the best characterized. This peptide hormone was identified a decade ago as a stimulator of food intake and to date remains the only known peripherally produced and centrally acting orexigenic hormone. In addition, subsequent studies identified numerous other functions of this peptide including the stimulation of gastrointestinal motility, the maintenance of energy homeostasis and an impact on reproduction. Moreover, ghrelin is also involved in the response to stress and assumed to play a role in coping functions and exert a modulatory action on immune pathways. Our knowledge on the regulation of ghrelin has markedly advanced during the past years by the identification of the ghrelin acylating enzyme, ghrelin-O-acyltransferase, and by the description of changes in expression, activation, and release under different metabolic as well as physically and psychically challenging conditions. However, our insight on regulatory processes of ghrelin at the cellular and subcellular levels is still very limited and warrants further investigation.
C1 [Stengel, Andreas] Charite, Dept Med, Div Psychosomat Med & Psychotherapy, D-13353 Berlin, Germany.
[Tache, Yvette] Univ Calif Los Angeles, Dept Med, Digest Dis Res Ctr, Los Angeles, CA 90024 USA.
[Tache, Yvette] Univ Calif Los Angeles, Dept Med, Ctr Neurobiol Stress, Div Digest Dis, Los Angeles, CA 90024 USA.
[Tache, Yvette] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM ytache@mednet.ucla.edu
FU NIH [R01 DK-33061]; NUT [DK-41301]; VA Research Career Scientist;
Charite University funding
FX This work was supported by NIH R01 DK-33061, NUT (enter Grant DK-41301
(Animal Core), VA Research Career Scientist (Yvette Tache), and Charite
University funding (Andreas Stengel). We thank Ms. Eugenia Hu for
careful reading of the manuscript.
NR 231
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PY 2012
VL 6
AR UNSP 24
DI 10.3389/fnins.2012.00024
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA V35RF
UT WOS:000209165300040
PM 22355282
ER
PT J
AU Viveros, MP
Mendrek, A
Paus, T
Lopez-Rodriguez, AB
Marco, EM
Yehuda, R
Cohen, H
Lehrner, A
Wagner, EJ
AF Viveros, Maria-Paz
Mendrek, Adriana
Paus, Tomas
Belen Lopez-Rodriguez, Ana
Maria Marco, Eva
Yehuda, Rachel
Cohen, Hagit
Lehrner, Amy
Wagner, Edward J.
TI A comparative, developmental, and clinical perspective of
neurobehavioral sexual dimorphisms
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Review
DE sexual differentiation; adolescence; schizophrenia; depression; bipolar
disorders; posttraumatic disorders; addiction; animal models
AB Women and men differ in a wide variety of behavioral traits and in their vulnerability to developing certain mental disorders. This review endeavors to explore how recent preclinical and clinical research findings have enhanced our understanding of the factors that underlie these disparities. We start with a brief overview of some of the important genetic, molecular, and hormonal determinants that contribute to the process of sexual differentiation. We then discuss the importance of animal models in studying the mechanisms responsible for sex differences in neuropsychiatric disorders (e.g., drug dependence) with a special emphasis on experimental models based on the neurodevelopmental and "three hits" hypotheses. Next, we describe the most common brain phenotypes observed in vivo with magnetic resonance imaging. We discuss the challenges in interpreting these phenotypes vis-a-vis the underlying neurobiology and revisit the known sex differences in brain structure from birth, through adolescence, and into adulthood. This is followed by a presentation of pertinent clinical and epidemiological data that point to important sex differences in the prevalence, course, and expression of psychopathologies such as schizophrenia, and mood disorders including major depression and posttraumatic stress disorder. Recent evidence implies that mood disorders and psychosis share some common genetic predispositions and neurobiological bases. Therefore, modern research is emphasizing dimensional representation of mental disorders and conceptualization of schizophrenia and major depression as a continuum of cognitive deficits and neurobiological abnormalities. Herein, we examine available evidence on cerebral sexual dimorphism to verify if sex differences vary quantitatively and/or qualitatively along the psychoses-depression continuum. Finally, sex differences in the prevalence of posttraumatic disorder and drug abuse have been described, and we consider the genomic and molecular data supporting these differences.
C1 [Viveros, Maria-Paz; Belen Lopez-Rodriguez, Ana; Maria Marco, Eva] Univ Complutense, Fac Biol, Physiol Dept Anim Physiol 2, Hlth Res Inst,Hosp Clin San Carlos, E-28040 Madrid, Spain.
[Mendrek, Adriana] Bishops Univ, Dept Psychol, Sherbrooke, PQ, Canada.
[Paus, Tomas] Univ Toronto, Rotman Res Inst, Toronto, ON, Canada.
[Paus, Tomas] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
[Yehuda, Rachel] Mt Sinai Sch Med, New York, NY USA.
[Yehuda, Rachel; Cohen, Hagit] Ben Gurion Univ Negev, Fac Hlth Sci, Minist Hlth, Anxiety & Stress Res Unit,Mental Hlth Ctr, IL-84105 Beer Sheva, Israel.
[Lehrner, Amy] James J Peters Vet Affairs Med Ctr, Traumat Stress Studies Div, Bronx, NY USA.
[Wagner, Edward J.] Western Univ Hlth Sci, Coll Osteopath Med Pacific, Dept Basic Med Sci, Pomona, CA USA.
RP Viveros, MP (reprint author), Univ Complutense, Fac Biol, Dept Fisiol Fisiol Anim 2, C Jose Antonio Novais 2, E-28040 Madrid, Spain.
EM pazviver@bio.ucm.es
RI Lopez-Rodriguez, Ana Belen/A-8384-2015; Marco, Eva/K-8224-2015; Viveros,
Maria-Paz/S-6855-2016
OI Marco, Eva/0000-0002-2457-475X;
FU Instituto de Salud Carlos III, Redes tematicas de Investigacion
Cooperativa en salud (ISCIII y FEDER): Red de trastornos adictivos
[RD06/0001/1013]; GRUPOS UCM-BSCH [951579]; Ministerio de Ciencia e
Innovacion [BFU2009-10109]; Plan Nacional sobre Drogas [SAS/1250/2009]
FX This work was supported by Instituto de Salud Carlos III, Redes
tematicas de Investigacion Cooperativa en salud (ISCIII y FEDER): Red de
trastornos adictivos RD06/0001/1013; GRUPOS UCM-BSCH - 951579;
Ministerio de Ciencia e Innovacion BFU2009-10109, and Plan Nacional
sobre Drogas at SAS/1250/2009 official notification.
NR 257
TC 13
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U1 2
U2 8
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PY 2012
VL 6
AR UNSP 84
DI 10.3389/fnins.2012.00084
PG 21
WC Neurosciences
SC Neurosciences & Neurology
GA V35RF
UT WOS:000209165300093
PM 22701400
ER
PT J
AU de Oliveira, RM
Sarkander, J
Kazantsev, AG
Outeiro, TF
AF de Oliveira, Rita Machado
Sarkander, Jana
Kazantsev, Aleksey G.
Outeiro, Tiago Fleming
TI SIRT2 as a therapeutic target for age-related disorders
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Review
DE SIRT2; aging; metabolic syndrome; cancer; neurodegenerative disorder
AB Sirtuin proteins are conserved regulators of aging that have recently emerged as important modifiers of several diseases which commonly occur later in life such as cancer, diabetes, cardiovascular, and neurodegenerative diseases. In mammals, there are seven sirtuins (SIRT1-7), which display diversity in subcellular localization and function. SIRT1 has received much of attention due to its possible impact on longevity, while important biological and therapeutic roles of other sirtuins have been underestimated and just recently recognized. Here we focus on SIRT2, a member of the sirtuin family, and discuss its role in cellular and tissue-specific functions. This review summarizes the main scientific advances on SIRT2 protein biology and explores its potential as a therapeutic target for treatment of age-related disorders.
C1 [de Oliveira, Rita Machado; Sarkander, Jana; Outeiro, Tiago Fleming] Inst Mol Med, Cell & Mol Neurosci Unit, Lisbon, Portugal.
[Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Kazantsev, Aleksey G.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA.
[Outeiro, Tiago Fleming] Fac Med Lisbon, Inst Fisiol, Lisbon, Portugal.
[Outeiro, Tiago Fleming] Univ Med Gottingen, Ctr Mol Physiol Brain, Dept Neurodegenerat & Restorat Res, Gottingen, Germany.
RP Kazantsev, AG (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA.
EM akazantsev@partners.org; touteiro@gmail.com
RI de Oliveira, Rita/E-9696-2015
OI de Oliveira, Rita/0000-0002-0970-4501
FU Michael J. Fox Foundation; European Commission; FCT
[SFRH/BPD/41416/2007]; NIH [1U01NS066912-01A]
FX We are grateful to Hugo Vicente Miranda for graphical support in the
execution of Figure 1. Tiago Fleming Outeiro was supported by the
Michael J. Fox Foundation, by a Marie Curie International Reintegration
Grant (Neurofold) from the European Commission and an EMBO Installation
Grant. Rita Machado de Oliveira is supported by FCT
(SFRH/BPD/41416/2007). Aleksey G. Kazantsev is supported by NIH
1U01NS066912-01A.
NR 91
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U1 1
U2 14
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PY 2012
VL 3
AR UNSP 82
DI 10.3389/fphar.2012.00082
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA V35XE
UT WOS:000209177700078
PM 22563317
ER
PT J
AU Durazzo, TC
Hutchison, KE
Fryer, SL
Mon, A
Meyerhoff, DJ
AF Durazzo, Timothy C.
Hutchison, Kent E.
Fryer, Susanna L.
Mon, Anderson
Meyerhoff, Dieter J.
TI Associations of cigarette smoking and polymorphisms in brain-derived
neurotrophic factor and catechol-O-methyltransferase with neurocognition
in alcohol dependent individuals during early abstinence
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Article
DE cigarette smoking; brain-derived neurotrophic factor;
catechol-O-methyltransferase; neurocognition; alcohol dependence
AB Chronic cigarette smoking and polymorphisms in brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) are associated with neurocognition in normal controls and those with various neuropsychiatric conditions. The influence of BDNF and COMT on neurocognition in alcohol dependence is unclear. The primary goal of this report was to investigate the associations of single nucleotide polymorphisms (SNPs) in BDNF Val66Met (rs6265) and COMT Val158Met (rs4680) with neurocognition in a treatment-seeking alcohol dependent cohort and determine if neurocognitive differences between non-smokers and smokers previously observed in this cohort persist when controlled for these functional SNPs. Genotyping was conducted on 70 primarily male treatment-seeking alcohol dependent participants (ALC) who completed a comprehensive neuropsychological battery after 33 +/- 9 days of monitored abstinence. After controlling for COMT and BDNF genotypes, smoking ALC performed significantly worse than non-smoking ALC on the domains of auditory-verbal and visuospatial learning and memory, cognitive efficiency, general intelligence, processing speed, and global neurocognition. In smoking ALC, greater number of years of smoking over lifetime was related to poorer performance on multiple domains after controlling for genotypes and alcohol consumption. In addition, COMT Met homozygotes were superior to Val homozygotes on measures of executive skills and showed trends for higher general intelligence and visuospatial skills, while COMT Val/Met heterozygotes showed significantly better general intelligence than Val homozygotes. COMT Val homozygotes performed better than heterozygotes on auditory-verbal memory. BDNF genotype was not related to any neurocognitive domain. The findings are consistent with studies in normal controls and neuropsychiatric cohorts that reported COMT Met carriers demonstrated better performance on measures of executive skills and general intelligence. Results also indicated that the poorer performance of smoking compared to non-smoking ALC across multiple neurocognitive domains was not mediated by COMT or BDNF genotype. Overall, the findings lend support to the expanding clinical movement to make smoking cessation programs available to smokers at the inception of treatment for alcohol/substance use disorders.
C1 [Durazzo, Timothy C.; Fryer, Susanna L.; Mon, Anderson; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA.
[Durazzo, Timothy C.; Fryer, Susanna L.; Mon, Anderson; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Hutchison, Kent E.] Univ Colorado, Boulder, CO 80309 USA.
RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA.
EM timothy.durazzo@ucsf.edu
FU National Institute on Alcohol Abuse and Alcoholism [AA10788, AA012238];
National Institute on Drug Abuse [DA24136]
FX This material is the result of work supported by the National Institute
on Alcohol Abuse and Alcoholism (AA10788 to Dieter J. Meyerhoff;
AA012238 to Kent E. Hutchison) and the National Institute on Drug Abuse
(DA24136 to Timothy C. Durazzo) with resources and the use of facilities
at the San Francisco Veterans Administration Medical Center, San
Francisco, CA, USA. We thank Mary Rebecca Young, Kathleen Altieri, Ricky
Chen, and Drs. Peter Banys and Ellen Herbst of the Veterans
Administration Substance Abuse Day Hospital (which routinely offers
smoking cessation with substance abuse treatment), and Dr. David Pating,
Karen Moise, and their colleagues at the Kaiser Permanente Chemical
Dependency Recovery Program in San Francisco for their valuable
assistance in recruiting participants. We thank Dr. Wendy Ooteman for
assistance in collecting blood samples for DNA extraction. We also wish
to extend our gratitude to the study participants, who made this
research possible.
NR 86
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U1 1
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PY 2012
VL 3
AR UNSP 178
DI 10.3389/fphar.2012.00178
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA V35XE
UT WOS:000209177700172
PM 23087644
ER
PT J
AU Kazantsev, AG
Outeiro, TF
AF Kazantsev, Aleksey G.
Outeiro, Tiago F.
TI Editorial on special topic: sirtuins in metabolism, aging, and disease
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Editorial Material
C1 [Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Kazantsev, Aleksey G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Outeiro, Tiago F.] Univ Med Goettingen, Dept NeuroDegenerat & Restorat Res, Gottingen, Germany.
RP Kazantsev, AG (reprint author), Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
EM akazantsev@partners.org
NR 0
TC 3
Z9 3
U1 0
U2 1
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PY 2012
VL 3
AR UNSP 71
DI 10.3389/fphar.2012.00071
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA V35XE
UT WOS:000209177700069
PM 22536186
ER
PT J
AU Martinez-Pastor, B
Mostoslavsky, R
AF Martinez-Pastor, Barbara
Mostoslavsky, Raul
TI Sirtuins, metabolism, and cancer
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Review
DE SIRT1; SIRT6; SIRT3; Warburg effect; cancer metabolism; DNA repair;
genomic instability; sirtuin biology
AB More than a decade ago, sirtuins were discovered as a highly conserved family of NAD+dependent enzymes that extend lifespan in lower organisms. In mammals, sirtuins are key regulators of stress responses and metabolism, influencing a range of diseases, including diabetes, neurodegeneration, and cancer. In recent years, new functions of sirtuins have been characterized, uncovering the underlying mechanisms of their multifaceted role in metabolism. Here, we specifically review recent progress on the role of sirtuins in DNA repair and energy metabolism, further discussing the implication of sirtuins in the biology of cancer.
C1 [Martinez-Pastor, Barbara; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
RP Mostoslavsky, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, 185 Cambridge St, Boston, MA 02114 USA.
EM rmostoslavsky@mgh.harvard.edu
NR 61
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U2 5
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PY 2012
VL 3
AR UNSP 22
DI 10.3389/fphar.2012.00022
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA V35XE
UT WOS:000209177700022
PM 22363287
ER
PT J
AU Spires-Jones, TL
Fox, LM
Rozkalne, A
Pitstick, R
Carlson, GA
Kazantsev, AG
AF Spires-Jones, Tara L.
Fox, Leora M.
Rozkalne, Anete
Pitstick, Rose
Carlson, George A.
Kazantsev, Aleksey G.
TI Inhibition of sirtuin 2 with sulfobenzoic acid derivative AK1 is
non-toxic and potentially neuroprotective in a mouse model of
frontotemporal dementia
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Article
DE tauopathy; frontotemporal dementia; Alzheimer; sirtuin; neuroprotection
AB Tauopathies including tau-associated Frontotemporal dementia (FTD) and Alzheimer's disease are characterized pathologically by the formation of tau-containing neurofibrillary aggregates and neuronal loss, which contribute to cognitive decline. There are currently no effective treatments to prevent or slow this neural systems failure. The rTg4510 mouse model, which expresses a mutant form of the tau protein associated with FTD with Parkinsonism-17, undergoes dramatic hippocampal and cortical neuronal loss making it an ideal model to study treatments for FTD-related neuronal loss. Sirtuins are a family of proteins involved in cell survival that have the potential to modulate neuronal loss in neurodegenerative disorders. Here we tested the hypothesis that sirtuin 2 (SIRT2) inhibition would be non-toxic and prevent neurodegeneration in rTg4510 brain. In this study we delivered SIRT2 inhibitor AK1 directly to the hippocampus with an osmotic minipump and confirmed that it reached the target region both with histological assessment of delivery of a dye and with a pharmacodynamic marker, ABCA1 transcription, which was upregulated with AK1 treatment. AK1 treatment was found to be safe in wild-type mice and in the rTg4510 mouse model, and further, it provided some neuroprotection in the rTg4510 hippocampal circuitry. This study provides proof-of-concept for therapeutic benefits of SIRT2 inhibitors in both tau-associated FTD and Alzheimer's disease, and suggests that development of potent, brain permeable SIRT2 inhibitors is warranted.
C1 [Spires-Jones, Tara L.; Fox, Leora M.; Rozkalne, Anete; Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
[Pitstick, Rose; Carlson, George A.] McLaughlin Res Inst, Great Falls, MT USA.
RP Spires-Jones, TL (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, 114 16 St, Charlestown, MA 02129 USA.
EM tspires@partners.org
OI Spires-Jones, Tara/0000-0003-2530-0598
FU Alzheimer's Disease Drug Discovery Foundation; Association for
Frontotemporal Degeneration; Harvard Medical School Claflin Award; NIH
[AG08487, K99AG33670]; Alzheimer's Association Zenith Award; M. J.
Murdock Charitable Trust; Montana's Department of Commerce;
Browning-Kimball Foundation; Oakland family; Sletten Construction
FX This study was funded by the Alzheimer's Disease Drug Discovery
Foundation and the Association for Frontotemporal Degeneration, Harvard
Medical School Claflin Award, NIH grants AG08487, K99AG33670, and the
Alzheimer's Association Zenith Award. Renovations to McLaughlin Research
Institute's Animal Resource Center were funded by major grants and
donations from the M. J. Murdock Charitable Trust, Montana's Department
of Commerce, the Browning-Kimball Foundation, the Oakland family,
Sletten Construction, and Ian & Nancy Davidson. We thank Prof Brad Hyman
for his discussions on the project.
NR 23
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PY 2012
VL 3
AR UNSP 42
DI 10.3389/fphar.2012.00042
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA V35XE
UT WOS:000209177700042
PM 22416232
ER
PT J
AU Chen, Z
Barbieri, R
AF Chen, Zhe
Barbieri, Riccardo
TI Editorial: engineering approaches to study cardiovascular physiology:
modeling, estimation, and signal processing
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Editorial Material
C1 [Chen, Zhe; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab,Dept Anesthesia Crit Care &, Boston, MA 02138 USA.
[Chen, Zhe; Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
RP Chen, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab,Dept Anesthesia Crit Care &, Boston, MA 02138 USA.
EM zhechen@mit.edu
OI Barbieri, Riccardo/0000-0001-9381-3833; Chen, Zhe/0000-0002-6483-6056
NR 10
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U1 0
U2 1
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PY 2012
VL 3
AR UNSP 425
DI 10.3389/fphys.2012.00425
PG 2
WC Physiology
SC Physiology
GA V35UH
UT WOS:000209173000418
PM 23133425
ER
PT J
AU Chen, Z
Purdon, PL
Brown, EN
Barbieri, R
AF Chen, Zhe
Purdon, Patrick L.
Brown, Emery N.
Barbieri, Riccardo
TI A unified point process probabilistic framework to assess heartbeat
dynamics and autonomic cardiovascular control
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Review
DE autonomic cardiovascular control; heart rate variability; baroreflex
sensitivity; respiratory sinus arrhythmia; point process;
Wiener-Volterra expansion; general anesthesia
AB In recent years, time-varying inhomogeneous point process models have been introduced for assessment of instantaneous heartbeat dynamics as well as specific cardiovascular control mechanisms and hemodynamics. Assessment of the model's statistics is established through the Wiener-Volterra theory and a multivariate autoregressive (AR) structure. A variety of instantaneous cardiovascular metrics, such as heart rate (HR), heart rate variability (HRV), respiratory sinus arrhythmia (RSA), and baroreceptor-cardiac reflex (baroreflex) sensitivity (BRS), are derived within a parametric framework and instantaneously updated with adaptive and local maximum likelihood estimation algorithms. Inclusion of second-order non-linearities, with subsequent bispectral quantification in the frequency domain, further allows for definition of instantaneous metrics of non-linearity. We here present a comprehensive review of the devised methods as applied to experimental recordings from healthy subjects during propofol anesthesia. Collective results reveal interesting dynamic trends across the different pharmacological interventions operated within each anesthesia session, confirming the ability of the algorithm to track important changes in cardiorespiratory elicited interactions, and pointing at our mathematical approach as a promising monitoring tool for an accurate, non-invasive assessment in clinical practice. We also discuss the limitations and other alternative modeling strategies of our point process approach.
C1 [Chen, Zhe; Purdon, Patrick L.; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA.
[Chen, Zhe; Purdon, Patrick L.; Brown, Emery N.; Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Brown, Emery N.] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Chen, Z (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA.
EM zhechen@mit.edu
OI Barbieri, Riccardo/0000-0001-9381-3833; Chen, Zhe/0000-0002-6483-6056
FU NIH [R01-HL084502, DP1-OD003646, K25-NS05758, DP2-OD006454]; CRC UL1
[RR025758]
FX The authors thank L. Citi, K. Habeeb, G, Harrell, It Merhar, E. T.
Pierce, A. Salazar, C. Tavares, and J. Walsh (Massachusetts General
Hospital) for assistance with data collection and interpretation.
Preliminary results of this article have been presented in Proc. IEEE
EMBC'10, Buenos Aires, and Proc. IEEE EMBC'11, Boston, MA. The work as
supported in part by NIH Grants R01-HL084502 (Riccardo Barbieri),
DP1-OD003646 (Emery N. Brown), K25-NS05758 (Patrick I. Purdon),
DP2-OD006454 (Patrick I. Purdon), as well as a CRC UL1 grant RR025758.
NR 72
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PY 2012
VL 3
AR UNSP 4
DI 10.3389/fphys.2012.00004
PG 14
WC Physiology
SC Physiology
GA V35UH
UT WOS:000209173000004
PM 22375120
ER
PT J
AU Dehghani, N
Hatsopoulos, NG
Haga, ZD
Parker, RA
Greger, B
Halgren, E
Cash, SS
Destexhe, A
AF Dehghani, Nima
Hatsopoulos, Nicholas G.
Haga, Zach D.
Parker, Rebecca A.
Greger, Bradley
Halgren, Eric
Cash, Sydney S.
Destexhe, Alain
TI Avalanche analysis from multielectrode ensemble recordings in cat,
monkey, and human cerebral cortex during wakefulness and sleep
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Article
DE criticality; self-organization; brain dynamics; scale invariance;
complexity; power-law
AB Self-organized critical states are found in many natural systems, from earthquakes to forest fires, they have also been observed in neural systems, particularly, in neuronal cultures. However, the presence of critical states in the awake brain remains controversial. Here, we compared avalanche analyses performed on different in vivo preparations during wakefulness, slow-wave sleep, and REM sleep, using high density electrode arrays in cat motor cortex (96 electrodes), monkey motor cortex and premotor cortex and human temporal cortex (96 electrodes) in epileptic patients. In neuronal avalanches defined from units (up to 160 single units), the size of avalanches never clearly scaled as power-law, but rather scaled exponentially or displayed intermediate scaling. We also analyzed the dynamics of local field potentials (LFPs) and in particular LFP negative peaks (nLFPs) among the different electrodes (up to 96 sites in temporal cortex or up to 128 sites in adjacent motor and premotor cortices). In this case, the avalanches defined from nLFPs displayed power-law scaling in double logarithmic representations, as reported previously in monkey. However, avalanche defined as positive LFP (pLFP) peaks, which are less directly related to neuronal firing, also displayed apparent power-law scaling. Closer examination of this scaling using the more reliable cumulative distribution function (CDF) and other rigorous statistical measures, did not confirm power-law scaling. The same pattern was seen for cats, monkey, and human, as well as for different brain states of wakefulness and sleep. We also tested other alternative distributions. Multiple exponential fitting yielded optimal fits of the avalanche dynamics with bi-exponential distributions. Collectively, these results show no clear evidence for power-law scaling or self-organized critical states in the awake and sleeping brain of mammals, from cat to man.
C1 [Dehghani, Nima; Destexhe, Alain] CNRS, Lab Computat Neurosci, Unite Neurosci Informat & Complexite, Gif Sur Yvette, France.
[Hatsopoulos, Nicholas G.; Haga, Zach D.] Univ Chicago, Dept Organismal Biol & Anat, Comm Computat Neurosci, Chicago, IL 60637 USA.
[Parker, Rebecca A.] Univ Utah, Interdept Program Neurosci, Salt Lake City, UT USA.
[Greger, Bradley] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA.
[Halgren, Eric] Univ Calif San Diego, Multimodal Imaging Lab, Dept Neurosci, La Jolla, CA 92093 USA.
[Halgren, Eric] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
[Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Dehghani, N (reprint author), CNRS, Lab Computat Neurosci, Unite Neurosci Informat & Complexite, 1 Ave Terrasse, Gif Sur Yvette, France.
EM dehghani@unic.cnrs-gif.fr; destexhe@unic.cnrs-gif.fr
OI Dehghani, Nima/0000-0003-2032-8903; Destexhe, Alain/0000-0001-7405-0455;
Greger, Bradley/0000-0002-6702-7596
FU Centre National de la Recherche Scientifique (CNRS, France); Agence
Nationale de la Recherche (ANR, France); European Community Future and
Emerging Technologies program (BRAINSCALES grant) [FP7-269921]; National
Institutes of Health (NIH) [5R01N5062092, R01 EB009282]; DARPA
[BAA05-26]; Ecole de Neurosciences de Paris (ENP)
FX Research supported by Centre National de la Recherche Scientifique
(CNRS, France), Agence Nationale de la Recherche (ANR, France), European
Community Future and Emerging Technologies program (BRAINSCALES grant
FP7-269921), the National Institutes of Health (NIH grants 5R01N5062092,
R01 EB009282), and DARPA (BAA05-26, Revolutionizing Prosthetics). Nima
Dehghani is supported by a fellowship from Ecole de Neurosciences de
Paris (ENP).
NR 32
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U1 0
U2 2
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PY 2012
VL 3
AR UNSP 302
DI 10.3389/fphys.2012.00302
PG 18
WC Physiology
SC Physiology
GA V35UH
UT WOS:000209173000296
PM 22934053
ER
PT J
AU Kang, JX
AF Kang, Jing X.
TI Reduction of heart rate by omega-3 fatty acids and the potential
underlying mechanisms
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Review
DE omega-3 fatty acids; cardiac sudden death; heart rate; membrane
electrical excitability; ion channel inhibition
AB An elevated resting heart rate is one of the strongest predictors of cardiovascular mortality and is independently associated with sudden cardiac death (SCD). Agents capable of reducing heart rate without significant side effects are therefore of particular interest for the prevention of SCD. Recent human and animal studies have shown that omega-3 fatty acids can reduce heart rate. Our work has shown that omega-3 fatty acids significantly reduce membrane electrical excitability of the cardiac myocyte by lowering its resting membrane potential and the duration of the refractory period through inhibition of ion channels. We propose that these actions may be the underlying mechanisms for the omega-3 fatty acid-induced reduction of heart rate observed in both humans and animals. The heart rate lowering capability of omega-3 fatty acids may contribute to their preventive effect against SCD.
C1 [Kang, Jing X.] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA.
[Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA.
RP Kang, JX (reprint author), Massachusetts Gen Hosp, Lab Lipid Med & Technol, 149 13th St,Room 4001, Charlestown, MA 02129 USA.
EM kang.jing@mgh.harvard.edu
NR 41
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U1 1
U2 2
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PY 2012
VL 3
AR UNSP 416
DI 10.3389/fphys.2012.00416
PG 6
WC Physiology
SC Physiology
GA V35UH
UT WOS:000209173000409
PM 23115552
ER
PT J
AU Lai, CPK
Breakefield, XO
AF Lai, Charles Pin-Kuang
Breakefield, Xandra Owen
TI Role of exosomes/microvesicles in the nervous system and use in emerging
therapies
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Review
DE microvesicles; exosomes; neuron; neuroregeneration; neurodegeneration;
development; cancer; therapy
AB Extracellular membrane vesicles (EMVs) are nanometer sized vesicles, including exosomes and microvesicles capable of transferring DNAs, mRNAs, microRNAs, non-coding RNAs, proteins, and lipids among cells without direct cell-to-cell contact, thereby representing a novel form of intercellular communication. Many cells in the nervous system have been shown to release EMVs, implicating their active roles in development, function, and pathologies of this system. While substantial progress has been made in understanding the biogenesis, biophysical properties, and involvement of EMVs in diseases, relatively less information is known about their biological function in the normal nervous system. In addition, since EMVs are endogenous vehicles with low immunogenicity, they have also been actively investigated for the delivery of therapeutic genes/molecules in treatment of cancer and neurological diseases. The present review summarizes current knowledge about EMV functions in the nervous system under both physiological and pathological conditions, as well as emerging EMV-based therapies that could be applied to the nervous system in the foreseeable future.
C1 [Lai, Charles Pin-Kuang; Breakefield, Xandra Owen] Harvard Univ, Sch Med, Dept Neurol, Neurosci Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Lai, Charles Pin-Kuang; Breakefield, Xandra Owen] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
[Lai, Charles Pin-Kuang; Breakefield, Xandra Owen] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA.
RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, 13th St,Bldg 149, Charlestown, MA 02129 USA.
EM breakefield@hms.harvard.edu
RI Lai, Charles/D-5442-2017
FU NIH/NCI [CA141150, CA069246]; Canadian Institutes of Health Research
FX We wish to thank Ms. Suzanne McDavitt for skilled editorial assistance.
This review was supported by grants NIH/NCI CA141150 and CA069246
(Xandra Owen Breakefield) and the Canadian Institutes of Health Research
(Charles Pin-Kuang Lai).
NR 200
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PY 2012
VL 3
AR UNSP 228
DI 10.3389/fphys.2012.00228
PG 14
WC Physiology
SC Physiology
GA V35UH
UT WOS:000209173000223
PM 22754538
ER
PT J
AU Momen-Heravi, F
Balaj, L
Alian, S
Tigges, J
Toxavidis, V
Ericsson, M
Distel, RJ
Ivanov, AR
Skog, J
Kuo, WP
AF Momen-Heravi, Fatemeh
Balaj, Leonora
Alian, Sara
Tigges, John
Toxavidis, Vasilis
Ericsson, Maria
Distel, Robert J.
Ivanov, Alexander R.
Skog, Johan
Kuo, Winston Patrick
TI Alternative methods for characterization of extracellular vesicles
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Review
DE characterization; concentration; methods; exosome; extracellular
vesicles; microvesicles; size
AB Extracellular vesicles (ECVs) are nano-sized vesicles released by all cells in vitro as well as in vivo. Their role has been implicated mainly in cell-cell communication, but also in disease biomarkers and more recently in gene delivery. They represent a snapshot of the cell status at the moment of release and carry bioreactive macromolecules such as nucleic acids, proteins, and lipids. A major limitation in this emerging new field is the availability/awareness of techniques to isolate and properly characterize ECVs. The lack of gold standards makes comparing different studies very difficult and may potentially hinder some ECVs-specific evidence. Characterization of ECVs has also recently seen many advances with the use of Nanoparticle Tracking Analysis, flow cytometry, cryo-electron microscopy instruments, and proteomic technologies. In this review, we discuss the latest developments in translational technologies involving characterization methods including the facts in their support and the challenges they face.
C1 [Momen-Heravi, Fatemeh; Distel, Robert J.; Kuo, Winston Patrick] Harvard Univ, Sch Med, Harvard Catalyst Lab Innovat Translat Technol, Boston, MA 02115 USA.
[Balaj, Leonora] Massachusetts Gen Hosp, Dept Neurol & Radiol, Boston, MA 02114 USA.
[Alian, Sara] Harvard Univ, Sch Med, Biopolymers Facil, Boston, MA 02115 USA.
[Tigges, John; Toxavidis, Vasilis] Harvard Univ, Sch Med, Harvard Stem Cell Inst, BIDMC Flow Cytometry Core Facil, Boston, MA 02115 USA.
[Ericsson, Maria] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Distel, Robert J.] Dana Farber Canc Inst, Translat Res Lab, Boston, MA 02115 USA.
[Ivanov, Alexander R.] Northeastern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA.
[Skog, Johan] Exosome Diagnost Inc, New York, NY USA.
[Kuo, Winston Patrick] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
RP Kuo, WP (reprint author), Harvard Univ, Sch Med, Harvard Catalyst Lab Innovat Translat Technol, 4 Blackfan Circle,Room 144, Boston, MA 02115 USA.
EM wkuo@catalyst.harvard.edu
OI Momen-Heravi, Fatemeh/0000-0003-4534-1450
FU Harvard Catalyst - The Harvard Clinical and Translational Science Center
(NIH) [UL1 RR 025758]; Harvard University; academic health care centers
FX This work was conducted, at least in part, through the Harvard Catalyst
Laboratory for Innovative Translational Technologies (HC-LITT) with
support from Harvard Catalyst - The Harvard Clinical and Translational
Science Center (NIH 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 53
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U1 1
U2 28
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PY 2012
VL 3
AR 354
DI 10.3389/fphys.2012.00354
PG 8
WC Physiology
SC Physiology
GA V35UH
UT WOS:000209173000348
PM 22973237
ER
PT J
AU Momen-Heravi, F
Balaj, L
Alian, S
Trachtenberg, AJ
Hochberg, FH
Skog, J
Kuo, WP
AF Momen-Heravi, Fatemeh
Balaj, Leonora
Alian, Sara
Trachtenberg, Alexander J.
Hochberg, Fred H.
Skog, Johan
Kuo, Winston Patrick
TI Impact of biofluid viscosity on size and sedimentation efficiency of the
isolated microvesicles
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Article
DE biofluids; viscosity; micovesicles; sedimentation efficiency; size;
ultracentrifugation
AB Microvesicles are nano-sized lipid vesicles released by all cells in vivo and in vitro. They are released physiologically under normal conditions but their rate of release is higher under pathological conditions such as tumors. Once released they end up in the systemic circulation and have been found and characterized in all biofluids such as plasma, serum, cerebrospinal fluid, breast milk, ascites, and urine. Microvesicles represent the status of the donor cell they are released from and they are currently under intense investigation as a potential source for disease biomarkers. Currently, the "gold standard" for isolating microvesicles is ultracentrifugation, although alternative techniques such as affinity purification have been explored. Viscosity is the resistance of a fluid to a deforming force by either shear or tensile stress. The different chemical and molecular compositions of biofluids have an effect on its viscosity and this could affect movements of the particles inside the fluid. In this manuscript we addressed the issue of whether viscosity has an effect on sedimentation efficiency of microvesicles using ultracentrifugation. We used different biofluids and spiked them with polystyrene beads and assessed their recovery using the Nanoparticle Tracking Analysis. We demonstrate that MVs recovery inversely correlates with viscosity and as a result, sample dilutions should be considered prior to ultracentrifugation when processing any biofluids.
C1 [Momen-Heravi, Fatemeh; Trachtenberg, Alexander J.; Kuo, Winston Patrick] Harvard Univ, Sch Med, Harvard Catalyst Lab Innovat Translat Technol, Boston, MA 02115 USA.
[Balaj, Leonora; Hochberg, Fred H.] Massachusetts Gen Hosp, Dept Neurol & Radiol, Boston, MA 02114 USA.
[Balaj, Leonora] Canc Ctr Amsterdam, Neurooncol Res Grp, Amsterdam, Netherlands.
[Alian, Sara] Harvard Univ, Sch Med, Biopolymers Facil, Boston, MA 02115 USA.
[Skog, Johan] Exosome Diagnost Inc, New York, NY USA.
[Kuo, Winston Patrick] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
RP Kuo, WP (reprint author), Harvard Univ, Sch Med, Harvard Catalyst Lab Innovat Translat Technol, 4 Blackfan Circle,Room 144, Boston, MA 02115 USA.
EM wkuo@catalyst.harvard.edu
OI Momen-Heravi, Fatemeh/0000-0003-4534-1450
FU Harvard Catalyst/The Harvard Clinical and Translational Science Center
(NIH Award) [UL1 RR 025758]; Harvard University
FX We thank Xandra Breakefield for helpful discussions. This work was
conducted, at least in part, through the Harvard Catalyst Laboratory for
Innovative Translational Technologies (HC-LITT) with support from
Harvard Catalyst/The Harvard Clinical and Translational Science Center
(NIH 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 27
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U1 2
U2 9
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PY 2012
VL 3
AR UNSP 162
DI 10.3389/fphys.2012.00162
PG 6
WC Physiology
SC Physiology
GA V35UH
UT WOS:000209173000159
PM 22661955
ER
PT J
AU Yuan, JZ
Liu, YN
Tan, T
Guha, S
Gukovsky, I
Gukovskaya, A
Pandol, SJ
AF Yuan, Jingzhen
Liu, Yannan
Tan, Tanya
Guha, Sushovan
Gukovsky, Ilya
Gukovskaya, Anna
Pandol, Stephen J.
TI Protein kinase D regulates cell death pathways in experimental
pancreatitis
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Article
DE pancreatic acinar cells; CCK; CID755673; CRT0066101; apoptosis; necrosis
AB Inflammation and acinar cell necrosis are two major pathological responses of acute pancreatitis, a serious disorder with no current therapies directed to its molecular pathogenesis. Serine/threonine protein kinase D family, which includes PKD/PKD1, PKD2, and PKD3, has been increasingly implicated in the regulation of multiple physiological and pathophysiological effects. We recently reported that PKD/PKD1, the predominant PKD isoform expressed in rat pancreatic acinar cells, mediates early events of pancreatitis including NE-kappa B activation and inappropriate intracellular digestive enzyme activation. In current studies, we investigated the role and mechanisms of PKD/PKD1 in the regulation of necrosis in pancreatic acinar cells by using two novel small molecule PKD inhibitors CID755673 and CR10066101 and molecular approaches in in vitro and in vivo experimental models of acute pancreatitis. Our results demonstrated that both CID755673 and CR10066101 are PKD-specific inhibitors and that PKD/PKD1 inhibition by either the chemical inhibitors or specific PKD/PKD1 siRNAs attenuated necrosis while promoting apoptosis induced by pathological doses of cholecystokinin-octapeptide (CCK) in pancreatic acinar cells. Conversely, up-regulation of PKD expression in pancreatic acinar cells increased necrosis and decreased apoptosis. We further showed that PKD/PKD1 regulated several key cell death signals including inhibitors of apoptotic proteins, caspases, receptor-interacting protein kinase 1 to promote necrosis. PKD/PKD1 inhibition by CID755673 significantly ameliorated necrosis and severity of pancreatitis in an in vivo experimental model of acute pancreatitis. Thus, our studies indicate that PKD/PKD1 is a key mediator of necrosis in acute pancreatitis and that PKD/PKD1 may represent a potential therapeutic target in acute pancreatitis.
C1 [Yuan, Jingzhen; Liu, Yannan; Tan, Tanya; Gukovsky, Ilya; Gukovskaya, Anna; Pandol, Stephen J.] Univ Calif Los Angeles, South California Res Ctr Alcohol Liver & Pancreat, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
[Liu, Yannan] Beijing Hosp, Beijing, Peoples R China.
[Guha, Sushovan] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA.
RP Yuan, JZ (reprint author), Univ Calif Los Angeles, South California Res Ctr Alcohol Liver & Pancreat, Vet Affairs Greater Los Angeles Healthcare Syst, West Los Angeles VA Healthcare Ctr, 11301 Wilshire Blvd,Bldg 258,Room 340, Los Angeles, CA 90073 USA.
EM jzyuan@ucla.edu
FU Department of Veterans Affairs Merits Grant; Southern California
Research Center for Alcoholic Liver and Pancreatic Diseases (NIH)
[P50-A11999]; UCLA Center of Excellence in Pancreatic Diseases (NIH)
[1P01AT0003960-01]; Lee Summer Student Research Award from Southern
California Research Center for Liver and Pancreatic Diseases
FX The authors would like to thank Dr. Aurelia Lugea for discussion and
help in animal experiment design and TUNEL staining, Dr. Olga Mareninova
for discussion of acinar cell staining. The authors also thank Dr. Edwin
Thrower (Yale University School of Medicine) and Dr. Christopher R.
Ireson and his group at the Cancer Research Technology Discovery
Laboratories, London, UK for providing us with CR10066101. This study
was supported by the Department of Veterans Affairs Merits Grant and the
Southern California Research Center for Alcoholic Liver and Pancreatic
Diseases (NIH Grant P50-A11999); UCLA Center of Excellence in Pancreatic
Diseases (NIH Grant 1P01AT0003960-01); and Lee Summer Student Research
Award from Southern California Research Center for Liver and Pancreatic
Diseases (to Tanya Tan).
NR 51
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PY 2012
VL 3
AR UNSP 60
DI 10.3389/fphys.2012.00060
PG 17
WC Physiology
SC Physiology
GA V35UH
UT WOS:000209173000059
PM 22470346
ER
PT J
AU Zhang, Z
Sun, K
Saloner, DA
Wallace, AW
Ge, L
Baker, AJ
Guccione, JM
Ratcliffe, MB
AF Zhang, Zhihong
Sun, Kay
Saloner, David A.
Wallace, Arthur W.
Ge, Liang
Baker, Anthony J.
Guccione, Julius M.
Ratcliffe, Mark B.
TI The benefit of enhanced contractility in the infarct borderzone: a
virtual experiment
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Article
DE myocardial Infarction; borderzone; finite element
AB Objectives: Contractile function in the normally perfused infarct borderzone (BZ) is depressed. However, the impact of reduced BZ contractility on left ventricular (LV) pump function is unknown. As a consequence, there have been no therapies specifically designed to improve BZ contractility. We tested the hypothesis that an improvement in borderzone contractility will improve LV pump function. Methods: From a previously reported study, magnetic resonance imaging (MRI) images with non-invasive tags were used to calculate 3D myocardial strain in five sheep 16 weeks after anteroapical myocardial infarction. Animal-specific finite element (FE) models were created using MRI data and LV pressure obtained at early diastolic filling. Analysis of borderzone function using those FE models has been previously reported. Chamber stiffness, pump function (Starling's law) and stress in the fiber, cross fiber, and circumferential directions were calculated. Animal-specific FE models were performed for three cases: (a) impaired BZ contractility (INJURED); (b) BZ-contractility fully restored (100% BZ IMPROVEMENT); or (c) BZ-contractility partially restored (50% BZ IMPROVEMENT). Results: 100% BZ IMPROVEMENT and 50% BZ IMPROVEMENT both caused an upward shift in the Starling relationship, resulting in a large (36 and 26%) increase in stroke volume at LVPED = 20 mmHg (8.0 ml, p < 0.001). Moreover, there were a leftward shift in the end-systolic pressure volume relationship, resulting in a 7 and 5% increase in LVPES at 110 mmHg (7.7 ml, p < 0.005). It showed that even 50% BZ IMPROVEMENT was sufficient to drive much of the calculated increase in function. Conclusion: Improved borderzone contractility has a beneficial effect on LV pump function. Partial improvement of borderzone contractility was sufficient to drive much of the calculated increase in function. Therapies specifically designed to improve borderzone contractility should be developed.
C1 [Zhang, Zhihong; Sun, Kay; Ge, Liang; Guccione, Julius M.; Ratcliffe, Mark B.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA.
[Zhang, Zhihong; Sun, Kay; Saloner, David A.; Wallace, Arthur W.; Ge, Liang; Baker, Anthony J.; Guccione, Julius M.; Ratcliffe, Mark B.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[Saloner, David A.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA.
[Wallace, Arthur W.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA.
[Ge, Liang; Guccione, Julius M.; Ratcliffe, Mark B.] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA.
[Baker, Anthony J.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA.
EM mark.ratcliffe@va.gov
FU NIH [R01-HL-77921, R01-HL-63348]
FX This study was supported by NIH grant R01-HL-77921 (Dr. Guccione), and
R01-HL-63348 (Dr. Ratcliffe). This support is gratefully acknowledged.
NR 19
TC 3
Z9 3
U1 0
U2 0
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PY 2012
VL 3
AR UNSP 86
DI 10.3389/fphys.2012.00086
PG 6
WC Physiology
SC Physiology
GA V35UH
UT WOS:000209173000084
PM 22509168
ER
PT J
AU Clark, DG
AF Clark, David Glenn
TI Storage costs and heuristics interact to produce patterns of aphasic
sentence comprehension performance
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE aphasia; syntax; semantics; sentence comprehension
AB Background: Despite general agreement that aphasic individuals exhibit difficulty understanding complex sentences, the nature of sentence complexity itself is unresolved. In addition, aphasic individuals appear to make use of heuristic strategies for understanding sentences. This research is a comparison of predictions derived from two approaches to the quantification of sentence complexity, one based on the hierarchical structure of sentences, and the other based on dependency locality theory (DLT). Complexity metrics derived from these theories are evaluated under various assumptions of heuristic use.
Method: A set of complexity metrics was derived from each general theory of sentence complexity and paired with assumptions of heuristic use. Probability spaces were generated that summarized the possible patterns of performance across 16 different sentence structures. The maximum likelihood of comprehension scores of 42 aphasic individuals was then computed for each probability space and the expected scores from the best-fitting points in the space were recorded for comparison to the actual scores. Predictions were then compared using measures of fit quality derived from linear mixed effects models.
Results: All three of the metrics that provide the most consistently accurate predictions of patient scores rely on storage costs based on the DLT. Patients appear to employ an Agent Theme heuristic, but vary in their tendency to accept heuristically generated interpretations. Furthermore, the ability to apply the heuristic may be degraded in proportion to aphasia severity.
Conclusion: DLT-derived storage costs provide the best prediction of sentence comprehension patterns in aphasia. Because these costs are estimated by counting incomplete syntactic dependencies at each point in a sentence, this finding suggests that aphasia is associated with reduced availability of cognitive resources for maintaining these dependencies.
C1 [Clark, David Glenn] Birmingham VA Med Ctr, Birmingham, AL USA.
[Clark, David Glenn] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA.
RP Clark, DG (reprint author), Univ Alabama Birmingham, Dept Neurol, 1720 7th Ave South SC 620C, Birmingham, AL 35294 USA.
EM dgclark@uab.edu
NR 64
TC 0
Z9 0
U1 3
U2 5
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PY 2012
VL 3
AR 135
DI 10.3389/fpsyg.2012.00135
PG 19
WC Psychology, Multidisciplinary
SC Psychology
GA V31DI
UT WOS:000208863900147
PM 22590462
ER
PT J
AU Gow, DW
Caplan, DN
AF Gow, David W., Jr.
Caplan, David N.
TI New levels of language processing complexity and organization revealed
by Granger causation
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Review
DE Granger causation analysis; MEG; EEG; effective connectivity; rich-club
connectivity; small world connectivity; superior temporal gyrus; speech
perception
AB Granger causation analysis of high spatiotemporal resolution reconstructions of brain activation offers a new window on the dynamic interactions between brain areas that support language processing. Premised on the observation that causes both precede and uniquely predict their effects, this approach provides an intuitive, model-free means of identifying directed causal interactions in the brain. It requires the analysis of all non-redundant potentially interacting signals, and has shown that even "early" processes such as speech perception involve interactions of many areas in a strikingly large network that extends well beyond traditional left hemisphere perisylvian cortex that play out over hundreds of milliseconds. In this paper we describe this technique and review several general findings that reframe the way we think about language processing and brain function in general. These include the extent and complexity of language processing networks, the central role of interactive processing dynamics, the role of processing hubs where the input from many distinct brain regions are integrated, and the degree to which task requirements and stimulus properties influence processing dynamics and inform our understanding of "language-specific" localized processes.
C1 [Gow, David W., Jr.; Caplan, David N.] Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA.
[Gow, David W., Jr.] Salem State Univ, Dept Psychol, Salem, MA USA.
[Gow, David W., Jr.; Caplan, David N.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Gow, David W., Jr.; Caplan, David N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Gow, DW (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Cognit & Behav Neurol Grp, 175 Cambridge St,Suite S340, Boston, MA 02114 USA.
EM gow@helix.mgh.harvard.edu
FU NIDCD NIH HHS [R01 DC003108]
NR 101
TC 7
Z9 7
U1 1
U2 7
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PY 2012
VL 3
AR 506
DI 10.3389/fpsyg.2012.00506
PG 11
WC Psychology, Multidisciplinary
SC Psychology
GA V31DJ
UT WOS:000208864000214
PM 23293611
ER
PT J
AU Kerr, DL
McLaren, DG
Mathy, RM
Nitschke, JB
AF Kerr, Deborah L.
McLaren, Donald G.
Mathy, Robin M.
Nitschke, Jack B.
TI Controllability modulates the anticipatory response in the human
ventromedial prefrontal cortex
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE controllability; anticipation; vmPFC; amygdala; fMRI; PPI; phobia
AB Research has consistently shown that control is critical to psychological functioning, with perceived lack of control considered to play a crucial role in the manifestation of symptoms in psychiatric disorders. In a model of behavioral control based on non-human animal work, Maier et al. (2006) posited that the presence of control activates areas of the ventromedial prefrontal cortex (vmPFC), which in turn inhibit the normative stress response in the dorsal raphe nucleus and amygdala. To test Maier's model in humans, we investigated the effects of control over potent aversive stimuli by presenting video clips of snakes to 21 snake phobics who were otherwise healthy with no comorbid psychopathologies. Based on prior research documenting that disrupted neural processing during the anticipation of adverse events can be influenced by different forms of cognitive processing such as perceptions of control, analyses focused on the anticipatory activity preceding the videos. We found that phobics exhibited greater vmPFC activity during the anticipation of snake videos when they had control over whether the videos were presented as compared to when they had no control over the presentation of the videos. In addition, observed functional connectivity between the vmPFC and the amygdala is consistent with previous work documenting vmPFC inhibition of the amygdala. Our results provide evidence to support the extension of Maier's model of behavioral control to include anticipatory function in humans.
C1 [Kerr, Deborah L.; Nitschke, Jack B.] Univ Wisconsin, Waisman Ctr Brain Imaging & Behav, Madison, WI 53705 USA.
[Kerr, Deborah L.; Nitschke, Jack B.] Univ Wisconsin, Dept Psychol, Madison, WI 53705 USA.
[McLaren, Donald G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[McLaren, Donald G.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[McLaren, Donald G.] Edith Nourse Rogers Mem VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bedford, MA USA.
[McLaren, Donald G.] Harvard Univ, Sch Med, Boston, MA USA.
[Mathy, Robin M.] Univ Oxford, Kellogg Coll, Oxford, England.
[Mathy, Robin M.] Univ Cambridge, Wolfson Coll, Cambridge, England.
[Mathy, Robin M.] Cent Oregon Commun Coll, Dept Social Sci, Bend, OR USA.
[Nitschke, Jack B.] Univ Wisconsin, Dept Psychiat, Madison, WI 53705 USA.
RP Kerr, DL (reprint author), Univ Wisconsin, Waisman Ctr Brain Imaging & Behav, 1500 Highland Ave, Madison, WI 53705 USA.
EM kerr.deborah@gmail.com
OI McLaren, Donald/0000-0002-0566-4610
FU NIA NIH HHS [K23 AG027171, P01 AG036694]; NICHD NIH HHS [P30 HD003352];
NIMH NIH HHS [K02 MH082130, K08 MH063984, R01 MH074847]
NR 76
TC 9
Z9 9
U1 1
U2 3
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PY 2012
VL 3
AR 557
DI 10.3389/fpsyg.2012.00557
PG 11
WC Psychology, Multidisciplinary
SC Psychology
GA V31DJ
UT WOS:000208864000263
PM 23550176
ER
PT J
AU Lebrecht, S
Bar, M
Barrett, LF
Tarr, MJ
AF Lebrecht, Sophie
Bar, Moshe
Barrett, Lisa Feldman
Tarr, Michael J.
TI Micro-valences: perceiving affective valence in everyday objects
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE affective valence; visual object perception; object recognition;
micro-valence; object preference
AB Perceiving the affective valence of objects influences how we think about and react to the world around us. Conversely, the speed and quality with which we visually recognize objects in a visual scene can vary dramatically depending on that scene's affective content. Although typical visual scenes contain mostly "everyday" objects, the affect perception in visual objects has been studied using somewhat atypical stimuli with strong affective valences (e.g., guns or roses). Here we explore whether affective valence must be strong or overt to exert an effect on our visual perception. We conclude that everyday objects carry subtle affective valences "micro-valences" which are intrinsic to their perceptual representation.
C1 [Lebrecht, Sophie] Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA.
[Bar, Moshe; Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA.
[Bar, Moshe; Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA.
[Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA.
[Tarr, Michael J.] Carnegie Mellon Univ, Ctr Neural Basis Cognit, Dept Psychol, Pittsburgh, PA 15213 USA.
RP Tarr, MJ (reprint author), Carnegie Mellon Univ, Ctr Neural Basis Cognit, Mellon Inst 115, 4400 Fifth Ave, Pittsburgh, PA 15213 USA.
EM michaeltarr@cmu.edu
NR 53
TC 19
Z9 19
U1 1
U2 2
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PY 2012
VL 3
AR 107
DI 10.3389/fpsyg.2012.00107
PG 5
WC Psychology, Multidisciplinary
SC Psychology
GA V31DI
UT WOS:000208863900119
PM 22529828
ER
PT J
AU Marinkovic, K
Rosen, BQ
Cox, B
Kovacevic, S
AF Marinkovic, Ksenija
Rosen, Burke Q.
Cox, Brendan
Kovacevic, Sanja
TI Event-related theta power during lexical-semantic retrieval and decision
conflict is modulated by alcohol intoxication: anatomically constrained
MEG
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE lexical decision; pseudowords; lexical-semantic retrieval; conflict
processing; inferior frontal; anterior cingulate; temporal cortex
AB Language processing is commonly characterized by an event-related increase in theta power (4-7 Hz) in scalp EEG. Oscillatory brain dynamics underlying alcohol's effects on language are poorly understood despite impairments on verbal tasks. To investigate how moderate alcohol intoxication modulates event-related theta activity during visual word processing, healthy social drinkers (N = 22, 11 females) participated in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. They performed a double-duty lexical decision task as they detected real words among non-words. An additional requirement to respond to all real words that also referred to animals induced response conflict. High density whole-head MEG signals and midline scalp EEG data were decomposed for each trial with Morlet wavelets. Each person's reconstructed cortical surface was used to constrain noise-normalized distributed minimum norm inverse solutions for theta frequencies. Alcohol intoxication increased reaction time and marginally affected accuracy. The overall spatio-temporal pattern is consistent with the left-lateralized fronto-temporal activation observed in language studies applying time-domain analysis. Event-related theta power was sensitive to the two functions manipulated by the task. First, theta estimated to the left-lateralized fronto-temporal areas reflected lexical-semantic retrieval, indicating that this measure is well suited for investigating the neural basis of language functions. While alcohol attenuated theta power overall, it was particularly deleterious to semantic retrieval since it reduced theta to real words but not pseudowords. Second, a highly overlapping prefrontal network comprising lateral prefrontal and anterior cingulate cortex was sensitive to decision conflict and was also affected by intoxication, in agreement with previous studies indicating that executive functions are especially vulnerable to alcohol intoxication.
C1 [Marinkovic, Ksenija; Rosen, Burke Q.; Kovacevic, Sanja] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
[Cox, Brendan] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Cox, Brendan] Harvard Univ, Sch Med, Boston, MA USA.
RP Marinkovic, K (reprint author), Univ Calif San Diego, Dept Radiol, 9500 Gilman Dr 0841, La Jolla, CA 92093 USA.
EM xenia@ucsd.edu
FU NCRR NIH HHS [S10 RR031599]; NIAAA NIH HHS [R01 AA016624, K01 AA013402]
NR 143
TC 9
Z9 9
U1 3
U2 6
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PY 2012
VL 3
AR 121
DI 10.3389/fpsyg.2012.00121
PG 14
WC Psychology, Multidisciplinary
SC Psychology
GA V31DI
UT WOS:000208863900133
PM 22536192
ER
PT J
AU Schendan, HE
Ganis, G
AF Schendan, Haline E.
Ganis, Giorgio
TI Electrophysiological potentials reveal cortical mechanisms for mental
imagery, mental simulation, and grounded (embodied) cognition
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE mental imagery; visual shape perception; object categorization; face
identification; semantic memory priming; visual knowledge; embodiment
and grounded cognition; event-related potential
AB Grounded cognition theory proposes that cognition, including meaning, is grounded in sensorimotor processing. The mechanism for grounding cognition is mental simulation, which is a type of mental imagery that re-enacts modal processing. To reveal top-down, cortical mechanisms for mental simulation of shape, event-related potentials were recorded to face and object pictures preceded by mental imagery. Mental imagery of the identical face or object picture (congruous condition) facilitated not only categorical perception (VPP/N170) but also later visual knowledge [N3(00) complex] and linguistic knowledge (N400) for faces more than objects, and strategic semantic analysis (late positive complex) between 200 and 700 ms. The later effects resembled semantic congruity effects with pictures. Mental imagery also facilitated category decisions, as a P3 peaked earlier for congruous than incongruous (other category) pictures, resembling the case when identical pictures repeat immediately. Thus mental imagery mimics semantic congruity and immediate repetition priming processes with pictures. Perception control results showed the opposite for faces and were in the same direction for objects: Perceptual repetition adapts (and so impairs) processing of perceived faces from categorical perception onward, but primes processing of objects during categorical perception, visual knowledge processes, and strategic semantic analysis. For both imagery and perception, differences between faces and objects support domain-specificity and indicate that cognition is grounded in modal processing. Altogether, this direct neural evidence reveals that top-down processes of mental imagery sustain an imagistic representation that mimics perception well enough to prime subsequent perception and cognition. Findings also suggest that automatic mental simulation of the visual shape of faces and objects operates between 200 and 400 ms, and strategic mental simulation operates between 400 and 700 ms.
C1 [Schendan, Haline E.; Ganis, Giorgio] Univ Plymouth, Sch Psychol, Plymouth PL4 8AA, Devon, England.
[Schendan, Haline E.; Ganis, Giorgio] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Ganis, Giorgio] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP Schendan, HE (reprint author), Univ Plymouth, Sch Psychol, Plymouth PL4 8AA, Devon, England.
EM haline.schendan@plymouth.ac.uk
OI Ganis, Giorgio/0000-0001-6175-2618; Schendan, Haline/0000-0001-8925-5605
NR 142
TC 9
Z9 10
U1 5
U2 14
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PY 2012
VL 3
AR 329
DI 10.3389/fpsyg.2012.00329
PG 22
WC Psychology, Multidisciplinary
SC Psychology
GA V31DJ
UT WOS:000208864000046
PM 23049515
ER
PT J
AU Shapiro, KA
Moo, LR
Caramazza, A
AF Shapiro, Kevin A.
Moo, Lauren R.
Caramazza, Alfonso
TI Neural specificity for grammatical operations is revealed by
content-independent fMR adaptation
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE nouns; verbs; grammatical class; inflection; fMRI; adaptation
AB The ability to generate novel sentences depends on cognitive operations that specify the syntactic function of nouns, verbs, and other words retrieved from the mental lexicon. Although neuropsychological studies suggest that such operations rely on neural circuits distinct from those encoding word form and meaning, it has not been possible to characterize this distinction definitively with neuroimaging. We used functional magnetic resonance imaging (fMRI) to show that a brain area engaged in a given grammatical operation can be identified uniquely by a monotonic decrease in activation as that operation is repeated. We applied this methodology to identify areas involved selectively in the operation of inflection of nouns or verbs. By contrast, areas involved in processing word meaning do not show this monotonic adaptation across stimuli. These results are the first to demonstrate adaptation in the fMR signal evoked not by specific stimuli, but by well-defined cognitive linguistic operations.
C1 [Shapiro, Kevin A.; Caramazza, Alfonso] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Shapiro, Kevin A.] Childrens Hosp Boston, Dept Med, Boston, MA USA.
[Shapiro, Kevin A.; Moo, Lauren R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Caramazza, Alfonso] Univ Trento, Ctr Mind Brain Sci, Rovereto, Italy.
RP Caramazza, A (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA.
EM caram@wjh.harvard.edu
NR 55
TC 5
Z9 5
U1 1
U2 2
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PY 2012
VL 3
AR 26
DI 10.3389/fpsyg.2012.00026
PG 9
WC Psychology, Multidisciplinary
SC Psychology
GA V31DI
UT WOS:000208863900040
PM 22347206
ER
PT J
AU Wiecek, E
Pasquale, LR
Fiser, J
Dakin, S
Bex, PJ
AF Wiecek, Emily
Pasquale, Louis R.
Fiser, Jozsef
Dakin, Steven
Bex, Peter J.
TI Effects of peripheral visual field loss on eye movements during visual
search
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE eye movements; visual search; low-vision; glaucoma; peripheral vision;
natural scenes
AB Natural vision involves sequential eye movements that bring the fovea to locations selected by peripheral vision. How peripheral visual field loss (PVFL) affects this process is not well understood. We examine how the location and extent of PVFL affects eye movement behavior in a naturalistic visual search task. Ten patients with PVFL and 13 normally sighted subjects with full visual fields (EVE) completed 30 visual searches monocularly. Subjects located a 4 degrees x 4 degrees target, pseudo-randomly selected within a 26 degrees x 11 degrees natural image. Eye positions were recorded at 50 Hz. Search duration, fixation duration, saccade size, and number of saccades per trial were not significantly different between PVFL and EVE groups (p > 0.1). A chi(2) test showed that the distributions of saccade directions for PVFL and FVL subjects were significantly different in 8 out of 10 cases (p < 0.01). Humphrey Visual Field pattern deviations for each subject were compared with the spatial distribution of eye movement directions. There were no significant correlations between saccade directional bias and visual field sensitivity across the 10 patients. Visual search performance was not significantly affected by PVFL. An analysis of eye movement directions revealed patients with PVFL show a biased directional distribution that was not directly related to the locus of vision loss, challenging feed-forward models of eye movement control. Consequently, many patients do not optimally compensate for visual field loss during visual search.
C1 [Wiecek, Emily; Pasquale, Louis R.; Bex, Peter J.] Massachusetts Eye & Ear Infirm, Boston, MA 02118 USA.
[Wiecek, Emily; Pasquale, Louis R.; Bex, Peter J.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Wiecek, Emily; Dakin, Steven] UCL, Inst Ophthalmol, London, England.
[Pasquale, Louis R.] Harvard Univ, Sch Med, Dept Med, Charming Div Network Med, Boston, MA USA.
[Fiser, Jozsef] Brandeis Univ, Volen Natl Ctr Complex Syst, Waltham, MA USA.
[Dakin, Steven] NHS Fdn Trust, Moorfields Eye Hosp, NIHR Biomed Res Ctr Ophthalmol, London, England.
RP Wiecek, E (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02118 USA.
EM emily.wiecek@schepens.harvard.edu
OI Dakin, Steven/0000-0002-3548-9104
FU NEI NIH HHS [R01 EY019281]
NR 49
TC 5
Z9 5
U1 0
U2 4
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PY 2012
VL 3
AR 472
DI 10.3389/fpsyg.2012.00472
PG 13
WC Psychology, Multidisciplinary
SC Psychology
GA V31DJ
UT WOS:000208864000182
PM 23162511
ER
PT J
AU Peretti, CS
Peretti, C
Chouinard, VA
Chouinard, G
AF Peretti, Charles-Siegfried
Peretti, Charles
Chouinard, Virginie-Anne
Chouinard, Guy
BE Tunali, NE
TI Endogenous Attention in Normal Elderly, Presymptomatic Huntington's
Disease and Huntington's Disease Subjects
SO HUNTINGTON'S DISEASE - CORE CONCEPTS AND CURRENT ADVANCES
LA English
DT Article; Book Chapter
ID ALZHEIMERS-DISEASE; VISUOSPATIAL ATTENTION; SPATIAL ATTENTION;
VISUAL-ATTENTION; SEARCH; OBJECT; INHIBITION; SELECTION; NETWORKS;
DEMENTIA
C1 [Peretti, Charles-Siegfried; Peretti, Charles] Univ Paris 06, Psychiat Serv, Hop St Antoine, Paris, France.
[Chouinard, Virginie-Anne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, McLean Adult Psychiat,Residency Training Program, Boston, MA USA.
[Peretti, Charles-Siegfried; Chouinard, Virginie-Anne; Chouinard, Guy] McGill Univ, Clin Psychopharmacol Unit, Montreal, PQ H3A 2T5, Canada.
[Chouinard, Guy] Univ Montreal, Fernand Seguin Res Ctr, Montreal, PQ, Canada.
RP Peretti, CS (reprint author), Univ Paris 06, Psychiat Serv, Hop St Antoine, Paris, France.
NR 39
TC 0
Z9 0
U1 0
U2 0
PU INTECH EUROPE
PI RIJEKA
PA JANEZA TRDINE9, RIJEKA, 51000, CROATIA
BN 978-953-307-953-0
PY 2012
BP 233
EP 242
D2 10.5772/1470
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA BE5XH
UT WOS:000373607700010
ER
PT S
AU Mahanian, M
Fiala, M
Mizwicki, MT
La Cava, A
AF Mahanian, Michelle
Fiala, Milan
Mizwicki, Mathew T.
La Cava, Antonio
BE Aggarwal, BB
Krishnan, S
Guha, S
TI Immune Modulation of Inflammation in Neurodegenerative Diseases
Alzheimer's Disease and Amyotrophic Lateral Sclerosis
SO INFLAMMATION, LIFESTYLE AND CHRONIC DISEASES: THE SILENT LINK
SE Oxidative Stress and Disease
LA English
DT Article; Book Chapter
ID CEREBRAL AMYLOID ANGIOPATHY; INNATE IMMUNITY; BETA-PROTEIN; MOUSE MODEL;
MACROPHAGES; ACTIVATION; MICROGLIA; CELLS; MICE; ALS
C1 [Mahanian, Michelle; Fiala, Milan; La Cava, Antonio] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Fiala, Milan] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA.
[Mizwicki, Mathew T.] Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA.
RP Mahanian, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
NR 50
TC 0
Z9 0
U1 0
U2 0
PU CRC PRESS-TAYLOR & FRANCIS GROUP
PI BOCA RATON
PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA
SN 2155-0255
BN 978-1-4398-3990-4; 978-1-4398-3989-8
J9 OXIDAT STRESS DIS
PY 2012
BP 41
EP 55
PG 15
WC Primary Health Care; Immunology
SC General & Internal Medicine; Immunology
GA BC8CS
UT WOS:000355550900003
ER
PT J
AU Rauch, SD
Geller, LN
AF Rauch, Steven D.
Geller, Lisa N.
TI Comparing treatments for idiopathic sudden sensorineural hearing loss
SO JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH
LA English
DT Editorial Material
C1 [Rauch, Steven D.; Geller, Lisa N.] Harvard Univ, Sch Med, Mass Eye & Ear Infirm, Boston, MA 02163 USA.
RP Rauch, SD (reprint author), Harvard Univ, Sch Med, Mass Eye & Ear Infirm, Boston, MA 02163 USA.
EM steven_rauch@meei.harvard.edu
NR 2
TC 0
Z9 0
U1 0
U2 0
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 2042-6305
EI 2042-6313
J9 J COMP EFFECT RES
JI J. Comp. Eff. Res.
PD JAN
PY 2012
VL 1
IS 1
BP 5
EP 7
DI 10.2217/CER.11.8
PG 3
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA V32SF
UT WOS:000208970200002
PM 24237291
ER
PT J
AU Schaer, M
Cuadra, MB
Schmansky, N
Fischl, B
Thiran, JP
Eliez, S
AF Schaer, Marie
Cuadra, Meritxell Bach
Schmansky, Nick
Fischl, Bruce
Thiran, Jean-Philippe
Eliez, Stephan
TI How to Measure Cortical Folding from MR Images: a Step-by-Step Tutorial
to Compute Local Gyrification Index
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Medicine; Issue 59; neuroimaging; brain; cortical complexity; cortical
development
AB Cortical folding (gyrification) is determined during the first months of life, so that adverse events occurring during this period leave traces that will be identifiable at any age. As recently reviewed by Mangin and colleagues(2), several methods exist to quantify different characteristics of gyrification. For instance, sulcal morphometry can be used to measure shape descriptors such as the depth, length or indices of interhemispheric asymmetry(3). These geometrical properties have the advantage of being easy to interpret. However, sulcal morphometry tightly relies on the accurate identification of a given set of sulci and hence provides a fragmented description of gyrification. A more fine-grained quantification of gyrification can be achieved with curvature-based measurements, where smoothed absolute mean curvature is typically computed at thousands of points over the cortical surface(4). The curvature is however not straightforward to comprehend, as it remains unclear if there is any direct relationship between the curvedness and a biologically meaningful correlate such as cortical volume or surface. To address the diverse issues raised by the measurement of cortical folding, we previously developed an algorithm to quantify local gyrification with an exquisite spatial resolution and of simple interpretation. Our method is inspired of the Gyrification Index(5), a method originally used in comparative neuroanatomy to evaluate the cortical folding differences across species. In our implementation, which we name local Gyrification Index (lGI(1)), we measure the amount of cortex buried within the sulcal folds as compared with the amount of visible cortex in circular regions of interest. Given that the cortex grows primarily through radial expansion(6), our method was specifically designed to identify early defects of cortical development.
In this article, we detail the computation of local Gyrification Index, which is now freely distributed as a part of the FreeSurfer Software (http://surfer.nmr.mgh.harvard.edu/, Martinos Center for Biomedical Imaging, Massachusetts General Hospital). FreeSurfer provides a set of automated reconstruction tools of the brain's cortical surface from structural MRI data. The cortical surface extracted in the native space of the images with sub-millimeter accuracy is then further used for the creation of an outer surface, which will serve as a basis for the lGI calculation. A circular region of interest is then delineated on the outer surface, and its corresponding region of interest on the cortical surface is identified using a matching algorithm as described in our validation study(1). This process is repeatedly iterated with largely overlapping regions of interest, resulting in cortical maps of gyrification for subsequent statistical comparisons (Fig. 1). Of note, another measurement of local gyrification with a similar inspiration was proposed by Toro and colleagues(7), where the folding index at each point is computed as the ratio of the cortical area contained in a sphere divided by the area of a disc with the same radius. The two implementations differ in that the one by Toro et al. is based on Euclidian distances and thus considers discontinuous patches of cortical area, whereas ours uses a strict geodesic algorithm and include only the continuous patch of cortical area opening at the brain surface in a circular region of interest.
C1 [Schaer, Marie; Eliez, Stephan] Univ Geneva, Sch Med, Dept Psychiat, CH-1211 Geneva 4, Switzerland.
[Cuadra, Meritxell Bach; Thiran, Jean-Philippe] Ecole Polytech Fed Lausanne, Signal Proc Lab, CH-1015 Lausanne, Switzerland.
[Cuadra, Meritxell Bach] Univ Hosp Ctr, Dept Radiol, Zagreb, Croatia.
[Cuadra, Meritxell Bach] Univ Lausanne, CH-1015 Lausanne, Switzerland.
[Schmansky, Nick; Fischl, Bruce] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
RP Schaer, M (reprint author), Univ Geneva, Sch Med, Dept Psychiat, CH-1211 Geneva 4, Switzerland.
EM marie.schaer@unige.ch
OI Thiran, Jean-Philippe/0000-0003-2938-9657
FU National Center of Competence in Research (NCCR) "SYNAPSY - The Synaptic
Bases of Mental Diseases" - Swiss National Science Foundation
[51AU40_125759]; Swiss National Research Fund [323500-111165,
3200-063135.00/1, 3232-063134.00/1, PP0033-102864, 32473B-121996];
Center for Biomedical Imaging (CIBM) of the Geneva-Lausanne
Universities; EPFL; foundation Leenaards; foundation Louis-Jeantet;
National Center for Research Resources (NCRR BIRN Morphometric Project)
[BIRN002, U24 RR021382]; National Institutes of Health through the NIH
Roadmap for Medical Research [U54 EB005149]; Autism & Dyslexia Project -
Ellison Medical Foundation
FX This research was supported by the National Center of Competence in
Research (NCCR) "SYNAPSY - The Synaptic Bases of Mental Diseases"
financed by the Swiss National Science Foundation (no 51AU40_125759).
Development of the local Gyrification Index was supported by grants from
the Swiss National Research Fund to Dr. Marie Schaer (323500-111165) and
to Dr. Stephan Eliez (3200-063135.00/1, 3232-063134.00/1, PP0033-102864
and 32473B-121996) and by the Center for Biomedical Imaging (CIBM) of
the Geneva-Lausanne Universities and the EPFL, as well as the
foundations Leenaards and Louis-Jeantet. Support for the development of
FreeSurfer software was provided in part by the National Center for
Research Resources (P41-RR14075, and the NCRR BIRN Morphometric Project
BIRN002, U24 RR021382), the National Institute for Biomedical Imaging
and Bioengineering (R01 EB001550, R01EB006758), the National Institute
for Neurological Disorders and Stroke (R01 NS052585-01) 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 NIH Roadmap for Medical
Research, Grant U54 EB005149. Additional support was provided by The
Autism & Dyslexia Project funded by the Ellison Medical Foundation.
NR 24
TC 11
Z9 11
U1 1
U2 1
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 JAN
PY 2012
IS 59
AR UNSP e3417
DI 10.3791/3417
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36PD
UT WOS:000209222600021
PM 22230945
ER
PT B
AU Kawai, T
Cosimi, AB
AF Kawai, Tatsuo
Cosimi, A. Benedict
BE Veroux, M
Veroux, P
TI Clinical Tolerance in Kidney Transplantation
SO KIDNEY TRANSPLANTATION: CHALLENGING THE FUTURE
LA English
DT Article; Book Chapter
DE Tolerance; Mixed Chimerism; Kidney Transplantation; Immunosuppression;
Central Tolerance; Peripheral Tolerance; Prope Tolerance; Costimulatory
Blockade; T-Cells Depletion; Blood Marrow Infusion
ID TOTAL-LYMPHOID IRRADIATION; RENAL-ALLOGRAFT REJECTION; DONOR
BONE-MARROW; NONHUMAN-PRIMATES; MONOCLONAL-ANTIBODY;
ORGAN-TRANSPLANTATION; LYMPHOHEMATOPOIETIC CHIMERISM; MAINTENANCE
IMMUNOSUPPRESSION; COSTIMULATION BLOCKADE; CELL TRANSPLANTATION
AB Induction of donor specific tolerance has been the ultimate goal in organ transplantation. Recent application of approaches to the induction of allograft tolerance in human kidney transplant recipients has been based upon preclinical studies in nonhuman primates, including 1) profound T cell depletion by powerful anti-T cell antibodies, 2) use of total lymphoid irradiation, 3) costimulatory blockade, 4) infusion of anergic cells 5) donor bone marrow (DBM) infusion without anticipation of engraftment and 6) DBM transplantation leading to Mixed Chimerism. Mixed Chimerism following DBM transplantation has to date been the most successful approach for induction of renal allograft tolerance in clinical kidney transplantation trials.
C1 [Kawai, Tatsuo; Cosimi, A. Benedict] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA.
RP Kawai, T (reprint author), Harvard Univ, Sch Med, Transplant Surg, White 510 55 Fruit St, Boston, MA 02114 USA.
EM tkawai@partners.org
NR 46
TC 0
Z9 0
U1 0
U2 0
PU BENTHAM SCIENCE PUBL
PI BUSUM
PA PO BOX 294, BUSUM, 1400 AG, NETHERLANDS
BN 978-1-60805-144-1; 978-1-60805-424-4
PY 2012
BP 370
EP 377
D2 10.2174/97816080514411120101
PG 8
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA BC9LD
UT WOS:000356536100027
ER
PT B
AU Kita, T
Feener, EP
AF Kita, Takeshi
Feener, Edward P.
BE Bader, M
TI Kallikrein-kinin system in the eye
SO KININS
LA English
DT Article; Book Chapter
ID ANGIOTENSIN-CONVERTING ENZYME; TRABECULAR MESHWORK CELLS; CORNEAL
EPITHELIAL-CELLS; PROLIFERATIVE DIABETIC-RETINOPATHY; RETINAL
VASCULAR-PERMEABILITY; PORCINE CILIARY ARTERY; HUMAN OCULAR-TISSUES;
SPHINCTER IN-VITRO; C-REACTIVE PROTEIN; NITRIC-OXIDE
C1 [Kita, Takeshi; Feener, Edward P.] Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Kita, T (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA.
EM Takeshi.Kita@joslin.harvard.edu; Edward.Feener@joslin.harvard.edu
NR 78
TC 0
Z9 0
U1 0
U2 0
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
BN 978-3-11-025235-4; 978-3-11-025234-7
PY 2012
BP 171
EP 186
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BE0HZ
UT WOS:000366059400012
ER
PT B
AU Pekow, CA
AF Pekow, Cynthia A.
BE Suckow, MA
Stevens, KA
Wilson, RP
TI Basic Experimental Methods in the Rabbit
SO LABORATORY RABBIT, GUINEA PIG, HAMSTER, AND OTHER RODENTS
SE American College of Laboratory Animal Medicine Series
LA English
DT Article; Book Chapter
ID ARTIFICIAL-INSEMINATION; ACCESS; CATHETERIZATION; COLLECTION; DEVICE;
BLOOD; SUBSTANCES; INTUBATION; ANIMALS; MODEL
C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
RP Pekow, CA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
NR 63
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
BN 978-0-12-380921-6; 978-0-12-380920-9
J9 AM COLL LAB
PY 2012
BP 243
EP 258
DI 10.1016/B978-0-12-380920-9.00010-9
PG 16
WC Veterinary Sciences
SC Veterinary Sciences
GA BA2YY
UT WOS:000333993900011
ER
PT S
AU Panda, B
Ecker, J
AF Panda, Britta
Ecker, Jeffrey
BE Berghella, V
TI Sickle cell disease
SO MATERNAL-FETAL EVIDENCE BASED GUIDELINES, 2ND EDITION
SE Series in Maternal-Fetal Medicine
LA English
DT Article; Book Chapter
ID PREGNANCY; EXPERIENCE; CRISIS
C1 [Panda, Britta; Ecker, Jeffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstetr Serv, Boston, MA 02134 USA.
RP Panda, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstetr Serv, Boston, MA 02134 USA.
NR 22
TC 0
Z9 0
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL ST, LONDON, EC2A 4LQ, ENGLAND
SN 2158-0871
BN 978-1-84184-823-5; 978-1-84184-822-8
J9 SER MATERN FETAL MED
PY 2012
BP 108
EP 112
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA BC6XH
UT WOS:000354561400017
ER
PT J
AU Costa, SCP
Schmitz, AM
Jahufar, FF
Boyd, JD
Cho, MY
Glicksman, MA
Lesser, CF
AF Costa, Sonia C. P.
Schmitz, Alexa M.
Jahufar, Fathima F.
Boyd, Justin D.
Cho, Min Y.
Glicksman, Marcie A.
Lesser, Cammie F.
TI A New Means To Identify Type 3 Secreted Effectors: Functionally
Interchangeable Class IB Chaperones Recognize a Conserved Sequence
SO MBIO
LA English
DT Article
ID ENTEROPATHOGENIC ESCHERICHIA-COLI; GRAM-NEGATIVE BACTERIA; III
SECRETION; SHIGELLA-FLEXNERI; SACCHAROMYCES-CEREVISIAE;
SODALIS-GLOSSINIDIUS; VIRULENCE PROTEINS; SYSTEM; IDENTIFICATION;
TRANSLOCATION
AB Many Gram-negative bacteria utilize specialized secretion systems to inject proteins (effectors) directly into host cells. Little is known regarding how bacteria ensure that only small subsets of the thousands of proteins they encode are recognized as substrates of the secretion systems, limiting their identification through bioinformatic analyses. Many of these proteins require chaperones to direct their secretion. Here, using the newly described protein interaction platform assay, we demonstrate that type 3 secretion system class IB chaperones from one bacterium directly bind their own effectors as well as those from other species. In addition, we observe that expression of class IB homologs from seven species, including pathogens and endosymbionts, mediate the translocation of effectors from Shigella directly into host cells, demonstrating that class IB chaperones are often functionally interchangeable. Notably, class IB chaperones bind numerous effectors. However, as previously proposed, they are not promiscuous; rather they recognize a defined sequence that we designate the conserved chaperone-binding domain (CCBD) sequence [(LMIF)(1)XXX(IV)(5)XX(IV)(8)X(N)(10)]. This sequence is the first defined amino acid sequence to be identified for any interspecies bacterial secretion system, i.e., a system that delivers proteins directly into eukaryotic cells. This sequence provides a new means to identify substrates of type III secretion systems. Indeed, using a pattern search algorithm for the CCBD sequence, we have identified the first two probable effectors from an endosymbiont, Sodalis glossinidius.
IMPORTANCE Many Gram-negative pathogens utilize type 3 secretion systems to deliver tens of effectors into host cells. In order to understand the diverse ways that these organisms cause disease, it is necessary to identify their effectors, many of which require chaperones to be secreted. Here we establish that class IB chaperones are not promiscuous, as previously proposed, but rather recognize a conserved effector sequence. We demonstrate that pattern search algorithms based on this defined sequence can be used to identify previously unknown effectors. Furthermore, we observe that class IB chaperones from at least seven bacterial species are functionally interchangeable. Not only do they bind and mediate the delivery of their own set of effectors into host cells but they also bind to type 3 substrates from other bacteria, suggesting that inhibitors that block chaperone-effector interactions could provide a novel means to effectively treat infections due to Gram-negative pathogens, including organisms resistant to currently available antibiotics.
C1 [Costa, Sonia C. P.; Schmitz, Alexa M.; Jahufar, Fathima F.; Cho, Min Y.; Lesser, Cammie F.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med Microbiol & Mol Genet, Cambridge, MA 02138 USA.
[Costa, Sonia C. P.; Schmitz, Alexa M.; Jahufar, Fathima F.; Boyd, Justin D.; Cho, Min Y.; Glicksman, Marcie A.; Lesser, Cammie F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Boyd, Justin D.; Glicksman, Marcie A.] Brigham & Womens Hosp, Lab Drug Discovery Neurodegenerat, Harvard NeuroDiscovery Ctr, Cambridge, MA USA.
RP Lesser, CF (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med Microbiol & Mol Genet, Cambridge, MA 02138 USA.
EM clesser@partners.org
FU NIH [R01 AI064285]; Rockefeller Brothers Fund; Goldman Philanthropic
Partnerships awarded
FX This work was conducted through support from the NIH (R01 AI064285) and
a Charles E. Culpeper Medical Scholarship from the Rockefeller Brothers
Fund and Goldman Philanthropic Partnerships awarded to C.F.L.
NR 45
TC 8
Z9 8
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD JAN-FEB
PY 2012
VL 3
IS 1
AR e00243-11
DI 10.1128/mBio.00243-11
PG 10
WC Microbiology
SC Microbiology
GA 933AK
UT WOS:000303331400021
ER
PT B
AU Sinke, CBA
Kret, ME
de Gelder, B
AF Sinke, Charlotte B. A.
Kret, Mariska E.
de Gelder, Beatrice
BE Berglund, B
Rossi, GB
Townsend, JT
Pendrill, LR
TI Body language Embodied perception of emotion
SO MEASUREMENT WITH PERSONS: THEORY, METHODS, AND IMPLEMENTATION AREAS
SE Scientific Psychology Series
LA English
DT Article; Book Chapter
ID NON-CONSCIOUS RECOGNITION; FACIAL EXPRESSIONS; ORBITOFRONTAL CORTEX;
BIOLOGICAL MOTION; SEX-DIFFERENCES; HUMAN AMYGDALA; HUMAN BRAIN;
AFFECTIVE BLINDSIGHT; LIGHT DISPLAYS; NEURAL SYSTEMS
C1 [Sinke, Charlotte B. A.; Kret, Mariska E.; de Gelder, Beatrice] Tilburg Univ, Fac Social & Behav Sci, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands.
[Sinke, Charlotte B. A.] Maastricht Univ, Dept Cognit Neurosci, Maastricht, Netherlands.
[Kret, Mariska E.] Univ Amsterdam, Dept Psychol, Amsterdam, Netherlands.
[de Gelder, Beatrice] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Sinke, CBA (reprint author), Tilburg Univ, Fac Social & Behav Sci, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands.
NR 99
TC 3
Z9 3
U1 2
U2 5
PU PSYCHOLOGY PRESS
PI HOVE
PA 27 CHURCH ROAD, HOVE BN3 2FA, E SUSSEX, ENGLAND
BN 978-1-136-72374-2; 978-1-84872-939-1
J9 SCI PSYCH S
PY 2012
BP 335
EP 352
PG 18
WC Mathematics, Interdisciplinary Applications; Social Sciences,
Mathematical Methods; Psychology, Mathematical
SC Mathematics; Mathematical Methods In Social Sciences; Psychology
GA BA7GA
UT WOS:000337512700016
ER
PT S
AU Shackleford, JA
Yang, Q
Lourenco, AM
Shusharina, N
Kandasamy, N
Sharp, GC
AF Shackleford, James A.
Yang, Qi
Lourenco, Ana M.
Shusharina, Nadya
Kandasamy, Nagarajan
Sharp, Gregory C.
BE Ayache, N
Delingette, H
Golland, P
Mori, K
TI Analytic Regularization of Uniform Cubic B-spline Deformation Fields
SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI
2012, PT II
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 15th International Conference on Medical Image Computing and
Computer-Assisted Intervention (MICCAI)
CY OCT 01-05, 2012
CL Nice, FRANCE
SP GE HealthCare, Philips, Siemens, Canon Median, ERC MedYMA, Medtronic, Aviesan, Dosisoft, IHU Strasbourg, IRCAD France, Kitware, Microsoft Res
DE deformable registration; b-spline; analytic regularization; thin-plate;
bending energy
ID NONRIGID REGISTRATION; IMAGES
AB Image registration is inherently ill-posed, and lacks a unique solution. In the context of medical applications, it is desirable to avoid solutions that describe physically unsound deformations within the patient anatomy. Among the accepted methods of regularizing non-rigid image registration to provide solutions applicable to medical practice is the penalty of thin-plate bending energy. In this paper, we develop an exact, analytic method for computing the bending energy of a three-dimensional B-spline deformation field as a quadratic matrix operation on the spline coefficient values. Results presented on ten thoracic case studies indicate the analytic solution is between 61-1371x faster than a numerical central differencing solution.
C1 [Shackleford, James A.; Shusharina, Nadya; Sharp, Gregory C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Yang, Qi] Heidelberg Univ, Med Fak Mannheim, Mannheim, Germany.
[Lourenco, Ana M.] Univ Lisbon, Fac Sci, Inst Biophys & Biomed Engn, P-1699 Lisbon, Portugal.
[Kandasamy, Nagarajan] Drexel Univ, Elect & Comp Engn Dept, Philadelphia, PA 19104 USA.
RP Shackleford, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
OI Shackleford, James/0000-0002-7987-651X
NR 14
TC 2
Z9 2
U1 0
U2 0
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0302-9743
BN 978-3-642-33418-4; 978-3-642-33417-7
J9 LECT NOTES COMPUT SC
PY 2012
VL 7511
BP 122
EP 129
PG 8
WC Computer Science, Artificial Intelligence; Computer Science, Theory &
Methods; Medical Informatics; Robotics; Radiology, Nuclear Medicine &
Medical Imaging
SC Computer Science; Medical Informatics; Robotics; Radiology, Nuclear
Medicine & Medical Imaging
GA BE3WG
UT WOS:000371316700016
ER
PT S
AU Toews, M
Wells, WM
Zollei, L
AF Toews, Matthew
Wells, William M., III
Zoellei, Lilla
BE Ayache, N
Delingette, H
Golland, P
Mori, K
TI A Feature-Based Developmental Model of the Infant Brain in Structural
MRI
SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI
2012, PT II
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 15th International Conference on Medical Image Computing and
Computer-Assisted Intervention (MICCAI)
CY OCT 01-05, 2012
CL Nice, FRANCE
SP GE HealthCare, Philips, Siemens, Canon Median, ERC MedYMA, Medtronic, Aviesan, Dosisoft, IHU Strasbourg, IRCAD France, Kitware, Microsoft Res
ID MAGNETIC-RESONANCE; CONSTRUCTION; NEWBORNS; GROWTH
AB In this paper, anatomical development is modeled as a collection of distinctive image patterns localized in space and time. A Bayesian posterior probability is defined over a random variable of subject age, conditioned on data in the form of scale-invariant image features. The model is automatically learned from a large set of images exhibiting significant variation, used to discover anatomical structure related to age and development, and fit to new images to predict age. The model is applied to a set of 230 infant structural MRIs of 92 subjects acquired at multiple sites over an age range of 8-590 days. Experiments demonstrate that the model can be used to identify age-related anatomical structure, and to predict the age of new subjects with an average error of 72 days.
C1 [Toews, Matthew; Wells, William M., III] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA.
[Zoellei, Lilla] Harvard Univ, Sch Med, Massachussetts Gen Hosp, Cambridge, MA 02138 USA.
RP Toews, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA.
EM mt@bwh.harvard.edu; sw@bwh.harvard.edu; lzollei@nmr.mgh.harvard.edu
NR 21
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0302-9743
BN 978-3-642-33418-4; 978-3-642-33417-7
J9 LECT NOTES COMPUT SC
PY 2012
VL 7511
BP 204
EP 211
PG 8
WC Computer Science, Artificial Intelligence; Computer Science, Theory &
Methods; Medical Informatics; Robotics; Radiology, Nuclear Medicine &
Medical Imaging
SC Computer Science; Medical Informatics; Robotics; Radiology, Nuclear
Medicine & Medical Imaging
GA BE3WG
UT WOS:000371316700026
ER
PT S
AU Pasternak, O
Shenton, ME
Westin, CF
AF Pasternak, Ofer
Shenton, Martha E.
Westin, Carl-Fredrik
BE Ayache, N
Delingette, H
Golland, P
Mori, K
TI Estimation of Extracellular Volume from Regularized Multi-shell
Diffusion MRI
SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI
2012, PT II
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 15th International Conference on Medical Image Computing and
Computer-Assisted Intervention (MICCAI)
CY OCT 01-05, 2012
CL Nice, FRANCE
SP GE HealthCare, Philips, Siemens, Canon Median, ERC MedYMA, Medtronic, Aviesan, Dosisoft, IHU Strasbourg, IRCAD France, Kitware, Microsoft Res
AB Diffusion MRI measures micron scale displacement of water molecules, providing unique insight into microstructural tissue architecture. However, current practical image resolution is in the millimeter scale, and thus diffusivities from many tissue compartments are averaged in each voxel, reducing the sensitivity and specificity of the measurement to subtle pathologies. Recent studies have pointed out that eliminating the contribution of extracellular water increases the sensitivity of the diffusion measures to tissue architecture. Moreover, in brain imaging, estimation of the extracellular volume appears to indicate pathological processes such as atrophy, edema and neuroinflammation. Here we study the free-water method, which assumes a bi-tensor model. We add low b-value shells to a regular DTI acquisition and present methods to improve the estimation of the model parameters using the extra information. In addition, we define a Laplace-Beltrami regularization operator that further stabilizes the multi-shell estimation.
C1 [Pasternak, Ofer; Shenton, Martha E.; Westin, Carl-Fredrik] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Shenton, Martha E.] VA Boston Healthcare Syst, Brockton, MA USA.
RP Pasternak, O (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
NR 12
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0302-9743
BN 978-3-642-33418-4; 978-3-642-33417-7
J9 LECT NOTES COMPUT SC
PY 2012
VL 7511
BP 305
EP 312
PG 8
WC Computer Science, Artificial Intelligence; Computer Science, Theory &
Methods; Medical Informatics; Robotics; Radiology, Nuclear Medicine &
Medical Imaging
SC Computer Science; Medical Informatics; Robotics; Radiology, Nuclear
Medicine & Medical Imaging
GA BE3WG
UT WOS:000371316700038
ER
PT S
AU Zenati, MA
Mahvash, M
AF Zenati, M. A.
Mahvash, M.
BE Gomes, P
TI Robotic systems for cardiovascular interventions
SO MEDICAL ROBOTICS: MINIMALLY INVASIVE SURGERY
SE Woodhead Publishing Series in Biomaterials
LA English
DT Article; Book Chapter
DE minimally invasive surgery; catheter; medical robots; snake robots;
continuum robots
ID ATRIAL-FIBRILLATION; SURGERY; MECHANICS
AB The evolving role of cardiac surgeons and cardiologists in performing cardiovascular interventions is examined and available commercial robots and proposed novel snake-like robots and robotic catheters for cardiovascular interventions are described.
C1 [Zenati, M. A.; Mahvash, M.] Harvard Univ, Sch Med, Boston, MA 02132 USA.
[Zenati, M. A.; Mahvash, M.] VA Boston Healthcare Syst, Cardiac Surg, West Roxbury, MA USA.
RP Zenati, MA (reprint author), Harvard Univ, Sch Med, 1400 VFW Pkwy, Boston, MA 02132 USA.
EM Marco_Zenati@hms.harvard.edu
NR 26
TC 0
Z9 0
U1 0
U2 0
PU WOODHEAD PUBL LTD
PI CAMBRIDGE
PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND
SN 2049-9485
BN 978-0-85709-739-2; 978-0-85709-130-7
J9 WOODH PUBL SER BIOM
PY 2012
VL 51
BP 78
EP 89
D2 10.1533/9780857097392
PG 12
WC Robotics; Surgery
SC Robotics; Surgery
GA BB0FC
UT WOS:000340136900005
ER
PT B
AU Mulpuri, K
Madan, S
Narayanan, U
Nicolaou, N
Noordin, S
Varghese, RA
Walker, J
AF Mulpuri, Kishore
Madan, Sanjeev
Narayanan, Uni
Nicolaou, Nick
Noordin, Shahryar
Varghese, Renjit A.
Walker, Janet
BA Sivananthan, S
Sherry, E
Warnke, P
Miller, MD
BF Sivananthan, S
Sherry, E
Warnke, P
Miller, MD
TI Neuromuscular disorders
SO MERCER'S TEXTBOOK OF ORTHOPAEDICS AND TRAUMA, 10TH EDITION
LA English
DT Article; Book Chapter
ID BRACHIAL-PLEXUS-PALSY; MARIE-TOOTH-DISEASE; BOTULINUM-TOXIN-A; SELECTIVE
DORSAL RHIZOTOMY; DIPLEGIC CEREBRAL-PALSY; RECTUS-FEMORIS TRANSFER;
RANDOMIZED CLINICAL-TRIAL; ANTERIOR TIBIAL-TENDON; GROSS MOTOR FUNCTION;
DUCHENNE MUSCULAR-DYSTROPHY
C1 [Mulpuri, Kishore] BC Childrens Hosp, Vancouver, BC, Canada.
[Madan, Sanjeev] Sheffield Childrens NHS Fdn Trust, Sheffield, S Yorkshire, England.
[Narayanan, Uni] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Narayanan, Uni] Univ Toronto, Toronto, ON, Canada.
[Nicolaou, Nick] East Sussex Hosp Trust Hastings, Conquest Hosp, Crowborough, E Sussex, England.
[Noordin, Shahryar] Univ British Columbia, Dept Orthopaed, Vancouver, BC V5Z 1M9, Canada.
[Varghese, Renjit A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Walker, Janet] Univ Kentucky, Dept Orthopaed Surg, Lexington, KY USA.
[Walker, Janet] Shriners Hosp Children, Lexington, KY USA.
RP Mulpuri, K (reprint author), BC Childrens Hosp, Vancouver, BC, Canada.
NR 212
TC 0
Z9 0
U1 0
U2 0
PU CRC PRESS-TAYLOR & FRANCIS GROUP
PI BOCA RATON
PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA
BN 978-1-4441-2876-5; 978-0-340-94203-1
PY 2012
BP 598
EP 625
PG 28
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA BD7FG
UT WOS:000362980500066
ER
PT B
AU Gao, S
Seker, E
Yarmush, ML
AF Gao, Shan
Seker, Erkin
Yarmush, Martin L.
BE Demirci, U
Khademhosseini, A
Langer, R
Blander, J
TI Microfluidics: On-Chip Platforms as In Vitro Disease Models
SO MICROFLUIDIC TECHNOLOGIES FOR HUMAN HEALTH
LA English
DT Article; Book Chapter
ID HEPATITIS-C VIRUS; LIVING CELL ARRAY; NERVE GROWTH-FACTOR;
EXTRACELLULAR-MATRIX; DRUG DEVELOPMENT; GENE-EXPRESSION; ENDOTHELIAL
DYSFUNCTION; PLATELET-ADHESION; CULTURE PLATFORM; SOFT LITHOGRAPHY
C1 [Gao, Shan; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA.
[Gao, Shan; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA 02114 USA.
[Seker, Erkin] Univ Calif Davis, Dept Elect & Comp Engn, Davis, CA 95616 USA.
[Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA.
RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA.
EM ireis@sbi.org
OI Seker, Erkin/0000-0003-2401-3562
NR 122
TC 0
Z9 0
U1 0
U2 0
PU WORLD SCIENTIFIC PUBL CO PTE LTD
PI SINGAPORE
PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE
BN 978-981-4405-52-2; 978-981-4405-51-5
PY 2012
BP 213
EP 239
PG 27
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA BB1RK
UT WOS:000341306800011
ER
PT B
AU Hanekamp, JS
Duran-Struuck, R
Sachs, DH
AF Hanekamp, John S.
Duran-Struuck, Raimon
Sachs, David H.
BE McAnulty, PA
Dayan, AD
Ganderup, NC
Hastings, KL
TI Transplantation in Miniature Swine
SO MINIPIG IN BIOMEDICAL RESEARCH
LA English
DT Article; Book Chapter
ID HEMATOPOIETIC-CELL TRANSPLANTATION; MAJOR HISTOCOMPATIBILITY COMPLEX;
MISMATCHED RENAL-ALLOGRAFTS; BONE-MARROW-TRANSPLANTATION;
LARGE-ANIMAL-MODEL; CLASS-I-DISPARATE; VERSUS-HOST-DISEASE;
POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; LEUKOCYTE DIFFERENTIATION
ANTIGENS; PRIMARILY VASCULARIZED ALLOGRAFTS
C1 [Hanekamp, John S.; Duran-Struuck, Raimon; Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA.
[Hanekamp, John S.; Duran-Struuck, Raimon; Sachs, David H.] Harvard Univ, Sch Med, Boston, MA USA.
RP Hanekamp, JS (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA.
NR 129
TC 5
Z9 5
U1 0
U2 0
PU CRC PRESS-TAYLOR & FRANCIS GROUP
PI BOCA RATON
PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA
BN 978-1-4398-1119-1; 978-1-4398-1118-4
PY 2012
BP 357
EP 372
PG 16
WC Medicine, Research & Experimental; Veterinary Sciences
SC Research & Experimental Medicine; Veterinary Sciences
GA BC6GS
UT WOS:000353913300025
ER
PT S
AU Puigserver, P
Guarente, L
AF Puigserver, Pere
Guarente, Leonard
BE Orrenius, S
Packer, L
Cadenas, E
TI Nuclear Chromatin Factors Defining Mitochondrial Bioenergetics
Implications in Age-Associated Diseases
SO MITOCHONDRIAL SIGNALING IN HEALTH AND DISEASE
SE Oxidative Stress and Disease
LA English
DT Article; Book Chapter
ID ACTIVATED PROTEIN-KINASE; TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA;
REGULATES ENERGY-METABOLISM; SMALL-MOLECULE ACTIVATORS; FATTY-ACID
OXIDATION; CALORIE RESTRICTION; LIFE-SPAN; SKELETAL-MUSCLE;
SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION
C1 [Puigserver, Pere] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Guarente, Leonard] MIT, Paul F Glenn Lab, Cambridge, MA 02139 USA.
[Guarente, Leonard] MIT, Dept Biol, Cambridge, MA USA.
RP Puigserver, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
NR 109
TC 0
Z9 0
U1 0
U2 0
PU CRC PRESS-TAYLOR & FRANCIS GROUP
PI BOCA RATON
PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA
SN 2155-0255
BN 978-1-4398-8003-6; 978-1-4398-8002-9
J9 OXIDAT STRESS DIS
PY 2012
BP 225
EP 243
PG 19
WC Cell Biology; Pharmacology & Pharmacy; Toxicology
SC Cell Biology; Pharmacology & Pharmacy; Toxicology
GA BC6TM
UT WOS:000354478600013
ER
PT J
AU Atilla-Gokcumen, GE
Muro, E
Sasse, S
Bedigian, A
Eggert, U
AF Atilla-Gokcumen, G. E.
Muro, E.
Sasse, S.
Bedigian, A.
Eggert, U.
TI Global lipid profiling of dividing cells reveals the significance of
sphingolipids during cytokinesis and at the midbody.
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Atilla-Gokcumen, G. E.; Bedigian, A.; Eggert, U.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Atilla-Gokcumen, G. E.; Sasse, S.; Bedigian, A.] Harvard Univ, Sch Med, Boston, MA USA.
[Muro, E.; Eggert, U.] Kings Coll London, London WC2R 2LS, England.
[Sasse, S.] Univ Munster, D-48149 Munster, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 1093
PG 1
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348603279
ER
PT J
AU Blower, MD
Schwarz, D
AF Blower, M. D.
Schwarz, D.
TI A calcium-activated RNase regulates ER morphology.
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Blower, M. D.; Schwarz, D.] Massachusetts Gen Hosp, Mol Biol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 2178
PG 2
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348607065
ER
PT J
AU Jambhekar, A
Nadarajan, S
Colaiacovo, M
Blower, M
AF Jambhekar, A.
Nadarajan, S.
Colaiacovo, M.
Blower, M.
TI RNA activates Aurora B kinase to promote meiotic spindle assembly.
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Jambhekar, A.; Blower, M.] Massachusetts Gen Hosp, Mol Biol, Boston, MA 02114 USA.
[Nadarajan, S.; Colaiacovo, M.] Harvard Univ, Sch Med, Genet, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 1968
PG 1
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348606077
ER
PT J
AU Joukov, V
Walter, JC
De Nicolo, A
AF Joukov, V.
Walter, J. C.
De Nicolo, A.
TI Cep192/Aurora A/Plx1 pericentriolar material-recruiting complex is a key
mediator of centrosome maturation.
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Joukov, V.; De Nicolo, A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Walter, J. C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 1952
PG 2
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348606061
ER
PT J
AU Kim, S
Beyer, BA
Lewis, C
Nadel, JA
AF Kim, S.
Beyer, B. A.
Lewis, C.
Nadel, J. A.
TI Normal CFTR inhibits a pro-inflammatory IL-1R-TACE-EGFR pathway in
airway epithelial cells.
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Kim, S.; Beyer, B. A.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA.
[Lewis, C.; Nadel, J. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 685
PG 1
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348602318
ER
PT J
AU Kollu, S
Brack, A
AF Kollu, S.
Brack, A.
TI Differential regulation of the mitotic spindle assembly checkpoint in
stem and progenitor cells.
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Kollu, S.; Brack, A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Kollu, S.; Brack, A.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 394
PG 2
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348602029
ER
PT J
AU Krukenberg, KA
Benes, CH
Steen, J
Mitchison, TJ
AF Krukenberg, K. A.
Benes, C. H.
Steen, J.
Mitchison, T. J.
TI Differential regulation of poly(ADP-ribose) polymerases in cancer cells
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Krukenberg, K. A.; Mitchison, T. J.] Harvard Univ, Sch Med, Boston, MA USA.
[Benes, C. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Steen, J.] Boston Childrens Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 846
PG 2
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348603035
ER
PT J
AU Kwon, M
Bagonis, M
Danuser, G
Pellmad, D
AF Kwon, M.
Bagonis, M.
Danuser, G.
Pellmad, D.
TI Molecular mechanisms governing extrinsic forces in mitotic spindle
organization.
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Kwon, M.; Pellmad, D.] Dana Farber Canc Inst, Pediat Oncol, HHMI, Boston, MA 02115 USA.
[Kwon, M.; Bagonis, M.; Danuser, G.; Pellmad, D.] Harvard Univ, Sch Med, Cell Biol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 1936
PG 2
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348606046
ER
PT J
AU Kwon, M
Bagonis, M
Danuser, G
Pellman, D
AF Kwon, M.
Bagonis, M.
Danuser, G.
Pellman, D.
TI Molecular mechanisms governing extrinsic forces in mitotic spindle
organization
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Kwon, M.; Pellman, D.] Dana Farber Canc Inst, Pediat Oncol, HHMI, Boston, MA 02115 USA.
[Kwon, M.; Bagonis, M.; Danuser, G.; Pellman, D.] Harvard Univ, Sch Med, Cell Biol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 73
PG 2
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348601073
ER
PT J
AU Le Corre, S
Drummond, IA
AF Le Corre, S.
Drummond, I. A.
TI The role of polycystins in the maintenance of extracellular matrix
integrity.
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Le Corre, S.; Drummond, I. A.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 2148
PG 1
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348607035
ER
PT J
AU Lee, RE
Savety, K
Gaudet, S
AF Lee, R. E.
Savety, K.
Gaudet, S.
TI Single-cell signaling dynamics reveal the logic of early response gene
transcription driven by NF-kB.
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Lee, R. E.; Savety, K.; Gaudet, S.] Dana Farber Canc Inst, Canc Biol, Boston, MA 02115 USA.
[Lee, R. E.; Gaudet, S.] Harvard Univ, Sch Med, Genet, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 2296
PG 2
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348607183
ER
PT J
AU Lee, RE
Savery, K
Gaudet, S
AF Lee, R. E.
Savery, K.
Gaudet, S.
TI Single-cell signaling dynamics reveal the logic of early response gene
transcription driven by NF-kB
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Lee, R. E.; Savery, K.; Gaudet, S.] Dana Farber Canc Inst, Canc Biol, Boston, MA 02115 USA.
[Lee, R. E.; Gaudet, S.] Harvard Univ, Sch Med, Genet, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 44
PG 2
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348601044
ER
PT J
AU Minchew, CL
Didenko, VV
AF Minchew, C. L.
Didenko, V. V.
TI Color-shifting FRET sensor for detection of phagocytic phase of
apoptosis.
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Minchew, C. L.; Didenko, V. V.] Baylor Coll Med, Neurosurg & Mol & Cellular Biol, Houston, TX 77030 USA.
[Minchew, C. L.; Didenko, V. V.] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 1708
PG 1
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348605076
ER
PT J
AU Voisine, C
Brehme, M
Rolland, T
Wachi, S
Orton, K
Reinhart, P
Vidal, M
Morimoto, R
Ge, H
AF Voisine, C.
Brehme, M.
Rolland, T.
Wachi, S.
Orton, K.
Reinhart, P.
Vidal, M.
Morimoto, R.
Ge, H.
TI The chaperome as a therapeutic space in aging and neurodegenerative
diseases
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Voisine, C.] NE Illinois Univ, Biol, Chicago, IL 60625 USA.
[Voisine, C.; Orton, K.; Morimoto, R.] Northwestern Univ, Mol Biosci, Evanston, IL USA.
[Brehme, M.; Wachi, S.; Reinhart, P.; Ge, H.] Proteostasis Therapeut Inc, Cambridge, MA USA.
[Brehme, M.; Rolland, T.; Vidal, M.] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA.
[Brehme, M.; Rolland, T.; Vidal, M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Brehme, M.; Rolland, T.; Vidal, M.] Harvard Univ, Sch Med, Genet, Boston, MA USA.
RI Brehme, Marc/G-8697-2015
OI Brehme, Marc/0000-0003-0694-331X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 126
PG 2
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348601126
ER
PT J
AU Zhang, X
Wang, W
Bedigian, AV
Eggert, U
AF Zhang, X.
Wang, W.
Bedigian, A. V.
Eggert, U.
TI G-protein-coupled receptors participate in cytokinesis.
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Zhang, X.; Bedigian, A. V.; Eggert, U.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Zhang, X.; Eggert, U.] Harvard Univ, Sch Med, Boston, MA USA.
[Zhang, X.; Wang, W.] Chinese Acad Sci, High Magnet Field Lab, Hefei, Peoples R China.
[Eggert, U.] Kings Coll London, London WC2R 2LS, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 1094
PG 1
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348603280
ER
PT J
AU Zhang, X
Wang, W
Bedigian, AV
Coughlin, ML
Mitchison, TJ
Eggert, U
AF Zhang, X.
Wang, W.
Bedigian, A. V.
Coughlin, M. L.
Mitchison, T. J.
Eggert, U.
TI Dopamine receptor D3 regulates endocytic sorting by a Prazosin-sensitive
interaction with the coatomer COPI.
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Zhang, X.; Bedigian, A. V.; Eggert, U.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Zhang, X.; Coughlin, M. L.; Mitchison, T. J.; Eggert, U.] Harvard Univ, Sch Med, Boston, MA USA.
[Zhang, X.; Wang, W.] Chinese Acad Sci, High Magnet Field Lab, Hefei, Peoples R China.
[Eggert, U.] Kings Coll London, London WC2R 2LS, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 589
PG 2
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348602223
ER
PT J
AU Zhu, J
Kwon, M
Bagonis, M
Pellman, D
Mogilner, A
AF Zhu, J.
Kwon, M.
Bagonis, M.
Pellman, D.
Mogilner, A.
TI Force-balance model of suppression of multipolar division in cancer
cells with extra centrosomes
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Meeting Abstract
C1 [Zhu, J.; Mogilner, A.] Univ Calif Davis, Math, Davis, CA USA.
[Zhu, J.; Mogilner, A.] Univ Calif Davis, Neurobiol Physiol & Behav, Davis, CA USA.
[Kwon, M.; Pellman, D.] Harvard Univ, Sch Med, Pediat, Boston, MA USA.
[Kwon, M.; Pellman, D.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Bagonis, M.] Harvard Univ, Sch Med, Cell Biol, Boston, MA USA.
[Pellman, D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PY 2012
VL 23
MA 1160
PG 1
WC Cell Biology
SC Cell Biology
GA V38MX
UT WOS:000209348603345
ER
PT J
AU Novobrantseva, TI
Borodovsky, A
Wong, J
Klebanov, B
Zafari, M
Yucius, K
Querbes, W
Ge, P
Ruda, VM
Milstein, S
Speciner, L
Duncan, R
Barros, S
Basha, G
Cullis, P
Akinc, A
Donahoe, JS
Jayaprakash, KN
Jayaraman, M
Bogorad, RL
Love, K
Whitehead, K
Levins, C
Manoharan, M
Swirski, FK
Weissleder, R
Langer, R
Anderson, DG
De Fougerolles, A
Nahrendorf, M
Koteliansky, V
AF Novobrantseva, Tatiana I.
Borodovsky, Anna
Wong, Jamie
Klebanov, Boris
Zafari, Mohammad
Yucius, Kristina
Querbes, William
Ge, Pei
Ruda, Vera M.
Milstein, Stuart
Speciner, Lauren
Duncan, Rick
Barros, Scott
Basha, Genc
Cullis, Pieter
Akinc, Akin
Donahoe, Jessica S.
Jayaprakash, K. Narayanannair
Jayaraman, Muthusamy
Bogorad, Roman L.
Love, Kevin
Whitehead, Katie
Levins, Chris
Manoharan, Muthiah
Swirski, Filip K.
Weissleder, Ralph
Langer, Robert
Anderson, Daniel G.
De Fougerolles, Antonin
Nahrendorf, Matthias
Koteliansky, Victor
TI Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent
Myeloid Cells
SO MOLECULAR THERAPY-NUCLEIC ACIDS
LA English
DT Article
DE delivery; immune cell; siRNA
AB Leukocytes are central regulators of inflammation and the target cells of therapies for key diseases, including autoimmune, cardiovascular, and malignant disorders. Efficient in vivo delivery of small interfering RNA (siRNA) to immune cells could thus enable novel treatment strategies with broad applicability. In this report, we develop systemic delivery methods of siRNA encapsulated in lipid nanoparticles (LNP) for durable and potent in vivo RNA interference (RNAi)-mediated silencing in myeloid cells. This work provides the first demonstration of siRNA-mediated silencing in myeloid cell types of nonhuman primates (NHPs) and establishes the feasibility of targeting multiple gene targets in rodent myeloid cells. The therapeutic potential of these formulations was demonstrated using siRNA targeting tumor necrosis factor-a (TNFa) which induced substantial attenuation of disease progression comparable to a potent antibody treatment in a mouse model of rheumatoid arthritis (RA). In summary, we demonstrate a broadly applicable and therapeutically relevant platform for silencing disease genes in immune cells.
C1 [Novobrantseva, Tatiana I.; Borodovsky, Anna; Wong, Jamie; Klebanov, Boris; Zafari, Mohammad; Yucius, Kristina; Querbes, William; Ge, Pei; Milstein, Stuart; Speciner, Lauren; Duncan, Rick; Barros, Scott; Akinc, Akin; Jayaprakash, K. Narayanannair; Jayaraman, Muthusamy; Manoharan, Muthiah; De Fougerolles, Antonin; Koteliansky, Victor] Alnylam Pharmaceut, Cambridge, MA 02142 USA.
[Ruda, Vera M.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Ruda, Vera M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Ruda, Vera M.] Harvard Univ, Sch Med, Boston, MA USA.
[Basha, Genc; Cullis, Pieter] Univ British Columbia, Life Sci Inst, Vancouver, BC V5Z 1M9, Canada.
[Donahoe, Jessica S.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA USA.
[Bogorad, Roman L.; Love, Kevin; Whitehead, Katie; Levins, Chris; Langer, Robert; Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Love, Kevin; Whitehead, Katie; Levins, Chris; Langer, Robert; Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Love, Kevin; Whitehead, Katie; Levins, Chris; Langer, Robert; Anderson, Daniel G.] MIT, Div Hlth Sci Technol, Cambridge, MA 02139 USA.
RP Novobrantseva, TI (reprint author), Alnylam Pharmaceut, Cambridge, MA 02142 USA.
EM tnovobrantseva@alnylam.com
RI Bogorad, Roman/G-2609-2011
FU R01HL096576; NIAID [HHSN266200600012C]
FX We acknowledge Yoshiko Iwamoto, BS (CSB-MGH) for immunohistochemical
staining of spleens, Peter Waterman, BS; Brett Marinelli, BS, and
Florian Leuschner, MD (CSB-MGH) for help with imaging. We thank Drs
Brian Bettencourt and Greg Hinkle for designing initial sets of siRNA
and helping with statistical analysis. We greatly acknowledge the small,
medium, and large-scale RMA synthesis groups at Alnylam Pharmaceuticals
as well as analytical, duplex annealing, and QC groups for synthesizing
and characterizing RNAs. We thank Julia Hettinger, Patrick Karper, and
Yongfeng Jiang for help with toxicology studies. We are also thankful to
Dr John Maraganore for critical reading of the manuscript. This work was
in part supported by R01HL096576 (to M. N.) as well as a NIAID contract
HHSN266200600012C to Alnylam Pharmaceuticals. T. I. N., A.B., J.W.,
B.K., M.Z., K.Y., P.G., W.Q., S.M., L.S, R.D., A.A., K.N.J., M.J., M.M.,
A.d.F., and V.K. are current or former employees of Alnylam
Pharmaceuticals. The work of V.M.R., G.B., P.C., R.L.B., K.L., K.W.,
C.L., R.L., and D.G.A. is supported in part by Alnylam Pharmaceuticals.
NR 41
TC 54
Z9 54
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2162-2531
J9 MOL THER-NUCL ACIDS
JI Mol. Ther.-Nucl. Acids
PD JAN
PY 2012
VL 1
AR e4
DI 10.1038/mtna.2011.3
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA V31HL
UT WOS:000208874600004
PM 23344621
ER
PT B
AU Kyle, RA
Steensma, DP
AF Kyle, Robert A.
Steensma, David P.
BE Podar, K
Anderson, KC
TI A Short History of Multiple Myeloma
SO MULTIPLE MYELOMA - A NEW ERA OF TREATMENT STRATEGIES
LA English
DT Article; Book Chapter
DE Bence Jones protein; Kahler's disease; plasma cell; multiple myeloma;
immuno/electrophoresis; immunofixation; angiogenesis; urethane;
Melphalan; prednisone; stem cell transplantation; thalidomide;
lenalidomide
ID LENALIDOMIDE PLUS DEXAMETHASONE; BONE-MARROW-TRANSPLANTATION; PROTEASOME
INHIBITOR PS-341; OVERCOMES DRUG-RESISTANCE; BENCE-JONES PROTEINS;
COMBINATION CHEMOTHERAPY; CLINICAL EXPERIENCES; GAMMA-GLOBULIN;
THALIDOMIDE; MELPHALAN
AB Although multiple myeloma has probably been present for centuries, the first well-documented case was published less than 160 years ago. The famous patient, Thomas Alexander McBean excreted large amounts of a peculiar protein that was studied by Henry Bence Jones. Jones was a well-recognized physician as well as chemist. Less than a half-century ago, Bence Jones protein was found to consist of monoclonal light chains. Otto Kahler described a patient with autopsy-proven multiple myeloma; this patient survived eight years after the onset of symptoms despite the absence of effective therapy. The discovery of Roentgen's rays facilitated the diagnosis of multiple myeloma. Serum electrophoresis followed by immunofixation allowed physicians to readily make the diagnosis. Melphalan was introduced for therapy half a century ago but little progress was made until autologous stem cell transplantation became available almost 20 years ago. This was followed by the introduction of the "novel" agents thalidomide, bortezomib and lenalidomide in the last decade.
C1 [Kyle, Robert A.] Mayo Clin, Div Hematol, 200 First St SW, Rochester, MN 55905 USA.
[Steensma, David P.] Harvard Med Sch, Dana Farber Canc Inst, Brigham & Womens Hosp, Dept Hematol Malignancies, Boston, MA USA.
RP Kyle, RA (reprint author), Mayo Clin, Div Hematol, 200 First St SW, Rochester, MN 55905 USA.
EM kyle.robert@mayo.edu
NR 72
TC 0
Z9 0
U1 0
U2 0
PU BENTHAM SCIENCE PUBL
PI SHARJAH
PA EXECUTIVE STE Y-2, P.O. BOX 7917, SAIF ZONE, SHARJAH, 1400 AG, U ARAB
EMIRATES
BN 978-1-60805-297-4; 978-1-60805-609-5
PY 2012
BP 3
EP 14
D2 10.2174/97816080529741120101
PG 12
WC Oncology; Hematology
SC Oncology; Hematology
GA BF8JC
UT WOS:000385077300003
ER
PT B
AU Podar, K
Kaufmann, JL
Laubach, JP
Lonial, S
Richardson, PG
Anderson, KC
AF Podar, Klaus
Kaufmann, Jonathan L.
Laubach, Jacob P.
Lonial, Sagar
Richardson, Paul G.
Anderson, Kenneth C.
BE Podar, K
Anderson, KC
TI Guideline to Multiple Myeloma Treatment Strategies
SO MULTIPLE MYELOMA - A NEW ERA OF TREATMENT STRATEGIES
LA English
DT Article; Book Chapter
DE Clinical features; monoclonal gammopathy of unknown significance (MGUS);
smoldering multiple myeloma (SMM); CRAB; staging (Durie-Salmon;
International Staging System); upfront therapy; autologous stem cell
transplantation (ASCT); maintenance therapy; salvage therapy; bone
disease
ID STEM-CELL TRANSPLANTATION; HIGH-DOSE MELPHALAN; NEWLY-DIAGNOSED MYELOMA;
LENALIDOMIDE PLUS DEXAMETHASONE; RANDOMIZED CONTROLLED-TRIAL;
BONE-MARROW-TRANSPLANTATION; PREVIOUSLY TREATED PATIENTS; OVERCOMES
DRUG-RESISTANCE; HIGH RESPONSE RATES; ELDERLY-PATIENTS
AB Multiple Myeloma (MM) is a clonal plasma cell malignancy with a highly heterogeneous genetic background, characterized by bone marrow (BM) plasmacytosis, production of monoclonal proteins, osteolytic bone lesions, renal disease, anemia, hypercalcemia, and immunodeficiency. The inclusion of thalidomide, bortezomib, and lenalidomide into conventional cytotoxic and transplantation regimens, first in relapsed and refractory and now also in newly diagnosed MM, has fundamentally changed treatment in MM during the last decade and steadily improved MM patient outcome.
C1 [Podar, Klaus; Laubach, Jacob P.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Myeloma Ctr, Boston, MA USA.
[Podar, Klaus] Heidelberg Univ, Natl Ctr Tumor Dis NCT, Med, Heidelberg, Germany.
[Podar, Klaus; Richardson, Paul G.; Anderson, Kenneth C.] Heidelberg Univ, Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
[Kaufmann, Jonathan L.; Lonial, Sagar] Emory Univ, Winship Canc Inst, Sch Med, Dept Hematol & Med Oncol,Med, Atlanta, GA 30322 USA.
[Lonial, Sagar] Emory Univ, Winship Canc Inst, Sch Med, Dept Hematol & Med Oncol,Clin Affairs, Atlanta, GA 30322 USA.
RP Podar, K (reprint author), Natl Ctr Tumor Dis, Neuenheimer Feld 410, Heidelberg, Germany.
EM klaus.podar@med.uni-heidelberg.de
NR 123
TC 0
Z9 0
U1 0
U2 0
PU BENTHAM SCIENCE PUBL
PI SHARJAH
PA EXECUTIVE STE Y-2, P.O. BOX 7917, SAIF ZONE, SHARJAH, 1400 AG, U ARAB
EMIRATES
BN 978-1-60805-297-4; 978-1-60805-609-5
PY 2012
BP 73
EP 87
D2 10.2174/97816080529741120101
PG 15
WC Oncology; Hematology
SC Oncology; Hematology
GA BF8JC
UT WOS:000385077300006
ER
PT B
AU Vallet, S
Raje, N
AF Vallet, Sonia
Raje, Noopur
BE Podar, K
Anderson, KC
TI Pathogenesis and Treatment of Bone Disease in Multiple Myeloma
SO MULTIPLE MYELOMA - A NEW ERA OF TREATMENT STRATEGIES
LA English
DT Article; Book Chapter
DE Osteoclasts (OCs); osteoblasts (OBs); receptor activator of NF-kappa B
ligand (RANKL),osteoprotegerin (OPG); OC activating factors (OAFs);
dickkopf (DKK) 1; bisphosphonates; denosumab; osteonecrosis of the jaw
(ONJ); activin A; B-cell activating factor (BAFF)
ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; KAPPA-B LIGAND; HISTONE
DEACETYLASE INHIBITOR; CELL-ACTIVATING FACTOR; IN-VIVO; OSTEOCLAST
FORMATION; MARROW MICROENVIRONMENT; RECEPTOR ACTIVATOR; TUMOR BURDEN;
MURINE MODEL
AB More than 80% of multiple myeloma (MM) patients present with bone involvement frequently develop serious complications that negatively affect both quality of life and overall survival. Bone disease in MM is a consequence of unbalanced remodeling resulting in the development of osteolytic lesions. Generalized osteoclast (OC) activation is the underlying mechanism coupled with osteoblast (OB) inhibition. The molecular events leading to this imbalance of the OC/OB axis is a result of the interaction of MM cells with bone cells within the bone marrow milieu and consequent cytokine deregulation. Here we will discuss the pathogenesis, clinical sequelae and therapeutic strategies for the treatment of MM bone disease. We will focus on novel therapeutic strategies under investigation to restore bone homeostasis. Such approaches are being studied not only with the goal of alleviating morbidity from bone disease but also for their resultant anti-MM activity.
C1 [Vallet, Sonia; Raje, Noopur] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA.
RP Raje, N (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, POB 216,55 Fruit St, Boston, MA 02114 USA.
EM nraje@partners.org
NR 76
TC 0
Z9 0
U1 0
U2 0
PU BENTHAM SCIENCE PUBL
PI SHARJAH
PA EXECUTIVE STE Y-2, P.O. BOX 7917, SAIF ZONE, SHARJAH, 1400 AG, U ARAB
EMIRATES
BN 978-1-60805-297-4; 978-1-60805-609-5
PY 2012
BP 97
EP 106
D2 10.2174/97816080529741120101
PG 10
WC Oncology; Hematology
SC Oncology; Hematology
GA BF8JC
UT WOS:000385077300008
ER
PT B
AU Roccaro, AM
Vacca, A
Rossi, G
Ghobrial, I
AF Roccaro, Aldo M.
Vacca, Angelo
Rossi, Giuseppe
Ghobrial, Irene
BE Podar, K
Anderson, KC
TI The Multiple Myeloma Bone Marrow Microenvironment
SO MULTIPLE MYELOMA - A NEW ERA OF TREATMENT STRATEGIES
LA English
DT Article; Book Chapter
DE Bone marrow stromal cells (BMSCs); cell adhesion mediated drug
resistance (CAM-DR); extracellular matrix (ECM); adhesion molecules;
interleukin-6; insulin-like-growth-factor 1; vascular endothelial growth
factor (VEGF); bone marrow niches; B-cell activating factor (BAFF); a
proliferation-inducing ligand (APRIL); stromal derived factor-1 (SDF-1);
hypoxia; BM endothelial cells (BMECs); angiogenesis
ID MEDIATED DRUG-RESISTANCE; NF-KAPPA-B; CELL-LINES; HEMATOLOGIC
MALIGNANCIES; ENDOTHELIAL-CELLS; CXCR4 ANTAGONIST; GENE-EXPRESSION;
STROMAL CELLS; G-CSF; INTERLEUKIN-6
AB Multiple myeloma (MM) is a plasma cell malignancy that characteristically involves extensive infiltration of bone marrow (BM), with the formation of plasmacytomas, as clusters of malignant plasma cells inside or outside the BM milieu. Despite limits to our understanding of the molecular events of neoplastic transformation in MM, substantial advances have been made in understanding the biology of the disease through the study of the BM microenvironment, which appears to be fundamental for the proliferation, survival, and resistance of myeloma; providing the preclinical evidences for targeting MM cells and BMSCs as an anti-tumor strategy in this disease.
C1 [Roccaro, Aldo M.] Harvard Med Sch, Dana Farber Canc Inst, Med, Boston, MA USA.
[Ghobrial, Irene] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol,Med, Dept Med,Kirsch Lab Waldenstrom Macroglobulinemia, Boston, MA USA.
[Roccaro, Aldo M.; Rossi, Giuseppe] Spedali Civili Brescia, Dept Hematol, Brescia, BS, Italy.
[Vacca, Angelo] Univ Bari, Sch Med, Dept Internal Med & Clin Oncol, Bari, BA, Italy.
RP Roccaro, AM (reprint author), Harvard Med Sch, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM aldo_roccaro@dfci.harvard.edu
NR 68
TC 0
Z9 0
U1 0
U2 0
PU BENTHAM SCIENCE PUBL
PI SHARJAH
PA EXECUTIVE STE Y-2, P.O. BOX 7917, SAIF ZONE, SHARJAH, 1400 AG, U ARAB
EMIRATES
BN 978-1-60805-297-4; 978-1-60805-609-5
PY 2012
BP 128
EP 137
D2 10.2174/97816080529741120101
PG 10
WC Oncology; Hematology
SC Oncology; Hematology
GA BF8JC
UT WOS:000385077300011
ER
PT B
AU Fulciniti, M
Neri, P
Tagliaferri, P
Tassone, P
AF Fulciniti, Mariateresa
Neri, Paola
Tagliaferri, Pierosandro
Tassone, Pierfrancesco
BE Podar, K
Anderson, KC
TI Mouse Models of Multiple Myeloma: Advantages and Pitfalls
SO MULTIPLE MYELOMA - A NEW ERA OF TREATMENT STRATEGIES
LA English
DT Article; Book Chapter
DE Xenograft mouse models; diffuse xenograft mouse models; SCID mouse;
SCID-hu mouse; SCID rab mouse; NOD/SCID mouse; 5TMM; VK*myc; LAG
lambda-1 model
ID IN-VIVO MODEL; SCID-HU MOUSE; INTERLEUKIN-6 TRANSGENIC MICE; MARROW
ENDOTHELIAL-CELLS; BONE-MARROW; MURINE MODEL; DRUG DEVELOPMENT; C-MYC;
INHIBITS OSTEOCLASTOGENESIS; C57BL/KALWRIJ MOUSE
AB Multiple myeloma (MM) is a complex disease which strongly relies on a network of humoral and cellular interactions within the human bone marrow milieu. Although outcomes of anti-MM treatments have improved over the past decade, the disease is still incurable. Translational research for the development of novel therapeutic approaches against MM requires experimental preclinical models able to recapitulate the disease microenvironment. Over the last few years, a variety of murine MM models have been developed. These models have significantly improved our understanding of the disease and led to the development of new therapeutics. We here review the most known models of MM and discuss both advantages and pitfalls.
C1 [Fulciniti, Mariateresa] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
[Neri, Paola] Univ Calgary, Div Hematol & Bone Marrow Transplant, Calgary, AB, Canada.
[Tagliaferri, Pierosandro; Tassone, Pierfrancesco] Magna Graecia Univ Catanzaro, Med Oncol Unit, Med, Catanzaro, Italy.
[Tagliaferri, Pierosandro; Tassone, Pierfrancesco] T Campanella Canc Ctr, Catanzaro, Italy.
RP Fulciniti, M (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
EM mariateresa_fulciniti@dfci.harvard.edu
NR 104
TC 0
Z9 0
U1 0
U2 0
PU BENTHAM SCIENCE PUBL
PI SHARJAH
PA EXECUTIVE STE Y-2, P.O. BOX 7917, SAIF ZONE, SHARJAH, 1400 AG, U ARAB
EMIRATES
BN 978-1-60805-297-4; 978-1-60805-609-5
PY 2012
BP 149
EP 160
D2 10.2174/97816080529741120101
PG 12
WC Oncology; Hematology
SC Oncology; Hematology
GA BF8JC
UT WOS:000385077300013
ER
PT B
AU Podar, K
Hideshima, T
Chauhan, D
Anderson, KC
AF Podar, Klaus
Hideshima, Teru
Chauhan, Dharminder
Anderson, Kenneth C.
BE Podar, K
Anderson, KC
TI New Therapeutic Strategies in Multiple Myeloma
SO MULTIPLE MYELOMA - A NEW ERA OF TREATMENT STRATEGIES
LA English
DT Article; Book Chapter
DE Bone marrow microenvironment; thalidomide; bortezomib;
ubiquitin-proteasome system; (UPR); salinosporamidine A (NPI-0052);
nutilins; aggresomes; signaling pathways; IL-6. VEGF; TNF alpha; SDF-1;
CD40; BAFF/ APRIL; IGF-1; Ras/ MEK/ MAPK; PI3K/ Akt; STAT/ Jak; NF kappa
B; Wnt
ID NF-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; BONE-MARROW MICROENVIRONMENT;
MEDIATED DRUG-RESISTANCE; LENALIDOMIDE PLUS DEXAMETHASONE; PROTEASOME
INHIBITOR BORTEZOMIB; PLASMA-CELL DIFFERENTIATION; TRANSCRIPTION FACTOR
XBP-1; SMALL-MOLECULE ANTAGONISTS; UNFOLDED PROTEIN RESPONSE
AB The development of multiple myeloma (MM) is a complex multi-step process involving both early and late genetic changes in the tumor cell as well as selective supportive conditions by the bone marrow (BM) microenvironment. Based predominantly on our understanding of the functional importance of the MM BM microenvironment and its interrelation with the MM cell, which triggers tumor cell homing, seeding, proliferation, and survival, a multitude of new molecular targets have been identified. The clinical approval of four derived agents, thalidomide, its immunomodulatory derivative Len, the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin have fundamentally changed treatment regimens in MM during the last decade. Moreover, based on a pathophysiologic rationale a multitude of additional agents, most prominently carfilzomib, pomalidomide, vorinostat, and perifosine have demonstrated promising preclinical and early/advanced clinical activity indicating the evolvement of further treatment advancements in near future.
C1 [Podar, Klaus; Hideshima, Teru; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA.
[Podar, Klaus] Heidelberg Univ, Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
RP Podar, K (reprint author), Natl Ctr Tumor Dis, Neuenheimer Feld 410, Heidelberg, Germany.
EM klaus.podar@med.uni-heidelberg.de
NR 204
TC 0
Z9 0
U1 0
U2 0
PU BENTHAM SCIENCE PUBL
PI SHARJAH
PA EXECUTIVE STE Y-2, P.O. BOX 7917, SAIF ZONE, SHARJAH, 1400 AG, U ARAB
EMIRATES
BN 978-1-60805-297-4; 978-1-60805-609-5
PY 2012
BP 161
EP 183
D2 10.2174/97816080529741120101
PG 23
WC Oncology; Hematology
SC Oncology; Hematology
GA BF8JC
UT WOS:000385077300014
ER
PT B
AU Tai, YT
AF Tai, Yu-Tzu
BE Podar, K
Anderson, KC
TI Antibody-based Therapies in Multiple Myeloma
SO MULTIPLE MYELOMA - A NEW ERA OF TREATMENT STRATEGIES
LA English
DT Article; Book Chapter
DE Rituximab; tocilizumab; elotuzumab; HuLuc63; daratumumab; anti-HM1.24
mAb; mapatumumab; milatuzumab; CNTO 328; denosumab; BHQ880; ACE-011;
atacicept; bevacizumab
ID ANTI-CD40 MONOCLONAL-ANTIBODY; BONE-MARROW ENVIRONMENT; SUPER-ANTAGONIST
SANT7; CELL-ACTIVATING FACTOR; KAPPA-B; PHASE-I; CLINICAL-IMPLICATIONS;
RHEUMATOID-ARTHRITIS; THERAPEUTIC ANTIBODY; PRECLINICAL MODELS
AB The unmet need for improved multiple myeloma (MM) therapy has stimulated clinical development of monoclonal antibodies (mAbs) targeting either MM cells or cells of the bone marrow (BM) microenvironment. In contrast to small-molecule inhibitors, therapeutic mAbs present the potential to specifically target tumor cells and directly induce an immune response to lyse tumor cells. Unique immune-effector mechanisms are only triggered by therapeutic mAbs but not by small molecule targeting agents. Although therapeutic murine mAbs or chimeric mAbs can cause immunogenicity, the advancement of genetic recombination for humanizing rodent mAbs has allowed large-scale production and designation of mAbs with better affinities, efficient selection, decreasing immunogenicity, and improved effector functions. These advancements of antibody engineering technologies has largely overcome the critical obstacle of antibody immunogenicity and enabled the development and subsequent Food and Drug Administration (FDA) approval of therapeutic Abs for cancer and other diseases.
C1 [Tai, Yu-Tzu] Harvard Med Sch, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA.
RP Tai, YT (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA.
EM yu-tzu_tai@dfci.harvard.edu
NR 96
TC 0
Z9 0
U1 0
U2 0
PU BENTHAM SCIENCE PUBL
PI SHARJAH
PA EXECUTIVE STE Y-2, P.O. BOX 7917, SAIF ZONE, SHARJAH, 1400 AG, U ARAB
EMIRATES
BN 978-1-60805-297-4; 978-1-60805-609-5
PY 2012
BP 184
EP 199
D2 10.2174/97816080529741120101
PG 16
WC Oncology; Hematology
SC Oncology; Hematology
GA BF8JC
UT WOS:000385077300015
ER
PT B
AU Amiji, MM
Hornicek, F
Duan, ZF
AF Amiji, Mansoor M.
Hornicek, Francis
Duan, Zhenfeng
BE Srirajaskanthan, R
Preedy, VR
TI Gene Silencing with siRNA Encapsulated Nanoparticles to Overcome Tumor
Multidrug Resistance
SO NANOMEDICINE AND CANCER
LA English
DT Article; Book Chapter
ID SMALL INTERFERING RNA; DRUG-RESISTANCE; CANCER-CELLS; OVARIAN-CANCER;
POLYMERIC NANOPARTICLES; PACLITAXEL RESISTANCE; CO-DELIVERY;
DOXORUBICIN; MODULATION; REVERSAL
AB Multidrug resistance (MDR) is a major obstacle in the successful treatment of human cancer. Experimental evidence from multiple laboratories implicates a wide range of mechanisms including over-expression of multidrug resistance 1 gene (MDR-1) and antiapoptotic genes that contribute to the drug resistant phenotype. Reversing MDR has been a high priority goal of clinical and investigational oncology, but still remains elusive. RNA interference (RNAi) has emerged as a powerful tool for sequence-specific gene silencing strategy. RNAi can be achieved by using small interfering RNA (siRNA) for target gene silencing in tumor cells. Synthetic, plasmid-based siRNA, and viral-based short hairpin RNA (shRNA) can significantly block MDR-1 and antiapoptotic gene expressions in drug resistant tumor cells. Although the RNAi technology is an excellent candidate to reverse MDR in cancer therapy, several serious challenges remain including unstable and rapid degradation by systemic and cellular nuclei and poor membrane permeability of siRNA for routine clinical application. Nanotechnology-based systems have been developed to deliver a variety of therapeutic agents, including nucleic acid constructs, into specific cells. Nanoparticulate formulations have recently emerged as alternatives to plasmid or viral vectors for the delivery of siRNA. This review summarizes current developments in drug resistant gene silencing with nanoparticle-encapsulated siRNA to overcome MDR in human cancer.
C1 [Amiji, Mansoor M.] Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Boston, MA 02115 USA.
[Hornicek, Francis; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA.
[Hornicek, Francis; Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Boston, MA 02114 USA.
RP Amiji, MM (reprint author), Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, 360 Huntington Ave, Boston, MA 02115 USA.
EM m.amiji@neu.edu; fhornicek@partners.org; zduan@partners.org
NR 28
TC 0
Z9 0
U1 0
U2 0
PU CRC PRESS-TAYLOR & FRANCIS GROUP
PI BOCA RATON
PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA
BN 978-1-4398-9159-9; 978-1-57808-727-3
PY 2012
BP 290
EP 306
PG 17
WC Biotechnology & Applied Microbiology; Oncology; Nanoscience &
Nanotechnology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Oncology; Science & Technology -
Other Topics; Research & Experimental Medicine
GA BC7TS
UT WOS:000355207500016
ER
PT J
AU Elia, J
Glessner, JT
Wang, K
Takahashi, N
Shtir, CJ
Hadley, D
Sleiman, PMA
Zhang, HT
Kim, CE
Robison, R
Lyon, GJ
Flory, JH
Bradfield, JP
Imielinski, M
Hou, CP
Frackelton, EC
Chiavacci, RM
Sakurai, T
Rabin, C
Middleton, FA
Thomas, KA
Garris, M
Mentch, F
Freitag, CM
Steinhausen, HC
Todorov, AA
Reif, A
Rothenberger, A
Franke, B
Mick, EO
Roeyers, H
Buitelaar, J
Lesch, KP
Banaschewski, T
Ebstein, RP
Mulas, F
Oades, RD
Sergeant, J
Sonuga-Barke, EJS
Renner, TJ
Romanos, M
Romanos, J
Warnke, A
Walitza, S
Meyer, J
Palmason, H
Seitz, C
Loo, SK
Smalley, SL
Biederman, J
Kent, L
Asherson, P
Anney, RJL
Gaynor, JW
Shaw, P
Devoto, M
White, PS
Grant, SFA
Buxbaum, JD
Rapoport, JL
Williams, NM
Nelson, SF
Faraone, SV
Hakonarson, H
AF Elia, Josephine
Glessner, Joseph T.
Wang, Kai
Takahashi, Nagahide
Shtir, Corina J.
Hadley, Dexter
Sleiman, Patrick M. A.
Zhang, Haitao
Kim, Cecilia E.
Robison, Reid
Lyon, Gholson J.
Flory, James H.
Bradfield, Jonathan P.
Imielinski, Marcin
Hou, Cuiping
Frackelton, Edward C.
Chiavacci, Rosetta M.
Sakurai, Takeshi
Rabin, Cara
Middleton, Frank A.
Thomas, Kelly A.
Garris, Maria
Mentch, Frank
Freitag, Christine M.
Steinhausen, Hans-Christoph
Todorov, Alexandre A.
Reif, Andreas
Rothenberger, Aribert
Franke, Barbara
Mick, Eric O.
Roeyers, Herbert
Buitelaar, Jan
Lesch, Klaus-Peter
Banaschewski, Tobias
Ebstein, Richard P.
Mulas, Fernando
Oades, Robert D.
Sergeant, Joseph
Sonuga-Barke, Edmund J. S.
Renner, Tobias J.
Romanos, Marcel
Romanos, Jasmin
Warnke, Andreas
Walitza, Susanne
Meyer, Jobst
Palmason, Haukur
Seitz, Christiane
Loo, Sandra K.
Smalley, Susan L.
Biederman, Joseph
Kent, Lindsey
Asherson, Philip
Anney, Richard J. L.
Gaynor, J. William
Shaw, Philip
Devoto, Marcella
White, Peter S.
Grant, Struan F. A.
Buxbaum, Joseph D.
Rapoport, Judith L.
Williams, Nigel M.
Nelson, Stanley F.
Faraone, Stephen V.
Hakonarson, Hakon
TI Genome-wide copy number variation study associates metabotropic
glutamate receptor gene networks with attention deficit hyperactivity
disorder
SO NATURE GENETICS
LA English
DT Article
ID SPONTANEOUSLY HYPERTENSIVE-RAT; AUTISM SPECTRUM DISORDERS; HIDDEN-MARKOV
MODEL; SNP GENOTYPING DATA; DEFICIT/HYPERACTIVITY-DISORDER; MICE
LACKING; CHILDREN; ADHD; REPLICATION; LINKAGE
AB Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms. CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 x 10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 x 10(-6)). We saw GRM7 deletions in six cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was duplicated in eight cases. We experimentally validated the observed variants using quantitative RT-PCR. A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in similar to 10% of the cases (P = 4.38 x 10(-10)) after correction for occurrence in the controls. We identified rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts.
C1 [Glessner, Joseph T.; Wang, Kai; Hadley, Dexter; Sleiman, Patrick M. A.; Zhang, Haitao; Kim, Cecilia E.; Flory, James H.; Bradfield, Jonathan P.; Imielinski, Marcin; Hou, Cuiping; Frackelton, Edward C.; Chiavacci, Rosetta M.; Thomas, Kelly A.; Garris, Maria; Mentch, Frank] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Elia, Josephine] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Elia, Josephine] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat, Philadelphia, PA 19104 USA.
[Takahashi, Nagahide; Sakurai, Takeshi; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, Lab Mol Neuropsychiat, New York, NY USA.
[Shtir, Corina J.] Univ Calif Los Angeles, Dept Human Genet & Psychiat, Los Angeles, CA USA.
[Robison, Reid; Lyon, Gholson J.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA.
[Rabin, Cara; Shaw, Philip] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Middleton, Frank A.; Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA.
[Freitag, Christine M.] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosom & psyc, Frankfurt, Germany.
[Steinhausen, Hans-Christoph; Asherson, Philip] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland.
[Steinhausen, Hans-Christoph] Aarhus Univ Hosp, Aalborg Psychiat Hosp, DK-8000 Aarhus, Denmark.
[Steinhausen, Hans-Christoph] Univ Basel, Inst Psychol, Basel, Switzerland.
[Todorov, Alexandre A.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Reif, Andreas; Lesch, Klaus-Peter] Univ Wurzburg, Attent Deficit Hyperact Disorder Clin Res Network, Unit Mol Psychiat, Dept Psychiat Psychosomat & Psychotherapy, D-97070 Wurzburg, Germany.
[Rothenberger, Aribert] Univ Gottingen, Gottingen, Germany.
[Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Donders Inst Brain Cognit & Behav,Ctr Neurosci, NL-6525 ED Nijmegen, Netherlands.
[Mick, Eric O.; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Roeyers, Herbert] Univ Ghent, Dept Expt Clin & Hlth Psychol, B-9000 Ghent, Belgium.
[Buitelaar, Jan] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands.
[Banaschewski, Tobias] Heidelberg Univ, Dept Child & Adolescent Psychiat & Psychotherapy, Cent Inst Mental Hlth, D-6800 Mannheim, Germany.
[Ebstein, Richard P.] Natl Univ Singapore, Dept Psychol, Queenstown, Singapore.
[Mulas, Fernando] La Fe Univ Hosp, Fac Med, Dept Neuropaediat, Valencia, Spain.
[Oades, Robert D.] Univ Duisburg Essen, Clin Child & Adolescent Psychiat, Essen, Germany.
[Sergeant, Joseph] Vrije Univ Amsterdam, Amsterdam, Netherlands.
[Sonuga-Barke, Edmund J. S.] Univ Southampton, Sch Psychol, Inst Disorder Impulse & Attent, Southampton, Hants, England.
[Sonuga-Barke, Edmund J. S.] Univ Ghent, Dept Expt Clin & Hlth Psychol, B-9000 Ghent, Belgium.
[Sonuga-Barke, Edmund J. S.] NYU, Ctr Child Study, New York, NY USA.
[Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Warnke, Andreas; Walitza, Susanne] Univ Wurzburg, Dept Child & Adolescent Psychiat Psychosomat & Ps, Wurzburg, Germany.
[Romanos, Marcel] Univ Hosp Munich, Dept Child & Adolescent Psychiat Psychosomat & Ps, Munich, Germany.
[Meyer, Jobst; Palmason, Haukur] Univ Trier, Dept Neurobehav Genet, Inst Psychobiol, Trier, Germany.
[Seitz, Christiane] Univ Saarland, Dept Child & Adolescent Psychiat, D-6650 Homburg, Germany.
[Loo, Sandra K.; Smalley, Susan L.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
[Kent, Lindsey] Bute Med Sch, St Andrews, Fife, Scotland.
[Anney, Richard J. L.] St James Hosp, Dept Psychiat, Trinity Ctr Hlth Sci, Dublin 8, Ireland.
[Gaynor, J. William; Hakonarson, Hakon] Childrens Hosp Philadelphia, Div Cardiothorac Surg, Philadelphia, PA 19104 USA.
[Devoto, Marcella; Grant, Struan F. A.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA.
[Devoto, Marcella; Grant, Struan F. A.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
[Devoto, Marcella] Univ Roma La Sapienza, Dipartimento Med Sperimentale, Rome, Italy.
[Devoto, Marcella] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[White, Peter S.] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA.
[White, Peter S.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Williams, Nigel M.] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
[Hakonarson, Hakon] Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA.
RP Hakonarson, H (reprint author), Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
EM hakonarson@email.chop.edu
RI Lyon, Gholson/D-2765-2014; Renner, Tobias/I-2120-2013; Franke,
Barbara/D-4836-2009; Nelson, Stanley/D-4771-2009; Sonuga-Barke,
Edmund/D-9137-2011; Buitelaar, Jan/E-4584-2012; Lesch,
Klaus-Peter/J-4906-2013; Romanos, Marcel/D-7695-2017;
OI Lyon, Gholson/0000-0002-5869-0716; Kent, Lindsey/0000-0002-5315-3399;
Mick, Eric/0000-0001-8505-8145; Buxbaum, Joseph/0000-0001-8898-8313;
Franke, Barbara/0000-0003-4375-6572; Buitelaar, Jan/0000-0001-8288-7757;
Lesch, Klaus-Peter/0000-0001-8348-153X; Walitza,
Susanne/0000-0002-8161-8683; Anney, Richard/0000-0002-6083-407X;
Faraone, Stephen/0000-0002-9217-3982
FU US National Institutes of Health (NIH) [R01MH62873]; NIH [K23MH066275];
Pfizer; CHOP; University of Pennsylvania National Center for Research
Resources [UL1-RR-024134]; Cotswold Foundation; US Department of Health
and Human Services [1RC2MH089924]; Seaver Foundation; NIMH
[P50MH066392]; Deutsche Forschungsgemeinschaft [KFO 125, SFB 581, SFB
TRR 58, ME 1923/5-1, ME 1923/5-3]; Bundesministerium fur Bildung und
Forschung (BMBF) [01GV0605]
FX We thank the IMAGE, IMAGE II and PUWMa consortium investigators and the
NIMH for making the genotype data available. Funding support for
International Multi-Center ADHD Genetics (IMAGE) and IMAGE II Projects
was provided by US National Institutes of Health (NIH) grant R01MH62873
to S. V. F., and the genotyping of samples was provided through the
Genetic Association Information Network (GAIN). The dataset used for the
IMAGE analyses described in this manuscript were obtained from the
database of Genotype and Phenotype (dbGaP), which is found at
http://www.ncbi.nlm.nih.gov/gap, through dbGaP accession numbers
phs000016.v2.p2 (ADHD IMAGE), phs000020.v2.p1 (depression) and
phs000019.v1.p1 (psoriasis). Samples and associated phenotype data for
the GAIN Major Depression: Stage 1 Genome-wide Association In Population
Based Samples Study (principal investigator, P. F. Sullivan, University
of North Carolina) were provided by D. I. Boomsma and E. de Geus, Vrije
Universiteit Amsterdam (principal investigators, Netherlands Twin
Register); B. W. Penninx, Vrije Universiteit Medical Center Amsterdam;
F. Zitman, Leiden University Medical Center, Leiden; and W. Nolen,
University Medical Center Groningen (principal investigators and site
principal investigators, Netherlands Study of Depression and Anxiety).
Samples and associated phenotype data for the Collaborative Association
Study of Psoriasis were provided by J.T. Elder (University of Michigan,
Ann Arbor, Michigan), G. G. Krueger (University of Utah, Salt Lake City,
Utah), A. Bowcock (Washington University, St. Louis, Missouri) and G. R.
Abecasis (University of Michigan, Ann Arbor, Michigan). Samples and
associated phenotype data for the International Multi-Center ADHD
Genetics Project were provided by the following investigators: S. V. F.
(principal investigator), R.J.L.A., P. A., J.S., R. P. E., B. F., M.
Gill, A. Miranda, F. Mulas, R. D. O., H. R., A. Rothenberger, T. B., J.
Buitelaar, E. Sonuga-Barke and H.-C. S. (site principal investigators),
M. Daly, C. Lange, N. Laird, J. Su and B. Neale (statistical analysis
team). Samples and associated phenotype data were accessed through an
authorized data access request by H. H. and S. F. A. G. Data collection
for the PUWMa sample was supported by NIH grants to S. V. F., J.
Biederman, S. Smalley, R. Todd and A. A. T. GWAS genotyping of the PUWMa
samples was completed by Genizon and was provided through a grant for
genotyping services to S. V. F. The PUWMa consortium represents a
Pfizer-funded collaboration among the University of California Los
Angeles, Washington University and Massachussetts General Hospital. We
thank M. C. O'Donovan, M. Gill, M. J. Owen, P. A. Holmans, A. Thapar, B.
M. Neale and A. Miranda for contributing DNA samples and phenotypes to
the study and for editing the manuscript. We thank G. DePalma, T.
Topner, A. Guiney and H. Zhang for providing samples for the qRT-PCR CNV
validation.; The study was supported by an Institutional Development
Award to the Center for Applied Genomics from CHOP (H. H.), which funded
all of the discovery genome-wide genotyping for this study. This work
was additionally supported in part by NIH grant K23MH066275 (J. E.),
University of Pennsylvania National Center for Research Resources
Clinical and Translational Science Awards grant UL1-RR-024134 (J. E.),
by a Research Development Award from the Cotswold Foundation (H. H. and
S. F. A. G.) and by US Department of Health and Human Services grant
1RC2MH089924 (H. H.). N. T., T. S. and J. D. B. received support from
the Seaver Foundation and a Conte Center for Neuroscience of Mental
Disorders grant from the NIMH (P50MH066392).; Sample and phenotype data
collection of parts of the IMAGE II cohort was supported by the Deutsche
Forschungsgemeinschaft (KFO 125, SFB 581 and SFB TRR 58 to K.-P.L. and
A. Reif, ME 1923/5-1 and ME 1923/5-3 to C.M.F. and J.M.) and the
Bundesministerium fur Bildung und Forschung (BMBF 01GV0605 to K.-P.L.).
NR 58
TC 110
Z9 111
U1 1
U2 14
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 JAN
PY 2012
VL 44
IS 1
BP 78
EP U113
DI 10.1038/ng.1013
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 870JA
UT WOS:000298664000018
PM 22138692
ER
PT S
AU Uhlmann, EJ
Plotkin, SR
AF Uhlmann, Erik J.
Plotkin, Scott R.
BE Ahmad, SI
TI NEUROFIBROMATOSES
SO NEURODEGENERATIVE DISEASES
SE Advances in Experimental Medicine and Biology
LA English
DT Article; Book Chapter
ID TUMOR-SUPPRESSOR GENE; VESTIBULAR SCHWANNOMA GROWTH;
DIAGNOSTIC-CRITERIA; CELL-PROLIFERATION; CYCLIN D1; NF2 GENE; FAMILIAL
SCHWANNOMATOSIS; RHABDOID TUMORS; SIZE-CONTROL; TYPE-1 GENE
AB The studies of familial tumor predisposition syndromes have contributed immensely to our understanding of oncogenesis. Neurofibromatosis 1, neurofibromatosis 2 and schwannomatosis are inherited autosomal dominant neurocutaneous disorders with complete penetrance. They are clinically and genetically distinct and considerable knowledge has been gathered about their pathogenesis. In this chapter, the genetics, molecular mechanism of disease, as well as clinical features, diagnosis and treatment are discussed.
C1 [Uhlmann, Erik J.; Plotkin, Scott R.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA.
RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA.
EM splotkin@partners.org
NR 78
TC 12
Z9 12
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 0065-2598
BN 978-1-4614-0652-5; 978-1-4614-0653-2
J9 ADV EXP MED BIOL
JI Adv.Exp.Med.Biol.
PY 2012
VL 724
BP 266
EP 277
D2 10.1007/978-1-4614-0653-2
PG 12
WC Medicine, Research & Experimental; Clinical Neurology; Neurosciences
SC Research & Experimental Medicine; Neurosciences & Neurology
GA BA2XJ
UT WOS:000333978900022
PM 22411249
ER
PT J
AU Bakhtiari, R
Zurcher, NR
Rogier, O
Russo, B
Hippolyte, L
Granziera, C
Araabi, BN
Ahmadabadi, MN
Hadjikhani, N
AF Bakhtiari, Reyhaneh
Zuercher, Nicole R.
Rogier, Ophelie
Russo, Britt
Hippolyte, Loyse
Granziera, Cristina
Araabi, Babak Nadjar
Ahmadabadi, Majid Nili
Hadjikhani, Nouchine
TI Differences in white matter reflect atypical developmental trajectory in
autism: A Tract-based Spatial Statistics study
SO NEUROIMAGE-CLINICAL
LA English
DT Article
DE Diffusion Tensor Imaging; Autism spectrum disorder; Brain connectivity;
Fractional anisotropy; Brain development; Brain maturation
AB Autism is a neurodevelopmental disorder in which white matter (WM) maturation is affected. We assessed WM integrity in 16 adolescents and 14 adults with high-functioning autism spectrum disorder (ASD) and in matched neurotypical controls (NT) using diffusion weighted imaging and Tract-based Spatial Statistics. Decreased fractional anisotropy (FA) was observed in adolescents with ASD in tracts involved in emotional face processing, language, and executive functioning, including the inferior fronto-occipital fasciculus and the inferior and superior longitudinal fasciculi. Remarkably, no differences in FA were observed between ASD and NT adults.
We evaluated the effect of age on WM development across the entire age range. Positive correlations between FA values and age were observed in the right inferior fronto-occipital fasciculus, the left superior longitudinal fasciculus, the corpus callosum, and the cortical spinal tract of ASD participants, but not in NT participants.
Our data underscore the dynamic nature of brain development in ASD, showing the presence of an atypical process of WM maturation, that appears to normalize over time and could be at the basis of behavioral improvements often observed in high-functioning autism. (C) 2012 The Authors. Published by Elsevier Inc. Open access under CC BY-NC-ND license.
C1 [Bakhtiari, Reyhaneh; Araabi, Babak Nadjar; Ahmadabadi, Majid Nili] Univ Tehran, Coll Engn, Sch Elect & Comp Engn, Control & Intelligent Proc Ctr Excellence, Tehran, Iran.
[Bakhtiari, Reyhaneh; Araabi, Babak Nadjar; Ahmadabadi, Majid Nili] Inst Res Fundamental Sci IPM, Dept Cognit Sci, Tehran, Iran.
[Bakhtiari, Reyhaneh; Zuercher, Nicole R.; Rogier, Ophelie; Russo, Britt; Hippolyte, Loyse; Granziera, Cristina; Hadjikhani, Nouchine] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lausanne, Switzerland.
[Hadjikhani, Nouchine] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Sch Med, Charlestown, MA USA.
RP Hadjikhani, N (reprint author), MGH HMS HST Athinoula A Martinos Ctr Biomed Imagi, 149 13th St, Charlestown, MA 02129 USA.
EM nouchine@nmr.mgh.harvard.edu
RI Nadjar Araabi, Babak/C-5069-2017;
OI Nadjar Araabi, Babak/0000-0002-5283-263X; Hadjikhani,
Nouchine/0000-0003-4075-3106; Granziera, Cristina/0000-0002-4917-8761
FU Swiss National Foundation [PP00P3-130191/PPOOB-110741]; Centre
d'Imagerie BioMedicale (CIBM) of the University of Lausanne (UNIL);
Swiss Federal Institute of Technology Lausanne (EPFL); University of
Geneva (UniGe); Centre Hospitalier Universitaire Vaudois (CHUV);
Hopitaux Universitaires de Geneve (HUG); Leenaards; Jeantet Foundations
FX We thank K. Metrailler for her support in participants' recruitment, C.
Burget for her administrative assistance, and A. Lissot for his help
with data analysis and technical support. Funding: This work was
supported by the Swiss National Foundation grant
#PP00P3-130191/PPOOB-110741 to NH, and by the Centre d'Imagerie
BioMedicale (CIBM) of the University of Lausanne (UNIL), the Swiss
Federal Institute of Technology Lausanne (EPFL), the University of
Geneva (UniGe), the Centre Hospitalier Universitaire Vaudois (CHUV), the
Hopitaux Universitaires de Geneve (HUG) and the Leenaards and the
Jeantet Foundations.
NR 105
TC 15
Z9 15
U1 1
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2012
VL 1
IS 1
BP 48
EP 56
DI 10.1016/j.nicl.2012.09.001
PG 9
WC Neuroimaging
SC Neurosciences & Neurology
GA V37LG
UT WOS:000209276700006
PM 24179736
ER
PT J
AU Lord, LD
Allen, P
Expert, P
Howes, O
Broome, M
Lambiotte, R
Fusar-Poli, P
Valli, I
McGuire, P
Turkheimer, FE
AF Lord, Louis-David
Allen, Paul
Expert, Paul
Howes, Oliver
Broome, Matthew
Lambiotte, Renaud
Fusar-Poli, Paolo
Valli, Isabel
McGuire, Philip
Turkheimer, Federico E.
TI Functional brain networks before the onset of psychosis: A prospective
fMRI study with graph theoretical analysis
SO NEUROIMAGE-CLINICAL
LA English
DT Article
DE Graph theory; At-risk mental state; Schizophrenia; Cingulate; fMRI
AB Individuals with an at-risk mental state (ARMS) have a risk of developing a psychotic disorder significantly greater than the general population. However, it is not currently possible to predict which ARMS individuals will develop psychosis from clinical assessment alone. Comparison of ARMS subjects who do, and do not, develop psychosis can reveal which factors are critical for the onset of illness. In the present study, 37 patients with an ARMS were followed clinically at least 24 months subsequent to initial referral. Functional MRI data were collected at the beginning of the follow-up period during performance of an executive task known to recruit frontal lobe networks and to be impaired in psychosis. Graph theoretical analysis was used to compare the organization of a functional brain network in ARMS patients who developed a psychotic disorder following the scan (ARMS-T) to those who did not become ill during the same follow-up period (ARMS-NT) and aged-matched controls. The global properties of each group's representative network were studied (density, efficiency, global average path length) as well as regionally-specific contributions of network nodes to the organization of the system (degree, farness-centrality, betweenness-centrality). We focused our analysis on the dorsal anterior cingulate cortex (ACC), a region known to support executive function that is structurally and functionally impaired in ARMS patients. In the absence of between-group differences in global network organization, we report a significant reduction in the topological centrality of the ACC in the ARMS-T group relative to both ARMS-NT and controls. These results provide evidence that abnormalities in the functional organization of the brain predate the onset of psychosis, and suggest that loss of ACC topological centrality is a potential biomarker for transition to psychosis. (C) 2012 The Authors. Published by Elsevier Inc. Open access under CC BY-NC-ND license.
C1 [Lord, Louis-David; Expert, Paul; Howes, Oliver; Turkheimer, Federico E.] Univ London Imperial Coll Sci Technol & Med, Dept Expt Med, London SW7 2AZ, England.
[Allen, Paul; Expert, Paul; Howes, Oliver; Fusar-Poli, Paolo; Valli, Isabel; McGuire, Philip; Turkheimer, Federico E.] Kings Coll London, Inst Psychiat, London WC2R 2LS, England.
[Expert, Paul] Univ London Imperial Coll Sci Technol & Med, Complex & Networks Grp, London SW7 2AZ, England.
[Lord, Louis-David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA.
[Lambiotte, Renaud] Univ Namur, Dept Math, Namur, Belgium.
[Broome, Matthew] Univ Warwick, Hlth Sci Res Inst, Coventry CV4 7AL, W Midlands, England.
[Allen, Paul; Fusar-Poli, Paolo; Valli, Isabel; McGuire, Philip] South London & Maudsley NHS Fdn, OASIS Team, London, England.
RP Lord, LD (reprint author), 149 Thirteenth St, Charlestown, MA 02129 USA.
EM LDL@nmr.mgh.harvard.edu
RI Howes, Oliver/E-7156-2010;
OI Howes, Oliver/0000-0002-2928-1972; Allen, Paul/0000-0001-8510-878X;
Lambiotte, Renaud/0000-0002-0583-4595
FU EPSRC [EP/E049451/1]; MRC [U.1200.04.007.00001.01]
FX The project has been funded in part by the EPSRC Grant EP/E049451/1 and
MRC Grant U.1200.04.007.00001.01.
NR 52
TC 10
Z9 10
U1 1
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1582
J9 NEUROIMAGE-CLIN
JI NeuroImage-Clin.
PY 2012
VL 1
IS 1
BP 91
EP 98
DI 10.1016/j.nicl.2012.09.008
PG 8
WC Neuroimaging
SC Neurosciences & Neurology
GA V37LG
UT WOS:000209276700011
PM 24179741
ER
PT J
AU Smith, MR
AF Smith, Matthew R.
TI Role of VEGFR and MET in Prostate Cancer and Bone Metastases
SO ONCOLOGIST
LA English
DT Meeting Abstract
C1 [Smith, Matthew R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PY 2012
VL 17
SU 3
MA 2
BP 1
EP 1
PG 1
WC Oncology
SC Oncology
GA 274LI
UT WOS:000328607500003
ER
PT J
AU Corcoran, RB
AF Corcoran, Ryan B.
TI Resistance to RAF Inhibition in BRAF Mutant Colorectal Cancer
SO ONCOLOGIST
LA English
DT Meeting Abstract
C1 [Corcoran, Ryan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PY 2012
VL 17
SU 3
MA 4
BP 2
EP 2
PG 1
WC Oncology
SC Oncology
GA 274LI
UT WOS:000328607500005
ER
PT J
AU Ramaswamy, S
AF Ramaswamy, Sridhar
TI Targeting Quiescent Cancer Cells
SO ONCOLOGIST
LA English
DT Meeting Abstract
C1 [Ramaswamy, Sridhar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PY 2012
VL 17
SU 3
MA 3
BP 2
EP 2
PG 1
WC Oncology
SC Oncology
GA 274LI
UT WOS:000328607500004
ER
PT J
AU Benes, C
AF Benes, Cyril
TI Systematic Identification of Genomic Markers of Drug Sensitivity in
Cancer Cells
SO ONCOLOGIST
LA English
DT Meeting Abstract
C1 [Benes, Cyril] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PY 2012
VL 17
SU 3
MA 5
BP 3
EP 3
PG 1
WC Oncology
SC Oncology
GA 274LI
UT WOS:000328607500006
ER
PT J
AU Sykes, DB
AF Sykes, David Brian
TI Identifying Small Molecules that Overcome Differentiation Arrest in
Acute Myeloid Leukemia
SO ONCOLOGIST
LA English
DT Meeting Abstract
C1 [Sykes, David Brian] Massachusetts Gen Hosp, Ctr Canc, Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PY 2012
VL 17
SU 3
MA 6
BP 3
EP 3
PG 1
WC Oncology
SC Oncology
GA 274LI
UT WOS:000328607500007
ER
PT J
AU Elia, AEH
AF Elia, Andrew E. H.
TI Proteomic Approaches to Study Ubiquitination and Protein Stability
SO ONCOLOGIST
LA English
DT Meeting Abstract
C1 [Elia, Andrew E. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PY 2012
VL 17
SU 3
MA 7
BP 4
EP 4
PG 1
WC Oncology
SC Oncology
GA 274LI
UT WOS:000328607500008
ER
PT J
AU Losman, JA
AF Losman, Julie-Aurore
TI Functional Studies of the Isocitrate Dehydrogenase (IDH) Oncoprotein
SO ONCOLOGIST
LA English
DT Meeting Abstract
C1 [Losman, Julie-Aurore] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PY 2012
VL 17
SU 3
MA 8
BP 4
EP 4
PG 1
WC Oncology
SC Oncology
GA 274LI
UT WOS:000328607500009
ER
PT J
AU Breakefield, X
AF Breakefield, Xandra
TI Exosomes as Biomarkers of the Genetic Status of Brain Tumors
SO ONCOLOGIST
LA English
DT Meeting Abstract
C1 [Breakefield, Xandra] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PY 2012
VL 17
SU 3
MA 10
BP 5
EP 5
PG 1
WC Oncology
SC Oncology
GA 274LI
UT WOS:000328607500011
ER
PT J
AU Wiecek, E
Dakin, S
Bex, P
AF Wiecek, E.
Dakin, S.
Bex, P.
TI Metamorphopsia and visual acuity
SO PERCEPTION
LA English
DT Meeting Abstract
C1 [Wiecek, E.; Dakin, S.] UCL, London WC1E 6BT, England.
[Bex, P.] Massachusetts Eye & Ear Infirm, Boston, MA USA.
EM emilywiecek@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PION LTD
PI LONDON
PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND
SN 0301-0066
EI 1468-4233
J9 PERCEPTION
JI Perception
PY 2012
VL 41
SU S
MA 125
BP 158
EP 159
PG 2
WC Ophthalmology; Psychology; Psychology, Experimental
SC Ophthalmology; Psychology
GA V31WA
UT WOS:000208912500499
ER
PT B
AU Sepulveda, JL
AF Sepulveda, Jorge L.
BE Dasgupta, A
Langman, LJ
TI Genetic Aspect of Opiate Metabolism and Addiction
SO PHARMACOGENOMICS OF ALCOHOL AND DRUGS OF ABUSE
LA English
DT Article; Book Chapter
ID OPIOID RECEPTOR GENE; METHADONE-MAINTENANCE TREATMENT; HUMAN
LIVER-MICROSOMES; SINGLE-NUCLEOTIDE POLYMORPHISM; P-GLYCOPROTEIN;
ALCOHOL DEPENDENCE; GLUCURONOSYLTRANSFERASE 2B7; HEROIN-ADDICTION;
N-DEMETHYLATION; CANCER-PATIENTS
C1 [Sepulveda, Jorge L.] Philadelphia VA Med Ctr, Pathol & Lab Med Serv, Philadelphia, PA 19104 USA.
[Sepulveda, Jorge L.] Univ Penn, Philadelphia, PA 19104 USA.
RP Sepulveda, JL (reprint author), Philadelphia VA Med Ctr, Pathol & Lab Med Serv, Philadelphia, PA 19104 USA.
NR 139
TC 0
Z9 0
U1 1
U2 3
PU CRC PRESS-TAYLOR & FRANCIS GROUP
PI BOCA RATON
PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA
BN 978-1-4398-5612-3; 978-1-4398-5611-6
PY 2012
BP 165
EP 194
D2 10.1201/b11879
PG 30
WC Substance Abuse; Pharmacology & Pharmacy
SC Substance Abuse; Pharmacology & Pharmacy
GA BC9LX
UT WOS:000356613400009
ER
PT B
AU Sepulveda, JL
AF Sepulveda, Jorge L.
BE Dasgupta, A
Langman, LJ
TI Methodologies in Pharmacogenetics Testing
SO PHARMACOGENOMICS OF ALCOHOL AND DRUGS OF ABUSE
LA English
DT Article; Book Chapter
ID DNA; DIAGNOSTICS; ASSAY; NANOPORE; INVADER
C1 [Sepulveda, Jorge L.] Philadelphia VA Med Ctr, Pathol & Lab Med Serv, Philadelphia, PA 19104 USA.
[Sepulveda, Jorge L.] Univ Penn, Philadelphia, PA 19104 USA.
RP Sepulveda, JL (reprint author), Philadelphia VA Med Ctr, Pathol & Lab Med Serv, Philadelphia, PA 19104 USA.
NR 27
TC 0
Z9 0
U1 0
U2 0
PU CRC PRESS-TAYLOR & FRANCIS GROUP
PI BOCA RATON
PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA
BN 978-1-4398-5612-3; 978-1-4398-5611-6
PY 2012
BP 211
EP 228
D2 10.1201/b11879
PG 18
WC Substance Abuse; Pharmacology & Pharmacy
SC Substance Abuse; Pharmacology & Pharmacy
GA BC9LX
UT WOS:000356613400011
ER
PT B
AU Farid, M
Spiegel, B
AF Farid, Mary
Spiegel, Brennan
BE Plevris, JN
Howden, CW
TI The Clinical Approach to Dyspepsia
SO PROBLEM-BASED APPROACH TO GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article; Book Chapter
ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PATIENTS; PEPTIC-ULCER
DISEASE; HELICOBACTER-PYLORI; MANAGEMENT
C1 [Farid, Mary] Univ Calif Los Angeles, Affiliated Training Program Digest Dis, Los Angeles, CA 90095 USA.
[Spiegel, Brennan] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA.
[Spiegel, Brennan] UCLA VA Ctr Outcomes Res & Educ, Los Angeles, CA USA.
RP Farid, M (reprint author), Univ Calif Los Angeles, Affiliated Training Program Digest Dis, Los Angeles, CA 90095 USA.
RI Plevris, John/O-3517-2014
NR 10
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
BN 978-1-4051-8227-0; 978-1-4443-4635-0
PY 2012
BP 39
EP 43
D2 10.1002/9781444346381
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA BA6GX
UT WOS:000337140200004
ER
PT S
AU Gopal, D
Ho, AL
Shah, A
Chi, JH
AF Gopal, Dipika
Ho, Allen L.
Shah, Amol
Chi, John H.
BE Jandial, R
Chen, MY
TI MOLECULAR BASIS OF INTERVERTEBRAL DISC DEGENERATION
SO REGENERATIVE BIOLOGY OF THE SPINE AND SPINAL CORD
SE Advances in Experimental Medicine and Biology
LA English
DT Article; Book Chapter
ID MESENCHYMAL STEM-CELLS; NUCLEUS PULPOSUS CELLS; AMINO-ACID COMPOSITION;
ISSLS PRIZE WINNER; IN-VIVO; MATRIX METALLOPROTEINASES;
ARTICULAR-CARTILAGE; GROWTH-FACTOR; REPLICATIVE SENESCENCE;
PHYSIOLOGICAL-FUNCTION
AB Intervertebral disc (IVD) degeneration is a disease of the discs connecting adjoining vertebrae in which structural damage leads to degeneration of the disc and surrounding area. Degeneration of the disc is considered to be a normal process of aging, but can accelerate faster than expected or be precipitated by other factors. The scientific community has come a long way in understanding the biological basis and interpreting the lifestyle implications of IVD degeneration. Of all the diseases of the intervertebral disc, degeneration is the most common and has earned much attention due to its diversity in presentation and potential multiorgan involvement. We will provide a brief overview of the anatomic, cellular, and molecular structure of the IVD, and delve into the cellular and molecular pathophysiology surrounding IVD degeneration. We will then highlight some of the newest developments in stem cell, protein, and genetic therapy for IVD degeneration.
C1 [Gopal, Dipika; Shah, Amol] Univ Calif San Diego, San Diego Sch Med, San Diego, CA 92103 USA.
[Ho, Allen L.] Harvard Univ, Harvard Med Sch, Cambridge, MA 02138 USA.
[Chi, John H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Neurosurg, Boston, MA 02115 USA.
RP Ho, AL (reprint author), Harvard Univ, Harvard Med Sch, Cambridge, MA 02138 USA.
EM allenlho@gmail.com
NR 128
TC 12
Z9 16
U1 0
U2 5
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0065-2598
BN 978-1-4614-4089-5; 978-1-4614-4090-1
J9 ADV EXP MED BIOL
JI Adv.Exp.Med.Biol.
PY 2012
VL 760
BP 114
EP 133
D2 10.1007/978-1-4614-4090-1
PG 20
WC Medicine, Research & Experimental; Neurosciences
SC Research & Experimental Medicine; Neurosciences & Neurology
GA BA2ST
UT WOS:000333849500008
PM 23281517
ER
PT S
AU Ruddy, KJ
Partridge, AH
AF Ruddy, Kathryn J.
Partridge, Ann H.
BE Quinn, GP
Vadaparampil, ST
TI The Unique Reproductive Concerns of Young Women with Breast Cancer
SO REPRODUCTIVE HEALTH AND CANCER IN ADOLESCENTS AND YOUNG ADULTS
SE Advances in Experimental Medicine and Biology
LA English
DT Article; Book Chapter
ID CHEMOTHERAPY-INDUCED AMENORRHEA; LONG-TERM AMENORRHEA; IN-VITRO
MATURATION; PREMENOPAUSAL WOMEN; ADJUVANT CHEMOTHERAPY; FERTILITY
PRESERVATION; OVARIAN RESERVE; EMBRYO CRYOPRESERVATION;
RANDOMIZED-TRIAL; TIME-COURSE
AB I am a 35 year old woman whose boyfriend found a mass in my breast two months ago. A biopsy showed it was breast cancer, and I was ultimately recommended to undergo chemotherapy and tamoxifen in addition to surgery. I told them I would very much like to be able to have children in the future, so my oncologist said I should consider embryo cryopreservation, as my likelihood of being able to conceive naturally after chemotherapy and at age 40, when the tamoxifen was finished, would not be high. However, she acknowledged that no one is sure whether ovarian stimulation prior to treatment, especially when my cancer was hormone sensitive, is safe. I met with a reproductive endocrinologist later that week, and we went over the pros and cons of fertility preservation options. My boyfriend I discussed it and we decided to move forward with embryo cryopreservation. Because my period had recently finished, I started ovarian stimulation quickly and had eggs harvested, fertilized with my boyfriend's sperm, and frozen less than two weeks later. I started chemotherapy the next day. While I realize there is uncertainty about the safety of pregnancy after breast cancer, knowing that I have taken steps to preserve my fertility is very reassuring to me as I begin my treatment. Diana, Breast Cancer Survivor
C1 [Ruddy, Kathryn J.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA.
RP Ruddy, KJ (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA.
EM kathryn_ruddy@dfci.harvard.edu; ann_partridge@dfci.harvard.edu
NR 75
TC 6
Z9 6
U1 1
U2 3
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0065-2598
BN 978-94-007-2491-4; 978-94-007-2492-1
J9 ADV EXP MED BIOL
JI Adv.Exp.Med.Biol.
PY 2012
VL 732
BP 77
EP 87
DI 10.1007/978-94-007-2492-1_6
D2 10.1007/978-94-007-2492-1
PG 11
WC Oncology; Reproductive Biology
SC Oncology; Reproductive Biology
GA BA3CI
UT WOS:000334104800008
PM 22210253
ER
PT S
AU Russell, KS
Rauch, PK
AF Russell, Kristin S.
Rauch, Paula K.
BE Quinn, GP
Vadaparampil, ST
TI Parenting with Cancer I: Developmental Perspective, Communication, and
Coping
SO REPRODUCTIVE HEALTH AND CANCER IN ADOLESCENTS AND YOUNG ADULTS
SE Advances in Experimental Medicine and Biology
LA English
DT Article; Book Chapter
ID QUALITY-OF-LIFE; BREAST-CANCER; PSYCHOLOGICAL DISTRESS;
BEHAVIORAL-PROBLEMS; TERMINAL ILLNESS; TELLING CHILDREN; GUIDANCE
PROGRAM; AGE-CHILDREN; PRIMARY-CARE; FAMILY
AB Mary is a 45-year-old married mother of three children, 6 year old Sarah, 10 year old Katie, and 15 year old Ethan. She was diagnosed with breast cancer several months ago, and she and her husband have discussed the diagnosis openly with all three children. She comes to the clinic for her first chemotherapy infusion. When the nurse, who knows her well, inquires about how things have been going with her children, Mary starts to cry. She says that Sarah, her youngest daughter, has been asking a lot of questions that are hard to answer; particularly upsetting is the question, "Why did you get cancer mommy and when will I get cancer?" Katie, her middle daughter, has been very anxious about Mary losing her hair and wants her to wear her wig all the time. Mary promised Katie she would, but she wishes she could take the wig off at home. She's not worried about her oldest, Ethan, because he is always out with his friends and never at home. She hasn't been checking in with him, and is hoping he's doing his schoolwork. She appreciates all the calls from neighbors and friends from church, but has been overwhelmed by the constant calls and offers of help. Mary, Adult Cancer Patient
C1 [Russell, Kristin S.; Rauch, Paula K.] Massachusetts Gen Hosp, Marjorie E Korff PACT Parenting Challenging Time, Boston, MA 02114 USA.
[Rauch, Paula K.] Massachusetts Gen Hosp, Child Psychiat Consultat Liaison Serv, Boston, MA 02114 USA.
RP Russell, KS (reprint author), Massachusetts Gen Hosp, Marjorie E Korff PACT Parenting Challenging Time, Boston, MA 02114 USA.
EM ksrussell@partners.org; prauch@partners.org
NR 47
TC 2
Z9 2
U1 1
U2 5
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0065-2598
BN 978-94-007-2491-4; 978-94-007-2492-1
J9 ADV EXP MED BIOL
JI Adv.Exp.Med.Biol.
PY 2012
VL 732
BP 131
EP 140
DI 10.1007/978-94-007-2492-1_10
D2 10.1007/978-94-007-2492-1
PG 10
WC Oncology; Reproductive Biology
SC Oncology; Reproductive Biology
GA BA3CI
UT WOS:000334104800012
PM 22210257
ER
PT S
AU Russell, KS
Rauch, PK
AF Russell, Kristin S.
Rauch, Paula K.
BE Quinn, GP
Vadaparampil, ST
TI Parenting with Cancer II: Parenting at Different Stages of Illness
SO REPRODUCTIVE HEALTH AND CANCER IN ADOLESCENTS AND YOUNG ADULTS
SE Advances in Experimental Medicine and Biology
LA English
DT Article; Book Chapter
ID QUALITY-OF-LIFE; BREAST-CANCER; PSYCHOLOGICAL DISTRESS;
BEHAVIORAL-PROBLEMS; TERMINAL ILLNESS; TELLING CHILDREN; AGE-CHILDREN;
ADOLESCENTS; FAMILY; IMPACT
AB Brian is a 54-year-old father of two boys (6 and 8) with pancreatic cancer. Alexandra, his oncology social worker, has met with Brian and his wife, Nancy, several times over the past year to discuss parenting issues. In their first meeting, Brian had just been diagnosed and the couple had not yet talked to their children. In the next meeting, Brian was about to have surgery and they discussed how to best prepare the children to visit him in the hospital. In preparation for her next meeting with the couple, Alexandra approaches Brian's medical team for information regarding the status of Brian's treatment and whether there will be a shift to end-of-life care this month. Alexandra needs input from the team in order to provide information about legacy leaving, end-of-life care, and funeral planning at an appropriate time. Brian, Adult Cancer Patient
C1 [Russell, Kristin S.; Rauch, Paula K.] Massachusetts Gen Hosp, Marjorie E Korff PACT Parenting Challenging Time, Boston, MA 02114 USA.
[Rauch, Paula K.] Massachusetts Gen Hosp, Child Psychiat Consultat Liaison Serv, Boston, MA 02114 USA.
RP Russell, KS (reprint author), Massachusetts Gen Hosp, Marjorie E Korff PACT Parenting Challenging Time, Boston, MA 02114 USA.
EM ksrussell@partners.org; prauch@partners.org
NR 29
TC 2
Z9 2
U1 0
U2 2
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0065-2598
BN 978-94-007-2491-4; 978-94-007-2492-1
J9 ADV EXP MED BIOL
JI Adv.Exp.Med.Biol.
PY 2012
VL 732
BP 141
EP 149
DI 10.1007/978-94-007-2492-1_11
D2 10.1007/978-94-007-2492-1
PG 9
WC Oncology; Reproductive Biology
SC Oncology; Reproductive Biology
GA BA3CI
UT WOS:000334104800013
PM 22210258
ER
PT J
AU Maguen, S
Cohen, B
Ren, L
Bosch, J
Kimerling, R
Seal, K
AF Maguen, Shira
Cohen, Beth
Ren, Li
Bosch, Jeane
Kimerling, Rachel
Seal, Karen
TI Gender Differences in Military Sexual Trauma and Mental Health Diagnoses
among Iraq and Afghanistan Veterans with Posttraumatic Stress Disorder
SO WOMENS HEALTH ISSUES
LA English
DT Article
AB Objective: We examined correlates of posttraumatic stress disorder (PTSD), including military sexual trauma (MST), in Iraq and Afghanistan veterans. We also compared mental health comorbidities by gender among veterans with PTSD, with and without MST.
Methods: Retrospective data analyses were conducted using Department of Veterans Affairs (VA) administrative data from 213,803 Iraq and Afghanistan veterans and the subset diagnosed with PTSD from April 1, 2002, to October 1, 2008. We used descriptive statistics and multivariate logistic regression compared by gender to investigate independent correlates and mental health comorbidities associated with PTSD, with and without MST.
Results: Among women with PTSD, 31% screened positive for MST; 1% of men with PTSD screened positive for MST. Among those with PTSD, veterans with MST had more comorbid mental health diagnoses than those without MST. Women with PTSD and MST were more likely to receive comorbid depression, anxiety, and eating disorder diagnoses, and men were more likely to receive comorbid substance use disorder diagnoses.
Conclusions: MST is associated with an increased prevalence of mental health disorders comorbid with PTSD. Better understanding comorbidity patterns will allow for targeted evaluation and treatment of returning veterans with MST. Published by Elsevier Inc.
C1 [Maguen, Shira; Cohen, Beth; Ren, Li; Bosch, Jeane; Seal, Karen] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[Maguen, Shira; Cohen, Beth; Seal, Karen] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA.
RP Maguen, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St,116-P, San Francisco, CA 94121 USA.
EM Shira.Maguen@va.gov
RI Schueter, nicos/A-3625-2014;
OI Kimerling, Rachel/0000-0003-0996-4212
FU NHLBI NIH HHS [K23 HL 094765-01]
NR 26
TC 54
Z9 54
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
EI 1878-4321
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD JAN-FEB
PY 2012
VL 22
IS 1
BP E61
EP E66
DI 10.1016/j.whi.2011.07.010
PG 6
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA V33SP
UT WOS:000209038800008
PM 21907590
ER
PT B
AU Milan, DJ
MacRae, CA
AF Milan, David J.
MacRae, Calum A.
BE McGrath, P
TI Cardiotoxicity Studies in Zebrafish
SO ZEBRAFISH: METHODS FOR ASSESSING DRUG SAFETY AND TOXICITY
LA English
DT Article; Book Chapter
ID TORSADE-DE-POINTES; LONG QT SYNDROME; CARDIAC REPOLARIZATION; COMMON
POLYMORPHISM; ARRHYTHMIA; INTERVAL; GENES; PROLONGATION; MECHANISMS;
VARIANTS
C1 [Milan, David J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Milan, David J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[MacRae, Calum A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
RP Milan, DJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
NR 28
TC 1
Z9 1
U1 0
U2 0
PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
BN 978-1-118-10216-9; 978-0-470-42513-8
PY 2012
BP 55
EP 63
PG 9
WC Toxicology; Veterinary Sciences; Virology
SC Toxicology; Veterinary Sciences; Virology
GA BA6HP
UT WOS:000337144400006
ER
PT B
AU Milan, DJ
MacRae, CA
AF Milan, David J.
MacRae, Calum A.
BE McGrath, P
TI In Vivo Recording of the Adult Zebrafish Electrocardiogram
SO ZEBRAFISH: METHODS FOR ASSESSING DRUG SAFETY AND TOXICITY
LA English
DT Article; Book Chapter
ID REPOLARIZATION; PROPRANOLOL; EXERCISE; MODELS; DRUGS
C1 [Milan, David J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Milan, David J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[MacRae, Calum A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
RP Milan, DJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
NR 12
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
BN 978-1-118-10216-9; 978-0-470-42513-8
PY 2012
BP 65
EP 72
PG 8
WC Toxicology; Veterinary Sciences; Virology
SC Toxicology; Veterinary Sciences; Virology
GA BA6HP
UT WOS:000337144400007
ER
PT B
AU Taylor, AM
Zon, LI
AF Taylor, Alison M.
Zon, Leonard I.
BE McGrath, P
TI Hematopoietic and Vascular System Toxicity
SO ZEBRAFISH: METHODS FOR ASSESSING DRUG SAFETY AND TOXICITY
LA English
DT Article; Book Chapter
ID IN-SITU HYBRIDIZATION; TRANSGENIC ZEBRAFISH; CELL-MIGRATION; GLOBIN
GENES; STEM-CELLS; TRANSPLANTATION; EXPRESSION; EMBRYOS; ERYTHROPOIESIS;
MYELOPOIESIS
C1 [Taylor, Alison M.; Zon, Leonard I.] Childrens Hosp Boston, Stem Cell Program, Boston, MA 02115 USA.
[Taylor, Alison M.; Zon, Leonard I.] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA.
RP Taylor, AM (reprint author), Childrens Hosp Boston, Stem Cell Program, Boston, MA 02115 USA.
NR 44
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
BN 978-1-118-10216-9; 978-0-470-42513-8
PY 2012
BP 73
EP 87
PG 15
WC Toxicology; Veterinary Sciences; Virology
SC Toxicology; Veterinary Sciences; Virology
GA BA6HP
UT WOS:000337144400008
ER
PT J
AU Elkin, EB
Snow, JG
Leoce, NM
Atoria, CL
Schrag, D
AF Elkin, Elena B.
Snow, Jacqueline G.
Leoce, Nicole M.
Atoria, Coral L.
Schrag, Deborah
TI Mammography capacity and appointment wait times: barriers to breast
cancer screening
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Mammography; Breast cancer; Screening; Access; Geography
ID QUALITY STANDARDS ACT; ACCESS; IMPACT; DIAGNOSIS; RATES; STAGE
AB To assess the impact of mammography capacity on appointment wait times.
We surveyed by telephone all mammography facilities federally certified in 2008 in California, Connecticut, Georgia, Iowa, New Mexico, and New York using a simulated patient format. County-level mammography capacity, defined as the number of mammography machines per 10,000 women aged 40 and older, was estimated from FDA facility certification records and US Census data.
1,614 (86%) of 1,882 mammography facilities completed the survey. Time until next available screening mammogram appointment was < 1 week at 55% of facilities, 1-4 weeks at 34% of facilities, and > 1 month at 11% of facilities. Facilities in counties with lower capacity had longer wait times, and a one-unit increase in county capacity was associated with 21% lower odds of a facility reporting a wait time > 1 month (p < 0.01). There was no association between wait time and the availability of evening or weekend appointments or digital mammography.
Lower mammography capacity is associated with longer wait times for screening mammograms.
Enhancement of mammography resources in areas with limited capacity may reduce wait times for screening mammogram appointments, thereby increasing access to services and rates of breast cancer screening.
C1 [Elkin, Elena B.; Atoria, Coral L.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Res Grp, New York, NY 10021 USA.
[Snow, Jacqueline G.] Chartis Grp, Chicago, IL USA.
[Leoce, Nicole M.] Columbia Univ, Mailman Sch Publ Hlth NML, New York, NY USA.
[Schrag, Deborah] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Boston, MA 02115 USA.
RP Elkin, EB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Res Grp, 1275 York Ave,Box 44, New York, NY 10021 USA.
EM elkine@mskcc.org
FU Susan G. Komen for the Cure [POP107806]; American Cancer Society
[MRSG-06-127-01-CPHPS]; National Cancer Institute [K07-CA118189]
FX This work was supported by grants from Susan G. Komen for the Cure
(POP107806, PI: Elkin), the American Cancer Society
(MRSG-06-127-01-CPHPS, PI: Elkin) and the National Cancer Institute
(K07-CA118189, PI: Elkin).
NR 23
TC 8
Z9 8
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JAN
PY 2012
VL 23
IS 1
BP 45
EP 50
DI 10.1007/s10552-011-9853-1
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 857XG
UT WOS:000297757400005
PM 22037904
ER
PT J
AU Subramanian, SL
Hull, RL
Zraika, S
Aston-Mourney, K
Udayasankar, J
Kahn, SE
AF Subramanian, S. L.
Hull, R. L.
Zraika, S.
Aston-Mourney, K.
Udayasankar, J.
Kahn, S. E.
TI cJUN N-terminal kinase (JNK) activation mediates islet amyloid-induced
beta cell apoptosis in cultured human islet amyloid polypeptide
transgenic mouse islets
SO DIABETOLOGIA
LA English
DT Article
DE Beta cell apoptosis; hIAPP; Islet amyloid; JNK activation
ID ENDOPLASMIC-RETICULUM STRESS; OXIDATIVE STRESS; HUMAN AMYLIN;
DIABETES-MELLITUS; ER STRESS; TYPE-2; EXPRESSION; INSULIN; GLUCOSE;
PROTEIN
AB Aggregation of human islet amyloid polypeptide (hIAPP) as islet amyloid is associated with increased beta cell apoptosis and reduced beta cell mass in type 2 diabetes. Islet amyloid formation induces oxidative stress, which contributes to beta cell apoptosis. The cJUN N-terminal kinase (JNK) pathway is a critical mediator of beta cell apoptosis in response to stress stimuli including oxidative stress and exogenous application of hIAPP. We determined whether amyloid formation by endogenous hIAPP mediates beta cell apoptosis through JNK activation and downstream signalling pathways.
hIAPP transgenic and non-transgenic mouse islets were cultured for up to 144 h in 16.7 mmol/l glucose to induce islet amyloid in the presence or absence of the amyloid inhibitor Congo Red or a cell-permeable JNK inhibitor. Amyloid, beta cell apoptosis, JNK signalling and activation of downstream targets in the intrinsic and extrinsic apoptotic pathways were measured.
JNK activation occurred with islet amyloid formation in hIAPP transgenic islets after 48 and 144 h in culture. Neither high glucose nor the hIAPP transgene alone was sufficient to activate JNK independent of islet amyloid. Inhibition of islet amyloid formation with Congo Red reduced beta cell apoptosis and partially decreased JNK activation. JNK inhibitor treatment reduced beta cell apoptosis without affecting islet amyloid. Islet amyloid increased mRNA levels of markers of the extrinsic (Fas, Fadd) and intrinsic (Bim [also known as Bcl2l11]) apoptotic pathways, caspase 3 and the anti-apoptotic molecule Bclxl (also known as Bcl2l1) in a JNK-dependent manner.
Islet amyloid formation induces JNK activation, which upregulates predominantly pro-apoptotic signals in both extrinsic and intrinsic pathways, resulting in beta cell apoptosis.
C1 [Subramanian, S. L.; Hull, R. L.; Zraika, S.; Aston-Mourney, K.; Udayasankar, J.; Kahn, S. E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA.
[Subramanian, S. L.; Hull, R. L.; Zraika, S.; Aston-Mourney, K.; Udayasankar, J.; Kahn, S. E.] Univ Washington, Seattle, WA 98108 USA.
RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM skahn@u.washington.edu
OI Aston-Mourney, Kathryn/0000-0003-1412-6715; Kahn,
Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087
FU Department of Veterans Affairs; National Institutes of Health
[DK-075998, DK-074404, DK-080945, DK-007247, DK-017047]; American
Diabetes Association; University of Washington; Juvenile Diabetes
Research Foundation
FX We thank B. Barrow, C. Braddock, M. Cone, C. Forsyth, M. Peters, M.
Watts and J. Willard for their excellent technical support. This work
was supported by the Department of Veterans Affairs and National
Institutes of Health grants DK-075998 (S. E. Kahn), DK-074404 (R. L.
Hull), DK-080945 (S. Zraika), DK-007247 and DK-017047. S. Subramanian
and K. Aston-Mourney were supported by an American Diabetes Association
Mentor-Based Fellowship. K. Aston-Mourney was also supported by a
University of Washington McAbee Fellowship. J. Udayasankar was supported
by a Juvenile Diabetes Research Foundation Postdoctoral Fellowship.
NR 47
TC 30
Z9 31
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD JAN
PY 2012
VL 55
IS 1
BP 166
EP 174
DI 10.1007/s00125-011-2338-7
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 857SI
UT WOS:000297739000023
PM 22038516
ER
PT J
AU Moon, HS
Chamberland, JP
Mantzoros, CS
AF Moon, H. -S.
Chamberland, J. P.
Mantzoros, C. S.
TI Amylin and leptin activate overlapping signalling pathways in an
additive manner in mouse GT1-7 hypothalamic, C2C12 muscle and AML12
liver cell lines
SO DIABETOLOGIA
LA English
DT Article
DE Amylin; Endoplasmic reticulum stress; Hypothalamus; Intracellular
signalling pathway; Leptin; Liver; Muscle
ID ENDOPLASMIC-RETICULUM STRESS; CENTRAL-NERVOUS-SYSTEM; DIET-INDUCED
OBESITY; PROTEIN-KINASE; HUMAN PHYSIOLOGY; IN-VIVO; INSULIN; RECEPTOR;
RESPONSIVENESS; PROLIFERATION
AB Aims/hypothesis It has been suggested that amylin amplifies leptin's effects and affects energy homeostasis synergistically with leptin in animals and humans. However, no previous study has reported on amylin and leptin signalling in hypothalamic, muscle and liver cells.
Methods Leptin and amylin signalling studies were performed in vitro in mouse GT1-7 hypothalamic, C2C12 muscle and AML12 liver cell lines.
Results Treatment of mouse GT1-7 and C2C12 cells with leptin or amylin increased signal transducer and activator of transcription 3 (STAT3) phosphorylation in a dose- and time-dependent manner. In mouse AML12 cells, leptin and amylin produced a biphasic response of STAT3 activity. Importantly, all leptin and amylin signalling pathways were saturable at leptin and amylin concentrations of similar to 100 and similar to 50 to 100 ng/ml, respectively. Leptin and amylin in combination activated STAT3, AMP-activated protein kinase (AMPK), extracellular signal-regulated kinase (ERK) 1/2 and Akt signalling pathways in an additive manner, effects that were abolished under endoplasmic reticulum (ER) stress. Leptin, but not amylin, increased IRS-1 phosphorylation in GT1-7 hypothalamic, but not in C2C12 muscle and AML12 liver cell lines.
Conclusions/interpretation Our data suggest that leptin and amylin have overlapping and additive, but not synergistic, effects in the activation of intracellular signalling pathways. ER stress may induce leptin and amylin resistance in hypothalamic, muscle and liver cell lines. These novel insights into the mode of action of leptin and amylin suggest that these hormones may play an additive role in regulating energy homeostasis in humans.
C1 [Mantzoros, C. S.] Harvard Univ, Dept Environm Hlth, Sch Publ Hlth, Boston, MA 02215 USA.
[Moon, H. -S.; Chamberland, J. P.; Mantzoros, C. S.] Harvard Univ, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Chamberland, J. P.; Mantzoros, C. S.] Harvard Univ, Endocrinol Sect, Boston VA Healthcare Syst, Sch Med, Boston, MA 02215 USA.
RP Mantzoros, CS (reprint author), Harvard Univ, Dept Environm Hlth, Sch Publ Hlth, FD-876,330 Brookline Ave, Boston, MA 02215 USA.
EM cmantzor@bidmc.harvard.edu
OI Chamberland, John/0000-0002-7862-1371
FU National Institute of Diabetes and Digestive and Kidney Diseases [58785,
79929, 81913, AG032030]; VA Merit award; Beth Israel Deaconess Medical
Center
FX The Mantzoros Laboratory is supported by National Institute of Diabetes
and Digestive and Kidney Diseases Grants 58785, 79929, 81913 and
AG032030 and a VA Merit award. The Mantzoros Laboratory is also
supported by a discretionary grant from Beth Israel Deaconess Medical
Center.
NR 42
TC 23
Z9 23
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD JAN
PY 2012
VL 55
IS 1
BP 215
EP 225
DI 10.1007/s00125-011-2332-0
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 857SI
UT WOS:000297739000028
PM 21997794
ER
PT J
AU Wu, Y
Viana, M
Thirumangalathu, S
Loeken, MR
AF Wu, Y.
Viana, M.
Thirumangalathu, S.
Loeken, M. R.
TI AMP-activated protein kinase mediates effects of oxidative stress on
embryo gene expression in a mouse model of diabetic embryopathy
SO DIABETOLOGIA
LA English
DT Article
DE AMP-activated kinase; Diabetic embryopathy; Diabetic pregnancy; Neural
tube defect; Pax3; Oxidative stress
ID NEURAL-TUBE DEFECTS; RADICAL SCAVENGING ENZYMES; VITAMIN-E; STEM-CELLS;
TRANSCRIPTIONAL ACTIVITY; SKELETAL-MUSCLE; COMPLEX III; PREGNANCY;
HYPOXIA; MECHANISM
AB Aims/hypothesis Neural tube defects (NTDs) are a common malformation associated with diabetic embryopathy. Maternal hyperglycaemia-induced oxidative stress inhibits the expression of Pax3, a gene that is essential for neural tube closure, and increases the incidence of NTDs. Because oxidative stress can stimulate AMP-activated kinase (AMPK) activity, and AMPK can regulate gene transcription, we hypothesised that increased AMPK activity would mediate the adverse effects of maternal hyperglycaemia-induced oxidative stress on Pax3 expression and NTDs.
Methods Pregnant mice were made transiently hyperglycaemic by glucose injection, or hypoxic by housing in a hypoxic chamber, or were treated with antimycin A to induce oxidative stress, and AMPK activity in the embryos was assayed. The effects of stimulating AMPK activity with 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) on Pax3 expression and NTDs were determined. Vitamin E or glutathione ethyl ester was used to reduce oxidative stress, and compound C was used to inhibit AMPK activation. Murine embryonic stem cells were employed as an in vitro model to study the effects of oxidative stress on AMPK activity and the effects of AMPK stimulation on Pax3 expression.
Results Maternal hyperglycaemia stimulated AMPK activity, and stimulation of AMPK with AICAR inhibited Pax3 expression (in vivo and in vitro) and increased NTDs (in vivo). Stimulation of AMPK by hyperglycaemia, hypoxia or antimycin A was inhibited by antioxidants. The AMPK inhibitor compound C blocked the effects of hyperglycaemia or AA on Pax3 expression and NTDs.
Conclusions/interpretation Stimulation of AMPK in embryos during a diabetic pregnancy mediates the effects of hyperglycaemia-induced oxidative stress to disturb the expression of the critical Pax3 gene, thereby causing NTDs.
C1 [Wu, Y.; Viana, M.; Thirumangalathu, S.; Loeken, M. R.] Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA.
[Wu, Y.; Viana, M.; Thirumangalathu, S.; Loeken, M. R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA.
EM mary.loeken@joslin.harvard.edu
RI Viana, Marta/L-4649-2014;
OI Viana, Marta/0000-0003-4718-4145; Loeken, Mary/0000-0002-8056-9816
FU National Institutes of Health [RO1DK58300]; National Institute of
Diabetes and Digestive and Kidney Diseases [P30DK036836]
FX We are grateful for assistance and advice on the AMPK assay from members
of the Goodyear Laboratory, and for culture of mESCs from F. Wang. M.
Horal and J. Blanchard provided technical support. This project was
supported by National Institutes of Health grant RO1DK58300 (to MRL) and
was assisted by core facilities supported by a Diabetes Endocrine
Research Center grant, P30DK036836, from the National Institute of
Diabetes and Digestive and Kidney Diseases.
NR 49
TC 19
Z9 21
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD JAN
PY 2012
VL 55
IS 1
BP 245
EP 254
DI 10.1007/s00125-011-2326-y
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 857SI
UT WOS:000297739000031
PM 21993711
ER
PT J
AU Wenger, A
Englund, M
Wirth, W
Hudelmaier, M
Kwoh, K
Eckstein, F
AF Wenger, Andrea
Englund, Martin
Wirth, Wolfgang
Hudelmaier, Martin
Kwoh, Kent
Eckstein, Felix
CA OAI Investigators
TI Relationship of 3D meniscal morphology and position with knee pain in
subjects with knee osteoarthritis: a pilot study
SO EUROPEAN RADIOLOGY
LA English
DT Article
DE Meniscus; Extrusion; Pain; Knee osteoarthritis; Magnetic resonance
imaging
ID BONE-MARROW LESIONS; CARTILAGE LOSS; MULTICENTER OSTEOARTHRITIS;
ARTICULAR-CARTILAGE; ELDERLY PERSONS; INITIATIVE OAI; RISK-FACTORS;
JOINT; ASSOCIATION; TEARS
AB To explore whether quantitative, three-dimensional measurements of meniscal position and size are associated with knee pain using a within-person, between-knee study design.
We studied 53 subjects (19 men, 34 women) from the Osteoarthritis Initiative, with identical radiographic OA grades in both knees, but frequent pain in one and no pain in the other knee. The tibial plateau and menisci were analyzed using coronally reconstructed double echo steady-state sequence with water excitation (DESSwe) MRI.
The medial meniscus covered a smaller proportion of the tibial plateau (-5%) and displayed greater extrusion of the body (+15%) in painful than in painless knees (paired t-test; p < 0.05). The external margin of the lateral meniscus showed greater extrusion of the body in painful knees (+22%; p = 0.03), but no significant difference in the position of its internal margin or tibial coverage. Medial or lateral extrusion a parts per thousand yen3 mm was more frequent in painful (n = 23) than in painless knees (n = 12; McNemar's test; p = 0.02). No significant association was observed between meniscal size and knee pain.
These data suggest a relationship between extrusion of the meniscal body, as measured with quantitative MRI, and knee pain in subjects with knee OA. Further studies need to confirm these findings and their clinical relevance.
Meniscal segmentation provides quantitative measures of meniscal size/position
Between-knee, within-person approaches can explore potential sources of knee pain
Meniscal extrusion may be a potential source of knee pain.
C1 [Wenger, Andrea; Wirth, Wolfgang; Hudelmaier, Martin; Eckstein, Felix] Paracelsus Med Univ, Inst Anat & Musculoskeletal Res, A-5020 Salzburg, Austria.
[Englund, Martin] Lund Univ, Dept Orthoped, Lund, Sweden.
[Englund, Martin] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA.
[Wirth, Wolfgang; Hudelmaier, Martin; Eckstein, Felix] Chondrometrics GmbH, Ainring, Germany.
[Kwoh, Kent] Univ Pittsburgh, Div Rheumatol & Clin Immunol, Pittsburgh, PA USA.
[Kwoh, Kent] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
RP Wenger, A (reprint author), Paracelsus Med Univ, Inst Anat & Musculoskeletal Res, Strubergasse 21, A-5020 Salzburg, Austria.
EM andrea.wenger@pmu.ac.at
RI Wirth, Wolfgang/C-8724-2011; Englund, Martin/J-7245-2012
OI Wirth, Wolfgang/0000-0002-2297-8283; Englund, Martin/0000-0003-3320-2437
FU OAI [N01-AR-2-2258, N01-AR-2-2259, N01-AR-2-2260, N01-AR-2-2261,
N01-AR-2-2262]; National Institutes of Health; Pfizer, Inc.; Novartis
Pharmaceuticals Corporation; Merck Research Laboratories;
GlaxoSmithKline; Paracelsus Medical University; Swedish Research
Council; Faculty of Medicine, Lund University; Royal Physiographic
Society in Lund; [AR054731]
FX The study and image acquisition was supported by the OAI (contract nos.
N01-AR-2-2258; N01-AR-2-2259; N01-AR-2-2260; N01-AR-2-2261;
N01-AR-2-2262) funded by the National Institutes of Health and conducted
by the OAI Study Investigators. Private funding partners include Pfizer,
Inc.; Novartis Pharmaceuticals Corporation; Merck Research Laboratories;
and GlaxoSmithKline. Private sector funding for the OAI is managed by
the Foundation for the National Institutes of Health. This manuscript
has received the approval of the OAI Publications Committee based on a
review of its scientific content and data interpretation.; The image
analysis was supported by funds from Paracelsus Medical University (PMU
Forschungsfond). Dr. Englund is supported by the Swedish Research
Council, the Faculty of Medicine, Lund University, and the Royal
Physiographic Society in Lund and Dr. Kwoh by grant AR054731. Felix
Eckstein is CEO and co- owner of Chondrometrics GmbH; he also provides
consulting services to MerckSerono, Novartis and Sanofi Aventis.
Wolfgang Wirth is co-owner of Chondrometrics GmbH.
NR 53
TC 28
Z9 28
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-7994
J9 EUR RADIOL
JI Eur. Radiol.
PD JAN
PY 2012
VL 22
IS 1
BP 211
EP 220
DI 10.1007/s00330-011-2234-z
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 857UX
UT WOS:000297749100022
PM 21842432
ER
PT J
AU Lima, XT
Janakiraman, V
Hughes, MD
Kimball, AB
AF Lima, Xinaida T.
Janakiraman, Vanitha
Hughes, Michael D.
Kimball, Alexandra B.
TI The Impact of Psoriasis on Pregnancy Outcomes
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; C-REACTIVE PROTEIN; RHEUMATOID-ARTHRITIS;
PRETERM BIRTH; RISK-FACTORS; WOMEN; AGE
AB Psoriasis is an inflammatory disease that affects women in their reproductive years. Other similar diseases have been associated with adverse pregnancy outcomes. We sought to assess whether pregnant women with psoriasis are at higher risk of developing complications, such as preterm birth (PTB) and low birth weight (LBW). A retrospective cohort, performed at two large tertiary centers, evaluated the outcomes of 162 pregnancies in 122 women with psoriasis and 501 pregnancies in 290 women without psoriasis. Univariable and multivariable analyses, adjusting for important demographic factors, comorbidities, or a propensity score, were performed to evaluate the association of psoriasis and a poor outcome composite (POC), including PTB (<37 gestational weeks) and LBW (<2,500 g). Repeated measures analysis was used to account for the multiple pregnancies per woman. Cesarean delivery, preeclampsia/eclampsia, and spontaneous abortion were also evaluated. For women with psoriasis, there was a 1.89-fold increase in odds of POC (95% CI 1.06-3.39) in the univariable analysis. This effect remained statistically significant in the multivariable analyses. Psoriasis was not associated with cesarean delivery, preeclampsia/eclampsia, and spontaneous abortion. This study has shown higher odds of POC in patients with psoriasis. Further larger population-based studies are required to confirm these findings.
C1 [Lima, Xinaida T.] Massachusetts Gen Hosp, Dept Dermatol, Unit Res Trials & Outcomes Skin, Boston, MA 02114 USA.
[Lima, Xinaida T.; Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Janakiraman, Vanitha] Massachusetts Gen Hosp, Dept Maternal Fetal Med, Boston, MA 02114 USA.
RP Lima, XT (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Unit Res Trials & Outcomes Skin, 50 Staniford St,Suite 240, Boston, MA 02114 USA.
EM xtlima@gmail.com
NR 20
TC 14
Z9 14
U1 0
U2 2
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 JAN
PY 2012
VL 132
IS 1
BP 85
EP 91
DI 10.1038/jid.2011.271
PG 7
WC Dermatology
SC Dermatology
GA 864JT
UT WOS:000298237000015
PM 21918537
ER
PT J
AU Lin, WM
Lewis, JM
Filler, RB
Modi, BG
Carlson, KR
Reddy, S
Thornberg, A
Saksena, G
Umlauf, S
Oberholzer, PA
Karpova, M
Getz, G
Mane, S
Garraway, LA
Dummer, R
Berger, CL
Edelson, RL
Girardi, M
AF Lin, William M.
Lewis, Julia M.
Filler, Renata B.
Modi, Badri G.
Carlson, Kacie R.
Reddy, Swapna
Thornberg, Adam
Saksena, Gordon
Umlauf, Sheila
Oberholzer, Patrick A.
Karpova, Maria
Getz, Gad
Mane, Shrikant
Garraway, Levi A.
Dummer, Reinhard
Berger, Carole L.
Edelson, Richard L.
Girardi, Michael
TI Characterization of the DNA Copy-Number Genome in the Blood of Cutaneous
T-Cell Lymphoma Patients
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID SEZARY-SYNDROME; IMATINIB MESYLATE; MYCOSIS-FUNGOIDES; PERIPHERAL-BLOOD;
BREAST-CANCER; CLASSIFICATION; IDENTIFICATION; ABERRATIONS; DEPENDENCY;
PREDICTION
AB Cutaneous T-cell lymphoma (CTCL) is a heterogeneous non-Hodgkin's lymphoma that may variably involve the skin, lymph nodes, and peripheral blood. Malignant burden ranges from cutaneous patches and plaques with little evidence of blood involvement to erythroderma often in association with frank leukemia, as in Sezary syndrome. Toward a better understanding of the pathogenesis of this CD4+ T-cell malignancy, we conducted a high-resolution genomic analysis combining DNA (23 samples) and mRNA (12 samples) data of peripheral blood isolates from CTCL patients across a spectrum of stages. Strikingly, even patients with limited involvement, e. g., normal CD4 counts, contained significant copy-number alterations. Defining genomic characteristics of CTCL blood involvement included gains on 8q and 17q, and deletions on 17p and chromosome 10. A consensus analysis of 108 leukemic CTCL samples demonstrated global similarities among patients with varied blood involvement, narrowing 38 of 62 loci. Toward an annotated framework for in vitro testing, we also characterized genomic alterations in five CTCL cell lines (HH, HUT78, PNO, SeAx, and Sez4), revealing intact core features of leukemic CTCL. Together, these studies produce the most comprehensive view of the leukemic CTCL genome to date, with implications for pathogenesis, molecular classification, and potential future therapeutic developments.
C1 [Lin, William M.; Lewis, Julia M.; Filler, Renata B.; Modi, Badri G.; Carlson, Kacie R.; Reddy, Swapna; Berger, Carole L.; Edelson, Richard L.; Girardi, Michael] Yale Univ, Dept Dermatol, Sch Med, New Haven, CT 06520 USA.
[Thornberg, Adam; Umlauf, Sheila; Mane, Shrikant] Keck Fdn, Microarray Facil, New Haven, CT USA.
[Saksena, Gordon; Oberholzer, Patrick A.; Getz, Gad; Garraway, Levi A.] Broad Inst, Canc Program, Cambridge, MA USA.
[Oberholzer, Patrick A.; Garraway, Levi A.] Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA.
[Karpova, Maria; Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland.
RP Girardi, M (reprint author), Yale Univ, Dept Dermatol, Sch Med, 333 Cedar St,POB 208059, New Haven, CT 06520 USA.
EM girardi@yale.edu
FU Yale Cancer Center; Skin Cancer Foundation; American Skin Association;
Etta S. Chidsey Award in Cancer Research; Yale School of Medicine;
Affymetrix
FX This study was supported by (1) Argall and Anna Hull Cancer Research
Award from the Yale Cancer Center, (2) Skin Cancer Foundation Research
grant, (3) American Skin Association Medical Student Award, (4) Etta S.
Chidsey Award in Cancer Research, (5) Yale School of Medicine Student
Fellowship, and (6) Affymetrix to WML as part of their Collaborators in
Cancer Research Program. Affymetrix had no scientific involvement in
this study. We also thank Martine Bagot, Armand Bensussan, and Anne
Marie-Cardine of INSERM; Eric Vonderheid and Alain Rook of University of
Pennsylvania; Emmanuel Contassot and Lars French of University Hospital
of Zurich; and Francine Foss of Yale University for their generosity in
providing CTCL cell lines.
NR 35
TC 11
Z9 12
U1 0
U2 3
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 JAN
PY 2012
VL 132
IS 1
BP 188
EP 197
DI 10.1038/jid.2011.254
PG 10
WC Dermatology
SC Dermatology
GA 864JT
UT WOS:000298237000027
PM 21881587
ER
PT J
AU Kobayashi, C
Shiina, T
Tokioka, A
Hattori, Y
Komori, T
Kobayashi-Miura, M
Takizawa, T
Takahara, K
Inaba, K
Inoko, H
Takeya, M
Dranoff, G
Sugita, M
AF Kobayashi, Chisa
Shiina, Takashi
Tokioka, Atsuko
Hattori, Yuki
Komori, Takaya
Kobayashi-Miura, Mikiko
Takizawa, Toshihiro
Takahara, Kazuhiko
Inaba, Kayo
Inoko, Hidetoshi
Takeya, Motohiro
Dranoff, Glenn
Sugita, Masahiko
TI GM-CSF-Independent CD1a Expression in Epidermal Langerhans Cells:
Evidence from Human CD1A Genome-Transgenic Mice
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Letter
ID COLONY-STIMULATING FACTOR; T-CELLS; DIFFERENTIATION; ANTIGENS
C1 [Kobayashi, Chisa; Tokioka, Atsuko; Hattori, Yuki; Komori, Takaya; Sugita, Masahiko] Kyoto Univ, Inst Virus Res, Lab Cell Regulat, Kyoto 606, Japan.
[Shiina, Takashi; Inoko, Hidetoshi] Tokai Univ, Sch Med, Dept Mol Life Sci, Isehara, Kanagawa 25911, Japan.
[Kobayashi-Miura, Mikiko] Shimane Univ, Fac Med, Dept Publ Hlth, Izumo, Shimane, Japan.
[Takizawa, Toshihiro] Nippon Med Sch, Dept Mol Anat, Tokyo 113, Japan.
[Takahara, Kazuhiko; Inaba, Kayo] Kyoto Univ, Grad Sch Biostudies, Immunobiol Lab, Kyoto, Japan.
[Takeya, Motohiro] Kumamoto Univ, Grad Sch Med Sci, Fac Life Sci, Dept Cell Pathol, Kumamoto, Japan.
[Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
RP Kobayashi, C (reprint author), Kyoto Univ, Inst Virus Res, Lab Cell Regulat, Kyoto 606, Japan.
EM msugita@virus.kyoto-u.ac.jp
FU NCI NIH HHS [P01 CA078378, R01 CA050947, P01 CA155258, R01 CA143083, P50
CA100707]
NR 9
TC 4
Z9 4
U1 1
U2 3
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 JAN
PY 2012
VL 132
IS 1
BP 241
EP 244
DI 10.1038/jid.2011.280
PG 4
WC Dermatology
SC Dermatology
GA 864JT
UT WOS:000298237000034
PM 21900947
ER
PT J
AU Brastianos, PK
Brastianos, HC
Hsu, W
Sciubba, DM
Kosztowski, T
Tyler, BM
Recinos, VR
Burger, P
Grossman, SA
AF Brastianos, Priscilla K.
Brastianos, Harry C.
Hsu, Wesley
Sciubba, Daniel M.
Kosztowski, Thomas
Tyler, Betty M.
Recinos, Violette Renard
Burger, Peter
Grossman, Stuart A.
TI The toxicity of intrathecal bevacizumab in a rabbit model of
leptomeningeal carcinomatosis
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Intrathecal bevacizumab; Carcinomatous meningitis; Leptomeningeal
carcinomatosis; Neoplastic meningitis; Rabbit model of leptomeningeal
carcinomatosis
ID ENDOTHELIAL GROWTH-FACTOR; HUMANIZED MONOCLONAL-ANTIBODY; METASTATIC
COLORECTAL-CANCER; INTRAVITREAL BEVACIZUMAB; MACULAR DEGENERATION; TUMOR
ANGIOGENESIS; INTRAOCULAR PHARMACOKINETICS; CHOROIDAL
NEOVASCULARIZATION; VASCULAR NORMALIZATION; ANTIANGIOGENIC THERAPY
AB Leptomeningeal carcinomatosis (LC) is a devastating complication of cancer. Intrathecal administration of cytotoxic chemotherapy adds little to survival which is measured in weeks. The potential toxicities and efficacy of intrathecally administered anti-angiogenic agents in this setting have not previously been explored. A well-characterized animal model was used to evaluate the neurotoxicity of intraventricularly administered bevacizumab (BCM). Thirty-three New Zealand White Rabbits were studied. Subcutaneous reservoirs and ventricular catheters (SRVC) were placed in eight rabbits, which were randomized to receive weekly intraventricular saline with or without BCM for four weeks. These rabbits were euthanized on day 36 and the brains were examined by a blinded neuropathologist. Twenty-five additional rabbits underwent cisternal injection of VX2 carcinoma cells with or without a single dose of BCM and were followed for survival. No clinical manifestations of neurotoxicity were noted in rabbits treated with intraventricular BCM. Similarly, no evidence of BCM neurotoxicity was identified in autopsied animals. The median survival of evaluable rabbits with LC treated with intraventricular saline (N = 13) was 15 days compared to 18 days for the animals receiving VX2 and one dose of BCM (N = 12). Conclusion: Intraventricular BCM can be administered to rabbits without clinical or pathologic neurotoxicity. Survival following one dose of BCM in rabbits with LC should be cautiously interpreted given uncertainties regarding the dose, schedule, and limited expected benefit of this non-rabbit antibody. This neurotoxicity study provides safety data to allow phase I/II studies in humans with treatment refractory LC.
C1 [Brastianos, Priscilla K.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Brastianos, Priscilla K.] Harvard Univ, Sch Med, Dept Med Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Brastianos, Harry C.; Grossman, Stuart A.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21231 USA.
[Brastianos, Harry C.] McMaster Univ, Dept Med, Hamilton, ON L8S 4L8, Canada.
[Hsu, Wesley; Sciubba, Daniel M.; Kosztowski, Thomas; Tyler, Betty M.; Recinos, Violette Renard] Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD 21205 USA.
[Burger, Peter] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA.
RP Brastianos, PK (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St,Smith 353, Boston, MA 02115 USA.
EM pbrastianos@partners.org
OI Brastianos, Priscilla/0000-0003-4470-8425
NR 51
TC 3
Z9 3
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD JAN
PY 2012
VL 106
IS 1
BP 81
EP 88
DI 10.1007/s11060-011-0655-9
PG 8
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 858MV
UT WOS:000297804000009
PM 21789699
ER
PT J
AU Norden, AD
Bartolomeo, J
Tanaka, S
Drappatz, J
Ciampa, AS
Doherty, LM
LaFrankie, DC
Ruland, S
Quant, EC
Beroukhim, R
Wen, PY
AF Norden, Andrew D.
Bartolomeo, Julia
Tanaka, Shota
Drappatz, Jan
Ciampa, Abigail S.
Doherty, Lisa M.
LaFrankie, Debra C.
Ruland, Sandra
Quant, Eudocia C.
Beroukhim, Rameen
Wen, Patrick Y.
TI Safety of concurrent bevacizumab therapy and anticoagulation in glioma
patients
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Glioma; Glioblastoma; Bevacizumab; Anticoagulation; Intracerebral
hemorrhage
ID SINGLE-AGENT BEVACIZUMAB; MOLECULAR-WEIGHT HEPARIN; HIGH-GRADE GLIOMAS;
VENOUS THROMBOEMBOLISM; TISSUE FACTOR; MEDICAL-MANAGEMENT; MALIGNANT
GLIOMAS; BRAIN-TUMORS; PHASE-II; RISK
AB Venous thromboembolic events (VTE) are common in glioma patients and are typically treated with anticoagulant medications. The anti-angiogenic agent bevacizumab (BVZ) increases the risks of both VTE and hemorrhagic complications. Little is known about the hemorrhagic risk of anticoagulation in glioma patients receiving BVZ. We reviewed medical records from 282 BVZ-treated patients at our center and identified 64 who received concurrent anticoagulant therapy. The risk and severity of hemorrhagic complications were assessed. Fisher's exact test was used to compare the risk of hemorrhage between subjects who received and did not receive anticoagulants. Forty-seven patients (73%) had glioblastoma, 15 (23%) anaplastic glioma, and 2 (3%) other tumors. Thirteen (20%) and 51 (80%) patients received warfarin and low-molecular-weight heparin, respectively. The indication for anticoagulation was deep venous thrombosis in 37 patients (58%), pulmonary embolism in 22 (34%), and both in 5 (8%). Thirteen patients (20%) experienced hemorrhage, of which four hemorrhages (6%) were serious (grade >= 3): one patient had grade 5 intracerebral hemorrhage (ICH), one grade 4 ICH, one grade 3 epistaxis, and one grade 3 gastrointestinal hemorrhage. ICH was seen in seven patients (11%), of which five (8%) were grade 1. Among 218 patients who did not receive anticoagulants, there were two (1%) serious hemorrhages (both grade 4 ICH). Both the serious hemorrhage rate and overall ICH rate were higher in patients who received anticoagulants (P = 0.03 and 0.02, respectively). Anticoagulant use during BVZ therapy may increase the risk of hemorrhage in glioma patients, although it is generally well tolerated.
C1 [Norden, Andrew D.; Bartolomeo, Julia; Tanaka, Shota; Drappatz, Jan; Ciampa, Abigail S.; Doherty, Lisa M.; LaFrankie, Debra C.; Ruland, Sandra; Quant, Eudocia C.; Beroukhim, Rameen; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA.
[Norden, Andrew D.; Tanaka, Shota; Drappatz, Jan; Quant, Eudocia C.; Beroukhim, Rameen; Wen, Patrick Y.] Brigham & Womens Hosp, Div Neurooncol, Dept Neurol, Boston, MA 02115 USA.
[Norden, Andrew D.; Drappatz, Jan; Quant, Eudocia C.; Beroukhim, Rameen; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA.
RP Wen, PY (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM patrick_wen@dfci.harvard.edu
NR 25
TC 32
Z9 32
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD JAN
PY 2012
VL 106
IS 1
BP 121
EP 125
DI 10.1007/s11060-011-0642-1
PG 5
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 858MV
UT WOS:000297804000013
PM 21706358
ER
PT J
AU Gilbert, MR
Kuhn, J
Lamborn, KR
Lieberman, F
Wen, PY
Mehta, M
Cloughesy, T
Lassman, AB
DeAngelis, LM
Chang, S
Prados, M
AF Gilbert, Mark R.
Kuhn, John
Lamborn, Kathleen R.
Lieberman, Frank
Wen, Patrick Y.
Mehta, Minesh
Cloughesy, Timothy
Lassman, Andrew B.
DeAngelis, Lisa M.
Chang, Susan
Prados, Michael
TI Cilengitide in patients with recurrent glioblastoma: the results of
NABTC 03-02, a phase II trial with measures of treatment delivery
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Glioblastoma; Pharmacokinetics; Tumor pharmacokinetics; Integrins
ID MALIGNANT GLIOMAS; BRAIN-TUMORS; INTEGRIN; ALPHA-V-BETA-3;
ALPHA(V)BETA(3); ANGIOGENESIS; EMD-121974; MECHANISMS; EXPRESSION;
PATTERNS
AB Cilengitide is a cyclic pentapeptide that is a specific inhibitor of the alpha v beta 3 and alpha v beta 5 integrins. Preclinical studies demonstrate antiangiogenic activity and anti-invasive activity in a number of glioma models. This study was designed to evaluate the efficacy and tumor delivery of cilengitide in patients with recurrent glioblastoma. Patients with recurrent glioblastoma who require a surgical resection for optimal clinical care received 3 intravenous doses of cilengitide at either 500 or 2000 mg (day -8, -4, -1) prior to undergoing tumor resection with corresponding blood samples for plasma to tumor comparisons. After recovery from surgery, patients were treated with cilengitide (2000 mg i.v. twice weekly, maximum of 2 years of treatment). The study accrued 30 patients with recurrent glioblastoma, 26 were evaluable for efficacy. The 6-month progression free survival rate was 12%. Cilengitide was detected in all tumor specimens with higher levels in the group receiving 2000 mg dosing while corresponding plasma concentrations were low, often below the lower limit of detection. These results confirm drug delivery and possibly retention in tumor. This study provides evidence that with established dosing, cilengitide is adequately delivered to the tumor, although as a single agent, efficacy in recurrent glioblastoma is modest. However, these results demonstrating drug delivery to tumor do support continued investigation of this agent as preliminary results from recent studies combining cilengitide with cytotoxic therapies are promising.
C1 [Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Kuhn, John] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Lamborn, Kathleen R.; Chang, Susan; Prados, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Lieberman, Frank] Univ Pittsburgh, Pittsburgh, PA USA.
[Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Mehta, Minesh] Univ Wisconsin, Madison, WI USA.
[Cloughesy, Timothy] Univ Calif Los Angeles, Los Angeles, CA USA.
[Lassman, Andrew B.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Gilbert, MR (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM mrgilbert@mdanderson.org
RI Gilbert, Mark/J-7494-2016;
OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713
FU NIH [U01 CA-062412]; Genentech
FX The Cilengitide was generously provided by Merck KgaA and the National
Cancer Institute, NIH. This study was sponsored by NIH Grant U01
CA-062412.; Mark R. Gilbert, MD: Research support from Genentech,
Advisory Affiliations with Merck, Genentech.
NR 23
TC 59
Z9 61
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD JAN
PY 2012
VL 106
IS 1
BP 147
EP 153
DI 10.1007/s11060-011-0650-1
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 858MV
UT WOS:000297804000017
PM 21739168
ER
PT J
AU Reardon, DA
Norden, AD
Desjardins, A
Vredenburgh, JJ
Herndon, JE
Coan, A
Sampson, JH
Gururangan, S
Peters, KB
McLendon, RE
Norfleet, JA
Lipp, ES
Drappatz, J
Wen, PY
Friedman, HS
AF Reardon, David A.
Norden, Andrew D.
Desjardins, Annick
Vredenburgh, James J.
Herndon, James E., II
Coan, April
Sampson, John H.
Gururangan, Sridharan
Peters, Katherine B.
McLendon, Roger E.
Norfleet, Julie A.
Lipp, Eric S.
Drappatz, Jan
Wen, Patrick Y.
Friedman, Henry S.
TI Phase II study of Gleevec (R) plus hydroxyurea (HU) in adults with
progressive or recurrent meningioma
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Meningioma; Platelet-derived growth factor receptor; Imatinib mesylate;
Hydroxyurea
ID GROWTH-FACTOR PDGF; BRAIN-TUMOR CONSORTIUM; IMATINIB MESYLATE; MITOGENIC
SIGNALS; CELL-GROWTH; EXPRESSION; RECEPTOR; CHEMOTHERAPY; TRANSDUCTION;
STIMULATION
AB We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea in patients with progressive/recurrent meningioma. A total of 21 patients with progressive/recurrent meningioma were enrolled in this dual center, single-arm, phase II trial. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg/day for patients not on CYP3A enzyme inducing anti-epileptic drugs (EIAEDs) and at 500 mg twice a day for patients on EIAEDs. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary endpoints were safety, radiographic response rate, and overall survival (OS). Best radiographic response was stable disease and was observed in 14 patients (67%). PFS-6 for all patients, those with grade I tumors (n = 8) and those with grade II or III tumors (n = 13) was 61.9, 87.5 and 46.2%, respectively. Patients with grade II or III tumors had poorer PFS and OS than those with grade I tumors, (P = 0.025 and P = 0.018) respectively. The only grade 3 or greater adverse event occurring in a parts per thousand yen10% of patients was anemia (10%). Imatinib plus hydroxyurea is well tolerated among patients with meningioma but has modest anti-tumor activity for this indication.
C1 [Reardon, David A.; Desjardins, Annick; Vredenburgh, James J.; Sampson, John H.; Gururangan, Sridharan; Peters, Katherine B.; Norfleet, Julie A.; Lipp, Eric S.; Friedman, Henry S.] Duke Univ, Med Ctr, Dept Surg, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
[Reardon, David A.; Gururangan, Sridharan; Friedman, Henry S.] Duke Univ, Med Ctr, Dept Pediat, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
[Norden, Andrew D.; Drappatz, Jan; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA.
[Desjardins, Annick; Vredenburgh, James J.; Peters, Katherine B.] Duke Univ, Med Ctr, Dept Med, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
[Herndon, James E., II; Coan, April] Duke Univ, Med Ctr, Dept Biostat, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
[McLendon, Roger E.] Duke Univ, Med Ctr, Dept Neurobiol, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
[McLendon, Roger E.] Duke Univ, Med Ctr, Dept Pathol, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
RP Reardon, DA (reprint author), Duke Univ, Med Ctr, Dept Surg, Preston Robert Tisch Brain Tumor Ctr, Box 3624, Durham, NC 27710 USA.
EM reard003@mc.duke.edu
OI Sykes, April/0000-0002-7667-8155
FU NIH [P50 NS20023, R37 CA011898]; Novartis Pharmaceuticals; Department of
Health and Human Services, Bethesda, Maryland
FX This study was financially supported by grants P50 NS20023 and R37
CA011898 from NIH, Department of Health and Human Services, Bethesda,
Maryland and a research grant from Novartis Pharmaceuticals. The
investigators wish to thank Wendy Gentry for her assistance in the
preparation of this manuscript.
NR 43
TC 29
Z9 29
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD JAN
PY 2012
VL 106
IS 2
BP 409
EP 415
DI 10.1007/s11060-011-0687-1
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 858KI
UT WOS:000297795200020
PM 21938530
ER
PT J
AU Sobota, A
Graham, DA
Neufeld, EJ
Heeney, MM
AF Sobota, Amy
Graham, Dionne A.
Neufeld, Ellis J.
Heeney, Matthew M.
TI Thirty-Day Readmission Rates Following Hospitalization for Pediatric
Sickle Cell Crisis at Freestanding Children's Hospitals: Risk Factors
and Hospital Variation
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE health services research; pediatrics; readmission rates; sickle cell
disease
ID DISEASE; PROGRAM
AB Background. Readmission within 30 days after hospitalization for sickle cell crisis was developed by The National Association of Children's Hospitals (NACHRI) to improve hospital quality, however, there have been few studies validating this. Procedure. We performed a retrospective examination of 12,104 hospitalizations for sickle crisis from July 1, 2006 and December 31, 2008 at 33 freestanding children's hospitals in the Pediatric Health Information System (PHIS) database. Hospitalizations met NACHRI criteria; inpatient admission, APR DRG code 662, age < 18, discharge home, and length of stay within 2 SD of the mean. We describe 30-day readmission rates, identify factors associated with readmission accounting for patient-level clustering and compare unadjusted versus adjusted variation in readmission rates. Results. We identified 4,762 patients with 12,104 qualifying hospitalizations (1-30 per patient). Two thousand seventy-four (17%) hospitalizations resulted in a readmission within 30 days. Significant factors associated with readmission were age (OR 1.06/year, P < 0.0001), inpatient use of steroids (OR 1.48, P = 0.01) admission for pain without other sickle complications (OR 1.52, P < 0.0001) and simple transfusion (OR 0.58, P = 0.0002). There was significant variation in readmission rates between hospitals, even after accounting for clustering by patient and hospital case mix. Conclusions. In a sample of free-standing children's hospitals, 17% of hospitalizations for sickle cell crisis result in readmission within 30 days. Older patients, those treated with steroids and those admitted for pain are more likely to be readmitted; simple transfusion is protective. Even after adjusting for case mix substantial hospital variation remains, but specific hospital to hospital comparisons differ depending on the exact methods used. Pediatr Blood Cancer 2012; 58: 61-65. (C) 2011 Wiley Periodicals, Inc.
C1 [Sobota, Amy; Neufeld, Ellis J.; Heeney, Matthew M.] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA.
[Sobota, Amy; Neufeld, Ellis J.; Heeney, Matthew M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Sobota, Amy; Graham, Dionne A.; Neufeld, Ellis J.; Heeney, Matthew M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Sobota, Amy] Boston Med Ctr, Boston, MA USA.
[Graham, Dionne A.] Childrens Hosp Boston, Clin Res Program, Boston, MA USA.
RP Sobota, A (reprint author), 300 Longwood Ave,AU-522, Boston, MA 02115 USA.
EM amy.sobota@childrens.harvard.edu
RI Heeney, Matthew/J-6838-2015
OI Sobota, Amy/0000-0003-3979-7435; Heeney, Matthew/0000-0002-1104-6843
FU Harvard Pediatric Health Services [AHRQ T32 NRSA: HS000063]; NIH
[HL004184]
FX Grant sponsor: Harvard Pediatric Health Services Research Fellowship;
Grant number: AHRQ T32 NRSA: HS000063; Grant sponsor: NIH K24; Grant
number: HL004184.
NR 27
TC 17
Z9 17
U1 0
U2 6
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JAN
PY 2012
VL 58
IS 1
BP 61
EP 65
DI 10.1002/pbc.23221
PG 5
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 856LD
UT WOS:000297641300013
PM 21674766
ER
PT J
AU Ho, HJ
Pyne, S
Lin, TI
AF Ho, Hsiu J.
Pyne, Saumyadipta
Lin, Tsung I.
TI Maximum likelihood inference for mixtures of skew Student-t-normal
distributions through practical EM-type algorithms
SO STATISTICS AND COMPUTING
LA English
DT Article
DE ECM algorithm; ECME algorithm; Flow cytometry; Outliers; ST mixtures;
STN mixtures
ID DENSITY-ESTIMATION; MODEL; ECM
AB This paper deals with the problem of maximum likelihood estimation for a mixture of skew Student-t-normal distributions, which is a novel model-based tool for clustering heterogeneous (multiple groups) data in the presence of skewed and heavy-tailed outcomes. We present two analytically simple EM-type algorithms for iteratively computing the maximum likelihood estimates. The observed information matrix is derived for obtaining the asymptotic standard errors of parameter estimates. A small simulation study is conducted to demonstrate the superiority of the skew Student-t-normal distribution compared to the skew t distribution. The proposed methodology is particularly useful for analyzing multimodal asymmetric data as produced by major biotechnological platforms like flow cytometry. We provide such an application with the help of an illustrative example.
C1 [Lin, Tsung I.] Natl Chung Hsing Univ, Dept Appl Math, Taichung 404, Taiwan.
[Lin, Tsung I.] Natl Chung Hsing Univ, Inst Stat, Taichung 404, Taiwan.
[Ho, Hsiu J.] Tunghai Univ, Dept Stat, Taichung 407, Taiwan.
[Pyne, Saumyadipta] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Lin, Tsung I.] China Med Univ, Dept Publ Hlth, Taichung 404, Taiwan.
RP Lin, TI (reprint author), Natl Chung Hsing Univ, Dept Appl Math, Taichung 404, Taiwan.
EM tilin@amath.nchu.edu.tw
FU National Science Council of Taiwan [NSC97-2118-M-005-001-MY2]
FX The authors would like to express his deepest gratitude to the Chief
Editor, the Associate Editor and two anonymous referees for their
valuable comments and suggestions that greatly improved this paper. This
research was supported by the National Science Council of Taiwan (Grant
NO. NSC97-2118-M-005-001-MY2).
NR 37
TC 14
Z9 15
U1 2
U2 10
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0960-3174
J9 STAT COMPUT
JI Stat. Comput.
PD JAN
PY 2012
VL 22
IS 1
BP 287
EP 299
DI 10.1007/s11222-010-9225-9
PG 13
WC Computer Science, Theory & Methods; Statistics & Probability
SC Computer Science; Mathematics
GA 855DH
UT WOS:000297543400020
ER
PT J
AU Merport, A
Bober, SL
Grose, A
Recklitis, CJ
AF Merport, Anna
Bober, Sharon L.
Grose, Amy
Recklitis, Christopher J.
TI Can the distress thermometer (DT) identify significant psychological
distress in long-term cancer survivors?: a comparison with the Brief
Symptom Inventory-18 (BSI-18)
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Cancer survivors; Psychological distress; Distress thermometer;
Screening
ID CHILDHOOD-CANCER; ADULT SURVIVORS; VALIDATION
AB As the number of cancer survivors continues to grow, identification of brief, valid psychological screening measures is critical for providing these survivors with appropriate psychosocial care. The distress thermometer (DT) is a one-item distress screening recommended by the National Comprehensive Cancer Network (NCCN) for screening cancer patients during their treatment.
In this study, the validity of the DT for identifying psychological distress in cancer survivors was evaluated by comparing results of the DT to the Brief Symptom Inventory-18 (BSI-18) in a sample of 120 survivors of adult onset cancer.
Results indicated that when using the NCCN suggested cutoff score of 5, the DT only identified 10 of the 21 BSI-18 positive cases of psychological distress (sensitivity 47.6%; specificity 90.9%). Using an alternative DT cutoff score of 4, 12 of the 21 BSI-18 positive cases were identified (sensitivity 51.7%; specificity 89.9%).
The results do not support the validity of the DT in survivors of adult cancers.
C1 [Merport, Anna; Bober, Sharon L.; Grose, Amy; Recklitis, Christopher J.] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02215 USA.
RP Merport, A (reprint author), Dana Farber Canc Inst, Perini Family Survivors Ctr, 450 Brookline Ave,D321, Boston, MA 02215 USA.
EM Christopher_Recklitis@dfci.harvard.edu
NR 25
TC 15
Z9 15
U1 1
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD JAN
PY 2012
VL 20
IS 1
BP 195
EP 198
DI 10.1007/s00520-011-1269-7
PG 4
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA 855DF
UT WOS:000297543200022
PM 21928051
ER
PT J
AU Holmes, B
Artinian, N
Anderson, L
Martin, J
Masri, J
Cloninger, C
Bernath, A
Bashir, T
Benavides-Serrato, A
Gera, J
AF Holmes, Brent
Artinian, Nicholas
Anderson, Lauren
Martin, Jheralyn
Masri, Janine
Cloninger, Cheri
Bernath, Andrew
Bashir, Tariq
Benavides-Serrato, Angelica
Gera, Joseph
TI Protor-2 interacts with tristetraprolin to regulate mRNA stability
during stress
SO CELLULAR SIGNALLING
LA English
DT Article
DE Protor-2; Tristetraprolin; mTORC2; mRNA stability; Stress
ID AU-RICH ELEMENTS; PROTEIN-KINASE; MTOR; BINDING; CANCER; RICTOR;
TURNOVER; GRANULES; ALPHA; DEADENYLATION
AB The A/U-rich RNA-binding protein tristetraprolin (TIP) is an mRNA destabilizing factor which plays a role in the regulated turnover of many transcripts encoding proteins involved in immune function and cell growth control. TTP also plays a role in stress-induced destabilization of mRNAs. Here we report the interaction of TTP with a component of the mTORC2 kinase, Protor-2 (PRR5-L, protein Q6MZQ0/FLJ14213/CAE45978). Protor-2 is structurally similar to human PRR5 and has been demonstrated to bind mTORC2 via Rictor and/or Sin1 and may signal downstream events promoting apoptosis. Protor-2 dissociates from mTORC2 upon hyperactivation of the kinase and is not required for mTORC2 integrity or activity. We identified Protor-2 in a yeast two-hybrid screen as a TTP interactor using the C-terminal mRNA decay domain of TTP as bait. The interaction of Protor-2 with TTP was also confirmed in vivo in co-immunoprecipitation experiments and Protor-2 was also detected in immunoprecipitates of Rictor. Protor-2 was shown to stimulate UP-mediated mRNA turnover of several TIP-associated mRNAs (TNF-alpha, GM-CSF, IL-3 and COX-2) in Jurkat cells when overexpressed while the half-lives of transcripts which do not decay via a TTP-mediated mechanism were unaffected. Knockdown of Protor-2 via RNAi inhibited TIP-mediated mRNA turnover of these TTP-associated mRNAs and inhibited association of TTP with cytoplasmic stress granules (SG) or mRNA processing bodies (P-bodies) following induction of the integrated stress response. These results suggest that Protor-2 associates with TTP to accelerate TTP-mediated mRNA turnover and functionally links the control of TIP-regulated mRNA stability to mTORC2 activity. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Holmes, Brent; Artinian, Nicholas; Anderson, Lauren; Martin, Jheralyn; Masri, Janine; Cloninger, Cheri; Bernath, Andrew; Bashir, Tariq; Benavides-Serrato, Angelica; Gera, Joseph] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Res & Dev, Los Angeles, CA 91343 USA.
[Gera, Joseph] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90048 USA.
[Gera, Joseph] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90048 USA.
[Gera, Joseph] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90048 USA.
RP Gera, J (reprint author), VA UCLA Med Ctr, Dept Res & Dev, 16111 Plummer St 151,Bldg 1,Rm C111A, North Hills, CA 91343 USA.
EM jgera@mednet.ucla.edu
FU NIH [RO1CA109312]; US Department of Veterans Affairs
FX We thank Drs. Michael Hall and William Rigby for providing cell lines
and antibodies, Dr. Robert Nishimura for critical reading of the
manuscript and Ardella Sherwood for excellent administrative assistance.
This work was supported, in part, by grants from the NIH (RO1CA109312)
and the US Department of Veterans Affairs.
NR 45
TC 7
Z9 7
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
J9 CELL SIGNAL
JI Cell. Signal.
PD JAN
PY 2012
VL 24
IS 1
BP 309
EP 315
DI 10.1016/j.cellsig.2011.09.015
PG 7
WC Cell Biology
SC Cell Biology
GA 852YH
UT WOS:000297392900034
PM 21964062
ER
PT B
AU Ghassemi, KA
Jensen, DM
AF Ghassemi, Kevin A.
Jensen, Dennis M.
BE Esrailian, E
TI NONVARICEAL UPPER GASTROINTESTINAL BLEEDING
SO GUT INSTINCTS: A CLINICIAN'S HANDBOOK OF DIGESTIVE AND LIVER DISEASES
LA English
DT Article; Book Chapter
ID MANAGEMENT
C1 [Ghassemi, Kevin A.; Jensen, Dennis M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA.
[Jensen, Dennis M.] UCLA Med Centet, W Los Angeles VA Med Ctr, CURE Digest Dis Res Ctr, Los Angeles, CA USA.
RP Ghassemi, KA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA
BN 978-1-55642-977-4
PY 2012
BP 59
EP 63
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA BWY89
UT WOS:000295343100009
ER
PT B
AU Kovacs, TOG
AF Kovacs, Thomas O. G.
BE Esrailian, E
TI ACID-PEPTIC DISORDERS
SO GUT INSTINCTS: A CLINICIAN'S HANDBOOK OF DIGESTIVE AND LIVER DISEASES
LA English
DT Article; Book Chapter
C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90095 USA.
RP Kovacs, TOG (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90095 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA
BN 978-1-55642-977-4
PY 2012
BP 65
EP 69
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA BWY89
UT WOS:000295343100010
ER
PT B
AU Bhat, YM
Singh, IM
AF Bhat, Yasser M.
Singh, Inder M.
BE Esrailian, E
TI BILIARY DISEASES
SO GUT INSTINCTS: A CLINICIAN'S HANDBOOK OF DIGESTIVE AND LIVER DISEASES
LA English
DT Article; Book Chapter
C1 [Bhat, Yasser M.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Bhat, Yasser M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Singh, Inder M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA
BN 978-1-55642-977-4
PY 2012
BP 85
EP 93
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA BWY89
UT WOS:000295343100013
ER
PT B
AU Eichler, AF
AF Eichler, April F.
BE Wen, PY
Schiff, D
Lee, EQ
TI Neurologic Complications of Topoisomerase Inhibitors
SO NEUROLOGIC COMPLICATIONS OF CANCER THERAPY
LA English
DT Article; Book Chapter
ID METASTATIC COLORECTAL-CANCER; HIGH-DOSE ETOPOSIDE; CEREBROSPINAL-FLUID
PHARMACOKINETICS; NERVOUS-SYSTEM LYMPHOMA; CARCINOMA CELL-LINE; I
CLINICAL-TRIAL; PHASE-I; IRINOTECAN CPT-11; LUNG-CANCER; CAMPTOTHECIN
NSC-100880
C1 [Eichler, April F.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Eichler, April F.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA.
RP Eichler, AF (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.
NR 76
TC 0
Z9 0
U1 0
U2 0
PU DEMOS MEDICAL PUBLICATIONS
PI NEW YORK
PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA
BN 978-1-936287-07-9
PY 2012
BP 49
EP 61
PG 13
WC Oncology; Clinical Neurology; Neurosciences
SC Oncology; Neurosciences & Neurology
GA BXD51
UT WOS:000295816500004
ER
PT B
AU Eichler, AF
AF Eichler, April F.
BE Wen, PY
Schiff, D
Lee, EQ
TI Neurologic Complications of Epothilones and Amino Acid Degraders
SO NEUROLOGIC COMPLICATIONS OF CANCER THERAPY
LA English
DT Article; Book Chapter
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; II CLINICAL-TRIAL; REFRACTORY
PROSTATE-CANCER; GROWTH-FACTOR RECEPTOR; GUINEA PIG SERUM; B-ANALOG;
L-ASPARAGINASE; IXABEPILONE BMS-247550; BREAST-CANCER; TUBULIN MUTATIONS
C1 [Eichler, April F.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Eichler, April F.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA.
RP Eichler, AF (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.
NR 38
TC 0
Z9 0
U1 0
U2 0
PU DEMOS MEDICAL PUBLICATIONS
PI NEW YORK
PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA
BN 978-1-936287-07-9
PY 2012
BP 63
EP 71
PG 9
WC Oncology; Clinical Neurology; Neurosciences
SC Oncology; Neurosciences & Neurology
GA BXD51
UT WOS:000295816500005
ER
PT B
AU Lee, EQ
Norden, AD
Schiff, D
Wen, PY
AF Lee, Eudocia Quant
Norden, Andrew D.
Schiff, David
Wen, Patrick Y.
BE Wen, PY
Schiff, D
Lee, EQ
TI Neurologic Complications of Targeted Therapy
SO NEUROLOGIC COMPLICATIONS OF CANCER THERAPY
LA English
DT Article; Book Chapter
ID PHASE-II TRIAL; POSTERIOR LEUKOENCEPHALOPATHY SYNDROME; REVERSIBLE
ENCEPHALOPATHY SYNDROME; RECURRENT MALIGNANT GLIOMAS; RELAPSED
MULTIPLE-MYELOMA; CELL LUNG-CANCER; PERIPHERAL NEUROPATHY; ENTEROVIRAL
MENINGOENCEPHALITIS; GLIOBLASTOMA-MULTIFORME; RITUXIMAB INFUSION
C1 [Lee, Eudocia Quant; Norden, Andrew D.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
[Schiff, David] Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA.
[Schiff, David] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA.
[Schiff, David] Univ Virginia Hlth Syst, Dept Med Hematol Oncol, Charlottesville, VA USA.
RP Lee, EQ (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
NR 62
TC 0
Z9 0
U1 0
U2 0
PU DEMOS MEDICAL PUBLICATIONS
PI NEW YORK
PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA
BN 978-1-936287-07-9
PY 2012
BP 149
EP 165
PG 17
WC Oncology; Clinical Neurology; Neurosciences
SC Oncology; Neurosciences & Neurology
GA BXD51
UT WOS:000295816500010
ER
PT B
AU Drappatz, J
AF Drappatz, Jan
BE Wen, PY
Schiff, D
Lee, EQ
TI Neurologic Complications Associated with Supportive Therapies
SO NEUROLOGIC COMPLICATIONS OF CANCER THERAPY
LA English
DT Article; Book Chapter
ID MOLECULAR-WEIGHT HEPARIN; METASTATIC BRAIN-TUMORS; RECOMBINANT FACTOR
VIIA; HIGH-GRADE GLIOMA; QUALITY-OF-LIFE; RECURRENT
GLIOBLASTOMA-MULTIFORME; NEUROLEPTIC MALIGNANT SYNDROME; VENOUS
THROMBOEMBOLISM; MOVEMENT-DISORDERS; DOUBLE-BLIND
C1 [Drappatz, Jan] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Drappatz, Jan] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
RP Drappatz, J (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.
NR 89
TC 0
Z9 0
U1 0
U2 0
PU DEMOS MEDICAL PUBLICATIONS
PI NEW YORK
PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA
BN 978-1-936287-07-9
PY 2012
BP 189
EP 199
PG 11
WC Oncology; Clinical Neurology; Neurosciences
SC Oncology; Neurosciences & Neurology
GA BXD51
UT WOS:000295816500012
ER
PT B
AU Lee, EQ
Wen, PY
AF Lee, Eudocia Quant
Wen, Patrick Y.
BE Wen, PY
Schiff, D
Lee, EQ
TI Common Neurologic Complications in Hematopoietic Stem Cell Transplant
Patients
SO NEUROLOGIC COMPLICATIONS OF CANCER THERAPY
LA English
DT Article; Book Chapter
ID BONE-MARROW-TRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; PROGRESSIVE
MULTIFOCAL LEUKOENCEPHALOPATHY; TOXOPLASMA-GONDII INFECTION; ORGAN
DYSFUNCTION SYNDROME; OF-THE-LITERATURE; CEREBRAL TOXOPLASMOSIS;
CARDIOVASCULAR RADIOLOGY; DISSEMINATED NOCARDIOSIS; TREATMENT STRATEGIES
C1 [Lee, Eudocia Quant; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
RP Lee, EQ (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
NR 86
TC 4
Z9 4
U1 0
U2 0
PU DEMOS MEDICAL PUBLICATIONS
PI NEW YORK
PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA
BN 978-1-936287-07-9
PY 2012
BP 395
EP 410
PG 16
WC Oncology; Clinical Neurology; Neurosciences
SC Oncology; Neurosciences & Neurology
GA BXD51
UT WOS:000295816500024
ER
PT J
AU Brunye, TT
Ditman, T
Giles, GE
Mahoney, CR
Kessler, K
Taylor, HA
AF Brunye, Tad T.
Ditman, Tali
Giles, Grace E.
Mahoney, Caroline R.
Kessler, Klaus
Taylor, Holly A.
TI Gender and autistic personality traits predict perspective-taking
ability in typical adults
SO PERSONALITY AND INDIVIDUAL DIFFERENCES
LA English
DT Article
DE Perspective-taking; Gender; Personality; Autistic traits; Individual
differences
ID SPECTRUM QUOTIENT AQ; FUNCTIONING AUTISM; MIND; EMPATHY; DISSOCIATION;
CHILDREN; THINK
AB Adopting another's visual perspective is exceedingly common and may underlie successful social interaction and empathizing with others. The individual differences responsible for success in perspective-taking, however, remain relatively undiscovered. We assessed whether gender and autistic personality traits in normal college student adults predict the ability to adopt another's visual perspective. In a task differentially recruiting VPT-1 which involves following another's line of sight, and VPT-2 which involves determining how another may perceive an object differently given their unique perspective (VPT-2), we found effects of both gender and autistic personality traits. Specifically, we demonstrate slowed VPT-2 but not VPT-1 performance in males and females with relatively high ASD-characteristic personality traits; this effect, however was markedly stronger in males than females. Results contribute to knowledge regarding ASD-related personality traits in the general population and the individual differences modulating perspective-taking abilities. Published by Elsevier Ltd.
C1 [Brunye, Tad T.] US Army NSRDEC, Attn AMSRD NSC WS P, Natick, MA 01760 USA.
[Brunye, Tad T.; Ditman, Tali; Giles, Grace E.; Mahoney, Caroline R.; Taylor, Holly A.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA.
[Ditman, Tali] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Kessler, Klaus] Univ Glasgow, Inst Neurosci & Psychol, Glasgow, Lanark, Scotland.
RP Brunye, TT (reprint author), US Army NSRDEC, Attn AMSRD NSC WS P, Kansas St, Natick, MA 01760 USA.
EM tbrunye@alumni.tufts.edu
OI Kessler, Klaus/0000-0001-7307-9539
NR 33
TC 14
Z9 14
U1 3
U2 23
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0191-8869
J9 PERS INDIV DIFFER
JI Pers. Individ. Differ.
PD JAN
PY 2012
VL 52
IS 1
BP 84
EP 88
DI 10.1016/j.paid.2011.09.004
PG 5
WC Psychology, Social
SC Psychology
GA 850WU
UT WOS:000297231100016
ER
PT J
AU Wilhelm, CJ
Murphy-Crews, A
Menasco, DJ
Huckans, MS
Loftis, JM
AF Wilhelm, Clare J.
Murphy-Crews, Aaron
Menasco, Daniel J.
Huckans, Marilyn S.
Loftis, Jennifer M.
TI Corticotropin releasing factor-1 receptor antagonism alters the
biochemical, but not behavioral effects of repeated interleukin-1 beta
administration
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Sickness behavior; Interleukin-1beta; Corticotropin releasing factor;
Forced swim test; p38 MAPK; Weight regulation; Cytokines
ID MAJOR DEPRESSIVE DISORDER; ACTIVATED PROTEIN-KINASE;
CHEMOTHERAPY-RELATED SYMPTOMS; INTERFERON-ALPHA; FORCED SWIM; SICKNESS
BEHAVIOR; CANCER; HORMONE; LIPOPOLYSACCHARIDE; RATS
AB Activation of the immune system via administration of cytokines is used for the treatment of chronic viral infections such as hepatitis C and for cancers resistant to radiotherapy. Cytokine-based treatments induce a range of "sickness" behaviors (e.g. depression, anxiety, pain, anorexia, and fatigue). Activation of the hypothalamic pituitary-adrenal axis via the induction of corticotropin releasing factor (CRF) may underlie these unwanted side effects. This study used repeated systemic injections of the pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) to model the sickness behaviors and biochemical effects of immune system activation. We assessed the ability of CRF type I receptor (CRF1) antagonism to reduce biochemical and behavioral signs of sickness induced by IL-1 beta treatment. Forty Wistar rats were assigned to one of four groups: 1) saline + vehicle; 2) saline + DMP904 (CRF1 antagonist); 3) IL-1 beta + vehicle; 4) IL-1 beta + DMP904. Rats received intraperitoneal injections of either DMP904 or vehicle and of IL-1 beta or saline for six days. Sickness behavior was evaluated using body weight assessments and forced swim testing (FST). Blood and brain samples were collected to measure cytokine, p38 mitogen-activated protein kinase (MAPK), and phospho-p38 MAPK levels using multiplex techniques. There were significant reductions in body weights and FST immobility times associated with IL-1 beta administration. Rats administered IL-1 beta had significantly higher serum levels of IL-1 beta, but not interferon-gamma. Within the hippocampus, IL-1 beta reduced levels of p38 MAPK, but had no impact on levels of phospho-p38 MAPK except in the presence of DMP904. When administered alone, DMP904 had no significant effect on p38 MAPK or phospho-p38 MAPK in the hippocampus, but when given with IL-1 beta led to increased phosphorylation of p38 MAPIC IL-1 beta and DMP904 reduced levels of p38 MAPK within the hypothalamus, while co-administration of IL-1 beta and DMP904 abolished the effects of either drug alone. IL-1 beta decreased immobility time in the FST, and led to reductions in body weight, changes in serum cytokine levels and p38 MAPK regulation within the hippocampus and hypothalamus. DMP904 blocked some of the neurochemical effects of IL-1 beta, but did not impact the behavioral measures, or serum cytokines. Thus, additional studies will be needed to determine whether CRF1 antagonism is an effective treatment for cytokine-induced sickness.
This article is part of a Special Issue entitled 'Anxiety and Depression'. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Wilhelm, Clare J.; Menasco, Daniel J.; Huckans, Marilyn S.; Loftis, Jennifer M.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA.
[Wilhelm, Clare J.; Huckans, Marilyn S.; Loftis, Jennifer M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA.
[Murphy-Crews, Aaron; Loftis, Jennifer M.] Reed Coll, Portland, OR 97202 USA.
[Huckans, Marilyn S.] Portland VA Med Ctr, Div Mental Hlth, Portland, OR 97239 USA.
RP Loftis, JM (reprint author), Portland VA Med Ctr, Res & Dev Serv R&D 16, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM wilhelmc@ohsu.edu; aaron.murphycrews@gmail.com; dmenasco@mac.com;
Marilyn.huckans@va.gov; loftisj@ohsu.edu
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development and Clinical Sciences Research and
Development; Department of Veterans Affairs, Veterans Health
Administration; Reed College (Portland, Oregon, USA); National Institute
of Mental Health [1-F32-MH071137-01]
FX This material is based upon work supported in part by the Department of
Veterans Affairs, Veterans Health Administration, Office of Research and
Development and Clinical Sciences Research and Development. JML and MSH
are supported by career development awards from the Department of
Veterans Affairs, Veterans Health Administration. This work was also
supported by Reed College (Portland, Oregon, USA) and the National
Institute of Mental Health (# 1-F32-MH071137-01). The authors would also
like to thank Bristol-Myers Squibb for generously providing the DMP904.
NR 76
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U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JAN
PY 2012
VL 62
IS 1
SI SI
BP 313
EP 321
DI 10.1016/j.neuropharm.2011.07.040
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 845MM
UT WOS:000296826800035
PM 21839099
ER
PT J
AU Anaya, DA
Cormier, JN
Xing, Y
Koller, P
Gaido, L
Hadfield, D
Chemaly, RF
Feig, BW
AF Anaya, Daniel A.
Cormier, Janice N.
Xing, Yan
Koller, Paul
Gaido, Lindsay
Hadfield, Donna
Chemaly, Roy F.
Feig, Barry W.
TI Development and Validation of a Novel Stratification Tool for
Identifying Cancer Patients at Increased Risk of Surgical Site Infection
SO ANNALS OF SURGERY
LA English
DT Article
ID LYMPH-NODE BIOPSY; WOUND-INFECTION; SURVEILLANCE NETWORK; POSTOPERATIVE
COMPLICATIONS; POSTDISCHARGE SURVEILLANCE; ANTIBIOTIC-PROPHYLAXIS;
MALIGNANT-MELANOMA; ABDOMINAL-SURGERY; CARDIAC-SURGERY; SYSTEM
AB Objective: To identify cancer-specific predictors of postoperative surgical site infection (SSI), and to develop a risk-stratification prognostic tool and compare its performance with traditional measures.
Background: The incidence and risk factors for SSI in cancer patients are unknown; current risk-stratification tools are not cancer-specific.
Methods: A prospective cohort study of patients undergoing elective operations (n = 503) at a tertiary cancer center was conducted. SSI was assessed using postdischarge active surveillance. Multivariate logistic regression analyses were performed to identify predictors of SSI, and beta-coefficients were used to create a scoring system. The sum of these was used to create a Risk of Surgical Site Infection in Cancer (RSSIC) score. The RSSIC was validated using bootstrapping techniques, and its discrimination was compared with the National Nosocomial Infection Surveillance (NNIS) risk index.
Results: The 30-day SSI incidence was 24%. Significant predictors of SSI included preoperative chemotherapy (OR = 1.94 [95% CI, 1.16-3.25]), clean-contaminated wounds (OR = 2.1 [95% CI, 1.24-3.55]), operative time = 2 hours (OR = 1.75 [95% CI, 1.01-3.04]) and = 4 hours (OR = 2.24 [95% CI, 1.22-4.1]), and surgical site: groin (OR = 4.65 [95% CI, 1.69-12.83]), and head/neck (OR = 0.12 [95% CI, 0.02-0.89]). The RSSIC score stratified patients into 4 risk strata for SSI. The performance of this score exceeded that of the NNIS score (AUC = 0.70 vs. 0.63, respectively; P = 0.01).
Conclusion: SSIs are common following cancer surgery. Preoperative chemotherapy, in addition to other common risk factors, was identified as a significant predictor for SSI in cancer patients. The RSSIC improves risk-stratification of cancer patients and identifies those that may benefit from more aggressive or novel preventive strategies.
C1 [Anaya, Daniel A.] Michael E DeBakey Dept Surg Surg Oncol, Houston, TX USA.
[Anaya, Daniel A.] Baylor Coll Med, Houston Hlth Serv, Houston, TX 77030 USA.
[Anaya, Daniel A.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Res Ctr Excellence, Houston, TX 77030 USA.
[Cormier, Janice N.; Xing, Yan; Koller, Paul; Feig, Barry W.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Gaido, Lindsay; Hadfield, Donna] Univ Texas MD Anderson Canc Ctr, Dept Nursing, Houston, TX 77030 USA.
[Chemaly, Roy F.] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Houston, TX 77030 USA.
RP Anaya, DA (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA.
EM danaya@bcm.edu
FU Houston VA HSR&D Center of Excellence [HFP90-020]
FX This work was supported in part by the Houston VA HSR&D Center of
Excellence (HFP90-020). The views expressed in this article are those of
the author(s) and do not necessarily represent the views of the
Department of Veterans Affairs.
NR 43
TC 6
Z9 10
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
J9 ANN SURG
JI Ann. Surg.
PD JAN
PY 2012
VL 255
IS 1
BP 134
EP 139
DI 10.1097/SLA.0b013e31823dc107
PG 6
WC Surgery
SC Surgery
GA 869ZM
UT WOS:000298638900021
PM 22143206
ER
PT J
AU Joshi, G
Petty, CR
Fried, R
Wozniak, J
Micco, JA
Henin, A
Doyle, R
Galdo, M
Kotarski, M
Caruso, J
Meller, B
Faraone, SV
Biederman, J
AF Joshi, Gagan
Petty, Carter R.
Fried, Ronna
Wozniak, Janet
Micco, Jamie A.
Henin, Aude
Doyle, Robert
Galdo, Maribel
Kotarski, Meghan
Caruso, Janet
Meller, Benjamin
Faraone, Stephen V.
Biederman, Joseph
TI Discriminant and concurrent validity of a simplified DSM-based
structured diagnostic instrument for the assessment of autism spectrum
disorders in youth and young adults
SO BMC PSYCHIATRY
LA English
DT Article
ID PERVASIVE DEVELOPMENTAL DISORDERS; RECIPROCAL SOCIAL-BEHAVIOR;
GENERAL-POPULATION; CHILDREN; TRAITS; RATES; MANIA; PDD
AB Background: To evaluate the concurrent and discriminant validity of a brief DSM-based structured diagnostic interview for referred individuals with autism spectrum disorders (ASDs).
Methods: To test concurrent validity, we assessed the structured interview's agreement in 123 youth with the expert clinician assessment and the Social Responsiveness Scale (SRS). Discriminant validity was examined using 1563 clinic-referred youth.
Results: The structured diagnostic interview and SRS were highly sensitive indicators of the expert clinician assessment. Equally strong was the agreement between the structured interview and SRS. We found evidence for high specificity for the structured interview.
Conclusions: A simplified DSM-based ASD structured diagnostic interview could serve as a useful diagnostic aid in the assessment of subjects with ASDs in clinical and research settings.
C1 [Joshi, Gagan; Petty, Carter R.; Fried, Ronna; Wozniak, Janet; Micco, Jamie A.; Henin, Aude; Doyle, Robert; Galdo, Maribel; Kotarski, Meghan; Caruso, Janet; Meller, Benjamin; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA.
[Joshi, Gagan; Petty, Carter R.; Fried, Ronna; Wozniak, Janet; Micco, Jamie A.; Henin, Aude; Doyle, Robert; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
RP Joshi, G (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA.
EM Joshi.Gagan@mgh.harvard.edu
OI Faraone, Stephen/0000-0002-9217-3982
FU Norma Fine Pediatric Psychopharmacology Fellowship Fund
FX This work was supported in part by a grant to the Alan and Lorraine
Bressler Center for study of Autism Spectrum Disorders and the Norma
Fine Pediatric Psychopharmacology Fellowship Fund.
NR 17
TC 3
Z9 3
U1 4
U2 17
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-244X
J9 BMC PSYCHIATRY
JI BMC Psychiatry
PD DEC 30
PY 2011
VL 11
AR 204
DI 10.1186/1471-244X-11-204
PG 7
WC Psychiatry
SC Psychiatry
GA 922QO
UT WOS:000302563100001
PM 22208391
ER
PT J
AU Bains, SS
Egede, LE
AF Bains, Sujeev S.
Egede, Leonard E.
TI Association of Health Literacy with Complementary and Alternative
Medicine Use: A Cross-Sectional Study in Adult Primary Care Patients
SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Article
ID QUALITY-OF-LIFE; BREAST-CANCER; SELF-CARE; CAM USE; ADHERENCE;
MEDICATION; THERAPIES; KNOWLEDGE; OUTCOMES; HYPERTENSION
AB Background: In the United States, it is estimated that 40% of adults utilize complementary and alternative medicine (CAM) therapies. Recently, national surveys report that over 90 million adults have inadequate health literacy. To date, no study has assessed health literacy and its effect on CAM use. The primary objective of this study was to assess the relationship between health literacy and CAM use independent of educational attainment. Second objective was to evaluate the differential effect of health literacy on CAM use by race.
Methods: 351 patients were recruited from an outpatient primary care clinic. Validated surveys assessed CAM use (I-CAM-Q), health literacy (REALM-R), and demographic information. We compared demographics by health literacy (adequate vs. inadequate) and overall and individual CAM categories by health literacy using chi square statistics. We found a race by health literacy interaction and ran sequential logistic regression models stratified by race to test the association between health literacy and overall CAM use (Model 1), Model 1 + education (Model 2), and Model 2 + other demographic characteristics (Model 3). We reported the adjusted effect of health literacy on CAM use for both whites and African Americans separately.
Results: 75% of the participants had adequate literacy and 80% used CAM. CAM use differed by CAM category. Among whites, adequate health literacy was significantly associated with increased CAM use in both unadjusted (Model 1, OR 7.68; p = 0.001) and models adjusted for education (Model 2, OR 7.70; p = 0.002) and other sociodemographics (Model 3, OR 9.42; p = 0.01). Among African Americans, adequate health literacy was not associated with CAM use in any of the models.
Conclusions: We found a race by literacy interaction suggesting that the relationship between health literacy and CAM use differed significantly by race. Adequate health literacy among whites is associated with increased CAM use, but not associated with CAM use in African Americans.
C1 [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 29401 USA.
[Bains, Sujeev S.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA.
RP Egede, LE (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
EM egedel@musc.edu
FU NIDDK NIH HHS [T35 DK007431, K24 DK093699]
NR 41
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Z9 11
U1 2
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6882
J9 BMC COMPLEM ALTERN M
JI BMC Complement. Altern. Med.
PD DEC 30
PY 2011
VL 11
AR 138
DI 10.1186/1472-6882-11-138
PG 7
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA 890LF
UT WOS:000300145400001
PM 22208873
ER
PT J
AU McNally, JM
McCarley, RW
McKenna, JT
Yanagawa, Y
Brown, RE
AF McNally, J. M.
McCarley, R. W.
McKenna, J. T.
Yanagawa, Y.
Brown, R. E.
TI COMPLEX RECEPTOR MEDIATION OF ACUTE KETAMINE APPLICATION ON IN VITRO
GAMMA OSCILLATIONS IN MOUSE PREFRONTAL CORTEX: MODELING GAMMA BAND
OSCILLATION ABNORMALITIES IN SCHIZOPHRENIA
SO NEUROSCIENCE
LA English
DT Article
DE schizophrenia; gamma oscillations; interneurons; parvalbumin; GABA; NMDA
ID METHYL-D-ASPARTATE; LONG-TERM DEPRESSION; RAT VISUAL-CORTEX; NETWORK
OSCILLATIONS; PHYSIOLOGICAL DYSFUNCTION; PROTEIN EXPRESSION; CORTICAL
NETWORKS; DOPAMINE NEURONS; NEURAL SYNCHRONY; 5-HT2 RECEPTORS
AB Schizophrenia (Sz), along with other neuropsychiatric disorders, is associated clinically with abnormalities in neocortical gamma frequency (30-80 Hz) oscillations. In Sz patients, these abnormalities include both increased and decreased gamma activity, and show a strong association with Sz symptoms. For several decades, administration of sub-anesthetic levels of ketamine has provided the most comprehensive experimental model of Sz-symptoms. While acute application of ketamine precipitates a psychotic-like state in a number of animal models, as well as humans, the underlying mechanisms behind this effect, including alteration of neuronal network properties, are incompletely understood, making an in vitro level analysis particularly important. Previous in vitro studies have had difficulty inducing gamma oscillations in neocortical slices maintained in submerged-type recording chambers necessary for visually guided whole-cell recordings from identified neurons. Consequently, here, we validated a modified method to evoke gamma oscillations using brief, focal application of the glutamate receptor agonist kainate (KA), in slices prepared from mice expressing green fluorescent protein in GABAergic interneurons (GAD67-GFP knock-in mice). Using this method, gamma oscillations dependent on activation of AMPA and GABA, receptors were reliably elicited in slices containing mouse pre-limbic cortex, the rodent analogue of the human dorsolateral prefrontal cortex. Examining the effects of ketamine on this model, we found that bath application of ketamine significantly potentiated KA-elicited gamma power, an effect mimicked by selective NMDAR antagonists including a selective antagonist of NMDARs containing the NR2B subunit. Importantly, ketamine, unlike more specific NMDAR antagonists, also reduced the peak frequency of KA-elicited oscillatory activity. Our findings indicate that this effect is mediated not through NMDAR, but through slowing the decay kinetics of GABA(A) receptor-mediated inhibitory postsynaptic currents in identified GABAergic interneurons. These in vitro findings may help explain the complexities of gamma findings in clinical studies of Sz and prove useful in developing new therapeutic strategies. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [McNally, J. M.; McCarley, R. W.; McKenna, J. T.; Brown, R. E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Neurosci Lab, Brockton, MA 02301 USA.
[McNally, J. M.; McCarley, R. W.; McKenna, J. T.; Brown, R. E.] Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02301 USA.
[Yanagawa, Y.] Gunma Univ, Grad Sch Med, Dept Genet & Behav Neurosci, Maebashi, Gumma 371, Japan.
[Yanagawa, Y.] JST, SORST, Maebashi, Gumma, Japan.
[Yanagawa, Y.] Japan Sci & Technol Agcy, CREST, Chiyoda Ku, Tokyo, Japan.
RP Brown, RE (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Neurosci Lab, 940 Belmont St,Res 151C, Brockton, MA 02301 USA.
EM ritchie_brown@hms.harvard.edu
RI McCarley, Robert/N-5562-2014;
OI McCarley, Robert/0000-0001-5705-7495; Brown, Ritchie/0000-0002-7164-4132
FU VA; ARRA [MH040799]; NIMH [MH094803, GAD67]; MEXT, Japan; Takeda Science
Foundation
FX We would like to thank Dr. Kevin Spencer for his comments and input on
this manuscript. This study was supported by the VA and by an ARRA
supplement to National Institute of Mental Health (NIMH) ROT grant
MH040799 "Neurophysiological studies of Schizophrenia" to R. W.
McCarley, NIMH R21 grant MH094803 "Modeling schizophrenia gamma deficits
using cell-specific RNAi knockdown of GAD67" to R.E. Brown, and
Grants-in Aids for Scientific Research from MEXT, Japan and Takeda
Science Foundation to Y. Yanagawa.
NR 70
TC 32
Z9 32
U1 4
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD DEC 29
PY 2011
VL 199
BP 51
EP 63
DI 10.1016/j.neuroscience.2011.10.015
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 863ZH
UT WOS:000298206300006
PM 22027237
ER
PT J
AU Newman, JC
Feldman, R
AF Newman, John C.
Feldman, Robin
TI Copyright and Open Access at the Bedside
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Newman, John C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA.
[Newman, John C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Feldman, Robin] Univ Calif Hastings Coll Law, Law & Biosci Project, San Francisco, CA USA.
RP Newman, JC (reprint author), San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA.
RI Newman, John/L-8112-2013
NR 4
TC 23
Z9 23
U1 0
U2 13
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 DEC 29
PY 2011
VL 365
IS 26
BP 2447
EP 2449
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 868SD
UT WOS:000298544600002
PM 22204721
ER
PT J
AU Fingold, DR
AF Fingold, Diane R.
TI The Road Less Traveled
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Fingold, Diane R.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Fingold, Diane R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Fingold, DR (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD DEC 29
PY 2011
VL 365
IS 26
BP 2449
EP 2451
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 868SD
UT WOS:000298544600003
PM 22204722
ER
PT J
AU Burger, RA
Brady, MF
Bookman, MA
Fleming, GF
Monk, BJ
Huang, H
Mannel, RS
Homesley, HD
Fowler, J
Greer, BE
Boente, M
Birrer, MJ
Liang, SX
AF Burger, Robert A.
Brady, Mark F.
Bookman, Michael A.
Fleming, Gini F.
Monk, Bradley J.
Huang, Helen
Mannel, Robert S.
Homesley, Howard D.
Fowler, Jeffrey
Greer, Benjamin E.
Boente, Matthew
Birrer, Michael J.
Liang, Sharon X.
CA Gynecologic Oncology Grp
TI Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; FACTOR EXPRESSION; PROGNOSTIC-SIGNIFICANCE;
ANTIANGIOGENIC THERAPY; MONOCLONAL-ANTIBODY; TUMOR ANGIOGENESIS; SOLID
TUMORS; PHASE-II; CARCINOMA; ASCITES
AB BACKGROUND
Vascular endothelial growth factor is a key promoter of angiogenesis and disease progression in epithelial ovarian cancer. Bevacizumab, a humanized anti-vascular endothelial growth factor monoclonal antibody, has shown single-agent activity in women with recurrent tumors. Thus, we aimed to evaluate the addition of bevacizumab to standard front-line therapy.
METHODS
In our double-blind, placebo-controlled, phase 3 trial, we randomly assigned eligible patients with newly diagnosed stage III (incompletely resectable) or stage IV epithelial ovarian cancer who had undergone debulking surgery to receive one of three treatments. All three included chemotherapy consisting of intravenous paclitaxel at a dose of 175 mg per square meter of body-surface area, plus carboplatin at an area under the curve of 6, for cycles 1 through 6, plus a study treatment for cycles 2 through 22, each cycle of 3 weeks' duration. The control treatment was chemotherapy with placebo added in cycles 2 through 22; bevacizumab-initiation treatment was chemotherapy with bevacizumab (15 mg per kilogram of body weight) added in cycles 2 through 6 and placebo added in cycles 7 through 22. Bevacizumab-throughout treatment was chemotherapy with bevacizumab added in cycles 2 through 22. The primary end point was progression-free survival.
RESULTS
Overall, 1873 women were enrolled. The median progression-free survival was 10.3 months in the control group, 11.2 in the bevacizumab-initiation group, and 14.1 in the bevacizumab-throughout group. Relative to control treatment, the hazard ratio for progression or death was 0.908 (95% confidence interval [CI], 0.795 to 1.040; P=0.16) with bevacizumab initiation and 0.717 (95% CI, 0.625 to 0.824; P<0.001) with bevacizumab throughout. At the time of analysis, 76.3% of patients were alive, with no significant differences in overall survival among the three groups. The rate of hypertension requiring medical therapy was higher in the bevacizumab-initiation group (16.5%) and the bevacizumab-throughout group (22.9%) than in the control group (7.2%). Gastrointestinal-wall disruption requiring medical intervention occurred in 1.2%, 2.8%, and 2.6% of patients in the control group, the bevacizumab-initiation group, and the bevacizumab-throughout group, respectively.
CONCLUSIONS
The use of bevacizumab during and up to 10 months after carboplatin and paclitaxel chemotherapy prolongs the median progression-free survival by about 4 months in patients with advanced epithelial ovarian cancer. (Funded by the National Cancer Institute and Genentech; ClinicalTrials.gov number, NCT00262847.)
C1 [Burger, Robert A.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Brady, Mark F.; Huang, Helen] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA.
[Bookman, Michael A.] Arizona Canc Ctr, Tucson, AZ USA.
[Fleming, Gini F.] Univ Chicago, Chicago, IL 60637 USA.
[Monk, Bradley J.] Creighton Univ, Sch Med, St Josephs Hosp & Med Ctr, Phoenix, AZ USA.
[Mannel, Robert S.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Homesley, Howard D.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Fowler, Jeffrey] Ohio State Univ, James Canc Hosp, Hilliard, OH 43026 USA.
[Greer, Benjamin E.] Seattle Canc Care Alliance, Seattle, WA USA.
[Boente, Matthew] Minnesota Oncol & Hematol, Minneapolis, MN USA.
[Birrer, Michael J.] Harvard Univ, Sch Med, Boston, MA USA.
[Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Liang, Sharon X.] N Shore Long Isl Jewish Hlth Syst, New Hyde Pk, NY USA.
RP Burger, RA (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA.
EM robert.a.burger@fccc.edu
FU National Cancer Institute; Genentech
FX Funded by the National Cancer Institute and Genentech;
ClinicalTrials.gov number, NCT00262847.; Supported by the National
Cancer Institute and Genentech.
NR 39
TC 641
Z9 653
U1 4
U2 38
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 DEC 29
PY 2011
VL 365
IS 26
BP 2473
EP 2483
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 868SD
UT WOS:000298544600008
PM 22204724
ER
PT J
AU Wang, LL
Lawrence, MS
Wan, YZ
Stojanov, P
Sougnez, C
Stevenson, K
Werner, L
Sivachenko, A
DeLuca, DS
Zhang, L
Zhang, WD
Vartanov, AR
Fernandes, SM
Goldstein, NR
Folco, EG
Cibulskis, K
Tesar, B
Sievers, QL
Shefler, E
Gabriel, S
Hacohen, N
Reed, R
Meyerson, M
Golub, TR
Lander, ES
Neuberg, D
Brown, JR
Getz, G
Wu, CJ
AF Wang, Lili
Lawrence, Michael S.
Wan, Youzhong
Stojanov, Petar
Sougnez, Carrie
Stevenson, Kristen
Werner, Lillian
Sivachenko, Andrey
DeLuca, David S.
Zhang, Li
Zhang, Wandi
Vartanov, Alexander R.
Fernandes, Stacey M.
Goldstein, Natalie R.
Folco, Eric G.
Cibulskis, Kristian
Tesar, Bethany
Sievers, Quinlan L.
Shefler, Erica
Gabriel, Stacey
Hacohen, Nir
Reed, Robin
Meyerson, Matthew
Golub, Todd R.
Lander, Eric S.
Neuberg, Donna
Brown, Jennifer R.
Getz, Gad
Wu, Catherine J.
TI SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PRE-MESSENGER-RNA; MUTATION STATUS; IN-VITRO; GENOME; ACTIVATION;
SURVIVAL; PATHWAYS; CELLS; SPLICEOSTATIN; REVEALS
AB BACKGROUND
The somatic genetic basis of chronic lymphocytic leukemia, a common and clinically heterogeneous leukemia occurring in adults, remains poorly understood.
METHODS We obtained DNA samples from leukemia cells in 91 patients with chronic lymphocytic leukemia and performed massively parallel sequencing of 88 whole exomes and whole genomes, together with sequencing of matched germline DNA, to characterize the spectrum of somatic mutations in this disease.
RESULTS
Nine genes that are mutated at significant frequencies were identified, including four with established roles in chronic lymphocytic leukemia (TP53 in 15% of patients, ATM in 9%, MYD88 in 10%, and NOTCH1 in 4%) and five with unestablished roles (SF3B1, ZMYM3, MAPK1, FBXW7, and DDX3X). SF3B1, which functions at the catalytic core of the spliceosome, was the second most frequently mutated gene (with mutations occurring in 15% of patients). SF3B1 mutations occurred primarily in tumors with deletions in chromosome 11q, which are associated with a poor prognosis in patients with chronic lymphocytic leukemia. We further discovered that tumor samples with mutations in SF3B1 had alterations in pre-messenger RNA (mRNA) splicing.
CONCLUSIONS
Our study defines the landscape of somatic mutations in chronic lymphocytic leukemia and highlights pre-mRNA splicing as a critical cellular process contributing to chronic lymphocytic leukemia.
C1 [Wang, Lili; Wan, Youzhong; Zhang, Li; Zhang, Wandi; Sievers, Quinlan L.; Wu, Catherine J.] Harvard Inst Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Wang, Lili; Wan, Youzhong; Zhang, Li; Zhang, Wandi; Vartanov, Alexander R.; Fernandes, Stacey M.; Goldstein, Natalie R.; Tesar, Bethany; Sievers, Quinlan L.; Meyerson, Matthew; Brown, Jennifer R.; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Stevenson, Kristen; Werner, Lillian; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Folco, Eric G.; Reed, Robin; Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Folco, Eric G.; Reed, Robin; Golub, Todd R.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Brown, Jennifer R.; Wu, Catherine J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Hacohen, Nir] Massachusetts Gen Hosp, Dept Med, Div Allergy Immunol & Rheumatol, Boston, MA 02114 USA.
[Brown, Jennifer R.; Wu, Catherine J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
RP Wu, CJ (reprint author), Harvard Inst Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Rm 416B,77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM cwu@partners.org
RI Meyerson, Matthew/E-7123-2012; Folco, Eric/M-2665-2013
FU Broad Institute through the National Human Genome Research Institute at
the National Institutes of Health [U54HG003067]; National Institutes of
Health [GM43375, K23 CA115682]; National Cancer Institute
[5R21CA115043-2]; Melton and Rosenbach Funds; Blavatnik Family
Foundation; Howard Hughes Medical Institute; Damon Runyon Cancer
Research Foundation [CI-38-07]
FX Supported by the Broad Institute through a grant from the National Human
Genome Research Institute at the National Institutes of Health
(U54HG003067) and by grants from the National Institutes of Health
(GM43375, to Drs. Folco and Reed, and K23 CA115682, to Dr. Brown), the
National Cancer Institute (5R21CA115043-2), the Melton and Rosenbach
Funds (to Dr. Brown), the Blavatnik Family Foundation (to Dr. Wu), the
Early Career Physician-Scientist Award of the Howard Hughes Medical
Institute (to Dr. Wu), and the Damon Runyon Cancer Research Foundation
(CI-38-07, to Dr. Wu). Dr. Brown is a Scholar of the American Society of
Hematology and a Scholar in Clinical Research of the Leukemia and
Lymphoma Society.
NR 35
TC 461
Z9 471
U1 2
U2 42
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 DEC 29
PY 2011
VL 365
IS 26
BP 2497
EP 2506
DI 10.1056/NEJMoa1109016
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 868SD
UT WOS:000298544600010
PM 22150006
ER
PT J
AU Tritos, NA
Schaefer, PW
Stein, TD
AF Tritos, Nicholas A.
Schaefer, Pamela W.
Stein, Thor D.
TI Case 40-2011: A 52-Year-Old Man with Weakness, Infections, and Enlarged
Adrenal Glands
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CORTICOTROPIN-RELEASING HORMONE; CUSHINGS-SYNDROME; NELSONS-SYNDROME;
DIFFERENTIAL-DIAGNOSIS; CONSENSUS STATEMENT; PITUITARY-ADENOMAS;
COMPLETE REMISSION; CYPROHEPTADINE; BROMOCRIPTINE; PROLIFERATION
C1 [Tritos, Nicholas A.] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA.
[Schaefer, Pamela W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Stein, Thor D.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Tritos, Nicholas A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Schaefer, Pamela W.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Stein, Thor D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA.
FU Pfizer
FX Dr. Tritos reports receiving research support, consulting fees, and
reimbursement for travel expenses from Pfizer. No other potential
conflict of interest relevant to this article was reported.
NR 20
TC 3
Z9 3
U1 0
U2 7
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 DEC 29
PY 2011
VL 365
IS 26
BP 2520
EP 2530
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 868SD
UT WOS:000298544600013
PM 22204728
ER
PT J
AU Wang, XD
Morgan, SC
Loeken, MR
AF Wang, Xiao Dan
Morgan, Sarah C.
Loeken, Mary R.
TI Pax3 Stimulates p53 Ubiquitination and Degradation Independent of
Transcription
SO PLOS ONE
LA English
DT Article
ID CARDIAC NEURAL CREST; EMBRYONIC STEM-CELLS; DOWNSTREAM TARGET GENES;
OUTFLOW TRACT SEPTATION; TUBE DEFECTS; DNA-BINDING;
WAARDENBURG-SYNDROME; MICROARRAY ANALYSIS; DIABETIC PREGNANCY; HUMAN
MELANOMAS
AB Background: Pax3 is a developmental transcription factor that is required for neural tube and neural crest development. We previously showed that inactivating the p53 tumor suppressor protein prevents neural tube and cardiac neural crest defects in Pax3-mutant mouse embryos. This demonstrates that Pax3 regulates these processes by blocking p53 function. Here we investigated the mechanism by which Pax3 blocks p53 function.
Methodology/Principal Findings: We employed murine embryonic stem cell (ESC)-derived neuronal precursors as a cell culture model of embryonic neuroepithelium or neural crest. Pax3 reduced p53 protein stability, but had no effect on p53 mRNA levels or the rate of p53 synthesis. Full length Pax3 as well as fragments that contained either the DNA-binding paired box or the homeodomain, expressed as GST or FLAG fusion proteins, physically associated with p53 and Mdm2 both in vitro and in vivo. In contrast, Splotch Pax3, which causes neural tube and neural crest defects in homozygous embryos, bound weakly, or not at all, to p53 or Mdm2. The paired domain and homeodomain each stimulated Mdm2-mediated ubiquitination of p53 and p53 degradation in the absence of the Pax3 transcription regulatory domains, whereas Splotch Pax3 did not stimulate p53 ubiquitination or degradation.
Conclusions/Significance: Pax3 inactivates p53 function by stimulating its ubiquitination and degradation. This process utilizes the Pax3 paired domain and homeodomain but is independent of DNA-binding and transcription regulation. Because inactivating p53 is the only required Pax3 function during neural tube closure and cardiac neural crest development, and inactivating p53 does not require Pax3-dependent transcription regulation, this indicates that Pax3 is not required to function as a transcription factor during neural tube closure and cardiac neural crest development. These findings further suggest novel explanations for PAX3 functions in human diseases, such as in neural crest-derived cancers and Waardenburg syndrome types 1 and 3.
C1 [Wang, Xiao Dan; Morgan, Sarah C.; Loeken, Mary R.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Dev & Stem Cell Biol,Dept Med, Boston, MA 02115 USA.
RP Wang, XD (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Dev & Stem Cell Biol,Dept Med, Boston, MA 02115 USA.
EM mary.loeken@joslin.harvard.edu
OI Loeken, Mary/0000-0002-8056-9816
FU Diabetes Endocrine Research Center of the Joslin Diabetes Center; DNA
sequencing Core of the Dana Farber/Harvard Cancer Center; [RO1 DK52865]
FX This work was supported by RO1 DK52865 (to MRL). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.; We appreciate the assistance of Jennifer
Waters and other members of the Nikon Imaging Center at Harvard Medical
School. Dr. Wei Gu provided plasmids encoding GST fusion proteins of
human p53 and HDM2 and helpful advice. We acknowledge the contributions
of core laboratories supported by the Diabetes Endocrine Research Center
of the Joslin Diabetes Center, and the DNA sequencing Core of the Dana
Farber/Harvard Cancer Center.
NR 59
TC 13
Z9 14
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 28
PY 2011
VL 6
IS 12
AR e29379
DI 10.1371/journal.pone.0029379
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 897SK
UT WOS:000300676300051
PM 22216266
ER
PT J
AU Wu, K
Feskanich, D
Fuchs, CS
Chan, AT
Willett, WC
Hollis, BW
Pollak, MN
Giovannucci, E
AF Wu, Kana
Feskanich, Diane
Fuchs, Charles S.
Chan, Andrew T.
Willett, Walter C.
Hollis, Bruce W.
Pollak, Michael N.
Giovannucci, Edward
TI Interactions between Plasma Levels of 25-Hydroxyvitamin D, Insulin-Like
Growth Factor (IGF)-1 and C-Peptide with Risk of Colorectal Cancer
SO PLOS ONE
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRE; IGF-BINDING PROTEIN-3; FACTOR
BINDING-PROTEIN-3 CONCENTRATIONS; MALE HEALTH-PROFESSIONALS; BODY-MASS
INDEX; FACTOR-I; VITAMIN-D; COLON-CANCER; LIFE-STYLE; POSTMENOPAUSAL
WOMEN
AB Background: Vitamin D status and levels of insulin-like growth factor (IGF)-1 and C-peptide have been implicated in colorectal carcinogenesis. However, in contrast to vitamin D IGF-1 is not an easily modifiable risk factor.
Methods: Combining data from the Health Professionals Follow up Study (HPFS) and the Nurses' Health Study cohort (NHS) additive and multiplicative interactions were examined between plasma 25-hydroxyvitamin D (25(OH) D) and IGF-1, IGFBP-3 as well as C-peptide levels in 499 cases and 992 matched controls. For the various analytes, being high or low was based on being either above (or equal) or below the medians, respectively.
Results: Compared to participants with high 25(OH) D and low IGF-1/IGFBP-3 ratio (reference group), participants with a high IGF-1/IGFBP-3 ratio were at elevated risk of colorectal cancer when 25(OH) D was low (odds ratio (OR): 2.05 (95% CI: 1.43 to 2.92), but not when 25(OH) D was high (OR: 1.20 (95% CI: 0.84 to 1.71, p(interaction): additive = 0.06, multiplicative = 0.25). Similarly, compared to participants with high 25(OH) D and low molar IGF-1/IGFBP-3 ratio and low C-peptide levels (reference group), participants with a combination of either high IGF-1/IGFBP-3 ratio or high C-peptide were at elevated risk for colorectal cancer when 25(OH) D was low (OR = 1.90, 95% CI: 1.22 to 2.94) but not when 25(OH) D was high (OR = 1.15, 95% CI: 0.74 to 1.77, p(interaction): additive = 0.004; multiplicative = 0.04).
Conclusion: The results from this study suggest that improving vitamin D status may help lower risk of colorectal cancer associated with higher IGF-1/IGFBP-3 ratio or C-peptide levels.
C1 [Wu, Kana; Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Feskanich, Diane; Fuchs, Charles S.; Chan, Andrew T.; Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA.
[Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Hollis, Bruce W.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA.
[Pollak, Michael N.] McGill Univ, Jewish Gen Hosp, Dept Med & Oncol, Montreal, PQ H3T 1E2, Canada.
RP Wu, K (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
EM kana.wu@channing.harvard.edu
RI Pollak, Michael/G-9094-2011
OI Pollak, Michael/0000-0003-3047-0604
FU National Cancer Institute, National Institutes of Health [CA055075,
CA49449, CA87969]
FX Grants CA055075, CA49449 and CA87969 from the National Cancer Institute,
National Institutes of Health. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 76
TC 16
Z9 17
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 28
PY 2011
VL 6
IS 12
AR e28520
DI 10.1371/journal.pone.0028520
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 897SK
UT WOS:000300676300005
PM 22216097
ER
PT J
AU Jimenez, NL
Flannick, J
Yahyavi, M
Li, J
Bardakjian, T
Tonkin, L
Schneider, A
Sherr, EH
Slavotinek, AM
AF Jimenez, Nelson Lopez
Flannick, Jason
Yahyavi, Mani
Li, Jiang
Bardakjian, Tanya
Tonkin, Leath
Schneider, Adele
Sherr, Elliott H.
Slavotinek, Anne M.
TI Targeted 'Next-Generation' sequencing in anophthalmia and microphthalmia
patients confirms SOX2, OTX2 and FOXE3 mutations
SO BMC MEDICAL GENETICS
LA English
DT Article
DE anophthalmia; microphthalmia; next-generation sequencing; SOX2; OTX2;
FOXE3
ID COLOBOMA; GENE; SPECTRUM; CHX10
AB Background: Anophthalmia/microphthalmia (A/M) is caused by mutations in several different transcription factors, but mutations in each causative gene are relatively rare, emphasizing the need for a testing approach that screens multiple genes simultaneously. We used next-generation sequencing to screen 15 A/M patients for mutations in 9 pathogenic genes to evaluate this technology for screening in A/M.
Methods: We used a pooled sequencing design, together with custom single nucleotide polymorphism (SNP) calling software. We verified predicted sequence alterations using Sanger sequencing.
Results: We verified three mutations - c.542delC in SOX2, resulting in p.Pro181Argfs*22, p.Glu105X in OTX2 and p. Cys240X in FOXE3. We found several novel sequence alterations and SNPs that were likely to be non-pathogenic p.Glu42Lys in CRYBA4, p.Val201Met in FOXE3 and p.Asp291Asn in VSX2. Our analysis methodology gave one false positive result comprising a mutation in PAX6 (c.1268A > T, predicting p.X423LeuextX*15) that was not verified by Sanger sequencing. We also failed to detect one 20 base pair (bp) deletion and one 3 bp duplication in SOX2.
Conclusions: Our results demonstrated the power of next-generation sequencing with pooled sample groups for the rapid screening of candidate genes for A/M as we were correctly able to identify disease-causing mutations. However, next-generation sequencing was less useful for small, intragenic deletions and duplications. We did not find mutations in 10/15 patients and conclude that there is a need for further gene discovery in A/M.
C1 [Jimenez, Nelson Lopez; Yahyavi, Mani; Slavotinek, Anne M.] Univ Calif San Francisco, Div Genet, Dept Pediat, San Francisco, CA 94143 USA.
[Flannick, Jason] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Flannick, Jason] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Li, Jiang; Sherr, Elliott H.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Bardakjian, Tanya; Schneider, Adele] Albert Einstein Med Ctr, Dept Pediat, Div Genet, Philadelphia, PA 19141 USA.
[Tonkin, Leath] Univ Calif Berkeley, Vincent J Coates Genom Sequencing Lab GSL QB3, Berkeley, CA 94720 USA.
RP Slavotinek, AM (reprint author), Univ Calif San Francisco, Div Genet, Dept Pediat, 533 Parnassus St,Room U585P, San Francisco, CA 94143 USA.
EM slavotia@peds.ucsf.edu
FU Eunice Kennedy Shriver National Institute of Child Health, National
Institutes of Health [K08HD053476-01A1]
FX Anne Slavotinek was funded by a K08 grant, K08HD053476-01A1, from The
Eunice Kennedy Shriver National Institute of Child Health, National
Institutes of Health.
NR 25
TC 7
Z9 7
U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD DEC 28
PY 2011
VL 12
AR 172
DI 10.1186/1471-2350-12-172
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 890QF
UT WOS:000300158800001
PM 22204637
ER
PT J
AU Wong, ES
Wang, BCM
Garrison, LP
Alfonso-Cristancho, R
Flum, DR
Arterburn, DE
Sullivan, SD
AF Wong, Edwin S.
Wang, Bruce C. M.
Garrison, Louis P.
Alfonso-Cristancho, Rafael
Flum, David R.
Arterburn, David E.
Sullivan, Sean D.
TI Examining the BMI-mortality relationship using fractional polynomials
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
ID BODY-MASS INDEX; ALL-CAUSE MORTALITY; FOLLOW-UP; EXCESS MORTALITY; LIFE
EXPECTANCY; UNITED-STATES; OLDER-ADULTS; OBESITY; WEIGHT; WOMEN
AB Background: Many previous studies estimating the relationship between body mass index (BMI) and mortality impose assumptions regarding the functional form for BMI and result in conflicting findings. This study investigated a flexible data driven modelling approach to determine the nonlinear and asymmetric functional form for BMI used to examine the relationship between mortality and obesity. This approach was then compared against other commonly used regression models.
Methods: This study used data from the National Health Interview Survey, between 1997 and 2000. Respondents were linked to the National Death Index with mortality follow-up through 2005. We estimated 5-year all-cause mortality for adults over age 18 using the logistic regression model adjusting for BMI, age and smoking status. All analyses were stratified by sex. The multivariable fractional polynomials (MFP) procedure was employed to determine the best fitting functional form for BMI and evaluated against the model that includes linear and quadratic terms for BMI and the model that groups BMI into standard weight status categories using a deviance difference test. Estimated BMI-mortality curves across models were then compared graphically.
Results: The best fitting adjustment model contained the powers -1 and -2 for BMI. The relationship between 5-year mortality and BMI when estimated using the MFP approach exhibited a J-shaped pattern for women and a U-shaped pattern for men. A deviance difference test showed a statistically significant improvement in model fit compared to other BMI functions. We found important differences between the MFP model and other commonly used models with regard to the shape and nadir of the BMI-mortality curve and mortality estimates.
Conclusions: The MFP approach provides a robust alternative to categorization or conventional linear-quadratic models for BMI, which limit the number of curve shapes. The approach is potentially useful in estimating the relationship between the full spectrum of BMI values and other health outcomes, or costs.
C1 [Wong, Edwin S.; Wang, Bruce C. M.; Garrison, Louis P.; Alfonso-Cristancho, Rafael; Sullivan, Sean D.] Univ Washington, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA.
[Wong, Edwin S.] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA USA.
[Flum, David R.] Univ Washington, Surg Outcomes Res Ctr, Seattle, WA 98195 USA.
[Arterburn, David E.] Grp Hlth Res Inst, Seattle, WA USA.
RP Wong, ES (reprint author), Univ Washington, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA.
EM eswong@uw.edu
FU HQ Air Force Surgeon General [FA7014-08-2-0002]; U.S. Air Force;
Department of Veterans Affairs [TPP 61-024]
FX This paper was written for the Bariatric Obesity Outcome Modeling
Collaborative. Members are listed at the end of the manuscript. This
work was supported by the HQ Air Force Surgeon General under Award No.
FA7014-08-2-0002. Opinions, interpretations, conclusions and
recommendations are those of the author and are not necessarily endorsed
by the U.S. Air Force. Dr. Wong was supported by the Department of
Veterans Affairs, Health Services Research and Development Post-Doctoral
Fellowship TPP 61-024.
NR 41
TC 15
Z9 15
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD DEC 28
PY 2011
VL 11
AR 175
DI 10.1186/1471-2288-11-175
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 890SQ
UT WOS:000300165600001
PM 22204699
ER
PT J
AU Peisley, A
Lin, C
Wu, B
Orme-Johnson, M
Liu, MY
Walz, T
Hur, S
AF Peisley, Alys
Lin, Cecilie
Wu, Bin
Orme-Johnson, McGhee
Liu, Mengyuan
Walz, Thomas
Hur, Sun
TI Cooperative assembly and dynamic disassembly of MDA5 filaments for viral
dsRNA recognition
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE pattern recognition receptor; receptor clustering; dynamic instability
ID DOUBLE-STRANDED-RNA; INDUCIBLE GENE-I; RIG-I; ANTIVIRAL RESPONSES;
HELICASE; MECHANISM; PROTEINS; IMMUNITY; FAMILY; DOMAIN
AB MDA5, an RIG-I-like helicase, is a conserved cytoplasmic viral RNA sensor, which recognizes dsRNA from a wide-range of viruses in a length-dependent manner. It has been proposed that MDA5 forms higher-order structures upon viral dsRNA recognition or during antiviral signaling, however the organization and nature of this proposed oligomeric state is unknown. We report here that MDA5 cooperatively assembles into a filamentous oligomer composed of a repeating segmental arrangement of MDA5 dimers along the length of dsRNA. Binding of MDA5 to dsRNA stimulates its ATP hydrolysis activity with little coordination between neighboring molecules within a filament. Individual ATP hydrolysis in turn renders an intrinsic kinetic instability to the MDA5 filament, triggering dissociation of MDA5 from dsRNA at a rate inversely proportional to the filament length. These results suggest a previously unrecognized role of ATP hydrolysis in control of filament assembly and disassembly processes, thereby autoregulating the interaction of MDA5 with dsRNA, and provides a potential basis for dsRNA length-dependent antiviral signaling.
C1 [Peisley, Alys; Wu, Bin; Orme-Johnson, McGhee; Hur, Sun] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
[Peisley, Alys; Wu, Bin; Hur, Sun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Lin, Cecilie; Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Liu, Mengyuan] Harvard Univ, Dept Mol Cellular Biol, Boston, MA 02115 USA.
[Walz, Thomas] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Hur, S (reprint author), Childrens Hosp, Immune Dis Inst, 300 Longwood Ave, Boston, MA 02115 USA.
EM hur@idi.harvard.edu
RI Wu, Bin/C-4715-2015
FU GlaxoSmithKline; Massachusetts Life Sciences Center; Pew Scholarship
FX We thank S. C. Harrison for discussions; A. Palmenberg for
encephalomyocarditis virus and Mengo virus cDNA; M. Eck for sharing the
multiangle light scattering instrument. A. P. and B. W. acknowledge
postdoctoral fellowships from GlaxoSmithKline. T. W. is an Investigator
in the Howard Hughes Medical Institute. S. H. is the recipient of a New
Investigator Award (Massachusetts Life Sciences Center) and a Pew
Scholarship.
NR 30
TC 94
Z9 95
U1 1
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 27
PY 2011
VL 108
IS 52
BP 21010
EP 21015
DI 10.1073/pnas.1113651108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 867UI
UT WOS:000298479900034
PM 22160685
ER
PT J
AU Aubert, RD
Kamphorst, AO
Sarkar, S
Vezys, V
Ha, SJ
Barber, DL
Ye, LL
Sharpe, AH
Freeman, GJ
Ahmed, R
AF Aubert, Rachael D.
Kamphorst, Alice O.
Sarkar, Surojit
Vezys, Vaiva
Ha, Sang-Jun
Barber, Daniel L.
Ye, Lilin
Sharpe, Arlene H.
Freeman, Gordon J.
Ahmed, Rafi
TI Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during
chronic viral infection
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; MHC CLASS-II; DISEASE PROGRESSION;
CANCER VACCINES; IMMUNE EVASION; RESPONSES; PERSISTENCE; MICE;
DIFFERENTIATION; IMMUNOTHERAPY
AB CD4 T cells play a critical role in regulating CD8 T-cell responses during chronic viral infection. Several studies in animal models and humans have shown that the absence of CD4 T-cell help results in severe dysfunction of virus-specific CD8 T cells. However, whether function can be restored in already exhausted CD8 T cells by providing CD4 T-cell help at a later time remains unexplored. In this study, we used a mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection to address this question. Adoptive transfer of LCMV-specific CD4 T cells into chronically infected mice restored proliferation and cytokine production by exhausted virus-specific CD8 T cells and reduced viral burden. Although the transferred CD4 T cells were able to enhance function in exhausted CD8 T cells, these CD4 T cells expressed high levels of the programmed cell death (PD)-1 inhibitory receptor. Blockade of the PD-1 pathway increased the ability of transferred LCMV-specific CD4 T cells to produce effector cytokines, improved rescue of exhausted CD8 T cells, and resulted in a striking reduction in viral load. These results suggest that CD4 T-cell immunotherapy alone or in conjunction with blockade of inhibitory receptors may be a promising approach for treating CD8 T-cell dysfunction in chronic infections and cancer.
C1 [Aubert, Rachael D.; Kamphorst, Alice O.; Sarkar, Surojit; Vezys, Vaiva; Ha, Sang-Jun; Barber, Daniel L.; Ye, Lilin; Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Aubert, Rachael D.; Kamphorst, Alice O.; Sarkar, Surojit; Vezys, Vaiva; Ha, Sang-Jun; Barber, Daniel L.; Ye, Lilin; Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Sharpe, Arlene H.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Ahmed, R (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
EM rahmed@emory.edu
RI vezys, vaiva/N-3144-2013;
OI Vezys, Vaiva/0000-0002-2520-809X; Ha, Sang-Jun/0000-0002-1192-6031
FU National Institutes of Health [R01 AI030048, P01 AI080192, P01
AI056299]; Cancer Research Institute's Irvington Institute
FX We thank B. T. Konieczny and H. Wu for technical assistance and members
of R.A.'s laboratory for helpful discussions. This work was supported by
National Institutes of Health Grants R01 AI030048 and P01 AI080192 (to
R.A.), P01 AI056299 (G.J.F., R.A., A.H.S.), and by the Cancer Research
Institute's Irvington Institute Fellowship Program (A.O.K.).
NR 48
TC 70
Z9 71
U1 0
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 27
PY 2011
VL 108
IS 52
BP 21182
EP 21187
DI 10.1073/pnas.1118450109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 867UI
UT WOS:000298479900063
PM 22160724
ER
PT J
AU Logan, AC
Gao, H
Wang, CL
Sahaf, B
Jones, CD
Marshall, EL
Buno, I
Armstrong, R
Fire, AZ
Weinberg, KI
Mindrinos, M
Zehnder, JL
Boyd, SD
Xiao, WZ
Davis, RW
Miklos, DB
AF Logan, Aaron C.
Gao, Hong
Wang, Chunlin
Sahaf, Bita
Jones, Carol D.
Marshall, Eleanor L.
Buno, Ismael
Armstrong, Randall
Fire, Andrew Z.
Weinberg, Kenneth I.
Mindrinos, Michael
Zehnder, James L.
Boyd, Scott D.
Xiao, Wenzhong
Davis, Ronald W.
Miklos, David B.
TI High-throughput VDJ sequencing for quantification of minimal residual
disease in chronic lymphocytic leukemia and immune reconstitution
assessment
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE next-generation sequencing; consensus-primed polymerase chain reaction;
immune reconstitution
ID STEM-CELL TRANSPLANTATION; POLYMERASE-CHAIN-REACTION;
VERSUS-HOST-DISEASE; ALLOGENEIC TRANSPLANTATION; FLOW-CYTOMETRY; RQ-PCR;
CLL; IMMUNOGLOBULIN; ERADICATION; RITUXIMAB
AB The primary cause of poor outcome following allogeneic hematopoietic cell transplantation (HCT) for chronic lymphocytic leukemia (CLL) is disease recurrence. Detection of increasing minimal residual disease (MRD) following HCT may permit early intervention to prevent clinical relapse; however, MRD quantification remains an uncommon diagnostic test because of logistical and financial barriers to widespread use. Here we describe a method for quantifying CLL MRD using widely available consensus primers for amplification of all Ig heavy chain (IGH) genes in a mixture of peripheral blood mononuclear cells, followed by high-throughput sequencing (HTS) for disease-specific IGH sequence quantification. To achieve accurate MRD quantification, we developed a systematic bioinformatic methodology to aggregate cancer clone sequence variants arising from systematic and random artifacts occurring during IGH-HTS. We then compared the sensitivity of IGH-HTS, flow cytometry, and allele-specific oligonucleotide PCR for MRD quantification in 28 samples collected from 6 CLL patients following allogeneic HCT. Using amplimer libraries generated with consensus primers from patient blood samples, we demonstrate the sensitivity of IGH-HTS with 454 pyrosequencing to be 10(-5), with a high correlation between quantification by allele-specific oligonucleotide PCR and IGH-HTS (r = 0.85). From the same dataset used to quantify MRD, IGH-HTS also allowed us to profile IGH repertoire reconstitution after HCT-information not provided by the other MRD methods. IGH-HTS using consensus primers will broaden the availability of MRD quantification in CLL and other B cell malignancies, and this approach has potential for quantitative evaluation of immune diversification following transplant and nontransplant therapies.
C1 [Gao, Hong; Wang, Chunlin; Mindrinos, Michael; Xiao, Wenzhong; Davis, Ronald W.] Stanford Genome Technol Ctr, Stanford, CA 94304 USA.
[Logan, Aaron C.; Sahaf, Bita; Miklos, David B.] Stanford Univ, Div Blood & Marrow Transplantat, Sch Med, Stanford, CA 94305 USA.
[Zehnder, James L.] Stanford Univ, Dept Med, Div Hematol, Sch Med, Stanford, CA 94305 USA.
[Jones, Carol D.; Marshall, Eleanor L.; Fire, Andrew Z.; Boyd, Scott D.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
Stanford Univ, Dept Pediat, Div Pediat Stem Cell Transplantat, Sch Med, Stanford, CA 94305 USA.
[Buno, Ismael] Hosp Gen Univ Gregorio Maranon, Dept Hematol, Madrid 28007, Spain.
[Xiao, Wenzhong] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Armstrong, Randall] Stanford Hosp & Clin, Stanford Cellular Therapeut & Transplantat Lab, Stanford, CA 94305 USA.
RP Davis, RW (reprint author), Stanford Genome Technol Ctr, Stanford, CA 94304 USA.
EM dbowe@stanford.edu; dmiklos@stanford.edu
RI Buno, Ismael/G-4524-2013;
OI Buno, Ismael/0000-0003-4931-9170; Logan, Aaron/0000-0002-1179-5879;
xiao, wenzhong/0000-0003-4944-6380
FU Leukemia and Lymphoma Translational Research Award [R618-09]; National
Cancer Institute [P01 CA049605]; Stanford University Cancer Institute;
Stanford Genome Technology Center National Institutes of Health [P01
HG000205]; Instituto de Salud Carlos III Bolsas de Ampliacion de
Estudios (Ministerio de Ciencia e Innovacion, Spain); American Society
of Hematology Research
FX We thank the patients who participated in this study and the bone marrow
transplant nurses, patient coordinators, and staff at Stanford
University Medical Center who made this work possible. This work was
supported by Leukemia and Lymphoma Translational Research Award R618-09,
National Cancer Institute Grant P01 CA049605, and the Stanford
University Cancer Institute. H. G. was supported by Stanford Genome
Technology Center National Institutes of Health Grant P01 HG000205. I.
B. was supported by an Instituto de Salud Carlos III Bolsas de
Ampliacion de Estudios grant (Ministerio de Ciencia e Innovacion,
Spain). A. C. L. is an American Society of Hematology Research Training
Award Fellow.
NR 37
TC 65
Z9 66
U1 1
U2 15
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 DEC 27
PY 2011
VL 108
IS 52
BP 21194
EP 21199
DI 10.1073/pnas.1118357109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 867UI
UT WOS:000298479900065
PM 22160699
ER
PT J
AU Eldaief, MC
Halko, MA
Buckner, RL
Pascual-Leone, A
AF Eldaief, Mark C.
Halko, Mark A.
Buckner, Randy L.
Pascual-Leone, Alvaro
TI Transcranial magnetic stimulation modulates the brain's intrinsic
activity in a frequency-dependent manner
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE network dynamics; resting-state functional MRI; hippocampus; medial
prefrontal cortex
ID STATE FUNCTIONAL CONNECTIVITY; DORSAL PREMOTOR CORTEX; DEFAULT MODE
NETWORK; PRIMARY MOTOR CORTEX; RESTING HUMAN BRAIN; REPETITIVE TMS;
MAJOR DEPRESSION; CEREBRAL-CORTEX; MACAQUE MONKEY; BLOOD-FLOW
AB Intrinsic activity in the brain is organized into networks. Although constrained by their anatomical connections, functional correlations between nodes of these networks reorganize dynamically. Dynamic organization implies that couplings between network nodes can be reconfigured to support processing demands. To explore such reconfigurations, we combined repetitive transcranial magnetic stimulation (rTMS) and functional connectivity MRI (fcMRI) to modulate cortical activity in one node of the default network, and assessed the effect of this upon functional correlations throughout the network. Two different frequencies of rTMS to the same default network node (the left posterior inferior parietal lobule, lpIPL) induced two topographically distinct changes in functional connectivity. High-frequency rTMS to lpIPL decreased functional correlations between cortical default network nodes, but not between these nodes and the hippocampal formation. In contrast, low frequency rTMS to lpIPL did not alter connectivity between cortical default network nodes, but increased functional correlations between lpIPL and the hippocampal formation. These results suggest that the default network is composed of (at least) two subsystems. More broadly, the finding that two rTMS stimulation regimens to the same default network node have distinct effects reveals that this node is embedded within a network that possesses multiple, functionally distinct relationships among its distributed partners.
C1 [Eldaief, Mark C.; Halko, Mark A.; Pascual-Leone, Alvaro] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA.
[Eldaief, Mark C.; Pascual-Leone, Alvaro] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cognit Neurol,Dept Neurol, Boston, MA 02215 USA.
[Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Buckner, Randy L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02215 USA.
[Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
RP Eldaief, MC (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA.
EM meldaief@bidmc.harvard.edu
RI Halko, Mark/G-8633-2016
OI Halko, Mark/0000-0002-7427-0789
FU Berenson-Allen Foundation; Harvard Clinical and Translational Science
Center [NCRR-NIH UL1 RR025758]; Klarman Foundation; Mind, Brain, and
Behavior Interfaculty Initiative at Harvard University; Beth Israel
Deaconess Medical Center; Harvard-Massachusetts Institute of Technology
Division of Health Sciences and Technology
FX We thank Andrew Ellison and the Center for Biomedical Imaging at Boston
University, Cleofe Pena Gomez for assistance with data processing, and
Michael D. Fox for useful discussions. Work on this study was supported
in part by the Berenson-Allen Foundation, the Harvard Clinical and
Translational Science Center (Harvard Catalyst; NCRR-NIH UL1 RR025758),
and the Klarman Foundation (to A.P.-L.). M.C.E. was supported by the
Mind, Brain, and Behavior Interfaculty Initiative at Harvard University
and the Clinical Investigators Training Program of the Beth Israel
Deaconess Medical Center and the Harvard-Massachusetts Institute of
Technology Division of Health Sciences and Technology.
NR 48
TC 56
Z9 56
U1 0
U2 14
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 27
PY 2011
VL 108
IS 52
BP 21229
EP 21234
DI 10.1073/pnas.1113103109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 867UI
UT WOS:000298479900071
PM 22160708
ER
PT J
AU Mathes, DW
Hwang, B
Graves, SS
Edwards, J
Chang, J
Storer, BE
Butts-Miwongtum, T
Sale, GE
Nash, RA
Storb, R
AF Mathes, David W.
Hwang, Billanna
Graves, Scott S.
Edwards, James
Chang, Jeff
Storer, Barry E.
Butts-Miwongtum, Tiffany
Sale, George E.
Nash, Richard A.
Storb, Rainer
TI Tolerance to Vascularized Composite Allografts in Canine Mixed
Hematopoietic Chimeras
SO TRANSPLANTATION
LA English
DT Article
DE Dog; Nonmyeloablative conditioning regimen; Mixed hematopoietic
chimerism; Skin grafting; Hematopoietic cell transplantation; CTA
transplantation; FoxP3; Tolerance; Vascularized Composite Allograft
ID TISSUE ALLOTRANSPLANT SURVIVAL; MESENCHYMAL STEM-CELLS; TOTAL-BODY
IRRADIATION; REGULATORY T-CELLS; LARGE-ANIMAL-MODEL; PHARMACOLOGICAL
IMMUNOSUPPRESSION; TRANSPLANTATION TOLERANCE; MARROW TRANSPLANTATION;
ADOPTIVE IMMUNOTHERAPY; MOLECULAR ANALYSIS
AB Background. Mixed donor-host chimerism, established through hematopoietic cell transplantation (HCT), is a reproducible strategy for the induction of tolerance toward solid organs. Here, we ask whether a nonmyeloablative conditioning regimen establishing mixed donor-host chimerism leads to tolerance of antigenic vascularized composite allografts.
Methods. Stable mixed chimerism was established in dogs given a sublethal dose (1-2 Gy) total body irradiation before and a short course of immunosuppression after dog leukocyte antigen-identical marrow transplantation. Vascularized composite allografts from marrow donors were performed after a median of 36 months (range, 4-54 months) after HCT.
Results. All marrow recipients maintained mixed donor-host hematopoietic chimerism and accepted vascularized composite allografts for periods ranging between 52 and 90 weeks; in turn, marrow donors rejected vascularized composite allografts from their respective marrow recipients within 18 to 29 days. Biopsies of muscle and skin of vascularized composite allografts from mixed chimeras showed few infiltrating cells compared with extensive infiltrates in biopsies of vascularized composite allografts from marrow donors. Elevated levels of CD3+ FoxP3+ T-regulatory cells were found in skin and muscle of vascularized composite allografts of mixed chimeras compared with normal tissues. In mixed chimeras, increased numbers of T-regulatory cells were found in draining compared with nondraining lymph nodes of vascularized composite allografts.
Conclusions. These data suggest that nonmyeloablative HCT may form the basis for future clinical applications of solid organ transplantation and that T-regulatory cells may function toward maintenance of the vascularized composite allograft.
C1 [Mathes, David W.; Hwang, Billanna; Graves, Scott S.; Chang, Jeff; Storer, Barry E.; Butts-Miwongtum, Tiffany; Sale, George E.; Nash, Richard A.; Storb, Rainer] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Mathes, David W.; Edwards, James; Chang, Jeff] Univ Washington, Dept Surg, Seattle, WA 98195 USA.
[Graves, Scott S.; Nash, Richard A.; Storb, Rainer] Univ Washington, Dept Med, Seattle, WA USA.
[Storer, Barry E.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Sale, George E.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Mathes, David W.] VA Puget Sound Hlth Care Syst, Plast Surg Serv, Seattle, WA USA.
RP Mathes, DW (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, POB 19024,D1-100,1100 Fairview Ave N, Seattle, WA 98109 USA.
EM dmathes@fhcrc.org
FU National Institutes of Health, Bethesda, MD [P01CA078902, P30CA015704];
National Endowment for Plastic Surgery; Plastic Surgery Educational
Foundation
FX This work was supported by the National Institutes of Health, Bethesda,
MD, grants P01CA078902 and P30CA015704.; David Mathes received support
from the National Endowment for Plastic Surgery Grant from the Plastic
Surgery Educational Foundation. Other authors declare no conflicts of
interest.
NR 50
TC 27
Z9 27
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD DEC 27
PY 2011
VL 92
IS 12
BP 1301
EP 1308
DI 10.1097/TP.0b013e318237d6d4
PG 8
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 863FW
UT WOS:000298149200007
PM 22082819
ER
PT J
AU Zhang, K
Pirooznia, M
Arabnia, HR
Yang, JY
Wang, LJ
Luo, ZJ
Deng, YP
AF Zhang, Ke
Pirooznia, Mehdi
Arabnia, Hamid R.
Yang, Jack Y.
Wang, Liangjiang
Luo, Zuojie
Deng, Youping
TI Genomic signatures and gene networking: challenges and promises
INTRODUCTION
SO BMC GENOMICS
LA English
DT Editorial Material
AB This is an editorial report of the supplement to BMC Genomics that includes 15 papers selected from the BIOCOMP' 10 - The 2010 International Conference on Bioinformatics & Computational Biology as well as other sources with a focus on genomics studies.
BIOCOMP' 10 was held on July 12-15 in Las Vegas, Nevada. The congress covered a large variety of research areas, and genomics was one of the major focuses because of the fast development in this field. We set out to launch a supplement to BMC Genomics with manuscripts selected from this congress and invited submissions. With a rigorous peer review process, we selected 15 manuscripts that showed work in cutting-edge genomics fields and proposed innovative methodology. We hope this supplement presents the current computational and statistical challenges faced in genomics studies, and shows the enormous promises and opportunities in the genomic future.
C1 [Zhang, Ke] Univ N Dakota, Sch Med & Hlth Sci, Bioinformat Core, Dept Pathol, Grand Forks, ND 58201 USA.
[Deng, Youping] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA.
[Pirooznia, Mehdi] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA.
[Arabnia, Hamid R.] Univ Georgia, Dept Comp Sci, Athens, GA 30602 USA.
[Yang, Jack Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Yang, Jack Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Wang, Liangjiang] Clemson Univ, Dept Genet & Biochem, Clemson, SC 29634 USA.
[Wang, Liangjiang] Greenwood Genet Ctr, JC Self Res Inst Human Genet, Greenwood, SC 29646 USA.
[Luo, Zuojie] Guangxi Med Univ, Hosp 1, Off President, Nanning, Guangxi, Peoples R China.
[Deng, Youping] Rush Univ, Med Ctr, Ctr Canc, Chicago, IL 60612 USA.
[Deng, Youping] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA.
RP Zhang, K (reprint author), Univ N Dakota, Sch Med & Hlth Sci, Bioinformat Core, Dept Pathol, Grand Forks, ND 58201 USA.
EM ke.zhang@med.und.edu; youping_deng@rush.edu
NR 15
TC 0
Z9 0
U1 0
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD DEC 23
PY 2011
VL 12
SU 5
AR I1
DI 10.1186/1471-2164-12-S5-I1
PG 3
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 940WB
UT WOS:000303922700001
PM 22369358
ER
PT J
AU Chen, ZX
Liu, JZ
Ng, HKT
Nadarajah, S
Kaufman, HL
Yang, JY
Deng, YP
AF Chen, Zhongxue
Liu, Jianzhong
Ng, Hon Keung Tony
Nadarajah, Saralees
Kaufman, Howard L.
Yang, Jack Y.
Deng, Youping
TI Statistical methods on detecting differentially expressed genes for
RNA-seq data
SO BMC SYSTEMS BIOLOGY
LA English
DT Article
ID 2 POISSON MEANS; NORMALIZATION; TESTS; RATIO; BIAS
AB Background: For RNA-seq data, the aggregated counts of the short reads from the same gene is used to approximate the gene expression level. The count data can be modelled as samples from Poisson distributions with possible different parameters. To detect differentially expressed genes under two situations, statistical methods for detecting the difference of two Poisson means are used. When the expression level of a gene is low, i.e., the number of count is small, it is usually more difficult to detect the mean differences, and therefore statistical methods which are more powerful for low expression level are particularly desirable. In statistical literature, several methods have been proposed to compare two Poisson means (rates). In this paper, we compare these methods by using simulated and real RNA-seq data.
Results: Through simulation study and real data analysis, we find that the Wald test with the data being log-transformed is more powerful than other methods, including the likelihood ratio test, which has similar power as the variance stabilizing transformation test; both are more powerful than the conditional exact test and Fisher exact test.
Conclusions: When the count data in RNA-seq can be reasonably modelled as Poisson distribution, the Wald-Log test is more powerful and should be used to detect the differentially expressed genes.
C1 [Chen, Zhongxue] Univ Texas Hlth Sci Ctr Houston, Ctr Clin & Translat Sci, Houston, TX 77030 USA.
[Kaufman, Howard L.; Deng, Youping] Rush Univ, Med Ctr, Ctr Canc, Chicago, IL 60612 USA.
[Liu, Jianzhong] Chem21 Grp Inc, Lake Forest, IL 60045 USA.
[Ng, Hon Keung Tony] So Methodist Univ, Dept Stat Sci, Dallas, TX 75275 USA.
[Nadarajah, Saralees] Univ Manchester, Sch Math, Manchester M13 9PL, Lancs, England.
[Kaufman, Howard L.] Rush Univ, Med Ctr, Dept Gen Surg & Immunol & Microbiol, Chicago, IL 60612 USA.
[Yang, Jack Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Yang, Jack Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Deng, Youping] Rush Univ, Med Ctr, Dept Internal Med & Biochem, Chicago, IL 60612 USA.
RP Chen, ZX (reprint author), Univ Texas Hlth Sci Ctr Houston, Ctr Clin & Translat Sci, Houston, TX 77030 USA.
EM Zhongxue.Chen@uth.tmc.edu; youping_deng@rush.edu
RI Chen, Zhongxue/K-1372-2013
OI Chen, Zhongxue/0000-0003-2537-7843
FU NIH [UL1 RR024148]
FX ZC would like to thank the support from the NIH grant (UL1 RR024148),
awarded to the University of Texas Health Science Center at Houston.
This article has been published as part of BMC Systems Biology Volume 5
Supplement 3, 2011: BIOCOMP 2010 - The 2010 International Conference on
Bioinformatics & Computational Biology: Systems Biology. The full
contents of the supplement are available online at
http://www.biomedcentral.com/1752-0509/5?issue=S3.
NR 16
TC 10
Z9 10
U1 1
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1752-0509
J9 BMC SYST BIOL
JI BMC Syst. Biol.
PD DEC 23
PY 2011
VL 5
SU 3
AR S1
DI 10.1186/1752-0509-5-S3-S1
PG 9
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 929FL
UT WOS:000303046600002
PM 22784615
ER
PT J
AU Land, WH
Qiao, XY
Margolis, DE
Ford, WS
Paquette, CT
Perez-Rogers, JF
Borgia, JA
Yang, JY
Deng, YP
AF Land, Walker H.
Qiao, Xingye
Margolis, Daniel E.
Ford, William S.
Paquette, Christopher T.
Perez-Rogers, Joseph F.
Borgia, Jeffrey A.
Yang, Jack Y.
Deng, Youping
TI Kernelized partial least squares for feature reduction and
classification of gene microarray data
SO BMC SYSTEMS BIOLOGY
LA English
DT Article
ID BREAST-CANCER; SHRUNKEN CENTROIDS; CLASS PREDICTION; EXPRESSION; LUNG;
SIGNATURES; SURVIVAL
AB Background: The primary objectives of this paper are: 1.) to apply Statistical Learning Theory (SLT), specifically Partial Least Squares (PLS) and Kernelized PLS (K-PLS), to the universal "feature-rich/case-poor" (also known as "large p small n", or "high-dimension, low-sample size") microarray problem by eliminating those features (or probes) that do not contribute to the "best" chromosome bio-markers for lung cancer, and 2.) quantitatively measure and verify (by an independent means) the efficacy of this PLS process. A secondary objective is to integrate these significant improvements in diagnostic and prognostic biomedical applications into the clinical research arena. That is, to devise a framework for converting SLT results into direct, useful clinical information for patient care or pharmaceutical research. We, therefore, propose and preliminarily evaluate, a process whereby PLS, K-PLS, and Support Vector Machines (SVM) may be integrated with the accepted and well understood traditional biostatistical "gold standard", Cox Proportional Hazard model and Kaplan-Meier survival analysis methods. Specifically, this new combination will be illustrated with both PLS and Kaplan-Meier followed by PLS and Cox Hazard Ratios (CHR) and can be easily extended for both the K-PLS and SVM paradigms. Finally, these previously described processes are contained in the Fine Feature Selection (FFS) component of our overall feature reduction/evaluation process, which consists of the following components: 1.) coarse feature reduction, 2.) fine feature selection and 3.) classification (as described in this paper) and prediction.
Results: Our results for PLS and K-PLS showed that these techniques, as part of our overall feature reduction process, performed well on noisy microarray data. The best performance was a good 0.794 Area Under a Receiver Operating Characteristic (ROC) Curve (AUC) for classification of recurrence prior to or after 36 months and a strong 0.869 AUC for classification of recurrence prior to or after 60 months. Kaplan-Meier curves for the classification groups were clearly separated, with p-values below 4.5e-12 for both 36 and 60 months. CHRs were also good, with ratios of 2.846341 (36 months) and 3.996732 (60 months).
Conclusions: SLT techniques such as PLS and K-PLS can effectively address difficult problems with analyzing biomedical data such as microarrays. The combinations with established biostatistical techniques demonstrated in this paper allow these methods to move from academic research and into clinical practice.
C1 [Land, Walker H.; Margolis, Daniel E.; Ford, William S.; Paquette, Christopher T.; Perez-Rogers, Joseph F.] SUNY Binghamton, Dept Bioengn, Binghamton, NY 13902 USA.
[Deng, Youping] Rush Univ, Med Ctr, Ctr Canc, Dept Internal Med, Chicago, IL 60612 USA.
[Qiao, Xingye] SUNY Binghamton, Dept Math Sci, Binghamton, NY 13902 USA.
[Borgia, Jeffrey A.] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA.
[Yang, Jack Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Yang, Jack Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Land, WH (reprint author), SUNY Binghamton, Dept Bioengn, Binghamton, NY 13902 USA.
EM wland@binghamton.edu; youpingdeng@rush.edu
FU NIH/NCMHD/RIMI [P20MD002725]; Binghamton University Harpur College
Dean's New Faculty; Howard Hughes Medical Institute
FX The research of YD was supported in part by the grant of NIH/NCMHD/RIMI
P20MD002725. The research of XQ was supported in part by Binghamton
University Harpur College Dean's New Faculty Startup Fund. The research
of CTP and JFPR was supported in part by a grant to the State University
of New York at Binghamton from the Howard Hughes Medical Institute
through the Precollege and Undergraduate Science Education Program. This
article has been published as part of BMC Systems Biology Volume 5
Supplement 3, 2011: BIOCOMP 2010 - The 2010 International Conference on
Bioinformatics & Computational Biology: Systems Biology. The full
contents of the supplement are available online at
http://www.biomedcentral.com/1752-0509/5?issue=S3.
NR 36
TC 2
Z9 3
U1 1
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1752-0509
J9 BMC SYST BIOL
JI BMC Syst. Biol.
PD DEC 23
PY 2011
VL 5
SU 3
AR S13
DI 10.1186/1752-0509-5-S3-S13
PG 18
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 929FL
UT WOS:000303046600014
PM 22784619
ER
PT J
AU Zhang, K
Liu, YL
Yang, JY
Arabnia, HR
Niemierko, A
Ghafoor, A
Li, WZ
Deng, YP
AF Zhang, Ke
Liu, Yunlong
Yang, Jack Y.
Arabnia, Hamid R.
Niemierko, Andrzej
Ghafoor, Arif
Li, Weizhong
Deng, Youping
TI From genes to networks: in systematic points of view INTRODUCTION
SO BMC SYSTEMS BIOLOGY
LA English
DT Editorial Material
AB We present a report of the BIOCOMP'10 - The 2010 International Conference on Bioinformatics & Computational Biology and other related work in the area of systems biology.
C1 [Zhang, Ke] Univ N Dakota, Sch Med & Hlth Sci, Dept Pathol, Grand Forks, ND 58201 USA.
[Deng, Youping] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA.
[Liu, Yunlong] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA.
[Liu, Yunlong] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA.
[Liu, Yunlong] Indiana Univ Sch Med, Ctr Med Genom, Indianapolis, IN USA.
[Yang, Jack Y.] Univ Calif San Diego, Ctr Res Biol Syst, La Jolla, CA 92093 USA.
[Yang, Jack Y.; Niemierko, Andrzej] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Yang, Jack Y.; Niemierko, Andrzej] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Arabnia, Hamid R.] Univ Georgia, Dept Comp Sci, Athens, GA 30602 USA.
[Ghafoor, Arif] Purdue Univ, Purdue Sch Elect & Comp Engn, W Lafayette, IN 47907 USA.
[Deng, Youping] Rush Univ, Med Ctr, Ctr Canc, Chicago, IL 60612 USA.
[Deng, Youping] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA.
RP Zhang, K (reprint author), Univ N Dakota, Sch Med & Hlth Sci, Dept Pathol, Grand Forks, ND 58201 USA.
EM ke.zhang@med.und.edu; youping_deng@rush.edu
NR 14
TC 1
Z9 1
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1752-0509
J9 BMC SYST BIOL
JI BMC Syst. Biol.
PD DEC 23
PY 2011
VL 5
SU 3
AR I1
DI 10.1186/1752-0509-5-S3-I1
PG 3
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 929FL
UT WOS:000303046600001
PM 22784614
ER
PT J
AU Khodyakov, D
Hempel, S
Rubenstein, L
Shekelle, P
Foy, R
Salem-Schatz, S
O'Neill, S
Danz, M
Dalal, S
AF Khodyakov, Dmitry
Hempel, Susanne
Rubenstein, Lisa
Shekelle, Paul
Foy, Robbie
Salem-Schatz, Susanne
O'Neill, Sean
Danz, Margie
Dalal, Siddhartha
TI Conducting Online Expert panels: a feasibility and experimental
replicability study
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
ID DELPHI TECHNIQUE; GUIDELINE DEVELOPMENT; CONSENSUS METHODS
AB Background: This paper has two goals. First, we explore the feasibility of conducting online expert panels to facilitate consensus finding among a large number of geographically distributed stakeholders. Second, we test the replicability of panel findings across four panels of different size.
Method: We engaged 119 panelists in an iterative process to identify definitional features of Continuous Quality Improvement (CQI). We conducted four parallel online panels of different size through three one-week phases by using the RAND's ExpertLens process. In Phase I, participants rated potentially definitional CQI features. In Phase II, they discussed rating results online, using asynchronous, anonymous discussion boards. In Phase III, panelists re-rated Phase I features and reported on their experiences as participants.
Results: 66% of invited experts participated in all three phases. 62% of Phase I participants contributed to Phase II discussions and 87% of them completed Phase III. Panel disagreement, measured by the mean absolute deviation from the median (MAD-M), decreased after group feedback and discussion in 36 out of 43 judgments about CQI features. Agreement between the four panels after Phase III was fair (four-way kappa = 0.36); they agreed on the status of five out of eleven CQI features. Results of the post-completion survey suggest that participants were generally satisfied with the online process. Compared to participants in smaller panels, those in larger panels were more likely to agree that they had debated each others' view points.
Conclusion: It is feasible to conduct online expert panels intended to facilitate consensus finding among geographically distributed participants. The online approach may be practical for engaging large and diverse groups of stakeholders around a range of health services research topics and can help conduct multiple parallel panels to test for the reproducibility of panel conclusions.
C1 [Khodyakov, Dmitry; Hempel, Susanne; Rubenstein, Lisa; Shekelle, Paul; O'Neill, Sean; Danz, Margie; Dalal, Siddhartha] RAND Corp, Santa Monica, CA 90401 USA.
[Rubenstein, Lisa; Danz, Margie] Vet Affairs Greater Los Angeles Sepulveda, North Hills, CA 91343 USA.
[Shekelle, Paul] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
[Foy, Robbie] Univ Leeds, Leeds Inst Hlth Sci, Leeds LS2 9JT, W Yorkshire, England.
[Salem-Schatz, Susanne] HealthCare Qual Initiat, Newton, MA 02459 USA.
[O'Neill, Sean] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Khodyakov, D (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90401 USA.
EM Dmitry_Khodyakov@rand.org
OI O'Neill, Sean/0000-0001-7759-8942
FU Robert Wood Johnson Foundation [65113, 67890]; RAND Corporation;
Veterans Health Administration
FX This study was supported by the Robert Wood Johnson Foundation (Grant ID
65113: Advancing the science of continuous quality improvement: A
framework for identifying, classifying and evaluating continuous quality
improvement studies and Grant ID 67890: Providing a framework for the
identification, classification, and evaluation of quality improvement
initiatives) and the RAND Corporation, with additional funding provided
by the Veterans Health Administration.
NR 30
TC 14
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U1 3
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD DEC 23
PY 2011
VL 11
AR 174
DI 10.1186/1471-2288-11-174
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 921FJ
UT WOS:000302463200001
PM 22196011
ER
PT J
AU Ni Chonghaile, T
Letai, A
AF Ni Chonghaile, Triona
Letai, Anthony
TI Who Put the "A" in Atg12: Autophagy or Apoptosis?
SO MOLECULAR CELL
LA English
DT Editorial Material
ID CELL-DEATH; MITOCHONDRIAL APOPTOSIS; BCL-2; PROTEINS; BECLIN-1
AB Much deliberation surrounds how the two homeostatic pathways, autophagy and apoptosis, converge; in the December 9 issue of Molecular Cell, Rubinstein et al. (2011) identify a proapoptotic role for the autophagic protein Atg12, based on a BH3-like domain, which enables binding and inhibition of antiapoptotic Bcl-2 family proteins.
C1 [Ni Chonghaile, Triona; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM anthony_letai@dfci.harvard.edu
FU NCI NIH HHS [P01 CA139980]
NR 10
TC 3
Z9 3
U1 0
U2 9
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 DEC 23
PY 2011
VL 44
IS 6
BP 844
EP 845
DI 10.1016/j.molcel.2011.12.007
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 872RO
UT WOS:000298827200002
PM 22195958
ER
PT J
AU Gerhart-Hines, Z
Dominy, JE
Blattler, SM
Jedrychowski, MP
Banks, AS
Lim, JH
Chim, H
Gygi, SP
Puigserver, P
AF Gerhart-Hines, Zachary
Dominy, John E., Jr.
Blaettler, Sharon M.
Jedrychowski, Mark P.
Banks, Alexander S.
Lim, Ji-Hong
Chim, Helen
Gygi, Steven P.
Puigserver, Pere
TI The cAMP/PKA Pathway Rapidly Activates SIRT1 to Promote Fatty Acid
Oxidation Independently of Changes in NAD(+)
SO MOLECULAR CELL
LA English
DT Article
ID ORPHAN NUCLEAR RECEPTOR; ELEGANS LIFE-SPAN; SKELETAL-MUSCLE;
GENE-EXPRESSION; TRANSCRIPTIONAL CONTROL; MITOCHONDRIAL-FUNCTION; PGC-1
COACTIVATORS; ENERGY-METABOLISM; REGULATES SIRT1; CELL-SURVIVAL
AB The NAD(+)-dependent deacetylase SIRT1 is an evolutionarily conserved metabolic sensor of the Sirtuin family that mediates homeostatic responses to certain physiological stresses such as nutrient restriction. Previous reports have implicated fluctuations in intracellular NAD(+) concentrations as the principal regulator of SIRT1 activity. However, here we have identified a cAMP-induced phosphorylation of a highly conserved serine (S434) located in the SIRT1 catalytic domain that rapidly enhanced intrinsic deacetylase activity independently of changes in NAD(+) levels. Attenuation of SIRT1 expression or the use of a nonphosphorylatable SIRT1 mutant prevented cAMP-mediated stimulation of fatty acid oxidation and gene expression linked to this pathway. Overexpression of SIRT1 in mice significantly potentiated the increases in fatty acid oxidation and energy expenditure caused by either pharmacological beta-adrenergic agonism or cold exposure. These studies support a mechanism of Sirtuin enzymatic control through the cAMP/PKA pathway with important implications for stress responses and maintenance of energy homeostasis.
C1 [Gerhart-Hines, Zachary; Dominy, John E., Jr.; Blaettler, Sharon M.; Banks, Alexander S.; Lim, Ji-Hong; Chim, Helen; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Gerhart-Hines, Zachary; Dominy, John E., Jr.; Blaettler, Sharon M.; Jedrychowski, Mark P.; Banks, Alexander S.; Lim, Ji-Hong; Chim, Helen; Gygi, Steven P.; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Gerhart-Hines, Zachary] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA.
RP Puigserver, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
EM pere_puigserver@dfci.harvard.edu
RI Banks, Alexander/B-4832-2012
OI Banks, Alexander/0000-0003-1787-6925
FU American Heart Association; NASA Kirschstein from the National
Institutes of Health; Swiss National Science Foundation; Dana-Farber
Cancer Institute; American Diabetes Association, Department of Defense;
National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases (NIH/NIDDK) [RO1 069966]
FX We thank members of the Puigserver lab for important discussions on the
project. We particularly thank Dr. Joseph Rodgers and Dr. Timothy Kelly
for critical reading of the manuscript and Dr. Wei Gu for providing the
SIRT1 transgenic mice. We also thank Dr. Fred Alt and Dr. Raul
Mostoslavsky for providing the WT and SIRT1 KO MEFs and Dr. John Denu
for providing reagents necessary for the coupled deacetylase assay. The
authors were supported in part by fellowships from the American Heart
Association (Z.G.-H.), NASA Kirschstein from the National Institutes of
Health (J.E.D.), and Swiss National Science Foundation (S.M.B.). The
research was supported from funds from the Dana-Farber Cancer Institute
and grants from the American Diabetes Association, Department of Defense
and National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases (NIH/NIDDK), RO1 069966 (P.P.). Z.G.-H.
and P.P. conceived of the project. Z.G.-H. designed and performed
cellular deacetylation and phosphorylation experiments, phosphorylation
mapping, in vitro kinase and Sirtuin activity assays, and mouse
experiments and wrote the manuscript. J.E.D. designed and performed
cellular deacetylation and phosphorylation experiments, phosphorylation
mapping, in vitro Sirtuin activity assays, and mouse experiments and
wrote the manuscript. S.M.B. and A.S.B. designed and performed mouse
experiments. M.P.J. and S.P.G. performed and analyzed mass spectrometry
experiments. J.-H.L. and N.C. performed cellular phosphorylation
experiments. P.P. designed experiments and wrote the manuscript.
NR 44
TC 120
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U1 1
U2 19
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 DEC 23
PY 2011
VL 44
IS 6
BP 851
EP 863
DI 10.1016/j.molcel.2011.12.005
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 872RO
UT WOS:000298827200005
PM 22195961
ER
PT J
AU Ram, O
Goren, A
Amit, I
Shoresh, N
Yosef, N
Ernst, J
Kellis, M
Gymrek, M
Issner, R
Coyne, M
Durham, T
Zhang, XL
Donaghey, J
Epstein, CB
Regev, A
Bernstein, BE
AF Ram, Oren
Goren, Alon
Amit, Ido
Shoresh, Noam
Yosef, Nir
Ernst, Jason
Kellis, Manolis
Gymrek, Melissa
Issner, Robbyn
Coyne, Michael
Durham, Timothy
Zhang, Xiaolan
Donaghey, Julie
Epstein, Charles B.
Regev, Aviv
Bernstein, Bradley E.
TI Combinatorial Patterning of Chromatin Regulators Uncovered by
Genome-wide Location Analysis in Human Cells
SO CELL
LA English
DT Article
ID LINKED MENTAL-RETARDATION; EMBRYONIC STEM-CELLS; HISTONE; POLYCOMB;
GENE; TRANSCRIPTION; PROTEINS; CHROMODOMAINS; MECHANISMS; ENHANCERS
AB Hundreds of chromatin regulators (CRs) control chromatin structure and function by catalyzing and binding histone modifications, yet the rules governing these key processes remain obscure. Here, we present a systematic approach to infer CR function. We developed ChIP-string, a meso-scale assay that combines chromatin immunoprecipitation with a signature readout of 487 representative loci. We applied ChIP-string to screen 145 antibodies, thereby identifying effective reagents, which we used to map the genome-wide binding of 29 CRs in two cell types. We found that specific combinations of CRs colocalize in characteristic patterns at distinct chromatin environments, at genes of coherent functions, and at distal regulatory elements. When comparing between cell types, CRs redistribute to different loci but maintain their modular and combinatorial associations. Our work provides a multiplex method that substantially enhances the ability to monitor CR binding, presents a large resource of CR maps, and reveals common principles for combinatorial CR function.
C1 [Ram, Oren; Goren, Alon; Amit, Ido; Shoresh, Noam; Yosef, Nir; Ernst, Jason; Kellis, Manolis; Gymrek, Melissa; Issner, Robbyn; Coyne, Michael; Durham, Timothy; Zhang, Xiaolan; Donaghey, Julie; Epstein, Charles B.; Regev, Aviv; Bernstein, Bradley E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Ram, Oren; Goren, Alon; Amit, Ido; Yosef, Nir; Gymrek, Melissa; Regev, Aviv; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Ram, Oren; Goren, Alon; Gymrek, Melissa; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ram, Oren; Goren, Alon; Gymrek, Melissa; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Ram, Oren; Goren, Alon; Gymrek, Melissa; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Ram, Oren; Goren, Alon; Gymrek, Melissa; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
[Ernst, Jason; Kellis, Manolis] MIT Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[Regev, Aviv] MIT, Dept Biol, Cambridge, MA 02140 USA.
RP Regev, A (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM aregev@broad.mit.edu; bernstein.bradley@mgh.harvard.edu
OI /0000-0002-6086-3903
FU EMBO; American Recovery and Reinvestment Act (ARRA) [U54 HG004570];
NHGRI; Howard Hughes Medical Institute; NIH; Burroughs Wellcome Fund
FX We thank B. Knoechel, C. Ye, J. Jaffe, and R. Mostoslavsky for helpful
discussions; G. Geiss and R. Boykin for help with assay development; R.
Raychowdhury and the Broad Sequencing Platform for technical assistance;
X. Li and Y. Shi for Plu1 antibody; D. Jang, J. Robinson, and T. Liefeld
for building the CRome portal; and L. Gaffney for figure preparation.
O.R. and A.G. were supported by an EMBO fellowship. The work was
supported by American Recovery and Reinvestment Act (ARRA) funds through
grant number U54 HG004570 (to B.E.B.), by an NHGRI CEGS grant (A.R. and
B.E.B), Howard Hughes Medical Institute (A.R. and B.E.B.), an NIH
PIONEER award (A.R.), and the Burroughs Wellcome Fund (A.R. and B.E.B.).
A.R. is a researcher of the Merkin Foundation for Stem Cell Research at
the Broad Institute.
NR 41
TC 172
Z9 175
U1 2
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 DEC 23
PY 2011
VL 147
IS 7
BP 1628
EP 1639
DI 10.1016/j.cell.2011.09.057
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 866SP
UT WOS:000298403400025
PM 22196736
ER
PT J
AU Yeh, JRJ
AF Yeh, Jing-Ruey J.
TI A Wnt Inhibitor with a Twist
SO CHEMISTRY & BIOLOGY
LA English
DT Editorial Material
ID EMBRYONIC STEM-CELLS; CARDIOMYOGENESIS; PATHWAY; CANCER
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
RP Yeh, JRJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
EM jyeh1@partners.org
FU NCI NIH HHS [R01 CA140188]; NIA NIH HHS [K01 AG031300]
NR 11
TC 0
Z9 0
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
J9 CHEM BIOL
JI Chem. Biol.
PD DEC 23
PY 2011
VL 18
IS 12
BP 1518
EP 1520
DI 10.1016/j.chembiol.2011.12.004
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 873OY
UT WOS:000298893900004
PM 22195553
ER
PT J
AU Dong, CK
Urgaonkar, S
Cortese, JF
Gamo, FJ
Garcia-Bustos, JF
Lafuente, MJ
Patel, V
Ross, L
Coleman, BI
Derbyshire, ER
Clish, CB
Serrano, AE
Cromwell, M
Barker, RH
Dvorin, JD
Duraisingh, MT
Wirth, DF
Clardy, J
Mazitschek, R
AF Dong, Carolyn K.
Urgaonkar, Sameer
Cortese, Joseph F.
Gamo, Francisco-Javier
Garcia-Bustos, Jose F.
Lafuente, Maria J.
Patel, Vishal
Ross, Leila
Coleman, Bradley I.
Derbyshire, Emily R.
Clish, Clary B.
Serrano, Adelfa E.
Cromwell, Mandy
Barker, Robert H., Jr.
Dvorin, Jeffrey D.
Duraisingh, Manoj T.
Wirth, Dyann F.
Clardy, Jon
Mazitschek, Ralph
TI Identification and Validation of Tetracyclic Benzothiazepines as
Plasmodium falciparum Cytochrome bc(1) Inhibitors
SO CHEMISTRY & BIOLOGY
LA English
DT Article
ID ATOVAQUONE RESISTANCE; ANTIMALARIAL-DRUGS; MALARIA PARASITES; IN-VITRO;
PROTON TRANSLOCATION; ENERGY TRANSDUCTION; ELECTRON-TRANSFER;
MOLECULAR-BASIS; MITOCHONDRIAL; COMPLEX
AB Here we report the discovery of tetracyclic benzothiazepines (BTZs) as highly potent and selective antimalarials along with the identification of the Plasmodium falciparum cytochrome bc(1) complex as the primary functional target of this novel compound class. Investigation of the structure activity relationship within this previously unexplored chemical scaffold has yielded inhibitors with low nanomolar activity. A combined approach employing genetically modified parasites, biochemical profiling, and resistance selection validated inhibition of cytochrome bc(1) activity, an essential component of the parasite respiratory chain and target of the widely used antimalarial drug atovaquone, as the mode of action of this novel compound class. Resistance to atovaquone is eroding the efficacy of this widely used antimalarial drug. Intriguingly, BTZ-based inhibitors retain activity against atovaquone resistant parasites, suggesting this chemical class may provide an alternative to atovaquone in combination therapy.
C1 [Urgaonkar, Sameer; Cortese, Joseph F.; Wirth, Dyann F.; Clardy, Jon; Mazitschek, Ralph] Broad Inst, Infect Dis Initiat, Cambridge, MA 02142 USA.
[Clish, Clary B.] Broad Inst, Metabolite Profiling Initiat, Cambridge, MA 02142 USA.
[Dong, Carolyn K.; Patel, Vishal; Coleman, Bradley I.; Dvorin, Jeffrey D.; Duraisingh, Manoj T.; Wirth, Dyann F.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Gamo, Francisco-Javier; Garcia-Bustos, Jose F.; Lafuente, Maria J.] GlaxoSmithKline R&D, DDW, Madrid 28760, Spain.
[Patel, Vishal; Ross, Leila; Derbyshire, Emily R.; Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Serrano, Adelfa E.] Univ Puerto Rico, Sch Med, Dept Microbiol & Med Zool, San Juan, PR 00936 USA.
[Cromwell, Mandy; Barker, Robert H., Jr.] Genzyme Corp, Drug & Biomat R&D, Waltham, MA 02451 USA.
[Dvorin, Jeffrey D.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
RP Clardy, J (reprint author), Broad Inst, Infect Dis Initiat, Cambridge, MA 02142 USA.
EM jon_clardy@hms.harvard.edu; rmazitschek@mgh.harvard.edu
RI Mazitschek, Ralph/E-3741-2013
OI Garcia-Bustos, Jose/0000-0002-6310-796X; Mazitschek,
Ralph/0000-0002-1105-689X
FU Medicines for Malaria Venture; Broad Institute (SPARC); NIH NICHD
[K12-HD000850]; NSF; Harvard Malaria Initiative; [NIH-G12RR03051]
FX We thank Roger Wiegand, Ted Sybertz, and the members of the Broad
Institute-Genzyme-MMV Malaria Drug Development Initiative for thoughtful
discussions; Stuart Schreiber and the Broad Chemical Biology Program for
access to key instrumentation and reagents; and Chris Johnson, Galina
Beletsky, and Stephen Jonston for analytical support. This work was
supported by grants from Medicines for Malaria Venture (to M.M.V.), The
Broad Institute (SPARC), the NIH NICHD K12-HD000850 (to J.D.D.), the NSF
Graduate Research Fellowship Program (to V.P.), the Harvard Malaria
Initiative (to D.F.W.), and partial infrastructure supported by
NIH-G12RR03051 (to A.E.S.)
NR 51
TC 21
Z9 22
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
J9 CHEM BIOL
JI Chem. Biol.
PD DEC 23
PY 2011
VL 18
IS 12
BP 1602
EP 1610
DI 10.1016/j.chembiol.2011.09.016
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 873OY
UT WOS:000298893900013
PM 22195562
ER
PT J
AU Peters, A
Pitcher, LA
Sullivan, JM
Mitsdoerffer, M
Acton, SE
Franz, B
Wucherpfennig, K
Turley, S
Carroll, MC
Sobel, RA
Bettelli, E
Kuchroo, VK
AF Peters, Anneli
Pitcher, Lisa A.
Sullivan, Jenna M.
Mitsdoerffer, Meike
Acton, Sophie E.
Franz, Bettina
Wucherpfennig, Kai
Turley, Shannon
Carroll, Michael C.
Sobel, Raymond A.
Bettelli, Estelle
Kuchroo, Vijay K.
TI Th17 Cells Induce Ectopic Lymphoid Follicles in Central Nervous System
Tissue Inflammation
SO IMMUNITY
LA English
DT Article
ID PROGRESSIVE MULTIPLE-SCLEROSIS; T(H)17 CELLS; PLATELET ACTIVATION;
RECEPTOR CLEC-2; HELPER-CELLS; AUTOIMMUNITY; PODOPLANIN; BLOOD; MICE;
DIFFERENTIATION
AB Ectopic lymphoid follicles are hallmarks of chronic autoimmune inflammatory diseases such as multiple sclerosis (MS), rheumatoid arthritis, Sjogren's syndrome, and myasthenia gravis. However, the effector cells and mechanisms that induce their development are unknown. Here we showed that in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, Th17 cells specifically induced ectopic lymphoid follicles in the central nervous system (CNS). Development of ectopic lymphoid follicles was partly dependent on the cytokine interleukin 17 (IL-17) and on the cell surface molecule Podoplanin (Pdp), which was expressed on Th17 cells, but not on other effector T cell subsets. Pdp was also crucial for the development of secondary lymphoid structures: Pdp-deficient mice lacked peripheral lymph nodes and had a defect in forming normal lymphoid follicles and germinal centers in spleen and lymph node remnants. Thus, Th17 cells are uniquely endowed to induce tissue inflammation, characterized by ectopic lymphoid follicles within the target organ.
C1 [Peters, Anneli; Sullivan, Jenna M.; Mitsdoerffer, Meike; Bettelli, Estelle; Kuchroo, Vijay K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
[Pitcher, Lisa A.; Carroll, Michael C.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Pitcher, Lisa A.; Carroll, Michael C.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp,Dept Pediat, Boston, MA 02115 USA.
[Pitcher, Lisa A.; Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Acton, Sophie E.; Franz, Bettina; Wucherpfennig, Kai; Turley, Shannon] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Sobel, Raymond A.] Stanford Univ, Sch Med, Palto Vet Adm Hlth Care Syst, Stanford, CA 94305 USA.
[Bettelli, Estelle] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
RP Bettelli, E (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
EM ebettelli@benaroyaresearch.org; vkuchroo@rics.bwh.harvard.edu
RI Acton, Sophie/G-9784-2012
OI Acton, Sophie/0000-0003-2704-716X
FU NIH [1R01NS059996, 5T32HL066987-09, R01NS045937, R01NS035685,
R37NS030843, R01A1044880, P01A1039671, P01NS038037]; Javits Neuroscience
Investigator Award; National Multiple Sclerosis Society (NMSS)
[TA3014A1/1, RG-2571]; Boehringer Ingelheim Fonds
FX We thank M. Ramirez (Boston University, Boston, MA) for generously
sharing Pdpn-/- mice with us. We thank D. Kozoriz for cell
sorting. A.P. is a graduate student jointly supervised by R. Heumann
(Ruhr-University Bochum, Germany) and V.K.K. This work was supported by
grants from the NIH (1R01NS059996 to E.B., 5T32HL066987-09 to LAP., and
R01NS045937, R01NS035685, R37NS030843, R01A1044880, P01A1039671,
P01NS038037, and a Javits Neuroscience Investigator Award to V.K.K.) and
the National Multiple Sclerosis Society (NMSS Transition Award
TA3014A1/1 to E.B. and RG-2571 to V.K.K.). A.P. is the recipient of a
Ph.D. scholarship by the Boehringer Ingelheim Fonds.
NR 30
TC 148
Z9 158
U1 3
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD DEC 23
PY 2011
VL 35
IS 6
BP 986
EP 996
DI 10.1016/j.immuni.2011.10.015
PG 11
WC Immunology
SC Immunology
GA 871ZX
UT WOS:000298777300016
PM 22177922
ER
PT J
AU Needham, PG
Mikoluk, K
Dhakarwal, P
Khadem, S
Snyder, AC
Subramanya, AR
Brodsky, JL
AF Needham, Patrick G.
Mikoluk, Kasia
Dhakarwal, Pradeep
Khadem, Shaheen
Snyder, Avin C.
Subramanya, Arohan R.
Brodsky, Jeffrey L.
TI The Thiazide-sensitive NaCl Cotransporter Is Targeted for
Chaperone-dependent Endoplasmic Reticulum-associated Degradation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TRANSMEMBRANE CONDUCTANCE REGULATOR; INTEGRAL MEMBRANE-PROTEINS;
EPITHELIAL SODIUM-CHANNELS; ER-ASSOCIATED DEGRADATION;
NA+-CL-COTRANSPORTER; UBIQUITIN-LIGASE; CYSTIC-FIBROSIS;
SACCHAROMYCES-CEREVISIAE; FUNCTIONAL EXPRESSION; INTRACELLULAR
TRAFFICKING
AB The thiazide-sensitive NaCl cotransporter (NCC, SLC12A3) mediates salt reabsorption in the distal nephron of the kidney and is the target of thiazide diuretics, which are commonly prescribed to treat hypertension. Mutations in NCC also give rise to Gitelman syndrome, a hereditary salt-wasting disorder thought in most cases to arise from impaired NCC biogenesis through enhanced endoplasmic reticulum-associated degradation (ERAD). Because the machinery that mediates NCC quality control is completely undefined, we employed yeast as a model heterologous expression system to identify factors involved in NCC degradation. We confirmed that NCC was a bona fide ERAD substrate in yeast, as the majority of NCC polypeptide was integrated into ER membranes, and its turnover rate was sensitive to proteasome inhibition. NCC degradation was primarily dependent on the ER membrane-associated E3 ubiquitin ligase Hrd1. Whereas several ER luminal chaperones were dispensable for NCC ERAD, NCC ubiquitination and degradation required the activity of Ssa1, a cytoplasmic Hsp70 chaperone. Compatible findings were observed when NCC was expressed in mammalian kidney cells, as the cotransporter was polyubiquitinated and degraded by the proteasome, and mammalian cytoplasmic Hsp70 (Hsp72) coexpression stimulated the degradation of newly synthesized NCC. Hsp70 also preferentially associated with the ER-localized NCC glycosylated species, indicating that cytoplasmic Hsp70 plays a critical role in selecting immature forms of NCC for ERAD. Together, these results provide the first survey of components involved in the ERAD of a mammalian SLC12 cation chloride cotransporter and provide a framework for future studies on NCC ER quality control.
C1 [Needham, Patrick G.; Mikoluk, Kasia; Brodsky, Jeffrey L.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15261 USA.
[Dhakarwal, Pradeep; Khadem, Shaheen; Snyder, Avin C.; Subramanya, Arohan R.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Dept Med, Pittsburgh, PA 15261 USA.
[Khadem, Shaheen; Subramanya, Arohan R.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA.
RP Needham, PG (reprint author), 3550 Terrace St,S832 Scaife Hall, Pittsburgh, PA 15261 USA.
EM ars129@pitt.edu
FU National Institutes of Health [DK79307, GM75061, DK84566]; United States
Department of Veterans Affairs; American Heart Association
[10BGIA3890010]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK79307 (to the Pittsburgh Center for Kidney
Research-Model Organisms Core), GM75061 (to J. L. B.), and DK84566 (to
A. R. S.). This work was also supported by a Mid-Level Career
Development Award from the United States Department of Veterans Affairs
(to A. R. S.) and James A. Shaver Fund of the American Heart Association
Grant 10BGIA3890010 (to A. R. S.).
NR 64
TC 23
Z9 23
U1 1
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 DEC 23
PY 2011
VL 286
IS 51
BP 43611
EP 43621
DI 10.1074/jbc.M111.288928
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 866SH
UT WOS:000298402300004
PM 22027832
ER
PT J
AU Biglione, S
Tsytsykova, AV
Goldfeld, AE
AF Biglione, Sebastian
Tsytsykova, Alla V.
Goldfeld, Anne E.
TI Monocyte-specific Accessibility of a Matrix Attachment Region in the
Tumor Necrosis Factor Locus
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FACTOR-ALPHA GENE; RNA-POLYMERASE-II; DROSOPHILA TOPOISOMERASE-II;
CREB-BINDING-PROTEIN; STRAND DNA CLEAVAGE; HISTONE HYPERACETYLATION; WEB
SERVER; TNF GENE; T-CELLS; EXPRESSION
AB Regulation of TNF gene expression is cell type-and stimulus-specific. We have previously identified highly conserved non-coding regulatory elements within DNase I-hypersensitive sites (HSS) located 9 kb upstream (HSS-9) and 3 kb downstream (HSS+3) of the TNF gene, which play an important role in the transcriptional regulation of TNF in T cells. They act as enhancers and interact with the TNF promoter and with each other, generating a higher order chromatin structure. Here, we report a novel monocyte-specific AT-rich DNase I-hypersensitive element located 7 kb upstream of the TNF gene (HSS-7), which serves as a matrix attachment region in monocytes. We show that HSS-7 associates with topoisomerase II alpha (Top2) in vivo and that induction of endogenous TNF mRNA expression is suppressed by etoposide, a Top2 inhibitor. Moreover, Top2 binds to and cleaves HSS-7 in in vitro analysis. Thus, HSS-7, which is selectively accessible in monocytes, can tether the TNF locus to the nuclear matrix via matrix attachment region formation, potentially promoting TNF gene expression by acting as a Top2 substrate.
C1 [Goldfeld, Anne E.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA.
RP Goldfeld, AE (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 200 Longwood Ave, Boston, MA 02115 USA.
EM goldfeld@idi.harvard.edu
FU National Institutes of Health [R01 GM076685]; Glaxo-SmithKline
FX This work was supported, in whole or in part, by National Institutes of
Health Grant R01 GM076685 (to A. E. G.). This work was also supported by
Glaxo-SmithKline (to A. E. G.).
NR 41
TC 4
Z9 4
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 DEC 23
PY 2011
VL 286
IS 51
BP 44126
EP 44133
DI 10.1074/jbc.M111.272476
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 866SH
UT WOS:000298402300053
PM 22027829
ER
PT J
AU Maiso, P
Liu, Y
Morgan, B
Azab, AK
Ren, PD
Martin, MB
Zhang, Y
Liu, Y
Sacco, A
Ngo, H
Azab, F
Quang, P
Rodig, SJ
Lin, CP
Roccaro, AM
Rommel, C
Ghobrial, IM
AF Maiso, Patricia
Liu, Yi
Morgan, Brittany
Azab, Abdel Kareem
Ren, Pingda
Martin, Michel B.
Zhang, Yong
Liu, Yang
Sacco, Antonio
Ngo, Hai
Azab, Feda
Quang, Phong
Rodig, Scott J.
Lin, Charles P.
Roccaro, Aldo M.
Rommel, Christian
Ghobrial, Irene M.
TI Defining the role of TORC1/2 in multiple myeloma
SO BLOOD
LA English
DT Article
ID BONE-MARROW MICROENVIRONMENT; WALDENSTROM MACROGLOBULINEMIA; MTOR
INHIBITOR; SYNERGISTIC ACTIVITY; MAMMALIAN TARGET; KINASE INHIBITOR;
CELLS; PATHWAY; RAPAMYCIN; CHEMOTAXIS
AB Mammalian target of rapamycin (mTOR) is a downstream serine/threonine kinase of the PI3K/Akt pathway that integrates signals from the tumor microenvironment to regulate multiple cellular processes. Rapamycin and its analogs have not shown significant activity in multiple myeloma (MM), likely because of the lack of inhibition of TORC2. In the present study, we investigated the baseline activity of the PI3K/Akt/mTOR pathway TORC1/2 in MM cell lines with different genetic abnormalities. TORC1/2 knockdown led to significant inhibition of the proliferation of MM cells, even in the presence of BM stromal cells. We also tested INK128, a dual TORC1/2 inhibitor, as a new therapeutic agent against these MM cell lines. We showed that dual TORC1/2 inhibition is much more active than TORC1 inhibition alone (rapamycin), even in the presence of cytokines or stromal cells. In vitro and in vivo studies showed that p-4EBP1 and p-Akt inhibition could be predictive markers of TORC2 inhibition in MM cell lines. Dual TORC1/2 inhibition showed better inhibition of adhesion to BM microenvironmental cells and inhibition of homing in vivo. These studies form the basis for further clinical testing of TORC1/2 inhibitors in MM. (Blood.2011;118(26):6860-6870)
C1 [Maiso, Patricia; Morgan, Brittany; Azab, Abdel Kareem; Zhang, Yong; Liu, Yang; Sacco, Antonio; Ngo, Hai; Azab, Feda; Quang, Phong; Roccaro, Aldo M.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Rodig, Scott J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA.
[Liu, Yi; Ren, Pingda; Martin, Michel B.; Rommel, Christian] Intellikine Inc, La Jolla, CA USA.
[Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 1B, Boston, MA 02115 USA.
EM irene_ghobrial@dfci.harvard.edu
RI Sacco, Antonio/K-4681-2016;
OI Sacco, Antonio/0000-0003-2945-9416; Maiso, Patricia/0000-0003-3745-1924;
Roccaro, Aldo/0000-0002-1872-5128
FU National Institutes of Health [R01CA125690-01]; Multiple Myeloma
Research Foundation
FX This study was supported in part by the National Institutes of Health
(R01CA125690-01) and by the Multiple Myeloma Research Foundation.
NR 35
TC 38
Z9 39
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 DEC 22
PY 2011
VL 118
IS 26
BP 6860
EP 6870
DI 10.1182/blood-2011-03-342394
PG 11
WC Hematology
SC Hematology
GA 866RY
UT WOS:000298401000023
PM 22045983
ER
PT J
AU Schiotz, M
Price, M
Frolich, A
Sogaard, J
Kristensen, JK
Krasnik, A
Ross, MN
Diderichsen, F
Hsu, J
AF Schiotz, Michaela
Price, Mary
Frolich, Anne
Sogaard, Jes
Kristensen, Jette K.
Krasnik, Allan
Ross, Murray N.
Diderichsen, Finn
Hsu, John
TI Something is amiss in Denmark: A comparison of preventable
hospitalisations and readmissions for chronic medical conditions in the
Danish Healthcare system and Kaiser Permanente
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
ID NHS; POPULATION; CALIFORNIA; COUNTRIES; PROGRAM; QUALITY; ACCESS;
IMPACT; ADULTS
AB Background: As many other European healthcare systems the Danish healthcare system (DHS) has targeted chronic condition care in its reform efforts. Benchmarking is a valuable tool to identify areas for improvement. Prior work indicates that chronic care coordination is poor in the DHS, especially in comparison with care in Kaiser Permanente (KP), an integrated delivery system based in the United States. We investigated population rates of hospitalisation and readmission rates for ambulatory care sensitive, chronic medical conditions in the two systems.
Methods: Using a historical cohort study design, age and gender adjusted population rates of hospitalisations for angina, heart failure, chronic obstructive pulmonary disease, and hypertension, plus rates of 30-day readmission and mortality were investigated for all individuals aged 65+ in the DHS and KP.
Results: DHS had substantially higher rates of hospitalisations, readmissions, and mean lengths of stay per hospitalisation, than KP had. For example, the adjusted angina hospitalisation rates in 2007 for the DHS and KP respectively were 1.01/100 persons (95% CI: 0.98-1.03) vs. 0.11/100 persons (95% CI: 0.10-0.13/100 persons); 21.6% vs. 9.9% readmission within 30 days (OR = 2.53; 95% CI: 1.84-3.47); and mean length of stay was 2.52 vs. 1.80 hospital days. Mortality up through 30 days post-discharge was not consistently different in the two systems.
Conclusions: There are substantial differences between the DHS and KP in the rates of preventable hospitalisations and subsequent readmissions associated with chronic conditions, which suggest much opportunity for improvement within the Danish healthcare system. Reductions in hospitalisations also could improve patient welfare and free considerable resources for use towards preventing disease exacerbations. These conclusions may also apply for similar public systems such as the US Medicare system, the NHS and other systems striving to improve the integration of care for persons with chronic conditions.
C1 [Schiotz, Michaela] Steno Diabet Ctr, Steno Hlth Promot Ctr, DK-2820 Gentofte, Denmark.
[Schiotz, Michaela; Krasnik, Allan; Diderichsen, Finn] Univ Copenhagen, Sect Hlth Serv Res, Dept Publ Hlth, Fac Hlth Sci, DK-1014 Copenhagen K, Denmark.
[Price, Mary; Hsu, John] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94612 USA.
[Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
[Hsu, John] Partners Hlth Care Syst, Boston, MA 02114 USA.
[Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Frolich, Anne] Bispebjerg Hosp, Copenhagen Hosp Cooperat, DK-2400 Copenhagen NV, Denmark.
[Sogaard, Jes] Danish Inst Hlth Serv Res, DK-2100 Copenhagen O, Denmark.
[Kristensen, Jette K.] Univ Aarhus, Dept Gen Practice, DK-8000 Aarhus, Denmark.
[Ross, Murray N.] Kaiser Permanente Inst Hlth Policy, Oakland, CA 94612 USA.
RP Schiotz, M (reprint author), Steno Diabet Ctr, Steno Hlth Promot Ctr, Niels Steensensvej 8, DK-2820 Gentofte, Denmark.
EM mlsz@steno.dk
FU Rockwool Foundation; Agency for Healthcare Research and Quality
FX Jennifer Green provided English text revision and correction. We thank
the Rockwool Foundation and the Agency for Healthcare Research and
Quality who funded this study.
NR 42
TC 10
Z9 10
U1 0
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 DEC 22
PY 2011
VL 11
AR 347
DI 10.1186/1472-6963-11-347
PG 10
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 876DT
UT WOS:000299088200001
PM 22192270
ER
PT J
AU Xu, D
O, TM
Shartava, A
Fowles, TC
Yang, JC
Fink, LM
Ward, DC
Mihm, MC
Waner, M
Ma, YP
AF Xu, Dan
O, Teresa M.
Shartava, Archil
Fowles, Taylor C.
Yang, Jianchang
Fink, Louis M.
Ward, David C.
Mihm, Martin C.
Waner, Milton
Ma, Yupo
TI Isolation, characterization, and in vitro propagation of infantile
hemangioma stem cells and an in vivo mouse model
SO JOURNAL OF HEMATOLOGY & ONCOLOGY
LA English
DT Article
DE Infantile hemangioma; stem cells; tumor spheres; SALL4
ID SALL4; THERAPY; PLURIPOTENCY; REGENERATION; FIBROBLASTS; REGULATOR;
EXPANSION; CHILDREN; MICE
AB Background: Infantile hemangiomas (IH) are the most common benign tumors of infancy. The typical clinical course consists of rapid growth during the first year of life, followed by natural and gradual involution over a multi-year time span through unknown cellular mechanisms. Some tumors respond to medical treatment with corticosteroids or beta-blockers, however, when this therapy fails or is incomplete, surgical extirpation may be necessary. Noninvasive therapies to debulk or eliminate these tumors would be an important advance. The development of an in vitro cell culture system and an animal model would allow new insights into the biological processes involved in the development and pathogenesis of IH.
Results: We observed that proliferative stage IH specimens contain significantly more SALL4+ and CD133+ cells than involuting tumors, suggesting a possible stem cell origin. A tumor sphere formation assay was adapted to culture IH cells in vitro. Cells in IH tumor spheres express GLUT1, indicative of an IH cell of origin, elevated levels of VEGF, and various stem/progenitor cell markers such as SALL4, KDR, Oct4, Nanog and CD133. These cells were able to self-renew and differentiate to endothelial lineages, both hallmarks of tumor stem cells. Treatment with Rapamycin, a potent mTOR/VEGF inhibitor, dramatically suppressed IH cell growth in vitro. Subcutaneous injection of cells from IH tumor spheres into immunodeficient NOD-SCID mice produced GLUT1 and CD31 positive tumors with the same cellular proliferation, differentiation and involution patterns as human hemangiomas.
Conclusions: The ability to propagate large numbers of IH stem cells in vitro and the generation of an in vivo mouse model provides novel avenues for testing IH therapeutic agents in the future.
C1 [O, Teresa M.; Waner, Milton] Vasc Birthmark Inst New York, New York, NY 10023 USA.
[Ma, Yupo] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA.
[Xu, Dan; Shartava, Archil; Fowles, Taylor C.; Yang, Jianchang; Fink, Louis M.] Nevada Canc Inst, Div Lab Med, Las Vegas, NV 89135 USA.
[Ward, David C.] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI USA.
[Mihm, Martin C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ma, Yupo] Chinese Acad Med Sci, Biopharmaceut Res Ctr, Suzhou, Peoples R China.
[Ma, Yupo] Peking Union Med Coll, Suzhou, Peoples R China.
RP O, TM (reprint author), Vasc Birthmark Inst New York, New York, NY 10023 USA.
EM to@vbiny.org; wanermd@chpnet.org; yupo.ma@stonybrook.edu
FU Birth Mark Foundation; NIH [R01HL087948]; Vascular Birthmark Foundation
FX This work was supported in part under grants: Birth Mark Foundation, NIH
R01HL087948, and Vascular Birthmark Foundation (to Y.M.).
NR 34
TC 21
Z9 23
U1 1
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-8722
J9 J HEMATOL ONCOL
JI J. Hematol. Oncol.
PD DEC 22
PY 2011
VL 4
AR 54
DI 10.1186/1756-8722-4-54
PG 11
WC Oncology; Hematology
SC Oncology; Hematology
GA 876JG
UT WOS:000299103200001
PM 22192404
ER
PT J
AU Venna, N
Gonzalez, RG
Zukerberg, LR
AF Venna, Nagagopal
Gonzalez, R. Gilberto
Zukerberg, Lawrence R.
TI Case 39-2011: A Woman in Her 90s with Unilateral Ptosis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID GUILLAIN-BARRE-SYNDROME; MYASTHENIA-GRAVIS; CLINICAL-FEATURES; THYMOMA
C1 [Venna, Nagagopal] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Venna, Nagagopal] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Zukerberg, Lawrence R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Venna, N (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
NR 19
TC 2
Z9 2
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 DEC 22
PY 2011
VL 365
IS 25
BP 2413
EP 2422
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 865OM
UT WOS:000298320200008
PM 22187989
ER
PT J
AU Mellman, I
Coukos, G
Dranoff, G
AF Mellman, Ira
Coukos, George
Dranoff, Glenn
TI Cancer immunotherapy comes of age
SO NATURE
LA English
DT Review
ID REGULATORY T-CELLS; RESISTANT PROSTATE-CANCER; ENDOTHELIAL
GROWTH-FACTOR; COLONY-STIMULATING FACTOR; DENDRITIC CELLS; ANTITUMOR
IMMUNITY; OVARIAN-CANCER; IN-VIVO; SUPPRESSOR-CELLS; PEPTIDE VACCINE
AB Activating the immune system for therapeutic benefit in cancer has long been a goal in immunology and oncology. After decades of disappointment, the tide has finally changed due to the success of recent proof-of-concept clinical trials. Most notable has been the ability of the anti-CTLA4 antibody, ipilimumab, to achieve a significant increase in survival for patients with metastatic melanoma, for which conventional therapies have failed. In the context of advances in the understanding of how tolerance, immunity and immunosuppression regulate antitumour immune responses together with the advent of targeted therapies, these successes suggest that active immunotherapy represents a path to obtain a durable and long-lasting response in cancer patients.
C1 [Mellman, Ira] Genentech Inc, San Francisco, CA 94080 USA.
[Coukos, George] Univ Penn, Sch Med, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA.
[Dranoff, Glenn] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Dranoff, Glenn] Brigham & Womens Hosp, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Mellman, I (reprint author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
EM mellman.ira@gene.com
FU NCI NIH HHS [P01 CA155258, P50 CA100707, P01 CA078378, R01 CA143083]
NR 99
TC 770
Z9 803
U1 71
U2 445
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 480
EP 489
DI 10.1038/nature10673
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000052
PM 22193102
ER
PT J
AU Fujiki, R
Hashiba, W
Sekine, H
Yokoyama, A
Chikanishi, T
Ito, S
Imai, Y
Kim, J
He, HH
Igarashi, K
Kanno, J
Ohtake, F
Kitagawa, H
Roeder, RG
Brown, M
Kato, S
AF Fujiki, Ryoji
Hashiba, Waka
Sekine, Hiroki
Yokoyama, Atsushi
Chikanishi, Toshihiro
Ito, Saya
Imai, Yuuki
Kim, Jaehoon
He, Housheng Hansen
Igarashi, Katsuhide
Kanno, Jun
Ohtake, Fumiaki
Kitagawa, Hirochika
Roeder, Robert G.
Brown, Myles
Kato, Shigeaki
TI GlcNAcylation of histone H2B facilitates its monoubiquitination
SO NATURE
LA English
DT Article
ID O-GLCNAC TRANSFERASE; BETA-N-ACETYLGLUCOSAMINE; HUMAN-CELLS;
TRANSCRIPTION; CHROMATIN; ACETYLATION; REPRESSION; LANGUAGE; GENES
AB Chromatin reorganization is governed by multiple post-translational modifications of chromosomal proteins and DNA(1,2). These histone modifications are reversible, dynamic events that can regulate DNA-driven cellular processes(3,4). However, the molecular mechanisms that coordinate histone modification patterns remain largely unknown. In metazoans, reversible protein modification by O-linked N-acetylglucosamine (GlcNAc) is catalysed by two enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA)(5,6). However, the significance of GlcNAcylation in chromatin reorganization remains elusive. Here we report that histone H2B is GlcNAcylated at residue S112 by OGT in vitro and in living cells. Histone GlcNAcylation fluctuated in response to extracellular glucose through the hexosamine biosynthesis pathway (HBP)(5,6). H2B S112 GlcNAcylation promotes K120 monoubiquitination, in which the GlcNAc moiety can serve as an anchor for a histone H2B ubiquitin ligase. H2B S112 GlcNAc was localized to euchromatic areas on fly polytene chromosomes. In a genome-wide analysis, H2B S112 GlcNAcylation sites were observed widely distributed over chromosomes including transcribed gene loci, with some sites co-localizing with H2B K120 monoubiquitination. These findings suggest that H2B S112 GlcNAcylation is a histone modification that facilitates H2BK120 monoubiquitination, presumably for transcriptional activation.
C1 [Fujiki, Ryoji; Hashiba, Waka; Sekine, Hiroki; Yokoyama, Atsushi; Chikanishi, Toshihiro; Ito, Saya; Imai, Yuuki; Ohtake, Fumiaki; Kitagawa, Hirochika; Kato, Shigeaki] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
[Kim, Jaehoon; Roeder, Robert G.] Rockefeller Univ, Lab Biochem & Mol Biol, New York, NY 10065 USA.
[He, Housheng Hansen; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[He, Housheng Hansen; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Igarashi, Katsuhide; Kanno, Jun] Natl Inst Hlth Sci, Div Cellular & Mol Toxicol, Setagaya Ku, Tokyo 1588501, Japan.
[Kato, Shigeaki] Japan Sci & Technol Agcy, ERATO, Kawaguchi, Saitama 3320012, Japan.
RP Kato, S (reprint author), Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1130032, Japan.
EM uskato@mail.ecc.u-tokyo.ac.jp
RI He, Housheng/G-9614-2011;
OI Brown, Myles/0000-0002-8213-1658; Kim, Jaehoon/0000-0003-4035-0438
FU Naito Foundation; Astellas foundation; Ministry of Education, Culture,
Sports, Science and Technology (MEXT); Japan Society for the Promotion
of Science
FX We thank A. Miyajima, S. Saito and N. Moriyama for experimental support,
and M. Yamaki for manuscript preparation. We also thank Y. Maekawa, J.
Seta and N. Iwasaki for support with MS. This work was supported in part
by The Naito Foundation, the Astellas foundation (to R. F.), the
Ministry of Education, Culture, Sports, Science and Technology (MEXT)
and the Japan Society for the Promotion of Science (to R.F. and S.K.).
NR 25
TC 128
Z9 137
U1 4
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 557
EP U188
DI 10.1038/nature10656
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000068
PM 22121020
ER
PT J
AU Wang, T
Molliver, DC
Jing, XT
Schwartz, ES
Yang, FC
Samad, OA
Ma, QF
Davis, BM
AF Wang, Ting
Molliver, Derek C.
Jing, Xiaotang
Schwartz, Erica S.
Yang, Fu-Chia
Samad, Omar Abdel
Ma, Qiufu
Davis, Brian M.
TI Phenotypic Switching of Nonpeptidergic Cutaneous Sensory Neurons
following Peripheral Nerve Injury
SO PLOS ONE
LA English
DT Article
ID DORSAL-ROOT GANGLION; GDNF FAMILY LIGANDS; NEUROTROPHIC FACTOR;
NEUROPATHIC PAIN; DRG NEURONS; SPINAL-CORD; RECEPTOR COMPONENTS;
TRIGEMINAL GANGLION; GENE-EXPRESSION; MESSENGER-RNA
AB In adult mammals, the phenotype of half of all pain-sensing (nociceptive) sensory neurons is tonically modulated by growth factors in the glial cell line-derived neurotrophic factor (GDNF) family that includes GDNF, artemin (ARTN) and neurturin (NRTN). Each family member binds a distinct GFRa family co-receptor, such that GDNF, NRTN and ARTN bind GFR alpha 1, -alpha 2, and -alpha 3, respectively. Previous studies revealed transcriptional regulation of all three receptors in following axotomy, possibly in response to changes in growth factor availability. Here, we examined changes in the expression of GFR alpha 1-3 in response to injury in vivo and in vitro. We found that after dissociation of adult sensory ganglia, up to 27% of neurons die within 4 days (d) in culture and this can be prevented by nerve growth factor (NGF), GDNF and ARTN, but not NRTN. Moreover, up-regulation of ATF3 (a marker of neuronal injury) in vitro could be prevented by NGF and ARTN, but not by GDNF or NRTN. The lack of NRTN efficacy was correlated with rapid and near-complete loss of GFR alpha 2 immunoreactivity. By retrogradely-labeling cutaneous afferents in vivo prior to nerve cut, we demonstrated that GFR alpha 2-positive neurons switch phenotype following injury and begin to express GFR alpha 3 as well as the capsaicin receptor, transient receptor potential vanilloid 1(TRPV1), an important transducer of noxious stimuli. This switch was correlated with down-regulation of Runtrelated transcription factor 1 (Runx1), a transcription factor that controls expression of GFR alpha 2 and TRPV1 during development. These studies show that NRTN-responsive neurons are unique with respect to their plasticity and response to injury, and suggest that Runx1 plays an ongoing modulatory role in the adult.
C1 [Wang, Ting; Molliver, Derek C.; Jing, Xiaotang; Schwartz, Erica S.; Davis, Brian M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
[Molliver, Derek C.; Davis, Brian M.] Univ Pittsburgh, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.
[Wang, Ting; Molliver, Derek C.; Jing, Xiaotang; Davis, Brian M.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA.
[Schwartz, Erica S.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA.
[Wang, Ting; Molliver, Derek C.; Jing, Xiaotang; Schwartz, Erica S.; Davis, Brian M.] Univ Pittsburgh, Pittsburgh Ctr Pain Res, Pittsburgh, PA USA.
[Yang, Fu-Chia; Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Yang, Fu-Chia; Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Samad, Omar Abdel] Yale Univ, Sch Med, Ctr Neurosci & Regenerat Res, New Haven, CT USA.
RP Wang, T (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
EM bmd1@pitt.edu
RI samad, omar/K-1921-2012;
OI Davis, Brian/0000-0002-4646-0569
FU NIH [NS31826, DK063922, NS056122, DEP18025, NS047572]
FX This work was supported by grants from the NIH with the following
assignment numbers: NS31826 (BMD), DK063922 (ESS), NS056122 (DCM),
DEP18025 and NS047572 (QM). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 56
TC 15
Z9 15
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 21
PY 2011
VL 6
IS 12
AR e28908
DI 10.1371/journal.pone.0028908
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 876NF
UT WOS:000299113600051
PM 22216140
ER
PT J
AU Sun, Q
Prasad, R
Rosenthal, E
Katiyar, SK
AF Sun, Qian
Prasad, Ram
Rosenthal, Eben
Katiyar, Santosh K.
TI Grape seed proanthocyanidins inhibit the invasive potential of head and
neck cutaneous squamous cell carcinoma cells by targeting EGFR
expression and epithelial-to-mesenchymal transition
SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Article
ID NF-KAPPA-B; GROWTH-FACTOR RECEPTOR; A431 CELLS; E-CADHERIN; CANCER;
FLUOROURACIL; PROGRESSION; ACTIVATION; BERBERINE; DOCETAXEL
AB Background: Head and neck squamous cell carcinoma (HNSCC) is responsible for over 20,000 deaths every year in United States. Most of the deaths are due, in large part, to its propensity to metastasize. We have examined the effect of bioactive component grape seed proanthocyanidins (GSPs) on human cutaneous HNSCC cell invasion and the molecular mechanisms underlying these effects using SCC13 cell line as an in vitro model.
Methods: The therapeutic effects of GSPs on cancer cell invasion were studied using Boyden chamber and wound healing assays. The effects of GSPs on the levels of various proteins related with cancer cell invasion were determined using western blot analysis.
Results: Using in vitro cell invasion assays, we observed that treatment of SCC13 cells with GSPs resulted in a concentration-dependent inhibition of cell invasion of these cells, which was associated with a reduction in the levels of epidermal growth factor receptor (EGFR). Treatment of cells with gefitinib and erlotinib, inhibitors of EGFR, or transient transfection of SCC13 cells with EGFR small interfering RNA, also inhibited invasion of these cells. The inhibition of cell invasion by GSPs was associated with the inhibition of the phosphorylation of ERK1/2, a member of mitogen-activated protein kinase family. Treatment of cells with UO126, an inhibitor of MEK, also inhibited the invasion potential of SCC13 cells. Additionally, inhibition of human cutaneous HNSCC cell invasion by GSPs was associated with reversal of epithelial-to-mesenchymal transition (EMT) process, which resulted in an increase in the levels of epithelial biomarker (E-cadherin) while loss of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin) in cells. Similar effect on EMT biomarkers was also observed when cells were treated with erlotinib.
Conclusion: The results obtained from this study indicate that grape seed proanthocyanidins have the ability to inhibit the invasion of human cutaneous HNSCC cells by targeting the EGFR expression and reversing the process of epithelial-to-mesenchymal transition. These data suggest that GSPs can be developed as a complementary and alternative medicine for the prevention of invasion/metastasis of HNSCC cells.
C1 [Sun, Qian; Prasad, Ram; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA.
[Rosenthal, Eben] Univ Alabama, Dept Surg Otolaryngol, Birmingham, AL USA.
[Rosenthal, Eben; Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
[Katiyar, Santosh K.] Univ Alabama, Nutr Obes Res Ctr, Birmingham, AL USA.
[Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA.
RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA.
EM skatiyar@uab.edu
FU Veterans Administration; National Cancer Institute/NCCAM/NIH [CA140197,
CA140832]; UAB Skin Diseases Research Center [AR050948-01]
FX work was supported by the funds from Veterans Administration Merit
Review Award (S.K.K.) and National Cancer Institute/NCCAM/NIH (CA140197,
CA140832). NHEK were obtained from the UAB Skin Diseases Research Center
(AR050948-01). The content of this article does not necessarily reflect
the views or policies of the funding sources.
NR 25
TC 18
Z9 19
U1 2
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6882
J9 BMC COMPLEM ALTERN M
JI BMC Complement. Altern. Med.
PD DEC 21
PY 2011
VL 11
AR 134
DI 10.1186/1472-6882-11-134
PG 12
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA 876AS
UT WOS:000299079800001
PM 22188922
ER
PT J
AU Holtzman, DM
Goate, A
Kelly, J
Sperling, R
AF Holtzman, David M.
Goate, Alison
Kelly, Jeffrey
Sperling, Reisa
TI Mapping the Road Forward in Alzheimer's Disease
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID NEURODEGENERATIVE DISEASES; ASSOCIATION WORKGROUPS; DIAGNOSTIC
GUIDELINES; NATIONAL INSTITUTE; COMMON VARIANTS; A-BETA;
RECOMMENDATIONS; CD2AP; EPHA1; MODEL
AB Alzheimer's disease (AD) is the most common cause of dementia and will lead to a worldwide public health crisis if it continues unchecked. Despite tremendous advances in our scientific understanding of AD, we still do not have effective ways to delay, prevent, or slow this disease. At the 2011 Abelson meeting, a diverse group of scientists discussed current challenges in the AD field and made recommendations in the areas of genetics, clinical trials, protein aggregation, and the cell biology of the nervous system. We hope these recommendations will boost research progress in AD and increase the likelihood of developing effective therapies in the near future.
C1 [Holtzman, David M.] Washington Univ, Dept Neurol, St Louis, MO 63110 USA.
[Goate, Alison] Washington Univ, Dept Psychiat, St Louis, MO 63110 USA.
[Holtzman, David M.; Goate, Alison] Washington Univ, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA.
[Holtzman, David M.; Goate, Alison] Washington Univ, Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA.
[Kelly, Jeffrey] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
[Kelly, Jeffrey] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA.
[Kelly, Jeffrey] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Sperling, Reisa] Harvard Univ, Sch Med, Ctr Alzheimer Res & Treatment, Massachusetts Gen Hosp,Brigham & Womens Hosp, Boston, MA 02446 USA.
RP Holtzman, DM (reprint author), Washington Univ, Dept Neurol, St Louis, MO 63110 USA.
EM holtzman@neuro.wustl.edu
FU NIA NIH HHS [K24 AG035007, P50 AG005681]
NR 21
TC 17
Z9 17
U1 0
U2 9
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD DEC 21
PY 2011
VL 3
IS 114
AR 114ps48
DI 10.1126/scitranslmed.3003529
PG 7
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 865PF
UT WOS:000298322100003
PM 22190237
ER
PT J
AU Rao, RC
Perry, LJP
AF Rao, Rajesh C.
Perry, Lynn J. Poole
TI Decreased Vision Following Eye Trauma
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID INTRALENTICULAR FOREIGN-BODY; BODIES; LENS
C1 [Rao, Rajesh C.; Perry, Lynn J. Poole] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.
RP Rao, RC (reprint author), Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, Retina Serv, 4921 Parkview Pl,Ste 12C, St Louis, MO 63110 USA.
EM rajeshcrao@gmail.com
OI Rao, Rajesh/0000-0002-5776-8366
NR 9
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD DEC 21
PY 2011
VL 306
IS 23
BP 2606
EP 2607
DI 10.1001/jama.2011.1832
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 864YQ
UT WOS:000298276800022
PM 22187280
ER
PT J
AU Gaudet, S
Langlois, MJ
Lue, RA
Rivard, N
Viel, A
AF Gaudet, Suzanne
Langlois, Marie-Josee
Lue, Robert A.
Rivard, Nathalie
Viel, Alain
TI The MEK2-binding tumor suppressor hDlg is recruited by E-cadherin to the
midbody ring
SO BMC CELL BIOLOGY
LA English
DT Article
ID MAP KINASE PATHWAY; HUMAN HOMOLOG; MITOTIC KINASE; PROTEIN-KINASE;
DISC-LARGE; DOMAIN; LOCALIZATION; CELLS; BINDING; MITOSIS
AB Background: The human homologue of the Drosophila Discs-large tumor suppressor protein, hDlg, is a multidomain cytoplasmic protein that localizes to the membrane at intercellular junction sites. At both synaptic junctions and epithelia cell-cell junctions, hDlg is known to recruit several signaling proteins into macromolecular complexes. hDlg is also found at the midbody, a small microtubule-rich structure bridging the two daughter cells during cytokinesis, but its function at this site is not clear.
Results: Here we describe the interaction of hDlg with the activated form of MEK2 of the canonical RAF/MEK/ERK pathway, a protein that is found at the midbody during cytokinesis. We show that both proteins localize to a substructure of the midbody, the midbody ring, and that the interaction between the PDZ domains of hDlg and the C-terminal portion of MEK2 is dependent on the phosphorylation of MEK2. Finally, we found that E-cadherin also localizes to the midbody and that its expression is required for the isoform-specific recruitment of hDlg, but not activated MEK2, to that structure.
Conclusion: Our results suggest that like at other cell-cell junction sites, hDlg is part of a macromolecular complex of structural and signaling proteins at the midbody.
C1 [Lue, Robert A.; Viel, Alain] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Gaudet, Suzanne] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Gaudet, Suzanne] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA.
[Gaudet, Suzanne] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Langlois, Marie-Josee; Rivard, Nathalie] Univ Sherbrooke, Fac Med & Sci Sante, Dept Anat & Cell Biol, Sherbrooke, PQ J1K 2R1, Canada.
RP Viel, A (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 16 Divin Ave, Cambridge, MA 02138 USA.
EM aviel@fas.harvard.edu
FU National Institute of Health [GM57314]; Canadian Institutes of Health
Research [MT-14405]; Canadian Research Chair in Signaling and Digestive
Physiopathology
FX We thank Robert Hale for his technical contribution during the early
phase of the study. This research was supported in part by funding from
the National Institute of Health (Grant GM57314 to D. Branton and R.A.L)
and from the Canadian Institutes of Health Research (Grant MT-14405 to
N.R.). Marie-Josee Langlois is a student scholar from the Natural
Sciences and Engineering Research Council of Canada. Nathalie Rivard is
a recipient of a Canadian Research Chair in Signaling and Digestive
Physiopathology. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 44
TC 6
Z9 6
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2121
J9 BMC CELL BIOL
JI BMC Cell Biol.
PD DEC 20
PY 2011
VL 12
AR 55
DI 10.1186/1471-2121-12-55
PG 12
WC Cell Biology
SC Cell Biology
GA 886GJ
UT WOS:000299841700001
PM 22185284
ER
PT J
AU Chen, JC
Brunzell, DH
Jackson, K
van der Vaart, A
Ma, JZ
Payne, TJ
Sherva, R
Farrer, LA
Gejman, P
Levinson, DF
Holmans, P
Aggen, SH
Damaj, I
Kuo, PH
Webb, BT
Anton, R
Kranzler, HR
Gelernter, J
Li, MD
Kendler, KS
Chen, XN
AF Chen, Jingchun
Brunzell, Darlene H.
Jackson, Kia
van der Vaart, Andrew
Ma, Jennie Z.
Payne, Thomas J.
Sherva, Richard
Farrer, Lindsay A.
Gejman, Pablo
Levinson, Douglas F.
Holmans, Peter
Aggen, Steven H.
Damaj, Imad
Kuo, Po-Hsiu
Webb, Bradley T.
Anton, Raymond
Kranzler, Henry R.
Gelernter, Joel
Li, Ming D.
Kendler, Kenneth S.
Chen, Xiangning
TI ACSL6 Is Associated with the Number of Cigarettes Smoked and Its
Expression Is Altered by Chronic Nicotine Exposure
SO PLOS ONE
LA English
DT Article
ID CANNABINOID RECEPTOR GENE; FAGERSTROM TOLERANCE QUESTIONNAIRE;
GENOME-WIDE ASSOCIATION; NEUROTROPHIC FACTOR; ALCOHOL DEPENDENCE;
AFRICAN-AMERICAN; ENDOCANNABINOID SYSTEM; CNR1 POLYMORPHISM;
WORKING-MEMORY; HEAVY SMOKING
AB Individuals with schizophrenia tend to be heavy smokers and are at high risk for tobacco dependence. However, the nature of the comorbidity is not entirely clear. We previously reported evidence for association of schizophrenia with SNPs and SNP haplotypes in a region of chromosome 5q containing the SPEC2, PDZ-GEF2 and ACSL6 genes. In this current study, analysis of the control subjects of the Molecular Genetics of Schizophrenia (MGS) sample showed similar pattern of association with number of cigarettes smoked per day (numCIG) for the same region. To further test if this locus is associated with tobacco smoking as measured by numCIG and FTND, we conducted replication and meta-analysis in 12 independent samples (n>16,000) for two markers in ACSL6 reported in our previous schizophrenia study. In the meta-analysis of the replication samples, we found that rs667437 and rs477084 were significantly associated with numCIG (p = 0.00038 and 0.00136 respectively) but not with FTND scores. We then used in vitro and in vivo techniques to test if nicotine exposure influences the expression of ACSL6 in brain. Primary cortical culture studies showed that chronic (5-day) exposure to nicotine stimulated ACSL6 mRNA expression. Fourteen days of nicotine administration via osmotic mini pump also increased ACSL6 protein levels in the prefrontal cortex and hippocampus of mice. These increases were suppressed by injection of the nicotinic receptor antagonist mecamylamine, suggesting that elevated expression of ACSL6 requires nicotinic receptor activation. These findings suggest that variations in the ACSL6 gene may contribute to the quantity of cigarettes smoked. The independent associations of this locus with schizophrenia and with numCIG in non-schizophrenic subjects suggest that this locus may be a common liability to both conditions.
C1 [Chen, Jingchun; Jackson, Kia; Aggen, Steven H.; Webb, Bradley T.; Kendler, Kenneth S.; Chen, Xiangning] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23284 USA.
[Chen, Jingchun; Jackson, Kia; Aggen, Steven H.; Webb, Bradley T.; Kendler, Kenneth S.; Chen, Xiangning] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA.
[Brunzell, Darlene H.; Damaj, Imad] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA.
[Brunzell, Darlene H.; Kendler, Kenneth S.] Virginia Commonwealth Univ, Inst Drug & Alcohol Studies, Richmond, VA USA.
[Brunzell, Darlene H.] Virginia Commonwealth Univ, Interdisciplinary Neurosci Program, Richmond, VA USA.
[van der Vaart, Andrew; Li, Ming D.] Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA USA.
[Ma, Jennie Z.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Payne, Thomas J.] Univ Mississippi, Med Ctr, Dept Otolaryngol & Communicat Sci, Jackson, MS 39216 USA.
[Sherva, Richard; Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA.
[Gejman, Pablo] NorthShore Univ HealthSyst Res Inst, Ctr Psychiat Genet, Evanston, IL USA.
[Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Holmans, Peter] Cardiff Univ, Sch Med, Med Resource Council,& Neurol,Biostat & Bioinform, Ctr Neuropsychiat Genet & Genom,Dept Psychol Med, Cardiff, S Glam, Wales.
[Kuo, Po-Hsiu] Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan.
[Anton, Raymond] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
[Kranzler, Henry R.] Univ Penn, Dept Psychiat, Treatment Res Ctr, Sch Med 3900, Philadelphia, PA 19104 USA.
[Kranzler, Henry R.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Gelernter, Joel] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
[Gelernter, Joel] Vet Affairs Connecticut Healthcare Ctr, West Haven, CT USA.
[Kendler, Kenneth S.; Chen, Xiangning] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA.
RP Chen, JC (reprint author), Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23284 USA.
EM xchen@vcu.edu
RI Webb, Bradley/B-1459-2009; Holmans, Peter/F-4518-2015;
OI Webb, Bradley/0000-0002-0576-5366; Holmans, Peter/0000-0003-0870-9412;
Kuo, Po-Hsiu/0000-0003-0365-3587; Farrer, Lindsay/0000-0001-5533-4225
FU National Institutes of Health [DA019498, DA011287]; Virginia Tobacco
Settlement Foundation [5100004ST]; Virginia Foundation for Healthy Youth
[8520667]
FX This study was supported by grants DA019498 to XC and DA011287 to KSK
from the National Institutes of Health, by funds from the Virginia
Tobacco Settlement Foundation through the Virginia Youth Tobacco Project
to Virginia Commonwealth University (subcontracted to KSK, #5100004ST)
and by a grant from Virginia Foundation for Healthy Youth 8520667 to
DHB. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 86
TC 5
Z9 5
U1 4
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 DEC 20
PY 2011
VL 6
IS 12
AR e28790
DI 10.1371/journal.pone.0028790
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 870JU
UT WOS:000298666200011
ER
PT J
AU Macaya, D
Ng, KK
Spector, M
AF Macaya, Daniel
Ng, Karen K.
Spector, Myron
TI Injectable Collagen-Genipin Gel for the Treatment of Spinal Cord Injury:
In Vitro Studies
SO ADVANCED FUNCTIONAL MATERIALS
LA English
DT Article
DE collagen; injectable scaffold; spinal cord injury
ID RAT CORTICAL-NEURONS; CROSS-LINKING; STEM-CELLS; MECHANICAL-PROPERTIES;
LOCALIZED DELIVERY; NEURITE OUTGROWTH; DRUG-DELIVERY; BLUE PIGMENTS;
NEURAL STEM; ADULT-RAT
AB Spinal cord injury (SCI) often results in a cavitary lesion, contained within the dura, which involves only a portion of the cord. Injectable biopolymers are an attractive treatment option for SCI to re-establish cell migratory pathways within the lesion while minimizing the collateral damage attendant to an open surgical procedure. In this study we evaluate a thermoresponsive soluble collagen gel incorporating genipin, an amine reactive covalent cross-linker with low cytotoxicity and fluorogenic attributes. Unlike previous studies, genipin is being investigated as an in situ covalent cross-linker that will continue to act on the gel after injection. Physical characterization studies show that the addition of genipin provides control over the mechanical and degradative behavior of the gel, to meet design specifications of an injectable material for neural tissues. Additionally, an improved in situ assay to predict the extent of cross-linking reaction is investigated. Encapsulation of mesenchymal stem cells (MSCs) in collagengenipin gels show the gels support cell viability and proliferation, and thus serve as a cell delivery vehicle. Neural stem cells are found to be more sensitive to genipin, with respect to toxicity, as compared to MSCs. From our studies, 0.25-0.5 mM is an appropriate genipin concentration to use for an in situ forming scaffold capable of delivering cells and therapeutic agents.
C1 [Spector, Myron] Harvard Univ, Tissue Engn & Orthopaed Res Lab, VA Boston Healthcare Syst, Brigham & Womens Hosp,Med Sch, Boston, MA 02130 USA.
[Macaya, Daniel] VA Boston Healthcare Syst, Harvard Massachusetts Inst Technol, Boston, MA 02130 USA.
[Ng, Karen K.] VA Boston Healthcare Syst, MIT, Boston, MA 02130 USA.
[Spector, Myron] Harvard Univ, Tissue Engn & Orthopaed Res Lab, VA Boston Healthcare Syst, Brigham & Womens Hosp,Med Sch, Boston, MA 02130 USA.
RP Macaya, D (reprint author), VA Boston Healthcare Syst, Harvard Massachusetts Inst Technol, Boston, MA 02130 USA.
EM mspector@rics.bwh.harvard.edu
FU NSF; VA Research Career Scientist Award; U.S. Department of Veterans
Affairs, Veterans Health Administration, Rehabilitation Research and
Development Service
FX D.M. was supported by an NSF Fellowship, and MS by a VA Research Career
Scientist Award. The work was supported in part by the U.S. Department
of Veterans Affairs, Veterans Health Administration, Rehabilitation
Research and Development Service.
NR 52
TC 22
Z9 23
U1 5
U2 28
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1616-301X
J9 ADV FUNCT MATER
JI Adv. Funct. Mater.
PD DEC 20
PY 2011
VL 21
IS 24
BP 4788
EP 4797
DI 10.1002/adfm.201101720
PG 10
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 861KN
UT WOS:000298017900024
ER
PT J
AU O'Donnell, CJ
Kavousi, M
Smith, AV
Kardia, SLR
Feitosa, MF
Hwang, SJ
Sun, YV
Province, MA
Aspelund, T
Dehghan, A
Hoffmann, U
Bielak, LF
Zhang, QY
Eiriksdottir, G
van Duijn, CM
Fox, CS
de Andrade, M
Kraja, AT
Sigurdsson, S
Elias-Smale, SE
Murabito, JM
Launer, LJ
van der Lugt, A
Kathiresan, S
Krestin, GP
Herrington, DM
Howard, TD
Liu, YM
Post, W
Mitchell, BD
O'Connell, JR
Shen, HQ
Shuldiner, AR
Altshuler, D
Elosua, R
Salomaa, V
Schwartz, SM
Siscovick, DS
Voight, BF
Bis, JC
Glazer, NL
Psaty, BM
Boerwinkle, E
Heiss, G
Blankenberg, S
Zeller, T
Wild, PS
Schnabel, RB
Schillert, A
Ziegler, A
Munzel, T
White, CC
Rotter, JI
Nalls, M
Oudkerk, M
Johnson, AD
Newman, AB
Uitterlinden, AG
Massaro, JM
Cunningham, J
Harris, TB
Hofman, A
Peyser, PA
Borecki, IB
Cupples, LA
Gudnason, V
Witteman, JCM
AF O'Donnell, Christopher J.
Kavousi, Maryam
Smith, Albert V.
Kardia, Sharon L. R.
Feitosa, Mary F.
Hwang, Shih-Jen
Sun, Yan V.
Province, Michael A.
Aspelund, Thor
Dehghan, Abbas
Hoffmann, Udo
Bielak, Lawrence F.
Zhang, Qunyuan
Eiriksdottir, Gudny
van Duijn, Cornelia M.
Fox, Caroline S.
de Andrade, Mariza
Kraja, Aldi T.
Sigurdsson, Sigurdur
Elias-Smale, Suzette E.
Murabito, Joanne M.
Launer, Lenore J.
van der Lugt, Aad
Kathiresan, Sekar
Krestin, Gabriel P.
Herrington, David M.
Howard, Timothy D.
Liu, Yongmei
Post, Wendy
Mitchell, Braxton D.
O'Connell, Jeffrey R.
Shen, Haiqing
Shuldiner, Alan R.
Altshuler, David
Elosua, Roberto
Salomaa, Veikko
Schwartz, Stephen M.
Siscovick, David S.
Voight, Benjamin F.
Bis, Joshua C.
Glazer, Nicole L.
Psaty, Bruce M.
Boerwinkle, Eric
Heiss, Gerardo
Blankenberg, Stefan
Zeller, Tanja
Wild, Philipp S.
Schnabel, Renate B.
Schillert, Arne
Ziegler, Andreas
Muenzel, Thomas
White, Charles C.
Rotter, Jerome I.
Nalls, Michael
Oudkerk, Matthijs
Johnson, Andrew D.
Newman, Anne B.
Uitterlinden, Andre G.
Massaro, Joseph M.
Cunningham, Julie
Harris, Tamara B.
Hofman, Albert
Peyser, Patricia A.
Borecki, Ingrid B.
Cupples, L. Adrienne
Gudnason, Vilmundur
Witteman, Jacqueline C. M.
CA CARDIoGRAM Consortium
TI Genome-Wide Association Study for Coronary Artery Calcification With
Follow-Up in Myocardial Infarction
SO CIRCULATION
LA English
DT Article
DE cardiac computed tomography; coronary artery calcification; coronary
atherosclerosis; genome-wide association studies; myocardial infarction
ID BEAM COMPUTED-TOMOGRAPHY; EXPERT CONSENSUS DOCUMENT; ABDOMINAL
AORTIC-ANEURYSM; BONE-MINERAL DENSITY; OLD-ORDER AMISH;
AMERICAN-COLLEGE; SEQUENCE VARIANT; BLOOD-PRESSURE; HEART-DISEASE; RISK
AB Background-Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI.
Methods and Results-Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P=7.58x10(-19)) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P=2.65x10(-11)) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene).
Conclusions-SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events. (Circulation. 2011;124:2855-2864.)
C1 [O'Donnell, Christopher J.; Hwang, Shih-Jen; Fox, Caroline S.; Murabito, Joanne M.; Johnson, Andrew D.; Massaro, Joseph M.; Cupples, L. Adrienne] NHLBIs Framingham Heart Study, Framingham, MA 01702 USA.
[O'Donnell, Christopher J.; Kardia, Sharon L. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA.
[O'Donnell, Christopher J.; Hwang, Shih-Jen; Fox, Caroline S.; Johnson, Andrew D.] NHLBI, Bethesda, MD 20892 USA.
[Kavousi, Maryam; Dehghan, Abbas; van Duijn, Cornelia M.; Elias-Smale, Suzette E.; Uitterlinden, Andre G.; Hofman, Albert; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Elias-Smale, Suzette E.] Erasmus Univ, Dept Radiol, Med Ctr, Rotterdam, Netherlands.
[Kavousi, Maryam; Dehghan, Abbas; van Duijn, Cornelia M.; Uitterlinden, Andre G.; Hofman, Albert; Witteman, Jacqueline C. M.] Netherlands Genom Initiat Sponsored Netherlands C, Rotterdam, Netherlands.
[Smith, Albert V.; Aspelund, Thor; Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur Iceland, Iceland.
[Kardia, Sharon L. R.; Sun, Yan V.; Bielak, Lawrence F.; Peyser, Patricia A.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Feitosa, Mary F.; Province, Michael A.; Zhang, Qunyuan; Kraja, Aldi T.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Gen, St Louis, MO 63110 USA.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Metab & Diabet,Dept Med, Boston, MA 02115 USA.
[de Andrade, Mariza] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[van der Lugt, Aad; Krestin, Gabriel P.] Erasmus MC, Dept Radiol, Rotterdam, Netherlands.
[Kathiresan, Sekar; Altshuler, David; Voight, Benjamin F.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA USA.
[Herrington, David M.; Howard, Timothy D.; Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Post, Wendy] Johns Hopkins Univ Hosp, Dept Med & Epidemiol, Baltimore, MD 21287 USA.
[Mitchell, Braxton D.; O'Connell, Jeffrey R.; Shen, Haiqing; Shuldiner, Alan R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Baltimore, MD 21218 USA.
[Altshuler, David; Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Elosua, Roberto] Inst Municipal Invest Med, Barcelona, Spain.
[Elosua, Roberto] CIBER Epidemiol & Salud Publ, Barcelona, Spain.
[Salomaa, Veikko] Natl Publ Hlth Inst, Chron Dis Epidemiol Unit, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland.
[Schwartz, Stephen M.; Siscovick, David S.; Bis, Joshua C.; Glazer, Nicole L.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Schwartz, Stephen M.; Siscovick, David S.; Bis, Joshua C.; Glazer, Nicole L.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Human Genet Ctr, Houston, TX USA.
[Boerwinkle, Eric] Inst Mol Med, Houston, TX USA.
[Heiss, Gerardo] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27515 USA.
[Blankenberg, Stefan; Zeller, Tanja; Wild, Philipp S.; Schnabel, Renate B.; Muenzel, Thomas] Univ Med Ctr Mainz, Dept Med 2, Mainz, Germany.
[Schillert, Arne; Ziegler, Andreas] Univ Lubeck, Inst Med Biometrie & Stat, Univ Klinikum Schleswig Holstein, Lubeck, Germany.
[White, Charles C.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Nalls, Michael] NIA, Neurogenet Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Oudkerk, Matthijs] Univ Groningen, Ctr Med Imaging NE Netherlands, Dept Radiol, Univ Med Ctr Groningen, Groningen, Netherlands.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Massaro, Joseph M.] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Cunningham, Julie] Mayo Clin, Coll Med, Rochester, MN USA.
RP O'Donnell, CJ (reprint author), NHLBIs Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM odonnellc@nhlbi.nih.gov; ppeyser@umich.edu
RI Aspelund, Thor/C-5983-2008; Willenborg, Christina/D-2668-2012; Johnson,
Andrew/G-6520-2013; Smith, Albert/K-5150-2015; Feitosa,
Mary/K-8044-2012; Altshuler, David/A-4476-2009; Elias-Smale,
Suzette/F-2410-2014; Schnabel, Renate/F-6527-2014; Newman,
Anne/C-6408-2013; Gudnason, Vilmundur/K-6885-2015; Peters,
Annette/A-6117-2011;
OI Aspelund, Thor/0000-0002-7998-5433; Willenborg,
Christina/0000-0001-5217-6882; Smith, Albert/0000-0003-1942-5845;
Feitosa, Mary/0000-0002-0933-2410; Murabito, Joanne/0000-0002-0192-7516;
Massaro, Joseph/0000-0002-2682-4812; Altshuler,
David/0000-0002-7250-4107; Newman, Anne/0000-0002-0106-1150; Gudnason,
Vilmundur/0000-0001-5696-0084; ELOSUA, ROBERTO/0000-0001-8235-0095;
Cupples, L. Adrienne/0000-0003-0273-7965; Ziegler,
Andreas/0000-0002-8386-5397; Mitchell, Braxton/0000-0003-4920-4744;
Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X
FU Intramural NIH HHS [Z01 HL006002-01, Z99 HL999999, ZIA HL006002-04];
NCATS NIH HHS [UL1 TR000005, UL1 TR000124]; NHLBI NIH HHS [R01 HL087647]
NR 64
TC 101
Z9 104
U1 0
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD DEC 20
PY 2011
VL 124
IS 25
BP 2855
EP U255
DI 10.1161/CIRCULATIONAHA.110.974899
PG 68
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 866VS
UT WOS:000298414900016
PM 22144573
ER
PT J
AU Weiser, MR
Gonen, M
Chou, JF
Kattan, MW
Schrag, D
AF Weiser, Martin R.
Goenen, Mithat
Chou, Joanne F.
Kattan, Michael W.
Schrag, Deborah
TI Predicting Survival After Curative Colectomy for Cancer: Individualizing
Colon Cancer Staging
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID COLORECTAL-CANCER; ADJUVANT CHEMOTHERAPY; RADICAL PROSTATECTOMY;
CLINICAL ONCOLOGY; AMERICAN SOCIETY; ROC CURVES; NOMOGRAM; REGRESSION;
ACCURACY; DISEASE
AB Purpose
Cancer staging determines extent of disease, facilitating prognostication and treatment decision making. The American Joint Committee on Cancer (AJCC) TNM classification system is the most commonly used staging algorithm for colon cancer, categorizing patients on the basis of only these three variables (tumor, node, and metastasis). The purpose of this study was to extend the seventh edition of the AJCC staging system for colon cancer to incorporate additional information available from tumor registries, thereby improving prognostic accuracy.
Methods
Records from 128,853 patients with primary colon cancer reported to the Surveillance, Epidemiology and End Results Program from 1994 to 2005 were used to construct and validate three survival models for patients with primary curative-intent surgery. Independent training/test data sets were used to develop and test alternative models. The seventh edition TNM staging system was compared with models supplementing TNM staging with additional demographic and tumor variables available from the registry by calculating a concordance index, performing calibration, and identifying the area under receiver operating characteristic (ROC) curves.
Results
Inclusion of additional registry covariates improved prognostic estimates. The concordance index rose from 0.60 (95% CI, 0.59 to 0.61) for the AJCC model, with T-and N-stage variables, to 0.68 (95% CI, 0.67 to 0.68) for the model including tumor grade, number of collected metastatic lymph nodes, age, and sex. ROC curves for the extended model had higher sensitivity, at all values of specificity, than the TNM system; calibration curves indicated no deviation from the reference line.
Conclusion
Prognostic models incorporating readily available data elements outperform the current AJCC system. These models can assist in personalizing treatment and follow-up for patients with colon cancer. J Clin Oncol 29: 4796-4802. (C) 2011 by American Society of Clinical Oncology
C1 [Weiser, Martin R.] Mem Sloan Kettering Canc Ctr, Dept Surg, Colorectal Serv, New York, NY 10065 USA.
[Schrag, Deborah] Dana Farber Canc Ctr, Boston, MA USA.
[Kattan, Michael W.] Cleveland Clin, Cleveland, OH 44106 USA.
RP Weiser, MR (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Colorectal Serv, 1275 York Ave,Room C-1075, New York, NY 10065 USA.
EM weiser1@mskcc.org
RI Gonen, Mithat/E-4826-2012
FU American Joint Committee on Cancer; Society of Memorial Sloan-Kettering
Cancer Center
FX Supported in part by a grant from the American Joint Committee on Cancer
(M.R.W.) and a grant from the Society of Memorial Sloan-Kettering Cancer
Center (M.R.W.).
NR 32
TC 30
Z9 32
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 DEC 20
PY 2011
VL 29
IS 36
BP 4796
EP 4802
DI 10.1200/JCO.2011.36.5080
PG 7
WC Oncology
SC Oncology
GA 863DD
UT WOS:000298142100015
PM 22084366
ER
PT J
AU Lennerz, JK
Kwak, EL
Ackerman, A
Michael, M
Fox, SB
Bergethon, K
Lauwers, GY
Christensen, JG
Wilner, KD
Haber, DA
Salgia, R
Bang, YJ
Clark, JW
Solomon, BJ
Iafrate, AJ
AF Lennerz, Jochen K.
Kwak, Eunice L.
Ackerman, Allison
Michael, Michael
Fox, Stephen B.
Bergethon, Kristin
Lauwers, Gregory Y.
Christensen, James G.
Wilner, Keith D.
Haber, Daniel A.
Salgia, Ravi
Bang, Yung-Jue
Clark, Jeffrey W.
Solomon, Benjamin J.
Iafrate, A. John
TI MET Amplification Identifies a Small and Aggressive Subgroup of
Esophagogastric Adenocarcinoma With Evidence of Responsiveness to
Crizotinib
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID HELICOBACTER-PYLORI INFECTION; GROWTH-FACTOR RECEPTOR; IN-SITU
HYBRIDIZATION; GASTRIC-CANCER; C-MET; GASTROESOPHAGEAL JUNCTION; GENE
AMPLIFICATION; PHASE-II; ACQUIRED-RESISTANCE; ESOPHAGEAL CANCER
AB Purpose
Amplification of the MET proto-oncogene in gastroesophageal cancer (GEC) may constitute a molecular marker for targeted therapy. We examined a GEC cohort with follow-up and reported the clinical response of four additional patients with MET-amplified tumors to the small molecule inhibitor crizotinib as part of an expanded phase I cohort study.
Patients and Methods
From 2007 to 2009, patients with GEC were genetically screened as a consecutive series of 489 tumors (stages 0, I, and II, 39%; III, 25%; IV, 36%; n = 222 esophageal, including n = 21 squamous carcinomas). MET, EGFR, and HER2 amplification status was assessed by using fluorescence in situ hybridization.
Results Ten (2%) of 489 patients screened harbored MET amplification; 23 (4.7%) harbored EGFR amplification; 45 (8.9%) harbored HER2 amplification; and 411 (84%) were wild type for all three genes (ie, negative). MET-amplified tumors were typically high-grade adenocarcinomas that presented at advanced stages (5%; n = 4 of 80). EGFR-amplified tumors showed the highest fraction of squamous cell carcinoma (17%; n = 4 of 23). HER2, MET, and EGFR amplification were, with one exception (MET and EGFR positive), mutually exclusive events. Survival analysis in patients with stages III and IV disease showed substantially shorter median survival in MET/EGFR-amplified groups, with a rank order for all groups by median survival (from most to least aggressive): MET (7.1 months; P < .001) less than EGFR (11.2 months; P = .16) less than HER2 (16.9 months; P = .89) when compared with the negative group (16.2 months). Two of four patients with MET-amplified tumors treated with crizotinib experienced tumor shrinkage (= 30% and -16%) and experienced progression after 3.7 and 3.5 months.
Conclusion
MET amplification defines a small and aggressive subset of GEC with indications of transient sensitivity to the targeted MET inhibitor crizotinib (PF-02341066). J Clin Oncol 29: 4803-4810. (C) 2011 by American Society of Clinical Oncology
C1 [Iafrate, A. John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Michael, Michael; Fox, Stephen B.; Solomon, Benjamin J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Christensen, James G.; Wilner, Keith D.] Pfizer, La Jolla, CA USA.
[Salgia, Ravi] Univ Chicago, Chicago, IL 60637 USA.
[Bang, Yung-Jue] Seoul Natl Univ Hosp, Seoul 110744, South Korea.
RP Iafrate, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
EM Aiafrate@partners.org
RI Bang, Yung Jue/J-2759-2012;
OI Fox, Stephen/0000-0002-7648-8896
FU Pfizer; National Cancer Institute [5R01CA125541-05]
FX Supported by Pfizer and by National Cancer Institute Grant No.
5R01CA125541-05 (R.S).
NR 49
TC 211
Z9 218
U1 1
U2 21
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 DEC 20
PY 2011
VL 29
IS 36
BP 4803
EP 4810
DI 10.1200/JCO.2011.35.4928
PG 8
WC Oncology
SC Oncology
GA 863DD
UT WOS:000298142100016
PM 22042947
ER
PT J
AU Okamoto, N
Yasukawa, M
Nguyen, C
Kasim, V
Maida, Y
Possemato, R
Shibata, T
Ligon, KL
Fukami, K
Hahn, WC
Masutomi, K
AF Okamoto, Naoko
Yasukawa, Mami
Nguyen, Christine
Kasim, Vivi
Maida, Yoshiko
Possemato, Richard
Shibata, Tatsuhiro
Ligon, Keith L.
Fukami, Kiyoko
Hahn, William C.
Masutomi, Kenkichi
TI Maintenance of tumor initiating cells of defined genetic composition by
nucleostemin
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID CANCER STEM-CELLS; TELOMERE LENGTH; PROLIFERATION; IDENTIFICATION;
PROTEIN; TRANSFORMATION; HETEROGENEITY; FIBROBLASTS; ACTIVATION;
INDUCTION
AB Recent work has identified a subset of cells resident in tumors that exhibit properties similar to those found in normal stem cells. Such cells are highly tumorigenic and may be involved in resistance to treatment. However, the genes that regulate the tumor initiating cell (TIC) state are unknown. Here, we show that overexpression of either of the nucleolar GTP-binding proteins nucleostemin (NS) or GNL3L drives the fraction of genetically defined tumor cells that exhibit markers and tumorigenic properties of TICs. Specifically, cells that constitutively express elevated levels of NS or GNL3L exhibit increased TWIST expression, phosphorylation of STAT3, expression of genes that induce pluripotent stem cells, and enhanced radioresistance; in addition, they form tumors even when small numbers of cells are implanted and exhibit an increased propensity to metastasize. GNL3L/NS forms a complex with the telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] and the SWItch-Sucrose NonFermentable (SWI-SNF) complex protein brahma-related gene 1 (BRG1), and the expression of each of these components is necessary to facilitate the cancer stem cell state. Together, these observations define a complex composed of TERT, BRG1, and NS/GNL3L that maintains the function of TICs.
C1 [Nguyen, Christine; Possemato, Richard; Ligon, Keith L.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Nguyen, Christine; Possemato, Richard; Ligon, Keith L.; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Nguyen, Christine; Possemato, Richard; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA USA.
[Okamoto, Naoko; Yasukawa, Mami; Kasim, Vivi; Maida, Yoshiko; Masutomi, Kenkichi] Natl Canc Ctr, Div Canc Stem Cell, Chuo Ku, Tokyo 1040045, Japan.
[Okamoto, Naoko; Fukami, Kiyoko] Tokyo Univ Pharm & Life Sci, Lab Genome & Biosignal, Tokyo 1920392, Japan.
[Nguyen, Christine] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA.
[Nguyen, Christine] MIT, Cambridge, MA 02142 USA.
[Hahn, William C.] Natl Canc Ctr, Canc Genom Project, Ctr Med Genom, Chuo Ku, Tokyo 1040045, Japan.
[Masutomi, Kenkichi] Japan Sci & Technol Agcy, PREST, Saitama 3320012, Japan.
RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM william_hahn@dfci.harvard.edu; kmasutom@ncc.go.jp
OI Kasim, Vivi/0000-0001-9182-8230
FU Japanese Ministry of Education, Culture, Sports, Science, and Technology
[21689012]; Japanese Ministry of Health, Labor, and Welfare; NOVARTIS
Foundation (Japan); Funding Program for Next Generation World-Leading
Researchers; US National Institutes of Health [R01 AG23145]; Japan
Society for the Promotion of Science
FX We thank A. Miyajima, S. Saito, S. Inanobe, S. Takahashi, T. Ochiya, and
R. Takahashi for their technical assistance. We thank H. Fine for the
gift of 308 cells. This work was supported, in part, by Grant-in-Aid for
Young Scientists (A) 21689012 (to K. M.) from the Japanese Ministry of
Education, Culture, Sports, Science, and Technology; by Third-Term
Comprehensive Control Research for Cancer (K. M.) from the Japanese
Ministry of Health, Labor, and Welfare; by the NOVARTIS Foundation
(Japan) for the Promotion of Science (K. M.); by the Funding Program for
Next Generation World-Leading Researchers (K. M.); and by Grant R01
AG23145 from the US National Institutes of Health (to W. C. H.). N.O.
was supported by a Research Fellow of the Japan Society for the
Promotion of Science.
NR 45
TC 47
Z9 48
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 20
PY 2011
VL 108
IS 51
BP 20388
EP 20393
DI 10.1073/pnas.1015171108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865CW
UT WOS:000298289400033
PM 21730156
ER
PT J
AU Simon, MD
Wang, CI
Kharchenko, PV
West, JA
Chapman, BA
Alekseyenko, AA
Borowsky, ML
Kuroda, MI
Kingston, RE
AF Simon, Matthew D.
Wang, Charlotte I.
Kharchenko, Peter V.
West, Jason A.
Chapman, Brad A.
Alekseyenko, Artyom A.
Borowsky, Mark L.
Kuroda, Mitzi I.
Kingston, Robert E.
TI The genomic binding sites of a noncoding RNA
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE chromatin-associated RNAs; chromatin-modifying complexes; RNase H
mapping
ID DROSOPHILA DOSAGE COMPENSATION; MALE X-CHROMOSOME; ANALYSIS REVEALS;
GENE-EXPRESSION; HEAT-SHOCK; CHROMATIN; COMPLEX; CELLS; TRANSCRIPTION;
PROTEINS
AB Long noncoding RNAs (lncRNAs) have important regulatory roles and can function at the level of chromatin. To determine where lncRNAs bind to chromatin, we developed capture hybridization analysis of RNA targets (CHART), a hybridization-based technique that specifically enriches endogenous RNAs along with their targets from reversibly cross-linked chromatin extracts. CHART was used to enrich the DNA and protein targets of endogenous lncRNAs from flies and humans. This analysis was extended to genome-wide mapping of roX2, a well-studied ncRNA involved in dosage compensation in Drosophila. CHART revealed that roX2 binds at specific genomic sites that coincide with the binding sites of proteins from the male-specific lethal complex that affects dosage compensation. These results reveal the genomic targets of roX2 and demonstrate how CHART can be used to study RNAs in a manner analogous to chromatin immunoprecipitation for proteins.
C1 [Simon, Matthew D.; West, Jason A.; Chapman, Brad A.; Borowsky, Mark L.; Kingston, Robert E.] Harvard Univ, Sch Med, Dept Genet, Dept Mol Biol,Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Wang, Charlotte I.; Alekseyenko, Artyom A.; Kuroda, Mitzi I.] Harvard Univ, Sch Med, Div Genet, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA.
[Kharchenko, Peter V.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
[Kharchenko, Peter V.] Childrens Hosp, Informat Program, Boston, MA 02115 USA.
RP Kingston, RE (reprint author), Harvard Univ, Sch Med, Dept Genet, Dept Mol Biol,Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM kingston@molbio.mgh.harvard.edu
RI West, Jason/I-4445-2014;
OI West, Jason/0000-0002-7252-8651; Chapman, Brad/0000-0002-3026-1856
FU National Institutes of Health National Institute of General Medical
Sciences [5R01GM043901, GM045744]; Helen Hay Whitney Foundation
FX We thank Jose Antao for suggesting cell culture conditions; Daniel
Locker for providing the DSP1 antisera; Shangtao Liu, Jerome Dejardin,
and members of the Kingston lab for helpful discussions; Sarah K. Bowman
for critical reading of this manuscript; and the Szostak Lab for
assistance and use of their DNA synthesizer. This research was funded by
grants from the National Institutes of Health National Institute of
General Medical Sciences (5R01GM043901 to R.E.K. and GM045744 to M.I.K)
and a Helen Hay Whitney Foundation postdoctoral fellowship (M.D.S.).
NR 66
TC 128
Z9 136
U1 3
U2 43
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 DEC 20
PY 2011
VL 108
IS 51
BP 20497
EP 20502
DI 10.1073/pnas.1113536108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865CW
UT WOS:000298289400052
PM 22143764
ER
PT J
AU Kelley, JM
Monach, PA
Ji, CY
Zhou, YB
Wu, JM
Tanaka, S
Mahr, AD
Johnson, S
McAlear, C
Cuthbertson, D
Carette, S
Davis, JC
Dellaripa, PF
Hoffman, GS
Khalidi, N
Langford, CA
Seo, P
St Clair, EW
Specks, U
Stone, JH
Spiera, RF
Ytterberg, SR
Merkel, PA
Edberg, JC
Kimberly, RP
AF Kelley, James M.
Monach, Paul A.
Ji, Chuanyi
Zhou, Yebin
Wu, Jianming
Tanaka, Sumiaki
Mahr, Alfred D.
Johnson, Sharleen
McAlear, Carol
Cuthbertson, David
Carette, Simon
Davis, John C., Jr.
Dellaripa, Paul F.
Hoffman, Gary S.
Khalidi, Nader
Langford, Carol A.
Seo, Phillip
St Clair, E. William
Specks, Ulrich
Stone, John H.
Spiera, Robert F.
Ytterberg, Steven R.
Merkel, Peter A.
Edberg, Jeffrey C.
Kimberly, Robert P.
TI IgA and IgG antineutrophil cytoplasmic antibody engagement of Fc
receptor genetic variants influences granulomatosis with polyangiitis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE genetic association; functional genomics; Fc receptor alleles
ID WEGENERS-GRANULOMATOSIS; HUMAN NEUTROPHILS; GAMMA-RIIIB; ALPHA-RI;
VASCULITIS; DISEASE; ASSOCIATION; AUTOANTIBODIES; ITAM
AB Granulomatosis with polyangiitis (Wegener's) is a rare autoimmune neutrophil-mediated vasculitis that can cause renal disease and mucosal manifestations. Antineutrophil cytoplasmic antibodies (ANCA) are present in many patients, vary in level over time, and induce neutrophil activation through engagement with Fc receptors (FcRs). Given roles for FcRs in ANCA-mediated neutrophil activation and IgA antibodies in mucosal immunity, we hypothesized that FcR genetics and previously unappreciated IgA ANCA affect clinical presentation. We assembled a total of 673 patients and 413 controls from two multicenter cohorts, performed ELISA and immunofluorescence assays to determine IgA and IgG ANCA positivity, and used Illumina, TaqMan, or Pyrosequencing to genotype eight haplotype-tagging SNPs in the IgA FcR (FCAR) and to determine NA1/NA2 genotype of FCGR3B, the most prevalent neutrophil IgG FcR. We evaluated neutrophil activation by measuring degranulation marker CD11b with flow cytometry or neutrophil extracellcular trap formation with confocal microscopy. Functional polymorphisms in FCGR3B and FCAR differed between patient groups stratified by renal involvement. IgA ANCA were found in similar to 30% of patients and were less common in patients with severe renal disease. Neutrophil stimulation by IgA or IgG ANCA led to degranulation and neutrophil extracellcular trap formation in a FcR allele-specific manner (IgA: FCAR P = 0.008; IgG: FCGR3B P = 0.003). When stimulated with IgA and IgG ANCA together, IgG ANCA induced neutrophil activation was reduced (P = 0.0001). FcR genotypes, IgA ANCA, and IgG ANCA are potential prognostic and therapeutic targets for understanding the pathogenesis and presentation of granulomatosis with polyangiitis (Wegener's).
C1 [Kelley, James M.; Ji, Chuanyi; Zhou, Yebin; Wu, Jianming; Tanaka, Sumiaki; Edberg, Jeffrey C.; Kimberly, Robert P.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Kelley, James M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Dellaripa, Paul F.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Kelley, James M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Dellaripa, Paul F.; Stone, John H.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Tanaka, Sumiaki] Kitasato Univ, Sch Med, Dept Internal Med, Sagamihara, Kanagawa 2520373, Japan.
[Monach, Paul A.; Mahr, Alfred D.; Johnson, Sharleen; McAlear, Carol; Merkel, Peter A.] Boston Univ, Dept Med, Boston, MA 02118 USA.
[Mahr, Alfred D.] Hop St Louis, Dept Med, F-75010 Paris, France.
[Cuthbertson, David] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA.
[Carette, Simon] Univ Toronto, Dept Med, Toronto, ON M5S 1A1, Canada.
[Davis, John C., Jr.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Dellaripa, Paul F.] Lahey Clin Fdn, Dept Rheumatol, Burlington, MA 01805 USA.
[Hoffman, Gary S.; Langford, Carol A.] Cleveland Clin Fdn, Dept Rheumat & Immunol Dis, Cleveland, OH 44195 USA.
[Khalidi, Nader] McMaster Univ, Dept Med, Hamilton, ON L8S 4L8, Canada.
[Seo, Phillip; Stone, John H.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21287 USA.
[St Clair, E. William] Duke Univ, Dept Med, Durham, NC 27713 USA.
[Specks, Ulrich; Ytterberg, Steven R.] Mayo Clin, Dept Med, Rochester, MN 55905 USA.
[Stone, John H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Spiera, Robert F.] Beth Israel Deaconess Med Ctr, Dept Med, New York, NY 10003 USA.
[Spiera, Robert F.] Hosp Special Surg, Dept Med, New York, NY 10021 USA.
RP Edberg, JC (reprint author), Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
EM jedberg@uab.edu; rpk@uab.edu
OI Zhou, Yebin/0000-0002-4410-1909; Kimberly, Robert/0000-0002-5330-3086
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
[U54AR057319]; National Center for Research Resources [U54 RR019497];
Office of Rare Diseases Research; National Institutes of Health
[R01-AR33062, R01-AR47799]; Ruthrauff family; University of Alabama
Health Sciences Foundation; American College of Rheumatology Research
and Education; Arthritis Foundation; [P60-AR48095]; [P30-AR48311];
[M01-RR00032]; [5UL1RR025777]; [T32-AR07450]
FX We thank Debbie McDuffie and Judy Cain [University of Alabama at
Birmingham (UAB)] for technical support, Ed Phillips (UAB) for
assistance with microscopy, and all of the patients and normal donors
for their participation in these studies. The Vasculitis Clinical
Research Consortium has received support from the National Institute of
Arthritis and Musculoskeletal and Skin Diseases (U54AR057319), the
National Center for Research Resources (U54 RR019497), and the Office of
Rare Diseases Research. The Vasculitis Clinical Research Consortium is
part of the Rare Diseases Clinical Research Network. This work was
funded by National Institutes of Health Grants R01-AR33062 and
R01-AR47799, as well as by support from the Ruthrauff family; the
Methodology Core of the UAB Multidisciplinary Clinical Research Center
was supported by Grant P60-AR48095; the Flow Cytometry Core of the UAB
Rheumatic Diseases Core Center by Grant P30-AR48311; and the specimen
repository was supported, in part, by Grants M01-RR00032 and
5UL1RR025777. J.M.K. was supported by Grant T32-AR07450, the University
of Alabama Health Sciences Foundation, and the American College of
Rheumatology Research and Education Fund; and P.A. Monach was supported
by the Arthritis Foundation.
NR 35
TC 22
Z9 22
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 DEC 20
PY 2011
VL 108
IS 51
BP 20736
EP 20741
DI 10.1073/pnas.1109227109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865CW
UT WOS:000298289400093
PM 22147912
ER
PT J
AU Romanino, K
Mazelin, L
Albert, V
Conjard-Duplany, A
Lin, S
Bentzinger, CF
Handschin, C
Puigserver, P
Zorzato, F
Schaeffer, L
Gangloff, YG
Ruegg, MA
AF Romanino, Klaas
Mazelin, Laetitia
Albert, Verena
Conjard-Duplany, Agnes
Lin, Shuo
Bentzinger, C. Florian
Handschin, Christoph
Puigserver, Pere
Zorzato, Francesco
Schaeffer, Laurent
Gangloff, Yann-Gael
Rueegg, Markus A.
TI Myopathy caused by mammalian target of rapamycin complex 1 (mTORC1)
inactivation is not reversed by restoring mitochondrial function
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; SKELETAL-MUSCLE; PROTECTS;
METABOLISM; ACTIVATION; DYSTROPHY; AUTOPHAGY; ATROPHY; GROWTH; PGC-1
AB Mammalian target of rapamycin complex 1 (mTORC1) is central to the control of cell, organ, and body size. Skeletal muscle-specific inactivation of mTORC1 in mice results in smaller muscle fibers, fewer mitochondria, increased glycogen stores, and a progressive myopathy that causes premature death. In mTORC1-deficient muscles, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), which regulates mitochondrial biogenesis and glucose homeostasis, is strongly down-regulated. Here we tested whether induction of mitochondrial biogenesis pharmacologically or by the overexpression of PGC-1 alpha is sufficient to reverse the phenotype of mice deficient for mTORC1. We show that both approaches normalize mitochondrial function, such as oxidative capacity and expression of mitochondrial genes. However, they do not prevent or delay the progressive myopathy. In addition, we find that mTORC1 has a much stronger effect than PGC-1 alpha on the glycogen content in muscle. This effect is based on the strong activation of PKB/Akt in mTORC1-deficient mice. We also show that activation of PKB/Akt not only affects glycogen synthesis but also diminishes glycogen degradation. Thus, our work provides strong functional evidence that mitochondrial dysfunction in mice with inactivated mTORC1 signaling is caused by the down-regulation of PGC-1 alpha. However, our data also show that the impairment of mitochondria does not lead directly to the lethal myopathy.
C1 [Romanino, Klaas; Albert, Verena; Lin, Shuo; Bentzinger, C. Florian; Handschin, Christoph; Rueegg, Markus A.] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland.
[Mazelin, Laetitia; Schaeffer, Laurent; Gangloff, Yann-Gael] Univ Lyon 1, Ctr Natl Rech Sci, Unite Mixte Rech 5239, Ecole Normale Super Lyon,Lab Biol Mol Cellule,Equ, F-69365 Lyon, France.
[Conjard-Duplany, Agnes] Univ Lyon, Lab Biochim & Physiopathol Metab, Equipe Accueil Univ, Fac Med Lyon Est, F-69372 Lyon 8, France.
[Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Zorzato, Francesco] Univ Basel Hosp, Dept Anesthesia, CH-4031 Basel, Switzerland.
[Zorzato, Francesco] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland.
RP Ruegg, MA (reprint author), Univ Basel, Biozentrum, CH-4056 Basel, Switzerland.
EM markus-a.ruegg@unibas.ch
RI Bentzinger, C. Florian/A-1151-2015; Handschin, Christoph/E-6886-2015
OI Handschin, Christoph/0000-0003-0603-1097
FU Cantons of Basel-Stadt and Baselland; Swiss Foundation for Research on
Muscle Disease; Swiss Life; Association Francaise Contres les
Myopathies; Agence Nationale de la Recherche
FX We thank Arnaud Ferry from the Universite Pierre et Marie Curie-Paris
for measurement of muscle force of the mTOR- mice. We are
indebted to the animal (Le Plateau de Biologie Experimental de la
Souris) and microscopy (Plateau Technique Imagerie/Microscopie)
facilities of the Institut Federatif de Recherche 128 Biosciences. This
work was supported by grants from the Cantons of Basel-Stadt and
Baselland, the Swiss Foundation for Research on Muscle Disease, and
Swiss Life (to M.A.R.) and from the Association Francaise Contres les
Myopathies (to M.A.R., L.S., and Y.-G.G.) and the Agence Nationale de la
Recherche (to L.S. and Y.-G.G.).
NR 23
TC 20
Z9 20
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 20
PY 2011
VL 108
IS 51
BP 20808
EP 20813
DI 10.1073/pnas.1111448109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865CW
UT WOS:000298289400105
PM 22143799
ER
PT J
AU Grant, RW
Ashburner, JM
Hong, CC
Chang, YC
Barry, MJ
Atlas, SJ
AF Grant, Richard W.
Ashburner, Jeffrey M.
Hong, Clemens C.
Chang, Yuchiao
Barry, Michael J.
Atlas, Steve J.
TI Defining Patient Complexity From the Primary Care Physician's
Perspective A Cohort Study
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID QUALITY-OF-CARE; SATISFACTION; VALIDATION; DISEASE; HEALTH
AB Background: Patients with complex health needs are increasingly the focus of health system redesign.
Objective: To characterize complex patients, as defined by their primary care physicians (PCPs), and to compare this definition with other commonly used algorithms.
Design: Cohort study.
Setting: 1 hospital-based practice, 4 community health centers, and 7 private practices in a primary care network in the United States.
Participants: 40 physicians who reviewed a random sample of 120 of their own patients.
Measurements: After excluding patients for whom they were not directly responsible, PCPs indicated which of their patients they considered complex. These patients were characterized, independent predictors of complexity were identified, and PCP-defined complexity was compared with 3 comorbidity-based methods (Charlson score, Higashi score, and a proprietary Centers for Medicare & Medicaid Services algorithm).
Results: Physicians identified 1126 of their 4302 eligible patients (26.2%) as complex and assigned a mean of 2.2 domains of complexity per patient (median, 2.0 [interquartile range, 1 to 3]). Mental health and substance use were identified as major issues in younger complex patients, whereas medical decision making and care coordination predominated in older patients (P < 0.001 for trends by decade). Major independent predictors of PCP-defined complexity (P < 0.001) included age (probability of complexity increased from 14.8% to 19.8% with age increasing from 55 to 65 years), poorly controlled diabetes (from 12.7% to 47.6% if hemoglobin A(1c) level >= 9%), use of antipsychotics (from 12.7% to 31.8%), alcohol-related diagnoses (from 12.9% to 27.4%), and inadequate insurance (from 12.5% to 19.2%). Classification agreement for complex patients ranged from 26.2% to 56.0% when PCP assignment was compared with each of the other methods.
Limitation: Results may not be generalizable to other primary care settings.
Conclusion: Primary care physicians identified approximately one quarter of their patients as complex. Medical, social, and behavioral factors all contributed to PCP-defined complexity. Physician-defined complexity had only modest agreement with 3 comorbidity-based algorithms.
C1 Harvard Univ, Sch Med, Boston, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Grant, Richard W.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA.
RP Grant, RW (reprint author), Kaiser Permanente, Div Res, 2101 Webster St,20th Floor, Oakland, CA 94612 USA.
EM Richard.W.Grant@KP.org; satlas@partners.org
OI Grant, Richard/0000-0002-6164-8025
FU Partners Community Healthcare, Inc.
FX Grant Support: By the Systems Improvement Grant Program of Partners
Community Healthcare, Inc.
NR 24
TC 50
Z9 50
U1 3
U2 21
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 DEC 20
PY 2011
VL 155
IS 12
BP 797
EP U39
DI 10.7326/0003-4819-155-12-201112200-00001
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA 864ZU
UT WOS:000298280500013
PM 22184686
ER
PT J
AU Zulman, DM
Nazi, KM
Turvey, CL
Wagner, TH
Woods, SS
An, LC
AF Zulman, Donna M.
Nazi, Kim M.
Turvey, Carolyn L.
Wagner, Todd H.
Woods, Susan S.
An, Larry C.
TI Patient Interest in Sharing Personal Health Record Information A
Web-Based Survey
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID SHARED MEDICAL-RECORD; SATISFACTION; EXCHANGE
AB Background: Electronic personal health record (PHR) systems are proliferating but largely have not realized their potential for enhancing communication among patients and their network of care providers.
Objective: To explore preferences about sharing electronic health information among users of the U.S. Department of Veterans Affairs (VA) PHR system, My HealtheVet.
Design: Web-based survey of a convenience sample.
Setting: My HealtheVet Web site from 7 July through 4 October 2010.
Participants: 18 471 users of My HealtheVet.
Measurements: Interest in shared PHR access and preferences about who would receive access, the information that would be shared, and the activities that users would delegate.
Results: Survey respondents were predominantly men (92%) and aged 50 to 64 years (51%) or 65 years or older (39%); approximately 39% reported poor or fair health status. Almost 4 of 5 respondents (79%) were interested in sharing access to their PHR with someone outside of their health system (62% with a spouse or partner, 23% with a child, 15% with another family member, and 25% with a non-VA health care provider). Among those who selected a family member other than a spouse or partner, 47% lived apart from the specified person. Preferences about degree of access varied on the basis of the type of information being shared, the type of activity being performed, and the respondent's relationship with the selected person.
Limitations: The survey completion rate was 40.8%. Results might not be generalizable to all My HealtheVet users.
Conclusion: In a large survey of PHR users in the VA system, most respondents were interested in sharing access to their electronic health information with caregivers and non-VA providers. Existing and evolving PHR systems should explore secure mechanisms for shared PHR access to improve information exchange among patients and the multiple persons involved in their health care.
C1 [Zulman, Donna M.] Stanford Univ, Ctr Hlth Care Evaluat, VA Palo Alto Hlth Care Syst, Menlo Pk, CA 94025 USA.
Vet Rural Hlth Resource Ctr Cent Reg, Iowa City, IA USA.
Vet Affairs Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA USA.
US Dept Vet Affairs, Washington, DC USA.
Vet Affairs Hlth Serv Res & Dev Serv, Portland, OR USA.
Univ Michigan, Ctr Hlth Commun Res, Ann Arbor, MI 48109 USA.
RP Zulman, DM (reprint author), Stanford Univ, Ctr Hlth Care Evaluat, VA Palo Alto Hlth Care Syst, 795 Willow Rd,152-MPD, Menlo Pk, CA 94025 USA.
EM dzulman@stanford.edu
FU Veterans Health Administration; Robert Wood Johnson Foundation
FX Grant Support: By the Veterans Health Administration and The Robert Wood
Johnson Foundation Clinical Scholars Program.
NR 31
TC 49
Z9 49
U1 5
U2 17
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 DEC 20
PY 2011
VL 155
IS 12
BP 805
EP U46
DI 10.7326/0003-4819-155-12-201112200-00002
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 864ZU
UT WOS:000298280500014
PM 22184687
ER
PT J
AU Jena, AB
Goldman, DP
Foster, SE
Califano, JA
AF Jena, Anupam B.
Goldman, Dana P.
Foster, Susan E.
Califano, Joseph A., Jr.
TI Prescription Medication Abuse and Illegitimate Internet-Based Pharmacies
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID UNITED-STATES; DRUGS
AB Abuse of controlled prescription medications in the United States exceeds that of all illicit drugs combined except marijuana and has grown considerably in the past decade. Although available through traditional channels, controlled prescription medications can also be purchased on the Internet without a prescription. This issue has gained the attention of federal regulators, law enforcement, and the media, but physician awareness of the problem is scarce. This article describes the nature of the problem and its magnitude, discusses the challenges to federal and private efforts to combat illegitimate online pharmacies, and outlines strategies for physicians to recognize and minimize the unwarranted effects of the availability of these medications on the Internet.
C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Wang Ambulatory Care Ctr, Boston, MA 02114 USA.
Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA.
RAND Corp, Santa Monica, CA USA.
Columbia Univ, Natl Ctr Addict & Substance Abuse, New York, NY USA.
RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Wang Ambulatory Care Ctr, 15 Parkman St, Boston, MA 02114 USA.
EM jena.anupam@mgh.harvard.edu
NR 18
TC 11
Z9 11
U1 2
U2 33
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 DEC 20
PY 2011
VL 155
IS 12
BP 848
EP 850
DI 10.7326/0003-4819-155-12-201112200-00008
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 864ZU
UT WOS:000298280500019
PM 22184692
ER
PT J
AU Xiao, WZ
Mindrinos, MN
Seok, J
Cuschieri, J
Cuenca, AG
Gao, H
Hayden, DL
Hennessy, L
Moore, EE
Minei, JP
Bankey, PE
Johnson, JL
Sperry, J
Nathens, AB
Billiar, TR
West, MA
Brownstein, BH
Mason, PH
Baker, HV
Finnerty, CC
Jeschke, MG
Lopez, MC
Klein, MB
Gamelli, RL
Gibran, NS
Arnoldo, B
Xu, WH
Zhang, YP
Calvano, SE
McDonald-Smith, GP
Schoenfeld, DA
Storey, JD
Cobb, JP
Warren, HS
Moldawer, LL
Herndon, DN
Lowry, SF
Maier, RV
Davis, RW
Tompkins, RG
AF Xiao, Wenzhong
Mindrinos, Michael N.
Seok, Junhee
Cuschieri, Joseph
Cuenca, Alex G.
Gao, Hong
Hayden, Douglas L.
Hennessy, Laura
Moore, Ernest E.
Minei, Joseph P.
Bankey, Paul E.
Johnson, Jeffrey L.
Sperry, Jason
Nathens, Avery B.
Billiar, Timothy R.
West, Michael A.
Brownstein, Bernard H.
Mason, Philip H.
Baker, Henry V.
Finnerty, Celeste C.
Jeschke, Marc G.
Lopez, M. Cecilia
Klein, Matthew B.
Gamelli, Richard L.
Gibran, Nicole S.
Arnoldo, Brett
Xu, Weihong
Zhang, Yuping
Calvano, Steven E.
McDonald-Smith, Grace P.
Schoenfeld, David A.
Storey, John D.
Cobb, J. Perren
Warren, H. Shaw
Moldawer, Lyle L.
Herndon, David N.
Lowry, Stephen F.
Maier, Ronald V.
Davis, Ronald W.
Tompkins, Ronald G.
CA Inflammation Host Response Injury
TI A genomic storm in critically injured humans
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID SCALE COLLABORATIVE PROJECT; ORIENTED RESEARCH CORE; STANDARD OPERATING
PROCEDURES; MULTIPLE ORGAN FAILURE; CLINICAL CARE; HOST RESPONSE; TRAUMA
PATIENT; GENE-EXPRESSION; IMMUNE-SYSTEM; INFLAMMATION
AB Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected "genomic storm." In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.
C1 [Xiao, Wenzhong; Mason, Philip H.; McDonald-Smith, Grace P.; Tompkins, Ronald G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA.
[Hayden, Douglas L.; Schoenfeld, David A.; Warren, H. Shaw; Inflammation Host Response Injury] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA.
[Cobb, J. Perren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care Med & Pain Med, Boston, MA 02114 USA.
[Xiao, Wenzhong; Mindrinos, Michael N.; Seok, Junhee; Gao, Hong; Xu, Weihong; Zhang, Yuping; Davis, Ronald W.] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA.
[Cuenca, Alex G.; Baker, Henry V.; Lopez, M. Cecilia; Moldawer, Lyle L.] Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA.
[Cuschieri, Joseph; Hennessy, Laura; Klein, Matthew B.; Gibran, Nicole S.; Maier, Ronald V.] Univ Washington, Sch Med, Dept Surg, Harborview Med Ctr, Seattle, WA 98104 USA.
[Moore, Ernest E.; Johnson, Jeffrey L.] Univ Colorado, Dept Surg, Denver, CO 80045 USA.
[Minei, Joseph P.; Arnoldo, Brett] Univ Texas SW Med Ctr Dallas, Dept Surg, Parkland Mem Hosp, Dallas, TX 75390 USA.
[Bankey, Paul E.] Univ Rochester, Dept Surg, Med Ctr, Rochester, NY 14642 USA.
[Billiar, Timothy R.] Univ Pittsburgh, Dept Surg, Presbyterian Med Ctr, Univ Hosp, Pittsburgh, PA 15213 USA.
[Nathens, Avery B.] St Michaels Hosp, Dept Surg, Toronto, ON M5B 1W8, Canada.
[West, Michael A.] Univ Calif San Francisco, Dept Surg, San Francisco Gen Hosp, San Francisco, CA 94110 USA.
[Brownstein, Bernard H.] Washington Univ, Dept Surg, Sch Med St Louis, St Louis, MO 63110 USA.
[Finnerty, Celeste C.; Herndon, David N.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA.
[Jeschke, Marc G.] Univ Toronto, Dept Surg, Div Plast & Reconstruct Surg, Toronto, ON M5G 1L5, Canada.
[Gamelli, Richard L.] Loyola Univ, Dept Surg, Stritch Sch Med, Maywood, IL 60153 USA.
[Calvano, Steven E.; Lowry, Stephen F.] Univ Med & Dent New Jersey, Dept Surg, Robert Wood Johnson Med Sch, New Brunswick, NJ 08901 USA.
[Storey, John D.] Princeton Univ, Dept Mol Biol, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
RP Tompkins, RG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA.
EM rtompkins@partners.org
RI Xu, Weihong/C-4175-2012;
OI xiao, wenzhong/0000-0003-4944-6380; Baker, Henry/0000-0002-8273-5320
FU National Institute of General Medical Sciences; [5U54 GM-062119-10]
FX This work was supported by grant 5U54 GM-062119-10, entitled
Inflammation and the Host Response to Injury, a Large-Scale
Collaborative Research Program (Glue Grant) funded by the National
Institute of General Medical Sciences. The clinical trial number
(ClinicalTrials.gov) is NCT00257231.
NR 40
TC 293
Z9 302
U1 6
U2 31
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD DEC 19
PY 2011
VL 208
IS 13
BP 2581
EP 2590
DI 10.1084/jem.20111354
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 875PT
UT WOS:000299045000005
PM 22110166
ER
PT J
AU Li, M
Mukasa, A
del-Mar Inda, M
Zhang, JH
Chin, L
Cavenee, W
Furnari, F
AF Li, Ming
Mukasa, Akitake
del-Mar Inda, Maria
Zhang, Jianhua
Chin, Lynda
Cavenee, Webster
Furnari, Frank
TI Guanylate binding protein 1 is a novel effector of EGFR-driven invasion
in glioblastoma
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID EPIDERMAL-GROWTH-FACTOR; CONFERS ENHANCED TUMORIGENICITY; FACTOR
RECEPTOR COMMON; GLIOMA-CELL INVASION; MATRIX METALLOPROTEINASES;
ENDOTHELIAL-CELLS; INFLAMMATORY CYTOKINES; NUCLEOTIDE-BINDING; MALIGNANT
GLIOMAS; TISSUE INHIBITORS
AB Although GBP1 (guanylate binding protein 1) was among the first interferon-inducible proteins identified, its function is still largely unknown. Epidermal growth factor receptor (EGFR) activation by amplification or mutation is one of the most frequent genetic lesions in a variety of human tumors. These include glioblastoma multiforme (GBM), which is characterized by independent but interrelated features of extensive invasion into normal brain parenchyma, rapid growth, necrosis, and angiogenesis. In this study, we show that EGFR activation promoted GBP1 expression in GBM cell lines through a signaling pathway involving Src and p38 mitogen-activated protein kinase. Moreover, we identified YY1 (Yin Yang 1) as the downstream transcriptional regulator regulating EGFR-driven GBP1 expression. GBP1 was required for EGFR-mediated MMP1 (matrix metalloproteinase 1) expression and glioma cell invasion in vitro. Although deregulation of GBP1 expression did not affect glioma cell proliferation, overexpression of GBP1 enhanced glioma cell invasion through MMP1 induction, which required its C-terminal helical domain and was independent of its GTPase activity. Reducing GBP1 levels by RNA interference in invasive GBM cells also markedly inhibited their ability to infiltrate the brain parenchyma of mice. GBP1 expression was high and positively correlated with EGFR expression in human GBM tumors and cell lines, particularly those of the neural subtype. Together, these findings establish GBP1 as a previously unknown link between EGFR activity and MMP1 expression and nominate it as a novel potential therapeutic target for inhibiting GBM invasion.
C1 [Li, Ming; Mukasa, Akitake; del-Mar Inda, Maria; Cavenee, Webster; Furnari, Frank] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
[Zhang, Jianhua; Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Zhang, Jianhua; Chin, Lynda] Harvard Univ, Sch Med, Boston, MA 02215 USA.
RP Furnari, F (reprint author), Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
EM ffurnari@ucsd.edu
RI li, ming/F-3495-2013
FU Goldhirsh Foundation; National Institutes of Health [P01-CA95616];
American Brain Tumor Association
FX This work was supported by an award from the Goldhirsh Foundation (to F.
Furnari) and National Institutes of Health grant P01-CA95616 (to W.
Cavenee, F. Furnari, and L. Chin). W. Cavenee is a fellow of the
National Foundation for Cancer Research. M. Li is partially supported by
an American Brain Tumor Association Fellowship in honor of Richard
Schaffner.
NR 53
TC 24
Z9 24
U1 0
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD DEC 19
PY 2011
VL 208
IS 13
BP 2657
EP 2673
DI 10.1084/jem.20111102
PG 17
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 875PT
UT WOS:000299045000013
PM 22162832
ER
PT J
AU Bezman, NA
Chakraborty, T
Bender, T
Lanier, LL
AF Bezman, Natalie A.
Chakraborty, Tirtha
Bender, Timothy
Lanier, Lewis L.
TI miR-150 regulates the development of NK and iNKT cells
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID NATURAL-KILLER-CELLS; RECEPTOR-GAMMA-CHAIN; FACTOR C-MYB; MHC CLASS-I;
TRANSCRIPTION FACTOR; T-CELL; B-CELL; GENE-EXPRESSION; INHIBITORY
RECEPTORS; LY49 RECEPTORS
AB Natural killer (NK) and invariant NK T (iNKT) cells are critical in host defense against pathogens and for the initiation of adaptive immune responses. miRNAs play important roles in NK and iNKT cell development, maturation, and function, but the roles of specific miRNAs are unclear. We show that modulation of miR-150 expression levels has a differential effect on NK and iNKT cell development. Mice with a targeted deletion of miR-150 have an impaired, cell lineage-intrinsic defect in their ability to generate mature NK cells. Conversely, a gain-of-function miR-150 transgene promotes the development of NK cells, which display a more mature phenotype and are more responsive to activation. In contrast, overexpression of miR-150 results in a substantial reduction of iNKT cells in the thymus and in the peripheral lymphoid organs. The transcription factor c-Myb has been shown to be a direct target of miR-150. Our finding of increased NK cell and decreased iNKT cell frequencies in Myb heterozygous bone marrow chimeras suggests that miR-150 differentially controls the development of NK and iNKT cell lineages by targeting c-Myb.
C1 [Bezman, Natalie A.; Lanier, Lewis L.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
[Bezman, Natalie A.; Lanier, Lewis L.] Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA.
[Chakraborty, Tirtha] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Chakraborty, Tirtha] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Bender, Timothy] Univ Virginia Hlth Syst, Dept Microbiol, Charlottesville, VA 22908 USA.
RP Lanier, LL (reprint author), Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
EM lewis.lanier@ucsf.edu
FU National Institutes of Health (NIH) [AI068129]; American Cancer Society
[117346-PF-09186-01-LIB]
FX T. Chakraborty was supported by grants from the National Institutes of
Health (NIH) to K. Rajewsky. N.A. Bezman is supported by post-doctoral
fellowship (117346-PF-09186-01-LIB) from the American Cancer Society.
This study was supported by NIH grant AI068129 and L. L. Lanier is an
American Cancer Society Professor.
NR 68
TC 86
Z9 91
U1 0
U2 10
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD DEC 19
PY 2011
VL 208
IS 13
BP 2717
EP 2731
DI 10.1084/jem.20111386
PG 15
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 875PT
UT WOS:000299045000017
PM 22124110
ER
PT J
AU Wesemann, DR
Magee, JM
Boboila, C
Calado, DP
Gallagher, MP
Portuguese, AJ
Manis, JP
Zhou, XL
Recher, M
Rajewsky, K
Notarangelo, LD
Alt, FW
AF Wesemann, Duane R.
Magee, Jennifer M.
Boboila, Cristian
Calado, Dinis Pedro
Gallagher, Michael P.
Portuguese, Andrew J.
Manis, John P.
Zhou, Xiaolong
Recher, Mike
Rajewsky, Klaus
Notarangelo, Luigi D.
Alt, Frederick W.
TI Immature B cells preferentially switch to IgE with increased direct S mu
to S epsilon recombination
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID SERUM IMMUNOGLOBULIN-E; END-JOINING PATHWAY; HEAVY-CHAIN GENE;
NF-KAPPA-B; V(D)J RECOMBINATION; IL-4 INDUCTION; RAG MUTATIONS;
BONE-MARROW; TRANSCRIPTION; EXPRESSION
AB Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces initially expressed C mu (IgM) constant regions (C(H)) exons with downstream C(H) exons. Stimulation of B cells with anti-CD40 plus interleukin-4 induces CSR from C mu to C gamma 1 (IgG1) and C epsilon (IgE), the latter of which contributes to the pathogenesis of atopic diseases. Although C epsilon CSR can occur directly from C mu, most mature peripheral B cells undergo CSR to C epsilon indirectly, namely from C mu to C gamma 1, and subsequently to C epsilon. Physiological mechanisms that influence CSR to C gamma 1 versus C. are incompletely understood. In this study, we report a role for B cell developmental maturity in IgE CSR. Based in part on a novel flow cytometric IgE CSR assay, we show that immature B cells preferentially switch to IgE versus IgG1 through a mechanism involving increased direct CSR from C mu to C epsilon. Our findings suggest that IgE dysregulation in certain immunodeficiencies may be related to impaired B cell maturation.
C1 [Wesemann, Duane R.; Magee, Jennifer M.; Boboila, Cristian; Calado, Dinis Pedro; Gallagher, Michael P.; Portuguese, Andrew J.; Zhou, Xiaolong; Rajewsky, Klaus; Alt, Frederick W.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Wesemann, Duane R.; Magee, Jennifer M.; Boboila, Cristian; Calado, Dinis Pedro; Gallagher, Michael P.; Portuguese, Andrew J.; Zhou, Xiaolong; Rajewsky, Klaus; Alt, Frederick W.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
[Recher, Mike; Notarangelo, Luigi D.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
[Manis, John P.] Childrens Hosp, Joint Program Transfus Med, Boston, MA 02115 USA.
[Manis, John P.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA.
[Wesemann, Duane R.; Magee, Jennifer M.; Boboila, Cristian; Gallagher, Michael P.; Portuguese, Andrew J.; Zhou, Xiaolong; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Wesemann, Duane R.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Wesemann, Duane R.; Magee, Jennifer M.; Boboila, Cristian; Gallagher, Michael P.; Portuguese, Andrew J.; Zhou, Xiaolong; Alt, Frederick W.] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Alt, FW (reprint author), Childrens Hosp, Program Cellular & Mol Med, 300 Longwood Ave, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu
RI Notarangelo, Luigi/F-9718-2016
OI Notarangelo, Luigi/0000-0002-8335-0262
FU National Institutes of Health [AI077595, AI076210, 5P01AI076210-02, R21
CA133781, K08AI89972]; Swiss National Science foundation (SNSF);
American Association of Allergy Asthma and Immunology; Burroughs
Wellcome Fund; CSL-Behring
FX This work was supported by National Institutes of Health grants AI077595
(to F. W. Alt), AI076210 (to F. W. Alt and L. D. Notarangelo),
5P01AI076210-02 (to L. D. Notarangelo), R21 CA133781 (to J.P. Manis),
and K08AI89972 (to D. R. Wesemann). M. Recher was supported by a grant
from the Swiss National Science foundation (SNSF). D. R. Wesemann was
also supported by an award from the American Association of Allergy
Asthma and Immunology and CSL-Behring, and holds a Career Award for
Medical Scientists from the Burroughs Wellcome Fund. F. W. Alt is an
Investigator of the Howard Hughes Medical Institute.
NR 67
TC 43
Z9 44
U1 0
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD DEC 19
PY 2011
VL 208
IS 13
BP 2733
EP 2746
DI 10.1084/jem.20111155
PG 14
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 875PT
UT WOS:000299045000018
PM 22143888
ER
PT J
AU Frazier-Wood, AC
Glasser, S
Garvey, WT
Kabagambe, EK
Borecki, IB
Tiwari, HK
Tsai, MY
Hopkins, PN
Ordovas, JM
Arnett, DK
AF Frazier-Wood, Alexis C.
Glasser, Stephen
Garvey, W. Timothy
Kabagambe, Edmond K.
Borecki, Ingrid B.
Tiwari, Hemant K.
Tsai, Michael Y.
Hopkins, Paul N.
Ordovas, Jose M.
Arnett, Donna K.
TI A clustering analysis of lipoprotein diameters in the metabolic syndrome
SO LIPIDS IN HEALTH AND DISEASE
LA English
DT Article
DE lipoprotein particle diameter; insulin resistance; nuclear resonance
spectroscopy; Metabolic Syndrome; latent class analysis; GOLDN; waist
circumference; hypertension; hypertriglyceridemia; fasting glucose
ID NUCLEAR-MAGNETIC-RESONANCE; INSULIN-RESISTANCE ATHEROSCLEROSIS; LDL
SIZE; PARTICLE-SIZE; MEN; HYPERINSULINEMIA; DISEASE
AB Background: The presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low-and high-density lipoprotein (VLDL HDL) particle diameters with components of the metabolic syndrome (MetS), although this has been the focus of less research. We aimed to explore the relationship of VLDL, LDL and HDL diameters to MetS and its features, and by clustering individuals by their diameters of VLDL, LDL and HDL particles, to capture information across all three fractions of lipoprotein into a unified phenotype.
Methods: We used nuclear magnetic resonance spectroscopy measurements on fasting plasma samples from a general population sample of 1,036 adults (mean +/- SD, 48.8 +/- 16.2 y of age). Using latent class analysis, the sample was grouped by the diameter of their fasting lipoproteins, and mixed effects models tested whether the distribution of MetS components varied across the groups.
Results: Eight discrete groups were identified. Two groups (N = 251) were enriched with individuals meeting criteria for the MetS, and were characterized by the smallest LDL/HDL diameters. One of those two groups, one was additionally distinguished by large VLDL, and had significantly higher blood pressure, fasting glucose, triglycerides, and waist circumference (WC; P < .001). However, large VLDL, in the absence of small LDL and HDL particles, did not associate with MetS features. These associations held after additionally controlling for VLDL, LDL and HDL particle concentrations.
Conclusions: While small LDL diameters remain associated with IR and the MetS, the occurrence of these in conjunction with a shift to overall larger VLDL diameter may identify those with the highest fasting glucose, TG and WC within the MetS. If replicated, the association of this phenotype with more severe IR-features indicated that it may contribute to identifying of those most at risk for incident type II diabetes and cardiometabolic disease.
C1 [Frazier-Wood, Alexis C.; Kabagambe, Edmond K.; Arnett, Donna K.] Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Frazier-Wood, Alexis C.; Tiwari, Hemant K.] Univ Alabama, Dept Biostat, Sect Stat Genet, Sch Publ Hlth, Birmingham, AL 35294 USA.
[Glasser, Stephen] Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA.
[Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA.
[Kabagambe, Edmond K.; Arnett, Donna K.] Univ Alabama, Sch Publ Hlth, Nutr Obes Res Ctr, Birmingham, AL 35294 USA.
[Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
[Tsai, Michael Y.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Hopkins, Paul N.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA.
[Ordovas, Jose M.] Tufts Univ, JM USDA HNRCA, Boston, MA 02111 USA.
[Ordovas, Jose M.] CNIC, Dept Epidemiol & Populat Genet, Madrid, Spain.
[Ordovas, Jose M.] IMDEA Food, Madrid, Spain.
RP Frazier-Wood, AC (reprint author), Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
EM LekkiWood@Gmail.com
RI Frazier-Wood, Alexis (Lekki)/B-8053-2010
OI Frazier-Wood, Alexis (Lekki)/0000-0001-7616-2119
FU NHLBI [U01HL072524]
FX This study was funded by NHLBI grant number U01HL072524. Financial
disclosures: None to declare. Disclosure: All authors declare that they
have no conflicts of interests.
NR 19
TC 3
Z9 4
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-511X
J9 LIPIDS HEALTH DIS
JI Lipids Health Dis.
PD DEC 19
PY 2011
VL 10
AR 237
DI 10.1186/1476-511X-10-237
PG 8
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 878SQ
UT WOS:000299277300001
PM 22182248
ER
PT J
AU Chan, AT
Lippman, SM
AF Chan, Andrew T.
Lippman, Scott M.
TI Aspirin and colorectal cancer prevention in Lynch syndrome
SO LANCET
LA English
DT Editorial Material
ID RANDOMIZED-TRIALS; RESISTANT STARCH
C1 [Lippman, Scott M.] Univ Texas MD Anderson Canc Ctr, Dept Thorac, Houston, TX 77030 USA.
[Lippman, Scott M.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Med Oncol, Houston, TX 77030 USA.
[Lippman, Scott M.] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA.
[Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA.
[Chan, Andrew T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA.
RP Lippman, SM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Thorac, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM slippman@mdanderson.org
NR 11
TC 10
Z9 10
U1 0
U2 4
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 DEC 17
PY 2011
VL 378
IS 9809
BP 2051
EP 2052
DI 10.1016/S0140-6736(11)61216-6
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 865EL
UT WOS:000298293600011
PM 22036018
ER
PT J
AU Zhang, L
Jiang, BN
Wu, YK
Strouthos, C
Sun, PZ
Su, J
Zhou, XB
AF Zhang, Le
Jiang, Beini
Wu, Yukun
Strouthos, Costas
Sun, Phillip Zhe
Su, Jing
Zhou, Xiaobo
TI Developing a multiscale, multi-resolution agent-based brain tumor model
by graphics processing units
SO THEORETICAL BIOLOGY AND MEDICAL MODELLING
LA English
DT Article
ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR; MULTICELLULAR PATTERNS;
EGF-RECEPTOR; CANCER; DYNAMICS; SYSTEMS; PHENOTYPES; MIGRATION; THERAPY
AB Multiscale agent-based modeling (MABM) has been widely used to simulate Glioblastoma Multiforme (GBM) and its progression. At the intracellular level, the MABM approach employs a system of ordinary differential equations to describe quantitatively specific intracellular molecular pathways that determine phenotypic switches among cells (e. g. from migration to proliferation and vice versa). At the intercellular level, MABM describes cell-cell interactions by a discrete module. At the tissue level, partial differential equations are employed to model the diffusion of chemoattractants, which are the input factors of the intracellular molecular pathway. Moreover, multiscale analysis makes it possible to explore the molecules that play important roles in determining the cellular phenotypic switches that in turn drive the whole GBM expansion. However, owing to limited computational resources, MABM is currently a theoretical biological model that uses relatively coarse grids to simulate a few cancer cells in a small slice of brain cancer tissue. In order to improve this theoretical model to simulate and predict actual GBM cancer progression in real time, a graphics processing unit (GPU)-based parallel computing algorithm was developed and combined with the multi-resolution design to speed up the MABM. The simulated results demonstrated that the GPU-based, multi-resolution and multiscale approach can accelerate the previous MABM around 30-fold with relatively fine grids in a large extracellular matrix. Therefore, the new model has great potential for simulating and predicting real-time GBM progression, if real experimental data are incorporated.
C1 [Zhang, Le; Jiang, Beini] Michigan Technol Univ, Dept Math Sci, Houghton, MI 49931 USA.
[Zhang, Le] Southwest Univ, Coll Comp & Informat Sci, Chongqing 400715, Peoples R China.
[Wu, Yukun] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
[Strouthos, Costas] Cyprus Inst, Computat Based Sci & Technol Res Ctr, CY-1645 Nicosia, Cyprus.
[Sun, Phillip Zhe] Massachusetts Gen Hosp, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA USA.
[Su, Jing; Zhou, Xiaobo] Methodist Hosp, Dept Pathol, Res Inst, Houston, TX 77030 USA.
[Su, Jing; Zhou, Xiaobo] Weill Cornell Med Coll, Houston, TX USA.
RP Zhang, L (reprint author), Michigan Technol Univ, Dept Math Sci, Houghton, MI 49931 USA.
EM zhangle@mtu.edu; XZhou@tmhs.org
RI Wu, Yukun/G-4292-2012; Su, Jing/B-3171-2013; Strouthos,
Costas/C-7086-2011;
OI Strouthos, Costas/0000-0001-9972-6925; Su, Jing/0000-0003-4917-6173
FU Michigan Tech University
FX This work has been supported by a start-up grant from Michigan Tech
University to Prof. Le Zhang.
NR 47
TC 4
Z9 4
U1 1
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4682
J9 THEOR BIOL MED MODEL
JI Theor. Biol. Med. Model.
PD DEC 16
PY 2011
VL 8
AR 46
DI 10.1186/1742-4682-8-46
PG 17
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 919AX
UT WOS:000302294100001
PM 22176732
ER
PT J
AU Matthews, LT
Ribaudo, HJ
Parekh, NK
Chen, JY
Binda, K
Ogwu, A
Makhema, J
Souda, S
Lockman, S
Essex, M
Shapiro, RL
AF Matthews, Lynn T.
Ribaudo, Heather J.
Parekh, Natasha K.
Chen, Jennifer Y.
Binda, Kelebogile
Ogwu, Anthony
Makhema, Joseph
Souda, Sajini
Lockman, Shahin
Essex, Max
Shapiro, Roger L.
TI Birth weight for gestational age norms for a large cohort of infants
born to HIV-negative women in Botswana compared with norms for U.S.-born
black infants
SO BMC PEDIATRICS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS-INFECTION; INTRAUTERINE GROWTH-RETARDATION;
PREGNANCY OUTCOMES; UNITED-STATES; ANTIRETROVIRAL THERAPY; HEAD
CIRCUMFERENCE; PERCENTILES; MORTALITY; PRETERM; RISK
AB Background: Standard values for birth weight by gestational age are not available for sub-Saharan Africa, but are needed to evaluate incidence and risk factors for intrauterine growth retardation in settings where HIV, antiretrovirals, and other in utero exposures may impact birth outcomes.
Methods: Birth weight data were collected from six hospitals in Botswana. Infants born to HIV-negative women between 26-44 weeks gestation were analyzed to construct birth weight for gestational age charts. These data were compared with published norms for black infants in the United States.
Results: During a 29 month period from 2007-2010, birth records were reviewed in real-time from 6 hospitals and clinics in Botswana. Of these, 11,753 live infants born to HIV-negative women were included in the analysis. The median gestational age at birth was 39 weeks (1st quartile 38, 3rd quartile 40 weeks), and the median birth weight was 3100 grams (1st quartile 2800, 3rd quartile 3400 grams). We constructed estimated percentile curves for birth weight by gestational age which demonstrate increasing slope during the third trimester and leveling off beyond 40 weeks. Compared with black infants in the United States, Botswana-born infants had lower median birth weight for gestational age from weeks 37 through 42 (p < .02).
Conclusions: We present birth weight for gestational age norms for Botswana, which are lower at term than norms for black infants in the United States. These findings suggest the importance of regional birth weight norms to identify and define risk factors for higher risk births. These data serve as a reference for Botswana, may apply to southern Africa, and may help to identify infants at risk for perinatal complications and inform comparisons among infants exposed to HIV and antiretrovirals in utero.
C1 [Matthews, Lynn T.; Shapiro, Roger L.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02115 USA.
[Matthews, Lynn T.] Massachusetts Gen Hosp, Div Infect Dis, Ctr Global Hlth, Boston, MA 02114 USA.
[Essex, Max] Harvard Univ, Sch Publ Hlth, Dept Immunol, Boston, MA 02115 USA.
[Essex, Max] Harvard Univ, Sch Publ Hlth, Dept Infect Dis, Boston, MA 02115 USA.
[Chen, Jennifer Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Binda, Kelebogile; Ogwu, Anthony; Makhema, Joseph; Souda, Sajini] Botswana Harvard AIDS Inst, Gaborone, Botswana.
[Lockman, Shahin] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Parekh, Natasha K.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
RP Matthews, LT (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 110 Francis St,Lowry Med Off Bldg,Suite GB, Boston, MA 02115 USA.
EM ltmatthe@bidmc.harvard.edu
FU Burroughs Wellcome Fund; American Society for Tropical Medicine and
Hygiene; K23 award [MH095655]; Harvard University Center for AIDS
Research Biostatistical Core (NIH) [AI060354]; Centers for Disease
Control and Prevention
FX Dr. Matthews is supported by a postdoctoral fellowship in infectious
diseases from the Burroughs Wellcome Fund and the American Society for
Tropical Medicine and Hygiene and by a K23 award (MH095655). Dr.
Ribaudo's work was supported by the Harvard University Center for AIDS
Research Biostatistical Core (NIH #AI060354). Dr. Shapiros' work was
supported by a grant from the Centers for Disease Control and Prevention
(President's Emergency Plan for AIDS Relief).
NR 52
TC 6
Z9 6
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2431
J9 BMC PEDIATR
JI BMC Pediatr.
PD DEC 16
PY 2011
VL 11
AR 115
DI 10.1186/1471-2431-11-115
PG 8
WC Pediatrics
SC Pediatrics
GA 891XG
UT WOS:000300249500002
PM 22176889
ER
PT J
AU Chen, M
Wang, K
Zhang, L
Li, C
Yang, YL
AF Chen, Min
Wang, Kai
Zhang, Liang
Li, Cheng
Yang, Yongliang
TI The Discovery of Putative Urine Markers for the Specific Detection of
Prostate Tumor by Integrative Mining of Public Genomic Profiles
SO PLOS ONE
LA English
DT Article
ID GENE-EXPRESSION PROFILES; CANCER PROGRESSION; BIOMARKERS; NETWORKS;
DATABASE; ANGIOGENESIS; CYTOSCAPE
AB Urine has emerged as an attractive biofluid for the noninvasive detection of prostate cancer (PCa). There is a strong imperative to discover candidate urinary markers for the clinical diagnosis and prognosis of PCa. The rising flood of various omics profiles presents immense opportunities for the identification of prospective biomarkers. Here we present a simple and efficient strategy to derive candidate urine markers for prostate tumor by mining cancer genomic profiles from public databases. Prostate, bladder and kidney are three major tissues from which cellular matters could be released into urine. To identify urinary markers specific for PCa, upregulated entities that might be shed in exosomes of bladder cancer and kidney cancer are first excluded. Through the ontology-based filtering and further assessment, a reduced list of 19 entities encoding urinary proteins was derived as putative PCa markers. Among them, we have found 10 entities closely associated with the process of tumor cell growth and development by pathway enrichment analysis. Further, using the 10 entities as seeds, we have constructed a protein-protein interaction (PPI) subnetwork and suggested a few urine markers as preferred prognostic markers to monitor the invasion and progression of PCa. Our approach is amenable to discover and prioritize potential markers present in a variety of body fluids for a spectrum of human diseases.
C1 [Chen, Min; Zhang, Liang; Yang, Yongliang] Dalian Univ Technol, Sch Life Sci & Biotechnol, Ctr Mol Med, Dalian, Peoples R China.
[Wang, Kai; Li, Cheng] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Chen, Min; Zhang, Liang] Dalian Univ Technol, Sch Software, Dalian, Peoples R China.
RP Chen, M (reprint author), Dalian Univ Technol, Sch Life Sci & Biotechnol, Ctr Mol Med, Dalian, Peoples R China.
EM cli@hsph.harvard.edu; everbright99@gmail.com
FU Fundamental Research Funds for the Central Universities [DUT11SM12];
National Science Foundation in China; Medical Board Oncology Department
[81000975]; National Institute of Health [R01 GM077122]
FX Work in the Y. Yang laboratory was supported by the Fundamental Research
Funds for the Central Universities (grant: DUT11SM12) and National
Science Foundation in China, Medical Board Oncology Department (grant:
81000975); K. Wang and C. Li were supported by National Institute of
Health grant R01 GM077122 (to C. Li). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 29
TC 9
Z9 9
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 16
PY 2011
VL 6
IS 12
AR e28552
DI 10.1371/journal.pone.0028552
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 870JD
UT WOS:000298664400007
PM 22194848
ER
PT J
AU Ahn, YY
Ahnert, SE
Bagrow, JP
Barabasi, AL
AF Ahn, Yong-Yeol
Ahnert, Sebastian E.
Bagrow, James P.
Barabasi, Albert-Laszlo
TI Flavor network and the principles of food pairing
SO SCIENTIFIC REPORTS
LA English
DT Article
ID COMPLEX WEIGHTED NETWORKS
AB The cultural diversity of culinary practice, as illustrated by the variety of regional cuisines, raises the question of whether there are any general patterns that determine the ingredient combinations used in food today or principles that transcend individual tastes and recipes. We introduce a flavor network that captures the flavor compounds shared by culinary ingredients. Western cuisines show a tendency to use ingredient pairs that share many flavor compounds, supporting the so-called food pairing hypothesis. By contrast, East Asian cuisines tend to avoid compound sharing ingredients. Given the increasing availability of information on food preparation, our data-driven investigation opens new avenues towards a systematic understanding of culinary practice.
C1 [Ahn, Yong-Yeol; Ahnert, Sebastian E.; Bagrow, James P.; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Ctr Complex Network Res, Boston, MA 02115 USA.
[Ahn, Yong-Yeol; Bagrow, James P.; Barabasi, Albert-Laszlo] Harvard Univ, Ctr Canc Syst Biol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ahn, Yong-Yeol] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47408 USA.
[Ahnert, Sebastian E.] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
RP Ahnert, SE (reprint author), Northeastern Univ, Dept Phys, Ctr Complex Network Res, Boston, MA 02115 USA.
EM sea31@cam.ac.uk; alb@neu.edu
FU James S. McDonnell Foundation 21st Century Initiative in Studying
Complex Systems
FX We thank M. I. Meirelles, S. Lehmann, D. Kudayarova, T. W. Lim, J.
Baranyi, H. This for discussions. This work was supported by the James
S. McDonnell Foundation 21st Century Initiative in Studying Complex
Systems.
NR 30
TC 42
Z9 42
U1 8
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD DEC 15
PY 2011
VL 1
AR 196
DI 10.1038/srep00196
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 896KQ
UT WOS:000300565100001
PM 22355711
ER
PT J
AU Popova, MK
He, W
Korenjak, M
Dyson, NJ
Moon, NS
AF Popova, Milena K.
He, Wei
Korenjak, Michael
Dyson, Nicholas J.
Moon, Nam-Sung
TI Rb deficiency during Drosophila eye development deregulates EMC, causing
defects in the development of photoreceptors and cone cells
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE rbf1; Retinoblastoma; emc; ID; Development
ID RETINOBLASTOMA PROTEIN; CYCLE EXIT; IN-VIVO; ID2; DIFFERENTIATION;
PROLIFERATION; FAMILY; MUTANT; TRANSCRIPTION; INHIBITION
AB Retinoblastoma tumor suppressor protein (pRb) regulates various biological processes during development and tumorigenesis. Although the molecular mechanism by which pRb controls cell cycle progression is well characterized, how pRb promotes cell-type specification and differentiation is less understood. Here, we report that Extra Macrochaetae (EMC), the Drosophila homolog of inhibitor of DNA binding/differentiation (ID), is an important protein contributing to the developmental defects caused by Rb deficiency. An emc allele was identified from a genetic screen designed to identify factors that, when overexpressed, cooperate with mutations in rbf1, which encodes one of the two Rb proteins found in Drosophila. EMC overexpression in an rbf1 hypomorphic mutant background induces cone cell and photoreceptor defects but has negligible effects in the wild-type background. Interestingly, a substantial fraction of the rbf1-null ommatidia normally exhibit similar cone cell and photoreceptor defects in the absence of ectopic EMC expression. Detailed EMC expression analyses revealed that RBF1 suppresses expression of both endogenous and ectopic EMC protein in photoreceptors, thus explaining the synergistic effect between EMC overexpression and rbf1 mutations, and the developmental defect observed in rbf1-null ommatidia. Our findings demonstrate that ID family proteins are an evolutionarily conserved determinant of Rb-deficient cells, and play an important role during development.
C1 [Popova, Milena K.; He, Wei; Moon, Nam-Sung] McGill Univ, Dept Biol, Dev Biol Res Initiat, Montreal, PQ H3A 1B1, Canada.
[Korenjak, Michael; Dyson, Nicholas J.] Massachusetts Gen Hosp Canc Res Ctr, Charlestown, MA 02129 USA.
[Korenjak, Michael; Dyson, Nicholas J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Moon, NS (reprint author), McGill Univ, Dept Biol, Dev Biol Res Initiat, 1205 Doctor Penfield Ave, Montreal, PQ H3A 1B1, Canada.
EM nam.moon@mcgill.ca
FU Canada Institute for Health Research (CIHR) [MOP-93666]; Natural Science
and Engineering Research Council (NSERC) of Canada [355760-2008];
National Institutes of Health [R01 GM53203, R01 GM81607]; NSERC; CIHR
FX This study was supported by Canada Institute for Health Research (CIHR)
[grant number MOP-93666]; Natural Science and Engineering Research
Council (NSERC) of Canada [grant number 355760-2008]; and National
Institutes of Health [grant numbers R01 GM53203, R01 GM81607]. M.K.P. is
a recipient of Alexander Graham Bell Canada Graduate Scholarship from
NSERC and N.S.M. is a recipient of New Investigators Salary Award from
CIHR. Deposited in PMC for release after 12 months.
NR 31
TC 5
Z9 5
U1 0
U2 2
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD DEC 15
PY 2011
VL 124
IS 24
BP 4203
EP 4212
DI 10.1242/jcs.088773
PG 10
WC Cell Biology
SC Cell Biology
GA 879FD
UT WOS:000299314200011
PM 22193959
ER
PT J
AU Szymanski, C
Levine, RA
Tribouilloy, C
Zheng, H
Handschumacher, MD
Tawakol, A
Hung, J
AF Szymanski, Catherine
Levine, Robert A.
Tribouilloy, Christophe
Zheng, Hui
Handschumacher, Mark D.
Tawakol, Ahmed
Hung, Judy
TI Impact of Mitral Regurgitation on Exercise Capacity and Clinical
Outcomes in Patients With Ischemic Left Ventricular Dysfunction
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID COLOR DOPPLER FLOW; PROGNOSTIC VALUE; HEART-FAILURE;
MYOCARDIAL-INFARCTION; SYSTOLIC DYSFUNCTION; EUROPEAN-ASSOCIATION; VENA
CONTRACTA; SEVERITY; ECHOCARDIOGRAPHY; JET
AB There is uncertainty and debate regarding whether ischemic mitral regurgitation (MR) is a secondary epiphenomenon resulting from left ventricular (LV) dysfunction or confers an independent effect on exercise capacity and outcomes. We tested whether ischemic MR negatively affects exercise capacity and cardiovascular morbidity and mortality in patients with coronary artery disease (CAD) and those with inferior wall motion abnormality independent of LV dysfunction. Clinical follow-up over 5 years was obtained in 77 patients (64 +/- 10 years old, LV ejection fraction 54 +/- 11%) with at least mild ischemic MR from CAD and evidence of inferior wall motion abnormality who had exercise stress testing with perfusion imaging within 24 hours of echocardiography. Patients with active heart failure, ischemia, intrinsic valve disease, pulmonary and vascular diseases were excluded. Exercise capacity (METs, peak double product) was tested for relation to MR (vena contracta [VC] and jet area), LV size and function, and pulmonary pressures. Cox proportional hazards analysis assessed whether MR predicted cardiovascular events including hospitalization for heart failure, acute coronary syndrome, and myocardial infarction and cardiovascular and total mortalities. Univariate correlation identified MR with VC (r = -0.674, p < 0.0001) and MR jet area (r = - 0.575, p < 0.0001) as determinants of decreased functional capacity evaluated by METs, with VC the stronger predictor. MR VC >2 mm (moderate ischemic MR) and age were independent predictors of cardiovascular events and death (hazard ratio 6.72 for MR, p = 0.04). In conclusion, in patients with CAD and LV inferior wall motion abnormality, MR negatively affects exercise capacity and is associated with increased cardiovascular morbidity and mortality. This effect appears independent of degree of LV dysfunction. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:1714-1720)
C1 [Szymanski, Catherine; Levine, Robert A.; Handschumacher, Mark D.; Hung, Judy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02115 USA.
[Zheng, Hui] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA.
[Szymanski, Catherine; Tribouilloy, Christophe] CHU Amiens Sud, Dept Cardiol, Amiens, France.
RP Hung, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02115 USA.
EM jhung@partners.org
FU Federation Francaise de Cardiologie
FX Dr. Catherine Szymanski was supported by a grant from the Federation
Francaise de Cardiologie.
NR 33
TC 13
Z9 13
U1 0
U2 3
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD DEC 15
PY 2011
VL 108
IS 12
BP 1714
EP 1720
DI 10.1016/j.amjcard.2011.07.045
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 865LM
UT WOS:000298312400005
PM 21943932
ER
PT J
AU Cutler, C
Kim, HT
Sun, LX
Sese, D
Glotzbecker, B
Armand, P
Koreth, J
Ho, V
Alyea, E
Ballen, K
Ritz, J
Soiffer, RJ
Milford, E
Antin, JH
AF Cutler, Corey
Kim, Haesook T.
Sun, Lixian
Sese, Doreen
Glotzbecker, Brett
Armand, Philippe
Koreth, John
Ho, Vincent
Alyea, Edwin
Ballen, Karen
Ritz, Jerome
Soiffer, Robert J.
Milford, Edgar
Antin, Joseph H.
TI Donor-specific anti-HLA antibodies predict outcome in double umbilical
cord blood transplantation
SO BLOOD
LA English
DT Article
ID BONE-MARROW; MEDIATED REJECTION; UNRELATED DONORS; ADULTS; ENGRAFTMENT;
IMPACT; RECIPIENTS; LEUKEMIA; INSIGHTS; UNIT
AB Using a uniform detection method for donor-specific anti-HLA antibodies (DSAs), we sought to determine the effect of preformed DSAs on outcomes in double umbilical cord blood transplantation. DSAs were associated with an increased incidence of graft failure (5.5% vs 18.2% vs 57.1% for none, single, or dual DSA positivity; P = .0001), prolongation of the time to neutrophil engraftment (21 vs 29 days for none vs any DSA; P = .04), and excess 100-day mortality or relapse (23.6% vs 36.4% vs 71.4% for none, single, or dual DSA positivity; P = .01). The intensity of DSA reactivity was correlated with graft failure (median of mean fluorescent intensity 17 650 vs 1 850; P = .039). There was inferior long-term progression-free and overall survival when comparing patients with DSAs against both umbilical cord blood units to those without DSAs (3-year progression-free survival, 0% vs 33.5%, P = .004; 3-year overall survival 0% vs 45.0%, P = .04). We conclude that identification of preformed DSAs in umbilical cord blood recipients should be performed and that the use of umbilical cord blood units where preformed host DSAs exist should be avoided. (Blood. 2011;118(25):6691-6697)
C1 [Cutler, Corey; Glotzbecker, Brett; Armand, Philippe; Koreth, John; Ho, Vincent; Alyea, Edwin; Ritz, Jerome; Soiffer, Robert J.; Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA.
[Kim, Haesook T.; Sun, Lixian] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Sese, Doreen; Milford, Edgar] Brigham & Womens Hosp, Histocompatibil & Tissue Typing Lab, Boston, MA 02115 USA.
[Ballen, Karen] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Cutler, C (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, 450 BrooklineAve, Boston, MA 02115 USA.
EM corey_cutler@dfci.harvard.edu
OI Ritz, Jerome/0000-0001-5526-4669
FU Patrick Carney Foundation; Stem Cell Cyclists of the Pan-Mass Challenge
FX This study was supported in part by the Patrick Carney Foundation. C. C.
is supported by the Stem Cell Cyclists of the Pan-Mass Challenge.
NR 30
TC 79
Z9 82
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 DEC 15
PY 2011
VL 118
IS 25
BP 6691
EP 6697
DI 10.1182/blood-2011-05-355263
PG 7
WC Hematology
SC Hematology
GA 863JC
UT WOS:000298157600033
PM 21940825
ER
PT J
AU Sarkar, D
Spencer, JA
Phillips, JA
Zhao, WA
Schafer, S
Spelke, DP
Mortensen, LJ
Ruiz, JP
Vemula, PK
Sridharan, R
Kumar, S
Karnik, R
Lin, CP
Karp, JM
AF Sarkar, Debanjan
Spencer, Joel A.
Phillips, Joseph A.
Zhao, Weian
Schafer, Sebastian
Spelke, Dawn P.
Mortensen, Luke J.
Ruiz, Juan P.
Vemula, Praveen Kumar
Sridharan, Rukmani
Kumar, Sriram
Karnik, Rohit
Lin, Charles P.
Karp, Jeffrey M.
TI Engineered cell homing
SO BLOOD
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; ROLLING IN-VIVO; BONE-MARROW; P-SELECTIN;
INFARCTED MYOCARDIUM; INFLAMMATION; EXPRESSION; MIGRATION; ADHESION;
LIGAND
AB One of the greatest challenges in cell therapy is to minimally invasively deliver a large quantity of viable cells to a tissue of interest with high engraftment efficiency. Low and inefficient homing of systemically delivered mesenchymal stem cells (MSCs), for example, is thought to be a major limitation of existing MSCbased therapeutic approaches, caused predominantly by inadequate expression of cell surface adhesion receptors. Using a platform approach that preserves the MSC phenotype and does not require genetic manipulation, we modified the surface of MSCs with a nanometer-scale polymer construct containing sialyl Lewis(x) (sLe(x)) that is found on the surface of leukocytes and mediates cell rolling within inflamed tissue. The sLex engineered MSCs exhibited a robust rolling response on inflamed endothelium in vivo and homed to inflamed tissue with higher efficiency compared with native MSCs. The modular approach described herein offers a simple method to potentially target any cell type to specific tissues via the circulation. (Blood. 2011; 118(25): e184-e191)
C1 [Sarkar, Debanjan; Phillips, Joseph A.; Zhao, Weian; Schafer, Sebastian; Spelke, Dawn P.; Ruiz, Juan P.; Vemula, Praveen Kumar; Sridharan, Rukmani; Kumar, Sriram; Karp, Jeffrey M.] Harvard Univ, Ctr Regenerat Therapeut, Brigham & Womens Hosp,Harvard Stem Cell Inst, Sch Med,Harvard Massachusetts Inst Technol,Div Hl, Cambridge, MA 02139 USA.
[Sarkar, Debanjan; Phillips, Joseph A.; Zhao, Weian; Schafer, Sebastian; Spelke, Dawn P.; Ruiz, Juan P.; Vemula, Praveen Kumar; Sridharan, Rukmani; Kumar, Sriram; Karp, Jeffrey M.] Harvard Univ, Dept Med, Brigham & Womens Hosp,Harvard Stem Cell Inst, Sch Med,Harvard Massachusetts Inst Technol,Div Hl, Cambridge, MA 02139 USA.
[Spencer, Joel A.; Mortensen, Luke J.; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Syst Biol, Adv Microscopy Program,Wellman Ctr Photomed, Boston, MA USA.
[Spencer, Joel A.] Tufts Univ, Dept Biomed Engn, Ctr Sci & Technol, Medford, MA 02155 USA.
[Karnik, Rohit] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
RP Karp, JM (reprint author), Harvard Univ, Ctr Regenerat Therapeut, Brigham & Womens Hosp,Harvard Stem Cell Inst, Sch Med,Harvard Massachusetts Inst Technol,Div Hl, 65 Landsdowne St, Cambridge, MA 02139 USA.
EM jkarp@rics.bwh.harvard.edu
RI Spencer, Joel/A-4590-2013; Sarkar, Debanjan/C-6093-2017;
OI Sarkar, Debanjan/0000-0002-6666-3152; Schafer,
Sebastian/0000-0002-6909-8275
FU American Heart Association [0970178N]; National Institutes of Health
[DE019191, HL095722, HL097172]; Massachusetts Institute of Technology;
Kauffman Foundation; Human Frontier Science Program (Postdoctoral
Fellowship)
FX This work was supported by the American Heart Association (grant
0970178N) and the National Institutes of Health (grants DE019191,
HL095722, and HL097172, J.M.K.) as well as the Massachusetts Institute
of Technology Undergraduate Research Opportunities Program. P. K. V. was
supported by Kauffman Foundation Entrepreneur (Postdoctoral Fellowship).
W.Z. was supported by the Human Frontier Science Program (Postdoctoral
Fellowship).
NR 35
TC 66
Z9 69
U1 2
U2 25
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 DEC 15
PY 2011
VL 118
IS 25
BP E184
EP E191
DI 10.1182/blood-2010-10-311464
PG 8
WC Hematology
SC Hematology
GA 863JC
UT WOS:000298157600001
PM 22034631
ER
PT J
AU Li, Y
Zhang, Q
Tian, R
Wang, Q
Zhao, JJ
Iglehart, JD
Wang, ZC
Richardson, AL
AF Li, Yang
Zhang, Qing
Tian, Ruiyang
Wang, Qi
Zhao, Jean J.
Iglehart, J. Dirk
Wang, Zhigang Charles
Richardson, Andrea L.
TI Lysosomal Transmembrane Protein LAPTM4B Promotes Autophagy and Tolerance
to Metabolic Stress in Cancer Cells
SO CANCER RESEARCH
LA English
DT Article
ID BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; MONITORING AUTOPHAGY;
MAMMALIAN-CELLS; APOPTOSIS; GENE; MECHANISMS; MATURATION; RESISTANCE;
SURVIVAL
AB Amplification of chromosome 8q22, which includes the gene for lysosomal associated transmembrane protein LAPTM4B, has been linked to de novo anthracycline resistance in primary breast cancers with poor prognosis. LAPTM4B overexpression can induce cytosolic retention of anthracyclines and decrease drug-induced DNA damage. In this study, we tested the hypothesis that LAPTM4B may contribute to tumor cell growth or survival in the absence of a chemotherapeutic exposure. In mammary cells, LAPTM4B protein was localized in lysosomes where its depletion increased membrane permeability, pH, cathepsin release, and cellular apoptosis. Loss of LAPTM4B also inhibited later stages of autophagy by blocking maturation of the autophagosome, thereby rendering cells more sensitive to nutrient deprivation or hypoxia. Conversely, enforced overexpression of LAPTM4B promoted autophagic flux and cell survival during in vitro starvation and stimulated more rapid tumor growth in vivo. Together, our results indicate that LAPTM4B is required for lysosome homeostasis, acidification, and function, and that LAPTM4B renders tumor cells resistant to lysosome-mediated cell death triggered by environmental and genotoxic stresses. Cancer Res; 71( 24); 7481-9. (C) 2011 AACR.
C1 [Li, Yang; Zhang, Qing; Tian, Ruiyang; Wang, Qi; Zhao, Jean J.; Iglehart, J. Dirk; Wang, Zhigang Charles; Richardson, Andrea L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Iglehart, J. Dirk; Richardson, Andrea L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
RP Richardson, AL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,Smith 936A, Boston, MA 02215 USA.
EM zhigang_wang@dfci.harvard.edu; arichardson@partners.org
FU Susan G. Komen For the Cure [KG080939]; Breast Cancer Research
Foundation; Terri Brodeur Breast Cancer Foundation; Dana-Farber Cancer
Institute; NCI Harvard SPORE in Breast Cancer [2 P50 CA89393-06]; DOD
[BC053041]
FX This work was supported by Susan G. Komen For the Cure (KG080939; to
A.L. Richardson, Z.C. Wang, Y. Li, R. Tian), Breast Cancer Research
Foundation (J.D. Iglehart, A.L. Richardson, Z.C. Wang), Terri Brodeur
Breast Cancer Foundation (Y. Li), and friends of Dana-Farber Cancer
Institute (Y. Li). The work was also supported by the NCI Harvard SPORE
in Breast Cancer (2 P50 CA89393-06) and a DOD concept award (BC053041).
NR 51
TC 38
Z9 39
U1 0
U2 14
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 DEC 15
PY 2011
VL 71
IS 24
BP 7481
EP 7489
DI 10.1158/0008-5472.CAN-11-0940
PG 9
WC Oncology
SC Oncology
GA 866TV
UT WOS:000298407900016
PM 22037872
ER
PT J
AU Cho, J
Pastorino, S
Zeng, Q
Xu, XY
Johnson, W
Vandenberg, S
Verhaak, R
Cherniack, AD
Watanabe, H
Dutt, A
Kwon, J
Chao, YS
Onofrio, RC
Chiang, D
Yuza, Y
Kesari, S
Meyerson, M
AF Cho, Jeonghee
Pastorino, Sandra
Zeng, Qing
Xu, Xiaoyin
Johnson, William
Vandenberg, Scott
Verhaak, Roel
Cherniack, Andrew D.
Watanabe, Hideo
Dutt, Amit
Kwon, Jihyun
Chao, Ying S.
Onofrio, Robert C.
Chiang, Derek
Yuza, Yuki
Kesari, Santosh
Meyerson, Matthew
TI Glioblastoma-Derived Epidermal Growth Factor Receptor Carboxyl-Terminal
Deletion Mutants Are Transforming and Are Sensitive to EGFR-Directed
Therapies
SO CANCER RESEARCH
LA English
DT Article
ID CONFERS ENHANCED TUMORIGENICITY; INTEGRATED GENOMIC ANALYSIS;
HUMAN-BRAIN TUMORS; PHASE-II TRIAL; RECURRENT GLIOBLASTOMA;
MONOCLONAL-ANTIBODY; KINASE INHIBITORS; MALIGNANT GLIOMAS; MULTIFORME;
AMPLIFICATION
AB Genomic alterations of the epidermal growth factor receptor (EGFR) gene play a crucial role in pathogenesis of glioblastoma multiforme (GBM). By systematic analysis of GBM genomic data, we have identified and characterized a novel exon 27 deletion mutation occurring within the EGFR carboxyl-terminus domain (CTD), in addition to identifying additional examples of previously reported deletion mutations in this region. We show that the GBM-derived EGFR CTD deletion mutants are able to induce cellular transformation in vitro and in vivo in the absence of ligand and receptor autophosphorylation. Treatment with the EGFR-targeted monoclonal antibody, cetuximab, or the small molecule EGFR inhibitor, erlotinib, effectively impaired tumorigenicity of oncogenic EGFR CTD deletion mutants. Cetuximab in particular prolonged the survival of intracranially xenografted mice with oncogenic EGFR CTD deletion mutants, compared with untreated control mice. Therefore, we propose that erlotinib and, especially, cetuximab treatment may be a promising therapeutic strategy in GBM patients harboring EGFR CTD deletion mutants. Cancer Res; 71(24); 7587-96. (C)2011 AACR.
C1 [Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Zeng, Qing; Xu, Xiaoyin] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Cho, Jeonghee; Kwon, Jihyun] Samsung Med Ctr, Genom Anal Ctr, Samsung Canc Res Inst, Seoul, South Korea.
[Pastorino, Sandra; Kesari, Santosh] UC San Diego, Dept Neurosci, Moores Canc Ctr, La Jolla, CA USA.
[Vandenberg, Scott] UC San Diego, Dept Pathol, La Jolla, CA USA.
[Verhaak, Roel; Cherniack, Andrew D.; Watanabe, Hideo; Dutt, Amit; Onofrio, Robert C.; Chiang, Derek; Yuza, Yuki; Meyerson, Matthew] Broad Inst MIT & Harvard, Cambridge, MA USA.
RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
EM skesari@ucsd.edu; matthew_meyerson@dfci.harvard.edu
RI Meyerson, Matthew/E-7123-2012; Dutt, Amit/I-1911-2013; Kesari,
Santosh/E-8461-2013
OI Dutt, Amit/0000-0002-1119-4774;
FU Novartis; Novartis and Genetech; National Cancer Institute
[R01CA116020]; NIH [K08CA124804, 3P30CA023100-25S8]; Sontag Foundation;
James S. McDonnell Foundation; Samsung Cancer Research Institute
FX M. Meyerson is a consultant to Novartis; receives research support from
Novartis and Genetech; is a founding advisor and consultant to, and an
equity holder in, foundation Medicine; and is a patent holder for EGFR
mutation testing, licensed to Genezyme Genetics. The other authors
disclosed no potential conflicts of interest.; This work was supported
in part by National Cancer Institute grant R01CA116020 to M. Meyerson,
NIH K08CA124804, NIH 3P30CA023100-25S8, Sontag Foundation distinguished
scientist award, James S. McDonnell Foundation to S. Kesari, and Samsung
Cancer Research Institute intramural grant to J. Cho.
NR 51
TC 34
Z9 34
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
IS 24
BP 7587
EP 7596
DI 10.1158/0008-5472.CAN-11-0821
PG 10
WC Oncology
SC Oncology
GA 866TV
UT WOS:000298407900026
PM 22001862
ER
PT J
AU Li, X
Utomo, A
Cullere, X
Choi, MM
Milner, DA
Venkatesh, D
Yun, SH
Mayadas, TN
AF Li, Xun
Utomo, Ahmad
Cullere, Xavier
Choi, Myunghwan Mark
Milner, Danny A., Jr.
Venkatesh, Deepak
Yun, Seok-Hyun
Mayadas, Tanya N.
TI The beta-Glucan Receptor Dectin-1 Activates the Integrin Mac-1 in
Neutrophils via Vav Protein Signaling to Promote Candida albicans
Clearance
SO CELL HOST & MICROBE
LA English
DT Article
ID PHOSPHOLIPASE C-GAMMA-2; FUNGAL-INFECTIONS; FAMILY PROTEINS; DENDRITIC
CELLS; INNATE IMMUNITY; HOST-DEFENSE; 3 CD11B/CD18; LECTIN SITE; SYK
KINASES; LIPID RAFTS
AB Resistance to fungal infections is attributed to engagement of host pattern-recognition receptors, notably the beta-glucan receptor Dectin-1 and the integrin Mac-1, which induce phagocytosis and antifungal immunity. However, the mechanisms by which these receptors coordinate fungal clearance are unknown. We show that upon ligand binding, Dectin-1 activates Mac-1 to also recognize fungal components, and this stepwise process is critical for neutrophil cytotoxic responses. Both Mac-1 activation and Dectin-1- and Mac-1-induced neutrophil effector functions require Vav1 and Vav3, exchange factors for RhoGTPases. Mac-1- or Vav1,3-deficient mice have increased susceptibility to systemic candidiasis that is not due to impaired neutrophil recruitment but defective intracellular killing of C. albicans yeast forms, and Mac-1 or Vav1,3 reconstitution in hematopoietic cells restores resistance. Our results demonstrate that antifungal immunity depends on Dectin-1-induced activation of Mac-1 functions that is coordinated by Vav proteins, a pathway that may localize cytotoxic responses of circulating neutrophils to infected tissues.
C1 [Li, Xun; Utomo, Ahmad; Cullere, Xavier; Milner, Danny A., Jr.; Venkatesh, Deepak; Mayadas, Tanya N.] Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol, Boston, MA 02115 USA.
[Li, Xun; Utomo, Ahmad; Cullere, Xavier; Milner, Danny A., Jr.; Venkatesh, Deepak; Mayadas, Tanya N.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Choi, Myunghwan Mark; Yun, Seok-Hyun] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Choi, Myunghwan Mark; Yun, Seok-Hyun] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Mayadas, TN (reprint author), Brigham & Womens Hosp, Dept Pathol, Ctr Excellence Vasc Biol, 75 Francis St, Boston, MA 02115 USA.
EM tmayadas@rics.bwh.harvard.edu
FU National Institutes of Health [R01 AR050800, HL065095, K01 AR054984];
American Lung Association
FX We are grateful to Gordon D. Brown (Univ. of Aberdeen, Aberdeen, UK) for
giving us permission to use materials from Dectin-1-/- mice,
Yoichiro lwakura (Institute of Medical Science, University of Tokyo,
Japan) for providing Dectin-1-/- mice, and Brendan Cormack
(John Hopkins, Baltimore, MD) for GFP-C. albicans. This work was
supported by National Institutes of Health grants, R01 AR050800 and
HL065095 (TM.) and K01 AR054984 (X.C.), and an American Lung Association
fellowship (AU.).
NR 58
TC 45
Z9 46
U1 0
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD DEC 15
PY 2011
VL 10
IS 6
BP 603
EP 615
DI 10.1016/j.chom.2011.10.009
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 873OV
UT WOS:000298893600010
PM 22177564
ER
PT J
AU De Preter, K
Mestdagh, P
Vermeulen, J
Zeka, F
Naranjo, A
Bray, I
Castel, V
Chen, CF
Drozynska, E
Eggert, A
Hogarty, MD
Ewalzycka-Swieszewska
London, WB
Noguera, R
Piqueras, M
Bryan, K
Schowe, B
van Sluis, P
Molenaar, JJ
Schramm, A
Schulte, JH
Stallings, RL
Versteeg, R
Laureys, G
Van Roy, N
Speleman, F
Vandesompele, J
AF De Preter, Katleen
Mestdagh, Pieter
Vermeulen, Joelle
Zeka, Fjoralba
Naranjo, Arlene
Bray, Isabella
Castel, Victoria
Chen, Caifu
Drozynska, Elzbieta
Eggert, Angelika
Hogarty, Michael D.
Ewalzycka-Swieszewska
London, Wendy B.
Noguera, Rosa
Piqueras, Marta
Bryan, Kenneth
Schowe, Benjamin
van Sluis, Peter
Molenaar, Jan J.
Schramm, Alexander
Schulte, Johannes H.
Stallings, Raymond L.
Versteeg, Rogier
Laureys, Genevieve
Van Roy, Nadine
Speleman, Frank
Vandesompele, Jo
TI miRNA Expression Profiling Enables Risk Stratification in Archived and
Fresh Neuroblastoma Tumor Samples
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GENE-EXPRESSION; PREDICTION; CLASSIFICATION; AMPLIFICATION; PROGNOSIS;
NETWORKS; RNA
AB Purpose: More accurate assessment of prognosis is important to further improve the choice of risk-related therapy in neuroblastoma (NB) patients. In this study, we aimed to establish and validate a prognostic miRNA signature for children with NB and tested it in both fresh frozen and archived formalin-fixed paraffin-embedded (FFPE) samples.
Experimental Design: Four hundred-thirty human mature miRNAs were profiled in two patient subgroups with maximally divergent clinical courses. Univariate logistic regression analysis was used to select miRNAs correlating with NB patient survival. A 25-miRNA gene signature was built using 51 training samples, tested on 179 test samples, and validated on an independent set of 304 fresh frozen tumor samples and 75 archived FFPE samples.
Results: The 25-miRNA signature significantly discriminates the test patients with respect to progression-free and overall survival (P < 0.0001), both in the overall population and in the cohort of high-risk patients. Multivariate analysis indicates that the miRNA signature is an independent predictor of patient survival after controlling for current risk factors. The results were confirmed in an external validation set. In contrast to a previously published mRNA classifier, the 25-miRNA signature was found to be predictive for patient survival in a set of 75 FFPE neuroblastoma samples.
Conclusions: In this study, we present the largest NB miRNA expression study so far, including more than 500 NB patients. We established and validated a robust miRNA classifier, able to identify a cohort of high-risk NB patients at greater risk for adverse outcome using both fresh frozen and archived material. Clin Cancer Res; 17(24); 7684-92. (C)2011 AACR.
C1 [De Preter, Katleen; Mestdagh, Pieter; Vermeulen, Joelle; Zeka, Fjoralba; Van Roy, Nadine; Speleman, Frank; Vandesompele, Jo] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium.
[Laureys, Genevieve] Ghent Univ Hosp, Dept Paediat Hematol & Oncol, B-9000 Ghent, Belgium.
[Naranjo, Arlene] Univ Florida, Childrens Oncol Grp, Gainesville, FL USA.
[Bray, Isabella; Bryan, Kenneth; Stallings, Raymond L.] Royal Coll Surgeons Ireland, Dept Canc Genet, Dublin 2, Ireland.
[Bray, Isabella; Bryan, Kenneth; Stallings, Raymond L.] Natl Childrens Res Ctr, Dublin, Ireland.
[Castel, Victoria] Hosp La Fe, Pediat Oncol Unit, E-46009 Valencia, Spain.
[Noguera, Rosa; Piqueras, Marta] Univ Valencia, Dept Pathol, Sch Med, Valencia, Spain.
[Chen, Caifu] Appl Biosyst Inc, Foster City, CA 94404 USA.
[Drozynska, Elzbieta; Ewalzycka-Swieszewska] Med Univ Gdansk, Dept Pediat Haematol Oncol & Endocrinol, Gdansk, Poland.
[Eggert, Angelika; Schramm, Alexander; Schulte, Johannes H.] Univ Childrens Hosp Essen, Dept Pediat Oncol & Haematol, Essen, Germany.
[Hogarty, Michael D.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[London, Wendy B.] Childrens Hosp Boston, Childrens Oncol Grp, Dana Farber Harvard Canc Ctr, Boston, MA USA.
[Schowe, Benjamin] Tech Univ Dortmund, Dept Comp Sci, Dortmund, Germany.
[van Sluis, Peter; Molenaar, Jan J.; Versteeg, Rogier] Univ Amsterdam, Acad Med Ctr, Dept Human Genet, NL-1105 AZ Amsterdam, Netherlands.
RP Vandesompele, J (reprint author), Ghent Univ Hosp, CMGG, Med Res Bldg MRB,2nd Floor,Room 120-055,Pintelaan, B-9000 Ghent, Belgium.
EM Joke.Vandesompele@UGent.be
RI Stallings, Raymond/A-7213-2008; Bray, Isabella/D-6179-2012; Schulte,
Johannes/G-3981-2010; De Preter, Katleen/I-7135-2013;
OI De Preter, Katleen/0000-0002-7726-5096; Bryan,
Kenneth/0000-0002-9550-8354; Castel, Victoria/0000-0002-3792-0615;
Vandesompele, Jo/0000-0001-6274-0184
FU Ghent University Research Fund (BOF) [01D31406]; Fund for Scientific
Research Flanders; Belgian Kid's Fund and the Fondation Nuovo-Soldati;
FOD [NKP_29_014]; Fondation Fournier Majoie pour l'Innovation; Belgian
Federal Public Health Service; Association Hubert Gouin "Enfance et
Cancer"; Flemish League against Cancer; Children Cancer Fund Ghent;
Belgian Society of Paediatric Haematology and Oncology; Fund for
Scientific Research Flanders [G.0198.08)]; Institute for the Promotion
of Innovation by Science and Technology in Flanders, Strategisch
basisonderzoek [IWT-SBO 60848]; Children's Oncology Group [U10 CA98413,
U10 CA98543]; Instituto Carlos III Spain [RD 06/0020/0102]; European
Community [037260]; Science Foundation Ireland [07/IN.1/B1776];
Children's Medical and Research Foundation; NIH [5R01CA127496]
FX This work was supported by Ghent University Research Fund (BOF 01D31406;
P. Mestdagh), the Fund for Scientific Research Flanders (K. De Preter),
the Belgian Kid's Fund and the Fondation Nuovo-Soldati (J. Vermeulen),
the FOD (NKP_29_014), the Fondation Fournier Majoie pour l'Innovation,
the Belgian Federal Public Health Service, the Association Hubert Gouin
"Enfance et Cancer", the Flemish League against Cancer, the Children
Cancer Fund Ghent, the Belgian Society of Paediatric Haematology and
Oncology, the Fund for Scientific Research Flanders (grant number:
G.0198.08), the Institute for the Promotion of Innovation by Science and
Technology in Flanders, Strategisch basisonderzoek (IWT-SBO 60848),
Children's Oncology Group grants (U10 CA98413 and U10 CA98543) and the
Instituto Carlos III, RD 06/0020/0102 Spain. This article presents
research results of the Belgian program of Interuniversity Poles of
Attraction, initiated by the Belgian State, Prime Minister's Office,
Science Policy Programming. We acknowledge the support of the European
Community (FP6: STREP: EET-pipeline, number: 037260). R. L. Stallings
was a recipient of grants from Science Foundation Ireland
(07/IN.1/B1776), the Children's Medical and Research Foundation, and the
NIH (5R01CA127496).
NR 25
TC 38
Z9 39
U1 1
U2 10
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 DEC 15
PY 2011
VL 17
IS 24
BP 7684
EP 7692
DI 10.1158/1078-0432.CCR-11-0610
PG 9
WC Oncology
SC Oncology
GA 866UL
UT WOS:000298410300020
PM 22031095
ER
PT J
AU Estabrook, NC
Chin-Sinex, H
Borgmann, AJ
Dhaemers, RM
Shapiro, RH
Gilley, D
Huda, N
Crooks, P
Sweeney, C
Mendonca, MS
AF Estabrook, Neil C.
Chin-Sinex, Helen
Borgmann, Anthony J.
Dhaemers, Ryan M.
Shapiro, Ronald H.
Gilley, David
Huda, Nazmul
Crooks, Peter
Sweeney, Christopher
Mendonca, Marc S.
TI Inhibition of NF-kappa B and DNA double-strand break repair by DMAPT
sensitizes non-small-cell lung cancers to X-rays
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE X-rays; DMAPT; NF-kappa B; A549; H1299; Double-strand DNA break repair;
Free radicals
ID BODY RADIATION-THERAPY; SESQUITERPENE LACTONE PARTHENOLIDE; STEREOTACTIC
RADIOTHERAPY; ANTICANCER DRUGS; MAMMALIAN CELLS; COMET ASSAY; PROSTATE;
DAMAGE; GROWTH; CHEMOTHERAPY
AB We investigated the efficacy and mechanism of dimethylaminoparthenolide (DMAPT), an NF-kappa B inhibitor, to sensitize human lung cancer cells to X-ray killing in vitro and in vivo. We tested whether DMAPT increased the effectiveness of single and fractionated X-ray treatment through inhibition of NF-kappa B and/or DNA double-strand break (DSB) repair. Treatment with DMAPT decreased plating efficiency, inhibited constitutive and radiation-induced NF-kappa B binding activity, and enhanced radiation-induced cell killing by dose modification factors of 1.8 and 1.4 in vitro. X-ray fractionation demonstrated that DMAPT inhibited split-dose recovery/repair, and neutral DNA comet assays confirmed that DMAPT altered the fast and slow components of X-ray-induced DNA DSB repair. Knockdown of the NF-kappa B family member p65 by siRNA increased radiation sensitivity and completely inhibited split-dose recovery in a manner very similar to DMAPT treatment. The data suggest a link between inhibition of NF-kappa B and inhibition of DSB repair by DMAPT that leads to enhancement of X-ray-induced cell killing in vitro in non-small-cell lung cancer cells. Studies of A549 tumor xenografts in nude mice demonstrated that DMAPT enhanced X-ray-induced tumor growth delay in vivo. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Estabrook, Neil C.; Chin-Sinex, Helen; Borgmann, Anthony J.; Dhaemers, Ryan M.; Shapiro, Ronald H.; Mendonca, Marc S.] Indiana Univ Sch Med, Dept Radiat Oncol, Indianapolis, IN 46202 USA.
[Gilley, David; Huda, Nazmul; Mendonca, Marc S.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Crooks, Peter] Univ Kentucky, Coll Pharm, Lexington, KY 40506 USA.
[Sweeney, Christopher] Dana Farber Canc Inst, Genitourinary Canc Program, Boston, MA 02115 USA.
RP Mendonca, MS (reprint author), Indiana Univ Sch Med, Dept Radiat Oncol, Indianapolis, IN 46202 USA.
EM mmendonc@iupui.edu
FU Indiana University Simon Cancer Center Lung Cancer Working Group;
Marvella Bayh Memorial Scholarship
FX This research was supported by an Indiana University Simon Cancer Center
Lung Cancer Working Group grant awarded to M.S.M. and by a Marvella Bayh
Memorial Scholarship for cancer research awarded to N.C.E. Drs.
Christopher Sweeney and Peter Crooks own stock in the company Leuchemix
developing the parthenolide derivative DMAPT for clinical use.
NR 45
TC 10
Z9 10
U1 0
U2 2
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 DEC 15
PY 2011
VL 51
IS 12
BP 2249
EP 2258
DI 10.1016/j.freeradbiomed.2011.09.029
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 860PK
UT WOS:000297960000015
PM 22019440
ER
PT J
AU Ramadas, RA
Roche, MI
Moon, JJ
Ludwig, T
Xavier, RJ
Medoff, BD
AF Ramadas, Ravisankar A.
Roche, Marly I.
Moon, James J.
Ludwig, Thomas
Xavier, Ramnik J.
Medoff, Benjamin D.
TI CARMA1 Is Necessary for Optimal T Cell Responses in a Murine Model of
Allergic Asthma
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NF-KAPPA-B; AIRWAY INFLAMMATION; LYMPHOCYTE DEVELOPMENT;
PERIPHERAL-TISSUES; ADAPTIVE IMMUNITY; ACTIVATION; PHOSPHORYLATION;
MEMORY; EXPRESSION; CARD11
AB CARMA1 is a lymphocyte-specific scaffold protein necessary for T cell activation. Deletion of CARMA1 prevents the development of allergic airway inflammation in a mouse model of asthma due to a defect in naive T cell activation. However, it is unknown if CARMA1 is important for effector and memory T cell responses after the initial establishment of inflammation, findings that would be more relevant to asthma therapies targeted to CARMA1. In the current study, we sought to elucidate the role of CARMA1 in T cells that have been previously activated. Using mice in which floxed CARMA1 exons can be selectively deleted in T cells by OX40-driven Cre recombinase (OX40(+/Cre)CARMA1(F/F)), we report that CD4(+) T cells from these mice have impaired T cell reactivation responses and NF-kappa B signaling in vitro. Furthermore, in an in vivo recall model of allergic airway inflammation that is dependent on memory T cell function, OX40(+/Cre) CARMA1(F/F) mice have attenuated eosinophilic airway inflammation, T cell activation, and Th2 cytokine production. Using MHC class II tetramers, we demonstrate that the development and maintenance of Ag-specific memory T cells is not affected in OX40(+/Cre)CARMA1(F/F) mice. In addition, adoptive transfer of Th2-polarized OX40(+/Cre)CARMA1(F/F) Ag-specific CD4(+) T cells into wild-type mice induces markedly less airway inflammation in response to Ag challenge than transfer of wild-type Th2 cells. These data demonstrate a novel role for CARMA1 in effector and memory T cell responses and suggest that therapeutic strategies targeting CARMA1 could help treat chronic inflammatory disorders such as asthma. The Journal of Immunology, 2011, 187: 6197-6207.
C1 [Ramadas, Ravisankar A.; Roche, Marly I.; Moon, James J.; Medoff, Benjamin D.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Ramadas, Ravisankar A.; Roche, Marly I.; Moon, James J.; Xavier, Ramnik J.; Medoff, Benjamin D.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Ramadas, Ravisankar A.; Roche, Marly I.; Moon, James J.; Medoff, Benjamin D.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
[Ramadas, Ravisankar A.; Roche, Marly I.; Moon, James J.; Medoff, Benjamin D.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Ludwig, Thomas] Columbia Univ, Inst Canc Genet, New York, NY USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
RP Medoff, BD (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA.
EM bmedoff@partners.org
RI Ludwig, Thomas/Q-6484-2016
OI Ludwig, Thomas/0000-0003-3461-2585
FU National Institutes of Health [R01HL088297-04, T32HL007874]
FX This work was supported by National Institutes of Health Grants
R01HL088297-04 (to B. D. M. and R.J.X.) and T32HL007874 (to B. D. M.).
NR 55
TC 6
Z9 9
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 DEC 15
PY 2011
VL 187
IS 12
BP 6197
EP 6207
DI 10.4049/jimmunol.1101348
PG 11
WC Immunology
SC Immunology
GA 863MG
UT WOS:000298167800009
PM 22075698
ER
PT J
AU Mahalingam, B
Ajroud, K
Alonso, JL
Anand, S
Adair, BD
Horenstein, AL
Malavasi, F
Xiong, JP
Arnaout, MA
AF Mahalingam, Bhuvaneshwari
Ajroud, Kaouther
Alonso, Jose Luis
Anand, Saurabh
Adair, Brian D.
Horenstein, Alberto L.
Malavasi, Fabio
Xiong, Jian-Ping
Arnaout, M. Amin
TI Stable Coordination of the Inhibitory Ca2+ Ion at the Metal
Ion-Dependent Adhesion Site in Integrin CD11b/CD18 by an
Antibody-Derived Ligand Aspartate: Implications for Integrin Regulation
and Structure-Based Drug Design
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID A-DOMAIN; I-DOMAIN; CARBOXYLATE-BINDING; CRYSTAL-STRUCTURE;
DIVALENT-CATION; CR3 CD11B/CD18; AFFINITY; COMPLEX; ALPHA(IIB)BETA(3);
RECOGNITION
AB A central feature of integrin interaction with physiologic ligands is the monodentate binding of a ligand carboxylate to a Mg2+ ion hexacoordinated at the metal ion-dependent adhesion site (MIDAS) in the integrin A domain. This interaction stabilizes the A domain in the high-affinity state, which is distinguished from the default low-affinity state by tertiary changes in the domain that culminate in cell adhesion. Small molecule ligand-mimetic integrin antagonists act as partial agonists, eliciting similar activating conformational changes in the A domain, which has contributed to paradoxical adhesion and increased patient mortality in large clinical trials. As with other ligand-mimetic integrin antagonists, the function-blocking mAb 107 binds MIDAS of integrin CD11b/CD18 A domain (CD11bA), but in contrast, it favors the inhibitory Ca2+ ion over the Mg2+ ion at MIDAS. We determined the crystal structures of the Fab fragment of mAb 107 complexed to the low-and high-affinity states of CD11bA. Favored binding of the Ca2+ ion at MIDAS is caused by the unusual symmetric bidentate ligation of a Fab-derived ligand Asp to a heptacoordinated MIDAS Ca2+ ion. Binding of the Fab fragment of mAb 107 to CD11bA did not trigger the activating tertiary changes in the domain or in the full-length integrin. These data show that the denticity of the ligand Asp/Glu can modify the divalent cation selectivity at MIDAS and hence integrin function. Stabilizing the Ca2+ ion at MIDAS by bidentate ligation to a ligand Asp/Glu may provide one approach for designing pure integrin antagonists. The Journal of Immunology, 2011, 187: 6393-6401.
C1 [Mahalingam, Bhuvaneshwari; Adair, Brian D.; Xiong, Jian-Ping; Arnaout, M. Amin] Harvard Univ, Massachusetts Gen Hosp, Div Nephrol, Struct Biol Program,Med Sch, Charlestown, MA 02129 USA.
[Mahalingam, Bhuvaneshwari; Ajroud, Kaouther; Alonso, Jose Luis; Anand, Saurabh; Adair, Brian D.; Xiong, Jian-Ping; Arnaout, M. Amin] Massachusetts Gen Hosp, Div Nephrol, Leukocyte Biol & Inflammat Program, Harvard Med Sch, Charlestown, MA 02129 USA.
[Horenstein, Alberto L.; Malavasi, Fabio] Univ Turin, Sch Med, Lab Immunogenet, Turin, Italy.
RP Arnaout, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Nephrol, Struct Biol Program,Med Sch, 149 13th St, Charlestown, MA 02129 USA.
EM aarnaout1@partners.org
RI Alonso, Jose Luis/G-7961-2012
FU National Institutes of Health (National Institute of Diabetes and
Digestive and Kidney Diseases)
FX This work was supported by grants from the National Institutes of Health
(National Institute of Diabetes and Digestive and Kidney Diseases).
NR 56
TC 10
Z9 10
U1 0
U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD DEC 15
PY 2011
VL 187
IS 12
BP 6393
EP 6401
DI 10.4049/jimmunol.1102394
PG 9
WC Immunology
SC Immunology
GA 863MG
UT WOS:000298167800030
PM 22095715
ER
PT J
AU Munoz-Fontela, C
Pazos, M
Delgado, I
Murk, W
Mungamuri, SK
Lee, SW
Garcia-Sastre, A
Moran, TM
Aaronson, SA
AF Munoz-Fontela, Cesar
Pazos, Michael
Delgado, Igotz
Murk, William
Mungamuri, Sathish Kumar
Lee, Sam W.
Garcia-Sastre, Adolfo
Moran, Thomas M.
Aaronson, Stuart A.
TI p53 Serves as a Host Antiviral Factor That Enhances Innate and Adaptive
Immune Responses to Influenza A Virus
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID T-CELL RESPONSES; DOUBLE-STRANDED-RNA; DENDRITIC CELLS; BONE-MARROW;
CUTTING EDGE; INFLAMMATORY RESPONSES; ANTIBODY-RESPONSES; INFECTION;
GENE; INTERFERON
AB Several direct target genes of the p53 tumor suppressor have been identified within pathways involved in viral sensing, cytokine production, and inflammation, suggesting a potential role of p53 in antiviral immunity. The increasing need to identify immune factors to devise host-targeted therapies against pandemic influenza A virus (IAV) led us to investigate the role of endogenous wildtype p53 on the immune response to IAV. We observed that the absence of p53 resulted in delayed cytokine and antiviral gene responses in lung and bone marrow, decreased dendritic cell activation, and reduced IAV-specific CD8(+) T cell immunity. Consequently, p53(-/-) mice showed a more severe IAV-induced disease compared with their wild-type counterparts. These findings establish that p53 influences the antiviral response to IAV, affecting both innate and adaptive immunity. Thus, in addition to its established functions as a tumor suppressor gene, p53 serves as an IAV host antiviral factor that might be modulated to improve anti-IAV therapy and vaccines. The Journal of Immunology, 2011, 187: 6428-6436.
C1 [Munoz-Fontela, Cesar; Delgado, Igotz; Murk, William; Mungamuri, Sathish Kumar; Aaronson, Stuart A.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA.
[Pazos, Michael; Garcia-Sastre, Adolfo; Moran, Thomas M.] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA.
[Lee, Sam W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
[Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY 10029 USA.
[Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA.
[Moran, Thomas M.] Mt Sinai Sch Med, Inst Immunol, New York, NY 10029 USA.
RP Aaronson, SA (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1 Gustave L Levy Pl,Box 1130, New York, NY 10029 USA.
EM Stuart.Aaronson@mssm.edu
RI Delgado, Igotz/N-1205-2014;
OI Delgado, Igotz/0000-0001-8675-2921; Garcia-Sastre,
Adolfo/0000-0002-6551-1827; Munoz-Fontela, Cesar/0000-0002-7725-2586
FU National Institutes of Health [P01 CA80058-11, R01 AI046954, U01
AI070469, U19 AI083025, U54 AI057158, U01 AI082970, R01 AI41111]; Center
for Research on Influenza Pathogenesis, a National Institute of Allergy
and Infectious Diseases-supported center [HHS266200700010C]; Basque
government
FX This work was supported by National Institutes of Health Grant P01
CA80058-11 (to S.A.A.) and was partly supported by National Institutes
of Health Grants R01 AI046954, U01 AI070469, U19 AI083025, and U54
AI057158; by the Center for Research on Influenza Pathogenesis, a
National Institute of Allergy and Infectious Diseases-supported center,
Contract HHS266200700010C (to A.G.-S.); by National Institutes of Health
Grants U01 AI082970 and R01 AI41111 (to T.M.M.); and by a postdoctoral
fellowship from the Basque government to I.D.
NR 48
TC 37
Z9 44
U1 1
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD DEC 15
PY 2011
VL 187
IS 12
BP 6428
EP 6436
DI 10.4049/jimmunol.1101459
PG 9
WC Immunology
SC Immunology
GA 863MG
UT WOS:000298167800034
PM 22105999
ER
PT J
AU Schinzel, RT
Ahfeldt, T
Lau, FH
Lee, YK
Cowley, A
Shen, T
Peters, D
Lum, DH
Cowan, CA
AF Schinzel, Robert T.
Ahfeldt, Tim
Lau, Frank H.
Lee, Youn-Kyoung
Cowley, Alicia
Shen, Tony
Peters, Derek
Lum, David H.
Cowan, Chad A.
TI Efficient Culturing and Genetic Manipulation of Human Pluripotent Stem
Cells
SO PLOS ONE
LA English
DT Article
ID LENTIVIRAL VECTORS; HUMAN BLASTOCYSTS; LINES; SURVIVAL
AB Human pluripotent stem cells (hPSC) hold great promise as models for understanding disease and as a source of cells for transplantation therapies. However, the lack of simple, robust and efficient culture methods remains a significant obstacle for realizing the utility of hPSCs. Here we describe a platform for the culture of hPSCs that 1) allows for dissociation and replating of single cells, 2) significantly increases viability and replating efficiency, 3) improves freeze/thaw viability 4) improves cloning efficiency and 5) colony size variation. When combined with standard methodologies for genetic manipulation, we found that the enhanced culture platform allowed for lentiviral transduction rates of up to 95% and electroporation efficiencies of up to 25%, with a significant increase in the total number of antibiotic-selected colonies for screening for homologous recombination. We further demonstrated the utility of the enhanced culture platform by successfully targeting the ISL1 locus. We conclude that many of the difficulties associated with culturing and genetic manipulation of hPSCs can be addressed with optimized culture conditions, and we suggest that the use of the enhanced culture platform could greatly improve the ease of handling and general utility of hPSCs.
C1 [Schinzel, Robert T.; Ahfeldt, Tim; Lee, Youn-Kyoung; Cowley, Alicia; Shen, Tony; Peters, Derek; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Schinzel, Robert T.; Ahfeldt, Tim; Lau, Frank H.; Lee, Youn-Kyoung; Cowley, Alicia; Shen, Tony; Peters, Derek; Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Schinzel, Robert T.; Ahfeldt, Tim; Lee, Youn-Kyoung; Peters, Derek; Cowan, Chad A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Schinzel, Robert T.] Free Univ Berlin, Inst Biol Mikrobiol, Fachbereich Biol, Berlin, Germany.
[Cowley, Alicia; Shen, Tony] Harvard Univ, Harvard Coll, Cambridge, MA 02138 USA.
[Lum, David H.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Lum, David H.] Univ Utah, Dept Oncol Sci, Salt Lake City, UT USA.
RP Schinzel, RT (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
EM ccowan@fas.harvard.edu
RI Ahfeldt, Tim/E-2935-2017;
OI Shen, Tony/0000-0002-7740-6389
FU Harvard Stem Cell Institute; Stowers Medical Research Institute
FX Funding was provided by a Junior Faculty Program Award from Harvard Stem
Cell Institute, and by the Stowers Medical Research Institute. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 16
TC 8
Z9 9
U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 15
PY 2011
VL 6
IS 12
AR e27495
DI 10.1371/journal.pone.0027495
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 866HE
UT WOS:000298370400004
PM 22194785
ER
PT J
AU Hooker, CI
Bruce, L
Lincoln, SH
Fisher, M
Vinogradov, S
AF Hooker, Christine I.
Bruce, Lori
Lincoln, Sarah Hope
Fisher, Melissa
Vinogradov, Sophia
TI Theory of Mind Skills Are Related to Gray Matter Volume in the
Ventromedial Prefrontal Cortex in Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Empathy; mentalizing; MRI; schizophrenia; social functioning; theory of
mind
ID VOXEL-BASED MORPHOMETRY; FRONTAL-LOBE PATHOLOGY; SOCIAL COGNITION;
1ST-EPISODE SCHIZOPHRENIA; PROGRESSIVE DECREASE; EMPATHIC ABILITIES;
NEURAL BASIS; BRAIN; METAANALYSIS; RECOGNITION
AB Background: Among individuals with schizophrenia, deficits in theory of mind (ToM) skills predict poor social functioning. Therefore, identifying the neural basis of ToM may assist the development of treatments that improve social outcomes. Despite growing evidence that the ventromedial prefrontal cortex (VMPFC) facilitates ToM skills among healthy individuals, methodological challenges, such as the influence of general cognitive deficits, have made it difficult to identify the relationship between ToM processing and VMPFC function in schizophrenia.
Methods: We used voxel-based morphometry and a multi-method behavioral assessment of ToM processing, including performance-based (Recognition of Faux Pas Test), self-report (Interpersonal Reactivity Index, Perspective-Taking), and interview-rated (Quality of Life Scale-Empathy score) ToM assessments, to investigate whether ToM skills were related to VMPFC gray matter volume (GMV). Standardized neuropsychological measures were used to assess global cognition. Twenty-one schizophrenia and 17 healthy control subjects participated.
Results: Between-group behavioral analyses showed that, as compared with healthy participants, schizophrenia participants had worse ToM performance and lower self-reported ToM processing in daily life. The between-group analysis of GMV showed that schizophrenia participants had less VMPFC GMV than healthy participants. Moreover, among schizophrenia participants, all three measures of ToM processing were associated with VMPFC GMV, such that worse ToM skills were related to less VMPFC GMV. This association remained strong for self-reported and interview-rated ToM skills, even when controlling for the influence of global cognition.
Conclusions: The findings suggest that among individuals with schizophrenia, reduced VMPFC GMV is associated with deficits using ToM skills to enhance social relationships.
C1 [Hooker, Christine I.; Bruce, Lori; Lincoln, Sarah Hope] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Fisher, Melissa; Vinogradov, Sophia] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Fisher, Melissa; Vinogradov, Sophia] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA.
RP Hooker, CI (reprint author), Harvard Univ, Dept Psychol, 820 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA.
EM chooker@wjh.harvard.edu
FU National Alliance for Research on Schizophrenia and Depression Young
Investigator Award; National Institute of Mental Health [MH71746,
MH68725-02]; Growth to Spur the Acceleration of New Technologies
(BRDG-SPAN) Grant
FX This work was supported by a National Alliance for Research on
Schizophrenia and Depression Young Investigator Award (CIH) and National
Institute of Mental Health Grants MH71746 (CIH) and MH68725-02 (SV).;
Sophia Vinogradov is a paid consultant on an National Institute of
Mental Health Biomedical Research, Development, and Growth to Spur the
Acceleration of New Technologies (BRDG-SPAN) Grant to Brain Plasticity
Inc. Christine Hooker, Melissa Fisher, Lori Bruce, and Sarah Hope
Lincoln report no biomedical financial interests or potential conflicts
of interest.
NR 87
TC 40
Z9 42
U1 4
U2 17
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 DEC 15
PY 2011
VL 70
IS 12
BP 1169
EP 1178
DI 10.1016/j.biopsych.2011.07.027
PG 10
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 860WW
UT WOS:000297980000012
PM 21917239
ER
PT J
AU Hurwitz, MD
Halabi, S
Archer, L
McGinnis, LS
Kuettel, MR
DiBiase, SJ
Small, EJ
AF Hurwitz, Mark D.
Halabi, Susan
Archer, Laura
McGinnis, Lamar S.
Kuettel, Michael R.
DiBiase, Steven J.
Small, Eric J.
TI Combination external beam radiation and brachytherapy boost with
androgen deprivation for treatment of intermediate-risk prostate cancer
SO CANCER
LA English
DT Article
DE prostate; brachytherapy; radiation; cooperative group trial; hormonal
therapy
ID RANDOMIZED CONTROLLED-TRIAL; CONFORMAL RADIATION; SEED IMPLANTATION;
ANTIGEN BOUNCE; FREE SURVIVAL; RADIOTHERAPY; THERAPY; TOXICITY;
SUPPRESSION
AB BACKGROUND: Combined transperineal prostate brachytherapy and external beam radiation therapy (EBRT) is widely used for treatment of prostate cancer. Long-term efficacy and toxicity results of a multicenter phase 2 trial assessing combination of EBRT and transperineal prostate brachytherapy boost with androgen deprivation therapy (ADT) for intermediate-risk prostate cancer are presented. METHODS: Intermediate-risk patients per Memorial Sloan-Kettering Cancer Center/National Comprehensive Cancer Network criteria received 6 months of ADT, and 45 grays (Gy) EBRT to the prostate and seminal vesicles, followed by transperineal prostate brachytherapy with I(125) (100 Gy) or Pd(103) (90 Gy). Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2 and Radiation Therapy Oncology Group late radiation morbidity scoring systems. Disease-free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant, or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive prostate-specific antigen rises >1.0 ng/mL after 18 months from treatment start), the 1997 American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan-Meier method was used to estimate DFS and overall survival. RESULTS: Sixty-one of 63 enrolled patients were eligible. Median follow-up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six-year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. Six deaths occurred; only 1 was attributed to prostate cancer. Six-year overall survival was 96.1%. CONCLUSIONS: In a cooperative setting, combination of EBRT and transperineal prostate brachytherapy boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate-risk prostate cancer. Cancer 2011; 117: 5579-88. (C) 2011 American Cancer Society.
C1 [Hurwitz, Mark D.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA.
[Hurwitz, Mark D.] Harvard Univ, Sch Med, Boston, MA USA.
[Halabi, Susan; Archer, Laura] Duke Univ, Med Ctr, Canc & Leukemia Grp Stat Ctr B, Durham, NC USA.
[McGinnis, Lamar S.] Presbyterian Hosp, Dept Radiat Oncol, Charlotte, NC USA.
[Kuettel, Michael R.] Roswell Pk Canc Inst, Dept Radiat Oncol, Buffalo, NY 14263 USA.
[DiBiase, Steven J.] Robert Wood Johnson Med Sch, Dept Radiat Oncol, Cherry Hill, NJ USA.
[Small, Eric J.] Univ Calif San Francisco, Comprehens Care Ctr, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
RP Hurwitz, MD (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, 75 Francis St,ASB1,L2, Boston, MA 02115 USA.
EM mhurwitz@lroc.harvard.edu
FU National Cancer Institute [CA31946, CA33601]; [CA32291]; [CA45808];
[CA59518]; [CA60138]; [CA45418]; [CA47577]; [CA114558-02];
[CA35421]; [CA21060]; [CA31983]; [CA37135]; [CA12046]; [CA47559];
[CA77406]; [CA03927]
FX This work was supported, in part, by grants from the National Cancer
Institute (CA31946) to the Cancer and Leukemia Group B (Monica M.
Bertagnolli, MD, Chair) and to the CALGB Statistical Center (Stephen
George, PhD, CA33601). M.D.H. was supported by CA32291. S.H. and L.A.
were supported by CA33601. L.S.M. was supported by CA45808. M.R.K. was
supported by CA59518. E.J.S. was supported by CA60138. The content of
this article 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. Community Clinical Oncology
Program, Wilmington, Delaware-Stephen Grubbs, MD, supported by CA45418;
Dana-Farber Cancer Institute, Boston, Massachusetts-Harold J. Burstein,
MD, PhD, supported by CA32291; Duke University Medical Center, Durham,
North Carolina-Jeffrey Crawford, MD, supported by CA47577; Missouri
Baptist Medical Center, St Louis, Missouri-Alan P. Lyss, MD, supported
by CA114558-02; Nevada Cancer Research Foundation Community Clinical
Oncology Program, Las Vegas, Nevada-John A. Ellerton, MD, supported by
CA35421; Roswell Park Cancer Institute, Buffalo, New York-Ellis Levine,
MD, supported by CA59518; Southeast Cancer Control Consortium Inc.
Community Clinical Oncology Program, Goldsboro, North Carolina-James N.
Atkins, MD, supported by CA45808; State University of New York Upstate
Medical University, Syracuse, New York-Stephen L. Graziano, MD,
supported by CA21060; University of Maryland Greenebaum Cancer Center,
Baltimore, Maryland-Martin Edelman, MD, supported by CA31983; University
of Massachusetts Medical School, Worcester, Massachusetts-William V.
Walsh, MD, supported by CA37135; University of Missouri/Ellis Fischel
Cancer Center, Columbia, Missouri-Michael C Perry, MD, supported by
CA12046; University of North Carolina at Chapel Hill, Chapel Hill, North
Carolina-Thomas C. Shea, MD, supported by CA47559; University of
Vermont, Burlington, Vermont-Steven M. Grunberg, MD, supported by
CA77406; and Wake Forest University School of Medicine, Winston-Salem,
North Carolina-David D Hurd, MD, supported by CA03927.
NR 25
TC 13
Z9 14
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD DEC 15
PY 2011
VL 117
IS 24
BP 5579
EP 5588
DI 10.1002/cncr.26203
PG 10
WC Oncology
SC Oncology
GA 855PB
UT WOS:000297575600017
PM 22535500
ER
PT J
AU Russel, S
Frand, AR
Ruvkun, G
AF Russel, Sascha
Frand, Alison R.
Ruvkun, Gary
TI Regulation of the C. elegans molt by pqn-47
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Molt (moult); C11orf9 MRF pqn-47; Poly glutamine protein; Endocrine
secretion
ID NEMATODE CAENORHABDITIS-ELEGANS; UNFOLDED PROTEIN RESPONSE; NUCLEAR
EXPORT; HETEROCHRONIC MUTANTS; INNATE IMMUNITY; GENES; DROSOPHILA;
LET-7; IDENTIFICATION; MICRORNAS
AB C. elegans molts at the end of each of its four larval stages but this cycle ceases at the reproductive adult stage. We have identified a regulator of molting, pqn-47. Null mutations in pqn-4 7 cause a developmental arrest at the first larval molt, showing that this gene activity is required to transit the molt. Mutants with weak alleles of pqn-47 complete the larval molts but fail to exit the molting cycle at the adult stage. These phenotypes suggest that pqn-47 executes key aspects of the molting program including the cessation of molting cycles. The pqn-47 gene encodes a protein that is highly conserved in animal phylogeny but probably misannotated in genome sequences due to much less significant homology to a yeast transcription factor. A PQN-47::GFP fusion gene is expressed in many neurons, vulval precursor cells, the distal tip cell (DTC), intestine, and the lateral hypodermal seam cells but not in the main body hypodermal syncytium (hyp7) that underlies, synthesizes, and releases most of the collagenous cuticle. A functional PQN-47::GFP fusion protein localizes to the cytoplasm rather than the nucleus at all developmental stages, including the periods preceding and during ecdysis when genetic analysis suggests that pqn-47 functions. The cytoplasmic localization of PQN-47::GFP partially overlaps with the endoplasmic reticulum, suggesting that PQN-47 is involved in the extensive secretion of cuticle components or hormones that occurs during molts. The mammalian and insect homologues of pqn-47 may serve similar roles in regulated secretion. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Russel, Sascha; Frand, Alison R.; Ruvkun, Gary] Harvard Univ, Massachusetts Gen Hosp, Dept Mol Biol, Sch Med,Dept Genet, Boston, MA 02114 USA.
RP Ruvkun, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Mol Biol, Sch Med,Dept Genet, Simches Res Bldg,185 Cambridge St,CPZN-7250, Boston, MA 02114 USA.
EM russel@molbio.mgh.harvard.edu; AFrand@mednet.ucla.edu;
ruvkun@molbio.mgh.harvard.edu
FU NIGMS NIH HHS [R01 GM044619]
NR 65
TC 7
Z9 8
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD DEC 15
PY 2011
VL 360
IS 2
BP 297
EP 309
DI 10.1016/j.ydbio.2011.09.025
PG 13
WC Developmental Biology
SC Developmental Biology
GA 854YV
UT WOS:000297531600004
PM 21989027
ER
PT J
AU Poulikakos, PI
Persaud, Y
Janakiraman, M
Kong, XJ
Ng, C
Moriceau, G
Shi, HB
Atefi, M
Titz, B
Gabay, MT
Salton, M
Dahlman, KB
Tadi, M
Wargo, JA
Flaherty, KT
Kelley, MC
Misteli, T
Chapman, PB
Sosman, JA
Graeber, TG
Ribas, A
Lo, RS
Rosen, N
Solit, DB
AF Poulikakos, Poulikos I.
Persaud, Yogindra
Janakiraman, Manickam
Kong, Xiangju
Ng, Charles
Moriceau, Gatien
Shi, Hubing
Atefi, Mohammad
Titz, Bjoern
Gabay, May Tal
Salton, Maayan
Dahlman, Kimberly B.
Tadi, Madhavi
Wargo, Jennifer A.
Flaherty, Keith T.
Kelley, Mark C.
Misteli, Tom
Chapman, Paul B.
Sosman, Jeffrey A.
Graeber, Thomas G.
Ribas, Antoni
Lo, Roger S.
Rosen, Neal
Solit, David B.
TI RAF inhibitor resistance is mediated by dimerization of aberrantly
spliced BRAF(V600E)
SO NATURE
LA English
DT Article
ID BRAF; KINASE; HETERODIMERIZATION; MELANOMA; PATHWAY; CRAF; MEK
AB Activated RAS promotes dimerization of members of the RAF kinase family(1-3). ATP-competitive RAF inhibitors activate ERK signalling(4-7) by transactivating RAF dimers(4). In melanomas with mutant BRAF(V600E), levels of RAS activation are low and these drugs bind to BRAF(V600E) monomers and inhibit their activity. This tumour-specific inhibition of ERK signalling results in a broad therapeutic index and RAF inhibitors have remarkable clinical activity in patients with melanomas that harbour mutant BRAF(V600E)(8). However, resistance invariably develops. Here, we identify a new resistance mechanism. We find that a subset of cells resistant to vemurafenib (PLX4032, RG7204) express a 61-kDa variant form of BRAF(V600E), p61BRAF(V600E), which lacks exons 4-8, a region that encompasses the RAS-binding domain. p61BRAF(V600E) shows enhanced dimerization in cells with low levels of RAS activation, as compared to full-length BRAF(V600E). In cells in which p61BRAF(V600E) is expressed endogenously or ectopically, ERK signalling is resistant to the RAF inhibitor. Moreover, a mutation that abolishes the dimerization of p61BRAF(V600E) restores its sensitivity to vemurafenib. Finally, we identified BRAF(V600E) splicing variants lacking the RAS-binding domain in the tumours of six of nineteen patients with acquired resistance to vemurafenib. These data support the model that inhibition of ERK signalling by RAF inhibitors is dependent on levels of RAS-GTP too low to support RAF dimerization and identify a novel mechanism of acquired resistance in patients: expression of splicing isoforms of BRAF(V600E) that dimerize in a RAS-independent manner.
C1 [Persaud, Yogindra; Janakiraman, Manickam; Solit, David B.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Poulikakos, Poulikos I.; Gabay, May Tal; Tadi, Madhavi; Rosen, Neal] Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol & Chem, New York, NY 10065 USA.
[Kong, Xiangju; Moriceau, Gatien; Shi, Hubing; Lo, Roger S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Div Dermatol, Los Angeles, CA 90095 USA.
[Ng, Charles; Atefi, Mohammad; Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Titz, Bjoern; Graeber, Thomas G.; Ribas, Antoni; Lo, Roger S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Salton, Maayan; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Dahlman, Kimberly B.; Sosman, Jeffrey A.] Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN 37232 USA.
[Wargo, Jennifer A.] Massachusetts Gen Hosp, Ctr Canc, Dept Surg, Boston, MA 02114 USA.
[Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA.
[Kelley, Mark C.] Vanderbilt Ingram Canc Ctr, Dept Surg, Nashville, TN 37232 USA.
[Chapman, Paul B.; Rosen, Neal; Solit, David B.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
RP Solit, DB (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
EM solitd@mskcc.org
RI Titz, Bjorn/B-9516-2008; Shi, Hubing/B-8445-2014;
OI Janakiraman, Manickam/0000-0003-4423-6237; Titz,
Bjoern/0000-0003-4414-4105; Graeber, Thomas/0000-0001-8574-9181; Shi,
Hubing/0000-0002-2926-3440
FU Vanderbilt-Ingram Cancer Center; T. J. Martell Foundation; National
Institutes of Health (NIH); Beene Foundation; Melanoma Research
Alliance; STARR Foundation; Burroughs Wellcome Fund; American Skin
Association; Joint Center for Translational Medicine; Sidney Kimmel
Foundation; Stand Up to Cancer; NIH, NCI, Center for Cancer Research;
Danny Federici Melanoma Fund; [T32 CACA062948-15]
FX We are grateful to M. Baccarini and C. Pritchard for the RAF knockout
mouse embryonic fibroblasts. We would like to thank K. Shokat, C. Zhang,
S. Chandarlapaty, C. Pratilas and K. Robzyk for useful discussions, C.
Liu for her technical expertise and T. J. Riley. We also thank D. Hucks
for technical assistance, P. L. Lyle for scoring the tumour sections,
and T. Chodon for assistance with tumour procurement. The ITR is
supported by the Vanderbilt-Ingram Cancer Center and the T. J. Martell
Foundation. This work has been funded by the National Institutes of
Health (NIH; R. S. L., N.R., D. B. S.), the Beene Foundation (D. B. S.),
the Melanoma Research Alliance (K. T. F., J. A. S. P. B. C., R. S. L.,
N.R., D. B. S.) and the STARR Foundation (N.R., D. B. S.). R. S. L. was
supported by the Burroughs Wellcome Fund, American Skin Association,
Joint Center for Translational Medicine, Sidney Kimmel Foundation, and
Stand Up to Cancer. T. M. was supported in part by the Intramural
Research Program of the NIH, NCI, Center for Cancer Research and P. B.
C. was supported in part by the Danny Federici Melanoma Fund. P. I. P.
was supported by T32 CACA062948-15.
NR 22
TC 572
Z9 581
U1 5
U2 77
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD DEC 15
PY 2011
VL 480
IS 7377
BP 387
EP U144
DI 10.1038/nature10662
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000056
PM 22113612
ER
PT J
AU Ryan, ET
Cronin, CG
Branda, JA
AF Ryan, Edward T.
Cronin, Carmel G.
Branda, John A.
TI Case 38-2011: A 34-Year-Old Man with Diarrhea and Weakness
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; FLACCID QUADRIPARESIS; PARALYSIS;
MICROSPORIDIOSIS; HYPOKALEMIA; ENTERITIS; GIARDIA
C1 [Ryan, Edward T.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
[Cronin, Carmel G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Cronin, Carmel G.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Branda, John A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
FU DiaSorin
FX Dr. Branda reports receiving grant support from DiaSorin. No other
potential conflict of interest relevant to this article was reported.
NR 21
TC 0
Z9 0
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD DEC 15
PY 2011
VL 365
IS 24
BP 2307
EP 2317
DI 10.1056/NEJMcpc1011322
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 861PN
UT WOS:000298031800013
ER
PT J
AU Lipsky, BA
Hoey, CT
Byren, I
AF Lipsky, Benjamin A.
Hoey, Christopher T.
Byren, Ivor
TI Chronic Bacterial Prostatitis: Enterococcal Disease? Reply
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Letter
ID URINARY-TRACT-INFECTIONS; MOXIFLOXACIN; DAPTOMYCIN; RESISTANCE
C1 [Lipsky, Benjamin A.] Univ Washington, Gen Med Serv, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
[Hoey, Christopher T.] VA Puget Sound Hlth Care Syst, Serv Pharm, Seattle, WA USA.
[Byren, Ivor] Univ Oxford, Dept Med, Oxford Radcliffe Hosp, Oxford OX1 2JD, England.
RP Lipsky, BA (reprint author), Univ Washington, Gen Med Serv, Dept Med, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S GMS 123, Seattle, WA 98108 USA.
EM balipsky@uw.edu
OI Lipsky, Benjamin A./0000-0001-9886-5114
NR 13
TC 1
Z9 1
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 DEC 15
PY 2011
VL 53
IS 12
BP 1307
EP U170
DI 10.1093/cid/cir715
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 851OF
UT WOS:000297279700031
ER
PT J
AU Jani, A
Epperson, E
Martin, J
Pacic, A
Ljubanovic, D
Martin, SL
Edelstein, CL
AF Jani, Alkesh
Epperson, Elaine
Martin, Jessica
Pacic, Arijana
Ljubanovic, Danica
Martin, Sandra L.
Edelstein, Charles L.
TI Renal Protection From Prolonged Cold Ischemia and Warm Reperfusion in
Hibernating Squirrels
SO TRANSPLANTATION
LA English
DT Article
DE Cold ischemia; Warm reperfusion; Hibernation
ID ARCTIC GROUND-SQUIRRELS; ISCHEMIA/REPERFUSION INJURY; ACCIDENTAL
HYPOTHERMIA; SUSPENDED ANIMATION; HYDROGEN-SULFIDE; LOW-TEMPERATURE;
APOPTOSIS; KIDNEY; PRESERVATION; SURVIVAL
AB Background. We have previously shown that cold ischemia (CI) results in massive increases in caspase-3 activity, tubular apoptosis, and brush border injury (BBI) in mouse kidneys. During hibernation, the 13-lined ground squirrel (GS) cycles through repeated CI during torpor, followed by warm ischemia/reperfusion (WI) during interbout arousal (IBA). We sought to determine whether CI and WI during hibernation caused caspase-3 activation, tubular apoptosis, acute tubular necrosis, or BBI, and reduced renal function. We also determined whether protection was dependent on the stage of hibernation.
Methods. Radiotelemeters were implanted in 1-year-old GS, and core body temperature was remotely monitored. GS kidneys at various stages of hibernation were subjected to ex vivo CI.
Results. Tubular apoptosis was not detected and caspase-3-like activity was not different between hibernating and summer kidneys. Despite prolonged CI followed by WI and reperfusion, acute tubular necrosis and apoptosis did not occur in hibernating kidneys. BBI was absent in torpid kidneys but significantly increased in IBA kidneys and associated with an increase in caspase-3-like activity, suggesting that IBA kidneys are more susceptible to injury than summer or torpid kidneys. Renal function and urine concentrating ability diminished during torpor but returned during IBA.
Conclusions. Despite BBI, IBA kidneys clear serum creatinine and concentrate urine. Kidneys from both summer and hibernating animals tolerated ex vivo CI, confirming that protection from apoptotic and necrotic cell death is independent of the stage of hibernation. An understanding of how renal protection occurs during hibernation may help in understanding the pathophysiology of delayed graft function.
C1 [Jani, Alkesh; Martin, Jessica; Edelstein, Charles L.] Univ Colorado, Div Renal Dis & Hypertens, Aurora, CO 80262 USA.
[Jani, Alkesh; Martin, Jessica; Edelstein, Charles L.] Univ Colorado, Denver Vet Affairs Med Ctr, Aurora, CO 80262 USA.
[Epperson, Elaine; Martin, Sandra L.] Univ Colorado, Dept Cell & Dev Biol, Aurora, CO 80262 USA.
[Pacic, Arijana; Ljubanovic, Danica] Univ Zagreb, Sch Med, Dept Pathol, Zagreb Univ Hosp Dubrava, Zagreb 41001, Croatia.
RP Jani, A (reprint author), Univ Colorado, Div Renal Dis & Hypertens, Anschutz Med Campus,Box C281,12700 East,19th Ave, Aurora, CO 80262 USA.
EM alkesh.jani@ucdenver.edu
FU NIH [K08DK69512, R01-HL-089049, RO1-DK-056851, RO1-DK-074835]
FX This study was supported by NIH grants K08DK69512 (A.J.), R01-HL-089049
(S. L. M.), and RO1-DK-056851 and RO1-DK-074835 (C. L. E.).
NR 44
TC 16
Z9 18
U1 2
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD DEC 15
PY 2011
VL 92
IS 11
BP 1215
EP 1221
DI 10.1097/TP.0b013e3182366401
PG 7
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 853DP
UT WOS:000297406700010
PM 22082817
ER
PT J
AU Baselga, J
Tolaney, S
Hart, L
Gomez, P
Gartner, E
DeCillis, A
Ruiz-Soto, R
Lager, J
Burris, H
AF Baselga, J.
Tolaney, S.
Hart, L.
Gomez, P.
Gartner, E.
DeCillis, A.
Ruiz-Soto, R.
Lager, J.
Burris, H.
TI A Phase 1/2 Dose-Escalation Study of SAR245408 (508) or SAR245409 (S09)
in Combination with Letrozole (L) in Subjects with Hormone
Receptor-Positive and HER2-Negative (HR+/HER2-) Breast Cancer (BC)
Refractory to a Nonsteroidal Aromatase Inhibitor (AI)
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Baselga, J.; Tolaney, S.; Hart, L.; Gomez, P.; Gartner, E.; DeCillis, A.; Ruiz-Soto, R.; Lager, J.; Burris, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Florida Canc Specialists Drug Dev Unit, Ft Myers, FL USA.
Vail dHebron Oncol Serv, Barcelona, Spain.
Wayne State Univ, Karmanos Canc Inst Hematol Oncol, Detroit, MI USA.
Exelixis, San Francisco, CA USA.
Sanofi, Cambridge, MA USA.
Sarah Canon Res Ctr, Nashville, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P1-17-09
DI 10.1158/0008-5472.SABCS11-P1-17-09
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800310
ER
PT J
AU Baselga, J
Schwartzberg, LS
Petrenciuc, O
Shan, M
Gradishar, WJ
AF Baselga, J.
Schwartzberg, L. S.
Petrenciuc, O.
Shan, M.
Gradishar, W. J.
TI Phase 3 Trial Comparing Capecitabine in Combination with Sorafenlb or
Placebo for Treatment of Locally Advanced or Metastatic HER2-Negative
Breast Cancer (RESILIENCE).
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Baselga, J.; Schwartzberg, L. S.; Petrenciuc, O.; Shan, M.; Gradishar, W. J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
Bayer HealthCare Pharmaceut, Barmen, Germany.
Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA OT3-01-09
DI 10.1158/0008-5472.SABCS11-OT3-01-09
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800038
ER
PT J
AU Baselga, J
Kim, SB
Im, SA
Hegg, R
Im, YH
Roman, L
Pedrini, JL
Cortes, J
Knott, A
Clark, E
Ross, GA
Swain, SM
AF Baselga, J.
Kim, S-B
Im, S-A
Hegg, R.
im, Y-H
Roman, L.
Pedrini, J. L.
Cortes, J.
Knott, A.
Clark, E.
Ross, G. A.
Swain, S. M.
TI A Phase III, Randomized, Double-Blind, Placebo-Controlled Registration
Trial To Evaluate the Efficacy and Safety of Pertuzumab plus Trastuzumab
plus Docetaxel vs. Placebo plus Trastuzumab plus Docetaxel in Patients
with Previously Untreated HER2-Positive Metastatic Breast Cancer
(CLEOPATRA)
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Baselga, J.; Kim, S-B; Im, S-A; Hegg, R.; im, Y-H; Roman, L.; Pedrini, J. L.; Cortes, J.; Knott, A.; Clark, E.; Ross, G. A.; Swain, S. M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea.
Seoul Natl Univ, Coll Med, Seoul, South Korea.
Hosp Perola Byington, Sao Paulo, Brazil.
Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea.
Leningrad Reg Oncol Dispensary, St Petersburg, Russia.
Conceicao Hosp, CPMEC Mastol Unit, Porto Alegre, RS, Brazil.
Vali dHebron Univ Hosp, Barcelona, Spain.
Roche Prod Ltd, Welwyn Garden City, Herts, England.
Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA S5-5
DI 10.1158/0008-5472.SABCS11-S5-5
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800269
ER
PT J
AU Chavarri-Guerra, Y
Liedke, P
Symecko, H
Moy, B
Higgins, M
St Louis, J
Finkelstein, D
Goss, P
AF Chavarri-Guerra, Y.
Liedke, P.
Symecko, H.
Moy, B.
Higgins, M.
St Louis, J.
Finkelstein, D.
Goss, P.
TI Global Patterns of Care for HER2/Neu Overexpressing Breast Cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Chavarri-Guerra, Y.; Liedke, P.; Symecko, H.; Moy, B.; Higgins, M.; St Louis, J.; Finkelstein, D.; Goss, P.] Massachusetts Gen Hosp, Avon Int Breast Canc Program, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P1-12-26
DI 10.1158/0008-5472.SABCS11-P1-12-26
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800294
ER
PT J
AU Chavarri-Guerra, Y
Liedke, PER
Symecko, H
Hammond, EE
Higgins, MJ
Finkelstein, D
Goss, PE
AF Chavarri-Guerra, Y.
Liedke, P. E. R.
Symecko, H.
Hammond, E. E.
Higgins, M. J.
Finkelstein, D.
Goss, P. E.
TI Patterns of Care of Newly Diagnosed Patients with Breast Cancer in
Mexico.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Chavarri-Guerra, Y.; Liedke, P. E. R.; Symecko, H.; Hammond, E. E.; Higgins, M. J.; Finkelstein, D.; Goss, P. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P1-11-12
DI 10.1158/0008-5472.SABCS11-P1-11-12
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800254
ER
PT J
AU Collins, LC
Gelber, S
Marotti, JD
Cole, K
Kereakoglow, S
Ruddy, KJ
Brachtel, EF
Schapira, L
Come, SE
Borges, VF
Schedin, PJ
Warner, E
Winer, E
Partridge, A
AF Collins, L. C.
Gelber, S.
Marotti, J. D.
Cole, K.
Kereakoglow, S.
Ruddy, K. J.
Brachtel, E. F.
Schapira, L.
Come, S. E.
Borges, V. F.
Schedin, P. J.
Warner, E.
Winer, E.
Partridge, A.
TI Molecular Phenotype of Breast Cancers in a Large Cohort of Young Women
According to Time Interval Since Pregnancy.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Collins, L. C.; Gelber, S.; Marotti, J. D.; Cole, K.; Kereakoglow, S.; Ruddy, K. J.; Brachtel, E. F.; Schapira, L.; Come, S. E.; Borges, V. F.; Schedin, P. J.; Warner, E.; Winer, E.; Partridge, A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Dartmouth Hitchcock Med Ctr, Hanover, NH USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Colorado, Ctr Canc, Boulder, CO 80309 USA.
Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P4-11-12
DI 10.1158/0008-5472.SABCS11-P4-11-12
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801314
ER
PT J
AU Cook, RS
Balko, JM
Rinehart, C
Miller, TW
Polyak, K
Prat, A
Perou, CM
Arteaga, CL
AF Cook, R. S.
Balko, J. M.
Rinehart, C.
Miller, T. W.
Polyak, K.
Prat, A.
Perou, C. M.
Arteaga, C. L.
TI ErbB3 Expression Is Required for Maintenance of Normal and Transformed
Luminal Breast Epithelial Cells
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Cook, R. S.; Balko, J. M.; Rinehart, C.; Miller, T. W.; Polyak, K.; Prat, A.; Perou, C. M.; Arteaga, C. L.] Vanderbilt Univ, Nashville, TN 37235 USA.
UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA.
Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA S2-6
DI 10.1158/0008-5472.SABCS11-52-6
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800047
ER
PT J
AU Coopey, SB
Mazzola, E
Buckley, JM
Sharko, J
Belli, AK
Kim, EMH
Polufriaginof, F
Parmigiani, G
Garber, JE
Smith, BL
Gadd, MA
Specht, MC
Guidi, AJ
Roche, CA
Hughes, KS
AF Coopey, S. B.
Mazzola, E.
Buckley, J. M.
Sharko, J.
Belli, A. K.
Kim, E. M. H.
Polufriaginof, F.
Parmigiani, G.
Garber, J. E.
Smith, B. L.
Gadd, M. A.
Specht, M. C.
Guidi, A. J.
Roche, C. A.
Hughes, K. S.
TI Clarifying the Risk of Breast Cancer in Women with Atypical Breast
Lesions.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Coopey, S. B.; Mazzola, E.; Buckley, J. M.; Sharko, J.; Belli, A. K.; Kim, E. M. H.; Polufriaginof, F.; Parmigiani, G.; Garber, J. E.; Smith, B. L.; Gadd, M. A.; Specht, M. C.; Guidi, A. J.; Roche, C. A.; Hughes, K. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Newton Wellesley Hosp, Newton, MA USA.
Wayne State Univ, Detroit, MI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA S4-4
DI 10.1158/0008-5472.SABCS11-S4-4
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800180
ER
PT J
AU Cortesi, L
De Nicolo, A
Medici, V
Marino, M
Turchetti, D
Pradella, LM
Rossi, G
Parisini, E
Federico, M
AF Cortesi, L.
De Nicolo, A.
Medici, V.
Marino, M.
Turchetti, D.
Pradella, L. M.
Rossi, G.
Parisini, E.
Federico, M.
TI Collective Evidence Suggests Neutrality for BRCA1 V1687I, a Novel
Sequence Variant in the Conserved THV Motif of the First BRCT Repeat.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Cortesi, L.; De Nicolo, A.; Medici, V.; Marino, M.; Turchetti, D.; Pradella, L. M.; Rossi, G.; Parisini, E.; Federico, M.] Univ Modena & Reggio Emilia, Modena, Italy.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Univ Bologna, Bologna, Italy.
Italian Inst Technol, Milan, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P2-07-03
DI 10.1158/0008-5472.SABCS11-P2-07-03
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699802226
ER
PT J
AU Dang, C
Tolaney, S
Najita, J
Gelman, R
Yardley, D
Marcom, K
Albain, K
Rugo, H
Miller, K
Ellis, M
Shapira, I
Wolff, A
Carey, L
Vandat, L
Burdette-Radoux, S
Budd, T
Krop, I
Burstein, H
Hudis, C
Winer, E
AF Dang, C.
Tolaney, S.
Najita, J.
Gelman, R.
Yardley, D.
Marcom, K.
Albain, K.
Rugo, H.
Miller, K.
Ellis, M.
Shapira, I.
Wolff, A.
Carey, L.
Vandat, L.
Burdette-Radoux, S.
Budd, T.
Krop, I.
Burstein, H.
Hudis, C.
Winer, E.
TI Cardiac Outcomes of Patients on Adjuvant Weekly Paclitaxel (T) and
Trastuzumab (H) for Node Negative, HER2 Positive Breast Cancer (BCA).
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 Mem Sloan Kettering Canc Ctr, New York, NY USA.
Dana Farber Canc Inst, Boston, MA USA.
Tennessee Oncol, Greeneville, TN USA.
Sarah Cannon Res Inst, Nashville, TN USA.
Duke Univ, Durham, NC 27706 USA.
Loyola Univ, Med Ctr, New Orleans, LA 70118 USA.
Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA.
Indiana Univ, Bloomington, IN 47405 USA.
Washington Univ, St Louis, MO 63130 USA.
North Shore Long Isl Jewish Med Ctr, New Hyde Pk, NY USA.
Johns Hopkins Univ, Baltimore, MD 21218 USA.
Univ N Carolina, Chapel Hill, NC 27515 USA.
Weill Cornell Med Coll, New York, NY USA.
Univ Vermont, Burlington, VT 05405 USA.
Cleveland Clin, Taussig Canc Inst Case, Cleveland, OH USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P2-18-02
DI 10.1158/0008-5472.SABCS11-P2-18-02
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801202
ER
PT J
AU De Los Santos, J
Cantor, A
Mcguire, K
Golshan, M
Meric-Bernstam, F
Horton, J
Nanda, R
Amos, K
Forero, A
Hudis, C
Meszoely, I
Hwang, S
AF De Los Santos, J.
Cantor, A.
Mcguire, K.
Golshan, M.
Meric-Bernstam, F.
Horton, J.
Nanda, R.
Amos, K.
Forero, A.
Hudis, C.
Meszoely, I.
Hwang, S.
TI Magnetic Resonance Imaging as a Predictor of Pathologic Response in
Patients Treated with Neoadjuvant Systemic Treatment for Operable Breast
Cancer (TBCRC 017).
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [De Los Santos, J.; Cantor, A.; Mcguire, K.; Golshan, M.; Meric-Bernstam, F.; Horton, J.; Nanda, R.; Amos, K.; Forero, A.; Hudis, C.; Meszoely, I.; Hwang, S.] Univ Alabama Birmingham, Birmingham, AL USA.
Univ N Carolina, Chapel Hill, NC USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Duke Univ, Med Ctr, Durham, NC USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Vanderbilt Univ, Nashville, TN 37235 USA.
Univ Chicago, Chicago, IL 60637 USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P2-08-02
DI 10.1158/0008-5472.SABCS11-P2-08-02
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800371
ER
PT J
AU De Los Santos, J
Cantor, A
Mcguire, K
Golshan, M
Meric-Bernstam, F
Horton, J
Nanda, R
Amos, K
Forero, A
Hudis, C
Meszoely, I
Hwang, S
AF De Los Santos, J.
Cantor, A.
Mcguire, K.
Golshan, M.
Meric-Bernstam, F.
Horton, J.
Nanda, R.
Amos, K.
Forero, A.
Hudis, C.
Meszoely, I.
Hwang, S.
TI Surgical Patterns of Care after Magnetic Resonance Imaging in the
Academic Setting in Patients with Operable Breast Cancer Treated with
Neoadjuvant Systemic Therapy: A Secondary Analysis of TBCRC 017
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [De Los Santos, J.; Cantor, A.; Mcguire, K.; Golshan, M.; Meric-Bernstam, F.; Horton, J.; Nanda, R.; Amos, K.; Forero, A.; Hudis, C.; Meszoely, I.; Hwang, S.] Univ Alabama Birmingham, Birmingham, AL USA.
Univ N Carolina, Chapel Hill, NC USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Duke Univ, Med Ctr, Durham, NC USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Vanderbilt Univ, Nashville, TN 37235 USA.
Univ Chicago, Chicago, IL 60637 USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P2-15-01
DI 10.1158/0008-5472.SABCS11-P2-15-01
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801435
ER
PT J
AU Dick, MG
Masciari, S
Miron, A
Miron, P
Foley, K
Gelman, R
Dillon, DA
Richardson, AL
Verselis, SJ
Lypas, G
Krop, IE
Garber, JE
AF Dick, M. G.
Masciari, S.
Miron, A.
Miron, P.
Foley, K.
Gelman, R.
Dillon, D. A.
Richardson, A. L.
Verselis, S. J.
Lypas, G.
Krop, I. E.
Garber, J. E.
TI Prevalence of Germline TP53 Mutations in Young Women with HER2-Positive
Breast Cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Dick, M. G.; Masciari, S.; Miron, A.; Miron, P.; Foley, K.; Gelman, R.; Dillon, D. A.; Richardson, A. L.; Verselis, S. J.; Lypas, G.; Krop, I. E.; Garber, J. E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 8
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P1-09-03
DI 10.1158/0008-5472.SABCS11-P1-09-03
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800146
ER
PT J
AU Freedman, RA
Hughes, ME
Ottesen, RA
He, Y
Weeks, JC
Wong, YN
Theriault, RL
Keating, NL
AF Freedman, R. A.
Hughes, M. E.
Ottesen, R. A.
He, Y.
Weeks, J. C.
Wong, Y-N
Theriault, R. L.
Keating, N. L.
TI Racial/Ethnic Differences in Adjuvant Trastuzumab Receipt for Women with
Breast Cancer within the National Comprehensive Cancer Network.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Freedman, R. A.; Hughes, M. E.; Ottesen, R. A.; He, Y.; Weeks, J. C.; Wong, Y-N; Theriault, R. L.; Keating, N. L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
City Hope Natl Med Ctr, Duarte, CA USA.
Harvard Univ, Sch Med, Boston, MA USA.
Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P1-11-02
DI 10.1158/10008-5472.SABCS11-P1-11-02
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800243
ER
PT J
AU Goss, PE
Richardson, H
Ingle, JN
Chlebowski, RT
Fabian, CJ
Garber, JE
Sarto, GE
Hiltz, A
Tu, D
Cheung, AM
AF Goss, P. E.
Richardson, H.
Ingle, J. N.
Chlebowski, R. T.
Fabian, C. J.
Garber, J. E.
Sarto, G. E.
Hiltz, A.
Tu, D.
Cheung, A. M.
TI Influence of Two Years of Exemestane on Bone Mineral Density in
Postmenopausal Women at Increased Risk of Developing Breast Cancer; a
Companion Study to the NCIC CTG MAP.3 Trial.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Goss, P. E.; Richardson, H.; Ingle, J. N.; Chlebowski, R. T.; Fabian, C. J.; Garber, J. E.; Sarto, G. E.; Hiltz, A.; Tu, D.; Cheung, A. M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Queens Univ, Kingston, ON, Canada.
Mayo Clin, Rochester, MN USA.
Los Angeles Biomed Res Inst, Torrance, CA USA.
Univ Kansas, Med Ctr, Westwood, KS USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Ctr Womens Hlth & Hlth Res, Madison, WI USA.
Toronto Gen Hosp, Toronto, ON, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P4-11-13
DI 10.1158/0008-5472.SABCS11-P4-11-13
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801315
ER
PT J
AU Goss, PE
Barrios, CH
Bell, R
Finkelstein, D
Iwata, H
Martin, M
Braun, A
Ke, C
Maniar, T
Braun, S
Dansey, R
Coleman, RE
AF Goss, P. E.
Barrios, C. H.
Bell, R.
Finkelstein, D.
Iwata, H.
Martin, M.
Braun, A.
Ke, C.
Maniar, T.
Braun, S.
Dansey, R.
Coleman, R. E.
TI A Phase 3 Randomized, Double Blind, Placebo-Controlled Multicenter Study
Comparing Denosumab with Placebo as Adjuvant Treatment for Women with
Early-Stage Breast Cancer Who Are at High Risk of Disease Recurrence
(D-CARE).
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Goss, P. E.; Barrios, C. H.; Bell, R.; Finkelstein, D.; Iwata, H.; Martin, M.; Braun, A.; Ke, C.; Maniar, T.; Braun, S.; Dansey, R.; Coleman, R. E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
PUCRS Sch Med, Porto Alegre, RS, Brazil.
Barwon Hlth, Geelong, Vic, Australia.
Aichi Canc Ctr Hosp, Nagoya, Aichi 464, Japan.
Hosp Gregorio Maranon, Madrid, Spain.
Amgen Inc, Thousand Oaks, CA 91320 USA.
Amgen Europe GmbH, Zug, Switzerland.
Univ Sheffield, Sheffield, S Yorkshire, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA OT1-01-03
DI 10.1158/0008-5472.SABCS11-OT1-01-03
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801004
ER
PT J
AU Henry, NL
Banerjee, M
Hayden, J
Yakim, E
Schott, AF
Stearns, V
Partridge, AH
Hayes, DF
AF Henry, N. L.
Banerjee, M.
Hayden, J.
Yakim, E.
Schott, A. F.
Stearns, V.
Partridge, A. H.
Hayes, D. F.
TI Predictors of Recovery of Ovarian Function during Aromatase Inhibitor
(AI) Therapy
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Henry, N. L.; Banerjee, M.; Hayden, J.; Yakim, E.; Schott, A. F.; Stearns, V.; Partridge, A. H.; Hayes, D. F.] Univ Michigan, Sch Med, Ann Arbor, MI USA.
Johns Hopkins Sch Med, Baltimore, MD 21205 USA.
Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA PD04-01
DI 10.1158/0008-5472.SABCS11-PD04-01
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800081
ER
PT J
AU Hershman, DL
Wilde, ET
Wright, JD
Buono, DL
Kalinsky, K
Malin, J
Tsai, WY
Neugut, AL
AF Hershman, D. L.
Wilde, E. T.
Wright, J. D.
Buono, D. L.
Kalinsky, K.
Malin, J.
Tsai, W. Y.
Neugut, A. L.
TI Uptake and Economic Impact of First-Cycle Colony Stimulating Factor Use
during the Adjuvant Treatment of Breast Cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Hershman, D. L.; Wilde, E. T.; Wright, J. D.; Buono, D. L.; Kalinsky, K.; Malin, J.; Tsai, W. Y.; Neugut, A. L.] Columbia Univ, New York, NY USA.
Mailman Sch Publ Hlth, New York, NY USA.
Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA PID06-04
DI 10.1158/0008-5472.SABCS11-P006-04
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800108
ER
PT J
AU Hortobagyi, GN
Piccart, M
Rugo, H
Burris, H
Campone, M
Noguchi, S
Gnant, M
Pritchard, KI
Vittori, L
Mukhopadhyay, P
Sahmoud, T
Lebwohl, D
Baselga, J
AF Hortobagyi, G. N.
Piccart, M.
Rugo, H.
Burris, H.
Campone, M.
Noguchi, S.
Gnant, M.
Pritchard, K. I.
Vittori, L.
Mukhopadhyay, P.
Sahmoud, T.
Lebwohl, D.
Baselga, J.
TI Everolimus for Postmenopausal Women with Advanced Breast Cancer: Updated
Results of the BOLERO-2 Phase Ill Trial.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Hortobagyi, G. N.; Piccart, M.; Rugo, H.; Burris, H.; Campone, M.; Noguchi, S.; Gnant, M.; Pritchard, K. I.; Vittori, L.; Mukhopadhyay, P.; Sahmoud, T.; Lebwohl, D.; Baselga, J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Inst Jules Bordet, B-1000 Brussels, Belgium.
Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
Sarah Cannon Res Inst, Nashville, TN USA.
Ctr Rech Cancerol, Inst Cancerol Ouest Rene Gauducheau, St Herblain, France.
Osaka Univ, Osaka, Japan.
Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria.
Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
Univ Toronto, Toronto, ON, Canada.
Novartis Pharma AG, Basel, Switzerland.
Novartis Pharmaceut, E Hanover, NJ USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 3
Z9 4
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA S3-7
DI 10.1158/0008-5472.SABCS11-S3-7
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800136
ER
PT J
AU Isakoff, SJ
Overmoyer, B
Tung, NM
Gelman, RS
Habin, K
Qian, J
Giranda, V
Shepherd, S
Garber, JE
Ellisen, LW
Winer, EP
Goss, PE
AF Isakoff, S. J.
Overmoyer, B.
Tung, N. M.
Gelman, R. S.
Habin, K.
Qian, J.
Giranda, V.
Shepherd, S.
Garber, J. E.
Ellisen, L. W.
Winer, E. P.
Goss, P. E.
TI A Phase II Trial Expansion Cohort of the PARP Inhibitor Veliparib
(ABT888) and Temozolomide in BRCA1/2 Associated Metastatic Breast
Cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Isakoff, S. J.; Overmoyer, B.; Tung, N. M.; Gelman, R. S.; Habin, K.; Qian, J.; Giranda, V.; Shepherd, S.; Garber, J. E.; Ellisen, L. W.; Winer, E. P.; Goss, P. E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Abbott Labs, Abbott Pk, IL 60064 USA.
NR 0
TC 1
Z9 1
U1 4
U2 4
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 DEC 15
PY 2011
VL 71
SU 24
MA P3-16-05
DI 10.1158/0008-5472.SABCS11-P3-16-05
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801182
ER
PT J
AU Larsen, MS
Bjerre, KD
Laenkholm, AV
Giobbie-Hurder, A
Ejlertsen, B
Lykkesfeldt, AE
Rasmussen, BB
AF Larsen, M. S.
Bjerre, K. D.
Laenkholm, A-V
Giobbie-Hurder, A.
Ejlertsen, B.
Lykkesfeldt, A. E.
Rasmussen, B. B.
TI BcI-2 as a Prognostic Marker in Breast Cancer Patients Receiving
Endocrine Therapy.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Larsen, M. S.; Bjerre, K. D.; Laenkholm, A-V; Giobbie-Hurder, A.; Ejlertsen, B.; Lykkesfeldt, A. E.; Rasmussen, B. B.] Herlev Hosp, DK-2730 Herlev, Denmark.
Rigshosp, DK-2100 Copenhagen, Denmark.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Danish Canc Soc, Inst Canc Biol, Copenhagen, Denmark.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P2-12-08
DI 10.1158/0008-5472.SABCS11-P2-12-08
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800441
ER
PT J
AU Lester-Coll, NH
Lee, JM
Gogineni, K
Hwang, WT
Schwartz, JS
Prosnitz, RG
AF Lester-Coll, N. H.
Lee, J. M.
Gogineni, K.
Hwang, W-T
Schwartz, J. S.
Prosnitz, R. G.
TI A Decision Analysis of Contralateral Prophylactic Mastectomy in Women
Undergoing Treatment for Sporadic Unilateral Breast Cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Lester-Coll, N. H.; Lee, J. M.; Gogineni, K.; Hwang, W-T; Schwartz, J. S.; Prosnitz, R. G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA PD02-02
DI 10.1158/0008-5472.SABCS11-PD02-02
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800063
ER
PT J
AU Liedke, PER
Szymonifka, J
Simon, SD
Barrios, CH
Bines, J
Finkelstein, D
Goss, PE
AF Liedke, P. E. R.
Szymonifka, J.
Simon, S. D.
Barrios, C. H.
Bines, J.
Finkelstein, D.
Goss, P. E.
TI Pregnancy-Associated Breast Cancer Does Not Have a Worse Outcome in the
4912 Women with Breast Cancer of the AMAZONA Project.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Liedke, P. E. R.; Szymonifka, J.; Simon, S. D.; Barrios, C. H.; Bines, J.; Finkelstein, D.; Goss, P. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Fed Sao Paulo, Sao Paulo, Brazil.
Pontificia Univ Catolica Rio Grande do Sul, Porto Alegre, RS, Brazil.
Inst Nacl Canc INCA, Rio De Janeiro, Brazil.
Brazilian Breast Canc Study Grp GBECAM, Sao Paulo, Brazil.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P1-08-17
DI 10.1158/0008-5472.SABCS11-P1-08-17
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800172
ER
PT J
AU Ligibel, JA
Segal, R
Pond, G
Dion, MJ
Pritchard, KI
Levine, M
Goodwin, PJ
AF Ligibel, J. A.
Segal, R.
Pond, G.
Dion, M-J
Pritchard, K. I.
Levine, M.
Goodwin, P. J.
TI Impact of the Lifestyle Intervention Study in Adjuvant Treatment of
Early Breast Cancer (LISA) Weight Loss Intervention upon Physical
Activity.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Ligibel, J. A.; Segal, R.; Pond, G.; Dion, M-J; Pritchard, K. I.; Levine, M.; Goodwin, P. J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Ottawa, Ottawa, ON, Canada.
McMaster Univ, Hamilton, ON, Canada.
Univ Toronto, Toronto, ON, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P4-12-05
DI 10.1158/0008-5472.SABCS11-P4-12-05
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801389
ER
PT J
AU Ligibel, JA
CeMalley, AJ
Fisher, M
Daniel, GW
Winer, EP
Keating, NL
AF Ligibel, J. A.
CeMalley, A. J.
Fisher, M.
Daniel, G. W.
Winer, E. P.
Keating, N. L.
TI Patterns of Bone Density Evaluation in a Community Population Treated
with Aromatase Inhibitors.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Ligibel, J. A.; CeMalley, A. J.; Fisher, M.; Daniel, G. W.; Winer, E. P.; Keating, N. L.] 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 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 DEC 15
PY 2011
VL 71
SU 24
MA P2-17-06
DI 10.1158/0008-5472.SABCS11-P2-17-06
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801102
ER
PT J
AU Lu, BD
Blum, JL
Cortes, J
Rugo, HS
Swanton, C
Eaton, L
Song, Y
Zhang, T
Ebbinghaus, SW
Baselga, J
AF Lu, B. D.
Blum, J. L.
Cortes, J.
Rugo, H. S.
Swanton, C.
Eaton, L.
Song, Y.
Zhang, T.
Ebbinghaus, S. W.
Baselga, J.
TI A Phase 2 Study of Ridaforolimus (RIDA) and Dalotuzumab (DALO) in
Estrogen Receptor Positive (ER plus ) Breast Cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Lu, B. D.; Blum, J. L.; Cortes, J.; Rugo, H. S.; Swanton, C.; Eaton, L.; Song, Y.; Zhang, T.; Ebbinghaus, S. W.; Baselga, J.] Merck Res Labs, Kenilworth, NJ USA.
US Oncol, Texas Oncol, Dallas, TX USA.
Vall DHebron Univ Hosp, Barcelona, Spain.
UCSF Hellen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
Royal Marsend Hosp, Sutton, Surrey, England.
Merck Res Labs, N Wales, PA USA.
Merck Res Labs, Boston, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA OT3-01-16
DI 10.1158/0008-5472.SABCS11-OT3-01-16
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800043
ER
PT J
AU Lubbe, W
Li, T
Hughes, M
Ottesen, R
Cristofanilli, M
Weeks, J
Wong, YN
AF Lubbe, W.
Li, T.
Hughes, M.
Ottesen, R.
Cristofanilli, M.
Weeks, J.
Wong, Y-N
TI Inflammatory Breast Cancer (IBC) in the National Comprehensive Cancer
Network (NCCN): The Disease, the Recurrence Pattern and the Outcome.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Lubbe, W.; Li, T.; Hughes, M.; Ottesen, R.; Cristofanilli, M.; Weeks, J.; Wong, Y-N] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
City Hope Natl Med Ctr, Ctr Canc, Duarte, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P4-20-02
DI 10.1158/0008-5472.SABCS11-P4-20-02
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801431
ER
PT J
AU Luoh, SW
Ramsey, B
Park, B
Keenan, E
AF Luoh, S-W
Ramsey, B.
Park, B.
Keenan, E.
TI Borderline Estrogen and Progesterone Receptor Expression and Efficacy of
Anti-Estrogen Therapy Analyzed by Subpopulation Treatment Effect Pattern
Plot Analysis
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Luoh, S-W; Ramsey, B.; Park, B.; Keenan, E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Portland VA Med Ctr, Portland, OR USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU 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 DEC 15
PY 2011
VL 71
SU 24
MA P5-13-19
DI 10.1158/0008-5472.SABCS11-P5-13-19
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699802089
ER
PT J
AU Malorni, L
Giuliano, M
Migliaccio, I
Wang, T
Creighton, CJ
Lupien, M
Hilsenbeck, SG
Healy, N
Mazumdar, A
Triyedi, MV
Jeselsohn, R
He, HH
Fu, X
Gutierrez, C
Brown, M
Brown, PH
Osborne, CK
Schiff, R
AF Malorni, L.
Giuliano, M.
Migliaccio, I.
Wang, T.
Creighton, C. J.
Lupien, M.
Hilsenbeck, S. G.
Healy, N.
Mazumdar, A.
Triyedi, M. V.
Jeselsohn, R.
He, H. H.
Fu, X.
Gutierrez, C.
Brown, M.
Brown, P. H.
Osborne, C. K.
Schiff, R.
TI AP-1 Blockade Potentiates the Anti-Tumor Effect of Endocrine Treatment
and Reverts the Resistant Phenotype in Hormone Receptor-Positive Breast
Cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Malorni, L.; Giuliano, M.; Migliaccio, I.; Wang, T.; Creighton, C. J.; Lupien, M.; Hilsenbeck, S. G.; Healy, N.; Mazumdar, A.; Triyedi, M. V.; Jeselsohn, R.; He, H. H.; Fu, X.; Gutierrez, C.; Brown, M.; Brown, P. H.; Osborne, C. K.; Schiff, R.] Baylor Coll Med, Houston, TX 77030 USA.
Hosp Prato, Prato, Italy.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Dartmouth Med Sch, Lebanon, NH USA.
UH Coll Pharm, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P4-01-18
DI 10.1158/0008-5472.SABCS11-P4-01-18
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801467
ER
PT J
AU Maunsell, E
Richardson, H
Ingle, JN
Ales-Martinez, JE
Chlebowski, RT
Fabian, CJ
Sarto, GE
Garber, JE
Pujol, P
Hiltz, A
Tu, D
Goss, PE
AF Maunsell, E.
Richardson, H.
Ingle, J. N.
Ales-Martinez, J. E.
Chlebowski, R. T.
Fabian, C. J.
Sarto, G. E.
Garber, J. E.
Pujol, P.
Hiltz, A.
Tu, D.
Goss, P. E.
TI Menopause-Specific and Health-Related Qualities of Life among
Post-Menopausal Women Taking Exemestane for Prevention of Breast Cancer:
Results from the NCIC CTG MAP.3 Placebo-Controlled Randomized Controlled
Trial
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Maunsell, E.; Richardson, H.; Ingle, J. N.; Ales-Martinez, J. E.; Chlebowski, R. T.; Fabian, C. J.; Sarto, G. E.; Garber, J. E.; Pujol, P.; Hiltz, A.; Tu, D.; Goss, P. E.] Univ Laval, Quebec City, PQ, Canada.
[Maunsell, E.; Richardson, H.; Ingle, J. N.; Ales-Martinez, J. E.; Chlebowski, R. T.; Fabian, C. J.; Sarto, G. E.; Garber, J. E.; Pujol, P.; Hiltz, A.; Tu, D.; Goss, P. E.] Queens Univ, Kingston, ON, Canada.
[Maunsell, E.; Richardson, H.; Ingle, J. N.; Ales-Martinez, J. E.; Chlebowski, R. T.; Fabian, C. J.; Sarto, G. E.; Garber, J. E.; Pujol, P.; Hiltz, A.; Tu, D.; Goss, P. E.] Mayo Clin, Rochester, MN USA.
[Maunsell, E.; Richardson, H.; Ingle, J. N.; Ales-Martinez, J. E.; Chlebowski, R. T.; Fabian, C. J.; Sarto, G. E.; Garber, J. E.; Pujol, P.; Hiltz, A.; Tu, D.; Goss, P. E.] Hosp Ntra Sra Sonsoles, Avila, Spain.
[Maunsell, E.; Richardson, H.; Ingle, J. N.; Ales-Martinez, J. E.; Chlebowski, R. T.; Fabian, C. J.; Sarto, G. E.; Garber, J. E.; Pujol, P.; Hiltz, A.; Tu, D.; Goss, P. E.] Los Angeles Biomed Res Inst, Torrance, CA USA.
[Maunsell, E.; Richardson, H.; Ingle, J. N.; Ales-Martinez, J. E.; Chlebowski, R. T.; Fabian, C. J.; Sarto, G. E.; Garber, J. E.; Pujol, P.; Hiltz, A.; Tu, D.; Goss, P. E.] Univ Kansas, Med Ctr, Westwood, KS USA.
[Maunsell, E.; Richardson, H.; Ingle, J. N.; Ales-Martinez, J. E.; Chlebowski, R. T.; Fabian, C. J.; Sarto, G. E.; Garber, J. E.; Pujol, P.; Hiltz, A.; Tu, D.; Goss, P. E.] Ctr Womens Hlth & Hlth Res, Madison, WI USA.
[Maunsell, E.; Richardson, H.; Ingle, J. N.; Ales-Martinez, J. E.; Chlebowski, R. T.; Fabian, C. J.; Sarto, G. E.; Garber, J. E.; Pujol, P.; Hiltz, A.; Tu, D.; Goss, P. E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Maunsell, E.; Richardson, H.; Ingle, J. N.; Ales-Martinez, J. E.; Chlebowski, R. T.; Fabian, C. J.; Sarto, G. E.; Garber, J. E.; Pujol, P.; Hiltz, A.; Tu, D.; Goss, P. E.] CHU Hop Arnaud de Villeneuve, Montpellier, France.
[Maunsell, E.; Richardson, H.; Ingle, J. N.; Ales-Martinez, J. E.; Chlebowski, R. T.; Fabian, C. J.; Sarto, G. E.; Garber, J. E.; Pujol, P.; Hiltz, A.; Tu, D.; Goss, P. E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA S6-1
DI 10.1158/0008-5472.SABCS11-56-1
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800302
ER
PT J
AU Mayer, EL
Ligibel, JA
Burstein, HJ
Peppercorn, JM
Miller, KD
Carey, LA
Dickler, MN
Mayer, IA
Forero, A
Eng-Wong, J
Pletcher, PJ
Ryabin, N
Gelman, R
Wolff, AC
Winer, EP
AF Mayer, E. L.
Ligibel, J. A.
Burstein, H. J.
Peppercorn, J. M.
Miller, K. D.
Carey, L. A.
Dickler, M. N.
Mayer, I. A.
Forero, A.
Eng-Wong, J.
Pletcher, P. J.
Ryabin, N.
Gelman, R.
Wolff, A. C.
Winer, E. P.
TI TBCRC 012: ABCDE, a Phase II Randomized Study of Adjuvant Bevacizumab,
Metronomic Chemotherapy (CM), Diet and Exercise after Preoperative
Chemotherapy for Breast Cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Mayer, E. L.; Ligibel, J. A.; Burstein, H. J.; Peppercorn, J. M.; Miller, K. D.; Carey, L. A.; Dickler, M. N.; Mayer, I. A.; Forero, A.; Eng-Wong, J.; Pletcher, P. J.; Ryabin, N.; Gelman, R.; Wolff, A. C.; Winer, E. P.] Dana Farber Canc Inst, Boston, MA 02115 USA.
Duke Univ, Med Ctr, Durham, NC USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Univ North Carolina Chapel Hill, Durham, NC USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Vanderbilt Univ, Nashville, TN 37235 USA.
Univ Alabama Birmingham, Birmingham, AL USA.
Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
Hoosier Oncol Grp, Indianapolis, IN USA.
Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA OT3-02-04
DI 10.1158/0008-5472.SABCS11-OT3-02-04
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800051
ER
PT J
AU Mayer, IA
Balko, JM
Kuba, MG
Sanders, ME
Yap, J
Li, Y
Winer, E
Arteaga, CL
AF Mayer, I. A.
Balko, J. M.
Kuba, M. G.
Sanders, M. E.
Yap, J.
Li, Y.
Winer, E.
Arteaga, C. L.
TI SU2C Phase Ib Study of pan-PI3K Inhibitor BKM120 Plus Aromatase
Inhibitor Letrozole in ER+/HER2-Metastatic Breast Cancer (MBC).
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Mayer, I. A.; Balko, J. M.; Kuba, M. G.; Sanders, M. E.; Yap, J.; Li, Y.; Winer, E.; Arteaga, C. L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA PD09-05
DI 10.1158/0008-5472.SABCS11-PD09-05
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800094
ER
PT J
AU Meisel, JL
Economy, KE
Zabicki-Calvillo, K
Gelber, S
Kereakoglow, S
Winer, EP
Partridge, AH
Mayer, EL
AF Meisel, J. L.
Economy, K. E.
Zabicki-Calvillo, K.
Gelber, S.
Kereakoglow, S.
Winer, E. P.
Partridge, A. H.
Mayer, E. L.
TI Multidisciplinary Treatment of Pregnancy-Associated Breast Cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Meisel, J. L.; Economy, K. E.; Zabicki-Calvillo, K.; Gelber, S.; Kereakoglow, S.; Winer, E. P.; Partridge, A. H.; Mayer, E. L.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P2-19-02
DI 10.1158/0008-5472.SABCS11-P2-19-02
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801158
ER
PT J
AU Metzger, O
Procter, M
de Azambuja, E
Viale, G
Leyland-Jones, B
Dowsett, M
Gelber, R
Gresko, E
Loi, S
Sotiriou, C
Piccart, M
AF Metzger, O.
Procter, M.
de Azambuja, E.
Viale, G.
Leyland-Jones, B.
Dowsett, M.
Gelber, R.
Gresko, E.
Loi, S.
Sotiriou, C.
Piccart, M.
TI The Magnitude of Trastuzumab Benefit in HER2-Positive (HER2+) Lobular
Breast Carcinoma (BC): Results of a HERA Trial Sub-Group Analysis.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Metzger, O.; Procter, M.; de Azambuja, E.; Viale, G.; Leyland-Jones, B.; Dowsett, M.; Gelber, R.; Gresko, E.; Loi, S.; Sotiriou, C.; Piccart, M.] Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium.
Frontier Sci Scotland Ltd, Kincraig, Kingussie, Scotland.
European Inst Oncol, Milan, Italy.
Emory Univ, Atlanta, GA 30322 USA.
Royal Marsden Hosp, London SW3 6JJ, England.
Inst Canc Res, London SW3 6JB, England.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Roche, Basel, Switzerland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P2-18-01
DI 10.1158/0008-5472.SABCS11-P2-18-01
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801191
ER
PT J
AU Miller, CL
Specht, MC
Ancukiewicz, M
Skolny, MN
Toole, JO
Taghian, AG
AF Miller, C. L.
Specht, M. C.
Ancukiewicz, M.
Skolny, M. N.
Toole, J. O.
Taghian, A. G.
TI Weight-Adjusted Change of Unilateral Arm Volumes for Quantification of
Lymphedema after Bilateral Breast Surgery.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Miller, C. L.; Specht, M. C.; Ancukiewicz, M.; Skolny, M. N.; Toole, J. O.; Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P4-14-01
DI 10.1158/0008-5472.SABCS11-P4-14-01
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801381
ER
PT J
AU Miller, TW
Fox, EM
Balko, JM
Meszoely, IM
Sanders, ME
Kuba, MG
Wagle, N
Garraway, LA
Maira, SM
Arteaga, CL
AF Miller, T. W.
Fox, E. M.
Balko, J. M.
Meszoely, I. M.
Sanders, M. E.
Kuba, M. G.
Wagle, N.
Garraway, L. A.
Maira, S-M
Arteaga, C. L.
TI ER Downregulation with Fulvestrant in Combination with pan-PI3K
Inhibitor BKM120 Synergizes Against ER+/PI3K-Mutant Breast Cancer
Xenografts In Vivo.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Miller, T. W.; Fox, E. M.; Balko, J. M.; Meszoely, I. M.; Sanders, M. E.; Kuba, M. G.; Wagle, N.; Garraway, L. A.; Maira, S-M; Arteaga, C. L.] Vanderbilt Univ, Nashville, TN 37235 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Novartis Inst Biomed Res, Basel, Switzerland.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 15
PY 2011
VL 71
SU 24
MA S3-4
DI 10.1158/0008-5472.SABCS11-53-4
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800102
ER
PT J
AU Moy, B
Shepherd, LE
Chapman, JAW
Le, MA
Gelmon, KA
Elliott, C
Ingle, JN
Goss, PE
AF Moy, B.
Shepherd, L. E.
Chapman, J-A W.
Le, Maitre A.
Gelmon, K. A.
Elliott, C.
Ingle, J. N.
Goss, P. E.
TI NCIC CTG MA.27: Clinical Tolerability and Overall Survival of Racial and
Ethnic Minority Women on Aromatase Inhibitor Therapy.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Moy, B.; Shepherd, L. E.; Chapman, J-A W.; Le, Maitre A.; Gelmon, K. A.; Elliott, C.; Ingle, J. N.; Goss, P. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
Natl Canc Inst, Canada Clin Trials Grp, Kingston, ON, Canada.
British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
Mayo Clin, Rochester, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P2-14-02
DI 10.1158/0008-5472.SABCS11-P2-14-02
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800411
ER
PT J
AU Olson, EM
Flores, LM
Najita, JS
Curley, C
Jeong, J
Murray, K
Savoie, JJ
Winer, EP
Krop, IE
AF Olson, E. M.
Flores, L. M.
Najita, J. S.
Curley, C.
Jeong, J.
Murray, K.
Savoie, J. J.
Winer, E. P.
Krop, I. E.
TI Prospective Validation and Characterization of HER2 Positive Circulating
Tumor Cells in Patients with HER2 Negative Metastatic Breast Cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Olson, E. M.; Flores, L. M.; Najita, J. S.; Curley, C.; Jeong, J.; Murray, K.; Savoie, J. J.; Winer, E. P.; Krop, I. E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P005-07
DI 10.1158/0008-5472.SABCS11-P005-07
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800104
ER
PT J
AU Omer, Z
Hwang, ES
Esserman, LJ
Ozanne, EM
AF Omer, Z.
Hwang, E. S.
Esserman, L. J.
Ozanne, E. M.
TI Words Matter: Influence of DCIS Diagnosis Terminology on Patient
Treatment Decisions
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Omer, Z.; Hwang, E. S.; Esserman, L. J.; Ozanne, E. M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P5-15-01
DI 10.1158/0008-5472.SABCS11-P5-15-01
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699802096
ER
PT J
AU Ozanne, E
Omer, Z
Carlson, K
AF Ozanne, E.
Omer, Z.
Carlson, K.
TI Automated Breast Cancer Risk Assessment: Identifying High Risk Women in
the Primary Care Setting.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Ozanne, E.; Omer, Z.; Carlson, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P4-10-04
DI 10.1158/0008-5472.SABCS11-P4-10-04
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801328
ER
PT J
AU Partridge, AH
Hughes, ME
Ottesen, R
Wong, YN
Edge, SB
Theriault, RL
Blayney, DW
Niland, JC
Winer, EP
Weeks, JC
Tamimi, RM
AF Partridge, A. H.
Hughes, M. E.
Ottesen, R.
Wong, Y-N
Edge, S. B.
Theriault, R. L.
Blayney, D. W.
Niland, J. C.
Winer, E. P.
Weeks, J. C.
Tamimi, R. M.
TI Age and Survival in Women with Early Stage Breast Cancer: An Analysis
Controlling for Tumor Subtype.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Partridge, A. H.; Hughes, M. E.; Ottesen, R.; Wong, Y-N; Edge, S. B.; Theriault, R. L.; Blayney, D. W.; Niland, J. C.; Winer, E. P.; Weeks, J. C.; Tamimi, R. M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
City Hope Natl Med Ctr, Duarte, CA USA.
Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Stanford Canc Ctr, Palo Alto, CA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 15
PY 2011
VL 71
SU 24
MA P1-08-05
DI 10.1158/0008-5472.SABCS11-P1-08-05
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800159
ER
PT J
AU Raj, A
Ko, N
Battaglia, T
Moy, B
AF Raj, A.
Ko, N.
Battaglia, T.
Moy, B.
TI Quality of Breast Cancer Care in a Boston Area Patient Navigator
Program.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Raj, A.; Ko, N.; Battaglia, T.; Moy, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
Boston Med Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P1-11-10
DI 10.1158/10008-5472.SABCS11-P1-11-10
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800252
ER
PT J
AU Rosenberg, SM
Tamimi, RM
Gelber, S
Kereakoglow, S
Borges, V
Come, S
Schapira, L
Winer, E
Partridge, A
AF Rosenberg, S. M.
Tamimi, R. M.
Gelber, S.
Kereakoglow, S.
Borges, V.
Come, S.
Schapira, L.
Winer, E.
Partridge, A.
TI Body Image Issues in Young Breast Cancer Patients: The Impact of
Chemotherapy, Hormone Treatment, and Surgery
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Rosenberg, S. M.; Tamimi, R. M.; Gelber, S.; Kereakoglow, S.; Borges, V.; Come, S.; Schapira, L.; Winer, E.; Partridge, A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Colorado, Ctr Canc, Denver, CO 80262 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA PD04-05
DI 10.1158/0008-5472.SABCS11-PD04-05
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800085
ER
PT J
AU Ruddy, KJ
Giobbie-Hurder, A
Giordano, SH
Goldfarb, S
Kereakoglow, S
Winer, EP
Partridge, AH
AF Ruddy, K. J.
Giobbie-Hurder, A.
Giordano, S. H.
Goldfarb, S.
Kereakoglow, S.
Winer, E. P.
Partridge, A. H.
TI Physical and Psychological Sequelae of Breast Cancer in Men.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Ruddy, K. J.; Giobbie-Hurder, A.; Giordano, S. H.; Goldfarb, S.; Kereakoglow, S.; Winer, E. P.; Partridge, A. H.] 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.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P4-19-03
DI 10.1158/0008-5472.SABCS11-P4-19-03
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801438
ER
PT J
AU Ryan, PD
Neven, P
Blackwell, KL
Dirix, LY
Barrios, CH
Miller, WH
Fein, LE
Fenton, D
Benner, RJ
Meech, SJ
Paccagnella, L
Sleight, B
Yee, D
Goss, PE
AF Ryan, P. D.
Neven, P.
Blackwell, K. L.
Dirix, L. Y.
Barrios, C. H.
Miller, W. H., Jr.
Fein, L. E.
Fenton, D.
Benner, R. J.
Meech, S. J.
Paccagnella, L.
Sleight, B.
Yee, D.
Goss, P. E.
TI Figitumumab Plus Exemestane Versus Exemestane as First-Line Treatment of
Postmenopausal Hormone Receptor-Positive Advanced Breast Cancer: A
Randomized, Open-Label Phase II Trial
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Ryan, P. D.; Neven, P.; Blackwell, K. L.; Dirix, L. Y.; Barrios, C. H.; Miller, W. H., Jr.; Fein, L. E.; Fenton, D.; Benner, R. J.; Meech, S. J.; Paccagnella, L.; Sleight, B.; Yee, D.; Goss, P. E.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Ryan, P. D.; Neven, P.; Blackwell, K. L.; Dirix, L. Y.; Barrios, C. H.; Miller, W. H., Jr.; Fein, L. E.; Fenton, D.; Benner, R. J.; Meech, S. J.; Paccagnella, L.; Sleight, B.; Yee, D.; Goss, P. E.] Univ Ziekenhuis Leuven, Leuven, Belgium.
[Ryan, P. D.; Neven, P.; Blackwell, K. L.; Dirix, L. Y.; Barrios, C. H.; Miller, W. H., Jr.; Fein, L. E.; Fenton, D.; Benner, R. J.; Meech, S. J.; Paccagnella, L.; Sleight, B.; Yee, D.; Goss, P. E.] Duke Univ, Med Ctr, Durham, NC USA.
[Ryan, P. D.; Neven, P.; Blackwell, K. L.; Dirix, L. Y.; Barrios, C. H.; Miller, W. H., Jr.; Fein, L. E.; Fenton, D.; Benner, R. J.; Meech, S. J.; Paccagnella, L.; Sleight, B.; Yee, D.; Goss, P. E.] Sint Augustinus, Oncol Ctr, Antwerp, Belgium.
[Ryan, P. D.; Neven, P.; Blackwell, K. L.; Dirix, L. Y.; Barrios, C. H.; Miller, W. H., Jr.; Fein, L. E.; Fenton, D.; Benner, R. J.; Meech, S. J.; Paccagnella, L.; Sleight, B.; Yee, D.; Goss, P. E.] PUCRS Sch Med, Porto Alegre, RS, Brazil.
[Ryan, P. D.; Neven, P.; Blackwell, K. L.; Dirix, L. Y.; Barrios, C. H.; Miller, W. H., Jr.; Fein, L. E.; Fenton, D.; Benner, R. J.; Meech, S. J.; Paccagnella, L.; Sleight, B.; Yee, D.; Goss, P. E.] McGill Univ, Jewish Gen Hosp, Segal Canc Ctr, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.
[Ryan, P. D.; Neven, P.; Blackwell, K. L.; Dirix, L. Y.; Barrios, C. H.; Miller, W. H., Jr.; Fein, L. E.; Fenton, D.; Benner, R. J.; Meech, S. J.; Paccagnella, L.; Sleight, B.; Yee, D.; Goss, P. E.] Ctr Oncol Rosario, Santa Fe, Argentina.
[Ryan, P. D.; Neven, P.; Blackwell, K. L.; Dirix, L. Y.; Barrios, C. H.; Miller, W. H., Jr.; Fein, L. E.; Fenton, D.; Benner, R. J.; Meech, S. J.; Paccagnella, L.; Sleight, B.; Yee, D.; Goss, P. E.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
[Ryan, P. D.; Neven, P.; Blackwell, K. L.; Dirix, L. Y.; Barrios, C. H.; Miller, W. H., Jr.; Fein, L. E.; Fenton, D.; Benner, R. J.; Meech, S. J.; Paccagnella, L.; Sleight, B.; Yee, D.; Goss, P. E.] Pfizer Inc, Groton, CT 06340 USA.
[Ryan, P. D.; Neven, P.; Blackwell, K. L.; Dirix, L. Y.; Barrios, C. H.; Miller, W. H., Jr.; Fein, L. E.; Fenton, D.; Benner, R. J.; Meech, S. J.; Paccagnella, L.; Sleight, B.; Yee, D.; Goss, P. E.] Univ Minnesota, Minneapolis, MN USA.
[Ryan, P. D.; Neven, P.; Blackwell, K. L.; Dirix, L. Y.; Barrios, C. H.; Miller, W. H., Jr.; Fein, L. E.; Fenton, D.; Benner, R. J.; Meech, S. J.; Paccagnella, L.; Sleight, B.; Yee, D.; Goss, P. E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P1-17-01
DI 10.1158/0008-5472.SABCS11-P1-17-01
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800303
ER
PT J
AU Santagata, S
Hu, R
Lin, NU
Mendillo, ML
Collins, LC
Hankinson, SE
Schnitt, SJ
Whitesell, L
Lindquist, S
Tamimi, RM
Ince, TA
AF Santagata, S.
Hu, R.
Lin, N. U.
Mendillo, M. L.
Collins, L. C.
Hankinson, S. E.
Schnitt, S. J.
Whitesell, L.
Lindquist, S.
Tamimi, R. M.
Ince, T. A.
TI High Levels of Nuclear Heat Shock Factor 1 (HSF1) Are Associated with
Poor Prognosis in Breast Cancer: Results from the Nurses' Health Study.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Santagata, S.; Hu, R.; Lin, N. U.; Mendillo, M. L.; Collins, L. C.; Hankinson, S. E.; Schnitt, S. J.; Whitesell, L.; Lindquist, S.; Tamimi, R. M.; Ince, T. A.] Brigham & Womens Hosp, Boston, MA 02115 USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Dana Farber Canc Ctr, Boston, MA USA.
Whitehead Inst Biomed Sci, Cambridge, MA USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P5-01-13
DI 10.1158/0008-5472.SABCS11-P5-01-13
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699802176
ER
PT J
AU Saura, C
Bendell, J
Jerusalem, G
Grana-Suarez, B
Su, S
Ru, Q
De Buck, S
Devisme, C
Bosch, A
Urruticoechea, A
Beck, JT
DiTomaso, E
Rouyrre, N
Sternberg, DW
Massacesi, C
Hirawat, S
Dirix, L
Baselga, J
AF Saura, C.
Bendell, J.
Jerusalem, G.
Grana-Suarez, B.
Su, S.
Ru, Q.
De Buck, S.
Devisme, C.
Bosch, A.
Urruticoechea, A.
Beck, J. T.
DiTomaso, E.
Rouyrre, N.
Sternberg, D. W.
Massacesi, C.
Hirawat, S.
Dirix, L.
Baselga, J.
TI Phase I/II Study of BKM120 in Combination with Trastuzumab in Patients
with HER2 Overexpressing Metastatic Breast Cancer Resistant to
Trastuzumab-Containing Therapy
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Saura, C.; Bendell, J.; Jerusalem, G.; Grana-Suarez, B.; Su, S.; Ru, Q.; De Buck, S.; Devisme, C.; Bosch, A.; Urruticoechea, A.; Beck, J. T.; DiTomaso, E.; Rouyrre, N.; Sternberg, D. W.; Massacesi, C.; Hirawat, S.; Dirix, L.; Baselga, J.] Hosp Valle De Hebron, Barcelona, Spain.
Sarah Cannon Res Inst, Nashville, TN USA.
CHU Sart Tilman, B-4000 Liege, Belgium.
Novartis Pharmaceut, Florham Pk, NJ USA.
Novartis Pharma AG, Basel, Switzerland.
Hosp Clin Univ Valencia, Valencia, Spain.
Catalan Inst Oncol, Barcelona, Spain.
Highlands Oncol Grp, Fayetteville, AZ USA.
Novartis Inst BioMed Res, Cambridge, MA USA.
Novartis Oncol, Paris, France.
Oncol Ctr AZ St Augustinus Oncol, Wlrijk, France.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA PD09-03
DI 10.1158/0008-5472.SABCS11-PD09-03
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800092
ER
PT J
AU Schoffski, P
De Benedictis, E
Gendreau, S
Gianni, L
Krop, I
Levy, G
Ware, J
Wildiers, H
Winer, EP
AF Schoffski, P.
De Benedictis, E.
Gendreau, S.
Gianni, L.
Krop, I.
Levy, G.
Ware, J.
Wildiers, H.
Winer, E. P.
TI A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and
Pharmacology of the PI3-Kinase Inhibitor GDC-0941 in Combination with
Paclitaxel and Bevacizumab in Patients with Locally Recurrent or
Metastatic Breast Cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Schoffski, P.; De Benedictis, E.; Gendreau, S.; Gianni, L.; Krop, I.; Levy, G.; Ware, J.; Wildiers, H.; Winer, E. P.] Catholic Univ, Leuven, Belgium.
Ist Nazl Tumori, I-20133 Milan, Italy.
Genentech Inc, San Francisco, CA 94080 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 3
TC 0
Z9 0
U1 2
U2 2
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 DEC 15
PY 2011
VL 71
SU 24
MA PD09-04
DI 10.1158/0008-5472.SABCS11-PD09-04
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800093
ER
PT J
AU Skolny, MN
Miller, CL
O'Toole, J
Sadek, B
Ancukiewicz, M
Taghain, AG
AF Skolny, M. N.
Miller, C. L.
O'Toole, J.
Sadek, B.
Ancukiewicz, M.
Taghain, A. G.
TI The Association between Breast Cancer Related Lymphedema's Risk Factors
and Likelihood of Edema Progression
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Skolny, M. N.; Miller, C. L.; O'Toole, J.; Sadek, B.; Ancukiewicz, M.; Taghain, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P5-17-03
DI 10.1158/0008-5472.SABCS11-P5-17-03
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699802106
ER
PT J
AU Smith, BL
AF Smith, B. L.
TI Advances in Axillary Surgery: Sentinel Nodes and beyond.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Smith, B. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA PL3-1
DI 10.1158/0008-5472.SABCS11-PL3-1
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800490
ER
PT J
AU Son, BH
Birkbak, NJ
Tian, R
Iglehart, D
Wang, ZC
Richardson, AL
AF Son, B. H.
Birkbak, N. J.
Tian, R.
Iglehart, D.
Wang, Z. C.
Richardson, A. L.
TI microRNA Profiles of Breast Tumors Identifies the miR 17-92 Cluster as a
Group of Potentially Essential Oncomirs in Triple Negative Breast
Cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Son, B. H.; Birkbak, N. J.; Tian, R.; Iglehart, D.; Wang, Z. C.; Richardson, A. L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
Asan Med Ctr, Seoul, South Korea.
Tech Univ Denmark, DK-2800 Lyngby, Denmark.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
NR 3
TC 0
Z9 0
U1 2
U2 2
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 DEC 15
PY 2011
VL 71
SU 24
MA PD10-07
DI 10.1158/0008-5472.SABCS11-PD10-07
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800143
ER
PT J
AU Sprecher, E
Lezon-Geyda, K
Sarkar, S
Bossuyt, V
Narayaan, M
Kumar, A
Krop, I
Winer, E
Tuck, D
Kleinstein, S
Harris, L
AF Sprecher, E.
Lezon-Geyda, K.
Sarkar, S.
Bossuyt, V.
Narayaan, M.
Kumar, A.
Krop, I.
Winer, E.
Tuck, D.
Kleinstein, S.
Harris, L.
TI Changes in Gene Expression after One Dose of Trastuzumab (T) in
HER2+Breast Cancer Cell Lines Predict Novel Pathways of Response in HER2
Positive Early Stage Breast Cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Sprecher, E.; Lezon-Geyda, K.; Sarkar, S.; Bossuyt, V.; Narayaan, M.; Kumar, A.; Krop, I.; Winer, E.; Tuck, D.; Kleinstein, S.; Harris, L.] Yale Univ, New Haven, CT USA.
Beckman Coulter, Pasadena, CA USA.
Stony Brook Univ Hosp, Stony Brook, NY USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P1-06-23
DI 10.1158/0008-5472.SABCS11-P1-06-23
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800230
ER
PT J
AU Tevaarwerk, AJ
Gray, R
Schneider, BP
Smith, ML
Wagner, LI
Miller, KD
Sparano, JA
AF Tevaarwerk, A. J.
Gray, R.
Schneider, B. P.
Smith, M. L.
Wagner, L. I.
Miller, K. D.
Sparano, J. A.
TI Survival in Metastatic Breast Cancer (MBC): No Evidence for Improved
Survival Following Distant Recurrence after Adjuvant Chemotherapy.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Tevaarwerk, A. J.; Gray, R.; Schneider, B. P.; Smith, M. L.; Wagner, L. I.; Miller, K. D.; Sparano, J. A.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA.
Indiana Univ, Simon Canc Ctr, Bloomington, IN 47405 USA.
Northwestern Univ, Chicago, IL 60611 USA.
Dana Farber Canc Inst, Boston, MA USA.
Montefiore Med Ctr, Albert Einstein Univ, Bronx, NY 10467 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P1-08-01
DI 10.1158/0008-5472.SABCS11-P1-08-01
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800154
ER
PT J
AU Tolaney, S
Burris, H
Gartner, E
Mayer, I
Saura, C
Maurer, M
DeCillis, A
Ruiz-Soto, R
Lager, J
Winer, E
Krop, I
AF Tolaney, S.
Burris, H.
Gartner, E.
Mayer, I.
Saura, C.
Maurer, M.
DeCillis, A.
Ruiz-Soto, R.
Lager, J.
Winer, E.
Krop, I.
TI A Phase 1/2 Study of SAR245408 (S08) in Combination with Trastuzumab (T)
or Paclitaxel (P) and T in Patients with HER2+Metastatic Breast Cancer
(MBC) Who Progressed on a Previous T-Based Regimen
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Tolaney, S.; Burris, H.; Gartner, E.; Mayer, I.; Saura, C.; Maurer, M.; DeCillis, A.; Ruiz-Soto, R.; Lager, J.; Winer, E.; Krop, I.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Tolaney, S.; Burris, H.; Gartner, E.; Mayer, I.; Saura, C.; Maurer, M.; DeCillis, A.; Ruiz-Soto, R.; Lager, J.; Winer, E.; Krop, I.] Sarah Canon Res Ctr, Nashville, TN USA.
[Tolaney, S.; Burris, H.; Gartner, E.; Mayer, I.; Saura, C.; Maurer, M.; DeCillis, A.; Ruiz-Soto, R.; Lager, J.; Winer, E.; Krop, I.] Wayne State Univ, Karmanos Canc Inst Hematol Oncol, Detroit, MI USA.
[Tolaney, S.; Burris, H.; Gartner, E.; Mayer, I.; Saura, C.; Maurer, M.; DeCillis, A.; Ruiz-Soto, R.; Lager, J.; Winer, E.; Krop, I.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Tolaney, S.; Burris, H.; Gartner, E.; Mayer, I.; Saura, C.; Maurer, M.; DeCillis, A.; Ruiz-Soto, R.; Lager, J.; Winer, E.; Krop, I.] Vall Hebron Univ Hosp, Barcelona, Spain.
[Tolaney, S.; Burris, H.; Gartner, E.; Mayer, I.; Saura, C.; Maurer, M.; DeCillis, A.; Ruiz-Soto, R.; Lager, J.; Winer, E.; Krop, I.] Columbia Univ, Med Ctr, New York, NY USA.
[Tolaney, S.; Burris, H.; Gartner, E.; Mayer, I.; Saura, C.; Maurer, M.; DeCillis, A.; Ruiz-Soto, R.; Lager, J.; Winer, E.; Krop, I.] Exelixis, San Francisco, CA USA.
[Tolaney, S.; Burris, H.; Gartner, E.; Mayer, I.; Saura, C.; Maurer, M.; DeCillis, A.; Ruiz-Soto, R.; Lager, J.; Winer, E.; Krop, I.] Sanofi, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P1-17-02
DI 10.1158/0008-5472.SABCS11-P1-17-02
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800304
ER
PT J
AU Tolaney, SM
Nechushtan, H
Berger, R
Kurzrock, R
Ron, IG
Schoffski, P
Awada, A
Yasenchak, CA
Burris, HA
Ramies, DA
Shen, X
Winer, EP
AF Tolaney, S. M.
Nechushtan, H.
Berger, R.
Kurzrock, R.
Ron, I. G.
Schoffski, P.
Awada, A.
Yasenchak, C. A.
Burris, H. A.
Ramies, D. A.
Shen, X.
Winer, E. P.
TI Cabozantinib (XL184) in Patients with Metastatic Breast Cancer: Results
from a Phase 2 Randomized Discontinuation Trial
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Tolaney, S. M.; Nechushtan, H.; Berger, R.; Kurzrock, R.; Ron, I. G.; Schoffski, P.; Awada, A.; Yasenchak, C. A.; Burris, H. A.; Ramies, D. A.; Shen, X.; Winer, E. P.] Dana Farber Canc Inst, Boston, MA 02115 USA.
Hadassah Ein Kerem Med Ctr, Jerusalem, Israel.
Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel.
Univ Ziekenhuis Gasthuisberg, Leuven, Flemish Brabant, Belgium.
Inst Jules Bordet, B-1000 Brussels, Belgium.
Northwest Canc Specialists PC, Tualatin, OR USA.
Sarah Cannon Res Inst, Nashville, TN USA.
Exelixis Inc, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P1-17-10
DI 10.1158/0008-5472.SABCS11-P1-17-10
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800311
ER
PT J
AU Tracy, MS
Meyer, ME
Sepucha, K
Gelber, S
Hirshfield-Bartek, J
Troyan, S
Morrow, M
Schapira, L
Come, S
Winer, E
Partridge, AH
AF Tracy, M. S.
Meyer, M. E.
Sepucha, K.
Gelber, S.
Hirshfield-Bartek, J.
Troyan, S.
Morrow, M.
Schapira, L.
Come, S.
Winer, E.
Partridge, A. H.
TI Perceptions, Knowledge and Satisfaction with Contralateral Prophylactic
Mastectomy among Young Women with Breast Cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Tracy, M. S.; Meyer, M. E.; Sepucha, K.; Gelber, S.; Hirshfield-Bartek, J.; Troyan, S.; Morrow, M.; Schapira, L.; Come, S.; Winer, E.; Partridge, A. H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Beth Isreal Deaconess Med Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P4-11-10
DI 10.1158/0008-5472.SABCS11-P4-11-10
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801311
ER
PT J
AU Tromberg, BJ
L'Heureux, DZ
Mankoff, DA
Zhang, Z
Cerussi, A
Mehta, R
Carpenter, PM
Butler, JA
Hylton, NM
Kaufman, P
Pogue, BW
Paulsen, K
Yodh, AG
Boas, D
Isakoff, S
AF Tromberg, B. J.
L'Heureux, D. Z.
Mankoff, D. A.
Zhang, Z.
Cerussi, A.
Mehta, R.
Carpenter, P. M.
Butler, J. A.
Hylton, N. M.
Kaufman, P.
Pogue, B. W.
Paulsen, K.
Yodh, A. G.
Boas, D.
Isakoff, S.
TI ACRIN 6691 Monitoring and Predicting Breast Cancer Neoadjuvant
Chemotherapy Response Using Diffuse Optical Spectroscopic Imaging
(DOSI).
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Tromberg, B. J.; L'Heureux, D. Z.; Mankoff, D. A.; Zhang, Z.; Cerussi, A.; Mehta, R.; Carpenter, P. M.; Butler, J. A.; Hylton, N. M.; Kaufman, P.; Pogue, B. W.; Paulsen, K.; Yodh, A. G.; Boas, D.; Isakoff, S.] Univ Calif Irvine, Irvine, CA USA.
Amer Coll Radiol Imaging Network, Philadelphia, PA USA.
Univ Washington, Seattle, WA 98195 USA.
Brown Univ, Providence, RI 02912 USA.
Univ Calif San Fransisco, San Francisco, CA USA.
Dartmouth Coll, Lebanon, NH USA.
Univ Penn, Philadelphia, PA 19104 USA.
Massachusetts Gen Hosp, Charlestown, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA OT2-05-02
DI 10.1158/0008-5472.SABCS11-OT2-05-02
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800016
ER
PT J
AU Vidal, M
Di Cosimo, S
Torrejon, D
Saura, C
Gomez-Pardo, P
Perez-Garcia, J
Munoz-Couselo, E
Bellet, M
Sanchez-Olle, G
De Mattos-Arruda, L
Oliveira, M
Tabernero, J
Baselga, J
Cortes, J
AF Vidal, M.
Di Cosimo, S.
Torrejon, D.
Saura, C.
Gomez-Pardo, P.
Perez-Garcia, J.
Munoz-Couselo, E.
Bellet, M.
Sanchez-Olle, G.
De Mattos-Arruda, L.
Oliveira, M.
Tabernero, J.
Baselga, J.
Cortes, J.
TI Survival Outcome with Bevacizumab: Activation of the
Phosphatidylinositol-3 Kinase (PI3K) Pathway Due to PIK3CA Mutations or
PTEN Loss Makes a Difference.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Vidal, M.; Di Cosimo, S.; Torrejon, D.; Saura, C.; Gomez-Pardo, P.; Perez-Garcia, J.; Munoz-Couselo, E.; Bellet, M.; Sanchez-Olle, G.; De Mattos-Arruda, L.; Oliveira, M.; Tabernero, J.; Baselga, J.; Cortes, J.] Univ Autonoma Barcelona, Vall dHebron Inst Oncol, Vall dHebron Univ Hosp, E-08193 Barcelona, Spain.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P5-13-01
DI 10.1158/0008-5472.SABCS11-P5-13-01
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699802068
ER
PT J
AU von Minckwitz, G
Baselga, J
Bradbury, I
de Azambuja, E
Scullion, MJ
Ross, G
Saini, KS
Piccart-Gebhart, M
AF von Minckwitz, G.
Baselga, J.
Bradbury, I.
de Azambuja, E.
Scullion, M. J.
Ross, G.
Saini, K. S.
Piccart-Gebhart, M.
TI Adjuvant Pertuzumab and Herceptin IN IniTial TherapY of Breast Cancer:
APHINITY (BIG 4-11/BO25126/TOC4939g).
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [von Minckwitz, G.; Baselga, J.; Bradbury, I.; de Azambuja, E.; Scullion, M. J.; Ross, G.; Saini, K. S.; Piccart-Gebhart, M.] German Breast Grp, Neu Isenburg, Germany.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Inst Jules Bordet, BrEAST Data Ctr, B-1000 Brussels, Belgium.
Roche, Welwyn Garden City, Herts, England.
Breast Int Grp Headquarters, Brussels, Belgium.
Breast Int Grp, Brussels, Belgium.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 15
PY 2011
VL 71
SU 24
MA OT1-02-04
DI 10.1158/0008-5472.SABCS11-OT1-02-04
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801009
ER
PT J
AU Wagner, LI
Zhao, F
Chapman, JAW
Cella, D
Shepherd, LE
Sledge, GW
Goss, PE
AF Wagner, L. I.
Zhao, F.
Chapman, J-A W.
Cella, D.
Shepherd, L. E.
Sledge, G. W.
Goss, P. E.
TI Patient-Reported Predictors of Early Treatment Discontinuation: NCIC
JMA.27/E1Z03 Quality of Life Study of Postmenopausal Women with Primary
Breast Cancer Randomized to Exemestane or Anastrozole
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Wagner, L. I.; Zhao, F.; Chapman, J-A W.; Cella, D.; Shepherd, L. E.; Sledge, G. W.; Goss, P. E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada.
Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA S6-2
DI 10.1158/0008-5472.SABCS11-56-2
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800313
ER
PT J
AU Winer, EP
AF Winer, E. P.
TI How To Use Endocrine Therapy for Breast Cancer: Beyond the Basics.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Winer, E. P.] Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA PL1-1
DI 10.1158/0008-5472.5ABC511-PL1
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800488
ER
PT J
AU Wood, ME
Kingsley, F
Ellerton, JA
Atkins, JN
Grubs, SS
Muss, HB
Garber, JE
AF Wood, M. E.
Kingsley, F.
Ellerton, J. A.
Atkins, J. N.
Grubs, S. S.
Muss, H. B.
Garber, J. E.
TI A Randomized Phase II Biomarker Study of Atorvastatin in Premenopausal
Women at Increased Risk for Breast Cancer.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Wood, M. E.; Kingsley, F.; Ellerton, J. A.; Atkins, J. N.; Grubs, S. S.; Muss, H. B.; Garber, J. E.] Univ Vermont, Burlington, VT USA.
Canc Consultants, Las Vegas, NV USA.
Southeastern Med Ctr, Winston Salem, NC USA.
Med Oncol Hematol Consultants, Newark, DE USA.
Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P3-11-04
DI 10.1158/0008-5472.SABCS11-P3-11-04
PG 1
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699801106
ER
PT J
AU Yap, JT
Locascio, T
Najita, JS
Mayer, IA
Hobday, TJ
Falkson, CI
Dees, EC
Gelman, RS
Rimawi, MF
Nanda, R
Berkowitz, J
Franchetti, Y
Wolff, AC
Winer, EP
Lin, NU
Van den Abbeele, AD
AF Yap, J. T.
Locascio, T.
Najita, J. S.
Mayer, I. A.
Hobday, T. J.
Falkson, C. I.
Dees, E. C.
Gelman, R. S.
Rimawi, M. F.
Nanda, R.
Berkowitz, J.
Franchetti, Y.
Wolff, A. C.
Winer, E. P.
Lin, N. U.
Van den Abbeele, A. D.
TI Metabolic Response by FOG-PET in Patients (pts) Receiving Trastuzumab
(T) and Lapatinib (L) for HER2+Metastatic Breast Cancer (MBC):
Correlative Analysis of TBCRC 003.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Yap, J. T.; Locascio, T.; Najita, J. S.; Mayer, I. A.; Hobday, T. J.; Falkson, C. I.; Dees, E. C.; Gelman, R. S.; Rimawi, M. F.; Nanda, R.; Berkowitz, J.; Franchetti, Y.; Wolff, A. C.; Winer, E. P.; Lin, N. U.; Van den Abbeele, A. D.] Dana Farber Canc Inst, Boston, MA 02115 USA.
Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
Mayo Clin, Rochester, MN USA.
Univ Alabama Birmingham, Birmingham, AL USA.
Univ N Carolina, Chapel Hill, NC USA.
Baylor Coll Med, Houston, TX 77030 USA.
Univ Chicago, Chicago, IL 60637 USA.
Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2011
VL 71
SU 24
MA P2-09-07
DI 10.1158/0008-5472.SABCS11-P2-09-07
PG 2
WC Oncology
SC Oncology
GA V43RZ
UT WOS:000209699800400
ER
PT J
AU Bachmann, LH
Hobbs, MM
Sena, AC
Sobel, JD
Schwebke, JR
Krieger, JN
McClelland, RS
Workowski, KA
AF Bachmann, Laura H.
Hobbs, Marcia M.
Sena, Arlene C.
Sobel, Jack D.
Schwebke, Jane R.
Krieger, John N.
McClelland, R. Scott
Workowski, Kimberly A.
TI Trichomonas vaginalis Genital Infections: Progress and Challenges
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED INFECTIONS;
RANDOMIZED CLINICAL-TRIAL; SINGLE-DOSE TREATMENT; HIV-NEGATIVE WOMEN;
RISK-FACTORS; METRONIDAZOLE; TINIDAZOLE; PREVALENCE; URETHRITIS
AB Trichomonas vaginalis (TV) infection is the most prevalent curable sexually transmitted infection in the United States and worldwide. Most TV infections are asymptomatic, and the accurate diagnosis of this infection has been limited by lack of sufficiently sensitive and specific diagnostic tests, particularly for men. To provide updates for the 2010 Centers for Disease Control and Prevention's Sexually Transmitted Diseases Treatment Guidelines, a PubMed search was conducted of all TV literature published from 9 January 2004 through 24 September 2008. Approximately 175 pertinent abstracts and articles were reviewed and discussed with national experts. This article describes advances in TV diagnostics which have led to an improved understanding of the epidemiology of this pathogen, as well as potential biologic and epidemiological interactions between TV and human immunodeficiency virus (HIV). New data on treatment outcomes, metronidazole-resistant TV, management of nitroimidazole-allergic patients, frequency of recurrent TV infection following treatment, and screening considerations for TV in certain populations are also presented.
C1 [Bachmann, Laura H.] Wake Forest Univ Hlth Sci, Infect Dis Sect, Winston Salem, NC 27157 USA.
[Bachmann, Laura H.] WG Bill Hefner Med Ctr, Infect Dis Sect, Salisbury, CT USA.
[Sena, Arlene C.] Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC USA.
[Hobbs, Marcia M.] Univ N Carolina, Dept Microbiol, Chapel Hill, NC USA.
[Hobbs, Marcia M.] Univ N Carolina, Dept Immunol, Chapel Hill, NC USA.
[Sobel, Jack D.] Wayne State Univ, Dept Med, Div Infect Dis, Detroit, MI 48202 USA.
[Schwebke, Jane R.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA.
[Krieger, John N.] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
[Krieger, John N.] VA Puget Sound Hlth Care Syst, Dept Urol, Seattle, WA USA.
[McClelland, R. Scott] Univ Washington, Dept Med, Seattle, WA USA.
[McClelland, R. Scott] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[McClelland, R. Scott] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Workowski, Kimberly A.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Workowski, Kimberly A.] Emory Univ, Dept Med, Div Infect Dis, Atlanta, GA 30322 USA.
RP Bachmann, LH (reprint author), Wake Forest Univ Hlth Sci, Infect Dis Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM lbachman@wfubmc.edu
FU Centers for Disease Control and Prevention
FX This article was published as part of a supplement entitled "Sexually
Transmitted Disease Treatment Guidelines" sponsored by the Centers for
Disease Control and Prevention.
NR 73
TC 33
Z9 37
U1 0
U2 12
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 DEC 15
PY 2011
VL 53
SU 3
BP S160
EP S172
DI 10.1093/cid/cir705
PG 13
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 847MY
UT WOS:000296978200012
PM 22080269
ER
PT J
AU Maughan-Brown, B
Venkataramani, AS
Nattrass, N
Seekings, J
Whiteside, AW
AF Maughan-Brown, Brendan
Venkataramani, Atheendar S.
Nattrass, Nicoli
Seekings, Jeremy
Whiteside, Alan W.
TI A Cut Above the Rest: Traditional Male Circumcision and HIV Risk Among
Xhosa Men in Cape Town, South Africa
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV; AIDS; prevention; circumcision; foreskin; Africa
ID PREVENTION; INFECTION; COMPLICATIONS; BEHAVIOR; EASTERN
AB Background: Randomized clinical trials have shown that medical male circumcision substantially reduces the risk of contracting HIV. However, relatively little is known about the relationship between traditional male circumcision and HIV risk. This article examines variations in traditional circumcision practices and their relationship to HIV status.
Methods: We used data from the fifth wave of the Cape Area Panel Study (n = 473) of young adults in Cape Town, South Africa, to determine attitudes towards circumcision, whether men were circumcised, at what age, and whether their foreskin had been fully or partially removed. Probit models were estimated to determine the association between extent and age of circumcision and HIV status.
Results: There was strong support for traditional male circumcision. 92.5% of the men reported being circumcised, with 10.5% partially circumcised. Partially circumcised men had a 7% point greater risk of being HIV positive than fully circumcised men (P < 0.05) and equal risk compared with uncircumcised men. Most (91%) men were circumcised between the ages of 17 and 22 years (mean 19.2 years), and HIV risk increased with age of circumcision (P < 0.10).
Conclusions: Efforts should be made to encourage earlier circumcisions and to work with traditional surgeons to reduce the number of partial circumcisions. Data on the extent and age of circumcision are necessary for meaningful conclusions to be drawn from survey data about the relationship between circumcision and HIV status.
C1 [Maughan-Brown, Brendan] Univ Cape Town, SALDRU, ZA-7701 Cape Town, South Africa.
[Venkataramani, Atheendar S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA.
[Nattrass, Nicoli] Univ Cape Town, AIDS & Soc Res Unit, ZA-7701 Cape Town, South Africa.
[Nattrass, Nicoli] Univ Cape Town, Dept Econ, ZA-7701 Cape Town, South Africa.
[Seekings, Jeremy] Univ Cape Town, Dept Sociol, ZA-7701 Cape Town, South Africa.
[Seekings, Jeremy] Univ Cape Town, Ctr Social Sci Res, ZA-7701 Cape Town, South Africa.
[Whiteside, Alan W.] Univ KwaZulu Natal, Hlth Econ & HIV AIDS Res Div, Durban, South Africa.
RP Maughan-Brown, B (reprint author), Univ Cape Town, SALDRU, ZA-7701 Cape Town, South Africa.
EM bren-dan.maughanbrown@gmail.com
FU US National Institute for Child Health and Human Development; Andrew W.
Mellon Foundation; National Institute on Aging; Health Economics &
HIV/AIDS Research Division (HEARD) at the University of KwaZulu-Natal;
European Union; Washington University School of Medicine Forum for
International Health and Tropical Medicine
FX Supported by the US National Institute for Child Health and Human
Development, the Andrew W. Mellon Foundation, the National Institute on
Aging, the Health Economics & HIV/AIDS Research Division (HEARD) at the
University of KwaZulu-Natal, and the European Union. Further information
is available from www.caps.uct.ac.za.; The authors would like to thank
Rebecca Thornton, seminar participants at the University of Cape Town
Centre for Social Science Research, and 2 anonymous referees for helpful
comments and suggestions. Dr. Venkataramani acknowledges the Washington
University School of Medicine Forum for International Health and
Tropical Medicine for funding travel to South Africa.
NR 28
TC 13
Z9 13
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD DEC 15
PY 2011
VL 58
IS 5
BP 499
EP 505
DI 10.1097/QAI.0b013e31823584c1
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 846RT
UT WOS:000296921600018
PM 21909030
ER
PT J
AU Neumann, J
Bahr, F
Horst, D
Kriegl, L
Engel, J
Luque, RM
Gerhard, M
Kirchner, T
Jung, A
AF Neumann, Jens
Bahr, Fiorina
Horst, David
Kriegl, Lydia
Engel, Jutta
Luque, Raquel Mejias
Gerhard, Markus
Kirchner, Thomas
Jung, Andreas
TI SOX2 expression correlates with lymph-node metastases and distant spread
in right-sided colon cancer
SO BMC CANCER
LA English
DT Article
DE SOX2; beta-catenin; Colon cancer; Metastasis
ID HUMAN COLORECTAL TUMORS; PLURIPOTENT STEM-CELLS; BETA-CATENIN;
MOLECULAR-FEATURES; HUMAN FIBROBLASTS; CD133 EXPRESSION; LOW SURVIVAL;
MARKER; GENE; CLASSIFICATION
AB Background: The transcription factor SOX2, which is involved in the induction of pluripotent stem cells and contributes to colorectal carcinogenesis, is associated with a poor prognosis in colon cancer (CC). Furthermore, SOX2 is a repressor of the transcriptional activity of beta-catenin in vitro. Since the majority of CC develop via an activation of the Wnt/beta-catenin signalling pathway, indicated by nuclear expression of beta-catenin, we wanted to investigate the expression patterns of SOX2 and beta-catenin and correlate them with the occurrence of lymph node and distant metastases as indicators of malignant progression.
Methods: The expression of SOX2 and beta-catenin was investigated in a case control study utilizing a matched pair collection (N = 114) of right-sided CCs with either corresponding distant metastases (N = 57) or without distant spread (N = 57) by applying immunohistochemistry.
Results: Elevated protein expression of SOX2 significantly correlated with the presence of lymph node (p = 0.006) and distant metastases (p = 0.022). Nuclear beta-catenin expression correlated significantly only with distant metastases (p = 0.001). Less than 10% of cases showed a coexpression of high levels of beta-catenin and SOX2. The positivity for both markers was also associated with a very high risk for lymph-node metastases (p = 0.007) and distant spread (p = 0.028).
Conclusion: We demonstrated that increased expression of either SOX2 or nuclear beta-catenin are associated with distant metastases in right-sided CC. Additionally, SOX2 is also associated with lymph-node metastases. These data underline the importance of stemness-associated markers for the identification of CC with high risk for distant spread.
C1 [Neumann, Jens; Bahr, Fiorina; Horst, David; Kriegl, Lydia; Kirchner, Thomas; Jung, Andreas] Univ Munich, Inst Pathol, D-8000 Munich, Germany.
[Horst, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Engel, Jutta] Univ Munich, Munchen Tumorzentrums Munchen Inst Med Informat, D-8000 Munich, Germany.
[Luque, Raquel Mejias; Gerhard, Markus] Tech Univ Munich, Inst Med Mikrobiol & Immunol, Munich, Germany.
RP Neumann, J (reprint author), Univ Munich, Inst Pathol, Thalkirchner Str 36, D-8000 Munich, Germany.
EM jens.neumann@med.uni-muenchen.de
RI Gerhard, Markus/N-3387-2014
OI Gerhard, Markus/0000-0001-9110-3950
FU Manfred Stolte-Stiftung, Germany
FX We thank A. Heier, I. Redich and A. Sendelhofert for excellent technical
assistance. This work was supported by the Manfred Stolte-Stiftung,
Germany (support to A.J. 2010)
NR 40
TC 42
Z9 46
U1 1
U2 9
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 DEC 14
PY 2011
VL 11
AR 518
DI 10.1186/1471-2407-11-518
PG 7
WC Oncology
SC Oncology
GA 886DG
UT WOS:000299831300001
PM 22168803
ER
PT J
AU Perk, S
Izamis, ML
Tolboom, H
Uygun, B
Berthiaume, F
Yarmush, ML
Uygun, K
AF Perk, Sinem
Izamis, Maria-Louisa
Tolboom, Herman
Uygun, Basak
Berthiaume, Francois
Yarmush, Martin L.
Uygun, Korkut
TI A Metabolic Index of Ischemic Injury for Perfusion-Recovery of Cadaveric
Rat Livers
SO PLOS ONE
LA English
DT Article
ID MONITORING BATCH PROCESSES; HYPOTHERMIC MACHINE PERFUSION; PRINCIPAL
COMPONENT ANALYSIS; COLD-STORAGE; NITRIC-OXIDE; REPERFUSION INJURY;
CARDIAC DEATH; TRANSPLANTATION; PRESERVATION; SURVIVAL
AB With over 110,000 patients waiting for organ transplantation, the current crisis in organ transplantation is based on a lack of donors after brain-death (DBD). A very large alternative pool of donor organs that remain untapped are the donors after cardiac death (DCD), recovered after cardiac activity has ceased and therefore sustained some ischemic injury. Machine perfusion has been proposed as a novel modality of organ preservation and treatment to render such cadaveric organs, and in particular livers, transplantable. Two key issues that remain unaddressed are how to assess whether a DCD liver is damaged beyond repair, and whether machine perfusion has rendered an injured organ sufficiently viable for transplantation. In this work, we present a metabolic analysis of the transient responses of cadaveric rat livers during normothermic machine perfusion (NMP), and develop an index of ischemia that enables evaluation of the organ ischemic injury level. Further, we perform a discriminant analysis to construct a classification algorithm with >0.98 specificity to identify whether a given perfused liver is ischemic or fresh, in effect a precursor for an index of transplantability and a basis for the use of statistical process control measures for automated feedback control of treatment of ischemic injury in DCD livers. The analyses yield an index based on squared prediction error (SPE) as log(SPE) >1.35 indicating ischemia. The differences between metabolic functions of fresh and ischemic livers during perfusion are outlined and the metabolites that varied significantly for ischemic livers are identified as ornithine, arginine, albumin and tyrosine.
C1 [Perk, Sinem; Izamis, Maria-Louisa; Uygun, Basak; Yarmush, Martin L.; Uygun, Korkut] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA.
[Perk, Sinem; Izamis, Maria-Louisa; Uygun, Basak; Yarmush, Martin L.; Uygun, Korkut] Shriners Hosp Children, Boston, MA USA.
[Tolboom, Herman] Univ Zurich Hosp, Div Cardiac & Vasc Surg, CH-8091 Zurich, Switzerland.
[Berthiaume, Francois; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA.
RP Perk, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA.
EM uygun.korkut@mgh.harvard.edu
RI Uygun, Basak/I-1792-2012
OI Uygun, Basak/0000-0002-2600-7900
FU National Institutes of Health [R01DK59766, R01EB008678, R00DK080942,
K99DK088962]; Shriners Hospitals for Children
FX Funding from the National Institutes of Health (R01DK59766, R01EB008678,
R00DK080942, K99DK088962), and the Shriners Hospitals for Children are
gratefully acknowledged. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 47
TC 13
Z9 13
U1 1
U2 4
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 DEC 14
PY 2011
VL 6
IS 12
AR e28518
DI 10.1371/journal.pone.0028518
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 866GS
UT WOS:000298369100045
PM 22194843
ER
PT J
AU Ryan, RJH
Nitta, M
Borger, D
Zukerberg, LR
Ferry, JA
Harris, NL
Iafrate, AJ
Bernstein, BE
Sohani, AR
Le, LP
AF Ryan, Russell J. H.
Nitta, Mai
Borger, Darrell
Zukerberg, Lawrence R.
Ferry, Judith A.
Harris, Nancy Lee
Iafrate, A. John
Bernstein, Bradley E.
Sohani, Aliyah R.
Le, Long Phi
TI EZH2 Codon 641 Mutations are Common in BCL2-Rearranged Germinal Center B
Cell Lymphomas
SO PLOS ONE
LA English
DT Article
ID FOLLICULAR LYMPHOMA; CANCER; EXPRESSION; MELANOMA; PROSTATE; FEATURES;
ENHANCER; DISTINCT; PROTEIN
AB Mutations at codon 641 of EZH2 are recurrent in germinal center B cell lymphomas, and the most common variants lead to altered EZH2 enzymatic activity and enhanced tri-methylation of histone H3 at lysine 27, a repressive chromatin modification. As an initial step toward screening patients for cancer genotype-directed therapy, we developed a screening assay for EZH2 codon 641 mutations amenable for testing formalin-fixed clinical specimens, based on the sensitive SNaPshot single nucleotide extension technology. We detected EZH2 mutations in 12/55 (22%) follicular lymphomas (FL), 5/35 (14%) diffuse large B cell lymphomas with a germinal center immunophenotype (GCB-DLBCL), and 2/11 (18%) high grade B cell lymphomas with concurrent rearrangements of BCL2 and MYC. No EZH2 mutations were detected in cases of Burkitt lymphoma (0/23). EZH2 mutations were frequently associated with the presence of BCL2 rearrangement (BCL2-R) in both the FL (28% of BCL-R cases versus 0% of BCL2-WT cases, p<0.05) and GCB-DLBCL groups (33% of BCL2-R cases versus 4% of BCL2-WT cases, p<0.04), and across all lymphoma types excluding BL (27% of BCL2-R cases versus 3% of BCL2-WT cases, p<0.003). We confirmed gain-of-function activity for all previously reported EZH2 codon 641 mutation variants. Our findings suggest that EZH2 mutations constitute an additional genetic "hit'' in many BCL2-rearranged germinal center B cell lymphomas. Our work may be helpful in the selection of lymphoma patients for future trials of pharmacologic agents targeting EZH2 and EZH2-regulated pathways.
C1 [Ryan, Russell J. H.; Nitta, Mai; Borger, Darrell; Zukerberg, Lawrence R.; Ferry, Judith A.; Harris, Nancy Lee; Iafrate, A. John; Bernstein, Bradley E.; Sohani, Aliyah R.; Le, Long Phi] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ryan, Russell J. H.; Bernstein, Bradley E.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA.
[Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Ryan, RJH (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
EM Ryan.Russell@mgh.harvard.edu
FU Department of Pathology, Massachusetts General Hospital; Howard Hughes
Medical Institute
FX Funding was provided by the Austin L. Vickery, Jr. Award Program,
Department of Pathology, Massachusetts General Hospital, and the Howard
Hughes Medical Institute. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 25
TC 55
Z9 56
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 14
PY 2011
VL 6
IS 12
AR e28585
DI 10.1371/journal.pone.0028585
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 866GS
UT WOS:000298369100058
PM 22194861
ER
PT J
AU Walcott, BP
Kuklina, EV
Nahed, BV
George, MG
Kahle, KT
Simard, JM
Asaad, WF
Coumans, JVCE
AF Walcott, Brian P.
Kuklina, Elena V.
Nahed, Brian V.
George, Mary G.
Kahle, Kristopher T.
Simard, J. Marc
Asaad, Wael F.
Coumans, Jean-Valery C. E.
TI Craniectomy for Malignant Cerebral Infarction: Prevalence and Outcomes
in US Hospitals
SO PLOS ONE
LA English
DT Article
ID ARTERY INFARCTION; DECOMPRESSIVE CRANIECTOMY; ISCHEMIC-STROKE;
HEMISPHERIC INFARCTION; BRAIN EDEMA; HEMICRANIECTOMY; MULTICENTER;
RECOVERY; SURGERY; TRIAL
AB Object: Randomized trials have demonstrated the efficacy of craniectomy for the treatment of malignant cerebral edema following ischemic stroke. We sought to determine the prevalence and outcomes related to this by using a national database.
Methods: Patient discharges with ischemic stroke as the primary diagnosis undergoing craniectomy were queried from the US Nationwide Inpatient Sample from 1999 to 2008. A subpopulation of patients was identified that underwent thrombolysis. Two primary end points were examined: in-hospital mortality and discharge to home/routine care. To facilitate interpretations, adjusted prevalence was calculated from the overall prevalence and two age-specific logistic regression models. The predictive margin was then generated using a multivariate logistic regression model to estimate the probability of in-hospital mortality after adjustment for admission type, admission source, length of stay, total hospital charges, chronic comorbidities, and medical complications.
Results: After excluding 71,996 patients with the diagnosis of intracranial hemorrhage and posterior intracranial circulation occlusion, we identified 4,248,955 adult hospitalizations with ischemic stroke as a primary diagnosis. The estimated rates of hospitalizations in craniectomy per 10,000 hospitalizations with ischemic stroke increased from 3.9 in 1999-2000 to 14.46 in 2007-2008 (p for linear trend<0.001). Patients 60+ years of age had in-hospital mortality of 44% while the 18-59 year old group was found to be 24%(p = 0.14). Outcomes were comparable if recombinant tissue plasminogen activator had been administered.
Conclusions: Craniectomy is being increasingly performed for malignant cerebral edema following large territory cerebral ischemia. We suspect that the increase in the annual incidence of DC for malignant cerebral edema is directly related to the expanding collection of evidence in randomized trials that the operation is efficacious when performed in the correct patient population. In hospital mortality is high for all patients undergoing this procedure.
C1 [Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.; Coumans, Jean-Valery C. E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.; Coumans, Jean-Valery C. E.] Harvard Univ, Sch Med, Boston, MA USA.
[Kuklina, Elena V.; George, Mary G.] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
[Simard, J. Marc] Univ Maryland, Sch Med, Dept Neurosurg, Baltimore, MD 21201 USA.
[Asaad, Wael F.] Brown Univ, Sch Med, Dept Neurosurg, Providence, RI 02912 USA.
RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
EM walcott.brian@mgh.harvard.edu
RI Asaad, Wael/I-8485-2012
OI Asaad, Wael/0000-0003-4406-9096
FU NHLBI NIH HHS [R01 HL082517]
NR 38
TC 19
Z9 19
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 14
PY 2011
VL 6
IS 12
AR e29193
DI 10.1371/journal.pone.0029193
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 866GS
UT WOS:000298369100166
PM 22195021
ER
PT J
AU Ma, CHE
Brenner, GJ
Omura, T
Samad, OA
Costigan, M
Inquimbert, P
Niederkofler, V
Salie, R
Sun, CC
Lin, HY
Arber, S
Coppola, G
Woolf, CJ
Samad, TA
AF Ma, Chi H. E.
Brenner, Gary J.
Omura, Takao
Samad, Omar A.
Costigan, Michael
Inquimbert, Perrine
Niederkofler, Vera
Salie, Rishard
Sun, Chia Chi
Lin, Herbert Y.
Arber, Silvia
Coppola, Giovanni
Woolf, Clifford J.
Samad, Tarek A.
TI The BMP Coreceptor RGMb Promotes While the Endogenous BMP Antagonist
Noggin Reduces Neurite Outgrowth and Peripheral Nerve Regeneration by
Modulating BMP Signaling
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID REPULSIVE GUIDANCE MOLECULE; SPINAL-CORD-INJURY; MORPHOGENETIC PROTEIN
CORECEPTOR; AXONAL GROWTH; SENSORY NEURONS; HUMAN BRAIN; IN-VITRO; BONE;
EXPRESSION; INHIBITION
AB Repulsive guidance molecule b(RGMb) is a bone morphogenetic protein(BMP) coreceptor and sensitizer of BMP signaling, highly expressed in adult dorsal root ganglion(DRG) sensory neurons. We used a murine RGMb knock-out to gain insight into the physiological role of RGMb in the DRG, and address whether RGMb-mediated modulation of BMP signaling influences sensory axon regeneration. No evidence for altered development of the PNS and CNS was detected in RGMb(-/-) mice. However, both cultured neonatal whole DRG explants and dissociated DRG neurons from RGMb(-/-) mice exhibited significantly fewer and shorter neurites than those from wild-type littermates, aphenomenon that could be fully rescued by BMP-2. Moreover, Noggin, an endogenous BMP signaling antagonist, inhibited neurite outgrowth in wild-type DRG explants from naive as well as nerve injury-preconditioned mice. Noggin is downregulated in the DRG after nerve injury, and its expression is highly correlated and inversely associated with the known regeneration-associated genes, which are induced in the DRG by peripheral axonal injury. We show that diminished BMP signaling in vivo, achieved either through RGMb deletion or BMP inhibition with Noggin, retarded early axonal regeneration after sciatic nerve crush injury. Our data suggest a positive modulatory contribution of RGMb and BMP signaling to neurite extension in vitro and early axonal regrowth after nerve injury in vivo and a negative effect of Noggin.
C1 [Samad, Tarek A.] Pfizer Inc, Neurosci Res Unit, Groton, CT 06340 USA.
[Ma, Chi H. E.; Omura, Takao; Costigan, Michael; Inquimbert, Perrine; Woolf, Clifford J.] Harvard Univ, Childrens Hosp Boston, Sch Med, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA.
[Brenner, Gary J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Sun, Chia Chi; Lin, Herbert Y.] Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA.
[Sun, Chia Chi; Lin, Herbert Y.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA.
[Sun, Chia Chi; Lin, Herbert Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Samad, Omar A.; Arber, Silvia] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA.
[Samad, Omar A.; Arber, Silvia] Yale Univ, Sch Med, Ctr Neurosci & Regenerat Res, New Haven, CT 06520 USA.
[Niederkofler, Vera; Salie, Rishard] Univ Basel, Dept Cell Biol, Biozentrum, CH-4056 Basel, Switzerland.
[Niederkofler, Vera; Salie, Rishard] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
[Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Neurol, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
[Ma, Chi H. E.] City Univ Hong Kong, Dept Biol & Chem, Kowloon, Hong Kong, Peoples R China.
RP Samad, TA (reprint author), Pfizer Inc, Neurosci Res Unit, Groton, CT 06340 USA.
EM Gjbrenner@partners.org; Tarek.samad@pfizer.com
RI samad, omar/K-1921-2012;
OI MA, Chi Him Eddie/0000-0003-2054-0445
FU NIH [NS038253, RDE017821A, NS044139]; Dr. Miriam and Sheldon G. Adelson
Medical Research Foundation; Hong Kong Croucher Foundation; Swiss
National Science Foundation; European Research Council; IRP-IFP
Switzerland
FX This work was supported by the NIH [Grants NS038253 and RDE017821A
(C.J.W.), and NS044139 (G.J.B.)], the Dr. Miriam and Sheldon G. Adelson
Medical Research Foundation, the Hong Kong Croucher Foundation
Fellowship (C. H. E. M.), the Swiss National Science Foundation, an
European Research Council Advanced Grant (S.A., V.N. and R. S.), and the
IRP-IFP Switzerland (M. C., G. C.). We thank Yin Xia, Qiufu Ma, Kenneth
Bloch, and Robert Griffin for their helpful input.
NR 48
TC 23
Z9 25
U1 1
U2 7
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 DEC 14
PY 2011
VL 31
IS 50
BP 18391
EP 18400
DI 10.1523/JNEUROSCI.4550-11.2011
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 861YA
UT WOS:000298055600017
PM 22171041
ER
PT J
AU Ussar, S
Vienberg, SG
Kahn, CR
AF Ussar, Siegfried
Vienberg, Sara G.
Kahn, C. Ronald
TI Receptor Antibodies as Novel Therapeutics for Diabetes
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID INSULIN-RESISTANCE; ENERGY-EXPENDITURE; FIBROBLAST; INHIBITOR
AB Antibodies to receptors can block or mimic hormone action. Taking advantage of receptor isoforms, co-receptors, and other receptor modulating proteins, antibodies and other designer ligands can enhance tissue specificity and provide new approaches to the therapy of diabetes and other diseases.
C1 [Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA 02215 USA.
RP Kahn, CR (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA.
EM c.ronald.kahn@joslin.harvard.edu
OI Ussar, Siegfried/0000-0001-7575-0920
FU Eli Lilly Foundation; Novo Nordisk A/S
FX C.R.K. has served as a consultant for Sanofi-Aventis, Five-Prime
Therapeutics, Sirtris/GSK, Catabasis, and Ember Therapeutics. He also
has received grant support from Eli Lilly Foundation and is a
co-inventor on patents related to diabetes and obesity therapeutics. S.
G. V. receives support from Novo Nordisk A/S.
NR 18
TC 5
Z9 5
U1 0
U2 3
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 DEC 14
PY 2011
VL 3
IS 113
AR 113ps47
DI 10.1126/scitranslmed.3003447
PG 3
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 862HP
UT WOS:000298081400002
PM 22174312
ER
PT J
AU Giardina, TD
Singh, H
AF Giardina, Traber Davis
Singh, Hardeep
TI Should Patients Get Direct Access to Their Laboratory Test Results? An
Answer With Many Questions
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID FOLLOW-UP; RECORDS; MAIL
C1 Houston Vet Affairs Hlth Serv Res & Dev, Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA.
Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA.
RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM hardeeps@bcm.edu
OI Davis Giardina, Traber/0000-0002-9184-6524
NR 10
TC 8
Z9 8
U1 2
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD DEC 14
PY 2011
VL 306
IS 22
BP 2502
EP 2503
DI 10.1001/jama.2011.1797
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 860YB
UT WOS:000297983300025
ER
PT J
AU Kinlay, S
AF Kinlay, Scott
TI The Trials and Tribulations of Percutaneous Coronary Intervention in
Hospitals Without On-site CABG Surgery
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID ACUTE MYOCARDIAL-INFARCTION; CARDIAC-SURGERY; BALLOON ANGIOPLASTY;
ARTERY DISEASE; OUTCOMES; METAANALYSIS; CENTERS; STANDBY
C1 [Kinlay, Scott] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiac Catheterizat Lab & Vasc Med,VA Boston Hea, Boston, MA 02115 USA.
RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Cardiac Catheterizat Lab & Vasc Med, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM scott.kinlay@va.gov
FU CSRD VA [I01 CX000440]
NR 23
TC 4
Z9 4
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD DEC 14
PY 2011
VL 306
IS 22
BP 2507
EP 2509
DI 10.1001/jama.2011.1824
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 860YB
UT WOS:000297983300028
PM 22166613
ER
PT J
AU Snuderl, M
Fazlollahi, L
Le, LP
Nitta, M
Zhelyazkova, BH
Davidson, CJ
Akhavanfard, S
Cahil, DP
Aldape, KD
Betensky, RA
Louis, DN
Iafrate, AJ
AF Snuderl, Matija
Fazlollahi, Ladan
Le, Long P.
Nitta, Mai
Zhelyazkova, Boryana H.
Davidson, Christian J.
Akhavanfard, Sara
Cahil, Daniel P.
Aldape, Kenneth D.
Betensky, Rebecca A.
Louis, David N.
Iafrate, A. John
TI Mosaic Amplification of Multiple Receptor Tyrosine Kinase Genes in
Glioblastoma
SO CANCER CELL
LA English
DT Article
ID CANCER; HETEROGENEITY; EVOLUTION; THERAPY; VEGFR2; KIT
AB Tumor heterogeneity has been implicated in tumor growth and progression as well as resistance to therapy. We present an example of genetic heterogeneity in human malignant brain tumors in which multiple closely related driver genes are amplified and activated simultaneously in adjacent intermingled cells. We have observed up to three different receptor tyrosine kinases (EGFR, MET, PDGFRA) amplified in single tumors in different cells in a mutually exclusive fashion. Each subpopulation was actively dividing, and the genetic changes resulted in protein production, and coexisting subpopulations shared common early genetic mutations indicating their derivation from a single precursor cell. The stable coexistence of different clones within the same tumor will have important clinical implications for tumor resistance to targeted therapies.
C1 [Snuderl, Matija; Fazlollahi, Ladan; Le, Long P.; Nitta, Mai; Zhelyazkova, Boryana H.; Davidson, Christian J.; Akhavanfard, Sara; Louis, David N.; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Snuderl, Matija; Fazlollahi, Ladan; Le, Long P.; Nitta, Mai; Zhelyazkova, Boryana H.; Davidson, Christian J.; Akhavanfard, Sara; Louis, David N.; Iafrate, A. John] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Cahil, Daniel P.] Dept Neurosurg, Houston, TX 77030 USA.
[Aldape, Kenneth D.] Dept Pathol, Houston, TX 77030 USA.
[Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Cahil, Daniel P.; Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
EM aiafrate@partners.org
OI Cahill, Daniel/0000-0003-2552-6546; Snuderl, Matija/0000-0003-0752-0917
NR 22
TC 256
Z9 260
U1 0
U2 13
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 DEC 13
PY 2011
VL 20
IS 6
BP 810
EP 817
DI 10.1016/j.ccr.2011.11.005
PG 8
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 864VV
UT WOS:000298269500014
PM 22137795
ER
PT J
AU Patel, VI
AF Patel, Virendra I.
TI Long-Term Survival After Open Repair and Thoracic Endovascular Aortic
Repair for Descending Thoracic Aortic Aneurysms
SO CIRCULATION
LA English
DT Editorial Material
DE Editorial; aortic surgery; endovascular graft; endovascular surgery;
epidemiology; peripheral vascular disease
ID STENT-GRAFT; EXPERIENCE; TRIAL; ENDOGRAFT; DISEASES
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA.
RP Patel, VI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,Wang ACC 440, Boston, MA 02114 USA.
EM vpatel4@partners.org
NR 18
TC 3
Z9 3
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD DEC 13
PY 2011
VL 124
IS 24
BP 2645
EP 2646
DI 10.1161/CIRCULATIONAHA.111.069641
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 866AI
UT WOS:000298351600013
PM 22155993
ER
PT J
AU Kwolek, CJ
AF Kwolek, Christopher J.
TI Are Improved Results for Hybrid Repair of Thoracoabdominal Aortic
Aneurysms Due to a Learning Curve or Better Patient Selection?
SO CIRCULATION
LA English
DT Editorial Material
DE Editorials; aneurysm; aortic; aneurysm, thoracic
ID OPEN SURGICAL REPAIR; STENT-GRAFT REPAIR; ENDOVASCULAR TREATMENT;
EXPERIENCE; TRIAL
C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA.
RP Kwolek, CJ (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, WAC 442,15 Parkman St, Boston, MA 02114 USA.
EM ckwolek@partners.org
NR 13
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD DEC 13
PY 2011
VL 124
IS 24
BP 2647
EP 2648
DI 10.1161/CIRCULATIONAHA.111.067009
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 866AI
UT WOS:000298351600014
PM 22155994
ER
PT J
AU Heist, EK
Mansour, M
Ruskin, JN
AF Heist, E. Kevin
Mansour, Moussa
Ruskin, Jeremy N.
TI Rate Control in Atrial Fibrillation Targets, Methods, Resynchronization
Considerations
SO CIRCULATION
LA English
DT Article
DE atrial fibrillation; cardiac resynchronization therapy
ID RHYTHM MANAGEMENT AFFIRM; LONG-TERM SURVIVAL; RADIOFREQUENCY CATHETER
MODIFICATION; ATRIOVENTRICULAR JUNCTION ABLATION;
CONGESTIVE-HEART-FAILURE; PULMONARY-VEIN ISOLATION; QUALITY-OF-LIFE;
CARDIAC-RESYNCHRONIZATION; SINUS RHYTHM; VENTRICULAR RATE
C1 [Ruskin, Jeremy N.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA.
RP Ruskin, JN (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA.
EM jruskin@partners.org
FU Deane Institute for Integrative Research in Atrial Fibrillation and
Stroke at Massachusetts General Hospital; Biotronik; Boston Scientific;
St. Jude Medical; Cardiofocus; Endosense; MC10; Voyage Medical; Biosense
Webster; Medtronic
FX Dr Mansour was supported in part by the Deane Institute for Integrative
Research in Atrial Fibrillation and Stroke at Massachusetts General
Hospital.; Dr Heist has received a research grant and honoraria from
Biotronik, he is a consultant for and has received a research grant and
honoraria from Boston Scientific, he has received honoraria from
Medtronic, he is a consultant for and has received honoraria from Sorin,
and he is a consultant for and has received a research grant and
honoraria from St. Jude Medical. Dr Mansour is a consultant for
Biosense-Webster and Boston Scientific; he has received research grants
from Cardiofocus, Endosense, and MC10; he is a consultant for Medtronic;
he is consultant for and has received a research grant from St. Jude
Medical; and he has received a research grant from Voyage Medical. Dr
Ruskin is a consultant for Astellas/Cardiome and Biosense Webster, and
has received fellowship support from Biosense Webster and Boston
Scientific; he is a member of the CardioFocus-Clinical Oversight
Committee (no compensation), the CardioInsight-Scientific Advisory
Board, and the CryoCath-Scientific Steering Committee (no compensation);
he is a consultant for and has received fellowship support from
Medtronic; he has received honoraria from Med-IQ; he is a consultant for
and a member of the Scientific Steering Committee for Pfizer; he is a
consultant and holds equity in Portola; he receives fellowship support
from St. Jude Medical; and he is a consultant for Third Rock Ventures.
NR 55
TC 12
Z9 13
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD DEC 13
PY 2011
VL 124
IS 24
BP 2746
EP 2755
DI 10.1161/CIRCULATIONAHA.111.019919
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 866AI
UT WOS:000298351600024
PM 22155996
ER
PT J
AU Sabatine, MS
AF Sabatine, Marc S.
TI Randomized, Controlled Trials
SO CIRCULATION
LA English
DT Editorial Material
C1 [Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
[Sabatine, Marc S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA.
EM msabatine@partners.org
FU National Institutes of Health; TIMI Study Group at Brigham; Women's
Hospital
FX Dr Sabatine is the Chairman of the TIMI Study Group, an Academic
Research Organization based at Brigham and Women's Hospital that
conducts cardiovascular clinical trials. These trials are funded by
grants to Brigham and Women's Hospital from both industry and the
National Institutes of Health.
NR 7
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD DEC 13
PY 2011
VL 124
IS 24
BP E832
EP E834
DI 10.1161/CIRCULATIONAHA.111.018218
PG 3
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 866AI
UT WOS:000298351600002
PM 22155998
ER
PT J
AU Reed, GW
Cannon, CP
AF Reed, Grant W.
Cannon, Christopher P.
TI Personalized Therapy Following Drug-Eluting Stenting Using Platelet
Function Testing and C-Reactive Protein
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE C-reactive protein; drug-eluting stent(s); editorial; platelet function
test
ID HEART-ASSOCIATION; TASK-FORCE; CORONARY; CONSENSUS
C1 [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA.
RP Cannon, CP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA.
EM cpcannon@partners.org
OI Reed, Grant/0000-0001-8234-3135
NR 10
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 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD DEC 13
PY 2011
VL 58
IS 25
BP 2640
EP 2641
DI 10.1016/j.jacc.2011.09.031
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 863DP
UT WOS:000298143300005
PM 22152949
ER
PT J
AU Qi, L
Parast, L
Cai, TX
Powers, C
Gervino, EV
Hauser, TH
Hu, FB
Doria, A
AF Qi, Lu
Parast, Layla
Cai, Tianxi
Powers, Christine
Gervino, Ernest V.
Hauser, Thomas H.
Hu, Frank B.
Doria, Alessandro
TI Genetic Susceptibility to Coronary Heart Disease in Type 2 Diabetes 3
Independent Studies
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE CHD; diabetes; genetics
ID ARTERY-DISEASE; ASSOCIATION ANALYSIS; CARDIOVASCULAR RISK; PLASMA
ADIPONECTIN; WOMEN; MELLITUS; LOCUS; MEN; CLASSIFICATION; POLYMORPHISM
AB Objectives The aim of this study was to evaluate whether coronary heart disease (CHD)-susceptibility loci identified by genome-wide association studies of the general population also contribute to CHD in type 2 diabetes.
Background No study has examined the effects of these genetic variants on CHD in diabetic patients.
Methods We genotyped 15 genetic markers of 12 loci in 3 studies of diabetic patients: the prospective Nurses' Health Study (309 CHD cases, and 544 control subjects) and Health Professional Follow-up Study (345 CHD cases, and 451 control subjects) and the cross-sectional Joslin Heart Study (422 CHD cases, and 435 control subjects).
Results Five single-nucleotide polymorphisms, rs4977574 (CDKN2A/2B), rs12526453 (PHACTR1), rs646776 (CELSR2-PSRC1-SORT1), rs2259816 (HNF1A), and rs11206510 (PCSK9) showed directionally consistent associations with CHD in the 3 studies, with combined odds ratios (ORs) ranging from 1.17 to 1.25 (p = 0.03 to 0.0002). None of the other single-nucleotide polymorphisms reached significance in individual or combined analyses. A genetic risk score (GRS) was created by combining the risk alleles of the 5 significantly associated loci. The OR of CHD/GRS unit was 1.19 (95% confidence interval: 1.13 to 1.26; p < 0.0001). Individuals with GRS >= 8 (19% of diabetic subjects) had almost a 2-fold increase in CHD risk (OR: 1.94, 95% confidence interval: 1.60 to 2.35) as compared with individuals with GRS <= 5 (30% of diabetic subjects). Prediction of CHD was significantly improved (p < 0.001) when the GRS was added to a model including clinical predictors in the combined samples.
Conclusions Our results illustrate the consistency and differences in the determinants of genetic susceptibility to CHD in diabetic patients and the general populations. (J Am Coll Cardiol 2011;58:2675-82) (C) 2011 by the American College of Cardiology Foundation
C1 [Qi, Lu; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Qi, Lu; Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Parast, Layla; Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Powers, Christine; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.
[Gervino, Ernest V.; Hauser, Thomas H.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA.
[Gervino, Ernest V.; Hauser, Thomas H.; Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA.
EM nhlqi@channing.harvard.edu; alessandro.doria@joslin.harvard.edu
FU National Institutes of Health [HL71981, HL034594, HL34594 CA87969,
HL73168, DK36836, DK46200]; American Heart Association [0730094N]
FX This study was supported by National Institutes of Health Grants
HL71981, HL034594, HL34594 CA87969, HL73168, DK36836 (Genetics Core of
the Diabetes and Endocrinology Research Center at the Joslin Diabetes
Center), and DK46200 (Boston Obesity Nutrition Research Center) and by
an American Heart Association Scientist Development Award (0730094N).
All authors have reported that they have no relationships relevant to
the contents of this paper to disclose.
NR 31
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 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD DEC 13
PY 2011
VL 58
IS 25
BP 2675
EP 2682
DI 10.1016/j.jacc.2011.08.054
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 863DP
UT WOS:000298143300011
PM 22152955
ER
PT J
AU Balachandran, K
Alford, PW
Wylie-Sears, J
Goss, JA
Grosberg, A
Bischoff, J
Aikawa, E
Levine, RA
Parker, KK
AF Balachandran, Kartik
Alford, Patrick W.
Wylie-Sears, Jill
Goss, Josue A.
Grosberg, Anna
Bischoff, Joyce
Aikawa, Elena
Levine, Robert A.
Parker, Kevin Kit
TI Cyclic strain induces dual-mode endothelial-mesenchymal transformation
of the cardiac valve
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE tight junctions; cytokines; activated myofibroblast
ID VASCULAR SMOOTH-MUSCLE; FUNCTIONAL MITRAL REGURGITATION; IN-VITRO;
INTERSTITIAL-CELLS; EPITHELIAL-CELLS; STRETCH; LEAFLET; TRANSITION;
ADAPTATION; ALIGNMENT
AB Endothelial-mesenchymal transformation (EMT) is a critical event for the embryonic morphogenesis of cardiac valves. Inducers of EMT during valvulogenesis include VEGF, TGF-beta 1, and wnt/beta-catenin (where wnt refers to the wingless-type mammary tumor virus integration site family of proteins), that are regulated in a spatiotemporal manner. EMT has also been observed in diseased, strain-overloaded valve leaflets, suggesting a regulatory role for mechanical strain. Although the preponderance of studies have focused on the role of soluble mitogens, we asked if the valve tissue microenvironment contributed to EMT. To recapitulate these microenvironments in a controlled, in vitro environment, we engineered 2D valve endothelium from sheep valve endothelial cells, using microcontact printing to mimic the regions of isotropy and anisotropy of the leaflet, and applied cyclic mechanical strain in an attempt to induce EMT. We measured EMT in response to both low (10%) and high strain (20%), where low-strain EMT occurred via increased TGF-beta 1 signaling and high strain via increased wnt/beta-catenin signaling, suggesting dual strain-dependent routes to distinguish EMT in healthy versus diseased valve tissue. The effect was also directionally dependent, where cyclic strain applied orthogonal to axis of the engineered valve endothelium alignment resulted in severe disruption of cell microarchitecture and greater EMT. Once transformed, these tissues exhibited increased contractility in the presence of endothelin-1 and larger basal mechanical tone in a unique assay developed to measure the contractile tone of the engineered valve tissues. This finding is important, because it implies that the functional properties of the valve are sensitive to EMT. Our results suggest that cyclic mechanical strain regulates EMT in a strain magnitude and directionally dependent manner.
C1 [Balachandran, Kartik; Alford, Patrick W.; Goss, Josue A.; Grosberg, Anna; Parker, Kevin Kit] Harvard Univ, Dis Biophys Grp, Wyss Inst Biol Inspired Engn, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Wylie-Sears, Jill; Bischoff, Joyce; Aikawa, Elena; Levine, Robert A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Wylie-Sears, Jill; Bischoff, Joyce] Vasc Biol Program, Boston, MA 02115 USA.
[Wylie-Sears, Jill; Bischoff, Joyce] Childrens Hosp, Dept Surg, 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 Parker, KK (reprint author), Harvard Univ, Dis Biophys Grp, Wyss Inst Biol Inspired Engn, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM kkparker@seas.harvard.edu
RI Balachandran, Kartik/J-2612-2013; Grosberg, Anna/B-3017-2014;
OI Bischoff, Joyce/0000-0002-6367-1974
FU Harvard Catalyst Grant [5UL1RR025758]; National Institutes of Health
[5U01HL100408-02]; Harvard Materials Research Science and Engineering
Center; Wyss Institute for Biologically Inspired Engineering
FX We acknowledge funding from the Harvard Catalyst Grant (5UL1RR025758),
National Institutes of Health (5U01HL100408-02), Harvard Materials
Research Science and Engineering Center, and the Wyss Institute for
Biologically Inspired Engineering. The authors also acknowledge the
Harvard Center for Nanoscale Systems for the use of clean room
facilities.
NR 60
TC 56
Z9 58
U1 1
U2 16
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 13
PY 2011
VL 108
IS 50
BP 19943
EP 19948
DI 10.1073/pnas.1106954108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861QR
UT WOS:000298034800028
PM 22123981
ER
PT J
AU Hettmer, S
Liu, JN
Miller, CM
Lindsay, MC
Sparks, CA
Guertin, DA
Bronson, RT
Langenau, DM
Wagers, AJ
AF Hettmer, Simone
Liu, Jianing
Miller, Christine M.
Lindsay, Melissa C.
Sparks, Cynthia A.
Guertin, David A.
Bronson, Roderick T.
Langenau, David M.
Wagers, Amy J.
TI Sarcomas induced in discrete subsets of prospectively isolated skeletal
muscle cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cancer stem cell; sarcoma oncogenes; preclinical screening platform
ID UNDIFFERENTIATED PLEOMORPHIC SARCOMA; MTOR INHIBITOR RAPAMYCIN;
CHILDRENS ONCOLOGY GROUP; EMBRYONAL RHABDOMYOSARCOMA; MOUSE MODEL;
STEM-CELLS; K-RAS; ALVEOLAR RHABDOMYOSARCOMAS; SATELLITE CELLS;
EXPRESSION
AB Soft-tissue sarcomas are heterogeneous cancers that can present with tissue-specific differentiation markers. To examine the cellular basis for this histopathological variation and to identify sarcoma-relevant molecular pathways, we generated a chimeric mouse model in which sarcoma-associated genetic lesions can be introduced into discrete, muscle-resident myogenic and mesenchymal cell lineages. Expression of Kirsten rat sarcoma viral oncogene [Kras(G12V)] and disruption of cyclin-dependent kinase inhibitor 2A (CDKN2A; p16p19) in prospectively isolated satellite cells gave rise to pleomorphic rhabdomyosarcomas (MyoD-, Myogenin-and Desmin-positive), whereas introduction of the same oncogenetic hits in nonmyogenic progenitors induced pleomorphic sarcomas lacking myogenic features. Transcriptional profiling demonstrated that myogenic and nonmyogenic Kras; p16p19(null) sarcomas recapitulate gene-expression signatures of human rhabdomyosarcomas and identified a cluster of genes that is concordantly up-regulated in both mouse and human sarcomas. This cluster includes genes associated with Ras and mechanistic target of rapamycin (mTOR) signaling, a finding consistent with activation of the Ras and mTOR pathways both in Kras; p16p19null sarcomas and in 26-50% of human rhabdomyosarcomas surveyed. Moreover, chemical inhibition of Ras or mTOR signaling arrested the growth of mouse Kras; p16p19(null) sarcomas and of human rhabdomyosarcoma cells in vitro and in vivo. Taken together, these data demonstrate the critical importance of lineage commitment within the tumor cell-of-origin in determining sarcoma histotype and introduce an experimental platform for rapid dissection of sarcoma-relevant cellular and molecular events.
C1 [Hettmer, Simone; Liu, Jianing; Miller, Christine M.; Lindsay, Melissa C.; Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
[Hettmer, Simone; Liu, Jianing; Miller, Christine M.; Lindsay, Melissa C.; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Hettmer, Simone; Liu, Jianing; Miller, Christine M.; Lindsay, Melissa C.; Langenau, David M.; Wagers, Amy J.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Hettmer, Simone; Liu, Jianing; Miller, Christine M.; Lindsay, Melissa C.; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02115 USA.
[Hettmer, Simone] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Hettmer, Simone] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Sparks, Cynthia A.; Guertin, David A.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
[Sparks, Cynthia A.; Guertin, David A.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA.
[Bronson, Roderick T.] Tufts Univ, Sch Vet, Dept Biomed Sci, North Grafton, MA 01536 USA.
[Langenau, David M.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Langenau, David M.] Massachusetts Gen Hosp, Dept Mol Pathol, Charlestown, MA 02129 USA.
RP Wagers, AJ (reprint author), Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
EM amy.wagers@joslin.harvard.edu
FU Burroughs-Wellcome Fund; Harvard Stem Cell Institute; Beckman
Foundation; Hope Street Kids, Patients Assistance League and Service
Bermuda/St. Baldrick's, Alex Lemonade Stand Foundation; Sarcoma
Foundation of America; ALSF; National Institutes of Health [K01AR055619,
R01CA154923, R21CA156056]
FX We thank G. Buruzula, J. LaVecchio, and S. Harris at The Joslin Diabetes
and Endocrinology Research Center (DERC) Flow Cytometry Core for flow
cytometry support; A. Pinkhasov at The Joslin DERC Histology Core for
help with tumor sectioning; J. Schroeder at The Joslin DERC Genomics
Core for microarray processing (funded by National Institutes of Health
Grant P30DK036836); A. Perez-Atayde for reviewing histopathological
findings, C. L. Unitt, T. Caron, and A. Kreshock at The
Dana-Farber/Harvard Cancer Center Histopathology Core for help with
immunohistochemistry; N. Gray for providing torin 1, and L. Wang, D.
Kirsch, and C. Keller for helpful comments on the manuscript. This work
was funded in part by grants from the Burroughs-Wellcome Fund, Harvard
Stem Cell Institute, and The Beckman Foundation (to A. J. W.), and from
Hope Street Kids, Patients Assistance League and Service Bermuda/St.
Baldrick's, Alex Lemonade Stand Foundation, and Bear Necessities (to S.
H.). D. M. L. is supported by the Sarcoma Foundation of America, ALSF,
and National Institutes of Health Grants K01AR055619, R01CA154923, and
R21CA156056.
NR 53
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Z9 34
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 13
PY 2011
VL 108
IS 50
BP 20002
EP 20007
DI 10.1073/pnas.1111733108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861QR
UT WOS:000298034800038
PM 22135462
ER
PT J
AU Pang, WW
Price, EA
Sahoo, D
Beerman, I
Maloney, WJ
Rossi, DJ
Schrier, SL
Weissman, IL
AF Pang, Wendy W.
Price, Elizabeth A.
Sahoo, Debashis
Beerman, Isabel
Maloney, William J.
Rossi, Derrick J.
Schrier, Stanley L.
Weissman, Irving L.
TI Human bone marrow hematopoietic stem cells are increased in frequency
and myeloid-biased with age
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE lineage potential; hematopoiesis; microarray; leukemia
ID DNA-DAMAGE; MICE; MECHANISM; DIFFERENTIATION; TRANSPLANTATION;
COMPARTMENT; PROGENITORS; POPULATION; HIERARCHY; DECLINE
AB In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. Though the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have been incompletely characterized. To elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated immunophenotypic HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged immunophenotypic human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared with young HSC. Gene expression profiling revealed that aged immunophenotypic human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, developmental potential, and gene expression profile of human HSC are similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process.
C1 [Pang, Wendy W.; Sahoo, Debashis; Weissman, Irving L.] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Ludwig Ctr Stem Cell Res, Stanford, CA 94305 USA.
[Pang, Wendy W.; Sahoo, Debashis; Weissman, Irving L.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
[Price, Elizabeth A.; Schrier, Stanley L.] Stanford Univ, Dept Internal Med, Div Hematol, Stanford, CA 94305 USA.
[Maloney, William J.] Stanford Univ, Dept Orthopaed Surg, Stanford, CA 94305 USA.
[Beerman, Isabel; Rossi, Derrick J.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
RP Pang, WW (reprint author), Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Ludwig Ctr Stem Cell Res, Stanford, CA 94305 USA.
EM wendy.pang@stanford.edu; irv@stanford.edu
FU Stanford Medical Scientist Training Program; Siebel Stem Cell Institute;
Thomas and Stacey Siebel Foundation; National Institute of Aging
[R01AG029124]
FX The authors thank Renee Mehra for administrative and logistical support;
Ravi Majeti, Christopher Park, Matthew Inlay, and Charles Chan for
helpful advice and discussions; Theresa Storm and Libuse Jerabek for
excellent laboratory management; Ken Cheung for statistical advice; and
the Stanford Functional Genomics Facility for array processing services.
Support for this work was provided by the Stanford Medical Scientist
Training Program (W. W. P.), a grant from the Siebel Stem Cell Institute
and the Thomas and Stacey Siebel Foundation (to D. S.), and National
Institute of Aging Grant R01AG029124 (to S. L. S. and I. L. W).
NR 45
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Z9 186
U1 2
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 13
PY 2011
VL 108
IS 50
BP 20012
EP 20017
DI 10.1073/pnas.1116110108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861QR
UT WOS:000298034800040
PM 22123971
ER
PT J
AU Germar, K
Dose, M
Konstantinou, T
Zhang, JW
Wang, HF
Lobry, C
Arnett, KL
Blacklow, SC
Aifantis, I
Aster, JC
Gounari, F
AF Germar, Kristine
Dose, Marei
Konstantinou, Tassos
Zhang, Jiangwen
Wang, Hongfang
Lobry, Camille
Arnett, Kelly L.
Blacklow, Stephen C.
Aifantis, Iannis
Aster, Jon C.
Gounari, Fotini
TI T-cell factor 1 is a gatekeeper for T-cell specification in response to
Notch signaling
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID HEMATOPOIETIC STEM-CELL; LINEAGE FATE; ADULT THYMUS; PROGENITORS; BETA;
DIFFERENTIATION; RECEPTOR; PATHWAY; ACTIVATION; THYMOCYTES
AB Although transcriptional programs associated with T-cell specification and commitment have been described, the functional hierarchy and the roles of key regulators in structuring/orchestrating these programs remain unclear. Activation of Notch signaling in uncommitted precursors by the thymic stroma initiates the T-cell differentiation program. One regulator first induced in these precursors is the DNA-binding protein T-cell factor 1 (Tcf-1), a T-cell-specific mediator of Wnt signaling. However, the specific contribution of Tcf-1 to early T-cell development and the signals inducing it in these cells remain unclear. Here we assign functional significance to Tcf-1 as a gatekeeper of T-cell fate and show that Tcf-1 is directly activated by Notch signals. Tcf-1 is required at the earliest phase of T-cell determination for progression beyond the early thymic progenitor stage. The global expression profile of Tcf-1-deficient progenitors indicates that basic processes of DNA metabolism are down-regulated in its absence, and the blocked T-cell progenitors become abortive and die by apoptosis. Our data thus add an important functional relationship to the road-map of T-cell development.
C1 [Germar, Kristine; Dose, Marei; Konstantinou, Tassos; Gounari, Fotini] Univ Chicago, Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA.
[Germar, Kristine] Tufts Univ, Grad Program Immunol, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA.
[Zhang, Jiangwen] Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA.
[Wang, Hongfang; Aster, Jon C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Lobry, Camille; Aifantis, Iannis] NYU, Inst Canc, Howard Hughes Med Inst, New York, NY 10016 USA.
[Lobry, Camille; Aifantis, Iannis] New York Univ, Inst Canc, Dept Pathol, New York, NY 10016 USA.
[Lobry, Camille; Aifantis, Iannis] New York Univ, Sch Med, Helen L & Martin S Kimmel Ctr Stem Cell Biol, New York, NY 10016 USA.
[Arnett, Kelly L.; Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Arnett, Kelly L.; Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Gounari, F (reprint author), Univ Chicago, Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA.
EM fgounari@uchicago.edu
RI Arnett, Kelly/C-4816-2012; Zhang, Jiangwen/A-7654-2013; lobry,
camille/A-6188-2015;
OI lobry, camille/0000-0003-0550-4921; Arnett, Kelly/0000-0001-5117-3647;
Dose, Marei/0000-0001-5394-9779
FU National Institutes of Health [R01AI059676, F31 AI830542, R01CA133379,
R01CA105129, R21CA141399, R01CA149655]; Leukemia and Lymphoma Society;
American Cancer Society [RSG0806801]; Irma T. Hirschl Charitable Trust;
Dana Foundation; Mallinckrodt Foundation; Gabrielle's Angels Foundation;
Alex's Lemonade Stand Foundation; Helen L. and Martin S. Kimmel Center
FX We thank J. Y. Park for excellent technical support for microarray
analysis and B. Kee for helpful suggestions. This work was supported in
part by National Institutes of Health Grants R01AI059676 (to F. G.) and
F31 AI830542 (to K. G.); R01CA133379, R01CA105129, R21CA141399, and
R01CA149655 (to I. A.); a Leukemia and Lymphoma Society Translational
Research Program grant (to I. A.); American Cancer Society Grant
RSG0806801 (to I. A.); the Irma T. Hirschl Charitable Trust; the Dana
Foundation; the Mallinckrodt Foundation; the Gabrielle's Angels
Foundation; and the Alex's Lemonade Stand Foundation (I. A.). C. L. is
supported by the Helen L. and Martin S. Kimmel Center for Stem Cell
Biology fellowship.
NR 45
TC 67
Z9 67
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 13
PY 2011
VL 108
IS 50
BP 20060
EP 20065
DI 10.1073/pnas.1110230108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861QR
UT WOS:000298034800048
PM 22109558
ER
PT J
AU Walker, LM
Sok, D
Nishimura, Y
Donau, O
Sadjadpour, R
Gautam, R
Shingai, M
Pejchal, R
Ramos, A
Simek, MD
Geng, Y
Wilson, IA
Poignard, P
Martin, MA
Burton, DR
AF Walker, Laura M.
Sok, Devin
Nishimura, Yoshiaki
Donau, Olivia
Sadjadpour, Reza
Gautam, Rajeev
Shingai, Masashi
Pejchal, Robert
Ramos, Alejandra
Simek, Melissa D.
Geng, Yu
Wilson, Ian A.
Poignard, Pascal
Martin, Malcolm A.
Burton, Dennis R.
TI Rapid development of glycan-specific, broad, and potent anti-HIV-1 gp120
neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID MONOCLONAL-ANTIBODIES; IN-VITRO; IMMUNODEFICIENCY; PROTECTION;
GLYCOPROTEIN; BINDING; SITE; VIVO; 2G12
AB It is widely believed that the induction of a broadly neutralizing antibody (bNAb) response will be a critical component of a successful vaccine against HIV. A significant fraction of HIV-infected individuals mount bNAb responses, providing support for the notion that such responses could be elicited through vaccination. Infection of macaques with simian immunodeficiency virus (SIV) or SIV/HIV chimeric virus (SHIV) has been widely used to model aspects of HIV infection, but to date, only limited bNAb responses have been described. Here, we screened plasma from 14 R5-tropic SHIV-infected macaques for broadly neutralizing activity and identified a macaque with highly potent cross-clade plasma NAb response. Longitudinal studies showed that the development of broad and autologous NAb responses occurred coincidentally in this animal. Serum-mapping studies, using pseudovirus point mutants and antigen adsorption assays, indicated that the plasma bNAbs are specific for epitopes that include carbohydrates and are critically dependent on the glycan at position 332 of Env gp120. The results described herein provide insight into the development and evolution of a broad response, suggest that certain bNAb specificities may be more rapidly induced by immunization than others, and provide a potential model for the facile study of the development of bNAb responses.
C1 [Nishimura, Yoshiaki; Donau, Olivia; Sadjadpour, Reza; Gautam, Rajeev; Shingai, Masashi; Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Walker, Laura M.; Sok, Devin; Ramos, Alejandra; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Walker, Laura M.; Sok, Devin; Ramos, Alejandra; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA.
[Pejchal, Robert; Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Pejchal, Robert; Wilson, Ian A.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA.
[Ramos, Alejandra; Simek, Melissa D.; Poignard, Pascal] Int AIDS Vaccine Initiat, New York, NY 10038 USA.
[Geng, Yu] ProSci Inc, Poway, CA 92064 USA.
[Burton, Dennis R.] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02142 USA.
[Burton, Dennis R.] Harvard Univ, Boston, MA 02142 USA.
RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM mmartin@niaid.nih.gov; burton@scripps.edu
RI poignard, pascal/N-6678-2013
FU International AIDS Vaccine Initiative through Neutralizing Antibody
Consortium; National Institute of Allergy and Infectious Diseases,
National Institutes of Health [AI33292, AI084817]; Ragon Institute of
Massachusetts General Hospital; Massachusetts Institute of Technology;
Harvard University
FX We thank C. Corbaci, C. Williams, and S. M. Eagol for figure
preparation. This study was funded by the International AIDS Vaccine
Initiative through Neutralizing Antibody Consortium, National Institute
of Allergy and Infectious Diseases, National Institutes of Health Grants
AI33292 (to D.R.B.) and AI084817 (to I.A.W.); the Ragon Institute of
Massachusetts General Hospital, Massachusetts Institute of Technology,
and Harvard University; and the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 25
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U1 0
U2 7
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 DEC 13
PY 2011
VL 108
IS 50
BP 20125
EP 20129
DI 10.1073/pnas.1117531108
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861QR
UT WOS:000298034800059
PM 22123961
ER
PT J
AU Davies, EA
Meterko, MM
Charns, MP
Seibert, MEN
Cleary, PD
AF Davies, Elizabeth A.
Meterko, Mark M.
Charns, Martin P.
Seibert, Marjorie E. Nealon
Cleary, Paul D.
TI Factors affecting the use of patient survey data for quality improvement
in the Veterans Health Administration
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
ID CENTERED CARE
AB Background: Little is known about how to use patient feedback to improve experiences of health care. The Veterans Health Administration (VA) conducts regular patient surveys that have indicated improved care experiences over the past decade. The goal of this study was to assess factors that were barriers to, or promoters of, efforts to improve care experiences in VA facilities.
Methods: We conducted case studies at two VA facilities, one with stable high scores on inpatient reports of emotional support between 2002 and 2006, and one with stable low scores over the same period. A semi-structured interview was used to gather information from staff who worked with patient survey data at the study facilities. Data were analyzed using a previously developed qualitative framework describing organizational, professional and data-related barriers and promoters to data use.
Results: Respondents reported more promoters than barriers to using survey data, and particularly support for improvement efforts. Themes included developing patient-centered cultures, quality improvement structures such as regular data review, and training staff in patient-centered behaviors. The influence of incentives, the role of nursing leadership, and triangulating survey data with other data on patients' views also emerged as important. It was easier to collect data on current organization and practice than those in the past and this made it difficult to deduce which factors might influence differing facility performance.
Conclusions: Interviews with VA staff provided promising examples of how systematic processes for using survey data can be implemented as part of wider quality improvement efforts. However, prospective studies are needed to identify the most effective strategies for using patient feedback to improve specific aspects of patient-centered care.
C1 [Davies, Elizabeth A.] Kings Coll London, Thames Canc Registry, London SE1 3QD, England.
[Meterko, Mark M.; Charns, Martin P.; Seibert, Marjorie E. Nealon] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA 02130 USA.
[Cleary, Paul D.] Yale Univ, Sch Med, Sch Publ Hlth, New Haven, CT 06520 USA.
RP Davies, EA (reprint author), Kings Coll London, Thames Canc Registry, 42 Weston St, London SE1 3QD, England.
EM Elizabeth.Davies@kcl.ac.uk
OI Charns, Martin/0000-0002-7102-5331
FU Agency for Healthcare Research and Quality [U18 HS016978]; New York City
based private independent foundation; Department of Health
FX EAD was partly funded as a Harkness Fellow by The Commonwealth Fund, a
New York City based private independent foundation. The views presented
here are those of the authors and not necessarily those of The
Commonwealth Fund, its director, officers, or staff.; EAD is employed by
the Thames Cancer Registry, King's College London which receives funding
from the Department of Health; the views expressed in this publication
are those of the authors and not necessarily those of the Department of
Health.; PDC was supported in part by a cooperative agreement with the
Agency for Healthcare Research and Quality: U18 HS016978.
NR 25
TC 11
Z9 11
U1 1
U2 9
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 DEC 12
PY 2011
VL 11
AR 334
DI 10.1186/1472-6963-11-334
PG 9
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 887WP
UT WOS:000299962800001
PM 22151714
ER
PT J
AU Weinger, K
Beverly, EA
Lee, Y
Sitnokov, L
Ganda, OP
Caballero, AE
AF Weinger, Katie
Beverly, Elizabeth A.
Lee, Yishan
Sitnokov, Lilya
Ganda, Om P.
Caballero, A. Enrique
TI The Effect of a Structured Behavioral Intervention on Poorly Controlled
Diabetes A Randomized Controlled Trial
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID LIFE-STYLE INTERVENTION; OF-THE-LITERATURE; GLYCEMIC CONTROL; INTENSIVE
TREATMENT; SELF-CARE; META-ANALYSIS; RISK-FACTORS; US ADULTS;
DEPRESSION; MELLITUS
AB Background: Although maintaining nearly normal glycemia delays onset and slows progression of diabetes complications, many patients with diabetes and their physicians struggle to achieve glycemic targets. The best methods to support patients as they follow diabetes prescriptions and recommendations are unclear.
Methods: To test the efficacy of a behavioral diabetes intervention in improving glycemia in long-duration, poorly controlled diabetes, we randomized 222 adults with diabetes (49% type 1) (mean [SD] age, 53 [12] years; mean [SD] disease duration 18 [12] years; mean [SD] hemoglobin A(1c) [HbA(1c)] concentration, 9.0% [1.1%]) to attend (1) a 5-session manual-based, educator-led structured group intervention with cognitive behavioral strategies (structured behavioral arm); (2) an educatorled attention control group education program (group attention control); or (3) unlimited individual nurse and dietitian education sessions for 6 months (individual control). Outcomes were baseline and 3-, 6-, and 12-month post-intervention HbA(1c) levels (primary) and frequency of diabetes self-care, 3-day pedometer readings, 24-hour diet recalls, average number of glucose checks, physical fitness, depression, coping style, self-efficacy, and quality of life (secondary).
Results: Linear mixed modeling found that all groups showed improved HbA(1c) levels (P < .001). However, the structured behavioral arm showed greater improvements than the group and individual control arms (3-month HbA(1c) concentration changes: -0.8% vs -0.4% and -0.4%, respectively (P = .04 for group x time interaction). Furthermore, participants with type 2 disease showed greater improvement than those with type 1 (P = .04 for type of diabetes x time interaction). Quality of life, glucose monitoring, and frequency of diabetes self-care did not differ by intervention over time.
Conclusions: A structured, cognitive behavioral program is more effective than 2 control interventions in improving glycemia in adults with long-duration diabetes. Educators can successfully use modified psychological and behavioral strategies.
C1 [Weinger, Katie; Beverly, Elizabeth A.; Lee, Yishan; Sitnokov, Lilya; Ganda, Om P.; Caballero, A. Enrique] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Weinger, Katie; Beverly, Elizabeth A.; Ganda, Om P.; Caballero, A. Enrique] Harvard Univ, Sch Med, Boston, MA USA.
[Sitnokov, Lilya] Univ Vermont, Burlington, VT 05405 USA.
RP Weinger, K (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA.
EM Katie.Weinger@joslin.harvard.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[R01 DK60115]; Diabetes and Endocrinology Research Core grant [NIH P30
DK36836]; Joslin Diabetes Center Clinical Research Center
FX This work was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) grant R01 DK60115 (K. W.), the
Diabetes and Endocrinology Research Core grant NIH P30 DK36836, and the
Joslin Diabetes Center Clinical Research Center. Abbott Laboratories,
Abbott Park, Illinois; LifeScan, Milpitas, California; and Roche
Diagnostics, Indianapolis, Indiana, contributed glucose meters and test
strips.
NR 44
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U1 0
U2 15
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 DEC 12
PY 2011
VL 171
IS 22
BP 1990
EP 1999
DI 10.1001/archinternmed.2011.502
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 860VD
UT WOS:000297975100004
PM 21986346
ER
PT J
AU Walter, LC
AF Walter, Louise C.
TI What Is the Right Cancer Screening Rate for Older Adults?
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID AGE 80 YEARS; WOMEN; MAMMOGRAPHY; BURDENS
C1 [Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA.
[Walter, Louise C.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA.
RP Walter, LC (reprint author), San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,181G, San Francisco, CA 94121 USA.
EM louise.walter@ucsf.edu
FU NCI NIH HHS [R01 CA134425, CA134425]
NR 10
TC 7
Z9 7
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 DEC 12
PY 2011
VL 171
IS 22
BP 2037
EP 2039
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 860VD
UT WOS:000297975100012
PM 22158574
ER
PT J
AU Hori, K
Sen, A
Kirchhausen, T
Artavanis-Tsakonas, S
AF Hori, Kazuya
Sen, Anindya
Kirchhausen, Tom
Artavanis-Tsakonas, Spyros
TI Synergy between the ESCRT-III complex and Deltex defines a
ligand-independent Notch signal
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID WING IMAGINAL DISC; DROSOPHILA-MELANOGASTER; ACTIVATION; PATHWAY;
PROTEIN; ENDOCYTOSIS; TRAFFICKING; SUPPRESSOR; RECEPTOR; SERRATE
AB The Notch signaling pathway defines a conserved mechanism that regulates cell fate decisions in metazoans. Signaling is modulated by a broad and multifaceted genetic circuitry, including members of the endocytic machinery. Several individual steps in the endocytic pathway have been linked to the positive or negative regulation of the Notch receptor. In seeking genetic elements involved in regulating the endosomal/lysosomal degradation of Notch, mediated by the molecular synergy between the ubiquitin ligase Deltex and Kurtz, the non-visual beta-arrestin in Drosophila, we identified Shrub, a core component of the ESCRT-III complex as a key modulator of this synergy. Shrub promotes the lysosomal degradation of the receptor by mediating its delivery into multi-vesicular bodies (MVBs). However, the interplay between Deltex, Kurtz, and Shrub can bypass this path, leading to the activation of the receptor. Our analysis shows that Shrub plays a pivotal rate-limiting step in late endosomal ligand-independent Notch activation, depending on the Deltex-dependent ubiquitinylation state of the receptor. This activation mode of the receptor emphasizes the complexity of Notch signal modulation in a cell and has significant implications for both development and disease.
C1 [Hori, Kazuya; Sen, Anindya; Kirchhausen, Tom; Artavanis-Tsakonas, Spyros] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Kirchhausen, Tom] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Artavanis-Tsakonas, Spyros] Coll France, F-75231 Paris 05, France.
RP Artavanis-Tsakonas, S (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
EM artavanis@hms.harvard.edu
FU National Institutes of Health [NS26084, CA98402, 07572]; JSPS; FSMA
FX This work was supported by National Institutes of Health grants NS26084
and CA98402 (S. Artavanis-Tsakonas), grant 07572 (T. Kirchhausen), a
JSPS Postdoctoral Fellowship for Research Abroad (K. Hori), and a
Postdoctoral Fellowship from the FSMA (A. Sen).
NR 60
TC 48
Z9 50
U1 1
U2 4
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 DEC 12
PY 2011
VL 195
IS 6
BP 1005
EP 1015
DI 10.1083/jcb.201104146
PG 11
WC Cell Biology
SC Cell Biology
GA 864ZD
UT WOS:000298278100010
PM 22162134
ER
PT J
AU Pendse, GV
Borsook, D
Becerra, L
AF Pendse, Gautam V.
Borsook, David
Becerra, Lino
TI A Simple and Objective Method for Reproducible Resting State Network
(RSN) Detection in fMRI
SO PLOS ONE
LA English
DT Article
ID INDEPENDENT COMPONENT ANALYSIS; BLIND SEPARATION; ICA MODELS;
IDENTIFIABILITY; SEPARABILITY; ARCHITECTURE; UNIQUENESS; BRAIN
AB Spatial Independent Component Analysis (ICA) decomposes the time by space functional MRI (fMRI) matrix into a set of 1-D basis time courses and their associated 3-D spatial maps that are optimized for mutual independence. When applied to resting state fMRI (rsfMRI), ICA produces several spatial independent components (ICs) that seem to have biological relevance - the so-called resting state networks (RSNs). The ICA problem is well posed when the true data generating process follows a linear mixture of ICs model in terms of the identifiability of the mixing matrix. However, the contrast function used for promoting mutual independence in ICA is dependent on the finite amount of observed data and is potentially non-convex with multiple local minima. Hence, each run of ICA could produce potentially different IC estimates even for the same data. One technique to deal with this run-to-run variability of ICA was proposed by [1] in their algorithm RAICAR which allows for the selection of only those ICs that have a high run-to-run reproducibility. We propose an enhancement to the original RAICAR algorithm that enables us to assign reproducibility p-values to each IC and allows for an objective assessment of both within subject and across subjects reproducibility. We call the resulting algorithm RAICAR-N (N stands for null hypothesis test), and we have applied it to publicly available human rsfMRI data (http://www.nitrc.org). Our reproducibility analyses indicated that many of the published RSNs in rsfMRI literature are highly reproducible. However, we found several other RSNs that are highly reproducible but not frequently listed in the literature.
C1 [Pendse, Gautam V.; Borsook, David; Becerra, Lino] Harvard Univ, McLean Hosp, Sch Med, PAIN Grp,Imaging & Anal Grp IMAG, Belmont, MA USA.
[Borsook, David; Becerra, Lino] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Pendse, GV (reprint author), Harvard Univ, McLean Hosp, Sch Med, PAIN Grp,Imaging & Anal Grp IMAG, Belmont, MA USA.
EM gpendse@mclean.harvard.edu
FU National Institutes of Health (NIH) [K24NS064050, R01NS065051]
FX This work was supported by the National Institutes of Health (NIH) under
the grants K24NS064050 (to DB) and R01NS065051 (to DB). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 38
TC 11
Z9 11
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 DEC 12
PY 2011
VL 6
IS 12
AR e27594
DI 10.1371/journal.pone.0027594
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 866FT
UT WOS:000298366600003
PM 22174743
ER
PT J
AU Huang, M
Kennedy, R
Ali, AM
Moreau, LA
Meetei, AR
D'Andrea, AD
Chen, CC
AF Huang, Min
Kennedy, Richard
Ali, Abdullah M.
Moreau, Lisa A.
Meetei, Amom Ruhikanta
D'Andrea, Alan D.
Chen, Clark C.
TI Human MutS and FANCM complexes function as redundant DNA damage sensors
in the Fanconi Anemia pathway
SO DNA REPAIR
LA English
DT Article
DE Fanconi Anemia; MutS homologs; DNA damage response; Sensor
ID COMPLEMENTATION GROUP-M; INTERSTRAND CROSS-LINKS; MISMATCH-REPAIR; CORE
COMPLEX; CELL-CYCLE; CHECKPOINT RESPONSE; MOLECULAR SWITCH; DEFICIENT
MICE; HMUTS-BETA; IN-VITRO
AB The Fanconi Anemia (FA) pathway encodes a DNA damage response activated by DNA damage-stalled replication forks. Current evidence suggests that the FA pathway initiates with DNA damage recognition by the FANCM complex (FANCM/FAAP24/MHF). However, genetic inactivation of FANCM in mouse and DT40 cells causes only a partial defect in the FA pathway activation, suggesting the existence of redundant DNA damage sensors. Here we show that the MutS homologs function in this capacity. A RNAi screen revealed that MSH2 silencing caused defective FA pathway activation, as assessed by damage-induced FANCD2 mono-ubiquitination. A similar FA pathway defect was observed with MSH3 or MSH6 silencing. MSH2 depletion caused cellular phenotypes associated with defective FA pathway, including mitomycin C hypersensitivity and chromosomal instability. Further, silencing of FANCM in MSH2 deficient HEC59 cells caused a more severe FA defect relative to comparable silencing in MSH2 complemented HEC59 + Chr2 cells, suggesting redundant functions between MSH2 and FANCM. Consistent with this hypothesis, depletion of MSH2 resulted in defective chromatin localization of the FA core complex upon DNA damage. Further, MSH2 was co-purified and co-immunoprecipitated with FA core complex components. Taken together, our results suggest that human MutS homologs and FANCM complexes function as redundant DNA damage sensors of the FA pathway. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Chen, Clark C.] Dana Farber Canc Inst, Dept Radiat Oncol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Ali, Abdullah M.; Meetei, Amom Ruhikanta] Univ Cincinnati, Coll Med, Cincinnati Childrens Res Fdn, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
[Chen, Clark C.] Beth Israel Deaconess Med Ctr, Div Neurosurg, Boston, MA 02115 USA.
RP Chen, CC (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Beth Israel Deaconess Med Ctr, 450 Brookline Ave, Boston, MA 02215 USA.
EM clark_chen@dfci.harvard.edu
RI Chen, Clark/C-8714-2013;
OI Chen, Clark/0000-0001-6258-9277; huang, min/0000-0001-6735-1612
FU National Institutes of Health [RO1HL52725, RO1DK43889, PO1150654,
P50CA105009-01, PO1HL54785]; Leukemia/Lymphoma Society [LLS2007]; Doris
Duke Charitable Foundation; Sontag Foundation; Burroughs Wellcome;
National Cancer Institute; Ohio Cancer Research Associates
FX We thank Dr. Thomas A. Kunkel for kindly providing the HEC59 and
HEC59+Chr2 cells. We thank Dr. Thiyam Ramsing Singh for the reagents and
Dr. Pascal Zinn for his assistance with the clonogenic assays. We thank
Jung Min Kim, George-Lucian Moldovan, Younghoon Kee, Eunmi Park and
Donniphat Dejsuphong for critical reading of this manuscript. This work
was supported by National Institutes of Health Grants RO1HL52725,
RO1DK43889, PO1150654, P50CA105009-01, PO1HL54785 (A.D.), a grant from
the Leukemia/Lymphoma Society LLS2007 (A.D.), the Doris Duke Charitable
Foundation Clinical Scientist Development Award (C.C.C.), the Sontag
Foundation Distinguished Scientist Award (C.C.C.), the Burroughs
Wellcome Fund Career Awards for Medical Sciences (C.C.C.) and an
National Cancer Institute K12 award (C.C.C.). A.R.M was supported by a
grant from Ohio Cancer Research Associates.
NR 55
TC 14
Z9 14
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD DEC 10
PY 2011
VL 10
IS 12
BP 1203
EP 1212
DI 10.1016/j.dnarep.2011.09.006
PG 10
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 864EU
UT WOS:000298220600003
PM 21975120
ER
PT J
AU Kennedy, RD
Bylesjo, M
Kerr, P
Davison, T
Black, JM
Kay, EW
Holt, RJ
Proutski, V
Ahdesmaki, M
Farztdinov, V
Goffard, N
Hey, P
McDyer, F
Mulligan, K
Mussen, J
O'Brien, E
Oliver, G
Walker, SM
Mulligan, JM
Wilson, C
Winter, A
O'Donoghue, D
Mulcahy, H
O'Sullivan, J
Sheahan, K
Hyland, J
Dhir, R
Bathe, OF
Winqvist, O
Manne, U
Shanmugam, C
Ramaswamy, S
Leon, EJ
Smith, WI
McDermott, U
Wilson, RH
Longley, D
Marshall, J
Cummins, R
Sargent, DJ
Johnston, PG
Harkin, DP
AF Kennedy, Richard D.
Bylesjo, Max
Kerr, Peter
Davison, Timothy
Black, Julie M.
Kay, Elaine W.
Holt, Robert J.
Proutski, Vitali
Ahdesmaki, Miika
Farztdinov, Vadim
Goffard, Nicolas
Hey, Peter
McDyer, Fionnuala
Mulligan, Karl
Mussen, Julie
O'Brien, Eamonn
Oliver, Gavin
Walker, Steven M.
Mulligan, Jude M.
Wilson, Claire
Winter, Andreas
O'Donoghue, Diarmuid
Mulcahy, Hugh
O'Sullivan, Jacintha
Sheahan, Kieran
Hyland, John
Dhir, Rajiv
Bathe, Oliver F.
Winqvist, Ola
Manne, Upender
Shanmugam, Chandrakumar
Ramaswamy, Sridhar
Leon, Eduardo J.
Smith, William I., Jr.
McDermott, Ultan
Wilson, Richard H.
Longley, Daniel
Marshall, John
Cummins, Robert
Sargent, Daniel J.
Johnston, Patrick G.
Harkin, D. Paul
TI Development and Independent Validation of a Prognostic Assay for Stage
II Colon Cancer Using Formalin-Fixed Paraffin-Embedded Tissue
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID COLORECTAL-CANCER; GENE-EXPRESSION; ADJUVANT CHEMOTHERAPY; MOLECULAR
MARKERS; RECURRENCE; RECOMMENDATIONS; ASSOCIATION; MICROARRAY; THERAPY
AB Purpose
Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples.
Patients and Methods
A gene signature was developed from a balanced set of 73 patients with recurrent disease (high risk) and 142 patients with no recurrence (low risk) within 5 years of surgery.
Results
The 634-probe set signature identified high-risk patients with a hazard ratio (HR) of 2.62 (P < .001) during cross validation of the training set. In an independent validation set of 144 samples, the signature identified high-risk patients with an HR of 2.53 (P < .001) for recurrence and an HR of 2.21 (P = .0084) for cancer-related death. Additionally, the signature was shown to perform independently from known prognostic factors (P < .001).
Conclusion
This gene signature represents a novel prognostic biomarker for patients with stage II colon cancer that can be applied to FFPE tumor samples.
C1 [Kennedy, Richard D.; McDermott, Ultan; Wilson, Richard H.; Longley, Daniel; Johnston, Patrick G.; Harkin, D. Paul] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7BL, Antrim, North Ireland.
[Kay, Elaine W.] Beaumont Hosp, Royal Coll Surg Ireland, Dublin, Ireland.
[O'Donoghue, Diarmuid; Mulcahy, Hugh; O'Sullivan, Jacintha; Sheahan, Kieran; Hyland, John] St Vincents Hosp, Ctr Colorectal Dis, Educ & Res Ctr, Dublin 4, Ireland.
[Kennedy, Richard D.; Bylesjo, Max; Kerr, Peter; Davison, Timothy; Black, Julie M.; Holt, Robert J.; Proutski, Vitali; Ahdesmaki, Miika; Farztdinov, Vadim; Goffard, Nicolas; Hey, Peter; McDyer, Fionnuala; Mulligan, Karl; Mussen, Julie; O'Brien, Eamonn; Oliver, Gavin; Walker, Steven M.; Wilson, Claire; Winter, Andreas; Johnston, Patrick G.; Harkin, D. Paul] Almac Diagnost, Craigavon, North Ireland.
[Manne, Upender; Shanmugam, Chandrakumar] Univ Alabama, Birmingham, AL USA.
[Smith, William I., Jr.] Suburban Hosp, Bethesda, MD USA.
[Marshall, John] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA.
[Ramaswamy, Sridhar; Leon, Eduardo J.] Massachusetts Gen Hosp, Ctr Canc, Richard B Simches Res Ctr, Boston, MA USA.
[Dhir, Rajiv] Univ Pittsburgh, Med Ctr, Shadyside Presbyterian Hosp, Pittsburgh, PA USA.
[Sargent, Daniel J.] Mayo Clin, Rochester, MN USA.
[Bathe, Oliver F.] Tom Baker Canc Clin, Calgary, AB, Canada.
[Winqvist, Ola] Karolinska Inst, Karolinska Hosp, S-10401 Stockholm, Sweden.
RP Harkin, DP (reprint author), Queens Univ Belfast, Ctr Canc Res & Cell Biol, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
EM paul.harkin@almacgroup.com
RI Kennedy, Richard/J-3489-2012; Kay, Elaine/D-8539-2013;
OI Kennedy, Richard/0000-0003-4737-6163; O'Sullivan,
Jacintha/0000-0001-8622-9858; Sargent, Daniel/0000-0002-2684-4741;
McDermott, Ultan/0000-0001-9032-4700; Ahdesmaki,
Miika/0000-0002-9091-7773
FU Almac Diagnostics
FX Supported by Almac Diagnostics.
NR 29
TC 77
Z9 77
U1 0
U2 5
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD DEC 10
PY 2011
VL 29
IS 35
BP 4620
EP 4626
DI 10.1200/JCO.2011.35.4498
PG 7
WC Oncology
SC Oncology
GA 863CZ
UT WOS:000298141700013
PM 22067406
ER
PT J
AU D'Amico, AV
Chen, MH
Crook, J
Armstrong, JG
Malone, S
Steigler, A
Dunne, M
Kantoff, PW
Denham, JW
AF D'Amico, Anthony V.
Chen, Ming-Hui
Crook, Juanita
Armstrong, John G.
Malone, Shawn
Steigler, Allison
Dunne, Mary
Kantoff, Philip W.
Denham, James W.
TI Duration of Short-Course Androgen Suppression Therapy and the Risk of
Death As a Result of Prostate Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; RADIATION-THERAPY; RADIOTHERAPY;
DEPRIVATION
AB Purpose
We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer-specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories.
Patients and Methods
Between February 2, 1996, and December 27, 2001, 761 men with unfavorable-risk PC were treated in Australia, New Zealand, Ireland, or the United States in a randomized trial with radiotherapy and 3, 4, or 6 months of AST (the study cohort). Competing risks regression was used to evaluate whether the duration of AST interacted with GS and was significantly associated with the risk of PCSM, adjusting for age, trial site, and PC prognostic factors.
Results
After a median follow-up of 10.9 years, 263 men died, 111 (42%) from PC. For all men, 6 versus 3 or 4 months of AST was associated with a reduced risk of PCSM (adjusted hazard ratio [AHR], 0.55; 95% CI, 0.36 to 0.82; P = .004). AHRs evaluating the impact of the duration of AST on the risk of PCSM were 0.67 (95% CI, 0.29 to 1.56; P = .35), 0.47 (95% CI, 0.25 to 0.85; P = .01), and 0.59 (95% CI, 0.30 to 1.19; P = .14) for men with GS <= 6, 7, and 8 to 10 PC, respectively. Therefore, the strongest evidence for this benefit was in men with GS 7 PC.
Conclusion
AST durations of no less than 6 months should be considered when treating GS 7 PC with conventional dose RT.
C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
[D'Amico, Anthony V.; Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Chen, Ming-Hui] Univ Connecticut, Storrs, CT USA.
[Crook, Juanita] Univ British Columbia, Kelowna, BC, Canada.
[Malone, Shawn] Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada.
[Armstrong, John G.; Dunne, Mary] St Lukes Hosp, Dublin, Ireland.
[Steigler, Allison; Denham, James W.] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia.
RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA.
EM adamico@partners.org
RI DENHAM, JAMES/G-7505-2013
OI DENHAM, JAMES/0000-0002-4177-9503
FU Schering-Plough; Ipsen; St Luke's Institute of Cancer Research; Friends
of St Luke's; Cancer Research Ireland
FX Supported in part by an unrestricted grant from Schering-Plough for data
management for the investigator-initiated, prospective, randomized
Dana-Farber Cancer Institute 95096 trial; Schering-Plough also provided
flutamide. The Irish Clinical Oncology Research Group 97-01 trial was
supported by Ipsen, St Luke's Institute of Cancer Research, Friends of
St Luke's, Cancer Research Ireland, and private donors.
NR 24
TC 7
Z9 7
U1 0
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 DEC 10
PY 2011
VL 29
IS 35
BP 4682
EP 4687
DI 10.1200/JCO.2011.37.0726
PG 6
WC Oncology
SC Oncology
GA 863CZ
UT WOS:000298141700022
PM 22042952
ER
PT J
AU Shinagare, AB
Ramaiya, NH
Jagannathan, JP
Hornick, JL
Swanson, RS
AF Shinagare, Atul B.
Ramaiya, Nikhil H.
Jagannathan, Jyothi P.
Hornick, Jason L.
Swanson, Richard S.
TI Primary Follicular Dendritic Cell Sarcoma of Liver Treated With
Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Regimen and
Surgery
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID TUMOR; DISEASE; ENTITY
C1 [Shinagare, Atul B.; Ramaiya, Nikhil H.; Jagannathan, Jyothi P.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Shinagare, Atul B.; Ramaiya, Nikhil H.; Jagannathan, Jyothi P.; Hornick, Jason L.; Swanson, Richard S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Shinagare, Atul B.; Ramaiya, Nikhil H.; Jagannathan, Jyothi P.; Hornick, Jason L.; Swanson, Richard S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 14
TC 7
Z9 9
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 DEC 10
PY 2011
VL 29
IS 35
BP E849
EP E851
DI 10.1200/JCO.2011.37.1906
PG 3
WC Oncology
SC Oncology
GA 863CZ
UT WOS:000298141700003
PM 22042944
ER
PT J
AU Ott, HC
Mathisen, DJ
AF Ott, Harald C.
Mathisen, Douglas J.
TI Bioartificial tissues and organs: are we ready to translate?
SO LANCET
LA English
DT Editorial Material
ID MATRIX; LUNGS
C1 [Ott, Harald C.; Mathisen, Douglas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg,Dept Surg, Boston, MA 02114 USA.
RP Ott, HC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg,Dept Surg, Boston, MA 02114 USA.
EM hott@partners.org
NR 12
TC 5
Z9 7
U1 0
U2 7
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 DEC 10
PY 2011
VL 378
IS 9808
BP 1977
EP 1978
DI 10.1016/S0140-6736(11)61791-1
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 863DY
UT WOS:000298144200006
PM 22119608
ER
PT J
AU Kohli, P
Cannon, CP
AF Kohli, Payal
Cannon, Christopher P.
TI Statins and safety: can we finally be reassured?
SO LANCET
LA English
DT Editorial Material
ID RANDOMIZED-TRIALS; LOWERING DRUGS; CHOLESTEROL; RISK; MORTALITY; CANCER;
PARTICIPANTS; METAANALYSIS; EFFICACY
C1 [Kohli, Payal; Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
RP Kohli, P (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA.
EM cpcannon@partners.org
NR 13
TC 9
Z9 10
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD DEC 10
PY 2011
VL 378
IS 9808
BP 1980
EP 1981
DI 10.1016/S0140-6736(11)61544-4
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 863DY
UT WOS:000298144200008
PM 22115875
ER
PT J
AU Johnson, T
Gaunt, TR
Newhouse, SJ
Padmanabhan, S
Tomaszewski, M
Kumari, M
Morris, RW
Tzoulaki, I
O'Brien, ET
Poulter, NR
Sever, P
Shields, DC
Thom, S
Wannamethee, SG
Whincup, PH
Brown, MJ
Connell, JM
Dobson, RJ
Howard, PJ
Mein, CA
Onipinla, A
Shaw-Hawkins, S
Zhang, Y
Smith, GD
Day, INM
Lawlor, DA
Goodall, AH
Fowkes, FG
Abecasis, GR
Elliott, P
Gateva, V
Braund, PS
Burton, PR
Nelson, CP
Tobin, MD
van der Harst, P
Glorioso, N
Neuvrith, H
Salvi, E
Staessen, JA
Stucchi, A
Devos, N
Jeunemaitre, X
Plouin, PF
Tichet, J
Juhanson, P
Org, E
Putku, M
Sober, S
Veldre, G
Viigimaa, M
Levinsson, A
Rosengren, A
Thelle, DS
Hastie, CE
Hedner, T
Lee, WK
Melander, O
Wahlstrand, B
Hardy, R
Wong, A
Cooper, JA
Palmen, J
Chen, L
Stewart, AFR
Wells, GA
Westra, HJ
Wolfs, MGM
Clarke, R
Franzosi, MG
Goel, A
Hamsten, A
Lathrop, M
Peden, JF
Seedorf, U
Watkins, H
Ouwehand, WH
Sambrook, J
Stephens, J
Casas, JP
Drenos, F
Holmes, MV
Kivimaki, M
Shah, S
Shah, T
Talmud, PJ
Whittaker, J
Wallace, C
Delles, C
Laan, M
Kuh, D
Humphries, SE
Nyberg, F
Cusi, D
Roberts, R
Newton-Cheh, C
Franke, L
Stanton, AV
Dominiczak, AF
Farrall, M
Hingorani, AD
Samani, NJ
Caulfield, MJ
Munroe, PB
AF Johnson, Toby
Gaunt, Tom R.
Newhouse, Stephen J.
Padmanabhan, Sandosh
Tomaszewski, Maciej
Kumari, Meena
Morris, Richard W.
Tzoulaki, Ioanna
O'Brien, Eoin T.
Poulter, Neil R.
Sever, Peter
Shields, Denis C.
Thom, Simon
Wannamethee, Sasiwarang G.
Whincup, Peter H.
Brown, Morris J.
Connell, John M.
Dobson, Richard J.
Howard, Philip J.
Mein, Charles A.
Onipinla, Abiodun
Shaw-Hawkins, Sue
Zhang, Yun
Smith, George Davey
Day, Ian N. M.
Lawlor, Debbie A.
Goodall, Alison H.
Fowkes, F. Gerald
Abecasis, Goncalo R.
Elliott, Paul
Gateva, Vesela
Braund, Peter S.
Burton, Paul R.
Nelson, Christopher P.
Tobin, Martin D.
van der Harst, Pim
Glorioso, Nicola
Neuvrith, Hani
Salvi, Erika
Staessen, Jan A.
Stucchi, Andrea
Devos, Nabila
Jeunemaitre, Xavier
Plouin, Pierre-Francois
Tichet, Jean
Juhanson, Peeter
Org, Elin
Putku, Margus
Sober, Siim
Veldre, Gudrun
Viigimaa, Margus
Levinsson, Anna
Rosengren, Annika
Thelle, Dag S.
Hastie, Claire E.
Hedner, Thomas
Lee, Wai K.
Melander, Olle
Wahlstrand, Bjoern
Hardy, Rebecca
Wong, Andrew
Cooper, Jackie A.
Palmen, Jutta
Chen, Li
Stewart, Alexandre F. R.
Wells, George A.
Westra, Harm-Jan
Wolfs, Marcel G. M.
Clarke, Robert
Franzosi, Maria Grazia
Goel, Anuj
Hamsten, Anders
Lathrop, Mark
Peden, John F.
Seedorf, Udo
Watkins, Hugh
Ouwehand, Willem H.
Sambrook, Jennifer
Stephens, Jonathan
Casas, Juan-Pablo
Drenos, Fotios
Holmes, Michael V.
Kivimaki, Mika
Shah, Sonia
Shah, Tina
Talmud, Philippa J.
Whittaker, John
Wallace, Chris
Delles, Christian
Laan, Mans
Kuh, Diana
Humphries, Steve E.
Nyberg, Fredrik
Cusi, Daniele
Roberts, Robert
Newton-Cheh, Christopher
Franke, Lude
Stanton, Alice V.
Dominiczak, Anna F.
Farrall, Martin
Hingorani, Aroon D.
Samani, Nilesh J.
Caulfield, Mark J.
Munroe, Patricia B.
CA Cardiogenics Consortium
Global BPgen Consortium
TI Blood Pressure Loci Identified with a Gene-Centric Array
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; QUANTITATIVE-TRAIT LOCI;
ESSENTIAL-HYPERTENSION; CARDIOVASCULAR-DISEASE; LINKAGE DISEQUILIBRIUM;
SUSCEPTIBILITY LOCI; COMMON VARIANTS; ANGIOTENSINOGEN; METAANALYSIS;
POPULATION
AB Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 x 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery, and follow-up data identified SNPs significantly associated with BP at p < 8.56 x 10(-7) at four further loci (NPR3, FIFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
C1 [Johnson, Toby; Newhouse, Stephen J.; Howard, Philip J.; Mein, Charles A.; Onipinla, Abiodun; Shaw-Hawkins, Sue; Zhang, Yun; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, Barts & London Genome Ctr, London EC1M 6BQ, England.
[Gaunt, Tom R.; Smith, George Davey; Day, Ian N. M.; Lawlor, Debbie A.] Univ Bristol, Sch Social & Community Med, Med Res Council MRC Ctr Causal Anal Translat Epid, Bristol BS8 2BN, Avon, England.
[Newhouse, Stephen J.] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, MRC Ctr Neurodegenerat Res, London SE5 8AF, England.
[Padmanabhan, Sandosh; Hastie, Claire E.; Lee, Wai K.; Shah, Sonia; Delles, Christian; Dominiczak, Anna F.] Univ Glasgow, Inst Cardiovasc & Med Sci, Coll Med Vet & Life Sci, Glasgow G12 8TA, Lanark, Scotland.
[Tomaszewski, Maciej; Goodall, Alison H.; Braund, Peter S.; Nelson, Christopher P.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.
[Tomaszewski, Maciej; Goodall, Alison H.; Braund, Peter S.; Burton, Paul R.; Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Hosp, Leicester Natl Inst Hlth Res NIHR Biomed Res Unit, Leicester LE3 9QP, Leics, England.
[Kumari, Meena; Seedorf, Udo; Ouwehand, Willem H.; Sambrook, Jennifer; Casas, Juan-Pablo; Hingorani, Aroon D.] UCL, Div Populat Hlth, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
[Morris, Richard W.; Wannamethee, Sasiwarang G.] UCL Med Sch, Dept Primary Care & Populat Hlth, Div Populat Hlth, London NW3 2PF, England.
[Tzoulaki, Ioanna] Univ Ioannina, Dept Hyg & Epidemiol, Ioannina 45110, Greece.
[Tzoulaki, Ioanna; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.
[O'Brien, Eoin T.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland.
[Poulter, Neil R.; Sever, Peter; Thom, Simon] Univ London Imperial Coll Sci Technol & Med, Int Ctr Circulatory Hlth, London W2 1PG, England.
[Shields, Denis C.] Univ Coll Dublin, Complex & Adapt Syst Lab, Dublin 4, Ireland.
[Whincup, Peter H.] St Georges Univ London, London SW17 0RE, England.
[Brown, Morris J.] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 2QQ, England.
[Connell, John M.] Univ Dundee, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Scotland.
[Dobson, Richard J.] Kings Coll London, S London & Maudsley Natl Hlth Serv Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, London SE5 8AF, England.
[Dobson, Richard J.] Kings Coll London, Inst Psychiat, London SE5 8AF, England.
[Fowkes, F. Gerald] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland.
[Abecasis, Goncalo R.; Gateva, Vesela] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48103 USA.
[Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, MRC Hlth Protect Agcy Ctr Environm & Hlth, London W2 1PG, England.
[Burton, Paul R.; Tobin, Martin D.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England.
[van der Harst, Pim] Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands.
[Glorioso, Nicola] Univ Sassari, Azienda Osped Univ, Hypertens & Related Dis Ctr, I-07100 Sassari, Italy.
[Neuvrith, Hani] IBM Res, Machine Learning & Data Min Grp, IL-31905 Haifa, Israel.
[Salvi, Erika; Stucchi, Andrea; Cusi, Daniele] Univ Milan, Dept Med Surg & Dent, I-20142 Milan, Italy.
[Salvi, Erika; Stucchi, Andrea; Cusi, Daniele] Univ Milan, Grad Sch Nephrol, San Paolo Hosp, Div Nephrol, I-20142 Milan, Italy.
[Salvi, Erika; Cusi, Daniele] Fdn Filarete, Genom & Bioinformat Unit, I-20139 Milan, Italy.
[Staessen, Jan A.] Univ Louvain, Dept Cardiovasc Sci, Div Hypertens & Cardiovasc Rehabil, BE-3000 Louvain, Belgium.
[Devos, Nabila; Jeunemaitre, Xavier; Plouin, Pierre-Francois] Paris Ctr Rech Cardiovasc, INSERM, UMRS 970, F-75015 Paris, France.
[Jeunemaitre, Xavier; Plouin, Pierre-Francois] Univ Paris 05, Fac Med, F-75908 Paris 15, France.
[Jeunemaitre, Xavier] Hop Europeen Georges Pompidou, AP HP, F-75908 Paris 15, France.
[Plouin, Pierre-Francois] Hop Europeen Georges Pompidou, Dept Genet, F-75908 Paris 15, France.
[Tichet, Jean] Inst Interreg Sante, F-37520 Tours, La Riche, France.
[Juhanson, Peeter; Org, Elin; Putku, Margus; Sober, Siim; Veldre, Gudrun; Shah, Tina; Laan, Mans] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia.
[Veldre, Gudrun] Univ Tartu, Dept Cardiol, EE-51014 Tartu, Estonia.
[Viigimaa, Margus] Tallinn Univ Technol, Inst Biomed Engn, EE-19086 Tallinn, Estonia.
[Viigimaa, Margus] N Estonia Med Ctr, Ctr Cardiol, EE-13419 Tallinn, Estonia.
[Levinsson, Anna; Wallace, Chris; Nyberg, Fredrik] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Publ Hlth & Community Med, S-40530 Gothenburg, Sweden.
[Rosengren, Annika] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Emergency & Cardiovasc Med, S-41685 Gothenburg, Sweden.
[Thelle, Dag S.] Univ Oslo, Inst Basic Med Sci, Dept Biostat, N-0317 Oslo, Norway.
[Hedner, Thomas; Wahlstrand, Bjoern] Univ Gothenburg, Sahlgrenska Acad, Inst Internal Med, SE-40530 Gothenburg, Sweden.
[Melander, Olle] Lund Univ, Dept Clin Sci, SE-20502 Malmo, Sweden.
[Melander, Olle] Skane Univ Hosp, Ctr Emergency Med, SE-20502 Malmo, Sweden.
[Hardy, Rebecca; Wong, Andrew; Talmud, Philippa J.; Kuh, Diana] MRC Unit Lifelong Hlth & Ageing, London WC1B 5JU, England.
[Cooper, Jackie A.; Palmen, Jutta; Watkins, Hugh; Drenos, Fotios; Whittaker, John; Humphries, Steve E.] UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London WC1E 6JF, England.
[Chen, Li; Stewart, Alexandre F. R.; Wells, George A.; Roberts, Robert] Univ Ottawa, Inst Heart, Ottawa Heart Genom Study, Ottawa, ON K1Y 4W7, Canada.
[Westra, Harm-Jan; Franke, Lude] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.
[Wolfs, Marcel G. M.] Univ Groningen, Univ Med Ctr Groningen, Med Biol Sect, Dept Pathol & Med Biol, NL-9700 RB Groningen, Netherlands.
[Clarke, Robert] Clin Trial Serv Unit, Oxford OX3 7LF, England.
[Franzosi, Maria Grazia] Ist Mario Negri, Dept Cardiovasc Res, I-20156 Milan, Italy.
[Goel, Anuj; Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Goel, Anuj; Farrall, Martin] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England.
Karolinska Univ, Hosp Solna, Ctr Mol Med, Karolinska Inst,Dept Med Solna,Atherosclerosis Re, S-17176 Stockholm, Sweden.
Ctr Natl Genotypage, F-91057 Evry, France.
Univ Munster, LIFA, Gesell Arterioskleroseforsch eV, D-48149 Munster, Germany.
[Hamsten, Anders; Lathrop, Mark; Peden, John F.] Univ Cambridge, Dept Haematol, Cambridge CB2 0PT, England.
[Hamsten, Anders; Lathrop, Mark; Peden, John F.] Natl Hlth Serv Blood & Transplant, Cambridge CB2 0PT, England.
[Hamsten, Anders] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
[Seedorf, Udo; Holmes, Michael V.] Univ London London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1E 7HT, England.
[Stephens, Jonathan] UCL, Dept Genet Evolut & Environm, UCL Genet Inst, London WC1E 6BT, England.
[Casas, Juan-Pablo] UCL, Rayne Inst, Div Med, Ctr Clin Pharmacol, London WC1E 6JJ, England.
[Holmes, Michael V.] GlaxoSmithKline, Med Res Ctr, Genet, Stevenage SG1 2NY, Herts, England.
[Kivimaki, Mika] Univ Cambridge, Cambridge Inst Med Res, Wellcome Trust Diabet & Inflammat Lab, Juvenile Diabet Res Fdn,Addenbrookes Hosp, Cambridge CB2 0XY, England.
[Wallace, Chris; Nyberg, Fredrik] AstraZeneca R&D, S-43183 Molndal, Sweden.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA.
[Stanton, Alice V.] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
RP Johnson, T (reprint author), Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, Barts & London Genome Ctr, Charterhouse Sq, London EC1M 6BQ, England.
EM t.johnson@qmul.ac.uk; p.b.munroe@qmul.ac.uk
RI Grobbee, Diederick/C-7651-2014; Laan, Maris/A-4100-2011; Kivimaki,
Mika/B-3607-2012; Dobson, Richard/C-9269-2011; Stewart,
Alexandre/A-5677-2011; Lucas, Gavin/D-4346-2012; Whittaker,
John/B-8609-2012; Stanton, Alice/F-4697-2012; Abecasis,
Goncalo/B-7840-2010; Newhouse, Stephen/C-9330-2011; Pfeufer,
Arne/B-6634-2013; Colaus, PsyColaus/K-6607-2013; Shah,
Sonia/N-7547-2013; Gaunt, Tom/O-3918-2014; Salvi, Erika/C-1033-2015;
Onland-Moret, N. Charlotte/G-9185-2011; Staessen, Jan/A-1065-2011;
Meitinger, Thomas/O-1318-2015; Burton, Paul/H-7527-2016; Matullo,
Giuseppe/K-6383-2016; Bochud, Murielle/A-3981-2010; Franke,
Lude/P-7036-2016; Padmanabhan, Sandosh/S-3963-2016; Wong,
Andrew/M-8899-2016; Davey Smith, George/A-7407-2013;
OI Wain, Louise/0000-0003-4951-1867; Marrugat, Jaume/0000-0003-3320-554X;
Watkins, Hugh/0000-0002-5287-9016; Lawlor, Debbie A/0000-0002-6793-2262;
Ouwehand, Willem/0000-0002-7744-1790; Morris,
Richard/0000-0001-7240-4563; Stewart, Alexandre/0000-0003-2673-9164;
Padmanabhan, Sandosh/0000-0003-3869-5808; Luben,
Robert/0000-0002-5088-6343; Humphries, Stephen E/0000-0002-8221-6547;
Kumari, Meena/0000-0001-9716-1035; Sacerdote,
Carlotta/0000-0002-8008-5096; Forouhi, Nita/0000-0002-5041-248X;
Wallace, Chris/0000-0001-9755-1703; Grobbee,
Diederick/0000-0003-4472-4468; Laan, Maris/0000-0002-8519-243X; Dobson,
Richard/0000-0003-4224-9245; Whittaker, John/0000-0002-3529-2379;
Newhouse, Stephen/0000-0002-1843-9842; Shah, Sonia/0000-0001-5860-4526;
Gaunt, Tom/0000-0003-0924-3247; Salvi, Erika/0000-0002-2724-2291;
Staessen, Jan/0000-0002-3026-1637; Bochud, Murielle/0000-0002-5727-0218;
Franke, Lude/0000-0002-5159-8802; Wong, Andrew/0000-0003-2079-4779;
Davey Smith, George/0000-0002-1407-8314; Seedorf,
Udo/0000-0003-4652-5358; Zeggini, Eleftheria/0000-0003-4238-659X; Org,
Elin/0000-0003-1451-9375; Shah, Tina/0000-0001-7724-7210; Wannamethee,
Sasiwarang/0000-0001-9484-9977; Kivimaki, Mika/0000-0002-4699-5627;
Stanton, Alice/0000-0002-4961-165X; Whincup, Peter/0000-0002-5589-4107;
Talmud, Philippa/0000-0002-5560-1933; Monsalve, Beatriz
Elena/0000-0002-5994-866X; Johnson, Toby/0000-0002-5998-3270; Abecasis,
Goncalo/0000-0003-1509-1825
FU Pfizer
FX Author and cohort acknowledgements and author contributions are cited in
the Supplemental Data. The following authors declare the following
potential conflicts of interest: F.N. is a full-time employee at
AstraZeneca. J.W. is a full-time employee at GlaxoSmithKline. N.R.P. has
received financial support and consultancy fees from several
pharmaceutical companies that manufacture either blood-pressure-lowering
or lipid-lowering agents or both. P.S. has received research awards from
Pfizer.
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PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD DEC 9
PY 2011
VL 89
IS 6
BP 688
EP 700
DI 10.1016/j.ajhg.2011.10.013
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 864AF
UT WOS:000298208700001
PM 22100073
ER
PT J
AU Hatziapostolou, M
Polytarchou, C
Aggelidou, E
Drakaki, A
Poultsides, GA
Jaeger, SA
Ogata, H
Karin, M
Struhl, K
Hadzopoulou-Cladaras, M
Iliopoulos, D
AF Hatziapostolou, Maria
Polytarchou, Christos
Aggelidou, Eleni
Drakaki, Alexandra
Poultsides, George A.
Jaeger, Savina A.
Ogata, Hisanobu
Karin, Michael
Struhl, Kevin
Hadzopoulou-Cladaras, Margarita
Iliopoulos, Dimitrios
TI An HNF4 alpha-miRNA Inflammatory Feedback Circuit Regulates
Hepatocellular Oncogenesis
SO CELL
LA English
DT Article
ID HEPATOCYTE NUCLEAR FACTOR-4-ALPHA; INTESTINAL EPITHELIAL-CELLS;
OXIDATIVE STRESS; TRANSCRIPTION FACTORS; STAT3 ACTIVATION; ELEGANS
GENOME; CANCER; CARCINOMA; EXPRESSION; MICRORNA
AB Hepatocyte nuclear factor 4 alpha (HNF4 alpha) is essential for liver development and hepatocyte function. Here, we show that transient inhibition of HNF4 alpha initiates hepatocellular transformation through a microRNA-inflammatory feedback loop circuit consisting of miR-124, IL6R, STAT3, miR-24, and miR-629. Moreover, we show that, once this circuit is activated, it maintains suppression of HNF4 alpha and sustains oncogenesis. Systemic administration of miR-124, which modulates inflammatory signaling, prevents and suppresses hepatocellular carcinogenesis by inducing tumor-specific apoptosis without toxic side effects. As we also show that this HNF4 alpha circuit is perturbed in human hepatocellular carcinomas, our data raise the possibility that manipulation of this microRNA feedback-inflammatory loop has therapeutic potential for treating liver cancer.
C1 [Hatziapostolou, Maria; Polytarchou, Christos; Iliopoulos, Dimitrios] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hatziapostolou, Maria; Polytarchou, Christos; Iliopoulos, Dimitrios] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA.
[Struhl, Kevin] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Aggelidou, Eleni; Hadzopoulou-Cladaras, Margarita] Aristotle Univ Thessaloniki, Dept Genet Dev & Mol Biol, Dev Biol Lab, Sch Biol, Thessaloniki 54124, Greece.
[Drakaki, Alexandra] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA.
[Poultsides, George A.] Stanford Univ, Med Ctr, Dept Surg, Stanford, CA 94305 USA.
[Jaeger, Savina A.] Novartis Inst Biomed Res, Dept Dev Mol Pathways, Cambridge, MA 02139 USA.
[Ogata, Hisanobu; Karin, Michael] Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Sch Med, La Jolla, CA 92093 USA.
RP Iliopoulos, D (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA.
EM dimitrios_iliopoulos@dfci.harvard.edu
RI Hatziapostolou, Maria/N-1820-2015
OI Hatziapostolou, Maria/0000-0003-2493-7028
FU DFCI CIA; National Institutes of Health [RO1-CA118165, P42-ES0100337]
FX This work was supported by DFCI CIA start-up funds to D.I. and research
grants to M.K. from the National Institutes of Health (RO1-CA118165 and
P42-ES0100337). We would like to thank the Nikon Imaging Center at
Harvard Medical School for their help with light microscopy. Also, we
would like to thank Hye-Jung Kim for her assistance with the flow
cytometry analysis and Virgilio Garcia for his technical support.
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD DEC 9
PY 2011
VL 147
IS 6
BP 1233
EP 1247
DI 10.1016/j.cell.2011.10.043
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 863FL
UT WOS:000298148100014
PM 22153071
ER
PT J
AU Weitz-Schmidt, G
Schurpf, T
Springer, TA
AF Weitz-Schmidt, Gabriele
Schuerpf, Thomas
Springer, Timothy A.
TI The C-Terminal alpha I Domain Linker as a Critical Structural Element in
the Conformational Activation of alpha I Integrins
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FUNCTION-ASSOCIATED ANTIGEN-1; ADHESION MOLECULE-1 ICAM-1;
BETA-PROPELLER DOMAIN; ALLOSTERIC SITE; CELL-ADHESION; SUBUNIT;
ANTIBODIES; BINDING; LFA-1; ALPHA-L-BETA-2
AB The activation of alpha/beta heterodimeric integrins is the result of highly coordinated rearrangements within both subunits. The molecular interactions between the two subunits, however, remain to be characterized. In this study, we use the integrin alpha(L)beta(2) to investigate the functional role of the C-linker polypeptide that connects the C-terminal end of the inserted (I) domain with the beta-propeller domain on the alpha subunit and is located at the interface with the beta I domain of the alpha chain. We demonstrate that shortening of the C-linker by eight or more amino acids results in constitutively active alpha(L)beta(2) in which the alpha I domain is no longer responsive to the regulation by the beta I domain. Despite this intersubunit uncoupling, both I domains remain individually sensitive to intrasubunit conformational changes induced by allosteric modulators. Interestingly, the length and not the sequence of the C-linker appears to be critical for its functionality in alpha/beta intersubunit communication. Using two monoclonal antibodies (R7.1 and CBRLFA-1/1) we further demonstrate that shortening of the C-linker results in the gradual loss of combinational epitopes that require both the alpha I and beta-propeller domains for full reactivity. Taken together, our findings highlight the role of the C-linker as a spring-like element that allows relaxation of the alpha I domain in the resting state and controlled tension of the alpha I domain during activation, exerted by the beta chain.
C1 [Weitz-Schmidt, Gabriele] Univ Basel, PharmaCtr, CH-4056 Basel, Switzerland.
[Weitz-Schmidt, Gabriele; Schuerpf, Thomas; Springer, Timothy A.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
[Weitz-Schmidt, Gabriele; Schuerpf, Thomas; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Weitz-Schmidt, G (reprint author), Univ Basel, PharmaCtr, Klingelbergstr 50-70, CH-4056 Basel, Switzerland.
EM gabriele.weitz-schmidt@unibas.ch; springer@idi.harvard.edu
RI Schurpf, Thomas/E-7380-2012
FU National Institutes of Health [CA31798]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant CA31798.
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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 DEC 9
PY 2011
VL 286
IS 49
BP 42115
EP 42122
DI 10.1074/jbc.M111.282830
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 863QI
UT WOS:000298180900022
PM 21965670
ER
PT J
AU Finlay-Schultz, J
Canastar, A
Short, M
El Gazzar, M
Coughlan, C
Leonard, S
AF Finlay-Schultz, Jessica
Canastar, Andrew
Short, Margaret
El Gazzar, Mohamed
Coughlan, Christina
Leonard, Sherry
TI Transcriptional Repression of the alpha 7 Nicotinic Acetylcholine
Receptor Subunit Gene (CHRNA7) by Activating Protein-2 alpha (AP-2
alpha)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID RNA-POLYMERASE-II; FACTOR AP-2; DNA-BINDING;
FUNCTIONAL-CHARACTERIZATION; LINKAGE ANALYSIS; CARCINOMA-CELLS;
FRONTAL-CORTEX; RETINOIC ACID; FACTOR EGR-1; SCHIZOPHRENIA
AB The CHRNA7 gene, which encodes the alpha 7 nicotinic acetylcholine receptor (alpha 7*nAChR), has been implicated as a candidate gene in schizophrenia. Expression of the alpha 7*nAChR mRNA and protein are reduced in multiple regions of post-mortem brain from patients diagnosed with schizophrenia. Transcriptional regulation may therefore be an important mechanism for the regulation of this gene. A 230-bp proximal promoter fragment, necessary for transcription in cultured neuroblastoma cells, was used to study a putative AP-2 alpha binding site. Mutation of the site indicates that AP-2 alpha plays a negative role in regulating CHRNA7 transcription. This was confirmed through knockdown and overexpression of AP-2 alpha. Electrophoretic mobility shift assays (EMSAs) identified positive DNA-protein interaction at this same site, and supershift assays indicate that the complex includes AP-2 alpha. The interaction was confirmed in cells using chromatin immunoprecipitation (ChIP). DNA methylation was discovered as an anomalous mechanism for CHRNA7 regulation in one cell line. These studies suggest a role for AP-2 alpha regulation of CHRNA7 mRNA expression in multiple tissues during development.
C1 [Finlay-Schultz, Jessica; Canastar, Andrew; El Gazzar, Mohamed; Leonard, Sherry] Univ Colorado Denver, Dept Psychiat, Aurora, CO 80045 USA.
[Finlay-Schultz, Jessica] Univ Colorado Denver, Dept Biochem & Mol Genet, Aurora, CO 80045 USA.
[Leonard, Sherry] Univ Colorado Denver, Dept Pharmacol, Aurora, CO 80045 USA.
[Coughlan, Christina] Univ Denver, Dept Biol Sci, Denver, CO 80208 USA.
[Short, Margaret; Leonard, Sherry] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA.
RP Leonard, S (reprint author), Univ Colorado Denver, Dept Psychiat, Mail Stop 8344,POB 6511,Anschutz Med Campus, Aurora, CO 80045 USA.
EM Sherry.Leonard@ucdenver.edu
FU National Institutes of Health [DA009457, MH081177]; Veterans Affairs
Medical Research Service Merit Review
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DA009457 and MH081177 and a Veterans Affairs Medical
Research Service Merit Review (to S. L.).
NR 75
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U1 0
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 DEC 9
PY 2011
VL 286
IS 49
BP 42123
EP 42132
DI 10.1074/jbc.M111.276014
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 863QI
UT WOS:000298180900023
PM 21979958
ER
PT J
AU Jayaraman, T
Tejero, J
Chen, BB
Blood, AB
Frizzell, S
Shapiro, C
Tiso, M
Hood, BL
Wang, XD
Zhao, XJ
Conrads, TP
Mallampalli, RK
Gladwin, MT
AF Jayaraman, Thottala
Tejero, Jesus
Chen, Bill B.
Blood, Arlin B.
Frizzell, Sheila
Shapiro, Calli
Tiso, Mauro
Hood, Brian L.
Wang, Xunde
Zhao, Xuejun
Conrads, Thomas P.
Mallampalli, Rama K.
Gladwin, Mark T.
TI 14-3-3 Binding and Phosphorylation of Neuroglobin during Hypoxia
Modulate Six-to-Five Heme Pocket Coordination and Rate of Nitrite
Reduction to Nitric Oxide
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; INDUCIBLE FACTOR-1-ALPHA;
OXIDATIVE STRESS; GLOBIN FAMILY; PROTEIN; BRAIN; CYTOGLOBIN; ACTIVATION;
CELLS; MECHANISMS
AB Neuroglobin protects neurons from hypoxia in vitro and in vivo; however, the underlying mechanisms for this effect remain poorly understood. Most of the neuroglobin is present in a hexacoordinate state with proximal and distal histidines in the heme pocket directly bound to the heme iron. At equilibrium, the concentration of the five-coordinate neuroglobin remains very low (0.1-5%). Recent studies have shown that post-translational redox regulation of neuroglobin surface thiol disulfide formation increases the open probability of the heme pocket and allows nitrite binding and reaction to form NO. We hypothesized that the equilibrium between the six-and five-coordinate states and secondary reactions with nitrite to form NO could be regulated by other hypoxia-dependent post-translational modification(s). Protein sequence models identified candidate sites for both 14-3-3 binding and phosphorylation. In both in vitro experiments and human SH-SY5Y neuronal cells exposed to hypoxia and glucose deprivation, we observed that 1) neuroglobin phosphorylation and protein-protein interactions with 14-3-3 increase during hypoxic and metabolic stress; 2) neuroglobin binding to 14-3-3 stabilizes and increases the half-life of phosphorylation; and 3) phosphorylation increases the open probability of the heme pocket, which increases ligand binding (CO and nitrite) and accelerates the rate of anaerobic nitrite reduction to form NO. These data reveal a series of hypoxia-dependent post-translational modifications to neuroglobin that regulate the six-to-five heme pocket equilibrium and heme access to ligands. Hypoxia-regulated reactions of nitrite and neuroglobin may contribute to the cellular adaptation to hypoxia.
C1 [Hood, Brian L.; Conrads, Thomas P.; Gladwin, Mark T.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Dept Pharmacol & Chem Biol, Sch Med, Pittsburgh, PA 15261 USA.
[Jayaraman, Thottala; Tejero, Jesus; Frizzell, Sheila; Shapiro, Calli; Tiso, Mauro; Zhao, Xuejun; Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15213 USA.
[Jayaraman, Thottala; Chen, Bill B.; Mallampalli, Rama K.; Gladwin, Mark T.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Dept Med, Pittsburgh, PA 15213 USA.
[Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA.
[Wang, Xunde] NHLBI, NIH, Bethesda, MD 20892 USA.
[Blood, Arlin B.] Loma Linda Univ, Sch Med, Dept Pediat, Div Neonatol, Loma Linda, CA 92354 USA.
RP Gladwin, MT (reprint author), Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Dept Pharmacol & Chem Biol, Sch Med, Pittsburgh, PA 15261 USA.
EM gladwinmt@upmc.edu
OI Tejero, Jesus/0000-0003-3245-9978
FU National Institutes of Health [R01 HL098032, R01 HL096973, P01 HL103455,
R01 HL096376, R01 HL097376, R01 HL098174]; Institute for Transfusion
Medicine; Hemophilia Center of Western Pennsylvania
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01 HL098032, R01 HL096973, and P01 HL103455 (to M. T. G.)
and R01 HL096376, R01 HL097376, and R01 HL098174 (to R. K. M.). This
work was also supported by the Institute for Transfusion Medicine and
the Hemophilia Center of Western Pennsylvania (to M. T. G.). M. Tiso and
M. T. Gladwin are listed as co-inventors on a patent application
entitled "Neuroglobin as a Six-to-Five Coordinate-regulated Nitrite
Reductase."
NR 48
TC 29
Z9 31
U1 2
U2 11
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 DEC 9
PY 2011
VL 286
IS 49
BP 42679
EP 42689
DI 10.1074/jbc.M111.271973
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 863QI
UT WOS:000298180900075
PM 21965683
ER
PT J
AU Holm, S
Ueland, T
Dahl, TB
Michelsen, AE
Skjelland, M
Russell, D
Nymo, SH
Krohg-Sorensen, K
Clausen, OP
Atar, D
Januzzi, JL
Aukrust, P
Jensen, JK
Halvorsen, B
AF Holm, Sverre
Ueland, Thor
Dahl, Tuva B.
Michelsen, Annika E.
Skjelland, Mona
Russell, David
Nymo, Stale H.
Krohg-Sorensen, Kirsten
Clausen, Ole Petter
Atar, Dan
Januzzi, James L.
Aukrust, Pal
Jensen, Jesper K.
Halvorsen, Bente
TI Fatty Acid Binding Protein 4 Is Associated with Carotid Atherosclerosis
and Outcome in Patients with Acute Ischemic Stroke
SO PLOS ONE
LA English
DT Article
ID EXPRESSION; PLAQUE; AP2; INFLAMMATION; MACROPHAGES; PLATELET; MICE
AB Background and Purpose: Fatty acid binding protein 4 (FABP4) has been shown to play an important role in macrophage cholesterol trafficking and associated inflammation. To further elucidate the role of FABP4 in atherogenesis in humans, we examined the regulation of FABP4 in carotid atherosclerosis and ischemic stroke.
Methods: We examined plasma FABP4 levels in asymptomatic (n = 28) and symptomatic (n = 31) patients with carotid atherosclerosis, as well as in 202 subjects with acute ischemic stroke. In a subgroup of patients we also analysed the expression of FABP4 within the atherosclerotic lesion. In addition, we investigated the ability of different stimuli with relevance to atherosclerosis to regulate FABP4 expression in monocytes/macrophages.
Results: FABP4 levels were higher in patients with carotid atherosclerosis, both systemically and within the atherosclerotic lesion, with particular high mRNA levels in carotid plaques from patients with the most recent symptoms. Immunostaining of carotid plaques localized FABP4 to macrophages, while activated platelets and oxidized LDL were potent stimuli for FABP4 expression in monocytes/macrophages in vitro. When measured at the time of acute ischemic stroke, high plasma levels of FABP4 were significantly associated with total and cardiovascular mortality during follow-up, although we did not find that addition of FABP4 to the fully adjusted multivariate model had an effect on the prognostic discrimination for allcause mortality as assessed by c-statistics.
Conclusions: FABP4 is linked to atherogenesis, plaque instability and adverse outcome in patients with carotid atherosclerosis and acute ischemic stroke.
C1 [Holm, Sverre; Ueland, Thor; Dahl, Tuva B.; Michelsen, Annika E.; Nymo, Stale H.; Aukrust, Pal; Halvorsen, Bente] Univ Oslo, Rikshosp, Oslo Univ Hosp, Internal Med Res Inst, N-0027 Oslo, Norway.
[Skjelland, Mona; Russell, David] Univ Oslo, Rikshosp, Oslo Univ Hosp, Dept Neurol, N-0027 Oslo, Norway.
[Krohg-Sorensen, Kirsten] Univ Oslo, Rikshosp, Oslo Univ Hosp, Dept Thorac & Cardiovasc Surg, N-0027 Oslo, Norway.
[Clausen, Ole Petter] Univ Oslo, Rikshosp, Oslo Univ Hosp, Inst Pathol, N-0027 Oslo, Norway.
[Aukrust, Pal] Univ Oslo, Rikshosp, Oslo Univ Hosp, Sect Clin Immunol & Infect Dis, N-0027 Oslo, Norway.
[Atar, Dan] Univ Oslo, Hosp Ulleval, Div Cardiol, Oslo, Norway.
[Russell, David; Clausen, Ole Petter; Atar, Dan; Aukrust, Pal; Halvorsen, Bente] Univ Oslo, Fac Med, Oslo, Norway.
[Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Jensen, Jesper K.] Odense Univ Hosp, Dept Cardiol, DK-5000 Odense, Denmark.
RP Holm, S (reprint author), Univ Oslo, Rikshosp, Oslo Univ Hosp, Internal Med Res Inst, N-0027 Oslo, Norway.
EM sverre.holm@rr-research.no
RI Skjelland, Mona/B-7362-2016;
OI Krohg-Sorensen, Kirsten/0000-0002-5713-809X
FU Research Council of Norway; University of Oslo; Norwegian Council of
Cardiovascular Research; Helse Sor-Ost; Medinnova Foundation
FX This work was supported by grants from the Research Council of Norway,
University of Oslo, Norwegian Council of Cardiovascular Research, Helse
Sor-Ost, and Medinnova Foundation. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 18
TC 18
Z9 20
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 DEC 9
PY 2011
VL 6
IS 12
AR e28785
DI 10.1371/journal.pone.0028785
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 866FK
UT WOS:000298365700073
PM 22174896
ER
PT J
AU Halvorsen, K
Schaak, D
Wong, WP
AF Halvorsen, Ken
Schaak, Diane
Wong, Wesley P.
TI Nanoengineering a single-molecule mechanical switch using DNA
self-assembly
SO NANOTECHNOLOGY
LA English
DT Article
ID ATOMIC-FORCE MICROSCOPY; SPECTROSCOPY; ADHESION; CHEMISTRY; STRENGTH;
PHYSICS; SHAPES; MOTION; BONDS
AB The ability to manipulate and observe single biological molecules has led to both fundamental scientific discoveries and new methods in nanoscale engineering. A common challenge in many single-molecule experiments is reliably linking molecules to surfaces, and identifying their interactions. We have met this challenge by nanoengineering a novel DNA-based linker that behaves as a force-activated switch, providing a molecular signature that can eliminate errant data arising from non-specific and multiple interactions. By integrating a receptor and ligand into a single piece of DNA using DNA self-assembly, a single tether can be positively identified by force-extension behavior, and receptor-ligand unbinding easily identified by a sudden increase in tether length. Additionally, under proper conditions the exact same pair of molecules can be repeatedly bound and unbound. Our approach is simple, versatile and modular, and can be easily implemented using standard commercial reagents and laboratory equipment. In addition to improving the reliability and accuracy of force measurements, this single-molecule mechanical switch paves the way for high-throughput serial measurements, single-molecule on-rate studies, and investigations of population heterogeneity.
C1 [Halvorsen, Ken; Schaak, Diane; Wong, Wesley P.] Harvard Univ, Rowland Inst Harvard, Cambridge, MA 02138 USA.
[Halvorsen, Ken; Wong, Wesley P.] Childrens Hosp Boston, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA USA.
[Halvorsen, Ken; Wong, Wesley P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Halvorsen, K (reprint author), Harvard Univ, Rowland Inst Harvard, Cambridge, MA 02138 USA.
EM wong@rowland.harvard.edu
FU Rowland Junior Fellows program
FX The authors would like to thank Teresa Kao and Daniel Cheng for
laboratory support, and William Shih and Ted Feldman for helpful
discussions. This work was supported by the Rowland Junior Fellows
program.
NR 32
TC 9
Z9 9
U1 3
U2 11
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0957-4484
EI 1361-6528
J9 NANOTECHNOLOGY
JI Nanotechnology
PD DEC 9
PY 2011
VL 22
IS 49
AR 494005
DI 10.1088/0957-4484/22/49/494005
PG 8
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
Physics, Applied
SC Science & Technology - Other Topics; Materials Science; Physics
GA 852PU
UT WOS:000297370700006
PM 22101354
ER
PT J
AU Xu, CJ
Mu, LY
Roes, I
Miranda-Nieves, D
Nahrendorf, M
Ankrum, JA
Zhao, WA
Karp, JM
AF Xu, Chenjie
Mu, Luye
Roes, Isaac
Miranda-Nieves, David
Nahrendorf, Matthias
Ankrum, James A.
Zhao, Weian
Karp, Jeffrey M.
TI Nanoparticle-based monitoring of cell therapy
SO NANOTECHNOLOGY
LA English
DT Review
ID MESENCHYMAL STEM-CELLS; IRON-OXIDE NANOPARTICLES; OPTICAL COHERENCE
TOMOGRAPHY; MULTIFUNCTIONAL MAGNETIC NANOPARTICLES; MESOPOROUS SILICA
NANOPARTICLES; POSITRON-EMISSION-TOMOGRAPHY; MARROW STROMAL CELLS;
IN-VIVO; QUANTUM DOTS; BIOMEDICAL APPLICATIONS
AB Exogenous cell therapy aims to replace/repair diseased or dysfunctional cells and promises to revolutionize medicine by restoring tissue and organ function. To develop effective cell therapy, the location, distribution and long-term persistence of transplanted cells must be evaluated. Nanoparticle (NP) based imaging technologies have the potential to track transplanted cells non-invasively. Here we summarize the most recent advances in NP-based cell tracking with emphasis on (1) the design criteria for cell tracking NPs, (2) protocols for cell labeling, (3) a comparison of available imaging modalities and their corresponding contrast agents, (4) a summary of preclinical studies on NP-based cell tracking and finally (5) perspectives and future directions.
C1 [Xu, Chenjie; Mu, Luye; Roes, Isaac; Miranda-Nieves, David; Ankrum, James A.; Zhao, Weian; Karp, Jeffrey M.] Harvard Univ, Sch Med, Brigham & Womens Hosp,Div Hlth Sci & Technol, Harvard Stem Cell Inst,Harvard MIT,Ctr Regenerat, Cambridge, MA 02139 USA.
[Xu, Chenjie; Mu, Luye; Roes, Isaac; Miranda-Nieves, David; Ankrum, James A.; Zhao, Weian; Karp, Jeffrey M.] Harvard Univ, Sch Med, Brigham & Womens Hosp,Div Hlth Sci & Technol, Harvard Stem Cell Inst,Harvard MIT,Dept Med, Cambridge, MA 02139 USA.
[Nahrendorf, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA.
RP Karp, JM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Div Hlth Sci & Technol, Harvard Stem Cell Inst,Harvard MIT,Ctr Regenerat, 65 Landsdowne St, Cambridge, MA 02139 USA.
EM jkarp@rics.bwh.harvard.edu
RI Ankrum, James/N-4175-2014; xu, chenjie/E-4075-2012;
OI Ankrum, James/0000-0003-3959-6158; Xu, Chenjie/0000-0002-8278-3912
FU National Institute of Health [HL097172, HL095722, DE019191]; American
Heart Association [0970178N]; International Human Frontier Science
Program Organization; MIT-UROP; John Reed Fund
FX This work was supported by National Institute of Health grants HL097172,
HL095722, and DE019191 to JMK and by the American Heart Association
grant #0970178N to JMK. WZ is supported by an International Human
Frontier Science Program Organization postdoctoral fellowship. DMN is
supported by the MIT-UROP program and John Reed Fund.
NR 174
TC 39
Z9 40
U1 0
U2 28
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0957-4484
EI 1361-6528
J9 NANOTECHNOLOGY
JI Nanotechnology
PD DEC 9
PY 2011
VL 22
IS 49
AR 494001
DI 10.1088/0957-4484/22/49/494001
PG 17
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
Physics, Applied
SC Science & Technology - Other Topics; Materials Science; Physics
GA 852PU
UT WOS:000297370700002
PM 22101191
ER
PT J
AU Stewart, DS
Savechenkov, PY
Dostalova, Z
Chiara, DC
Ge, R
Raines, DE
Cohen, JB
Forman, SA
Bruzik, KS
Miller, KW
AF Stewart, Deirdre S.
Savechenkov, Pavel Y.
Dostalova, Zuzana
Chiara, David C.
Ge, Rile
Raines, Douglas E.
Cohen, Jonathan B.
Forman, Stuart A.
Bruzik, Karol S.
Miller, Keith W.
TI p-(4-Azipentyl)propofol: A Potent Photoreactive General Anesthetic
Derivative of Propofol
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID NICOTINIC ACETYLCHOLINE-RECEPTOR; GATED ION CHANNELS; GABA(A) RECEPTOR;
BINDING-SITE; ETOMIDATE; IDENTIFICATION; DIAZIRINES; AGONIST; ANALOGS;
PHARMACOLOGY
AB We synthesized 2,6-diisopropyl-4-[3-(3-methyl-3H-diazirin-3-yl)propyl]phenol (p-(4-azipentyl)propofol), or p-4-AziC5-Pro, a novel photoactivable derivative of the general anesthetic propofol. p-4-AziC5-Pro has an anesthetic potency similar to that of propofol. Like propofol, the compound potentiates inhibitory GABA(A) receptor current responses and allosterically modulates binding to both agonist and benzodiazepine sites, assayed on heterologously expressed GABA(A) receptors. p-4-AziC5-Pro inhibits excitatory current responses of nACh receptors expressed in Xenopus oocytes and photoincorporates into native nACh receptor-enriched Torpedo membranes. Thus, p-4-AziCS-Pro is a functional general anesthetic that both modulates and photoincorporates into Cys-loop ligand-gated ion channels, making it an excellent candidate for use in identifying propofol binding sites.
C1 [Stewart, Deirdre S.; Dostalova, Zuzana; Ge, Rile; Raines, Douglas E.; Forman, Stuart A.; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Chiara, David C.; Cohen, Jonathan B.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Savechenkov, Pavel Y.; Bruzik, Karol S.] Univ Illinois, Coll Pharm, Chicago, IL 60612 USA.
RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 32 Fruit St, Boston, MA 02114 USA.
EM k_miller@helix.mgh.harvard.edu
FU National Institute for General Medicine [GM 58448]; Department of
Anesthesia, Critical Care and Pain Medicine, Massachusetts General
Hospital
FX This research was supported by a grant from the National Institute for
General Medicine to K.W.M. (Grant GM 58448) and by the Department of
Anesthesia, Critical Care and Pain Medicine, Massachusetts General
Hospital.
NR 39
TC 17
Z9 18
U1 1
U2 9
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 DEC 8
PY 2011
VL 54
IS 23
BP 8124
EP 8135
DI 10.1021/jm200943f
PG 12
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 853SG
UT WOS:000297445400014
PM 22029276
ER
PT J
AU Chabner, BA
AF Chabner, Bruce A.
TI Drug Shortages - A Critical Challenge for the Generic-Drug Market
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
RI Mendoza, Elvia/A-9361-2012
NR 4
TC 50
Z9 52
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD DEC 8
PY 2011
VL 365
IS 23
BP 2147
EP 2149
DI 10.1056/NEJMp1112633
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 857PQ
UT WOS:000297731400013
PM 22040167
ER
PT J
AU Smith, AK
Williams, BA
Lo, B
AF Smith, Alexander K.
Williams, Brie A.
Lo, Bernard
TI Discussing Overall Prognosis with the Very Elderly
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Smith, Alexander K.; Williams, Brie A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA.
[Lo, Bernard] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Smith, Alexander K.; Williams, Brie A.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Smith, AK (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA.
FU NCRR NIH HHS [KL2 RR024130]
NR 5
TC 31
Z9 31
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 DEC 8
PY 2011
VL 365
IS 23
BP 2149
EP 2151
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 857PQ
UT WOS:000297731400014
PM 22150033
ER
PT J
AU Sterling, TR
Villarino, ME
Borisov, AS
Shang, N
Gordin, F
Bliven-Sizemore, E
Hackman, J
Hamilton, CD
Menzies, D
Kerrigan, A
Weis, SE
Weiner, M
Wing, D
Conde, MB
Bozeman, L
Horsburgh, CR
Chaisson, RE
AF Sterling, Timothy R.
Villarino, M. Elsa
Borisov, Andrey S.
Shang, Nong
Gordin, Fred
Bliven-Sizemore, Erin
Hackman, Judith
Hamilton, Carol Dukes
Menzies, Dick
Kerrigan, Amy
Weis, Stephen E.
Weiner, Marc
Wing, Diane
Conde, Marcus B.
Bozeman, Lorna
Horsburgh, C. Robert, Jr.
Chaisson, Richard E.
CA TB Trials Consortium PREVENT TB
TI Three Months of Rifapentine and Isoniazid for Latent Tuberculosis
Infection
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PREVENTIVE THERAPY; UNITED-STATES; RANDOMIZED-TRIAL; CLINICAL-TRIAL;
HIV-INFECTION; RIFAMPIN; PYRAZINAMIDE; PHARMACOKINETICS;
IMMUNOCOMPETENT; RIFABUTIN
AB BACKGROUND
Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion.
METHODS
We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%.
RESULTS
In the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination-therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination-therapy group and 3.7% in the isoniazid-only group (P = 0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001).
CONCLUSIONS
The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.)
C1 [Villarino, M. Elsa; Borisov, Andrey S.; Shang, Nong; Bliven-Sizemore, Erin; Bozeman, Lorna] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Gordin, Fred] George Washington Univ, Washington, DC USA.
[Gordin, Fred] Washington DC Vet Affairs Med Ctr, Washington, DC USA.
[Hackman, Judith; Chaisson, Richard E.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Hamilton, Carol Dukes] Family Hlth Int, Durham, NC USA.
[Hamilton, Carol Dukes] Duke Univ, Durham, NC USA.
[Menzies, Dick] McGill Univ, Montreal Chest Inst, Montreal, PQ, Canada.
[Weis, Stephen E.] Univ N Texas Hlth Sci Ctr Ft Worth, Ft Worth, TX USA.
[Weiner, Marc] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Weiner, Marc] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Wing, Diane] S Texas Consortium, Harlingen, TX USA.
[Conde, Marcus B.] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil.
[Horsburgh, C. Robert, Jr.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Sterling, Timothy R.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
RP Sterling, TR (reprint author), A2209 Med Ctr N, 1161 21st Ave S, Nashville, TN 37232 USA.
EM timothy.sterling@vanderbilt.edu
RI Conde, Marcus/A-2501-2013
FU CDC; Bristol-Myers Squibb; Pfizer; Sanofi-Aventis; Otsuka America
Pharmaceutical
FX Supported by the CDC.; Dr. Sterling reports receiving research grant
funding from Bristol-Myers Squibb and Pfizer for HIV observational
studies; Dr. Hamilton, being employed by Family Health International;
Dr. Weiner, receiving research grant funding from Sanofi-Aventis; and
Dr. Horsburgh, receiving payments from Otsuka America Pharmaceutical for
scientific reviews of study protocols. No other potential conflict of
interest relevant to this article was reported.
NR 39
TC 239
Z9 249
U1 6
U2 27
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD DEC 8
PY 2011
VL 365
IS 23
BP 2155
EP 2166
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 857PQ
UT WOS:000297731400001
PM 22150035
ER
PT J
AU Kinane, TB
Shailam, R
Mark, EJ
AF Kinane, T. Bernard
Shailam, Randheer
Mark, Eugene J.
TI Case 37-2011: A 9-Month-Old Boy with Recurrent Tachypnea and Respiratory
Distress
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID NEUROENDOCRINE CELL HYPERPLASIA; INTERSTITIAL LUNG-DISEASE; INFANCY;
CHILDREN; PNEUMONITIS; SPECTRUM
C1 [Kinane, T. Bernard] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Shailam, Randheer] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Kinane, T. Bernard] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Shailam, Randheer] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Kinane, TB (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
NR 25
TC 2
Z9 2
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 DEC 8
PY 2011
VL 365
IS 23
BP 2221
EP 2228
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 857PQ
UT WOS:000297731400009
PM 22150041
ER
PT J
AU Asaad, WF
Eskandar, EN
AF Asaad, Wael F.
Eskandar, Emad N.
TI Encoding of Both Positive and Negative Reward Prediction Errors by
Neurons of the Primate Lateral Prefrontal Cortex and Caudate Nucleus
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ANTERIOR CINGULATE CORTEX; STRIATAL NEURONS; DORSAL STRIATUM;
DOPAMINERGIC-NEURONS; TEMPORAL PREDICTION; DELAYED-RESPONSE;
DECISION-MAKING; SIGNALS; DISSOCIATION; VALUES
AB Learning can be motivated by unanticipated success or unexpected failure. The former encourages us to repeat an action or activity, whereas the latter leads us to find an alternative strategy. Understanding the neural representation of these unexpected events is therefore critical to elucidate learning-related circuits. We examined the activity of neurons in the lateral prefrontal cortex (PFC) and caudate nucleus of monkeys as they performed a trial-and-error learning task. Unexpected outcomes were widely represented in both structures, and neurons driven by unexpectedly negative outcomes were as frequent as those activated by unexpectedly positive outcomes. Moreover, both positive and negative reward prediction errors (RPEs) were represented primarily by increases in firing rate, unlike the manner in which dopamine neurons have been observed to reflect these values. Interestingly, positive RPEs tended to appear with shorter latency than negative RPEs, perhaps reflecting the mechanism of their generation. Last, in the PFC but not the caudate, trial-by-trial variations in outcome-related activity were linked to the animals' subsequent behavioral decisions. More broadly, the robustness of RPE signaling by these neurons suggests that actor-critic models of reinforcement learning in which the PFC and particularly the caudate are considered primarily to be "actors" rather than "critics," should be reconsidered to include a prominent evaluative role for these structures.
C1 Massachusetts Gen Hosp, Rhodan Ctr Nervous Syst Repair, Dept Neurosurg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Asaad, WF (reprint author), Rhode Isl Hosp, APC 6th Floor,593 Eddy St, Providence, RI 02903 USA.
EM wfasaad@alum.mit.edu
RI Asaad, Wael/I-8485-2012
OI Asaad, Wael/0000-0003-4406-9096
FU National Eye Institute [1R01EY017658]; National Institute on Drug Abuse
[1R01NS063249]; National Science Foundation [IOB 0645886]; NIDA
[1P50MH086400-03]; Howard Hughes Medical Institute; Tosteson Fellowship
FX This work was supported by grants from the National Eye Institute
(1R01EY017658), National Institute on Drug Abuse (1R01NS063249),
National Science Foundation (IOB 0645886), NIDA Conte Award
1P50MH086400-03, and the Howard Hughes Medical Institute. W.F.A. was
also supported by a Tosteson Fellowship. We thank Anne-Marie Amacher,
Ming Cheng, John Gale, Kenway Louie, Matt Mian, Mayank Mehta, Shaun
Patel, Sameer Sheth, and Ziv Williams for helpful discussions or
technical assistance.
NR 57
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Z9 38
U1 0
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD DEC 7
PY 2011
VL 31
IS 49
BP 17772
EP 17787
DI 10.1523/JNEUROSCI.3793-11.2011
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA 861QX
UT WOS:000298035400004
PM 22159094
ER
PT J
AU Chan, AM
Baker, JM
Eskandar, E
Schomer, D
Ulbert, I
Marinkovic, K
Cash, SS
Halgren, E
AF Chan, Alexander M.
Baker, Janet M.
Eskandar, Emad
Schomer, Donald
Ulbert, Istvan
Marinkovic, Ksenija
Cash, Sydney S.
Halgren, Eric
TI First-Pass Selectivity for Semantic Categories in Human Anteroventral
Temporal Lobe
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID TRANSCRANIAL MAGNETIC STIMULATION; VISUAL OBJECT RECOGNITION;
DISTORTION-CORRECTED FMRI; WORD FORM AREA; MACAQUE MONKEY; NEURAL BASIS;
SPATIOTEMPORAL DYNAMICS; INFEROTEMPORAL CORTEX; CORTICAL AFFERENTS;
HUMAN BRAIN
AB How the brain encodes the semantic concepts represented by words is a fundamental question in cognitive neuroscience. Hemodynamic neuroimaging studies have robustly shown that different areas of posteroventral temporal lobe are selectively activated by images of animals versus manmade objects. Selective responses in these areas to words representing animals versus objects are sometimes also seen, but they are task-dependent, suggesting that posteroventral temporal cortex may encode visual categories, while more anterior areas encode semantic categories. Here, using the spatiotemporal resolution provided by intracranial macroelectrode and microelectrode arrays, we report category-selective responses to words representing animals and objects in human anteroventral temporal areas including inferotemporal, perirhinal, and entorhinal cortices. This selectivity generalizes across tasks and sensory modalities, suggesting that it represents abstract lexicosemantic categories. Significant category-specific responses are found in measures sensitive to synaptic activity (local field potentials, high gamma power, current sources and sinks) and unit-firing (multiunit and single-unit activity). Category-selective responses can occur at short latency (as early as 130 ms) in middle cortical layers and thus are extracted in the first pass of activity through the anteroventral temporal lobe. This activation may provide input to posterior areas for iconic representations when required by the task, as well as to the hippocampal formation for categorical encoding and retrieval of memories, and to the amygdala for emotional associations. More generally, these results support models in which the anteroventral temporal lobe plays a primary role in the semantic representation of words.
C1 [Chan, Alexander M.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Chan, Alexander M.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Baker, Janet M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Schomer, Donald] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Ulbert, Istvan] Hungarian Acad Sci, Inst Psychol, H-1394 Budapest, Hungary.
[Ulbert, Istvan; Halgren, Eric] Peter Pazmany Catholic Univ, Fac Informat Technol, H-1088 Budapest, Hungary.
[Marinkovic, Ksenija] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
RP Chan, AM (reprint author), 55 Fruit St,Their 423, Boston, MA 02114 USA.
EM amchan@mit.edu; ehalgren@ucsd.edu
RI Ulbert, Istvan/F-2213-2010
FU NDSEG; AMNTP; Frank H. Buck Scholarship; Rappaport Fellowship; OTKA
[K-81357]; NKTH-ANR Neurogen; NIH [NS18741]
FX This work was supported by an NDSEG Fellowship, an AMNTP grant, and the
Frank H. Buck Scholarship to A. M. C., a Rappaport Fellowship to S. S.
C., and OTKA K-81357 and NKTH-ANR Neurogen to I.U.. Overall support was
provided by NIH Grant NS18741. We thank A. R. Dykstra, C.J. Keller, N.
Dehghani, J. Cormier, R. Zepeda, J. Donoghue, and I. Sukhotinsky for
their helpful comments.
NR 110
TC 54
Z9 54
U1 0
U2 8
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 DEC 7
PY 2011
VL 31
IS 49
BP 18119
EP 18129
DI 10.1523/JNEUROSCI.3122-11.2011
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 861QX
UT WOS:000298035400033
PM 22159123
ER
PT J
AU Duran-Pinedo, AE
Paster, B
Teles, R
Frias-Lopez, J
AF Duran-Pinedo, Ana E.
Paster, Bruce
Teles, Ricardo
Frias-Lopez, Jorge
TI Correlation Network Analysis Applied to Complex Biofilm Communities
SO PLOS ONE
LA English
DT Article
ID GENE-COEXPRESSION NETWORK; SUBGINGIVAL PLAQUE; FUNCTIONAL-ORGANIZATION;
MICROBIAL COMMUNITIES; BACTERIAL DIVERSITY; ANALYSIS REVEALS;
PERIODONTITIS; MODULES; IDENTIFICATION; TRANSCRIPTOME
AB The complexity of the human microbiome makes it difficult to reveal organizational principles of the community and even more challenging to generate testable hypotheses. It has been suggested that in the gut microbiome species such as Bacteroides thetaiotaomicron are keystone in maintaining the stability and functional adaptability of the microbial community. In this study, we investigate the interspecies associations in a complex microbial biofilm applying systems biology principles. Using correlation network analysis we identified bacterial modules that represent important microbial associations within the oral community. We used dental plaque as a model community because of its high diversity and the well known species-species interactions that are common in the oral biofilm. We analyzed samples from healthy individuals as well as from patients with periodontitis, a polymicrobial disease. Using results obtained by checkerboard hybridization on cultivable bacteria we identified modules that correlated well with microbial complexes previously described. Furthermore, we extended our analysis using the Human Oral Microbe Identification Microarray (HOMIM), which includes a large number of bacterial species, among them uncultivated organisms present in the mouth. Two distinct microbial communities appeared in healthy individuals while there was one major type in disease. Bacterial modules in all communities did not overlap, indicating that bacteria were able to effectively re-associate with new partners depending on the environmental conditions. We then identified hubs that could act as keystone species in the bacterial modules. Based on those results we then cultured a not-yet-cultivated microorganism, Tannerella sp.OT286 (clone BU063). After two rounds of enrichment by a selected helper (Prevotella oris OT311) we obtained colonies of Tannerella sp.OT286 growing on blood agar plates. This system-level approach would open the possibility of manipulating microbial communities in a targeted fashion as well as associating certain bacterial modules to clinical traits (e. g.: obesity, Crohn's disease, periodontal disease, etc).
C1 [Duran-Pinedo, Ana E.; Paster, Bruce; Teles, Ricardo; Frias-Lopez, Jorge] Forsyth Inst, Cambridge, MA 02142 USA.
[Paster, Bruce; Teles, Ricardo; Frias-Lopez, Jorge] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
RP Duran-Pinedo, AE (reprint author), Forsyth Inst, Cambridge, MA 02142 USA.
EM jfrias@forsyth.org
NR 49
TC 39
Z9 41
U1 4
U2 48
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 DEC 7
PY 2011
VL 6
IS 12
AR e28438
DI 10.1371/journal.pone.0028438
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 863KK
UT WOS:000298161900039
PM 22163302
ER
PT J
AU Gupta, RK
Rosen, ED
Spiegelman, BM
AF Gupta, Rana K.
Rosen, Evan D.
Spiegelman, Bruce M.
TI Identifying Novel Transcriptional Components Controlling Energy
Metabolism
SO CELL METABOLISM
LA English
DT Review
ID ALTERED GENE-EXPRESSION; HUMAN PANCREATIC-ISLETS; PPAR-GAMMA; EPIGENOMIC
ANALYSIS; FACTOR-BINDING; OPEN CHROMATIN; GENOME; ADIPOGENESIS; REVEALS;
ENHANCERS
AB The investigation of metabolic regulation at the transcriptional level presents different challenges than those encountered in the study of other important problems like development or cancer. Levels of key components like glucose, insulin, and lipids can be modulated but rarely change in an all-or-none fashion, necessitating quantitative techniques that can be applied to multiple tissues and systems. This review examines recent advances in methods for studying transcriptional regulation, with special emphasis on metabolic science. We compare these methods for investigators trying to decide on the best approach for their particular physiological paradigm or model system.
C1 [Gupta, Rana K.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Gupta, Rana K.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Rosen, Evan D.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA.
RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM bruce_spiegelman@dfci.harvard.edu
FU National Institutes of Health (NIH) [K01 DK090120-02, R01 DK31405, R01
DK078061]
FX The authors thank M. Khandekar and S. Kleiner for helpful discussions
and P. Cohen for critical reading of the manuscript. The authors are
supported by National Institutes of Health (NIH) K01 DK090120-02 to
R.K.G., NIH R01 DK31405 to B.M.S., and NIH R01 DK078061 to E.D.R.
NR 57
TC 13
Z9 13
U1 0
U2 7
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 DEC 7
PY 2011
VL 14
IS 6
BP 739
EP 745
DI 10.1016/j.cmet.2011.11.007
PG 7
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 862VO
UT WOS:000298122400007
PM 22152302
ER
PT J
AU Warne, JP
Alemi, F
Reed, AS
Varonin, JM
Chan, H
Piper, ML
Mullin, ME
Myers, MG
Corvera, CU
Xu, AW
AF Warne, James P.
Alemi, Farzad
Reed, Alison S.
Varonin, Jillian M.
Chan, Helen
Piper, Merisa L.
Mullin, Mark E.
Myers, Martin G., Jr.
Corvera, Carlos U.
Xu, Allison W.
TI Impairment of Central Leptin-Mediated PI3K Signaling Manifested as
Hepatic Steatosis Independent of Hyperphagia and Obesity (Retracted
article. See vol. 21, pg. 648, 2015)
SO CELL METABOLISM
LA English
DT Article; Retracted Publication
ID INSULIN-RESISTANCE; ADIPOSE-TISSUE; LIPID-METABOLISM; NERVOUS-SYSTEM;
FOOD-INTAKE; MICE; LIVER; RECEPTOR; NEURONS; HYPOTHALAMUS
AB Hepatic steatosis is generally thought to develop via peripheral mechanisms associated with obesity. We show that chronic central infusion of leptin suppresses hepatic lipogenic gene expression and reduces triglyceride content via stimulation of hepatic sympathetic activity. This leptin function is independent of feeding and body weight but requires phosphatidylinositol 3-kinase (PI3K) signaling. Attenuation of leptin-induced PI3K signaling, brought about by transgenic expression of phosphatase and tensin homolog (PTEN) in leptin receptor neurons, leads to decreased hepatic sympathetic tone and increased triglyceride levels without affecting adiposity or hepatic insulin signaling. Central leptin's effects on hepatic norepinephrine levels and triglyceride content are blunted in these mutant mice. Simultaneous downregulation of PI3K and signal transducer and activator of transcription-3 (Stat3) in leptin receptor neurons does not exacerbate obesity but causes more severe hepatic steatosis. Together, our results indicate that central cellular leptin resistance in PI3K signaling manifests as hepatic steatosis without causing obesity.
C1 [Warne, James P.; Reed, Alison S.; Varonin, Jillian M.; Chan, Helen; Piper, Merisa L.; Mullin, Mark E.; Xu, Allison W.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
[Alemi, Farzad; Corvera, Carlos U.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Surg, San Francisco, CA 94143 USA.
[Myers, Martin G., Jr.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Myers, Martin G., Jr.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
RP Xu, AW (reprint author), Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
EM axu@diabetes.ucsf.edu
FU NIH [R01DK080427, T32DK07161, DERC P30 DK063720]
FX We thank Drs. Michael Schwartz, Robert Farese, Jr., Jacquelyn Maher, and
Jamila Newton for their evaluation of the manuscript. This work was
supported by research grant from the NIH (R01DK080427 to A.W.X.) and, in
part, by a NIH Pediatric Endocrine Training grant (T32DK07161) to A.S.R.
This work was also supported, in part, by core facilities funded by NIH
DERC P30 DK063720.
NR 44
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U1 1
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD DEC 7
PY 2011
VL 14
IS 6
BP 791
EP 803
DI 10.1016/j.cmet.2011.11.001
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 862VO
UT WOS:000298122400012
PM 22152304
ER
PT J
AU Remmele, S
Hesser, J
Paganetti, H
Bortfeld, T
AF Remmele, Steffen
Hesser, Juergen
Paganetti, Harald
Bortfeld, Thomas
TI A deconvolution approach for PET-based dose reconstruction in proton
radiotherapy
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; BEAM RANGE VERIFICATION; THERAPY;
DISTRIBUTIONS; ALGORITHM
AB Positron emitters are activated by proton beams in proton radiotherapy, and positron emission tomography (PET) images can thus be used for dose verification. Since a PET image is not directly proportional to the delivered radiation dose distribution, predicted PET images are compared to measured PET images and an agreement of both indicates a successful irradiation. Such predictions are given on the basis of Monte Carlo calculations or a filtering approach which uses a convolution of the planned dose with specific filter functions to estimate the PET activity. In this paper, we describe and evaluate a dose reconstruction method based on PET images which reverses the just mentioned convolution approach using appropriate deconvolution methods. Deconvolution is an ill-posed inverse problem, and suitable regularization techniques are required in order to guarantee a stable solution. The basic convolution approach is developed for homogeneous media and additional procedures are necessary to generalize the PET estimation to inhomogeneous media. This generalization formalism is used in our dose deconvolution approach as well. Various simulations demonstrate that the dose reconstruction method is able to reverse the PET estimation method both in homogeneous and inhomogeneous media. Measured PET images are however degraded by noise and artifacts and the dose reconstructions become more difficult and the results suffer from artifacts as well. Recently used in-room PET scanners allow a decreased delay time between irradiation and imaging, and thus the influence of short-lived positron emitters on the PET images increases considerably. We extended our dose reconstruction method to process PET images which contain several positron emitters and simulated results are shown.
C1 [Remmele, Steffen; Hesser, Juergen] Univ Heidelberg, Med Ctr Mannheim, D-6800 Mannheim, Germany.
[Remmele, Steffen; Paganetti, Harald; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Remmele, Steffen; Paganetti, Harald; Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Remmele, S (reprint author), Univ Heidelberg, Med Ctr Mannheim, D-6800 Mannheim, Germany.
EM steffen.remmele@medma.uni-heidelberg.de
FU National Cancer Institute [P01 CA021239]; BMBF FORSYS
FX The project described was supported in part by award number P01 CA021239
from the National Cancer Institute. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Cancer Institute or the National
Institutes of Health. The project was also supported by BMBF FORSYS.
Monte Carlo and measured PET data were provided by Antje Knopf and
Samuel Espana.
NR 30
TC 12
Z9 12
U1 0
U2 1
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 DEC 7
PY 2011
VL 56
IS 23
BP 7601
EP 7619
DI 10.1088/0031-9155/56/23/017
PG 19
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 858GR
UT WOS:000297784400017
PM 22086216
ER
PT J
AU Grijalva, CG
Chen, L
Delzell, E
Baddley, JW
Beukelman, T
Winthrop, KL
Griffin, MR
Herrinton, LJ
Liu, LY
Ouellet-Hellstrom, R
Patkar, NM
Solomon, DH
Lewis, JD
Xie, FL
Saag, KG
Curtis, JR
AF Grijalva, Carlos G.
Chen, Lang
Delzell, Elizabeth
Baddley, John W.
Beukelman, Timothy
Winthrop, Kevin L.
Griffin, Marie R.
Herrinton, Lisa J.
Liu, Liyan
Ouellet-Hellstrom, Rita
Patkar, Nivedita M.
Solomon, Daniel H.
Lewis, James D.
Xie, Fenglong
Saag, Kenneth G.
Curtis, Jeffrey R.
TI Initiation of Tumor Necrosis Factor-alpha Antagonists and the Risk of
Hospitalization for Infection in Patients With Autoimmune Diseases
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID MODIFYING ANTIRHEUMATIC DRUGS; RHEUMATOID-ARTHRITIS PATIENTS; SERIOUS
BACTERIAL-INFECTIONS; PLACEBO-CONTROLLED TRIALS; HAZARDS
REGRESSION-MODEL; OPPORTUNISTIC INFECTIONS; BIOLOGICS-REGISTER;
BRITISH-SOCIETY; FACTOR THERAPY; METAANALYSIS
AB Context Although tumor necrosis factor (TNF)-alpha antagonists are increasingly used in place of nonbiologic comparator medications, their safety profile remains incomplete.
Objectives To determine whether initiation of TNF-alpha antagonists compared with nonbiologic comparators is associated with an increased risk of serious infections requiring hospitalization.
Design, Setting, and Patients Within a US multi-institutional collaboration, we assembled retrospective cohorts (1998-2007) of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis, or ankylosing spondylitis (psoriasis and spondyloarthropathies) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid, and national Medicaid/Medicare. TNF-alpha antagonists and nonbiologic regimens were compared in disease-specific propensity score (PS)-matched cohorts using Cox regression models with nonbiologics as the reference. Baseline glucocorticoid use was evaluated as a separate covariate.
Main Outcome Measure Infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-alpha antagonists or nonbiologic regimens.
Results Study cohorts included 10 484 RA, 2323 IBD, and 3215 psoriasis and spondyloarthropathies matched pairs using TNF-alpha antagonists and comparator medications. Overall, we identified 1172 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. Among patients with RA, serious infection hospitalization rates were 8.16 (TNF-alpha antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR], 1.05 [95% CI, 0.91-1.21]). Among patients with IBD, rates were 10.91 (TNF-alpha antagonists) and 9.60 (comparator) per 100 person-years (aHR, 1.10 [95% CI, 0.83-1.46]). Among patients with psoriasis and spondyloarthropathies, rates were 5.41 (TNF-alpha antagonists) and 5.37 (comparator) per 100 person-years (aHR, 1.05 [95% CI, 0.76-1.45]). Among patients with RA, infliximab was associated with a significant increase in serious infections compared with etanercept (aHR, 1.26 [95% CI, 1.07-1.47]) and adalimumab (aHR, 1.23 [95% CI, 1.02-1.48]). Baseline glucocorticoid use was associated with a dose-dependent increase in infections.
Conclusion Among patients with autoimmune diseases, compared with treatment with nonbiologic regimens, initiation of TNF-alpha antagonists was not associated with an increased risk of hospitalizations for serious infections. JAMA. 2011;306(21):2331-2339 Published online November 6, 2011. doi:10.1001/jama.2011.1692
C1 [Grijalva, Carlos G.] Vanderbilt Univ, Sch Med, Div Pharmacoepidemiol, Dept Prevent Med, Nashville, TN 37212 USA.
[Chen, Lang; Delzell, Elizabeth; Baddley, John W.; Beukelman, Timothy; Patkar, Nivedita M.; Xie, Fenglong; Saag, Kenneth G.; Curtis, Jeffrey R.] Univ Alabama Birmingham, Birmingham, AL USA.
[Baddley, John W.] Birmingham VA Med Ctr, Birmingham, AL USA.
[Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Herrinton, Lisa J.; Liu, Liyan] Kaiser Permanente No Calif, Oakland, CA USA.
[Ouellet-Hellstrom, Rita] US FDA, Silver Spring, MD USA.
[Solomon, Daniel H.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Solomon, Daniel H.] Harvard Univ, Boston, MA 02115 USA.
[Lewis, James D.] Univ Penn, Dept Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Lewis, James D.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
RP Grijalva, CG (reprint author), Vanderbilt Univ, Sch Med, Div Pharmacoepidemiol, Dept Prevent Med, 1500 21st Ave S,Ste 2600, Nashville, TN 37212 USA.
EM carlos.grijalva@vanderbilt.edu
FU Amgen; Genentech; Centocor; Procter Gamble; Abbott; Eli Lilly;
Bristol-Myers Squibb; Takeda; Shire; Pfizer; Roche/Genentech; UCB
biopharma; CORRONA; Crescendo; Food and Drug Administration (FDA); US
Department of Health and Human Services (DHHS); Agency for Healthcare
Research and Quality (AHRQ) [U18 HS17919, R01HS018517]; National
Institutes of Health (NIH) [AR053351]; NIH via the University of Alabama
at Birmingham Center for Clinical and Translational Science [5KL2
RR025776-03]; National Institute of Arthritis and Musculoskeletal and
Skin Diseases [5P60AR56116]
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Delzell reported receiving
research support from Amgen. Dr Baddley reported consulting for Abbott
and Merck. Dr Herrinton reported receiving research support from
Genentech, Centocor, and Procter & Gamble. Dr Solomon reported receiving
research support from Amgen, Abbott, Eli Lilly, and Bristol-Myers
Squibb. Dr Lewis reported consulting for Genentech, Abbott, CORRONA
(Consortium of Rheumatology Researchers of North America Inc),
Millennium Pharmaceuticals, Elan, AstraZeneca, Procter & Gamble,
GlaxoSmithKline, Alios Therapeutics, Roche, and Amgen; he also reported
receiving research support from Centocor, Takeda, and Shire, and
consultant honoraria from Amgen and Pfizer. Dr Winthrop reported
receiving consultant fees from Genentech and Abbott, research support
from Pfizer, and speakers honoraria from Amgen and Pfizer. Dr Saag
reported receiving research support from Amgen, Genentech, and Pfizer.
Dr Curtis reported receiving consultant fees and research grants from
Roche/Genentech, UCB biopharma, Centocor, CORRONA, Amgen, Pfizer,
Bristol-Myers Squibb, Crescendo, and Abbott. Other authors reported no
conflicts.; This work was supported by the Food and Drug Administration
(FDA), US Department of Health and Human Services (DHHS), and the Agency
for Healthcare Research and Quality (AHRQ) grant U18 HS17919. Dr Curtis
receives support from the National Institutes of Health (NIH; AR053351)
and AHRQ (R01HS018517). Dr Beukelman was supported by NIH grant 5KL2
RR025776-03 via the University of Alabama at Birmingham Center for
Clinical and Translational Science. Drs Grijalva and Griffin receive
support from the National Institute of Arthritis and Musculoskeletal and
Skin Diseases, grant 5P60AR56116.
NR 51
TC 140
Z9 145
U1 1
U2 7
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 DEC 7
PY 2011
VL 306
IS 21
BP 2331
EP 2339
DI 10.1001/jama.2011.1692
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 856YH
UT WOS:000297680300018
PM 22056398
ER
PT J
AU Nguyen, PL
Je, YJ
Schutz, FAB
Hoffman, KE
Hu, JC
Parekh, A
Beckman, JA
Choueiri, TK
AF Nguyen, Paul L.
Je, Youjin
Schutz, Fabio A. B.
Hoffman, Karen E.
Hu, Jim C.
Parekh, Arti
Beckman, Joshua A.
Choueiri, Toni K.
TI Association of Androgen Deprivation Therapy With Cardiovascular Death in
Patients With Prostate Cancer A Meta-analysis of Randomized Trials
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID NEOADJUVANT HORMONAL-THERAPY; CONGESTIVE-HEART-FAILURE; QUALITY-OF-LIFE;
RADICAL PROSTATECTOMY; FOLLOW-UP; MYOCARDIAL-INFARCTION; EUROPEAN
ORGANIZATION; CLINICAL-TRIALS; LOCAL TREATMENT; MORTALITY
AB Context Whether androgen deprivation therapy (ADT) causes excess cardiovascular deaths in men with prostate cancer is highly controversial and was the subject of a joint statement by multiple medical societies and a US Food and Drug Administration safety warning.
Objective To perform a systematic review and meta-analysis of randomized trials to determine whether ADT is associated with cardiovascular mortality, prostate cancer-specific mortality (PCSM), and all-cause mortality in men with unfavorable-risk, non-metastatic prostate cancer.
Data Sources A search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases for relevant randomized controlled trials in English between January 1, 1966, and April 11, 2011.
Study Selection Inclusion required nonmetastatic disease, intervention group with gonadotropin-releasing hormone agonist-based ADT, control group with no immediate ADT, complete information on cardiovascular deaths, and median follow-up of more than 1 year.
Data Extraction Extraction was by 2 independent reviewers. Summary incidence, relative risk (RR), and CIs were calculated using random-effects or fixed-effects models.
Results Among 4141 patients from 8 randomized trials, cardiovascular death in patients receiving ADT vs control was not significantly different (255/2200 vs 252/1941 events; incidence, 11.0%; 95% CI, 8.3%-14.5%; vs 11.2%; 95% CI, 8.3%-15.0%; RR, 0.93; 95% CI, 0.79-1.10; P=.41). ADT was not associated with excess cardiovascular death in trials of at least 3 years (long duration) of ADT (11.5%; 95% CI, 8.1%-16.0%; vs 11.5%; 95% CI, 7.5%-17.3%; RR, 0.91; 95% CI, 0.75-1.10; P=.34) or in trials of 6 months or less (short duration) of ADT (10.5%; 95% CI, 6.3%-17.0%; vs 10.3%; 95% CI, 8.2%-13.0%; RR, 1.00; 95% CI, 0.73-1.37; P=.99). Among 4805 patients from 11 trials with overall death data, ADT was associated with lower PCSM (443/2527 vs 552/2278 events; 13.5%; 95% CI, 8.8%-20.3%; vs 22.1%; 95% CI, 15.1%-31.1%; RR, 0.69; 95% CI, 0.56-0.84; P<.001) and lower all-cause mortality (1140/2527 vs 1213/2278 events; 37.7%; 95% CI, 27.3%-49.4%; vs 44.4%; 95% CI, 32.5%-57.0%; RR, 0.86; 95% CI, 0.80-0.93; P<.001).
Conclusion In a pooled analysis of randomized trials in unfavorable-risk prostate cancer, ADT use was not associated with an increased risk of cardiovascular death but was associated with a lower risk of PCSM and all-cause mortality. JAMA. 2011;306(21):2359-2366
C1 [Nguyen, Paul L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA.
[Schutz, Fabio A. B.; Choueiri, Toni K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Lank Ctr Genitourinary Onco, Boston, MA 02115 USA.
[Je, Youjin] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
[Hu, Jim C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Hu, Jim C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA.
[Beckman, Joshua A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
[Parekh, Arti] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.
EM pnguyen@LROC.harvard.edu
OI Beckman, Joshua/0000-0001-8332-8439
FU JCRT Foundation; Doris Duke Clinical Research Fellowship; anonymous
Family Foundation
FX This work was supported by a JCRT Foundation grant; a Doris Duke
Clinical Research Fellowship; David and Cynthia Chapin; Richard, Nancy,
and Karis Cho; and a grant from an anonymous Family Foundation.
NR 33
TC 164
Z9 167
U1 4
U2 17
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD DEC 7
PY 2011
VL 306
IS 21
BP 2359
EP 2366
DI 10.1001/jama.2011.1745
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 856YH
UT WOS:000297680300021
PM 22147380
ER
PT J
AU Stevens, KN
Garcia-Closas, M
Fredericksen, Z
Kosel, M
Pankratz, VS
Hopper, JL
Dite, GS
Apicella, C
Southey, MC
Schmidt, MK
Broeks, A
Van 't Veer, LJ
Tollenaar, RAEM
Fasching, PA
Beckmann, MW
Hein, A
Ekici, AB
Johnson, N
Peto, J
Silva, ID
Gibson, L
Sawyer, E
Tomlinson, I
Kerin, MJ
Chanock, S
Lissowska, J
Hunter, DJ
Hoover, RN
Thomas, GD
Milne, RL
Perez, JIA
Gonzalez-Neira, A
Benitez, J
Burwinkel, B
Meindl, A
Schmutzler, RK
Bartrar, CR
Hamann, U
Ko, YD
Bruning, T
Chang-Claude, J
Hein, R
Wang-Gohrke, S
Dork, T
Schurmann, P
Bremer, M
Hillemanns, P
Bogdanova, N
Zalutsky, JV
Rogov, YI
Antonenkova, N
Lindblom, A
Margolin, S
Mannermaa, A
Kataja, V
Kosma, VM
Hartikainen, J
Chenevix-Trench, G
Chen, X
Peterlongo, P
Bonanni, B
Bernard, L
Manoukian, S
Wang, X
Cerhan, J
Vachon, CM
Olson, J
Giles, GG
Baglietto, L
McLean, CA
Severi, G
John, EM
Miron, A
Winqvist, R
Pylkas, K
Jukkola-Vuorinen, A
Grip, M
Andrulis, I
Knight, JA
Glendon, G
Mulligan, AM
Cox, A
Brock, IW
Elliott, G
Cross, SS
Pharoah, PP
Dunning, AM
Pooley, KA
Humphreys, MK
Wang, J
Kang, D
Yoo, KY
Noh, DY
Sangrajrang, S
Gabrieau, V
Brennan, P
Mckay, J
Anton-Culver, H
Ziogas, A
Couch, FJ
Easton, DF
AF Stevens, K. N.
Garcia-Closas, M.
Fredericksen, Z.
Kosel, M.
Pankratz, V. S.
Hopper, J. L.
Dite, G. S.
Apicella, C.
Southey, M. C.
Schmidt, M. K.
Broeks, A.
Van 't Veer, L. J.
Tollenaar, R. A. E. M.
Fasching, P. A.
Beckmann, M. W.
Hein, A.
Ekici, A. B.
Johnson, N.
Peto, J.
Silva, I. dos Santos
Gibson, L.
Sawyer, E.
Tomlinson, I.
Kerin, M. J.
Chanock, S.
Lissowska, J.
Hunter, D. J.
Hoover, R. N.
Thomas, G. D.
Milne, R. L.
Perez, J. I. Arias
Gonzalez-Neira, A.
Benitez, J.
Burwinkel, B.
Meindl, A.
Schmutzler, R. K.
Bartrar, C. R.
Hamann, U.
Ko, Y. D.
Bruening, T.
Chang-Claude, J.
Hein, R.
Wang-Gohrke, S.
Doerk, T.
Schuermann, P.
Bremer, M.
Hillemanns, P.
Bogdanova, N.
Zalutsky, J. V.
Rogov, Y. I.
Antonenkova, N.
Lindblom, A.
Margolin, S.
Mannermaa, A.
Kataja, V.
Kosma, V-M
Hartikainen, J.
Chenevix-Trench, G.
Chen, X.
Peterlongo, P.
Bonanni, B.
Bernard, L.
Manoukian, S.
Wang, X.
Cerhan, J.
Vachon, C. M.
Olson, J.
Giles, G. G.
Baglietto, L.
McLean, C. A.
Severi, G.
John, E. M.
Miron, A.
Winqvist, R.
Pylkaes, K.
Jukkola-Vuorinen, A.
Grip, M.
Andrulis, I.
Knight, J. A.
Glendon, G.
Mulligan, A. M.
Cox, A.
Brock, I. W.
Elliott, G.
Cross, S. S.
Pharoah, P. P.
Dunning, A. M.
Pooley, K. A.
Humphreys, M. K.
Wang, J.
Kang, D.
Yoo, K-Y
Noh, D-Y
Sangrajrang, S.
Gabrieau, V.
Brennan, P.
Mckay, J.
Anton-Culver, H.
Ziogas, A.
Couch, F. J.
Easton, D. F.
CA GENICA Network
kConFab Invest
Australian Ovarian Cancer Study Gr
TI Evaluation of variation in the phosphoinositide-3-kinase catalytic
subunit alpha oncogene and breast cancer risk
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE genetic susceptibility; neoplasms; association study
ID PIK3CA MUTATIONS; POOR-PROGNOSIS; HIGH-FREQUENCY; PTEN LOSS; GENE;
ASSOCIATION; CORRELATE; PATHWAY; OVARIAN
AB BACKGROUND: Somatic mutations in phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) are frequent in breast tumours and have been associated with oestrogen receptor (ER) expression, human epidermal growth factor receptor-2 overexpression, lymph node metastasis and poor survival. The goal of this study was to evaluate the association between inherited variation in this oncogene and risk of breast cancer.
METHODS: A single-nucleotide polymorphism from the PIK3CA locus that was associated with breast cancer in a study of Caucasian breast cancer cases and controls from the Mayo Clinic (MCBCS) was genotyped in 5436 cases and 5280 controls from the Cancer Genetic Markers of Susceptibility (CGEMS) study and in 30 949 cases and 29 788 controls from the Breast Cancer Association Consortium (BCAC).
RESULTS: Rs1607237 was significantly associated with a decreased risk of breast cancer in MCBCS, CGEMS and all studies of white Europeans combined (odds ratio (OR) = 0.97, 95% confidence interval (CI) 0.95-0.99, P = 4.6 x 10(-3)), but did not reach significance in the BCAC replication study alone (OR = 0.98, 95% CI 0.96-1.01, P = 0.139).
CONCLUSION: Common germline variation in PIK3CA does not have a strong influence on the risk of breast cancer British Journal of Cancer (2011) 105, 1934 - 1939. doi: 10.1038/bjc.2011.448 www.bjcancer.com Published online 27 October 2011 (C) 2011 Cancer Research UK
C1 [Couch, F. J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Stevens, K. N.; Fredericksen, Z.; Kosel, M.; Pankratz, V. S.; Wang, X.; Cerhan, J.; Vachon, C. M.; Olson, J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Garcia-Closas, M.] Inst Canc Res, Sect Epidemiol & Genet, London SW7 3RP, England.
[Garcia-Closas, M.; Johnson, N.] Breakthrough Breast Canc Res Ctr, London SW7 3RP, England.
[Hopper, J. L.; Dite, G. S.; Apicella, C.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia.
[Southey, M. C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia.
[Schmidt, M. K.; Broeks, A.; Van 't Veer, L. J.] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
[Tollenaar, R. A. E. M.] Leiden Univ, Med Ctr, NL-2333 ZA Leiden, Netherlands.
[Fasching, P. A.] Univ Calif Los Angeles, Div Hematol & Oncol, Dept Med, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Fasching, P. A.; Beckmann, M. W.; Hein, A.] Univ Erlangen Nurnberg, Dept Gynecol & Obstet, Univ Breast Ctr Franconia, Comprehens Canc Ctr Erlangen Nuremberg, D-91054 Erlangen, Germany.
[Ekici, A. B.] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany.
[Peto, J.; Silva, I. dos Santos; Gibson, L.] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1E 7HT, England.
[Sawyer, E.] Kings Coll London, Natl Inst Hlth Res NIHR, Comprehens Biomed Res Ctr, Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England.
[Sawyer, E.] Kings Coll Hosp NHS Fdn Trust, Guys Hosp, London SE1 9RT, England.
[Tomlinson, I.] Univ Oxford, Oxford Biomed Res Ctr Mol & Populat Genet, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Kerin, M. J.] Univ Hosp, NUIG Dept Surg, Inst Clin Sci, Galway 091524411, Ireland.
[Chanock, S.; Hoover, R. N.; Thomas, G. D.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Lissowska, J.] M Sklodowska Curie Mem Canc Ctr, Inst Oncol, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland.
[Hunter, D. J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Milne, R. L.] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain.
[Perez, J. I. Arias] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo 33012, Spain.
[Gonzalez-Neira, A.] Spanish Natl Canc Res Ctr CNIO, Human Gentyping Unit CeGen, Madrid, Spain.
[Benitez, J.] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid 28029, Spain.
[Burwinkel, B.] Univ Heidelberg Hosp, Dept Obstet & Gynecol, D-69120 Heidelberg, Germany.
[Burwinkel, B.] German Canc Res Ctr, Mol Epidemiol Grp, D-69120 Heidelberg, Germany.
[Meindl, A.] Tech Univ Munich, Dept Obstet & Gynaecol, D-80333 Munich, Germany.
[Schmutzler, R. K.] Univ Hosp Cologne, Div Mol Gynecooncol, Dept Obstet & Gynaecol, Ctr Mol Med Cologne CMMC, D-50931 Cologne, Germany.
[Bartrar, C. R.] Univ Heidelberg, Inst Human Genet, D-69120 Heidelberg, Germany.
[Hamann, U.] Deutsch Krebsforschungszentrum DKFZ, D-69120 Heidelberg, Germany.
[Ko, Y. D.] Evangel Kliniken Bonn gGmbH, Betriebsstatte Johanniter Krankenhaus, Dept Internal Med, D-53113 Bonn, Germany.
[Bruening, T.] German Social Accid Insurance IPA, Inst Prevent & Occupat Med, D-44789 Bochum, Germany.
[Chang-Claude, J.; Hein, R.] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Wang-Gohrke, S.] Univ Ulm, Dept Obstet & Gynecol, D-89081 Ulm, Germany.
[Doerk, T.; Schuermann, P.] Hannover Med Sch, Gynaecol Res Unit, D-30625 Hannover, Germany.
[Bremer, M.; Bogdanova, N.] Hannover Med Sch, Clin Radiat Oncol, D-30625 Hannover, Germany.
[Hillemanns, P.; Zalutsky, J. V.; Rogov, Y. I.; Antonenkova, N.] Hannover Med Sch, Clin Obstet & Gynaecol, D-30625 Hannover, Germany.
[Lindblom, A.] Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden.
[Margolin, S.] Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden.
[Mannermaa, A.; Kosma, V-M; Hartikainen, J.] Univ Eastern Finland, Inst Clin Med, Dept Pathol, FI-70211 Kuopio, Finland.
[Mannermaa, A.; Kosma, V-M; Hartikainen, J.] Kuopio Univ Hosp, Bioctr Kuopio, FI-70211 Kuopio, Finland.
[Kataja, V.] Univ Eastern Finland, Kuopio Univ Hosp, Inst Clin Med, Dept Oncol, FI-70211 Kuopio, Finland.
[Chenevix-Trench, G.; Chen, X.] Queensland Inst Med Res, Herston, Qld 4029, Australia.
[Peterlongo, P.] Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predicted Med, I-1620139 Milan, Italy.
[Peterlongo, P.] Fdn Ist FIRC Oncol Mol, IFOM, I-1620139 Milan, Italy.
[Bonanni, B.] Ist Europeo Oncol, Div Canc Prevent & Genet, I-20141 Milan, Italy.
[Bernard, L.] Ist Europeo Oncol, Dept Expt Oncol, I-1620139 Milan, Italy.
[Bernard, L.] Consortium Genom Technol Cogentech, I-1620139 Milan, Italy.
[Manoukian, S.] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Prevent Med, I-20133 Milan, Italy.
[Giles, G. G.; Baglietto, L.; Severi, G.] Canc Epidemiol Ctr, Canc Council Victoria, Carlton, Vic 3053, Australia.
[Giles, G. G.; Baglietto, L.; Severi, G.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Victoria 3010, Australia.
[McLean, C. A.] Alfred Hosp, Dept Anat Pathol, Prahran, Vic 3181, Australia.
[John, E. M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA 94538 USA.
[Miron, A.] Dana Farber Canc Inst, Dept Surg, Boston, MA 02215 USA.
[Winqvist, R.; Pylkaes, K.] Univ Oulu, Oulu Univ Hosp, Canc Genet Lab, Dept Clin Genet, Oulu 90220, Finland.
[Winqvist, R.; Pylkaes, K.] Univ Oulu, Oulu Univ Hosp, Bioctr Oulu, Oulu 90220, Finland.
[Jukkola-Vuorinen, A.] Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu 90220, Finland.
[Grip, M.] Univ Oulu, Oulu Univ Hosp, Dept Surg, Oulu 90220, Finland.
[Andrulis, I.; Glendon, G.] Ontario Canc Genet Network, Toronto, ON M5G 2C1, Canada.
[Andrulis, I.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada.
[Andrulis, I.] Univ Toronto, Dept Mol Genet, Toronto, ON M5A 2N4, Canada.
[Knight, J. A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Knight, J. A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON M5A 2N4, Canada.
[Mulligan, A. M.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5A 2N4, Canada.
[Mulligan, A. M.] St Michaels Hosp, Dept Lab Med, Toronto, ON M5B 1W8, Canada.
[Mulligan, A. M.] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada.
[Cox, A.; Brock, I. W.] Univ Sheffield, Fac Med Dent & Hlth, Sheffield S10 2RX, S Yorkshire, England.
[Elliott, G.] Univ Manchester, Med Genet Res Grp, Fac Med & Human Sci, Manchester M13 9PL, Lancs, England.
[Cross, S. S.] Univ Sheffield, Dept Neurosci, Fac Med Dent & Hlth, Sheffield S10 2RX, S Yorkshire, England.
[Pharoah, P. P.] United Kingdom Dept Oncol, Cambridge, England.
[Pharoah, P. P.] Dept Publ Hlth, Cambridge, England.
[Pharoah, P. P.] Primary Care Univ Cambridge, Cambridge, England.
[Dunning, A. M.; Pooley, K. A.; Easton, D. F.] Univ Cambridge, Dept Oncol, Cambridge CB2 0RE, England.
[Humphreys, M. K.; Wang, J.; Easton, D. F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
[Kang, D.; Yoo, K-Y; Noh, D-Y] Seoul Natl Univ, Coll Med, Seoul 110799, South Korea.
[Sangrajrang, S.] Natl Canc Inst, Bangkok 10400, Thailand.
[Gabrieau, V.; Brennan, P.; Mckay, J.] Int Agcy Res Canc, F-69372 Lyon 08, France.
[Anton-Culver, H.; Ziogas, A.] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92697 USA.
RP Couch, FJ (reprint author), Mayo Clin, Dept Lab Med & Pathol, 200 First St SW, Rochester, MN 55905 USA.
EM couch.fergus@mayo.edu
RI Bowtell, David/H-1007-2016; Bruning, Thomas/G-8120-2015; manoukian,
siranoush/E-7132-2017; Knight, Julia/A-6843-2012; Noh,
Dong-Young/G-5531-2011; Kang, Dae Hee/E-8631-2012; Yoo,
Keun-Young/J-5548-2012; Hein, Alexander/F-6999-2010; Kerin,
Michael/D-6748-2013; Ekici, Arif/C-3971-2013; Andrulis,
Irene/E-7267-2013; Dork, Thilo/J-8620-2012; Bernard, Loris/K-5953-2014;
Gonzalez-Neira, Anna/C-5791-2015; Garcia-Closas, Montserrat
/F-3871-2015; Hartikainen, Jaana/E-6256-2015
OI Bowtell, David/0000-0001-9089-7525; Bruning, Thomas/0000-0001-9560-5464;
manoukian, siranoush/0000-0002-6034-7562; Dite,
Gillian/0000-0002-2448-2548; Cerhan, James/0000-0002-7482-178X; Cross,
Simon/0000-0003-2044-1754; Lissowska, Jolanta/0000-0003-2695-5799;
Dunning, Alison Margaret/0000-0001-6651-7166; dos Santos Silva,
Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Giles,
Graham/0000-0003-4946-9099; Hein, Alexander/0000-0003-2601-3398;
Garcia-Closas, Montserrat /0000-0003-1033-2650;
FU Dutch Cancer Society [NKI 2001-2423, NKI 2007-3839]; Dutch National
Genomics Initiative; United States National Cancer Institute, National
Institutes of Health (NIH) [RFA-CA-06-503]; National Health and Medical
Research Council of Australia; New South Wales Cancer Council; Victorian
Health Promotion Foundation (Australia); Victorian Breast Cancer
Research Consortium; University Hospital Erlangen; Cancer Research UK;
Breakthrough Breast Cancer; NIHR Biomedical Research Centre; National
Cancer Research Network (NCRN); NIHR Comprehensive Biomedical Research
Centre; Guy's & St Thomas' NHS Foundation Trust; Oxford Biomedical
Research Centre; Genome Spain Foundation; Red Tematica de Investigacion
Cooperativa en Cancer; Asociacion Espanola Contra el Cancer; Fondo de
Investigacion Sanitario [PI081583, PI081120]; Deutsche Krebshilfe
[107054]; Dietmar-Hopp Foundation; Helmholtz society; German Cancer
Research Center (DKFZ); Hannover Medical School; German Academic
Exchange Program; Friends of Hannover Medical School; Finnish Cancer
Society; Academy of Finland [127220]; Kuopio University Hospital
[5654113, 5501]; University of Eastern Finland; NHMRC; National Breast
Cancer Foundation and Cancer Australia [628333]; National Breast Cancer
Foundation; National Health and Medical Research Council (NHMRC)
[199600, 209057, 251553, 504711]; Queensland Cancer Fund; Cancer
Councils of New South Wales, Victoria, Tasmania and South Australia;
Cancer Foundation of Western Australia; United States Army Medical
Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council of
Tasmania; Italian citizens; NIH [CA122340]; US Recovery act [CA122340Z];
VicHealth and Cancer Council Victoria; Finnish Cancer Foundation; Sigrid
Juselius Foundation; Academy of Finland; University of Oulu; Oulu
University Hospital; Breast Cancer Campaign and Yorkshire Cancer
Research; National Institutes of Health, National Cancer Institute
[CA-58860, CA-92044]; Lon V Smith Foundation [LVS-39420]
FX The ABCS study was funded by the Dutch Cancer Society (grants NKI
2001-2423; NKI 2007-3839), the Dutch National Genomics Initiative; ABCS
acknowledges all patients, and Sten Cornelissen, Richard van Hien, Flora
van Leeuwen, Vincent Smit and other contributors to the 'BOSOM' study
(ABCS). The ABCFS, NC-BCFR and OFBCR works were supported by the United
States National Cancer Institute, National Institutes of Health (NIH)
under RFA-CA-06-503 and through cooperative agreements with members of
the Breast Cancer Family Registry (BCFR) and Principal Investigators,
including Cancer Care Ontario (U01 CA69467), Northern California Cancer
Center (U01 CA69417), University of Melbourne (U01 CA69638). Samples
from the NC-BCFR were processed and distributed by the Coriell Institute
for Medical Research. The content of this manuscript does not
necessarily reflect the views or policies of the National Cancer
Institute or any of the collaborating centers in the BCFR, nor does
mention of trade names, commercial products or organisations imply
endorsement by the US Government or the BCFR. The ABCFS was also
supported by the National Health and Medical Research Council of
Australia, the New South Wales Cancer Council, the Victorian Health
Promotion Foundation (Australia) and the Victorian Breast Cancer
Research Consortium. JLH is a National Health and Medical Research
Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research
Consortium Group Leader. MCS is a NHMRC Senior Research Fellow and a
Victorian Breast Cancer Research Consortium Group Leader. BBCC is funded
in part by the ELAN fund of the University Hospital Erlangen. The BBCS
is funded by Cancer Research UK and Breakthrough Breast Cancer and
acknowledges NHS funding to the NIHR Biomedical Research Centre, and the
National Cancer Research Network (NCRN). ES is supported by NIHR
Comprehensive Biomedical Research Centre, Guy's & St Thomas' NHS
Foundation Trust in partnership with King's College London, United
Kingdom. IT is supported by the Oxford Biomedical Research Centre. The
CNIO-BCS was supported by the Genome Spain Foundation, the Red Tematica
de Investigacion Cooperativa en Cancer and grants from the Asociacion
Espanola Contra el Cancer and the Fondo de Investigacion Sanitario
(PI081583 and PI081120). We thank Charo Alonso, Tais Moreno, Guillermo
Pita, Primitiva Menendez and Pilar Zamora for their contribution to this
work. The GC-HBOC was collected within a project funded by the Deutsche
Krebshilfe (Grant number: 107054). It was supported by the Dietmar-Hopp
Foundation, the Helmholtz society and the German Cancer Research Center
(DKFZ). We thank Sandrine Tchatchou for genotyping. The HABCS was
supported by an intramural grant from Hannover Medical School. The HMBCS
was supported by short-term fellowships from the German Academic
Exchange Program (to NB), and the Friends of Hannover Medical School (to
NB). KARBAC acknowledges The Swedish Cancer Society and The Stockholm
Cancer Society. KBCP is supported by grants from the Finnish Cancer
Society; the Academy of Finland (grant number 127220); the special
Government Funding (EVO) of Kuopio University Hospital (grant number
5654113 and 5501) and by the strategic funding of the University of
Eastern Finland. We thank Mrs Helena Kemilainen, Mrs Aija Parkkinen and
Mrs Eija Myohanen for their skillful technical assistance.; We thank
Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and
staff, the heads and staff of the Family Cancer Clinics, and the
Clinical Follow Up Study (funded 2001-2009 by NHMRC and currently by
theNational Breast Cancer Foundation and Cancer Australia #628333) for
their contributions to this resource, and the many families who
contribute to kConFab. kConFab is supported by grants from the National
Breast Cancer Foundation, the National Health and Medical Research
Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils
of New South Wales, Victoria, Tasmania and South Australia, and the
Cancer Foundation of Western Australia Financial support for the AOCS
was provided by the United States Army Medical Research and Materiel
Command (DAMD17-01-1-0729); the Cancer Council of Tasmania and Cancer
Foundation of Western Australia; and the NHMRC [199600]. GC-T is
supported by the NHMRC. PP is supported by funds from Italian citizens
who allocated the 5 x 1000 share of their tax payment to the Fondazione
IRCCS Istituto Nazionale Tumori, according to Italian laws
(INT-Institutional strategic projects '5 x 1000'). MBCSG thanks Paolo
Radice, Bernard Peissel, Daniela Zaffaroni and Marco A Pierotti of the
Fondazione IRCCS Istituto Nazionale Tumori and Monica Barile of the
Istituto Europeo di Oncologia, Milano, Italy. MCBCS was supported by NIH
grant CA122340 and US Recovery act award CA122340Z. Many people have
contributed to the MCCS, including the original investigators and the
diligent teams who recruited the participants and who continue working
on follow-up. Finally, we express our gratitude to the many thousands of
Melbourne residents who continue to participate in the study. Cohort
recruitment was funded by VicHealth and Cancer Council Victoria. The
MCCS was further supported by Australian NHMRC grants 209057, 251553 and
504711 and by infrastructure provided by Cancer Council Victoria. OBCS
was supported by research grants from the Finnish Cancer Foundation, the
Sigrid Juselius Foundation, the Academy of Finland, the University of
Oulu and the Oulu University Hospital. SBCS was funded by the Breast
Cancer Campaign and Yorkshire Cancer Research. The authors acknowledge
Helen Cramp, Sue Higham, Dan Connley, Saba Balasubramanian. The UCIBCS
is supported by the National Institutes of Health, National Cancer
Institute grants CA-58860, CA-92044 and the Lon V Smith Foundation grant
LVS-39420.
NR 23
TC 2
Z9 2
U1 1
U2 8
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 DEC 6
PY 2011
VL 105
IS 12
BP 1934
EP 1939
DI 10.1038/bjc.2011.448
PG 6
WC Oncology
SC Oncology
GA 863CQ
UT WOS:000298140800018
PM 22033276
ER
PT J
AU Zile, MR
Gottdiener, JS
Hetzel, SJ
McMurray, JJ
Komajda, M
McKelvie, R
Baicu, CF
Massie, BM
Carson, PE
AF Zile, Michael R.
Gottdiener, John S.
Hetzel, Scott J.
McMurray, John J.
Komajda, Michel
McKelvie, Robert
Baicu, Catalin F.
Massie, Barry M.
Carson, Peter E.
CA I-PRESERVE Investigators
TI Prevalence and Significance of Alterations in Cardiac Structure and
Function in Patients With Heart Failure and a Preserved Ejection
Fraction
SO CIRCULATION
LA English
DT Article
DE heart failure; echocardiography; ventricular ejection fraction
ID VENTRICULAR DIASTOLIC DYSFUNCTION; SOCIETY-OF-CARDIOLOGY; HYPERTENSIVE
PATIENTS; SYSTOLIC FUNCTION; RANDOMIZED-TRIAL; COMMUNITY;
ECHOCARDIOGRAPHY; POPULATION; IRBESARTAN; OUTCOMES
AB Background-The purpose of this study was to examine the prevalence of abnormalities in cardiac structure and function present in patients with heart failure and a preserved ejection fraction (HFPEF) and to determine whether these alterations in structure and function were associated with cardiovascular morbidity and mortality.
Methods and Results-The Irbesartan in HFPEF trial (I-PRESERVE) enrolled 4128 patients; echocardiographic determination of left ventricular (LV) volume, mass, left atrial (LA) size, systolic function, and diastolic function were made at baseline in 745 patients. The primary end point was death or protocol-specific cardiovascular hospitalization. A secondary end point was the composite of heart failure death or heart failure hospitalization. Associations between baseline structure and function and patient outcomes were examined using univariate and multivariable Cox proportional hazard analyses. In this substudy, LV hypertrophy or concentric remodeling was present in 59%, LA enlargement was present in 66%, and diastolic dysfunction was present in 69% of the patients. Multivariable analyses controlling for 7 clinical variables (including log N-terminal pro-B-type natriuretic peptide) indicated that increased LV mass, mass/volume ratio, and LA size were independently associated with an increased risk of both primary and heart failure events (all P < 0.05).
Conclusions-Left ventricular hypertrophy or concentric remodeling, LA enlargement, and diastolic dysfunction were present in the majority of patients with HFPEF. Left ventricular mass and LA size were independently associated with an increased risk of morbidity and mortality. The presence of structural remodeling and diastolic dysfunction may be useful additions to diagnostic criteria and provide important prognostic insights in patients with HFPEF. Clinical Trial Registration-http://www.clinicaltrials.gov. Unique identifier: NCT00095238. (Circulation. 2011; 124: 2491-2501.)
C1 [Zile, Michael R.] Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA.
[Zile, Michael R.; Baicu, Catalin F.] Vet Affairs Med Ctr, RHJ Dept, Charleston, SC 29403 USA.
[Gottdiener, John S.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
[Hetzel, Scott J.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[McMurray, John J.] Univ Glasgow, British Heart Fdn Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
[Komajda, Michel] Univ Paris 06, Paris, France.
[Komajda, Michel] Hop La Pitie Salpetriere, Paris, France.
[McKelvie, Robert] McMaster Univ, Hamilton, ON, Canada.
[Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Carson, Peter E.] Georgetown Univ, Washington, DC USA.
[Carson, Peter E.] Washington DC VAMC, Washington, DC USA.
RP Zile, MR (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, Ashley River Towers,25 Courtenay Dr,Room 7067, Charleston, SC 29425 USA.
EM zilem@musc.edu
OI mcmurray, john/0000-0002-6317-3975
FU Bristol-Myers Squibb; Sanofi-aventis; Servier
FX Drs Zile, Gottdiener, and Carson report receiving consulting fees from
Bristol-Myers Squibb and Sanofi-aventis. Dr McMurray reports receiving
support from Bristol-Myers Squibb (to Glasgow University) for his work
on this trial. Dr Komajda reports receiving consulting fees from
Bristol-Myers Squibb and Servier and lecture fees from Sanofi-aventis.
Dr McKelvie reports receiving consulting fees and lecture fees from
Bristol-Myers Squibb and Sanofi-aventis. S.J. Hetzel reports being
employed by the Statistical Data Analysis Center at the University of
Wisconsin Madison, which conducted the statistical analysis for this
trial that was supported by Bristol-Myers Squibb and Sanofi-Aventis. Dr
Massie reports receiving grant support and consulting fees from
Bristol-Myers Squibb and Sanofi-aventis.
NR 38
TC 152
Z9 159
U1 2
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD DEC 6
PY 2011
VL 124
IS 23
BP 2491
EP 2501
DI 10.1161/CIRCULATIONAHA.110.011031
PG 11
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 863QW
UT WOS:000298183300013
PM 22064591
ER
PT J
AU Hillis, LD
Smith, PK
Anderson, JL
Bittl, JA
Bridges, CR
Byrne, JG
Cigarroa, JE
DiSesa, VJ
Hiratzka, LF
Hutter, AM
Jessen, ME
Keeley, EC
Lahey, SJ
Lange, RA
London, MJ
Mack, MJ
Patel, MR
Puskas, JD
Sabik, JF
Selnes, O
Shahian, DM
Trost, JC
Winniford, MD
AF Hillis, L. David
Smith, Peter K.
Anderson, Jeffrey L.
Bittl, John A.
Bridges, Charles R.
Byrne, John G.
Cigarroa, Joaquin E.
DiSesa, Verdi J.
Hiratzka, Loren F.
Hutter, Adolph M., Jr.
Jessen, Michael E.
Keeley, Ellen C.
Lahey, Stephen J.
Lange, Richard A.
London, Martin J.
Mack, Michael J.
Patel, Manesh R.
Puskas, John D.
Sabik, Joseph F.
Selnes, Ola
Shahian, David M.
Trost, Jeffrey C.
Winniford, Michael D.
TI 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery:
Executive Summary A Report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guidelines
SO CIRCULATION
LA English
DT Article
DE AHA Scientific Statements; acute coronary syndromes; anticoagulants;
antiplatelet agents; arrhythmias, cardiac; coronary angiography;
coronary artery revascularization; interventions: stents; drug therapy;
heart diseases; myocardial revascularization; platelet aggregation
inhibitor; ultrasound
ID ACUTE MYOCARDIAL-INFARCTION; LONG-TERM SURVIVAL;
RANDOMIZED-CONTROLLED-TRIAL; VACUUM-ASSISTED CLOSURE;
ACUTE-RENAL-FAILURE; HIGH-RISK PATIENTS; LEFT-VENTRICULAR DYSFUNCTION;
PREOPERATIVE STATIN THERAPY; DRUG-ELUTING STENTS; TRANSMYOCARDIAL LASER
REVASCULARIZATION
AB The medical profession should play a central role in evaluating the evidence related to drugs, devices, and procedures for the detection, management, and prevention of disease. When properly applied, expert analysis of available data on the benefits and risks of these therapies and procedures can improve the quality of care, optimize patient outcomes, and favorably affect costs by focusing resources on the most effective strategies. An organized and directed approach to a thorough review of evidence has resulted in the production of clinical practice guidelines that assist physicians in selecting the best management strategy for an individual patient. Moreover, clinical practice guidelines can provide a foundation for other applications, such as performance measures, appropriate use criteria, and both quality improvement and clinical decision support tools.
C1 [Hillis, L. David; Lange, Richard A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Smith, Peter K.] Duke Univ, Med Ctr Private Diagnost Clin, Durham, NC 27706 USA.
[Bridges, Charles R.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA.
[Byrne, John G.] Vanderbilt Univ, Med Ctr Div Cardiac Surg, Nashville, TN 37235 USA.
[Cigarroa, Joaquin E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[DiSesa, Verdi J.] Johns Hopkins Univ Hosp, Div Cardiac Surg, Baltimore, MD 21287 USA.
[Hutter, Adolph M., Jr.; Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Keeley, Ellen C.] Univ Virginia, Charlottesville, VA 22903 USA.
[Lahey, Stephen J.] Univ Connecticut, Storrs, CT USA.
[London, Martin J.] Univ Calif San Francisco, Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
[Mack, Michael J.] Heart Hosp Baylor Plano Cardiovasc Surg, Plano, TX USA.
[Patel, Manesh R.] Duke Univ, Med Ctr, Durham, NC 27706 USA.
[Puskas, John D.] Emory Univ Emory Healthcare, Atlanta, GA USA.
[Sabik, Joseph F.] Cleveland Clin Fdn, Cleveland, OH USA.
[Selnes, Ola] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA.
[Trost, Jeffrey C.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Winniford, Michael D.] Univ Mississippi, Med Ctr, University, MS 38677 USA.
RP Hillis, LD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
NR 495
TC 130
Z9 137
U1 2
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD DEC 6
PY 2011
VL 124
IS 23
BP 2610
EP 2642
DI 10.1161/CIR.0b013e31823b5fee
PG 33
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 863QW
UT WOS:000298183300023
PM 22064600
ER
PT J
AU Hillis, LD
Smith, PK
Anderson, JL
Bittl, JA
Bridges, CR
Byrne, JG
Cigarroa, JE
DiSesa, VJ
Hiratzka, LF
Hutter, AM
Jessen, ME
Keeley, EC
Lahey, SJ
Lange, RA
London, MJ
Mack, MJ
Patel, MR
Puskas, JD
Sabik, JF
Selnes, O
Shahian, DM
Trost, JC
Winniford, MD
AF Hillis, L. David
Smith, Peter K.
Anderson, Jeffrey L.
Bittl, John A.
Bridges, Charles R.
Byrne, John G.
Cigarroa, Joaquin E.
DiSesa, Verdi J.
Hiratzka, Loren F.
Hutter, Adolph M., Jr.
Jessen, Michael E.
Keeley, Ellen C.
Lahey, Stephen J.
Lange, Richard A.
London, Martin J.
Mack, Michael J.
Patel, Manesh R.
Puskas, John D.
Sabik, Joseph F.
Selnes, Ola
Shahian, David M.
Trost, Jeffrey C.
Winniford, Michael D.
TI 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery A
Report of the American College of Cardiology Foundation/American Heart
Association Task Force on Practice Guidelines
SO CIRCULATION
LA English
DT Article
DE AHA Scientific Statements; acute coronary syndromes; anticoagulants;
antiplatelet agents; arrhythmias, cardiac; coronary angiography;
coronary artery revascularization interventions: stents; drug therapy;
heart diseases; myocardial revascularization; platelet aggregation
inhibitor; ultrasound
ID ACUTE MYOCARDIAL-INFARCTION; INTERNAL-MAMMARY-ARTERY; LONG-TERM
SURVIVAL; RANDOMIZED-CONTROLLED-TRIAL; HIGH-RISK PATIENTS; IN-HOSPITAL
MORTALITY; ACUTE-RENAL-FAILURE; DRUG-ELUTING STENTS; NEW-YORK-STATE;
STERNAL WOUND-INFECTION
C1 [Hillis, L. David; Lange, Richard A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Smith, Peter K.] Duke Univ, Med Ctr Private Diagnost Clin, Durham, NC 27706 USA.
[Bridges, Charles R.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA.
[Byrne, John G.] Vanderbilt Univ, Med Ctr Div Cardiac Surg, Nashville, TN 37235 USA.
[Cigarroa, Joaquin E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[DiSesa, Verdi J.] Johns Hopkins Univ Hosp, Div Cardiac Surg, Baltimore, MD 21287 USA.
[Hutter, Adolph M., Jr.; Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jessen, Michael E.] UT SW Med Ctr, Dallas, TX USA.
[Keeley, Ellen C.] Univ Virginia, Charlottesville, VA 22903 USA.
[Lahey, Stephen J.] Univ Connecticut, Storrs, CT USA.
[London, Martin J.] Univ Calif San Francisco, Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
[Patel, Manesh R.] Duke Univ, Med Ctr, Durham, NC 27706 USA.
[Puskas, John D.] Emory Univ Emory Healthcare, Atlanta, GA USA.
[Sabik, Joseph F.] Cleveland Clin Fdn, Cleveland, OH USA.
[Selnes, Ola] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA.
[Trost, Jeffrey C.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Winniford, Michael D.] Univ Mississippi, Med Ctr, University, MS 38677 USA.
RP Hillis, LD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
NR 1260
TC 190
Z9 196
U1 7
U2 32
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD DEC 6
PY 2011
VL 124
IS 23
BP E652
EP U267
DI 10.1161/CIR.0b013e31823c074e
PG 176
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 863QW
UT WOS:000298183300002
PM 22064599
ER
PT J
AU Chang, FM
Lemmon, C
Lietha, D
Eck, M
Romer, L
AF Chang, Fumin
Lemmon, Christopher
Lietha, Daniel
Eck, Michael
Romer, Lewis
TI Tyrosine Phosphorylation of Rac1: A Role in Regulation of Cell Spreading
SO PLOS ONE
LA English
DT Article
ID FOCAL ADHESION KINASE; SRC FAMILY KINASES; IN-VIVO; DEPENDENT
REGULATION; STRUCTURAL BASIS; RHO GTPASES; PROTEIN; ACTIVATION;
DYNAMICS; FAK
AB Rac1 influences a multiplicity of vital cellular-and tissue-level control functions, making it an important candidate for targeted therapeutics. The activity of the Rho family member Cdc42 has been shown to be modulated by tyrosine phosphorylation at position 64. We therefore investigated consequences of the point mutations Y64F and Y64D in Rac1. Both mutations altered cell spreading from baseline in the settings of wild type, constitutively active, or dominant negative Rac1 expression, and were accompanied by differences in Rac1 targeting to focal adhesions. Rac1-Y64F displayed increased GTP-binding, increased association with beta PIX, and reduced binding with RhoGDI as compared with wild type Rac1. Rac1-Y64D had less binding to PAK than Rac1-WT or Rac1-64F. In vitro assays demonstrated that Y64 in Rac1 is a target for FAK and Src. Taken together, these data suggest a mechanism for the regulation of Rac1 activity by non-receptor tyrosine kinases, with consequences for membrane extension.
C1 [Chang, Fumin; Romer, Lewis] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
[Lemmon, Christopher] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
[Lietha, Daniel] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain.
[Eck, Michael] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA.
[Eck, Michael] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Romer, Lewis] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
[Romer, Lewis] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA.
[Romer, Lewis] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Romer, Lewis] Johns Hopkins Univ, Sch Med, Ctr Cell Dynam, Baltimore, MD 21205 USA.
RP Chang, FM (reprint author), Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
EM lromer@jhmi.edu
RI Lietha, Daniel/L-8041-2014
OI Lietha, Daniel/0000-0002-6133-6486
FU National Institutes of Health [AI061042, HL088203]; National Science
Foundation [MCB-0923661]; Department of Defense [BC06911]; Maryland Stem
Cell Research Fund [MSCRFE-0043-00]
FX This work was supported by grants to L.R. from the National Institutes
of Health (AI061042 and HL088203), the National Science Foundation
(MCB-0923661), the Department of Defense (BC06911), and MSCRFE-0043-00
from the Maryland Stem Cell Research Fund. None of these funding sources
had any role in conducting the research or preparing the manuscript.
NR 46
TC 16
Z9 18
U1 2
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 DEC 6
PY 2011
VL 6
IS 12
AR e28587
DI 10.1371/journal.pone.0028587
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 863OC
UT WOS:000298173500036
PM 22163037
ER
PT J
AU Olson, P
Chu, GC
Perry, SR
Nolan-Stevaux, O
Hanahan, D
AF Olson, Peter
Chu, Gerald C.
Perry, Samuel R.
Nolan-Stevaux, Olivier
Hanahan, Douglas
TI Imaging guided trials of the angiogenesis inhibitor sunitinib in mouse
models predict efficacy in pancreatic neuroendocrine but not ductal
carcinoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE tumor vasculature; experimental cancer therapeutics
ID GROWTH-FACTOR RECEPTOR; PHASE-III TRIAL; TUMOR VASCULATURE; SURVIVAL
BENEFIT; DRUG DEVELOPMENT; CANCER; GEMCITABINE; THERAPY; MICE;
ADENOCARCINOMA
AB Preclinical trials in mice represent a critical step in the evaluation of experimental therapeutics. Genetically engineered mouse models (GEMMs) represent a promising platform for the evaluation of drugs, particularly those targeting the tumor microenvironment. We evaluated sunitinib, an angiogenesis inhibitor that targets VEGF and PDGF receptor signaling, in two GEMMs of pancreatic cancer. Sunitinib did not reduce tumor burden in pancreatic ductal adenocarcinoma (PDAC), whereas tumor burden was reduced in the pancreatic neuroendocrine tumor (PNET) model, the latter results confirming and extending previous studies. To explore the basis for the lack of pathologic response in PDAC, we used noninvasive microbubble contrast-enhanced ultrasound imaging, which revealed that sunitinib reduced blood flow both in PDAC and in PNET, concomitant with a reduction in vessel density; nevertheless, PDAC tumors continued to grow, whereas PNET were growth impaired. These results parallel the response in humans, where sunitinib recently garnered FDA and European approval in PNET, whereas two antiangiogenic drugs failed to demonstrate efficacy in PDAC clinical trials. The demonstration of on-target activity but with discordant benefit in the PDAC and PNET GEMMs illustrates the potential value of linked preclinical and clinical trials.
C1 [Olson, Peter; Nolan-Stevaux, Olivier; Hanahan, Douglas] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
[Olson, Peter; Nolan-Stevaux, Olivier; Hanahan, Douglas] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Chu, Gerald C.; Perry, Samuel R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Chu, Gerald C.; Perry, Samuel R.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Chu, Gerald C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Hanahan, D (reprint author), Swiss Fed Inst Technol Lausanne, Swiss Inst Expt Canc Res, CH-1015 Lausanne, Switzerland.
EM dh@epfl.ch
FU National Institutes of Health (NIH) [5P01CA117969-04]; Gastrointestinal
Specialized Programs of Research Excellence in Gastrointestinal Cancers
[NIH 1P50CA127003-02]; The William K. Bowes Jr. Foundation; National
Cancer Institute [T32 CA09043]; Diabetes and Endocrinology Research
Center; Specialized Histopathology and Rodent Histopathology Cores
(Dana-Farber/Harvard Cancer Center)
FX We thank James Christensen (Pfizer, Inc.) for providing sunitinib and
Dana Hu-Lowe (Pfizer, Inc.) for critical reading of the manuscript. We
thank Marina Vayner, Susan Cacacho, Cristina Guinto, and Ehud Drori for
excellent technical assistance. Research by P.O., G.C.C., S.R.P.,
O.N.-S., and D.H. was supported by National Institutes of Health (NIH)
5P01CA117969-04 (Principal Investigator Ronald DePinho); P.O., O.N.-S.,
and D.H. were supported by Gastrointestinal Specialized Programs of
Research Excellence in Gastrointestinal Cancers NIH 1P50CA127003-02 and
by The William K. Bowes Jr. Foundation. D. H. is an American Cancer
Society Research Professor. P.O. acknowledges salary support from
National Cancer Institute Training Grant T32 CA09043 (Director J.
Michael Bishop), Molecular Analysis of Tumor Viruses. P.O., O.N.-S., and
D.H. acknowledge access to the University of California, San Francisco
(UCSF), Diabetes Center's Microscopy Core (funded by Diabetes and
Endocrinology Research Center) and to the Preclinical Therapeutic Core
at UCSF. G.C.C. and S.R.P recognize histology support provided by the
Specialized Histopathology and Rodent Histopathology Cores
(Dana-Farber/Harvard Cancer Center).
NR 41
TC 34
Z9 35
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 6
PY 2011
VL 108
IS 49
BP E1275
EP E1284
DI 10.1073/pnas.1111079108
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 856ZQ
UT WOS:000297683800004
PM 22084065
ER
PT J
AU Zhou, DW
Zhang, YY
Wu, H
Barry, E
Yin, Y
Lawrence, E
Dawson, D
Willis, JE
Markowitz, SD
Camargo, FD
Avruch, J
AF Zhou, Dawang
Zhang, Yongyou
Wu, Hongtan
Barry, Evan
Yin, Yi
Lawrence, Earl
Dawson, Dawn
Willis, Joseph E.
Markowitz, Sanford D.
Camargo, Fernando D.
Avruch, Joseph
TI Mst1 and Mst2 protein kinases restrain intestinal stem cell
proliferation and colonic tumorigenesis by inhibition of Yes-associated
protein (Yap) overabundance
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID HIPPO SIGNALING PATHWAY; GROWTH-CONTROL; SIZE-CONTROL;
COLORECTAL-CANCER; SELF-RENEWAL; BETA-CATENIN; ORGAN SIZE; NOTCH; WNT;
DIFFERENTIATION
AB Ablation of the kinases Mst1 and Mst2, orthologs of the Drosophila antiproliferative kinase Hippo, from mouse intestinal epithelium caused marked expansion of an undifferentiated stem cell compartment and loss of secretory cells throughout the small and large intestine. Although median survival of mice lacking intestinal Mst1/Mst2 is 13 wk, adenomas of the distal colon are common by this age. Diminished phosphorylation, enhanced abundance, and nuclear localization of the transcriptional coactivator Yes-associated protein 1 (Yap1) is evident in Mst1/Mst2-deficient intestinal epithelium, as is strong activation of beta-catenin and Notch signaling. Although biallelic deletion of Yap1 from intestinal epithelium has little effect on intestinal development, inactivation of a single Yap1 allele reduces Yap1 polypeptide abundance to nearly wild-type levels and, despite the continued Yap hypophosphorylation and preferential nuclear localization, normalizes epithelial structure. Thus, supraphysiologic Yap polypeptide levels are necessary to drive intestinal stem cell proliferation. Yap is overexpressed in 68 of 71 human colon cancers and in at least 30 of 36 colon cancer-derived cell lines. In colon-derived cell lines where Yap is overabundant, its depletion strongly reduces beta-catenin and Notch signaling and inhibits proliferation and survival. These findings demonstrate that Mst1 and Mst2 actively suppress Yap1 abundance and action in normal intestinal epithelium, an antiproliferative function that frequently is overcome in colon cancer through Yap1 polypeptide overabundance. The dispensability of Yap1 in normal intestinal homeostasis and its potent proliferative and prosurvival actions when overexpressed in colon cancer make it an attractive therapeutic target.
C1 [Zhou, Dawang; Wu, Hongtan; Yin, Yi; Avruch, Joseph] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA 02115 USA.
[Zhou, Dawang; Wu, Hongtan; Yin, Yi; Avruch, Joseph] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Zhou, Dawang; Wu, Hongtan; Yin, Yi; Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Zhou, Dawang; Wu, Hongtan] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China.
[Zhang, Yongyou; Markowitz, Sanford D.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44016 USA.
[Zhang, Yongyou; Dawson, Dawn; Willis, Joseph E.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44016 USA.
[Lawrence, Earl; Dawson, Dawn; Willis, Joseph E.; Markowitz, Sanford D.] Case Med Ctr, Ctr Comprehens Canc, Cleveland, OH 44016 USA.
[Barry, Evan; Camargo, Fernando D.] Childrens Hosp, Stem Cell Program, Cambridge, MA 02142 USA.
[Barry, Evan; Camargo, Fernando D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Barry, Evan; Camargo, Fernando D.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Avruch, J (reprint author), Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA 02115 USA.
EM avruch@molbio.mgh.harvard.edu
OI Zhou, Dawang/0000-0002-9053-5249
FU National Institutes of Health [RO1 DK17776, CA136567, CA127306]; Stand
Up to Cancer-American Association for Cancer Research initiative;
Fundamental Research Funds for the Central Universities of China
[T32DK007028, 2010111079]; Science Planning Program of Fujian Province
[2009J1010]
FX We thank James K. V. Willson for the VACO colon cancer cell lines, R.
Polakiewicz (Cell Signaling Inc.) for the antiYap1(Ser384P) antiserum,
and R. T. Bronson for mouse histologic analyses. This work was supported
in part by National Institutes of Health Grants RO1 DK17776 (to J.A.),
CA136567 (to J.A.), and CA127306 (to S.D.M.), by a grant from the Stand
Up to Cancer-American Association for Cancer Research initiative (to
F.D.C.), and by institutional funds. F.D.C. is a Pew Scholar in the
Biomedical Sciences. D.Z. is supported by the Fundamental Research Funds
for the Central Universities of China (T32DK007028, Project Number
2010111079) and by the Science Planning Program of Fujian Province
(Project Number 2009J1010).
NR 46
TC 69
Z9 69
U1 1
U2 34
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 6
PY 2011
VL 108
IS 49
BP E1312
EP E1320
DI 10.1073/pnas.1110428108
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 856ZQ
UT WOS:000297683800008
ER
PT J
AU Cope, EK
Goldstein-Daruech, N
Kofonow, JM
Christensen, L
McDermott, B
Monroy, F
Palmer, JN
Chiu, AG
Shirtliff, ME
Cohen, NA
Leid, JG
AF Cope, Emily K.
Goldstein-Daruech, Natalia
Kofonow, Jennifer M.
Christensen, Lanette
McDermott, Bridget
Monroy, Fernando
Palmer, James N.
Chiu, Alexander G.
Shirtliff, Mark E.
Cohen, Noam A.
Leid, Jeff G.
TI Regulation of Virulence Gene Expression Resulting from Streptococcus
pneumoniae and Nontypeable Haemophilus influenzae Interactions in
Chronic Disease
SO PLOS ONE
LA English
DT Article
ID UPPER RESPIRATORY-TRACT; ORAL MICROBIAL COMMUNITIES; CHRONIC
RHINOSINUSITIS; OTITIS-MEDIA; IN-VIVO; BIOFILM FORMATION;
PSEUDOMONAS-AERUGINOSA; CHINCHILLA MODEL; HUMAN HOST; BACTERIAL
AB Chronic rhinosinusitis (CRS) is a common inflammatory disease of the sinonasal cavity mediated, in part, by polymicrobial communities of bacteria. Recent molecular studies have confirmed the importance of Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) in CRS. Here, we hypothesize that interaction between S. pneumoniae and NTHi mixed-species communities cause a change in bacterial virulence gene expression. We examined CRS as a model human disease to validate these polymicrobial interactions. Clinical strains of S. pneumoniae and NTHi were grown in mono-and co-culture in a standard biofilm assay. Reverse transcriptase real-time PCR (RTqPCR) was used to measure gene expression of key virulence factors. To validate these results, we investigated the presence of the bacterial RNA transcripts in excised human tissue from patients with CRS. Consequences of physical or chemical interactions between microbes were also investigated. Transcription of NTHi type IV pili was only expressed in co-culture in vitro, and expression could be detected ex vivo in diseased tissue. S. pneumoniae pyruvate oxidase was up-regulated in co-culture, while pneumolysin and pneumococcal adherence factor A were down-regulated. These results were confirmed in excised human CRS tissue. Gene expression was differentially regulated by physical contact and secreted factors. Overall, these data suggest that interactions between H. influenzae and S. pneumoniae involve physical and chemical mechanisms that influence virulence gene expression of mixed-species biofilm communities present in chronically diseased human tissue. These results extend previous studies of population-level virulence and provide novel insight into the importance of S. pneumoniae and NTHi in CRS.
C1 [Cope, Emily K.; Christensen, Lanette; McDermott, Bridget; Monroy, Fernando; Leid, Jeff G.] No Arizona Univ, Dept Biol Sci, Flagstaff, AZ 86011 USA.
[Goldstein-Daruech, Natalia; Kofonow, Jennifer M.; Palmer, James N.; Chiu, Alexander G.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA.
[Cohen, Noam A.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA 19104 USA.
[Shirtliff, Mark E.] Univ Maryland, Sch Dent, Dept Microbial Pathogenesis, Baltimore, MD 21201 USA.
RP Cope, EK (reprint author), No Arizona Univ, Dept Biol Sci, Box 5640, Flagstaff, AZ 86011 USA.
EM Emily.Cope@nau.edu
RI Monroy, Francisco/N-2763-2013; Chiu, Alexander/J-1230-2014
OI Monroy, Francisco/0000-0001-6455-3083; Cohen, Noam/0000-0002-9462-3932;
Chiu, Alexander/0000-0002-7592-6575
FU Science Foundation Arizona [GRF 0204-08]; Flight Attendants Medical
Research Institute [103019]
FX This work was supported by Science Foundation Arizona GRF 0204-08
(http://www.sfaz.org) and the Flight Attendants Medical Research
Institute, Clinical Innovator Award #103019. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 62
TC 17
Z9 17
U1 0
U2 11
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 DEC 5
PY 2011
VL 6
IS 12
AR e28523
DI 10.1371/journal.pone.0028523
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 863NX
UT WOS:000298172800045
PM 22162775
ER
PT J
AU Osundiji, MA
Godes, ML
Evans, ML
Danial, NN
AF Osundiji, Mayowa A.
Godes, Marina L.
Evans, Mark L.
Danial, Nika N.
TI BAD Modulates Counterregulatory Responses to Hypoglycemia and Protective
Glucoprivic Feeding
SO PLOS ONE
LA English
DT Article
ID SENSITIVE K+ CHANNELS; VENTROMEDIAL HYPOTHALAMUS CONTRIBUTES; ALPHA-CELL
FUNCTION; GLUCAGON-SECRETION; BLOOD-GLUCOSE; FOOD-INTAKE; RAT-BRAIN;
ANTECEDENT HYPOGLYCEMIA; ENERGY HOMEOSTASIS; HORMONE RESPONSES
AB Hypoglycemia or glucoprivation triggers protective hormonal counterregulatory and feeding responses to aid the restoration of normoglycemia. Increasing evidence suggests pertinent roles for the brain in sensing glucoprivation and mediating counterregulation, however, the precise nature of the metabolic signals and molecular mediators linking central glucose sensing to effector functions are not fully understood. Here, we demonstrate that protective hormonal and feeding responses to hypoglycemia are regulated by BAD, a BCL-2 family protein with dual functions in apoptosis and metabolism. BAD-deficient mice display impaired glycemic and hormonal counterregulatory responses to systemic glucoprivation induced by 2-deoxy-D-glucose. BAD is also required for proper counterregulatory responses to insulin-induced hypoglycemia as evident from significantly higher glucose infusion rates and lower plasma epinephrine levels during hyperinsulinemic hypoglycemic clamps. Importantly, RNA interference-mediated acute knockdown of Bad in the brain provided independent genetic evidence for its relevance in central glucose sensing and proper neurohumoral responses to glucoprivation. Moreover, BAD deficiency is associated with impaired glucoprivic feeding, suggesting that its role in adaptive responses to hypoglycemia extends beyond hormonal responses to regulation of feeding behavior. Together, these data indicate a previously unappreciated role for BAD in the control of central glucose sensing.
C1 [Osundiji, Mayowa A.; Godes, Marina L.; Danial, Nika N.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Danial, Nika N.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Evans, Mark L.] Univ Cambridge, Dept Med, Metab Res Labs, Cambridge CB2 2QQ, England.
[Evans, Mark L.] Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England.
RP Osundiji, MA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
EM nika_danial@dfci.harvard.edu
FU Juvenile Diabetes Research Foundation [3-2010-472]; Burroughs Wellcome
Fund Career Award in Biomedical Sciences; United States National
Institutes of Health [K01CA10659, R01DK078081]
FX MAO was supported by a post-doctoral fellowship from the Juvenile
Diabetes Research Foundation (3-2010-472). NND is a recipient of the
Burroughs Wellcome Fund Career Award in Biomedical Sciences. This work
was supported by United States National Institutes of Health grants
K01CA10659 and R01DK078081 (NND). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 59
TC 6
Z9 6
U1 1
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 DEC 5
PY 2011
VL 6
IS 12
AR e28016
DI 10.1371/journal.pone.0028016
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 863NX
UT WOS:000298172800009
PM 22162752
ER
PT J
AU Rini, BI
Escudier, B
Tomczak, P
Kaprin, A
Szczylik, C
Hutson, TE
Michaelson, MD
Gorbunova, VA
Gore, ME
Rusakov, IG
Negrier, S
Ou, YC
Castellano, D
Lim, HY
Uemura, H
Tarazi, J
Cella, D
Chen, C
Rosbrook, B
Kim, S
Motzer, RJ
AF Rini, Brian I.
Escudier, Bernard
Tomczak, Piotr
Kaprin, Andrey
Szczylik, Cezary
Hutson, Thomas E.
Michaelson, M. Dror
Gorbunova, Vera A.
Gore, Martin E.
Rusakov, Igor G.
Negrier, Sylvie
Ou, Yen-Chuan
Castellano, Daniel
Lim, Ho Yeong
Uemura, Hirotsugu
Tarazi, Jamal
Cella, David
Chen, Connie
Rosbrook, Brad
Kim, Sinil
Motzer, Robert J.
TI Comparative effectiveness of axitinib versus sorafenib in advanced renal
cell carcinoma (AXIS): a randomised phase 3 trial
SO LANCET
LA English
DT Article
ID III TRIAL; SOLID TUMORS; DOUBLE-BLIND; SUNITINIB; EFFICACY; CANCER;
BEVACIZUMAB
AB Background The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis. So far, no phase 3 randomised trials comparing the effectiveness of one targeted agent against another have been reported. We did a randomised phase 3 study comparing axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor (VEGF) receptors, with sorafenib, an approved VEGF receptor inhibitor, as second-line therapy in patients with metastatic renal cell cancer.
Methods We included patients coming from 175 sites (hospitals and outpatient clinics) in 22 countries aged 18 years or older with confirmed renal clear-cell carcinoma who progressed despite first-line therapy containing sunitinib, bevacizumab plus interferon-alfa, temsirolimus, or cytokines. Patients were stratified according to Eastern Cooperative Oncology Group performance status and type of previous treatment and then randomly assigned (1: 1) to either axitinib (5 mg twice daily) or sorafenib (400 mg twice daily). Axitinib dose increases to 7 mg and then to 10 mg, twice daily, were allowed for those patients without hypertension or adverse reactions above grade 2. Participants were not masked to study treatment. The primary endpoint was progression-free survival (PFS) and was assessed by a masked, independent radiology review and analysed by intention to treat. This trial was registered on ClinicalTrials.gov, number NCT00678392.
Findings A total of 723 patients were enrolled and randomly assigned to receive axitinib (n=361) or sorafenib (n=362). The median PFS was 6.7 months with axitinib compared to 4.7 months with sorafenib (hazard ratio 0.665; 95% CI 0.544-0.812; one-sided p<0.0001). Treatment was discontinued because of toxic effects in 14 (4%) of 359 patients treated with axitinib and 29 (8%) of 355 patients treated with sorafenib. The most common adverse events were diarrhoea, hypertension, and fatigue in the axitinib arm, and diarrhoea, palmar-plantar erythrodysaesthesia, and alopecia in the sorafenib arm.
Interpretation Axitinib resulted in significantly longer PFS compared with sorafenib. Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma.
C1 [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44195 USA.
[Escudier, Bernard] Inst Gustave Roussy, Serv Immunotherapie, Villejuif, France.
[Tomczak, Piotr] Uniwersytet Med, Klin Onkol, Poznan, Poland.
[Kaprin, Andrey] Russian Res Ctr Roentgenol & Radiol, Moscow, Russia.
[Szczylik, Cezary] Cent Clin Hosp, Mil Med Inst, Klin Onkol, Warsaw, Poland.
[Hutson, Thomas E.] Baylor Sammons Texas Oncol Phys Assoc, Sammons Canc Ctr, Dallas, TX USA.
[Michaelson, M. Dror] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Gorbunova, Vera A.] State Inst Natl Canc Res Ctr, Dept Chemotherapy, Moscow, Russia.
[Gore, Martin E.] Royal Marsden Hosp, London SW3 6JJ, England.
[Rusakov, Igor G.] Hertzen Res Inst Oncol, Moscow, Russia.
[Ou, Yen-Chuan] Taichung Vet Gen Hosp, Dept Surg 160, Taichung, Taiwan.
[Castellano, Daniel] Hosp Univ 12 Octubre, Serv Oncol Med, Madrid, Spain.
[Lim, Ho Yeong] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea.
[Uemura, Hirotsugu] Kinki Univ Hosp, Dept Urol, Osaka, Japan.
[Tarazi, Jamal; Rosbrook, Brad; Kim, Sinil] Pfizer Inc, Clin Oncol, San Diego, CA USA.
[Cella, David] Northwestern Univ, Chicago, IL 60611 USA.
[Chen, Connie] Pfizer Inc, Global Outcomes Res, New York, NY USA.
[Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Rini, BI (reprint author), Cleveland Clin, Taussig Canc Inst, Main Campus,Mail Code R35,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM rinib2@ccf.org
OI Kaprin, A.D/0000-0001-8784-8415; Michaelson, Dror/0000-0001-9249-6338
FU Pfizer Inc.; Pfizer; AVEO; Bayer; Genentech; GlaxoSmithKline
FX Pfizer Inc.; BIR has served as a consultant for and received research
funding from Pfizer. DCe has served as a consultant for and received
research funding from Pfizer. MEG has served on the speakers' bureau and
as an adviser for Bayer and Pfizer. TEH has served as a consultant for
and received honoraria and research funding from AVEO, Bayer, Genentech,
GlaxoSmithKline, and Pfizer. RJM has served as a consultant for Pfizer.
SN has served as a consultant for Pfizer and Roche, and has received
honoraria from Novartis and Pfizer and research funding from
GlaxoSmithKline. BE has received honoraria from AVEO, Bayer,
GlaxoSmithKline, Novartis, and Pfizer. CS has served on an advisory
board for Pfizer. JT, CC, BR, and SK are employed by and own stock in
Pfizer. AK, DCa, VG, IR, HYL, YCO, HU, MDM, and PT declare that they
have no conflicts of interest.
NR 32
TC 725
Z9 738
U1 10
U2 63
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD DEC 3
PY 2011
VL 378
IS 9807
BP 1931
EP 1939
DI 10.1016/S0140-6736(11)61613-9
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 863AW
UT WOS:000298136200027
PM 22056247
ER
PT J
AU Wen, LS
Greysen, SR
Keszthelyi, D
Bracero, J
de Roos, PDG
AF Wen, Leana S.
Greysen, S. Ryan
Keszthelyi, Daniel
Bracero, Julio
de Roos, P. D. G.
TI Social accountability in health professionals' training
SO LANCET
LA English
DT Editorial Material
ID EDUCATION; SCHOOL; AREAS
C1 [Wen, Leana S.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Greysen, S. Ryan] Yale Univ, Sch Med, New Haven, CT USA.
[Keszthelyi, Daniel] Maastricht Univ, Med Ctr, Maastricht, Netherlands.
[Bracero, Julio] St Lukes Episcopal Hosp, Ponce, PR USA.
[de Roos, P. D. G.] Ter Gooi Ziekenhuis, Blaricum, Netherlands.
RP Wen, LS (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02115 USA.
EM Wen.Leana@gmail.com
RI Dharamsi, Shafik/H-3165-2011;
OI Wen, Leana/0000-0003-0259-0537
NR 12
TC 5
Z9 5
U1 2
U2 9
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 DEC 3
PY 2011
VL 378
IS 9807
BP E12
EP E13
DI 10.1016/S0140-6736(10)62314-8
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 863AW
UT WOS:000298136200001
PM 21477854
ER
PT J
AU Bhalla, K
Hwang, BJ
Choi, JH
Dewi, R
Ou, LH
Mclenithan, J
Twaddel, W
Pozharski, E
Stock, J
Girnum, GD
AF Bhalla, Kavita
Hwang, Bor Jang
Choi, Jang Hyun
Dewi, Ruby
Ou, Lihui
Mclenithan, John
Twaddel, William
Pozharski, Edwin
Stock, Jeffry
Girnum, Geoffrey D.
TI N-Acetylfarnesylcysteine Is a Novel Class of Peroxisome
Proliferator-activated Receptor gamma Ligand with Partial and Full
Agonist Activity in Vitro and in Vivo
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DIFFERENTIATION-RELATED PROTEIN; ADIPOSE-TISSUE MACROPHAGES; TYPE-2
DIABETES-MELLITUS; PPAR-GAMMA; INSULIN-RESISTANCE; ADIPOCYTE
DIFFERENTIATION; FATTY-ACIDS; METABOLIC DISEASE; GENE-EXPRESSION;
BINDING DOMAIN
AB The thiazolidedione (TZD) class of drugs is clinically approved for the treatment of type 2 diabetes. The therapeutic actions of TZDs are mediated via activation of peroxisome proliferator-activated receptor gamma (PPAR gamma). Despite their widespread use, concern exists regarding the safety of currently used TZDs. This has prompted the development of selective PPAR gamma modulators (SPPARMs), compounds that promote glucose homeostasis but with reduced side effects due to partial PPAR gamma agonism. However, this also results in partial agonism with respect to PPAR gamma target genes promoting glucose homeostasis. Using a gene expression-based screening approach we identified N-acetylfarnesylcysteine (AFC) as both a full and partial agonist depending on the PPAR gamma target gene (differential SPPARM). AFC activated PPAR gamma as effectively as rosiglitazone with regard to Adrp, Angpt14, and AdipoQ, but was a partial agonist of aP2, a PPAR gamma target gene associated with increased adiposity. Induction of adipogenesis by AFC was also attenuated compared with rosiglitazone. Reporter, ligand binding assays, and dynamic modeling demonstrate that AFC binds and activates PPAR gamma in a unique manner compared with other PPAR gamma ligands. Importantly, treatment of mice with AFC improved glucose tolerance similar to rosiglitazone, but AFC did not promote weight gain to the same extent. Finally, AFC had effects on adipose tissue remodeling similar to those of rosiglitazone and had enhanced antiinflammatory effects. In conclusion, we describe a new approach for the identification of differential SPPARMs and have identified AFC as a novel class of PPAR gamma ligand with both full and partial agonist activity in vitro and in vivo.
C1 [Bhalla, Kavita; Dewi, Ruby; Ou, Lihui; Girnum, Geoffrey D.] Harvard Univ, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Boston, MA 02215 USA.
[Hwang, Bor Jang; Girnum, Geoffrey D.] Harvard Univ, Sch Med, Dept Biochem & Mol Biol, Boston, MA 02215 USA.
[Choi, Jang Hyun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Mclenithan, John] Univ Maryland, Sch Med, Dept Endocrinol, Baltimore, MD 21201 USA.
[Twaddel, William] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Pozharski, Edwin] Univ Maryland, Sch Med, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
[Stock, Jeffry] Princeton Univ, Dept Mol Biol, Princeton, NJ 08554 USA.
RP Girnum, GD (reprint author), Univ Maryland Greenebaum Canc Ctr, Dept Biochem & Mol Biol, 655 W Baltimore St,BRB Rm 10-039, Baltimore, MD 21201 USA.
EM ggirnun@som.umaryland.edu
OI Pozharski, Edwin/0000-0001-7012-5376
FU National Institutes of Health [K01DK064685]; Maryland Cigarette
Restitution Fund; University of Maryland Nutrition Obesity Research
Center
FX The work was supported, in whole or in part, by National Institutes of
Health Grant K01DK064685. This work was also supported by Maryland
Cigarette Restitution Fund and a pilot grant from the University of
Maryland Nutrition Obesity Research Center (to G.D.G).
NR 75
TC 18
Z9 19
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD DEC 2
PY 2011
VL 286
IS 48
BP 41626
EP 41635
DI 10.1074/jbc.M111.257915
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 861YR
UT WOS:000298057500047
PM 21979952
ER
PT J
AU Boes, AD
Grafft, AH
Joshi, C
Chuang, NA
Nopoulos, P
Anderson, SW
AF Boes, Aaron D.
Grafft, Amanda Hornaday
Joshi, Charuta
Chuang, Nathaniel A.
Nopoulos, Peg
Anderson, Steven W.
TI Behavioral effects of congenital ventromedial prefrontal cortex
malformation
SO BMC NEUROLOGY
LA English
DT Article
ID ANTISOCIAL PERSONALITY-DISORDER; ANTERIOR COMMUNICATING ARTERY; FOCAL
CORTICAL DYSPLASIA; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX;
FRONTAL-LOBE DAMAGE; RESPONSE REVERSAL; IMPULSE CONTROL; NEURAL BASIS;
CONSEQUENCES
AB Background: A detailed behavioral profile associated with focal congenital malformation of the ventromedial prefrontal cortex (vmPFC) has not been reported previously. Here we describe a 14 year-old boy, B. W., with neurological and psychiatric sequelae stemming from focal cortical malformation of the left vmPFC.
Case Presentation: B.W.'s behavior has been characterized through extensive review Patience of clinical and personal records along with behavioral and neuropsychological testing. A central feature of the behavioral profile is severe antisocial behavior. He is aggressive, manipulative, and callous; features consistent with psychopathy. Other problems include: egocentricity, impulsivity, hyperactivity, lack of empathy, lack of respect for authority, impaired moral judgment, an inability to plan ahead, and poor frustration tolerance.
Conclusions: The vmPFC has a profound contribution to the development of human prosocial behavior. B. W. demonstrates how a congenital lesion to this cortical region severely disrupts this process.
C1 [Boes, Aaron D.] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA 02114 USA.
[Grafft, Amanda Hornaday] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA.
[Grafft, Amanda Hornaday] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA.
[Joshi, Charuta] Univ Iowa, Dept Pediat Neurol, Iowa City, IA 52242 USA.
[Chuang, Nathaniel A.] Rady Childrens Hosp San Diego, Dept Neuroradiol, San Diego, CA 92123 USA.
[Nopoulos, Peg] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Anderson, Steven W.] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA.
RP Boes, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Neurol, MC WACC 8-835,55 Fruit St, Boston, MA 02114 USA.
EM aboes@partners.org
FU National Institute of Neurological Disorders and Stroke (NINDS)
[PO19632]
FX We would like to thank BW and his family for their help in presenting
his story. We thank Martin Cassell, Ph.D., for his assistance with
neuroanatomy and further defining the lesion. We also thank Rosalind B.
Dietrich, who carefully reviewed the MRI data and offered many helpful
suggestions in accurately characterizing the lesion. This research was
supported by National Institute of Neurological Disorders and Stroke
(NINDS)PO19632. No authors report any conflicts of interest, financial
or otherwise.
NR 65
TC 12
Z9 13
U1 14
U2 42
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2377
J9 BMC NEUROL
JI BMC Neurol.
PD DEC 2
PY 2011
VL 11
AR 151
DI 10.1186/1471-2377-11-151
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA 890WT
UT WOS:000300177500001
PM 22136635
ER
PT J
AU Shang, WH
Qiao, JP
Gu, CX
Yin, W
Du, JL
Wang, W
Zhu, ML
Han, M
Lu, WD
AF Shang, Weihu
Qiao, Jinping
Gu, Chenxin
Yin, Wei
Du, Jinglei
Wang, Wei
Zhu, Meilin
Han, Mei
Lu, Weidong
TI Anticancer activity of an extract from needles and twigs of Taxus
cuspidata and its synergistic effect as a cocktail with 5-fluorouracil
SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Article
ID CHINESE HERBAL MEDICINES; LINES IN-VITRO; CELL-LINES; COMBINATION
CHEMOTHERAPY; GASTRIC-CANCER; MAIN TAXOIDS; PACLITAXEL; CARCINOMA;
THERAPY; LIQUID
AB Background: Botanical medicines are increasingly combined with chemotherapeutics as anticancer drug cocktails. This study aimed to assess the chemotherapeutic potential of an extract of Taxus cuspidata (TC) needles and twigs produced by artificial cuttage and its co-effects as a cocktail with 5-fluorouracil (5-FU).
Methods: Components of TC extract were identified by HPLC fingerprinting. Cytotoxicity analysis was performed by MTT assay or ATP assay. Apoptosis studies were analyzed by H & E, PI, TUNEL staining, as well as Annexin V/PI assay. Cell cycle analysis was performed by flow cytometry. 5-FU concentrations in rat plasma were determined by HPLC and the pharmacokinetic parameters were estimated using 3p87 software. Synergistic efficacy was subjected to median effect analysis with the mutually nonexclusive model using Calcusyn1 software. The significance of differences between values was estimated by using a one-way ANOVA.
Results: TC extract reached inhibition rates of 70-90% in different human cancer cell lines (HL-60, BGC-823, KB, Bel-7402, and HeLa) but only 5-7% in normal mouse T/B lymphocytes, demonstrating the broad-spectrum anticancer activity and low toxicity to normal cells of TC extract in vitro. TC extract inhibited cancer cell growth by inducing apoptosis and G(2)/M cell cycle arrest. Most interestingly, TC extract and 5-FU, combined as a cocktail, synergistically inhibited the growth of cancer cells in vitro, with Combination Index values (CI) ranging from 0.90 to 0.26 at different effect levels from IC50 to IC90 in MCF-7 cells, CI ranging from 0.93 to 0.13 for IC40 to IC90 in PC-3M-1E8 cells, and CI < 1 in A549 cells. In addition, the cocktail had lower cytotoxicity in normal human cell (HEL) than 5-FU used alone. Furthermore, TC extract did not affect the pharmacokinetics of 5-FU in rats.
Conclusions: The combinational use of the TC extract with 5-FU displays strong cytotoxic synergy in cancer cells and low cytotoxicity in normal cells. These findings suggest that this cocktail may have a potential role in cancer treatment.
C1 [Shang, Weihu; Qiao, Jinping; Gu, Chenxin; Yin, Wei; Du, Jinglei; Wang, Wei; Zhu, Meilin; Han, Mei] Beijing Normal Univ, Key Lab Radiopharmaceut, Minist Educ, Coll Chem, Beijing 100875, Peoples R China.
[Lu, Weidong] Harvard Univ, Sch Med, Leonard P Zakim Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Han, M (reprint author), Beijing Normal Univ, Key Lab Radiopharmaceut, Minist Educ, Coll Chem, Beijing 100875, Peoples R China.
EM hanmei@bnu.edu.cn; weidong_lu@dfci.harvard.edu
RI Lu, Weidong/C-3844-2008
OI Lu, Weidong/0000-0003-2838-6307
FU National Key Technology RD Program [2008BAI49B04]; China National
Science Foundation [81173139]; Hongdoushan Research Foundation
FX This work was funded by grants provided by the National Key Technology
R&D Program (2008BAI49B04), the China National Science Foundation
(81173139), and the Hongdoushan Research Foundation. We are grateful to
Mr. Yongyan Wang and Mr. Jianqiang Zou for program suggestions. We also
thank Mr. Zhiguo Wang for generously providing the samples of extract of
TC needles and twigs produced by artificial cuttage.
NR 42
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U1 2
U2 27
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6882
J9 BMC COMPLEM ALTERN M
JI BMC Complement. Altern. Med.
PD DEC 2
PY 2011
VL 11
AR 123
DI 10.1186/1472-6882-11-123
PG 11
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA 886GU
UT WOS:000299842900001
PM 22132732
ER
PT J
AU Chu, VC
Bhattacharya, S
Nomoto, A
Lin, JH
Zaidi, SK
Oberley, TD
Weinman, SA
Azhar, S
Huang, TT
AF Chu, Victor C.
Bhattacharya, Sayanti
Nomoto, Ann
Lin, Jiahui
Zaidi, Syed Kashif
Oberley, Terry D.
Weinman, Steven A.
Azhar, Salman
Huang, Ting-Ting
TI Persistent Expression of Hepatitis C Virus Non-Structural Proteins Leads
to Increased Autophagy and Mitochondrial Injury in Human Hepatoma Cells
SO PLOS ONE
LA English
DT Article
ID CORE PROTEIN; OXIDATIVE STRESS; MICROVILLAR LOCALIZATION;
SUPEROXIDE-DISMUTASE; SCAVENGER RECEPTOR; ROS PRODUCTION; NS5A PROTEIN;
ER STRESS; CLASS-B; REPLICATION
AB HCV infection is a major cause of chronic liver disease and liver cancer in the United States. To address the pathogenesis caused by HCV infection, recent studies have focused on the direct cytopathic effects of individual HCV proteins, with the objective of identifying their specific roles in the overall pathogenesis. However, this approach precludes examination of the possible interactions between different HCV proteins and organelles. To obtain a better understanding of the various cytopathic effects of and cellular responses to HCV proteins, we used human hepatoma cells constitutively replicating HCV RNA encoding either the full-length polyprotein or the non-structural proteins, or cells constitutively expressing the structural protein core, to model the state of persistent HCV infection and examined the combination of various HCV proteins in cellular pathogenesis. Increased reactive oxygen species (ROS) generation in the mitochondria, mitochondrial injury and degeneration, and increased lipid accumulation were common among all HCV protein-expressing cells regardless of whether they expressed the structural or non-structural proteins. Expression of the non-structural proteins also led to increased oxidative stress in the cytosol, membrane blebbing in the endoplasmic reticulum, and accumulation of autophagocytic vacuoles. Alterations of cellular redox state, on the other hand, significantly changed the level of autophagy, suggesting a direct link between oxidative stress and HCV-mediated activation of autophagy. With the widespread cytopathic effects, cells with the full-length HCV polyprotein showed a modest antioxidant response and exhibited a significant increase in population doubling time and a concomitant decrease in cyclin D1. In contrast, cells expressing the non-structural proteins were able to launch a vigorous antioxidant response with up-regulation of antioxidant enzymes. The population doubling time and cyclin D1 level were also comparable to that of control cells. Finally, the cytopathic effects of core protein appeared to focus on the mitochondria without remarkable disturbances in the cytosol.
C1 Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
[Nomoto, Ann; Zaidi, Syed Kashif; Azhar, Salman; Huang, Ting-Ting] VA Palo Alto Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Palo Alto, CA USA.
[Oberley, Terry D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI USA.
[Oberley, Terry D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[Weinman, Steven A.] Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66103 USA.
RP Chu, VC (reprint author), Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
EM tthuang@stanford.edu
RI Zaidi, Syed Kashif /A-6160-2013
OI Zaidi, Syed Kashif /0000-0003-2391-414X
FU National Institutes of Health [AA012863, HL33881, CA122499]; Stanford
Digestive Disease Center
FX This work is supported by funding from National Institutes of Health
grant AA012863 to SW, HL33881 to SA, and CA122499 to T-TH, and from
Stanford Digestive Disease Center to T-TH. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 58
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PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 2
PY 2011
VL 6
IS 12
AR e28551
DI 10.1371/journal.pone.0028551
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 863NO
UT WOS:000298171400106
PM 22164304
ER
PT J
AU Finsen, AV
Lunde, IG
Sjaastad, I
Ostli, EK
Lyngra, M
Jarstadmarken, HO
Hasic, A
Nygard, S
Wilcox-Adelman, SA
Goetinck, PF
Lyberg, T
Skrbic, B
Florholmen, G
Tonnessen, T
Louch, WE
Djurovic, S
Carlson, CR
Christensen, G
AF Finsen, Alexandra V.
Lunde, Ida G.
Sjaastad, Ivar
Ostli, Even K.
Lyngra, Marianne
Jarstadmarken, Hilde O.
Hasic, Almira
Nygard, Stale
Wilcox-Adelman, Sarah A.
Goetinck, Paul F.
Lyberg, Torstein
Skrbic, Biljana
Florholmen, Geir
Tonnessen, Theis
Louch, William E.
Djurovic, Srdjan
Carlson, Cathrine R.
Christensen, Geir
TI Syndecan-4 Is Essential for Development of Concentric Myocardial
Hypertrophy via Stretch-Induced Activation of the Calcineurin-NFAT
Pathway
SO PLOS ONE
LA English
DT Article
ID INDUCED CARDIAC-HYPERTROPHY; GLYCOGEN-SYNTHASE KINASE-3;
PHOSPHATASE-ACTIVITY; PRESSURE-OVERLOAD; AUTOINHIBITORY DOMAIN; FOCAL
ADHESIONS; HEART-FAILURE; PROTEIN; MECHANISMS; INHIBITION
AB Sustained pressure overload leads to compensatory myocardial hypertrophy and subsequent heart failure, a leading cause of morbidity and mortality. Further unraveling of the cellular processes involved is essential for development of new treatment strategies. We have investigated the hypothesis that the transmembrane Z-disc proteoglycan syndecan-4, a co-receptor for integrins, connecting extracellular matrix proteins to the cytoskeleton, is an important signal transducer in cardiomyocytes during development of concentric myocardial hypertrophy following pressure overload. Echocardiographic, histochemical and cardiomyocyte size measurements showed that syndecan-4(-/-) mice did not develop concentric myocardial hypertrophy as found in wild-type mice, but rather left ventricular dilatation and dysfunction following pressure overload. Protein and gene expression analyses revealed diminished activation of the central, pro-hypertrophic calcineurin-nuclear factor of activated T-cell (NFAT) signaling pathway. Cardiomyocytes from syndecan-4(-/-)-NFAT-luciferase reporter mice subjected to cyclic mechanical stretch, a hypertrophic stimulus, showed minimal activation of NFAT (1.6-fold) compared to 5.8-fold increase in NFAT-luciferase control cardiomyocytes. Accordingly, overexpression of syndecan-4 or introducing a cell-permeable membrane-targeted syndecan-4 polypeptide (gain of function) activated NFATc4 in vitro. Pull-down experiments demonstrated a direct intracellular syndecan-4-calcineurin interaction. This interaction and activation of NFAT were increased by dephosphorylation of serine 179 (pS179) in syndecan-4. During pressure overload, phosphorylation of syndecan-4 was decreased, and association between syndecan-4, calcineurin and its co-activator calmodulin increased. Moreover, calcineurin dephosphorylated pS179, indicating that calcineurin regulates its own binding and activation. Finally, patients with hypertrophic myocardium due to aortic stenosis had increased syndecan-4 levels with decreased pS179 which was associated with increased NFAT activation. In conclusion, our data show that syndecan-4 is essential for compensatory hypertrophy in the pressure overloaded heart. Specifically, syndecan-4 regulates stretch-induced activation of the calcineurin-NFAT pathway in cardiomyocytes. Thus, our data suggest that manipulation of syndecan-4 may provide an option for therapeutic modulation of calcineurin-NFAT signaling.
C1 [Finsen, Alexandra V.; Lunde, Ida G.; Sjaastad, Ivar; Lyngra, Marianne; Jarstadmarken, Hilde O.; Hasic, Almira; Nygard, Stale; Skrbic, Biljana; Florholmen, Geir; Louch, William E.; Carlson, Cathrine R.; Christensen, Geir] Oslo Univ Hosp Ulleval, Expt Med Res Inst, Oslo, Norway.
[Finsen, Alexandra V.; Lunde, Ida G.; Sjaastad, Ivar; Lyngra, Marianne; Jarstadmarken, Hilde O.; Hasic, Almira; Nygard, Stale; Skrbic, Biljana; Florholmen, Geir; Tonnessen, Theis; Louch, William E.; Carlson, Cathrine R.; Christensen, Geir] Univ Oslo, Ctr Heart Failure Res, Oslo, Norway.
[Finsen, Alexandra V.] Univ Oslo, Rikshosp, Oslo Univ Hosp, Dept Cardiol, N-0027 Oslo, Norway.
[Finsen, Alexandra V.] Univ Oslo, Rikshosp, Oslo Univ Hosp, Internal Med Res Inst, N-0027 Oslo, Norway.
[Ostli, Even K.; Djurovic, Srdjan] Oslo Univ Hosp Ulleval, Dept Med Genet, Oslo, Norway.
[Sjaastad, Ivar] Oslo Univ Hosp Ulleval, Dept Cardiol, Oslo, Norway.
[Nygard, Stale] Univ Oslo, Dept Math, Oslo, Norway.
[Nygard, Stale] Oslo Univ Hosp, Bioinformat Core Facil, Oslo, Norway.
[Wilcox-Adelman, Sarah A.] Boston Biomed Res Inst, Watertown, MA USA.
[Goetinck, Paul F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA.
[Lyberg, Torstein] Oslo Univ Hosp Ulleval, Clin Res Ctr, Oslo, Norway.
[Skrbic, Biljana; Tonnessen, Theis] Oslo Univ Hosp Ulleval, Dept Cardiothorac Surg, Oslo, Norway.
RP Finsen, AV (reprint author), Oslo Univ Hosp Ulleval, Expt Med Res Inst, Oslo, Norway.
EM a.v.finsen@medisin.uio.no
RI Nygard, Stale/H-2148-2012
FU Norwegian Research Council; South-Eastern Regional Health Authority;
University of Oslo, Rakel; Otto Kr. Bruun's Fund; Joh. H. Andresens
Medical Fund; Ella and Kristian Nyrrod Fund; American Heart Association
[0250523N]; National Institutes of Health [HD-37490]
FX This project was funded by the Norwegian Research Council, the
South-Eastern Regional Health Authority, Anders Jahre's Fund for the
Promotion of Science, Molecular Life Sciences at the University of Oslo,
Rakel and Otto Kr. Bruun's Fund, Joh. H. Andresens Medical Fund, Ella
and Kristian Nyrrod Fund, the American Heart Association; AHA Grant
0250523N and National Institutes of Health; NICHD Grant HD-37490. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 53
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U2 12
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PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 2
PY 2011
VL 6
IS 12
AR e28302
DI 10.1371/journal.pone.0028302
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 863NO
UT WOS:000298171400066
PM 22164265
ER
PT J
AU Hsu, WC
Okeke, E
Cheung, S
Keenan, H
Tsui, T
Cheng, K
King, GL
AF Hsu, William C.
Okeke, Eyiuche
Cheung, Sophia
Keenan, Hillary
Tsui, Tracy
Cheng, Kyle
King, George L.
TI A Cross-Sectional Characterization of Insulin Resistance by Phenotype
and Insulin Clamp in East Asian Americans with Type 1 and Type 2
Diabetes
SO PLOS ONE
LA English
DT Article
ID ACID-BINDING PROTEIN; PREVALENCE; MEN; RETINOL-BINDING-PROTEIN-4;
POPULATION; COHORT
AB Objective: Classic features of type 1 and type 2 diabetes may not apply in Asian Americans, due to shared absence of common HLA DR-DQ genotype, low prevalence of positive anti-islet antibodies and low BMI in both types of diabetes. Our objective was to characterize diabetic phenotypes in Asian Americans by clamp and clinical features.
Materials/Methods: This was a cross-sectional study conducted in a referral center. Thirty East young Asian American adult volunteers (27.6 +/- 5.5 years) with type 1, type 2 diabetes or controls underwent hyperinsulinemic euglycemic clamp to assess insulin resistance and DEXA to assess adiposity.
Results: Gender, BMI, waist/hip ratio, leptin, LDL, anti-GAD, anti-IA2 antibodies and C-reactive protein were similar among three groups. Serum C-peptide, adiponectin, free fatty acid, HDL concentrations and truncal fat by DEXA, were different between diabetic groups. Glucose disposal rate by clamp was lowest in type 2 diabetes, followed by type 1 diabetes and controls (5.43 +/- 2.70, 7.62 +/- 2.59, 8.61 +/- 2.37 mg/min/kg, respectively, p = 0.001). Free fatty acid concentration universally plummeted during steady state of the clamp procedure regardless of diabetes types in all three groups. Adipocyte fatty acid binding protein in the entire cohort (r = -0.625, p = 0.04) and controls (r = -0.869, p = 0.046) correlated best with insulin resistance, independent of BMI.
Conclusions: Type 2 diabetes in Asian Americans was associated with insulin resistance despite having low BMI as type 1 diabetes, suggesting a potential role for targeting insulin resistance apart from weight loss. Adipocyte fatty acid binding protein, strongly associated with insulin resistance, independent of adiposity in the young Asian American population, may potentially serve as a biomarker to identify at-risk individuals. Larger studies are needed to confirm this finding.
C1 [Hsu, William C.; Okeke, Eyiuche; Cheung, Sophia; Tsui, Tracy; Cheng, Kyle; King, George L.] Joslin Diabet Ctr, Asian Amer Diabet Initiat, Boston, MA 02215 USA.
[Keenan, Hillary; King, George L.] Joslin Diabet Ctr, Dianne Nunnally Hoppes Lab Diabet Complicat, Boston, MA 02215 USA.
RP Hsu, WC (reprint author), Joslin Diabet Ctr, Asian Amer Diabet Initiat, Boston, MA 02215 USA.
EM William.hsu@joslin.harvard.edu
FU Harvard Catalyst | The Harvard Clinical and Translational Science Center
(National Institutes of Health) [UL1 RR 025758]; Harvard University;
Joslin Diabetes Center
FX The study was conducted with support provided by Joslin Diabetes
Center's Asian American Diabetes Fund, an internal fund. This work was
conducted with support from Harvard Catalyst | The Harvard Clinical and
Translational Science Center (National Institutes of Health 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. The funder had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 2
PY 2011
VL 6
IS 12
AR e28311
DI 10.1371/journal.pone.0028311
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 863NO
UT WOS:000298171400068
PM 22164267
ER
PT J
AU Tsibris, AMN
Pal, U
Schure, AL
Veazey, RS
Kunstman, KJ
Henrich, TJ
Klasse, PJ
Wolinsky, SM
Kuritzkes, DR
Moore, JP
AF Tsibris, Athe M. N.
Pal, Urboshi
Schure, Allison L.
Veazey, Ronald S.
Kunstman, Kevin J.
Henrich, Timothy J.
Klasse, P. J.
Wolinsky, Steven M.
Kuritzkes, Daniel R.
Moore, John P.
TI SHIV-162P3 Infection of Rhesus Macaques Given Maraviroc Gel Vaginally
Does Not Involve Resistant Viruses
SO PLOS ONE
LA English
DT Article
ID R5 HIV-1 INFECTION; CCR5 INHIBITORS; SHIV CHALLENGE; IN-VIVO; TYPE-1;
TRANSMISSION; PROGRESSION; CORECEPTOR; PROTECTION; ENVELOPE
AB Maraviroc (MVC) gels are effective at protecting rhesus macaques from vaginal SHIV transmission, but breakthrough infections can occur. To determine the effects of a vaginal MVC gel on infecting SHIV populations in a macaque model, we analyzed plasma samples from three rhesus macaques that received a MVC vaginal gel (day 0) but became infected after high-dose SHIV-162P3 vaginal challenge. Two infected macaques that received a placebo gel served as controls. The infecting SHIV-162P3 stock had an overall mean genetic distance of 0.294 +/- 0.027%; limited entropy changes were noted across the envelope (gp160). No envelope mutations were observed consistently in viruses isolated from infected macaques at days 14-21, the time of first detectable viremia, nor selected at later time points, days 42-70. No statistically significant differences in MVC susceptibilities were observed between the SHIV inoculum (50% inhibitory concentration [IC(50)] 1.87 nM) and virus isolated from the three MVC-treated macaques (MVC IC(50) 1.18 nM, 1.69 nM, and 1.53 nM, respectively). Highlighter plot analyses suggested that infection was established in each MVC-treated animal by one founder virus genotype. The expected Poisson distribution of pairwise Hamming Distance frequency counts was observed and a phylogenetic analysis did not identify infections with distinct lineages from the challenge stock. These data suggest that breakthrough infections most likely result from incomplete viral inhibition and not the selection of MVC-resistant variants.
C1 [Tsibris, Athe M. N.; Schure, Allison L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Tsibris, Athe M. N.; Henrich, Timothy J.; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Boston, MA USA.
[Pal, Urboshi] Cornell Univ, Ithaca, NY USA.
[Veazey, Ronald S.] Tulane Natl Primate Res Ctr, Covington, LA USA.
[Kunstman, Kevin J.; Wolinsky, Steven M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Henrich, Timothy J.; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Klasse, P. J.; Moore, John P.] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA.
RP Tsibris, AMN (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM atsibris@partners.org
RI Wolinsky, Steven/B-2893-2012;
OI Wolinsky, Steven/0000-0002-9625-6697
FU Harvard Clinical and Translational Science Center [UL1 RR025758];
Pfizer; [K08 AI081547]; [R37 AI055357]; [U19 AI076982]
FX AMNT was supported by K08 AI081547. TJH was supported by the KL2 Medical
Research Investigator Training (MeRIT) program of Harvard Catalyst, The
Harvard Clinical and Translational Science Center UL1 RR025758. This
work was supported in part by R37 AI055357 (DRK) and U19 AI076982 (JPM).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.; AMNT has served
as a consultant to Merck. DRK has served as a consultant to and has
received honoraria and/or research grant support from Pfizer. All other
authors report no conflicts. This does not alter the authors' adherence
to all the PLoS ONE policies on sharing data and materials.
NR 51
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U2 0
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PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 2
PY 2011
VL 6
IS 12
AR e28047
DI 10.1371/journal.pone.0028047
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 863NO
UT WOS:000298171400026
PM 22164225
ER
PT J
AU Wang, Z
Chen, J
Boyd, JE
Zhang, HY
Jia, XZ
Qiu, JY
Xiao, ZP
AF Wang, Zhen
Chen, Jue
Boyd, Jennifer E.
Zhang, Haiyin
Jia, Xiuzhen
Qiu, Jianyin
Xiao, Zeping
TI Psychometric Properties of the Chinese Version of the Perceived Stress
Scale in Policewomen
SO PLOS ONE
LA English
DT Article
ID PSYCHOLOGICAL STRESS; DEPRESSION; VALIDATION; ANXIETY; DISEASE; WOMEN
AB Background: The 10-item Perceived Stress Scale (PSS-10) is one of most widely used instruments to measure a global level of perceived stress in a range of clinical and research settings. This study was conducted to examine the psychometric properties of the Simplified Chinese version of the PSS-10 in policewomen.
Methodology: A total of 240 policewomen were recruited in this study. The Simplified Chinese versions of the PSS-10, the Beck Depression Inventory Revised (BDI-II), and the Beck Anxiety Inventory (BAI) were administered to all participants, and 36 of the participants were re-tested two weeks after the initial testing.
Principal Findings: The overall Cronbach's alpha was 0.86, and the test-retest reliability coefficient was 0.68. Exploratory Factor Analysis (EFA) yielded 2 factors with eigenvalues of 4.76 and 1.48, accounting for 62.41% of variance. Factor 1 consisted of 6 items representing "negative feelings''; whereas Factor 2 consisted of 4 items representing "positive feelings''. The item loadings ranged from 0.72 to 0.83. The Confirmatory factor analysis (CFA) indicated a very good fit of this two-factor model to this sample. The PSS-10 significantly correlated with both BDI-II and BAI, indicating an acceptable concurrent validity.
Conclusions: The Simplified Chinese version of the PSS-10 demonstrated adequate psychometric properties for evaluating stress levels. The results support its use among the Chinese population.
C1 [Wang, Zhen; Chen, Jue; Zhang, Haiyin; Jia, Xiuzhen; Qiu, Jianyin; Xiao, Zeping] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai 200030, Peoples R China.
[Boyd, Jennifer E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Boyd, Jennifer E.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Wang, Z (reprint author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai 200030, Peoples R China.
EM xiaozeping@gmail.com
FU National Natural Science Fundation [30800370]; Shanghai Pujiang Program
[09PJ1408900]
FX This study was supported by grants from the National Natural Science
Fundation (30800370) and the Shanghai Pujiang Program (09PJ1408900). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 28
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U1 3
U2 20
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 DEC 2
PY 2011
VL 6
IS 12
AR e28610
DI 10.1371/journal.pone.0028610
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 863NO
UT WOS:000298171400113
PM 22164311
ER
PT J
AU Hong, W
Li, JR
Wang, B
Chen, LF
Niu, WY
Yao, Z
Baniahmad, A
AF Hong, Wei
Li, Jinru
Wang, Bo
Chen, Linfeng
Niu, Wenyan
Yao, Zhi
Baniahmad, Aria
TI Epigenetic involvement of Alien/ESET complex in thyroid hormone-mediated
repression of E2F1 gene expression and cell proliferation
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Corepressor; Thyroid hormone receptor; Histone methyltransferase; ESET
ID HISTONE H3; METHYLATION; RECEPTOR; TRANSCRIPTION; METHYLTRANSFERASES;
EUCHROMATIN; PROTEIN
AB The ligand-bound thyroid hormone receptor (TR) is known to repress via a negative IRE (nTRE) the expression of E2F1, a key transcription factor that controls the G1/S phase transition. Alien has been identified as a novel interacting factor of E2F1 and acts as a corepressor of E2F1. The detailed molecular mechanism by which Alien inhibits E2F1 gene expression remains unclear. Here, we report that the histone H3 lysine 9 (H3K9) methyltransferase (HMT) ESET is an integral component of the corepressor Alien complex and the Alien/ESET complex is recruited to both sites, the E2F1 and the nTRE site of the E2F1 gene while the recruitment to the negative thyroid hormone response element (nTRE) is induced by the ligand-bound TR beta 1 within the E2F1 gene promoter. We show that, overexpression of ESET promotes, whereas knockdown of ESET releases, the inhibition of TR beta 1-regulated gene transcription upon T3 stimulation; and H3K9 methylation is required for TR beta 1-repressed transcription. Furthermore, depletion of ESET impairs thyroid hormone-repressed proliferation as well as the G1/S transition of the cell cycle. Taken together, our data indicate that ESET is involved in TR beta 1-mediated transcription repression and provide a molecular basis of thyroid hormone-induced repression of proliferation. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Hong, Wei; Niu, Wenyan; Yao, Zhi] Tianjin Med Univ, Dept Immunol, Tianjin 300070, Peoples R China.
[Hong, Wei; Li, Jinru; Wang, Bo] Tianjin Med Univ, Coll Basic Med, Tianjin 300070, Peoples R China.
[Chen, Linfeng] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Baniahmad, Aria] Jena Univ Hosp, Inst Human Genet, D-07740 Jena, Germany.
RP Hong, W (reprint author), Tianjin Med Univ, Dept Immunol, Tianjin 300070, Peoples R China.
EM hongwei@tijmu.edu.cn; aban@mti.uni-jena.de
FU Tianjin Municipal Science and Technology Commission [09JCYBJC09800,
09ZCZDSF04500]; National Basic Research Program [2009CB918903]; DFG
[1457/3]; German Research Council
FX We thank David Fisher for critically reading the manuscript. This work
was supported by Grants 09JCYBJC09800 and 09ZCZDSF04500 from the Tianjin
Municipal Science and Technology Commission, a Grant 2009CB918903 of
National Basic Research Program and DFG 1457/3 from the German Research
Council.
NR 22
TC 5
Z9 5
U1 0
U2 11
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 DEC 2
PY 2011
VL 415
IS 4
BP 650
EP 655
DI 10.1016/j.bbrc.2011.10.130
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 861OT
UT WOS:000298029800022
PM 22079090
ER
PT J
AU Eikermann, M
Vetrivelan, R
Grosse-Sundrup, M
Henry, ME
Hoffmann, U
Yokota, S
Saper, CB
Chamberlin, NL
AF Eikermann, Matthias
Vetrivelan, Ramalingam
Grosse-Sundrup, Martina
Henry, Mark E.
Hoffmann, Ulrike
Yokota, Shigefumi
Saper, Clifford B.
Chamberlin, Nancy L.
TI The ventrolateral preoptic nucleus is not required for isoflurane
general anesthesia
SO BRAIN RESEARCH
LA English
DT Article
DE Hypothalamus; Isoflurane; Rat; Sleep; Sleep deprivation
ID EYE-MOVEMENT SLEEP; RIGHTING REFLEX; BASAL FOREBRAIN; ADENOSINE;
NEURONS; DEPRIVATION; ACTIVATION; RECEPTORS; PATHWAYS; STATE
AB Neurons of the ventrolateral preoptic nucleus (VLPO) promote sleep and VLPO loss produces insomnia. Previous studies show that general anesthetics including isoflurane activate VLPO neurons, and may contribute to their sedative effects. However, it is not clear to what extent the activation of VLPO neurons contributes to general anesthesia. We tested whether destruction of the VLPO neurons would affect the onset, depth, or recovery from isoflurane's general anesthetic effects. The VLPO was ablated in 25 rats by bilateral local injection of orexin-saporin, and polysomnography was performed to measure baseline sleep loss and responses to isoflurane anesthesia at 1% and 2%. Eight rats received sham (saline) injections. We measured isoflurane effects on time to loss of righting reflex, onset of continuous slow wave activity, and burst suppression; burst-suppression ratio; and time to recovery of righting reflex and desynchronized EEG. VLPO neuron cell loss was quantified by post hoc histology. Loss of VLPO neurons as well as lesion size were associated with cumulative sleep loss (r=0.77 and r=0.62, respectively), and cumulative sleep loss was the strongest predictor of high sensitivity to anesthesia, expressed as decreased time to loss of righting reflex (-0.59), increased burst-suppression ratio (r=0.52), and increased emergence time (r=0.54); an interaction-effect of isoflurane dose was observed (burst-suppression ratio: p<0.001). We conclude that the sleep loss caused by ablation of VLPO neurons sensitizes animals to the general anesthetic effects of isoflurane, but that the sedation produced by VLPO neurons themselves is not required for isoflurane anesthesia. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Vetrivelan, Ramalingam; Grosse-Sundrup, Martina; Henry, Mark E.; Hoffmann, Ulrike; Yokota, Shigefumi; Saper, Clifford B.; Chamberlin, Nancy L.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Eikermann, Matthias; Vetrivelan, Ramalingam; Grosse-Sundrup, Martina; Henry, Mark E.; Hoffmann, Ulrike; Yokota, Shigefumi; Saper, Clifford B.; Chamberlin, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA.
[Eikermann, Matthias; Grosse-Sundrup, Martina] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA.
[Eikermann, Matthias] Univ Klinikum Essen, Klin Anasthesie & Intens Med, Essen, Germany.
[Yokota, Shigefumi] Shimane Univ, Sch Med, Dept Anat & Morphol Neurosci, Izumo, Shimane 6938501, Japan.
RP Chamberlin, NL (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, 330 Brookline Ave,E-711 CLS, Boston, MA 02215 USA.
EM nchamber@bidmc.harvard.edu
FU National Institute of Health (Bethesda, MD, USA) [P50 HL060292,
HL095491, AG09975, NS072337]; German Research Council [DFG-EI684/2-1]
FX This work was supported by grants from the National Institute of Health
(Bethesda, MD, USA, P50 HL060292, HL095491, AG09975 and NS072337), and a
grant from the German Research Council (DFG-EI684/2-1).
NR 26
TC 7
Z9 7
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD DEC 2
PY 2011
VL 1426
BP 30
EP 37
DI 10.1016/j.brainres.2011.10.018
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 859ST
UT WOS:000297896800003
PM 22041226
ER
PT J
AU Treusch, S
Hamamichi, S
Goodman, JL
Matlack, KES
Chung, CY
Baru, V
Shulman, JM
Parrado, A
Bevis, BJ
Valastyan, JS
Han, H
Lindhagen-Persson, M
Reiman, EM
Evans, DA
Bennett, DA
Olofsson, A
DeJager, PL
Tanzi, RE
Caldwell, KA
Caldwell, GA
Lindquist, S
AF Treusch, Sebastian
Hamamichi, Shusei
Goodman, Jessica L.
Matlack, Kent E. S.
Chung, Chee Yeun
Baru, Valeriya
Shulman, Joshua M.
Parrado, Antonio
Bevis, Brooke J.
Valastyan, Julie S.
Han, Haesun
Lindhagen-Persson, Malin
Reiman, Eric M.
Evans, Denis A.
Bennett, David A.
Olofsson, Anders
DeJager, Philip L.
Tanzi, Rudolph E.
Caldwell, Kim A.
Caldwell, Guy A.
Lindquist, Susan
TI Functional Links Between A beta Toxicity, Endocytic Trafficking, and
Alzheimer's Disease Risk Factors in Yeast
SO SCIENCE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ALPHA-SYNUCLEIN; SACCHAROMYCES-CEREVISIAE;
ENDOPLASMIC-RETICULUM; IDENTIFIES VARIANTS; COMMON VARIANTS; PEPTIDE;
OLIGOMERS; MEMBRANE; CELLS
AB A beta (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled A beta toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to A beta was previously unknown. The factors identified in yeast modified A beta toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, A beta impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between A beta, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.
C1 [Treusch, Sebastian; Hamamichi, Shusei; Goodman, Jessica L.; Matlack, Kent E. S.; Chung, Chee Yeun; Baru, Valeriya; Bevis, Brooke J.; Valastyan, Julie S.; Han, Haesun; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Treusch, Sebastian; Matlack, Kent E. S.; Baru, Valeriya; Valastyan, Julie S.; Lindquist, Susan] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA.
[Hamamichi, Shusei; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA.
[Shulman, Joshua M.; DeJager, Philip L.] Brigham & Womens Hosp, Inst Neurosci, Program Translat NeuroPsychiat Genom, Dept Neurol, Boston, MA 02115 USA.
[Shulman, Joshua M.; DeJager, Philip L.] Brigham & Womens Hosp, Inst Neurosci, Program Translat NeuroPsychiat Genom, Dept Psychiat, Boston, MA 02115 USA.
[Valastyan, Julie S.; DeJager, Philip L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Shulman, Joshua M.; DeJager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Parrado, Antonio; Tanzi, Rudolph E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA.
[Lindhagen-Persson, Malin; Olofsson, Anders] Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden.
[Reiman, Eric M.] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ 85004 USA.
[Reiman, Eric M.] Arizona Alzheimers Consortium, Phoenix, AZ 85004 USA.
[Reiman, Eric M.] Univ Arizona, Banner Alzheimers Inst, Phoenix, AZ 85006 USA.
[Reiman, Eric M.] Univ Arizona, Dept Psychiat, Phoenix, AZ 85006 USA.
[Evans, Denis A.] Rush Univ, Med Ctr, Dept Internal Med, Rush Inst Hlth Aging, Chicago, IL 60612 USA.
[Bennett, David A.] Rush Univ, Med Ctr, Dept Neurol Sci, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
RP Lindquist, S (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM lindquist_admin@wi.mit.edu
FU Howard Hughes Medical Institute; National Research Service Award
fellowship [F32 NS067782-02]; Cure Alzheimer's Fund; NIH [K08AG034290,
P30AG10161, R01AG15819, R01AG17917]; Kempe foundation; Alzheimerfonden
FX We thank L. Chibnik, B. Keenan, and D. Ng for helpful discussions; D.
Wittrup, V. Lee, M. Vidal, and C. Link for materials; and J. Corneveaux,
M. Huentelman, and other Translational Genomics investigators for
assistance with the human study cohorts and participants in the
Religious Orders Study and the Rush Memory and Aging Project. This work
was supported by a Howard Hughes Medical Institute Collaborative
Innovation Award; National Research Service Award fellowship F32
NS067782-02; the Cure Alzheimer's Fund; NIH grants K08AG034290,
P30AG10161, R01AG15819, and R01AG17917; the Kempe foundation; and
Alzheimerfonden. This paper is dedicated to Nell Matheney, Zhao Xindi,
Rochelle Glatt, Matyas Topolszki, their families, and the countless
other victims of Alzheimer's disease.
NR 42
TC 137
Z9 138
U1 3
U2 36
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD DEC 2
PY 2011
VL 334
IS 6060
BP 1241
EP 1245
DI 10.1126/science.1213210
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 855HD
UT WOS:000297553600041
PM 22033521
ER
PT J
AU Anastasiou, D
Poulogiannis, G
Asara, JM
Boxer, MB
Jiang, JK
Shen, M
Bellinger, G
Sasaki, AT
Locasale, JW
Auld, DS
Thomas, CJ
Vander Heiden, MG
Cantley, LC
AF Anastasiou, Dimitrios
Poulogiannis, George
Asara, John M.
Boxer, Matthew B.
Jiang, Jian-kang
Shen, Min
Bellinger, Gary
Sasaki, Atsuo T.
Locasale, Jason W.
Auld, Douglas S.
Thomas, Craig J.
Vander Heiden, Matthew G.
Cantley, Lewis C.
TI Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes
to Cellular Antioxidant Responses
SO SCIENCE
LA English
DT Article
ID OXIDATIVE STRESS; TUMOR-SUPPRESSOR; CELLS; ROS; METABOLISM; CANCER;
ISOFORM; PROTEIN
AB Control of intracellular reactive oxygen species (ROS) concentrations is critical for cancer cell survival. We show that, in human lung cancer cells, acute increases in intracellular concentrations of ROS caused inhibition of the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation of Cys(358). This inhibition of PKM2 is required to divert glucose flux into the pentose phosphate pathway and thereby generate sufficient reducing potential for detoxification of ROS. Lung cancer cells in which endogenous PKM2 was replaced with the Cys(358) to Ser(358) oxidation-resistant mutant exhibited increased sensitivity to oxidative stress and impaired tumor formation in a xenograft model. Besides promoting metabolic changes required for proliferation, the regulatory properties of PKM2 may confer an additional advantage to cancer cells by allowing them to withstand oxidative stress.
C1 [Anastasiou, Dimitrios; Poulogiannis, George; Asara, John M.; Bellinger, Gary; Sasaki, Atsuo T.; Locasale, Jason W.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA 02115 USA.
[Anastasiou, Dimitrios; Poulogiannis, George; Sasaki, Atsuo T.; Locasale, Jason W.; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Asara, John M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Boxer, Matthew B.; Jiang, Jian-kang; Shen, Min; Auld, Douglas S.; Thomas, Craig J.] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA.
[Bellinger, Gary; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Vander Heiden, Matthew G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Cantley, LC (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA 02115 USA.
EM lewis_cantley@hms.harvard.edu
RI Cantley, Lewis/D-1800-2014;
OI Cantley, Lewis/0000-0002-1298-7653; Locasale, Jason/0000-0002-7766-3502
FU Japanese Society for the Promotion of Science; Kanae Foundation for
Research Abroad; NIH [R03MH085679, 1P30CA147882, R01-GM056203-13,
P01-CA089021, P01-CA117969-04]; Burroughs Wellcome Fund; Damon Runyon
Cancer Research Foundation; Smith family; Starr Cancer Consortium;
Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research; National Human Genome Research Institute,
NIH
FX We thank V. Toxavidis and J. Tigges (Beth Israel Deaconess Medical
Center flow cytometry facility) for support with flow cytometry
applications; X. Yang and S. Breitkopf for technical assistance with
mass spectrometry; Ross Dickins and Scott Lowe (Cold Spring Harbor
Laboratory) for the gift of tamoxifen-inducible Cre-expressing
retroviral plasmid; and C. Benes, N. Wu, A. Shaywitz, B. Emerling, A.
Saci, G. DeNicola, K. Courtney, A. Couvillon, S. Soltoff, A. Carracedo,
A. Grassian, J. Brugge, and members of the Cantley lab for helpful
discussions. L. C. C. is a cofounder of Agios Pharmaceuticals, a company
that seeks to develop novel therapeutics that target cancer metabolism.
G. P. is a Pfizer Fellow of the Life Sciences Research Foundation. A. T.
S. is a Genentech Fellow and supported by the Japanese Society for the
Promotion of Science and the Kanae Foundation for Research Abroad. M. G.
V. H. is supported by the NIH (R03MH085679 and 1P30CA147882), the
Burroughs Wellcome Fund, the Damon Runyon Cancer Research Foundation,
and the Smith family. This work was supported by grants from the NIH
(R01-GM056203-13, P01-CA089021, and P01-CA117969-04 to L. C. C), the
Starr Cancer Consortium (L. C. C. and M. G. V. H.), the Molecular
Libraries Initiative of the National Institutes of Health Roadmap for
Medical Research, and the Intramural Research Program of the National
Human Genome Research Institute, NIH (M. B. B., J. J., M. S., D. S. A.,
and C. J. T.). We apologize to colleagues whose work we could not cite
because of space limitations.
NR 28
TC 371
Z9 379
U1 10
U2 91
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD DEC 2
PY 2011
VL 334
IS 6060
BP 1278
EP 1283
DI 10.1126/science.1211485
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 855HD
UT WOS:000297553600051
PM 22052977
ER
PT J
AU Margalit, DN
Mamon, HJ
Ancukiewicz, M
Kobayashi, W
Ryan, DP
Blaszkowsky, LS
Clark, J
Willett, CG
Hong, TS
AF Margalit, Danielle N.
Mamon, Harvey J.
Ancukiewicz, Marek
Kobayashi, Wendy
Ryan, David P.
Blaszkowsky, Lawrence S.
Clark, Jeffrey
Willett, Christopher G.
Hong, Theodore S.
TI TOLERABILITY OF COMBINED MODALITY THERAPY FOR RECTAL CANCER IN ELDERLY
PATIENTS AGED 75 YEARS AND OLDER
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Colorectal cancer; Elderly; Chemoradiation; Combined modality therapy;
Treatment tolerability
ID PREOPERATIVE RADIOTHERAPY; RANDOMIZED-TRIAL; STAGE-II; ADJUVANT
CHEMOTHERAPY; POSTOPERATIVE CHEMORADIOTHERAPY; GERIATRIC ASSESSMENT;
SURVIVAL; POPULATION; IMPACT; CHEMORADIATION
AB Purpose: To determine the rate of treatment deviations during combined modality therapy for rectal cancer in elderly patients aged 75 years and older.
Methods and Materials: We reviewed the records of consecutively treated patients with rectal cancer aged 75 years and older treated with combined modality therapy at Massachusetts General Hospital and Brigham & Women's Hospital from 2002 to 2007. The primary endpoint was the rate of treatment deviation, defined as a treatment break, dose reduction, early discontinuation of therapy, or hospitalization during combined modality therapy. Patient comorbidity was rated using the validated Adult Comorbidity Evaluation 27 Test (ACE-27) comorbidity index. Fisher's exact test and the Mantel-Haenszel trend test were used to identify predictors of treatment tolerability.
Results: Thirty-six eligible patients had a median age of 79.0 years (range, 75-87 years); 53% (19/36) had no or mild comorbidity and 47% (17/36) had moderate or severe comorbidity. In all, 58% of patients (21/36) were treated with preoperative chemoradiotherapy (CRT) and 33% (12/36) with postoperative CRT. Although 92% patients (33/36) completed the planned radiotherapy (RT) dose, 25% (9/36) required an RT-treatment break, 11% (4/36) were hospitalized, and 33% (12/36) had a dose reduction, break, or discontinuation of concurrent chemotherapy. In all, 39% of patients (14/36) completed >= 4 months of adjuvant chemotherapy, and 17% (6/36) completed therapy without a treatment deviation. More patients with no to mild comorbidity completed treatment than did patients with moderate to severe comorbidity (21% vs. 12%, p = 0.66). The rate of deviation did not differ between patients who had preoperative or postoperative CRT (19% vs. 17%, p = 1.0).
Conclusions: The majority of elderly patients with rectal cancer in this series required early termination of treatment, treatment interruptions, or dose reductions. These data suggest that further intensification of combined modality therapy for rectal cancer should be performed with caution in elderly patients, who require aggressive supportive care to complete treatment. (C) 2011 Elsevier Inc.
C1 [Ancukiewicz, Marek; Kobayashi, Wendy; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Margalit, Danielle N.] Harvard Radiat Oncol Program, Boston, MA USA.
[Mamon, Harvey J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Willett, Christopher G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA.
[Ryan, David P.; Blaszkowsky, Lawrence S.; Clark, Jeffrey] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Hong, TS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA.
EM tshong1@partners.org
NR 33
TC 15
Z9 15
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD DEC 1
PY 2011
VL 81
IS 5
BP E735
EP E741
DI 10.1016/j.ijrobp.2010.12.056
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 973DK
UT WOS:000306334300008
PM 21377289
ER
PT J
AU Sher, DJ
Posner, MR
Tishler, RB
Sarlis, NJ
Haddad, RI
Holupka, EJ
Devlin, PM
AF Sher, David J.
Posner, Marshall R.
Tishler, Roy B.
Sarlis, Nicholas J.
Haddad, Robert I.
Holupka, Edward J.
Devlin, Phillip M.
TI RELATIONSHIP BETWEEN RADIATION TREATMENT TIME AND OVERALL SURVIVAL AFTER
INDUCTION CHEMOTHERAPY FOR LOCALLY ADVANCED HEAD-AND-NECK CARCINOMA: A
SUBSET ANALYSIS OF TAX 324
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Head-and-neck cancer; Chemoradiotherapy; Induction chemotherapy;
Radiation treatment time; Radiation field design
ID 1ST REPORT; CANCER; RADIOTHERAPY; THERAPY; FLUOROURACIL; CISPLATIN;
PREDICTOR; DOCETAXEL; TRIAL
AB Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC).
Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of >= 70 Gy. Radiotherapy treatment time was analyzed as binary (<= 8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR).
Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR.
Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC. (C) 2011 Elsevier Inc.
C1 [Sher, David J.; Tishler, Roy B.; Devlin, Phillip M.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Haddad, Robert I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Posner, Marshall R.] Mt Sinai Sch Med, Div Hematol Oncol, New York, NY USA.
[Sarlis, Nicholas J.] Sanofi Aventis US, Bridgewater, NJ USA.
[Haddad, Robert I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Holupka, Edward J.] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA.
RP Sher, DJ (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM dsher@partners.org
FU Sanofi-Aventis Groupe; Sanofi-Aventis
FX This analysis was not funded by Sanofi-Aventis US and was performed
independently by the authors. However, the parent clinical trial (TAX
324) was sponsored by Sanofi-Aventis Groupe. M.R.P. has received
honoraria and research funding and served as a consultant for
Sanofi-Aventis. R.B.T. has received honoraria and served as a consultant
for Sanofi-Aventis. N.J.S. has received salary from and holds stock and
stock options in Sanofi-Aventis. R.I.H. has received honoraria and
served as a consultant for Sanofi-Aventis.
NR 15
TC 19
Z9 19
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD DEC 1
PY 2011
VL 81
IS 5
BP E813
EP E818
DI 10.1016/j.ijrobp.2010.12.005
PG 6
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 973DK
UT WOS:000306334300018
PM 21300455
ER
PT J
AU Sher, DJ
Wee, JO
Punglia, RS
AF Sher, David J.
Wee, Jon O.
Punglia, Rinaa S.
TI COST-EFFECTIVENESS ANALYSIS OF STEREOTACTIC BODY RADIOTHERAPY AND
RADIOFREQUENCY ABLATION FOR MEDICALLY INOPERABLE, EARLY-STAGE NON-SMALL
CELL LUNG CANCER
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Stereotactic radiation therapy; Inoperable lung cancer;
Cost-effectiveness analysis
ID PROSPECTIVE PHASE-II; RADIATION-THERAPY; CONFORMAL RADIOTHERAPY; NODAL
IRRADIATION; CARCINOMA; CHEMOTHERAPY; TOXICITY; SURVIVAL; TRIALS; TUMORS
AB Purpose: The standard management of medically inoperable Stage I non-small-cell lung cancer (NSCLC) conventionally has been fractionated three-dimensional conformal radiation therapy (3D-CRT). The relatively poor local control rate and inconvenience associated with this therapy have prompted the development of stereotactic body radiotherapy (SBRT), a technique that delivers very high doses of irradiation typically over 3 to 5 sessions. Radiofrequency ablation (RFA) has also been investigated as a less costly, single-day therapy that thermally ablates small, peripheral tumors. The cost-effectiveness of these three techniques has never been compared.
Methods and Materials: We developed a Markov model to describe health states of 65-year-old men with medically inoperable NSCLC after treatment with 3D-CRT, SBRT, and RFA. Given their frail state, patients were assumed to receive supportive care after recurrence. Utility values, recurrence risks, and costs were adapted from the literature. Sensitivity analyses were performed to model uncertainty in these parameters.
Results: The incremental cost-effectiveness ratio for SBRT over 3D-CRT was $6,000/quality-adjusted life-year, and the incremental cost-effectiveness ratio for SBRT over RFA was $14,100/quality-adjusted life-year. One-way sensitivity analysis showed that the results were robust across a range of tumor sizes, patient utility values, and costs. This result was confirmed with probabilistic sensitivity analyses that varied local control rates and utilities.
Conclusion: In comparison to 3D-CRT and RFA, SBRT was the most cost-effective treatment for medically inoperable NSCLC over a wide range of treatment and disease assumptions. On the basis of efficacy and cost, SBRT should be the primary treatment approach for this disease. (C) 2011 Elsevier Inc.
C1 [Sher, David J.; Punglia, Rinaa S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Sher, David J.; Punglia, Rinaa S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
RP Sher, DJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM dsher@lroc.harvard.edu
FU National Institutes of Health [1K07 CA118629 (R.S.P.).]
FX Supported in part from National Institutes of Health grant 1K07 CA118629
(R.S.P.).
NR 26
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U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD DEC 1
PY 2011
VL 81
IS 5
BP E767
EP E774
DI 10.1016/j.ijrobp.2010.10.074
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 973DK
UT WOS:000306334300012
PM 21300476
ER
PT J
AU Wang, D
Bosch, W
Kirsch, DG
Al Lozi, R
El Naqa, I
Roberge, D
Finkelstein, SE
Petersen, I
Haddock, K
Chen, YLE
Saito, NG
Hitchcock, YJ
Wolfson, AH
Delaney, TF
AF Wang, Dian
Bosch, Walter
Kirsch, David G.
Al Lozi, Rawan
El Naqa, Issam
Roberge, David
Finkelstein, Steven E.
Petersen, Ivy
Haddock, Kmichael
Chen, Yen-Lin E.
Saito, Naoyuki G.
Hitchcock, Ying J.
Wolfson, Aaron H.
Delaney, Thomas F.
TI VARIATION IN THE GROSS TUMOR VOLUME AND CLINICAL TARGET VOLUME FOR
PREOPERATIVE RADIOTHERAPY OF PRIMARY LARGE HIGH-GRADE SOFT TISSUE
SARCOMA OF THE EXTREMITY AMONG RTOG SARCOMA RADIATION ONCOLOGISTS
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Sarcoma; Target definition; Radiotherapy
ID POSTOPERATIVE RADIOTHERAPY; ALGORITHM
AB Purpose: To evaluate variability in the definition of preoperative radiotherapy gross tumor volume (GTV) and clinical target volume (CTV) delineated by sarcoma radiation oncologists.
Methods and Materials: Extremity sarcoma planning CT images along with the corresponding diagnostic MRI from two patients were distributed to 10 Radiation Therapy Oncology Group sarcoma radiation oncologists with instructions to define GTV and CTV using standardized guidelines. The CT data with contours were then returned for central analysis. Contours representing statistically corrected 95% (V95) and 100% (V100) agreement were computed for each structure.
Results: For the GTV, the minimum, maximum, mean (SD) volumes (mL) were 674, 798, 752 +/- 35 for the lower extremity case and 383, 543, 447 +/- 46 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 882, 761, and 752 for the lower, and 587, 461, and 455 for the upper extremity, respectively. The overall GTV agreement was judged to be almost perfect in both lower and upper extremity cases (kappa = 0.9 [p < 0.0001] and kappa = 0.86 [p < 0.0001]). For the CTV, the minimum, maximum, mean (SD) volumes (mL) were 1145, 1911, 1605 +/- 211 for the lower extremity case and 637, 1246, 1006 +/- 180 for the upper extremity case. The volume (cc) of the union, V95, and V100 were 2094, 1609, and 1593 for the lower, and 1533, 1020, and 965 for the upper extremity cases, respectively. The overall CTV agreement was judged to be almost perfect in the lower extremity case (kappa = 0.85 [p < 0.0001]) but only substantial in the upper extremity case (kappa = 0.77 [p < 0.0001]).
Conclusions: Almost perfect agreement existed in the GTV of these two representative cases. Tshere was no significant disagreement in the CTV of the lower extremity, but variation in the CTV of upper extremity was seen, perhaps related to the positional differences between the planning CT and the diagnostic MRI. (C) 2011 Elsevier Inc.
C1 [Wang, Dian] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53045 USA.
[Bosch, Walter; Al Lozi, Rawan; El Naqa, Issam] Washington Univ, St Louis, MO USA.
[Kirsch, David G.] Duke Univ, Durham, NC USA.
[Roberge, David] McGill Univ, Ctr Hlth, Montreal, PQ, Canada.
[Finkelstein, Steven E.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Petersen, Ivy; Haddock, Kmichael] Mayo Clin, Rochester, MN USA.
[Chen, Yen-Lin E.; Delaney, Thomas F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Saito, Naoyuki G.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Hitchcock, Ying J.] Univ Utah, Salt Lake City, UT USA.
[Wolfson, Aaron H.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
RP Wang, D (reprint author), Med Coll Wisconsin, Dept Radiat Oncol, 8701 Watertown Plank Rd, Milwaukee, WI 53045 USA.
EM dwang@mcw.edu
FU ATC from the National Institutes of Health [U24 CA81647]
FX This study is supported by ATC Grant U24 CA81647 from the National
Institutes of Health.
NR 16
TC 8
Z9 8
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD DEC 1
PY 2011
VL 81
IS 5
BP E775
EP E780
DI 10.1016/j.ijrobp.2010.11.033
PG 6
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 973DK
UT WOS:000306334300013
PM 21277104
ER
PT J
AU Patti, JA
AF Patti, John A.
TI The Demand for Proof of Quality
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 3
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 DEC
PY 2011
VL 8
IS 12
BP 817
EP 817
DI 10.1016/j.jacr.2011.10.015
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KG
UT WOS:000306202200001
PM 22136992
ER
PT J
AU Boland, GWL
Thrall, JH
Gazelle, GS
Samir, A
Rosenthal, DI
Dreyer, KJ
Alkasab, TK
AF Boland, Giles W. L.
Thrall, James H.
Gazelle, G. Scott
Samir, Anthony
Rosenthal, Daniel I.
Dreyer, Keith J.
Alkasab, Tarik K.
TI Decision Support for Radiologist Report Recommendations
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Editorial Material
ID SYSTEMS
C1 [Boland, Giles W. L.; Thrall, James H.; Gazelle, G. Scott; Samir, Anthony; Rosenthal, Daniel I.; Dreyer, Keith J.; Alkasab, Tarik K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, White Bldg 270C,55 Fruit St, Boston, MA 02114 USA.
EM gboland@partners.org
OI Alkasab, Tarik/0000-0002-4433-9482; Samir, Anthony/0000-0002-7801-8724
NR 26
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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 DEC
PY 2011
VL 8
IS 12
BP 819
EP 823
DI 10.1016/j.jacr.2011.08.003
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KG
UT WOS:000306202200003
PM 22136994
ER
PT J
AU Borra, RJH
Sorensen, AG
AF Borra, Ronald J. H.
Sorensen, A. Gregory
TI Incidental Findings in Brain MRI Research: What Do We Owe Our Subjects?
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE Incidental imaging findings; imaging algorithms; ethics
ID PRACTICAL CONSIDERATIONS; IMAGING RESEARCH; IMAGES
AB Concern regarding incidental findings on brain MRI studies has been increasing with the growing use of MRI as tool for scientific investigation. In this article, the authors provide an overview of possible approaches to address incidental findings. Incidental findings are surprisingly common (5%-20% of all examinations), although the percentage of clinically serious abnormalities is low (0.3%-3.4%). At present, there is no consensus concerning the optimal strategy on how to deal with incidental findings, in particular how to fulfill ethical responsibilities appropriately within the constraints of available resources. There are a variety of responses possible, and currently, reasonable guidelines exist for formulating a plan tailored to the needs of each institution that will meet the reasonable expectations of subjects participating in brain research studies.
C1 [Borra, Ronald J. H.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Borra, Ronald J. H.; Sorensen, A. Gregory] Harvard Univ, Sch Med, Boston, MA USA.
[Borra, Ronald J. H.] Turku Univ Hosp, Med Imaging Ctr SW Finland, FIN-20520 Turku, Finland.
RP Borra, RJH (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA.
EM ronald.borra@tyks.fi
OI Borra, Ronald/0000-0001-8072-1243
FU Sigrid Juselius Foundation; Instrumentarium Research Foundation; Academy
of Finland; Paulo Foundation; Finnish Medical Foundation; AstraZeneca;
Exelixis; Genentech; Novartis; Schering-Plough; Siemens;
Takeda-Millennium
FX Dr Borra is supported by grants from the Sigrid Juselius Foundation, the
Instrumentarium Research Foundation, the Academy of Finland, the Paulo
Foundation, and the Finnish Medical Foundation. Dr Sorensen has received
commercial research grants from AstraZeneca, Exelixis, Genentech,
Novartis, Schering-Plough, Siemens, and Takeda-Millennium and is a
consultant or advisory board member for EPIX Pharmaceuticals,
AstraZeneca, Genentech, Takeda-Millennium, Bayer/Schering, Olea Medical,
Mitsubishi, Novartis, and Siemens.
NR 28
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U1 0
U2 5
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 DEC
PY 2011
VL 8
IS 12
BP 848
EP 852
DI 10.1016/j.jacr.2011.08.009
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KG
UT WOS:000306202200011
PM 22137002
ER
PT J
AU Casalino, DD
Remer, EM
Arellano, RS
Bishoff, JT
Coursey, CA
Dighe, M
Eggli, DF
Fulgham, P
Israel, GM
Lazarus, E
Leyendecker, JR
Nikolaidis, P
Papanicolaou, N
Prasad, S
Ramchandani, P
Sheth, S
Vikram, R
AF Casalino, David D.
Remer, Erick M.
Arellano, Ronald S.
Bishoff, Jay T.
Coursey, Courtney A.
Dighe, Manjiri
Eggli, Douglas F.
Fulgham, Pat
Israel, Gary M.
Lazarus, Elizabeth
Leyendecker, John R.
Nikolaidis, Paul
Papanicolaou, Nicholas
Prasad, Srinivasa
Ramchandani, Parvati
Sheth, Sheila
Vikram, Raghunandan
TI ACR Appropriateness Criteria (R) Posttreatment Follow-up of Prostate
Cancer
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE Appropriateness Criteria; prostate; prostate cancer; posttreatment;
imaging
ID ASSESSING BIOCHEMICAL FAILURE; POSITRON-EMISSION-TOMOGRAPHY;
EXTERNAL-BEAM RADIOTHERAPY; ULTRASOUND-GUIDED BIOPSY; LYMPH-NODE
METASTASES; RADICAL PROSTATECTOMY; LOCAL RECURRENCE; RADIATION-THERAPY;
BONE-SCINTIGRAPHY; COMPUTED-TOMOGRAPHY
AB Although prostate cancer can be effectively treated, recurrent or residual disease after therapy is not uncommon and is usually detected by a rise in prostate-specific antigen. Patients with biochemical prostate-specific antigen relapse should undergo a prompt search for the presence of local recurrence or distant metastatic disease, each requiring different forms of therapy. Various imaging modalities and image-guided procedures may be used in the evaluation of these patients. Literature on the indications and usefulness of these radiologic studies and procedures in specific clinical settings is reviewed.
The ACR Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
C1 [Casalino, David D.; Nikolaidis, Paul] Northwestern Univ, Chicago, IL 60611 USA.
[Remer, Erick M.] Cleveland Clin, Cleveland, OH 44106 USA.
[Arellano, Ronald S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bishoff, Jay T.] Intermt Urol Inst, Murray, UT USA.
[Bishoff, Jay T.; Fulgham, Pat] Amer Urol Assoc, Linthicum, MD USA.
[Coursey, Courtney A.] Emory Univ Hosp, Atlanta, GA 30322 USA.
[Dighe, Manjiri] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Eggli, Douglas F.] Penn State Univ, Hershey, PA USA.
[Eggli, Douglas F.] Soc Nucl Med, Reston, VA USA.
[Fulgham, Pat] Presbyterian Med Ctr, Dallas, TX USA.
[Israel, Gary M.] Yale Univ, Sch Med, New Haven, CT USA.
[Lazarus, Elizabeth] Rhode Isl Hosp, Providence, RI USA.
[Leyendecker, John R.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Papanicolaou, Nicholas; Ramchandani, Parvati] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Prasad, Srinivasa] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Sheth, Sheila] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Vikram, Raghunandan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Casalino, DD (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA.
EM david.casalino@nmff.org
NR 75
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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 DEC
PY 2011
VL 8
IS 12
BP 863
EP 871
DI 10.1016/j.jacr.2011.09.003
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KG
UT WOS:000306202200014
PM 22137005
ER
PT J
AU Swartz, J
King, HS
Rider, EA
AF Swartz, Julia
King, Howard S.
Rider, Elizabeth A.
TI Behavioral Health Screening and Referral in the Pediatric Office
SO PEDIATRIC ANNALS
LA English
DT Article
ID PRIMARY-CARE; COMMUNICATION; COMPETENCES; CHILDREN
C1 [Swartz, Julia; Rider, Elizabeth A.] CEHL, Holbrook, MA USA.
[Swartz, Julia; King, Howard S.] New Direct Behav Hlth Compass Med PC, Holbrook, MA USA.
[Rider, Elizabeth A.] Harvard Univ, Sch Med, Boston, MA USA.
[Rider, Elizabeth A.] Childrens Hosp, Acad Programs, Inst Professionalism & Eth Practice, Boston, MA 02115 USA.
[Rider, Elizabeth A.] Massachusetts Gen Hosp, Programs Commun Skills, Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA.
RP Rider, EA (reprint author), 1153 Ctr St,Suite 31, Boston, MA 02130 USA.
EM erider@hms.harvard.edu
FU Sydney R. Baer, Jr. Foundation; Massachusetts Department of Mental
Health; Alden Trust; Project INTERFACE (Newton Public Schools); Project
INTERFACE (US Department of Education); Locke Educational Fund
FX The authors acknowledge the Sydney R. Baer, Jr. Foundation,
Massachusetts Department of Mental Health, The Alden Trust, Project
INTERFACE (Newton Public Schools and the US Department of Education),
and the Locke Educational Fund for their generous funding, as well as
Gordon Harper, MD; David Robinson, EdD; Alyce Getler, PsyD; and H. E.
Longmaid III, MD, for their insightful comments; Courtney Gomes, MEd,
for her help with initial treatment listings; and their course
participants, patients, and their families.
NR 25
TC 0
Z9 0
U1 2
U2 4
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0090-4481
J9 PEDIATR ANN
JI Pediatr. Annu.
PD DEC
PY 2011
VL 40
IS 12
BP 610
EP 616
DI 10.3928/00904481-20111103-07
PG 7
WC Pediatrics
SC Pediatrics
GA 965CO
UT WOS:000305743900007
PM 22148276
ER
PT J
AU Mason, ZD
Pearlman, J
Cooper, RA
Laferrier, JZ
AF Mason, Zachary D.
Pearlman, Jon
Cooper, Rory A.
Laferrier, Justin Z.
TI Comparison of prosthetic feet prescribed to active individuals using ISO
standards
SO PROSTHETICS AND ORTHOTICS INTERNATIONAL
LA English
DT Article
DE Prosthetic feet; testing of prosthetic and orthotic components
ID WHEELCHAIR-RELATED ACCIDENTS; UNITED-STATES; AMPUTEES; INJURY; SAFETY;
LIFE
AB Background: Little research has been done on the robustness of prosthetic feet prescribed to military personnel, and manufacturers are not required to test their products prior to sale. This is problematic because the prosthetic feet used by active individuals are subjected to loading conditions not seen in normal gait.
Objectives: To evaluate whether commercially available heavy-duty prosthetic feet intended for use by military personnel meet ISO 10328 standards.
Study Design: Bench testing of heavy-duty prosthetic feet using ISO 10328 standards.
Methods: Prosthetic feet from three different manufacturers were tested according to ISO 10328 standards, using a testing frame fitted with axial load and displacement transducers. Pass/fail information was recorded as well as the stiffness and creep of each foot before and after cyclic testing.
Results: All feet passed the ISO 10328 standards at the highest loading level, and some significant differences were found within a given model of prosthesis when comparing stiffness and creep before and after cyclic testing.
Conclusions: This study demonstrated that manufacturers of heavy-duty prosthetic feet adhere to the voluntary ISO 10328 standards. However, these standards may be insufficient because the tests simulate only idealized gait. Further development of the standards may be necessary to reproduce the circumstances that occur during extreme usage to ensure that prosthetic feet do not fail.
C1 [Mason, Zachary D.; Pearlman, Jon; Cooper, Rory A.; Laferrier, Justin Z.] Human Engn Res Labs, Pittsburgh, PA 15206 USA.
[Mason, Zachary D.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA.
[Pearlman, Jon; Cooper, Rory A.; Laferrier, Justin Z.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Pearlman, Jon; Cooper, Rory A.; Laferrier, Justin Z.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA.
RP Pearlman, J (reprint author), Human Engn Res Labs, 7180 Highland Dr 151R-1H, Pittsburgh, PA 15206 USA.
EM jlp46@pitt.edu
OI Pearlman, Jon/0000-0003-0830-9136
FU Telemedicine and Advanced Technology Research Center [W81XWH-07-1-0716]
FX This study was funded by the Telemedicine and Advanced Technology
Research Center under contract number W81XWH-07-1-0716.
NR 28
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Z9 0
U1 1
U2 8
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0309-3646
J9 PROSTHET ORTHOT INT
JI Prosthet. Orthot. Int.
PD DEC
PY 2011
VL 35
IS 4
BP 418
EP 424
DI 10.1177/0309364611421692
PG 7
WC Orthopedics; Rehabilitation
SC Orthopedics; Rehabilitation
GA 962TM
UT WOS:000305568000013
PM 22031596
ER
PT J
AU George, M
Fletcher, M
AF George, Maureen
Fletcher, Monica
TI Pulmonary rehabilitation in the management of COPD: more than one way to
skin a cat
SO PRIMARY CARE RESPIRATORY JOURNAL
LA English
DT Editorial Material
ID RESPIRATORY SOCIETY; PROGRAMS; DISEASE; IMPACT
C1 [Fletcher, Monica] Educ Hlth, Warwick CV34 4AB, England.
[George, Maureen] Univ Penn, Sch Nursing, Dept Family & Community Hlth, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA.
[George, Maureen] Ctr Global Womens Hlth, Philadelphia, PA USA.
RP Fletcher, M (reprint author), Educ Hlth, 10 Church St, Warwick CV34 4AB, England.
EM m.fletcher@educationforhealth.org
NR 16
TC 0
Z9 0
U1 0
U2 3
PU PRIMARY CARE RESPIRATORY SOC-PCRS UK
PI WATERBECK
PA EDITORIAL OFFICE, SMITHY HOUSE, WATERBECK, LOCKERBIE DG11 3EY, SCOTLAND
SN 1471-4418
J9 PRIM CARE RESP J
JI Prim. Care Respir. J.
PD DEC
PY 2011
VL 20
IS 4
BP 355
EP 356
DI 10.4104/pcrj.2011.00100
PG 2
WC Primary Health Care; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 945MT
UT WOS:000304279300005
PM 22089280
ER
PT J
AU Chou, SHY
Feske, SK
Simmons, SL
Konigsberg, RGJ
Orzell, SC
Marckmann, A
Bourget, G
Bauer, DJ
De Jager, PL
Du, R
Arai, K
Lo, EH
Ning, MM
AF Chou, S. H. -Y.
Feske, S. K.
Simmons, S. L.
Konigsberg, R. G. J.
Orzell, S. C.
Marckmann, A.
Bourget, G.
Bauer, D. J.
De Jager, P. L.
Du, R.
Arai, K.
Lo, E. H.
Ning, M. M.
TI Elevated Peripheral Neutrophils and Matrix Metalloproteinase 9 as
Biomarkers of Functional Outcome Following Subarachnoid Hemorrhage
SO TRANSLATIONAL STROKE RESEARCH
LA English
DT Article
DE Subarachnoid hemorrhage; Biomarker; Matrix metalloproteinase;
Inflammation; Neutrophils; Vasospasm; Outcome
ID MATRIX METALLOPROTEINASES; CEREBRAL VASOSPASM; EXTRACELLULAR
PROTEOLYSIS; PLASMINOGEN ACTIVATORS; BRAIN-INJURY; INFLAMMATION;
LEUKOCYTOSIS; ANEURYSM; ARTERIES; BURDEN
AB There is growing evidence supporting the role of inflammation in early brain injury and cerebral vasospasm following subarachnoid hemorrhage (SAH). Matrix metalloproteinases (MMPs) are released by inflammatory cells and can mediate early brain injury via disruption of the extracellular matrix and mediate vasospasm by cleaving endothelin-1 into vasoactive fragments. We hypothesize that inflammation marked by neutrophil elevation and MMP-9 release in human SAH is associated with vasospasm and with poor clinical outcome. We enrolled consecutive SAH subjects (N=55), banked serial blood and cerebrospinal fluid (CSF) samples, and evaluated their 3-month modified Rankin scores (mRS). Vasospasm was defined as >50% vessel caliber reduction on angiography 6-8 days post-SAH. A poor outcome was defined as mRS>2. We compared blood leukocyte and neutrophil counts during post-SAH days 0-14 with respect to vasospasm and 3-month outcome. In a subset of SAH subjects (N=35), we compared blood and CSF MMP-9 by enzyme-linked immunosorbent assay (ELISA) on post-SAH days 0-1, 2-3, 4-5, 6-8, and 10-14 with respect to vasospasm and to 3-month outcome. Persistent elevation of blood leukocyte (p=0.0003) and neutrophil (p=0.0002) counts during post-SAH days 0-14 are independently associated with vasospasm after adjustment for major confounders. In the same time period, blood neutrophil count (post-SAH days 2-3, p=0.018), blood MMP-9 (post-SAH days 4-5, p=0.045), and CSF MMP-9 (post-SAH days 2-3, p=0.05) are associated with poor 3-month SAH clinical outcome. Neutrophil count correlates with blood MMP-9 (post-SAH days 6-8, R=0.39; p=0.055; post-SAH days 10-14, R=0.79; p<0.0001), and blood MMP-9 correlates with CSF MMP-9 (post-SAH days 4-5, R=0.72; p=0.0002). Elevation of CSF MMP-9 during post-SAH days 0-14 is associated with poor 3-month outcome (p =0.0078). Neither CSF nor blood MMP-9 correlates with vasospasm. Early rise in blood neutrophil count and blood and CSF MMP-9 are associated with poor 3-month SAH clinical outcome. In blood, neutrophil count correlates with MMP-9 levels, suggesting that neutrophils may be an important source of blood MMP-9 early in SAH. Similarly, CSF and blood MMP-9 correlate positively early in the course of SAH, suggesting that blood may be an important source of CSF MMP-9. Blood and CSF MMP-9 are associated with clinical outcome but not with vasospasm, suggesting that MMP-9 may mediate brain injury independent of vasospasm in SAH. Future in vitro studies are needed to investigate the role of MMP-9 in SAH-related brain injury. Larger clinical studies are needed to validate blood and CSF MMP-9 as potential biomarkers for SAH outcome.
C1 [Arai, K.; Lo, E. H.; Ning, M. M.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Chou, S. H. -Y.; Feske, S. K.; De Jager, P. L.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Bourget, G.] Calif State Univ Fullerton, Dept Math, Boston, MA USA.
[Du, R.] Harvard Univ, Brigham & Womens Hosp, Dept Neurosurg, Sch Med, Boston, MA 02115 USA.
[Arai, K.; Lo, E. H.] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Lo, EH (reprint author), Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
EM lo@helix.mgh.harvard.edu; MingMing_Ning@hms.harvard.edu
RI Du, Rose/I-5402-2012; Chou, Sherry/G-5779-2015;
OI Du, Rose/0000-0003-2641-6496; Gould, Susannah/0000-0002-7434-4960
FU Deparment of Neurology, Brigham and Women's Hospital; American Heart
Association [10CRP2610341]; Harvard CTSC/NIH [5KL2RR025757]; NINDS
[K23-NS073806, R21-NS52498, R01-NS48422, R37-NS37074, P01-NS55104]
FX The authors thank Drs. F. A. Sorond and G. V. Henderson (Deparment of
Neurology, Brigham and Women's Hospital) for subject recruitment, Dr. A.
H. Ropper (Deparment of Neurology, Brigham and Women's Hospital) for
advice and funding support, and the Harvard Clinical Translational
Science Center for supporting study infrastructure.; This study was
sponsored by the American Heart Association (10CRP2610341, Chou),
Harvard CTSC/NIH (5KL2RR025757, Chou), NINDS (K23-NS073806, Chou;
R21-NS52498, Ning; R01-NS48422, Ning; R37-NS37074, Lo; P01-NS55104, Lo),
and a departmental research discretionary fund (Chou).
NR 36
TC 44
Z9 48
U1 1
U2 5
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 DEC
PY 2011
VL 2
IS 4
SI SI
BP 600
EP 607
DI 10.1007/s12975-011-0117-x
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 943YJ
UT WOS:000304163700017
PM 22207885
ER
PT J
AU Morse, LR
Xu, Y
Solomon, B
Boyle, L
Yoganathan, S
Stashenko, P
Battaglino, RA
AF Morse, Leslie R.
Xu, Yan
Solomon, Bethlehem
Boyle, Lara
Yoganathan, Subbiah
Stashenko, Philip
Battaglino, Ricardo A.
TI Severe Spinal Cord Injury Causes Immediate Multi-cellular Dysfunction at
the Chondro-Osseous Junction
SO TRANSLATIONAL STROKE RESEARCH
LA English
DT Article
DE Rehabilitation medicine; Spinal cord injury; Osteoporosis; Osteoblast;
Chondrocyte
ID BONE-MINERAL DENSITY; GROWTH-PLATE; ARTICULAR-CARTILAGE; OSTEOPOROSIS;
FRACTURES; KNEE; RATS; METABOLISM; EXPRESSION; MANAGEMENT
AB Spinal cord injury is associated with rapid bone loss and arrested long bone growth due to mechanisms that are poorly understood. In this study, we sought to determine the effects of severe T10 contusion spinal cord injury on the sublesional bone microenvironment in adolescent rats. A severe lower thoracic (vertebral T10) spinal cord injury was generated by weight drop (10 gx50 mm). Severely injured and body weight-matched uninjured male Sprague-Dawley rats were studied. At 3 and 5 days post-injury, we performed histological analysis of the distal femoral metaphysis, TUNEL assay, immunohistochemistry, real-time PCR, and western blot analysis compared to uninjured controls. We observed severe hindlimb functional deficits typical of this model. We detected uncoupled remodeling with increased osteoclast activity in the absence of osteoblast activity. We detected osteoblast, osteocyte, and chondrocyte apoptosis with suppressed osteoblast and chondrocyte proliferation and growth plate arrest due to spinal cord injury. We also detected altered gene expression in both whole bone extracts and bone marrow monocytes following spinal cord injury. We conclude that spinal cord injury results in altered gene expression of key regulators of osteoblast and chondrocyte activity. This leads to premature cellular apoptosis, suppressed cellular proliferation, growth plate arrest, and uncoupled bone remodeling in sublesional bone with unopposed osteoclastic resorption.
C1 [Morse, Leslie R.] Harvard Univ, Dept PMR, Sch Med, Forsyth Inst, Boston, MA 02118 USA.
[Morse, Leslie R.] Spaulding Harvard Spinal Cord Injury Model Syst, Spaulding Rehabil Hosp, Boston, MA USA.
[Morse, Leslie R.; Xu, Yan; Solomon, Bethlehem; Boyle, Lara; Yoganathan, Subbiah; Stashenko, Philip; Battaglino, Ricardo A.] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA.
[Morse, Leslie R.] Harvard Univ, Dept Phys Med & Rehabil, Sch Med, Boston, MA 02118 USA.
[Stashenko, Philip; Battaglino, Ricardo A.] Harvard Univ, Dept Oral Med Infect & Immun, Sch Dent Med, Boston, MA 02118 USA.
[Xu, Yan] Kunming Med Univ, Dept Med Microbiol & Immunol, Kunming, Yunnan, Peoples R China.
RP Morse, LR (reprint author), Harvard Univ, Dept PMR, Sch Med, Forsyth Inst, 140 Fenway, Boston, MA 02118 USA.
EM lmorse4@partners.org
RI battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015
OI Morse, Leslie/0000-0002-7426-6341
FU NIH/NICHD [K12HD001097-08]
FX Grant sponsor: NIH/NICHD Grant number K12HD001097-08 (L.M.)
NR 32
TC 5
Z9 5
U1 0
U2 2
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 DEC
PY 2011
VL 2
IS 4
SI SI
BP 643
EP 650
DI 10.1007/s12975-011-0118-9
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 943YJ
UT WOS:000304163700021
PM 22368723
ER
PT J
AU Bedard, PL
Singhal, SK
Ignatiadis, M
Bradbury, I
Haibe-Kains, B
Desmedt, C
Loi, S
Evans, DB
Michiels, S
Dixon, JM
Miller, WR
Piccart, MJ
Sotiriou, C
AF Bedard, Philippe L.
Singhal, Sandeep K.
Ignatiadis, Michail
Bradbury, Ian
Haibe-Kains, Benjamin
Desmedt, Christine
Loi, Sherene
Evans, Dean B.
Michiels, Stefan
Dixon, J. Michael
Miller, William R.
Piccart, Martine J.
Sotiriou, Christos
TI Low residual proliferation after short-term letrozole therapy is an
early predictive marker of response in high proliferative ER-positive
breast cancer
SO ENDOCRINE-RELATED CANCER
LA English
DT Article
ID GENE-EXPRESSION SIGNATURE; POSTMENOPAUSAL WOMEN; DOUBLE-BLIND; MOLECULAR
SUBTYPES; HISTOLOGIC GRADE; RANDOMIZED-TRIAL; GENOMIC GRADE; TAMOXIFEN;
PROGNOSIS; MULTICENTER
AB The gene expression grade index (GGI) is a 97-gene algorithm that measures proliferation and divides intermediate histological grade tumors into two distinct groups. We investigated the association between early changes in GGI and clinical response to neoadjuvant letrozole and compared this to Ki67 values. The paired gene expression data at the beginning and after 10-14 days of neoadjuvant letrozole treatment were available for 52 post-menopausal patients with estrogen receptor (ER)-positive breast cancer. Baseline values and changes in GGI, Ki67, and RNA expression modules representing oncogenic signaling pathways were compared to sonographic tumor volume changes after 3 months of treatment in the subsets of patients defined by high and low baseline GGI. The clinical response was observed in 80% genomic low-grade (24/30) and 59% genomic high-grade (13/22) tumors (P=0.10). Low residual proliferation after 10-14 days of neoadjuvant letrozole therapy, measured by either GGI or Ki67, was associated with sonographic response in genomic high-grade (GGI, P=0.003; Ki67, P=0.017) but not genomic low-grade (GGI, P=0.25; Ki67, P=1.0) tumors. The analysis of expression modules suggested that sonographic response to letrozole in genomic high-grade tumors was associated with an early reduction in IGF1 signaling (unadjusted P=0.018). The major conclusion of this study is that the early assessment of proliferation after short-term endocrine therapy may be useful to evaluate endocrine responsiveness, particularly in genomic high-grade ER-positive breast cancer. Endocrine-Related Cancer (2011) 18 721-730
C1 [Singhal, Sandeep K.; Ignatiadis, Michail; Haibe-Kains, Benjamin; Desmedt, Christine; Loi, Sherene; Michiels, Stefan; Piccart, Martine J.; Sotiriou, Christos] Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab JC Heuson, B-1000 Brussels, Belgium.
[Bedard, Philippe L.] Univ Toronto, Dept Med, Div Med Oncol & Hematol, Princess Margaret Hosp, Toronto, ON, Canada.
[Bradbury, Ian] Queens Univ Belfast, Sch Med, Royal Victoria Hosp, Belfast, Antrim, North Ireland.
[Haibe-Kains, Benjamin] Univ Libre Bruxelles, Machine Learning Grp, B-1000 Brussels, Belgium.
[Evans, Dean B.] Novartis Inst BioMed Res, Basel, Switzerland.
[Dixon, J. Michael] Breakthrough Breast Res Grp, Edinburgh, Midlothian, Scotland.
[Miller, William R.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Haibe-Kains, Benjamin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Haibe-Kains, Benjamin] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Sotiriou, C (reprint author), Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab JC Heuson, Rue Heger Bordet 1, B-1000 Brussels, Belgium.
EM christos.sotiriou@bordet.be
RI Haibe-Kains, Benjamin/D-3702-2011; Michiels, Stefan/L-1516-2013; Loi,
Sherene/H-1979-2016;
OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Michiels,
Stefan/0000-0002-6963-2968; Loi, Sherene/0000-0001-6137-9171; Desmedt,
Christine/0000-0002-5223-5579
FU Novartis; Canadian Association of Medical Oncologists; Breakthrough
Breast Cancer; Breast Cancer Research Foundation; Fondation de la
Recherche Scientifique; MEDIC foundation
FX The clinical study was supported by an unrestricted educational grant
from Novartis, funding from the Canadian Association of Medical
Oncologists (P L Bedard), Breakthrough Breast Cancer (J M Dixon), the
Breast Cancer Research Foundation (C Sotiriou), the Fondation de la
Recherche Scientifique (C Sotiriou), and the MEDIC foundation (C
Sotiriou). Presented in part at the 2009 San Antonio Breast Cancer
Symposium.
NR 37
TC 3
Z9 3
U1 0
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD DEC
PY 2011
VL 18
IS 6
BP 721
EP 730
DI 10.1530/ERC-11-0180
PG 10
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA 918IN
UT WOS:000302242800014
PM 21984694
ER
PT J
AU Thomas, B
Mimiaga, MJ
Kumar, S
Swaminathan, S
Safren, SA
Mayer, KH
AF Thomas, Beena
Mimiaga, Matthew J.
Kumar, Senthil
Swaminathan, Soumya
Safren, Steven A.
Mayer, Kenneth H.
TI HIV in Indian MSM: Reasons for a concentrated epidemic & strategies for
prevention
SO INDIAN JOURNAL OF MEDICAL RESEARCH
LA English
DT Review
DE HIV; India; men who have sex with men; MSM; mental health; stigma
ID PSYCHOSOCIAL HEALTH-PROBLEMS; SEXUAL RISK BEHAVIOR; BRIEF INTERVENTIONS;
ALCOHOL-PROBLEMS; HOMOSEXUAL MEN; ANDHRA-PRADESH; SOUTH-INDIA;
INFECTION; PREVALENCE; CHENNAI
AB Men who have sex with men (MSM) in India are disproportionately likely to be HIV-infected, and face distinct psychosocial challenges. Understanding the unique socio-cultural issues of MSM in India and how they relate to HIV risk could maximize the utility of future prevention efforts. This review discusses: (i) the importance of addressing co-occurring mental health issues, such as depression, which may interfere with MSM's ability to benefit from traditional risk reduction counselling, (ii) reducing HIV-related stigma among health providers, policymakers and the lay public, and (iii) the role for non-governmental organizations that work with the community to play in providing culturally relevant HIV prevention programmes for MSM.
C1 [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA.
[Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02138 USA.
[Mimiaga, Matthew J.; Safren, Steven A.; Mayer, Kenneth H.] Fenway Inst, Boston, MA USA.
[Mayer, Kenneth H.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02115 USA.
RP Thomas, B (reprint author), Natl Inst Res TB, 1 Satyamoorthy Rd, Madras 600031, Tamil Nadu, India.
EM beenaelli09@gmail.com
FU Indo-U.S. collaborative; NIMH [R-21 MH085314]; ICMR
FX Some research reported was supported by Indo-U.S. collaborative grants
(R-21 MH085314 from NIMH) to Dr Steven Safren and from ICMR to Dr Beena
Thomas. The content of the article does not reflect the views of NIH or
ICMR, and is solely the authors'.
NR 71
TC 27
Z9 29
U1 3
U2 6
PU INDIAN COUNCIL MEDICAL RES
PI NEW DELHI
PA PO BOX 4911 ANSARI NAGAR, NEW DELHI 110029, INDIA
SN 0971-5916
J9 INDIAN J MED RES
JI Indian J. Med. Res.
PD DEC
PY 2011
VL 134
IS 6
BP 920
EP 929
PG 10
WC Immunology; Medicine, General & Internal; Medicine, Research &
Experimental
SC Immunology; General & Internal Medicine; Research & Experimental
Medicine
GA 914QH
UT WOS:000301965900017
PM 22310824
ER
PT J
AU Salerno, A
Dixon, LB
Myers, RW
Smith, AM
Lamberti, JS
Jewell, TC
Essock, SM
AF Salerno, Anthony
Dixon, Lisa B.
Myers, Robert W.
Smith, Anne M.
Lamberti, J. Steven
Jewell, Thomas C.
Essock, Susan M.
TI A Public-Academic Partnership to Support a State Mental Health
Authority's Strategic Planning and Policy Decisions
SO PSYCHIATRIC SERVICES
LA English
DT Article
AB Mental health authorities across the country face numerous challenges in developing effective and practical strategies to adopt and sustain research-supported and stakeholder-endorsed mental health practices. This column describes how an academic center assists a mental health authority in making policy decisions by the use of advisory panels of multiple stakeholders, including members of the research community, advocacy organizations, service providers, and consumers. An advisory panel that focused on services involving family members for adults with serious mental health problems serves as a case example. (Psychiatric Services 62:1413-1415, 2011)
C1 [Salerno, Anthony; Essock, Susan M.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA.
[Salerno, Anthony] NYU, Silver Sch Social Work, McSilver Inst Poverty Policy & Res, New York, NY USA.
[Dixon, Lisa B.] Univ Maryland, Sch Med, Div Hlth Serv Res, Baltimore, MD 21201 USA.
[Dixon, Lisa B.] US Dept Vet Affairs, Capitol Hlth Care Network Mental Illness Res Educ, Baltimore, MD USA.
[Myers, Robert W.] New York State Off Mental Hlth, Div Adult Serv, Albany, NY USA.
[Smith, Anne M.; Jewell, Thomas C.] Univ Rochester, Dept Psychiat, Family Inst Educ Practice & Res, Rochester, NY USA.
[Jewell, Thomas C.] Columbia Univ, Ctr Practice Innovat, New York, NY USA.
[Lamberti, J. Steven] Univ Rochester, Med Ctr, Severe Mental Disorders Program, Dept Psychiat, Rochester, NY 14642 USA.
[Essock, Susan M.] Columbia Univ, Div Mental Hlth Serv & Policy Res, New York, NY USA.
RP Salerno, A (reprint author), 92 Winchester Dr, Monroe, NY 10950 USA.
EM anthony.salerno@nyu.edu
FU New York State Office of Mental Health (NYSOMH); Center for Practice
Innovations
FX The authors acknowledge the financial support provided by the New York
State Office of Mental Health (NYSOMH) to the Family Institute for
Education, Practice, and Research at the University of Rochester to
develop, field test, and improve the CCFC model. Furthermore, the NYSOMH
supported the Center for Practice Innovations, which organized the
advisory panel.
NR 5
TC 4
Z9 4
U1 0
U2 1
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD DEC
PY 2011
VL 62
IS 12
BP 1413
EP 1415
PG 3
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 912OI
UT WOS:000301809100002
PM 22193785
ER
PT J
AU Rao, RD
Cobleigh, MA
Gray, R
Graham, ML
Norton, L
Martino, S
Budd, GT
Ingle, JN
Wood, WC
AF Rao, Ruta D.
Cobleigh, Melody A.
Gray, Robert
Graham, Mark L., II
Norton, Larry
Martino, Silvana
Budd, George Thomas
Ingle, James N.
Wood, William C.
TI Phase III double-blind, placebo-controlled, prospective randomized trial
of adjuvant tamoxifen vs. tamoxifen and fenretinide in postmenopausal
women with positive receptors (EB193): an intergroup trial coordinated
by the Eastern Cooperative Oncology Group
SO MEDICAL ONCOLOGY
LA English
DT Article
DE Tamoxifen; Fenretinide; Postmenopausal; Retinoid; Retinamides;
Adenocarcinoma of the breast; Nyctalopia; Estrogen and progesterone
positive
ID BREAST-CANCER CELLS; GROWTH-FACTOR-I; TRANS-RETINOIC ACID; RAT
MAMMARY-CANCER; SURGICAL REMOVAL; VITAMIN-A;
N-(4-HYDROXYPHENYL)RETINAMIDE; APOPTOSIS; PREVENTION; RISK
AB Fenretinide and tamoxifen have additive antitumor effects preclinically. We performed a randomized, placebo-controlled, double-blind adjuvant trial in breast cancer patients treated for 5 years with tamoxifen, with or without fenretinide. Between October 1995 and October 1999, 426 postmenopausal women with hormone receptor-positive breast cancer were randomized. Patients were monitored for efficacy and toxicity. Four hundred and nineteen patients were evaluable. The study was terminated early due to slow accrual. There were no significant differences between treatment groups in DFS, TTR or survival. More patients stopped treatment early on the fenretinide arm than on placebo (P = 0.02). Grade 3/4 toxicities, including visual problems and musculoskeletal complaints were more common in patients receiving fenretinide (P = 0.007). A Night Blindness Questionnaire was used to monitor nyctalopia, which was slightly, but not significantly, more common on fenretinide. In this underpowered study, no significant difference was observed in efficacy between treatment groups. This trial provides important toxicity information about fenretinide, a retinoid that has been used in the prevention setting, because it is the only placebo-controlled, double-blind randomized study ever performed.
C1 [Rao, Ruta D.; Cobleigh, Melody A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Gray, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Graham, Mark L., II] Waverly Heme Onc, Cary, NC USA.
[Norton, Larry] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Martino, Silvana] Angeles Clin & Res Inst, Santa Monica, CA USA.
[Budd, George Thomas] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Ingle, James N.] Mayo Clin, Rochester, MN USA.
[Wood, William C.] Emory Univ, Atlanta, GA 30322 USA.
RP Rao, RD (reprint author), Rush Univ, Med Ctr, 1725 W Harrison St,Suite 809, Chicago, IL 60612 USA.
EM ruta_d_rao@rush.edu
FU Public Health Service [CA23318, CA66636, CA21115, CA47559, CA07968,
CA04919, CA25224, CA37404]; National Cancer Institute, National
Institutes of Health; Department of Health and Human Services
FX This study was conducted by the Eastern Cooperative Oncology Group
(Robert L. Comis, M. D., Chair) and supported in part by Public Health
Service Grants CA23318, CA66636, CA21115, CA47559, CA07968, CA04919,
CA25224, and CA37404 and from the National Cancer Institute, National
Institutes of Health and the Department of Health and Human Services.
Its contents are solely the responsibility of the authors and do not
necessarily represent the official views of the National Cancer
Institute.
NR 34
TC 1
Z9 1
U1 0
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1357-0560
J9 MED ONCOL
JI Med. Oncol.
PD DEC
PY 2011
VL 28
SU 1
BP S39
EP S47
DI 10.1007/s12032-010-9682-1
PG 9
WC Oncology
SC Oncology
GA 902OG
UT WOS:000301047200006
PM 20878269
ER
PT J
AU Jones, B
Underwood, TSA
Carabe-Fernandez, A
Timlin, C
Dale, RG
AF Jones, B.
Underwood, T. S. A.
Carabe-Fernandez, A.
Timlin, C.
Dale, R. G.
TI Fast neutron relative biological effects and implications for charged
particle therapy
SO BRITISH JOURNAL OF RADIOLOGY
LA English
DT Article
ID LINEAR-QUADRATIC MODEL; PROTON-BEAM THERAPY; EFFECTIVENESS RBE; ION
RADIOTHERAPY; ENERGY-TRANSFER; CELL-LINES; IRRADIATION; VALUES
AB In two fast neutron data sets, comprising in vitro and in vivo experiments, an inverse relationship is found between the low-linear energy transfer (LET) alpha/beta ratio and the maximum value of relative biological effect (RBEmax), while the minimum relative biological effect (RBEmin) is linearly related to the square root of the low-LET alpha/beta ratio. RBEmax is the RBE at near zero dose and can be represented by the ratio of the alpha parameters at high- and low-LET radiation exposures. RBEmin is the RBE at very high dose and can be represented by the ratio of the square roots of the beta parameters at high- and low-LET radiation exposures. In principle, it may be possible to use the low-LET alpha/beta ratio to predict RBEmax and RBEmin, providing that other LET-related parameters, which reflect intercept and slopes of these relationships, are used. These two limits of RBE determine the intermediate values of RBE at any dose per fraction; therefore, it is possible to find the RBE at any dose per fraction. Although these results are obtained from fast neutron experiments, there are implications for charged particle therapy using protons (when RBE is scaled downwards) and for heavier ion beams (where the magnitude of RBE is similar to that for fast neutrons). In the case of fast neutrons, late reacting normal tissue systems and very slow growing tumours, which have the smallest values of the low-LET alpha/beta ratio, are predicted to have the highest RBE values at low fractional doses, but the lowest values of RBE at higher doses when they are compared with early reacting tissues and fast growing tumour systems that have the largest low-LET alpha/beta ratios.
C1 [Jones, B.; Underwood, T. S. A.] Univ Oxford, Gray Inst Radiat Oncol & Biol, Oxford OX3 7DQ, England.
[Jones, B.; Underwood, T. S. A.; Timlin, C.; Dale, R. G.] Univ Oxford, Particle Therapy Canc Res Inst, Oxford OX3 7DQ, England.
[Carabe-Fernandez, A.] Massachusetts Gen Hosp, Proton Therapy Ctr, Boston, MA 02114 USA.
[Dale, R. G.] Charing Cross Hosp, Dept Radiat Phys & Radiobiol, Imperial Coll Sch Med, London, England.
RP Jones, B (reprint author), Univ Oxford, Gray Inst Radiat Oncol & Biol, Old Rd Res Campus, Oxford OX3 7DQ, England.
EM Bleddyn.Jones@rob.ox.ac.uk
NR 21
TC 10
Z9 10
U1 0
U2 3
PU BRITISH INST RADIOLOGY
PI LONDON
PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND
SN 0007-1285
J9 BRIT J RADIOL
JI Br. J. Radiol.
PD DEC
PY 2011
VL 84
SI 1
BP S11
EP S18
DI 10.1259/bjr/67509851
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 901CK
UT WOS:000300939100003
PM 22374547
ER
PT J
AU Feng, AN
Zhang, LH
Fan, XS
Huang, Q
Ye, Q
Wu, HY
Yang, J
AF Feng, An Ning
Zhang, Li Hua
Fan, Xiang Shan
Huang, Qin
Ye, Qing
Wu, Hong Yan
Yang, Jun
TI Expression of SIRT1 in Gastric Cardiac Cancer and Its Clinicopathologic
Significance
SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE SIRT1; p53; Ki-67; gastric cardiac carcinoma; prognosis
ID ESOPHAGOGASTRIC JUNCTION; ANDROGEN RECEPTOR; PROSTATE-CANCER; REGULATES
SIRT1; POOR-PROGNOSIS; CELL-GROWTH; ADENOCARCINOMA; P53; CARCINOMA; DNA
AB SIRT1 is a deacetylase that modifies gene expression. Some researchers have found that SIRT1 is upregulated in malignant tumor tissues. Therefore, this study investigated the SIRT1 expression in gastric cardiac carcinoma and its correlation with clinicopathologic features and prognosis. Tissue microarray technique and immunohistochemical stains were used to detect the expression of SIRT1, p53, and Ki-67 in 176 gastric cardiac carcinoma tissues and 32 normal gastric cardiac region tissues. SIRT1 expression in gastric cardiac carcinoma was significantly higher than that in normal gastric cardiac tissues and was associated with lymphatic metastasis, TNM stage, survival rate and mean survival time. Expression of Ki-67 in the SIRT1 positive group was significantly higher than that in the negative group. In conclusion, high expression of SIRT1 in gastric cardiac carcinoma was correlated with lymphatic metastasis, TNM stage, proliferative status and prognosis. SIRT1 might be a biological parameter to evaluate malignant degree and prognosis of gastric cardiac carcinoma.
C1 [Zhang, Li Hua] Southeast Univ, Affiliated Zhongda Hosp, Dept Pathol, Nanjing 210009, Jiangsu, Peoples R China.
[Feng, An Ning; Fan, Xiang Shan; Ye, Qing; Wu, Hong Yan; Yang, Jun] Nanjing Univ, Sch Med, Affiliated Nanjing Drum Tower Hosp, Nanjing, Jiangsu, Peoples R China.
[Huang, Qin] VA Boston Healthcare Syst, Boston, MA USA.
RP Zhang, LH (reprint author), Southeast Univ, Affiliated Zhongda Hosp, Dept Pathol, 87 Dingjia Qiao, Nanjing 210009, Jiangsu, Peoples R China.
EM njlihua@yahoo.com.cn
FU Medical Technology Development of Nanjing Public Health Bureau, China
[ZKX07011]
FX This work was supported by the major project of Medical Technology
Development of Nanjing Public Health Bureau, China (Grant No.:
ZKX07011).
NR 46
TC 31
Z9 35
U1 0
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1066-8969
J9 INT J SURG PATHOL
JI Int. J. Surg. Pathol.
PD DEC
PY 2011
VL 19
IS 6
BP 743
EP 750
DI 10.1177/1066896911412181
PG 8
WC Pathology; Surgery
SC Pathology; Surgery
GA 895OL
UT WOS:000300505600005
PM 21865267
ER
PT J
AU Covello, R
Licci, S
Pichi, B
Spriano, G
Vidiri, A
Morelli, L
Rosenberg, AE
AF Covello, Renato
Licci, Stefano
Pichi, Barbara
Spriano, Giuseppe
Vidiri, Antonello
Morelli, Luca
Rosenberg, Andrew E.
TI Low-Grade Myofibroblastic Sarcoma of the Larynx
SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE low-grade myofibroblastic sarcoma; head and neck; larynx
ID OF-THE-LITERATURE; SOFT-TISSUE SARCOMAS; SPINDLE-CELL TUMORS;
MYOFIBROSARCOMA; NECK; HEAD; DIFFERENTIATION
AB Low-grade myofibroblastic sarcoma is an uncommon sarcoma with myofibroblastic differentiation. It occurs in a wide variety of sites and has a predilection for the head and neck region. Biologically, low-grade myofibroblastic sarcoma has a propensity for local recurrence and is associated with a low risk of metastatic spread. Histologically, it can mimic a variety of different types of benign and malignant processes and often requires immunohistochemical analysis for its accurate identification. This report describes a case and discusses the differential diagnosis of a low-grade myofibroblastic sarcoma that arose in the larynx of a 69-year-old woman with a history of metastatic skin melanoma. To the best of the authors' knowledge this is the first description in the English literature of low-grade myofibroblastic sarcoma originating in the larynx.
C1 [Licci, Stefano] Santo Spirito Hosp, Dept Pathol, I-00193 Rome, Italy.
[Covello, Renato; Pichi, Barbara; Spriano, Giuseppe; Vidiri, Antonello] Natl Canc Inst Regina Elena, Rome, Italy.
[Morelli, Luca] Santa Chiara Hosp, Trento, Italy.
[Rosenberg, Andrew E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Licci, S (reprint author), Santo Spirito Hosp, Dept Pathol, Lungotevere Sassia 1, I-00193 Rome, Italy.
EM stefano.licci@hotmail.it
NR 32
TC 5
Z9 8
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1066-8969
J9 INT J SURG PATHOL
JI Int. J. Surg. Pathol.
PD DEC
PY 2011
VL 19
IS 6
BP 822
EP 826
DI 10.1177/1066896910393958
PG 5
WC Pathology; Surgery
SC Pathology; Surgery
GA 895OL
UT WOS:000300505600023
PM 21233102
ER
PT J
AU Vogl, DT
Wang, T
Perez, WS
Stadtmauer, EA
Heitjan, DF
Lazarus, HM
Kyle, RA
Kamble, R
Weisdorf, D
Roy, V
Gibson, J
Ballen, K
Holmberg, L
Bashey, A
McCarthy, PL
Freytes, C
Maharaj, D
Maiolino, A
Vesole, D
Hari, P
AF Vogl, Dan T.
Wang, Tao
Perez, Waleska S.
Stadtmauer, Edward A.
Heitjan, Daniel F.
Lazarus, Hillard M.
Kyle, Robert A.
Kamble, Ram
Weisdorf, Daniel
Roy, Vivek
Gibson, John
Ballen, Karen
Holmberg, Leona
Bashey, Asad
McCarthy, Philip L.
Freytes, Cesar
Maharaj, Dipnarine
Maiolino, Angelo
Vesole, David
Hari, Parameswaran
TI Effect of Obesity on Outcomes after Autologous Hematopoietic Stem Cell
Transplantation for Multiple Myeloma
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Obesity; Myeloma; Autologous transplantation; Chemotherapy; Radiation
therapy; Melphalan
ID BODY-MASS INDEX; HIGH-DOSE CHEMOTHERAPY; RECEIVING ADJUVANT
CHEMOTHERAPY; TREATMENT-RELATED TOXICITY; ADVERSE PROGNOSTIC-FACTOR;
OPERABLE BREAST-CANCER; MARROW TRANSPLANTATION; RANDOMIZED TRIAL;
MORTALITY; WEIGHT
AB Obesity has implications for chemotherapy dosing and selection of patients for therapy. Autologous hematopoietic stem cell transplant (AutoHCT) improves outcomes for patients with multiple myeloma, but optimal chemotherapy dosing for obese patients is poorly defined. We analyzed the outcomes of 1087 recipients of AutoHCT for myeloma reported to the CIBMTR between 1995 and 2003 who received high-dose melphalan conditioning, with or without total body irradiation (TBI). We categorized patients by body mass index (BMI) as normal, overweight, obese, or severely obese. There was no overall effect of BMI on progression-free survival (PFS), overall survival (OS), progression, or nonrelapse mortality (NRM). In patients receiving melphalan and TBI conditioning, obese and severely obese patients had superior PFS and OS compared with normal and overweight patients, but the clinical significance of this finding is unclear. More obese patients were more likely to receive a reduced dose of melphalan, but there was no evidence that melphalan or TBI dosing variability affected PFS. Therefore, current common strategies of dosing melphalan do not impair outcomes for obese patients, and obesity should not exclude patients from consideration of autologous transplantation. Further research is necessary to optimize dosing of both chemotherapy and radiation in obese patients. Biol Blood Marrow Transplant 17: 1765-1774 (2011) (C) 2011 American Society for Blood and Marrow Transplantation
C1 [Vogl, Dan T.; Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Wang, Tao; Perez, Waleska S.; Hari, Parameswaran] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Heitjan, Daniel F.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Kyle, Robert A.] Mayo Clin, Rochester, MN USA.
[Kamble, Ram] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Weisdorf, Daniel] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA.
[Roy, Vivek] Mayo Clin, Jacksonville, FL 32224 USA.
[Gibson, John] Royal Prince Alfred Hosp, Inst Haematol, Camperdown, NSW 2050, Australia.
[Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Holmberg, Leona] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Bashey, Asad] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA.
[McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Freytes, Cesar] S Vet Hlth Care Syst, San Antonio, TX USA.
[Freytes, Cesar] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Maharaj, Dipnarine] Bethesda Hlth City, Boynton Beach, FL USA.
[Maiolino, Angelo] Hosp Univ Clementino Fraga Filho, Rio De Janeiro, Brazil.
[Hari, Parameswaran] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
RP Vogl, DT (reprint author), Univ Penn, Abramson Canc Ctr, 3400 Civic Ctr Blvd,Perelman Ctr 2 W, Philadelphia, PA 19104 USA.
EM dan.vogl@uphs.upenn.edu
OI Vogl, Dan/0000-0002-2935-2566; Hari, Parameswaran/0000-0002-8800-297X
FU Leukemia & Lymphoma Society; American Society of Hematology; National
Cancer Institute (NCI) [K23CA130074, U24-CA7651.8]; National Heart, Lung
and Blood Institute (NHLBI); National Institute of Allergy and
Infectious Diseases (MAID); NFILBI [5U0 IFIL069294]; Health Resources
and Services Administration (HRWDHHS); Office of Naval Research
[N00014-06-1-0704, N00014-08-I-0058]; AABB; Aetna; American Society for
Blood and Marrow Transplantation; Amgen, Inc
FX Dr. Vogl is supported by a Special Fellow in Clinical Research Award
from the Leukemia & Lymphoma Society, a Scholar Award from the American
Society of Hematology, and grant K23CA130074 from the National Cancer
Institute (NCI).; Financial disclosure: The CIBMTR is supported by
Public I-Tealth Service Grant/Cooperative Agreement U24-CA7651.8 from
the NCI, the National Heart, Lung and Blood Institute (NHLBI), and the
National Institute of Allergy and Infectious Diseases (MAID); a
Grant/Cooperative Agreement 5U0 IFIL069294 from NFILBI and NCI; a
contract I-MST-1234200637015C with the Health Resources and Services
Administration (HRWDHH.S); 2 Grants, N00014-06-1-0704 and
N00014-08-I-0058, from the Office of Naval Research; and grants from
AABB; Aetna; American Society for Blood and Marrow Transplantation;
Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin;
Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare
Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin
Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross
and Blue Shield Association; Bone Marrow Foundation; Buchanan Family
Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT;
Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and
Prevention; Children's Leukemia Research Association; ClinImmune Labs;
CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals;
Cylex Inc.; CytoTherm; DOR 1BioPharma, Inc.; 1Dynal :Biotech, an
Invitrogen Company; Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European
Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE
Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.;
HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases
Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; The Leukemia
NR 37
TC 21
Z9 21
U1 0
U2 3
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 DEC
PY 2011
VL 17
IS 12
BP 1765
EP 1774
DI 10.1016/j.bbmt.2011.05.005
PG 10
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 895CB
UT WOS:000300472700007
PM 21624486
ER
PT J
AU Farag, SS
Maharry, K
Zhang, MJ
Perez, WS
George, SL
Mrozek, K
DiPersio, J
Bunjes, DW
Marcucci, G
Baer, MR
Cairo, M
Copelan, E
Cutler, CS
Isola, L
Lazarus, HM
Litzow, MR
Marks, DI
Ringden, O
Rizzieri, DA
Soiffer, R
Larson, RA
Tallman, MS
Bloomfield, CD
Weisdorf, DJ
AF Farag, Sherif S.
Maharry, Kati
Zhang, Mei-Jie
Perez, Waleska S.
George, Stephen L.
Mrozek, Krzysztof
DiPersio, John
Bunjes, Donald W.
Marcucci, Guido
Baer, Maria R.
Cairo, Mitchell
Copelan, Edward
Cutler, Corey S.
Isola, Luis
Lazarus, Hillard M.
Litzow, Mark R.
Marks, David I.
Ringden, Olle
Rizzieri, David A.
Soiffer, Robert
Larson, Richard A.
Tallman, Martin S.
Bloomfield, Clara D.
Weisdorf, Daniel J.
CA Ctr Int Blood & Marrow Transplant
TI Comparison of Reduced-Intensity Hematopoietic Cell Transplantation with
Chemotherapy in Patients Age 60-70 Years with Acute Myelogenous Leukemia
in First Remission
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Acute myeloid leukemia; Allogeneic; Chemotherapy; Reduced-intensity
ID ACUTE MYELOID-LEUKEMIA; RISK MYELODYSPLASTIC SYNDROME;
BONE-MARROW-TRANSPLANTATION; COOPERATIVE-ONCOLOGY-GROUP; IDENTICAL
SIBLING DONORS; OLDER PATIENTS; POSTREMISSION THERAPY; ELDERLY-PATIENTS;
GROUP-B; ADULTS
AB We compared the outcomes of patients age 60-70 years with acute myelogenous leukemia receiving reduced-intensity allogeneic hematopoietic cell transplantation (HCT) in first remission (CRI) reported to the Center for International Blood and Marrow Research (n = 94) with the outcomes in patients treated with induction and postremission chemotherapy on Cancer and Leukemia Group B protocols (n = 96). All patients included had been in CRI for at least 4 months. The HCT recipients were slightly younger than the chemotherapy patients (median age, 63 years vs 65 years; P <.001), but there were no significant between-group differences in the proportion with therapy-related leukemia or in different cytogenetic risk groups. Time from diagnosis to CRI was longer for the HCT recipients (median, 44 days vs 38 days; P =.031). Allogeneic HCT was associated with significantly lower risk of relapse (32% vs 81% at 3 years; P <.001), higher nonrelapse mortality (36% vs 4% at 3 years; P <.001), and longer leukemia-free survival (32% vs 15% at 3 years; P =.001). Although overall survival was longer for HCT recipients, the difference was not statistically significant (37% vs 25% at 3 years; P =.08). Our findings suggest that reduced-intensity conditioning allogeneic HCT in patients age 60-70 with acute myelogenous leukemia in CRI reduces relapse and improves leukemia-free survival. Strategies that reduce nonrelapse mortality may yield significant improvements in overall survival. Biol Blood Marrow Transplant 17: 1796-1803 (2011) (C) 2011 American Society for Blood and Marrow Transplantation
C1 [Farag, Sherif S.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA.
[Maharry, Kati; Mrozek, Krzysztof; Marcucci, Guido; Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Dept Med, Columbus, OH 43210 USA.
[Maharry, Kati; George, Stephen L.] Duke Univ, Med Ctr, Canc & Leukemia Grp B Stat Ctr, Durham, NC USA.
[Zhang, Mei-Jie; Perez, Waleska S.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[DiPersio, John] Barnes Jewish Hosp, Dept Med, St Louis, MO 63110 USA.
[Bunjes, Donald W.] Univ Ulm Klinikum, Ulm, Germany.
[Baer, Maria R.] Univ Maryland, Dept Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Cairo, Mitchell] Columbia Univ, Dept Med, Med Ctr, New York, NY USA.
[Copelan, Edward] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Cutler, Corey S.; Soiffer, Robert] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
[Isola, Luis] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Litzow, Mark R.] Mayo Clin, Rochester, MN USA.
[Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England.
[Ringden, Olle] Karolinska Univ Hosp, Huddinge, Sweden.
[Rizzieri, David A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Larson, Richard A.] Univ Chicago Hosp, Dept Med, Chicago, IL 60637 USA.
[Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Dept Med, Minneapolis, MN 55455 USA.
RP Farag, SS (reprint author), Indiana Univ Sch Med, Dept Internal Med, Div Hematol & Oncol, Walther Hall R3,C414,980 W Walnut St, Indianapolis, IN 46202 USA.
EM ssfarag@iupui.edu
RI Mrozek, Krzysztof/A-3142-2008;
OI Larson, Richard/0000-0001-9168-3203
FU National Cancer Institute, NCI [CA101140, CA31946, CA77658, CA33601,
CA41287, CA47545, CA03927, CA47577, CA35279, CA32291, CA16058]; Coleman
Leukemia Research Fund; Public Health Service Grant from the National
Cancer Institute [U24CA76518]; National Heart, Lung and Blood Institute;
National Institute of Allergy and Infectious Diseases; National Heart,
Lung and Blood Institute [5U01HL069294]; National Cancer Institute;
Health Resources and Services Administration [HHSH234200637015C]; Office
of Naval Research [N00014-06-1-0704, N00014-08-10058]; AABB; Allos, Inc;
Amgen, Inc
FX This research was supported in part by grants from the National Cancer
Institute to Cancer and Leukemia Group B (CA101140, CA31946, CA77658,
CA33601, CA41287, CA47545, CA03927, CA47577, CA35279, and CA32291), NCI
CA16058, and the Coleman Leukemia Research Fund.; Financial Disclosure:
The Center for International Blood and Marrow Research is supported by
Public Health Service Grant/Cooperative Agreement U24CA76518 from the
National Cancer Institute, National Heart, Lung and Blood Institute, and
National Institute of Allergy and Infectious Diseases; Grant/Cooperative
Agreement 5U01HL069294 from the National Heart, Lung and Blood Institute
and National Cancer Institute; Contract HHSH234200637015C from the
Health Resources and Services Administration; Grants N00014-06-1-0704
and N00014-08-10058 from the Office of Naval Research; and grants from
AABB; Allos, Inc; Amgen, Inc; Anonymous donation to the Medical College
of Wisconsin; Astellas Pharma US, Inc; Be the Match Foundation; Biogen
IDEC; BioMarin Pharmaceutical, Inc; Biovitrum AB; Blood Center of
Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow
Foundation; Buchanan Family Foundation; CaridianBCT; Celgene
Corporation; CellGenix, GmbH; Children's Leukemia Research Association;
ClinImmune Labs; CTI Clinical Trial and Consulting Services; Eisai, Inc;
Genentech, Inc; Genzyme Corporation; Histogenetics, Inc; HKS Medical
Information Systems; Hospira, Inc; Kirin Brewery Co, Ltd; The Leukemia
and Lymphoma Society; Merck & Company; The Medical College of Wisconsin;
Millennium Pharmaceuticals, Inc; Miller Pharmacal Group; Milliman USA,
Inc; Miltenyi Biotec, Inc; National Marrow Donor Program; Nature
Publishing Group; Novartis Oncology; Oncology Nursing Society; Osiris
Therapeutics, Inc; Otsuka America Pharmaceutical, Inc; Pall Life
Sciences; Pfizer Inc; Schering Corporation; Sigma-Tau Pharmaceuticals;
Soligenix, Inc; StemCyte, Inc; StemSoft Software, Inc; Sysmex America,
Inc; THERAKOS, Inc; Vidacare Corporation; ViraCor Laboratories;
ViroPharma, Inc; and Wellpoint, Inc The views expressed in this paper do
not reflect the official policy or position of the National Institutes
of Health, Department of the Navy, Department of Defense, or any other
agency of the U.S. Government.
NR 37
TC 50
Z9 51
U1 0
U2 4
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 DEC
PY 2011
VL 17
IS 12
BP 1796
EP 1803
DI 10.1016/j.bbmt.2011.06.005
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 895CB
UT WOS:000300472700011
PM 21699879
ER
PT J
AU Ziebell, AL
Clasie, B
Wroe, A
Schulte, RW
Reinhard, MI
Dowdell, SJ
Lerch, ML
Petasecca, M
Perevertaylo, VL
Zinets, OS
Anokhin, IE
Rosenfeld, AB
AF Ziebell, A. L.
Clasie, B.
Wroe, A.
Schulte, R. W.
Reinhard, M. I.
Dowdell, S. J.
Lerch, M. L.
Petasecca, M.
Perevertaylo, V. L.
Zinets, O. S.
Anokhin, I. E.
Rosenfeld, A. B.
TI Solid state diode - Ionization chamber method for measuring out-of-field
neutron dose in proton therapy
SO RADIATION MEASUREMENTS
LA English
DT Article
DE Out-of-field dosimetry; Silicon diode; Proton therapy; Neutron dose
ID I-N-DIODES; EQUIVALENT; DOSIMETRY
AB In proton therapy neutrons are introduced to out-of-field regions inside the patient. Clinicians would like to know the absorbed dose being deposited by neutrons separately to that from protons, so as to be able to directly apply their own dose equivalent weighting factors based on their opinion of the biological risk posed by neutrons in this region. The purpose of this study is to investigate a novel approach to experimentally separating the proton and neutron contributions to the absorbed dose in out-of-field regions. The method pairs specially designed silicon PIN diodes with a standard clinical ionization chamber. The sensitivity of the Si diode to non-ionizing energy losses in silicon is exploited, and can be quantified by measuring the shift in forward voltage for a fixed injection current, pre and post irradiation. The mathematical relations that describe the response of the diode and the ionization chamber can be solved simultaneously to give the contributions to the absorbed dose from protons and neutrons separately. Experimental measurements were made at the Loma Linda University Medical Center (LLUMC), Loma Linda, and Massachusetts General Hospital (MGH), Boston, proton therapy facilities. Experimental separation of the partial proton and neutron contributions to the absorbed dose measured at positions lateral to a typical prostate therapy treatment field delivered to a Lucite phantom was successfully performed and compared with results from a GEANT4 simulation. The experimental results matched well with simulation confirming the validity and promise of the novel approach. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Ziebell, A. L.; Dowdell, S. J.; Lerch, M. L.; Petasecca, M.; Rosenfeld, A. B.] Univ Wollongong, Ctr Med Radiat Phys, Wollongong, NSW, Australia.
[Reinhard, M. I.] Australian Nucl Sci & Technol Org, Sydney, NSW, Australia.
[Clasie, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Clasie, B.] Harvard Univ, Sch Med, Boston, MA USA.
[Wroe, A.; Schulte, R. W.] Loma Linda Univ, Med Ctr, Loma Linda, CA USA.
[Zinets, O. S.; Anokhin, I. E.] Ukrainian Acad Sci, Inst Nucl Res, UA-252028 Kiev, Ukraine.
RP Ziebell, AL (reprint author), Univ Wollongong, Ctr Med Radiat Phys, Wollongong, NSW, Australia.
EM amy.ziebell@gmail.com
RI Lerch, Michael/C-3303-2014; Petasecca, Marco/C-6436-2014; Rosenfeld,
Anatoly/D-1989-2014;
OI Petasecca, Marco/0000-0001-5958-7457; Lerch, Michael/0000-0002-2406-9972
NR 19
TC 2
Z9 2
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-4487
J9 RADIAT MEAS
JI Radiat. Meas.
PD DEC
PY 2011
VL 46
IS 12
SI SI
BP 1638
EP 1642
DI 10.1016/j.radmeas.2011.05.022
PG 5
WC Nuclear Science & Technology
SC Nuclear Science & Technology
GA 894WY
UT WOS:000300459400071
ER
PT J
AU Mancini, GBJ
Hartigan, PM
Bates, ER
Sedlis, SP
Maron, DJ
Spertus, JA
Berman, DS
Kostuk, WJ
Shaw, LJ
Weintraub, WS
Teo, KK
Dada, M
Chaitman, BR
O'Rourke, RA
Boden, WE
AF Mancini, G. B. John
Hartigan, Pamela M.
Bates, Eric R.
Sedlis, Steven P.
Maron, David J.
Spertus, John A.
Berman, Daniel S.
Kostuk, William J.
Shaw, Leslee J.
Weintraub, William S.
Teo, Koon K.
Dada, Marcin
Chaitman, Bernard R.
O'Rourke, Robert A.
Boden, William E.
CA Coordinators, CI
TI Angiographic Disease Progression and Residual Risk of Cardiovascular
Events While on Optimal Medical Therapy Observations From the COURAGE
Trial
SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE coronary artery disease; angiography; angioplasty; atherosclerotic
plaque; rupture; revascularization
ID CORONARY-ARTERY-DISEASE; FRACTIONAL FLOW RESERVE; ATHEROSCLEROTIC
PLAQUES; INTERVENTION; TOMOGRAPHY; CULPRIT; LESIONS
AB Background-The extent to which recurrent events in patients with stable coronary artery disease is attributable to progression of an index lesion originally >= 50% diameter stenosis (DS) but not revascularized or originally <50% DS is unknown during optimal medical therapy (OMT).
Methods and Results-In the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 205 patients assigned to OMT plus percutaneous coronary intervention (PCI) and 284 patients assigned to OMT only had symptom-driven angiograms suitable for analysis. Percentages of patients in the OMT + PCI and OMT-only cohorts with index lesions originally <50% DS were 30% and 32%, respectively; 20% and 68% had index lesions originally >= 50% DS. In both groups, index lesions originally <50% or >= 50% DS represented <4% and <25% of all such lesions, respectively. The only angiographic predictor of myocardial infarction or acute coronary syndrome was the number of lesions originally >= 50% DS that had not been revascularized (odds ratio, 1.15; confidence limits, 1.01-1.31; P<0.04).
Conclusions-Lesions originally <50% DS were index lesions in one third of patients referred for symptom-driven repeat angiography, but represented <4% of all such lesions. Nonrevascularized lesions originally >= 50% DS were more often index lesions in OMT-only patients, but still represented a minority (<25%) of all such lesions. These findings underscore the need for improved therapies to arrest plaque progression and reliable strategies for selecting stenoses warranting PCI.
C1 [Mancini, G. B. John] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Hartigan, Pamela M.] Connecticut VA Healthcare Syst, Vet Affairs Cooperat Studies Program, Coordinating Ctr, West Haven, CT USA.
[Bates, Eric R.] Univ Michigan, Med Ctr, Ann Arbor, MI USA.
[Sedlis, Steven P.] Univ Sch Med, VA New York Harbor Hlth Care Syst, New York, NY USA.
[Maron, David J.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Spertus, John A.] Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA.
[Berman, Daniel S.] Univ Calif Los Angeles, Cedars Sinai Heart Inst, Los Angeles, CA USA.
[Kostuk, William J.] Univ Western Ontario, London Hlth Sci Ctr, London, ON, Canada.
[Shaw, Leslee J.] Emory Univ, Sch Med, Atlanta, GA USA.
[Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA.
[Teo, Koon K.] McMaster Univ, Med Ctr, Hamilton, ON, Canada.
[Dada, Marcin] Hartford Hosp, Hartford, CT 06115 USA.
[Chaitman, Bernard R.] St Louis Univ Hosp, St Louis, MO USA.
[O'Rourke, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[O'Rourke, Robert A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Boden, William E.] Buffalo Gen Hosp, Buffalo, NY 14203 USA.
[Boden, William E.] SUNY Buffalo, Buffalo, NY 14260 USA.
RP Mancini, GBJ (reprint author), Vancouver Hosp Res Pavil, Room 489,828 10th Ave, Vancouver, BC V5Z 1M9, Canada.
EM mancini@mail.ubc.ca
OI Sedlis, Steven/0000-0002-8194-8017
FU Merck; National Heart, Lung, and Blood Institute; American Heart
Association; American College of Cardiology Foundation; Lilly;
BMS/Sanofi; Cordis; United Healthcare; Gilead; St Jude Medical
FX Dr Mancini has received grant funding from Merck (>$10 000) and
honoraria from Merck (>$10 000), GlaxoSmithKline (>$10 000),
AstraZeneca, and Pfizer. Dr Spertus has received grant funding of >$10
000 from the National Heart, Lung, and Blood Institute; American Heart
Association; American College of Cardiology Foundation; Lilly;
BMS/Sanofi; Cordis; and EvaHeart and consulting fees <$10 000 from
United Healthcare, Gilead, and St Jude Medical.
NR 16
TC 21
Z9 23
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7640
J9 CIRC-CARDIOVASC INTE
JI Circ.-Cardiovasc. Interv.
PD DEC
PY 2011
VL 4
IS 6
BP 545
EP 552
DI 10.1161/CIRCINTERVENTIONS.110.960062
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 896EZ
UT WOS:000300549500005
PM 22045968
ER
PT J
AU Azadani, AN
Tseng, EE
AF Azadani, Ali N.
Tseng, Elaine E.
TI Transcatheter Heart Valves for Failing Bioprostheses State-of-the-Art
Review of Valve-in-Valve Implantation
SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE valve-in-valve implantation; transcatheter heart valve; transcatheter
aortic valve implantation
ID SEVERE AORTIC REGURGITATION; EDWARDS-SAPIEN VALVE; HIGH-RISK PATIENTS;
COREVALVE REVALVING SYSTEM; DEGENERATED BIOPROSTHESIS; ENERGY-LOSS;
FOLLOW-UP; REPLACEMENT; STENOSIS; PERFORMANCE
C1 [Tseng, Elaine E.] Univ Calif San Francisco, Div Cardiothorac Surg, Dept Surg, Med Ctr, San Francisco, CA 94143 USA.
[Azadani, Ali N.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Tseng, EE (reprint author), Univ Calif San Francisco, Div Cardiothorac Surg, Dept Surg, Med Ctr, 500 Parnassus Ave,Suite 405W,Box 0118, San Francisco, CA 94143 USA.
EM elaine.tseng@ucsfmedctr.org
FU American Heart Association; Northern California Institute for Research
and Education
FX This study was funded by an American Heart Association Grant-in-Aid and
Northern California Institute for Research and Education. No relevant
industry relationship is reported.
NR 81
TC 19
Z9 19
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7640
J9 CIRC-CARDIOVASC INTE
JI Circ.-Cardiovasc. Interv.
PD DEC
PY 2011
VL 4
IS 6
BP 621
EP U189
DI 10.1161/CIRCINTERVENTIONS.111.964478
PG 51
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 896EZ
UT WOS:000300549500014
PM 22186106
ER
PT J
AU Zipse, L
Kearns, K
Nicholas, M
Marantz, A
AF Zipse, Lauryn
Kearns, Kevin
Nicholas, Marjorie
Marantz, Alec
TI A MEG Investigation of Single-Word Auditory Comprehension in Aphasia
SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH
LA English
DT Article
DE aphasia; electrophysiology; semantics
ID LEFT-HEMISPHERE LESIONS; LEXICAL DECISION TASK; BRAIN POTENTIALS;
AUTOMATIC ACCESS; BROCAS-APHASIA; OLDER ADULTS; TIME-COURSE; LANGUAGE;
AGE; MAGNETOENCEPHALOGRAPHY
AB Purpose: To explore whether individuals with aphasia exhibit differences in the M350, an electrophysiological marker of lexical activation, compared with healthy controls.
Method: Seven people with aphasia, 9 age-matched controls, and 10 younger controls completed an auditory lexical decision task while cortical activity was recorded with magnetoencephalography. There were 2 stimulus conditions of interest: identity primed (i.e., a word preceded by itself) and semantic primed (i.e., a word preceded by a semantically related word). Latency and amplitude of the M350 response as well as reaction time were measured.
Results: Consistent with the age-matched control group, the group with aphasia showed both identity and semantic priming behaviorally. In contrast to the control groups, the group with aphasia did not show either semantic or identity priming of the M350 response. This group also demonstrated longer M350 latencies than either control group. Furthermore, within this group, M350 latency was positively correlated with a measure of semantic impairment.
Conclusions: These findings highlight the usefulness of temporally sensitive measures when studying aphasia and demonstrate that the latency of electrophysiological markers is of interest in this population. In particular, increased M350 latency appears to be indicative of a semantic processing impairment.
C1 [Zipse, Lauryn; Nicholas, Marjorie] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA.
[Kearns, Kevin] SUNY Coll Fredonia, Fredonia, NY 14063 USA.
[Marantz, Alec] NYU, New York, NY USA.
RP Zipse, L (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA.
EM lzipse@mghihp.edu
FU NIDCD NIH HHS [5T32DC000038-20]
NR 70
TC 1
Z9 1
U1 0
U2 6
PU AMER SPEECH-LANGUAGE-HEARING ASSOC
PI ROCKVILLE
PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA
SN 1092-4388
J9 J SPEECH LANG HEAR R
JI J. Speech Lang. Hear. Res.
PD DEC 1
PY 2011
VL 54
IS 6
BP 1577
EP 1596
DI 10.1044/1092-4388(2011/10-0067)
PG 20
WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
GA 891KL
UT WOS:000300215600008
PM 21862679
ER
PT J
AU Parker, MA
AF Parker, Mark A.
TI Biotechnology in the Treatment of Sensorineural Hearing Loss:
Foundations and Future of Hair Cell Regeneration
SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH
LA English
DT Article
DE stem cell; gene therapy; hearing loss; hair cell; regeneration;
development
ID NEURAL STEM-CELLS; MOUSE INNER-EAR; COCHLEAR IMPLANT USERS; MEDIATED
GENE-TRANSFER; AVIAN AUDITORY EPITHELIUM; SPIRAL GANGLION NEURONS;
SEVERE ACOUSTIC TRAUMA; QUALITY-OF-LIFE; NERVOUS-SYSTEM; CHICK COCHLEA
AB Purpose: To provide an overview of the methodologies involved in the field of hair cell regeneration. First, the author provides a tutorial on the biotechnological foundations of this field to assist the reader in the comprehension and interpretation of the research involved in hair cell regeneration. Next, the author presents a review of stem cell and gene therapy and provides a critical appraisal of their application to hair cell regeneration. The methodologies used in these approaches are highlighted.
Method: The author conducted a narrative review of the fields of cellular, molecular, and developmental biology, tissue engineering, and stem cell and gene therapy using the PubMed database.
Results: The use of biotechnological approaches to the treatment of hearing loss-approaches such as stem cell and gene therapy-has led to new methods of regenerating cochlear hair cells in mammals.
Conclusions: Incredible strides have been made in assembling important pieces of the puzzle that comprise hair cell regeneration. However, mammalian hair cell regeneration using stem cell and gene therapy are years-if not decades-away from being clinically feasible. If the goals of the biological approaches are met, these therapies may represent future treatments for hearing loss.
C1 [Parker, Mark A.] Emerson Coll, Boston, MA 02116 USA.
[Parker, Mark A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Parker, Mark A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
RP Parker, MA (reprint author), Emerson Coll, Boston, MA 02116 USA.
EM mark_parker@meei.harvard.edu
FU NIDCD NIH HHS [R03 DC010065-03, R03 DC010065, R03DC010065]
NR 189
TC 6
Z9 8
U1 0
U2 8
PU AMER SPEECH-LANGUAGE-HEARING ASSOC
PI ROCKVILLE
PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA
SN 1092-4388
J9 J SPEECH LANG HEAR R
JI J. Speech Lang. Hear. Res.
PD DEC 1
PY 2011
VL 54
IS 6
BP 1709
EP 1731
DI 10.1044/1092-4388(2011/10-0149)
PG 23
WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
GA 891KL
UT WOS:000300215600017
PM 21386039
ER
PT J
AU Glanc, P
Andreotti, RF
Lee, SI
Allison, SOD
Bennett, GL
Brown, DL
Dubinsky, T
Javitt, MC
Mitchell, DG
Podrasky, AE
Shipp, TD
Siegel, CL
Wong-You-Cheong, JJ
Zelop, CM
AF Glanc, Phyllis
Andreotti, Rochelle F.
Lee, Susanna I.
Allison, Sandra O. DeJesus
Bennett, Genevieve L.
Brown, Douglas L.
Dubinsky, Theodore
Javitt, Marcia C.
Mitchell, Donald G.
Podrasky, Ann E.
Shipp, Thomas D.
Siegel, Cary Lynn
Wong-You-Cheong, Jade J.
Zelop, Carolyn M.
TI ACR Appropriateness Criteria (R) Assessment of Gravid Cervix
SO ULTRASOUND QUARTERLY
LA English
DT Article
DE appropriateness criteria; cervix; preterm birth; gravid; ultrasound
ID ULTRASOUND-INDICATED CERCLAGE; PRETERM PREMATURE RUPTURE; TRANSVAGINAL
ULTRASOUND; DIGITAL EXAMINATION; UTERINE CERVIX; TRANSFUNDAL PRESSURE;
MICROBIAL INVASION; INCOMPETENT CERVIX; INTACT MEMBRANES;
RANDOMIZED-TRIAL
AB It is well recognized that preterm birth is the leading cause of perinatal mortality and morbidity. There is a significant association between cervix length and preterm birth risk. Most authorities consider a cervical length <3 cm as the lower limit of normal. A cervical length >3 cm has a high negative predictive value for delivery less than 34 weeks. A cervical length of <15 mm is moderately predictive (similar to 70%) of preterm birth within 48 hours. Cervical length is normally distributed and should remain relatively constant until the third trimester. Transabdominal US is the least reliable method of cervical length assessment. The most reliable method of documenting cervical length is transvaginal ultrasound (TVUS). Transperineal US is an alternative for imaging if TVUS is contraindicated, such as with premature rupture of membranes. However, the resolution is decreased compared to TVUS. Short cervix length is the single most important predictive finding for premature delivery. This observation should prompt consultation for high risk obstetrical care and consideration of other management options such as cerclage or activity restriction.
The ACR Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed biennially by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging.
C1 [Glanc, Phyllis] Sunnybrook Hlth Sci Ctr, Dept Med Imaging, Toronto, ON M4N 3M5, Canada.
[Andreotti, Rochelle F.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Lee, Susanna I.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Allison, Sandra O. DeJesus] Georgetown Univ Hosp, Washington, DC 20007 USA.
[Bennett, Genevieve L.] NYU Med Ctr, New York, NY 10016 USA.
[Brown, Douglas L.] Mayo Clin, Rochester, MN USA.
[Dubinsky, Theodore] Univ Washington, Sch Med, Seattle, WA USA.
[Javitt, Marcia C.] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Mitchell, Donald G.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
[Podrasky, Ann E.] Baptist Hosp Miami, S Miami Ctr Women & Infants, Miami, FL USA.
[Shipp, Thomas D.] Diagnost Ultrasound Associates, Boston, MA USA.
[Siegel, Cary Lynn] Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Wong-You-Cheong, Jade J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Zelop, Carolyn M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Shipp, Thomas D.; Zelop, Carolyn M.] Amer Coll Obstetricians & Gynecologists, Washington, DC USA.
RP Glanc, P (reprint author), Sunnybrook Hlth Sci Ctr, Dept Med Imaging, 2075 Bayview, Toronto, ON M4N 3M5, Canada.
EM phyllis.glanc@sunnybrook.ca
NR 51
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-8771
J9 ULTRASOUND Q
JI Ultrasound Q.
PD DEC
PY 2011
VL 27
IS 4
BP 275
EP 280
DI 10.1097/RUQ.0b013e3182394123
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 893OY
UT WOS:000300366400006
PM 22124410
ER
PT J
AU Laxminarayan, S
Tadmor, G
Diamond, SG
Miller, E
Franceschini, MA
Brooks, DH
AF Laxminarayan, Srinivas
Tadmor, Gilead
Diamond, Solomon G.
Miller, Eric
Franceschini, Maria Angela
Brooks, Dana H.
TI Modeling habituation in rat EEG-evoked responses via a neural mass model
with feedback
SO BIOLOGICAL CYBERNETICS
LA English
DT Article
DE Neural mass model; Evoked response; Habituation prediction; Low order
model
ID CEREBELLAR PURKINJE-CELL; ACTIVE MEMBRANE MODEL; POTENTIALS; SIMULATION;
FRAMEWORK; DYNAMICS; MEG/EEG; EEG/MEG
AB Habituation is a generic property of the neural response to repeated stimuli. Its strength often increases as inter-stimuli relaxation periods decrease. We propose a simple, broadly applicable control structure that enables a neural mass model of the evoked EEG response to exhibit habituated behavior. A key motivation for this investigation is the ongoing effort to develop model-based reconstruction of multi-modal functional neuroimaging data. The control structure proposed here is illustrated and validated in the context of a biophysical neural mass model, developed by Riera et al. (Hum Brain Mapp 27(11): 896-914, 2006; 28(4): 335-354, 2007), and of simplifications thereof, using data from rat EEG response to medial nerve stimuli presented at frequencies from 1 to 8 Hz. Performance was tested by predictions of both the response to the next stimulus based on the current one, and also of continued stimuli trains over 4-s time intervals based on the first stimulus in the interval, with similar success statistics. These tests demonstrate the ability of simple generative models to capture key features of the evoked response, including habituation.
C1 [Laxminarayan, Srinivas; Tadmor, Gilead; Brooks, Dana H.] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA.
[Diamond, Solomon G.] Thayer Sch Engn Dartmouth, Hanover, NH 03755 USA.
[Miller, Eric] Tufts Univ, Dept Elect & Comp Engn, Medford, MA 02155 USA.
[Franceschini, Maria Angela] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Laxminarayan, S (reprint author), Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA.
EM slaxmina@ece.neu.edu
RI Miller, Eric/B-2546-2008;
OI Miller, Eric/0000-0002-3156-6002; Diamond, Solomon/0000-0002-7589-2942
FU Bernard M. Gordon Center for Subsurface Sensing and Imaging Systems
under National Science Foundation (NSF) [EEC-9986821]; [RO1EB001954]
FX The authors would like to thank David Boas for his helpful suggestions,
and Ilkka Nissila and Weicheng Wu, for collecting the data sets. The
authors would also like to thank the reviewers for their suggestions on
the context of our study with respect to the mechanism of habituation in
neuronal responses, and the tools used for model estimation. Their
suggestions have been very helpful in driving and guiding us to prepare
what we believe is a better presentation of our study. The study of the
first, second, and last authors was supported in part by the Bernard M.
Gordon Center for Subsurface Sensing and Imaging Systems
(Gordon-CenSSIS) under the Engineering Research Centers Program of the
National Science Foundation (NSF) (award EEC-9986821), and by
RO1EB001954. The authors declare that they have no conflict of interest.
The study was approved by the Animal Care Committee of Massachusetts
General Hospital.
NR 39
TC 1
Z9 1
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-1200
J9 BIOL CYBERN
JI Biol. Cybern.
PD DEC
PY 2011
VL 105
IS 5-6
BP 371
EP 397
DI 10.1007/s00422-012-0472-z
PG 27
WC Computer Science, Cybernetics; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA 889TF
UT WOS:000300095600008
PM 22282292
ER
PT J
AU Barrett, LF
AF Barrett, Lisa Feldman
TI Was Darwin Wrong About Emotional Expressions?
SO CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE
LA English
DT Article
DE Darwin; emotion; emotional expression
ID FACIAL EXPRESSIONS; BASIC EMOTIONS; PSYCHOLOGICAL CONSTRUCTION;
CONGENITALLY BLIND; PERCEPTION; BEHAVIOR; CONTEXT; METAANALYSIS;
RECOGNITION; EXPERIENCE
AB Emotional expressions have endured as a topic of profound scientific interest for over a century, in part due to Darwin's classic volume, The Expression of Emotions in Man and Animals. Since its publication, there has been a strong, spirited debate over the origin, nature, and function of emotional expressions. In this article, I consider two basic questions: What did Darwin really write about emotional expressions, and how well does his account match the modern, conventional, "basic emotion" account? And does the scientific evidence specifically support the modern account of Darwin's view, or are there alternative hypotheses that provide good ( or even better) interpretations for the data at hand? I discuss the various ways that Darwin might be correct ( and incorrect) about how emotions and their manifestations have been sculpted by natural selection.
C1 [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA.
[Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA.
[Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA.
RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, Boston, MA 02115 USA.
EM barrett@neu.edu
NR 49
TC 31
Z9 31
U1 3
U2 41
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0963-7214
J9 CURR DIR PSYCHOL SCI
JI Curr. Dir. Psychol.
PD DEC
PY 2011
VL 20
IS 6
BP 400
EP 406
DI 10.1177/0963721411429125
PG 7
WC Psychology, Multidisciplinary
SC Psychology
GA 889XP
UT WOS:000300109400011
ER
PT J
AU Habibi, E
Masoudi-Nejad, A
Abdolmaleky, HM
Haggarty, SJ
AF Habibi, Ehsan
Masoudi-Nejad, Ali
Abdolmaleky, Hamid Mostafavi
Haggarty, Stephen J.
TI Emerging roles of epigenetic mechanisms in Parkinson's disease
SO FUNCTIONAL & INTEGRATIVE GENOMICS
LA English
DT Review
DE Parkinson's disease; Epigenetics; Neurodegenerative disorders;
Neurodevelopmental disorders; Psychiatric disorders; Systems biology
ID RUBINSTEIN-TAYBI-SYNDROME; HISTONE DEMETHYLASE LSD1; MYOCYTE ENHANCER
FACTOR-2; CPG-BINDING PROTEIN-2; FRAGILE-X-SYNDROME; ALPHA-SYNUCLEIN;
HUNTINGTONS-DISEASE; DNA METHYLATION; ALZHEIMER-DISEASE; GENE-EXPRESSION
AB Epigenetic mechanisms have emerged as important components of a variety of human diseases, including cancer and central nervous system disorders. Despite recent studies highlighting the role of epigenetic mechanisms in several neurodegenerative and neuropsychiatric disorders, to date, there has been a paucity of studies exploring the role of epigenetic factors in Parkinson's disease (PD). PD is a progressive neurological disorder with characteristic motor and non-motor symptoms, including a range of neuropsychiatric features, for which neither preventative nor effective long-term treatment strategies are available. It is one of the most common neurodegenerative disorders and the second most prevalent after Alzheimer's disease. In this review, we present several lines of evidence suggesting that epigenetic factors may play an important role in the pathogenesis of PD and propose on this basis a framework to guide future investigations into epigenetic mechanisms and systems biology of PD. These notions, together with technical advances in the ability to perform genome-wide analysis of epigenomic states, and newly available small-molecule probes targeting chromatin-modifying enzymes, may help design new treatment strategies for PD and other human diseases involving epigenetic dysregulation.
C1 [Habibi, Ehsan; Masoudi-Nejad, Ali] Univ Tehran, Lab Syst Biol & Bioinformat LBB, Inst Biochem & Biophys, Tehran, Iran.
[Habibi, Ehsan; Masoudi-Nejad, Ali] Univ Tehran, Ctr Excellence Biomath, Tehran, Iran.
[Abdolmaleky, Hamid Mostafavi] Boston Univ, Sch Med, Genet Program, Boston, MA 02118 USA.
[Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA.
RP Masoudi-Nejad, A (reprint author), Univ Tehran, Lab Syst Biol & Bioinformat LBB, Inst Biochem & Biophys, Tehran, Iran.
EM amasoudin@ibb.ut.ac.ir; haggarty@chgr.mgh.harvard.edu
OI Haggarty, Stephen J./0000-0002-7872-168X
FU Iran National Science Foundation; National Institute On Drug Abuse
[R01DA028301]
FX Part of this project has been funded by Iran National Science Foundation
(www.insf.org). S.J.H. is supported by Award Number R01DA028301 from the
National Institute On Drug Abuse. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institute On Drug Abuse or the National
Institutes of Health.
NR 158
TC 18
Z9 20
U1 5
U2 31
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1438-793X
J9 FUNCT INTEGR GENOMIC
JI Funct. Integr. Genomics
PD DEC
PY 2011
VL 11
IS 4
BP 523
EP 537
DI 10.1007/s10142-011-0246-z
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 889SM
UT WOS:000300093500002
PM 21892731
ER
PT J
AU Kato, K
Yasutake, M
Yonetsu, T
Kim, SJ
Xing, L
Kratlian, CM
Takano, M
Mizuno, K
Jang, IK
AF Kato, Koji
Yasutake, Masahiro
Yonetsu, Taishi
Kim, Soo Joong
Xing, Lei
Kratlian, Christina M.
Takano, Masamichi
Mizuno, Kyoichi
Jang, Ik-Kyung
TI Intracoronary Imaging Modalities for Vulnerable Plaques
SO JOURNAL OF NIPPON MEDICAL SCHOOL
LA English
DT Review
DE vulnerable plaque; virtual histology intravascular ultrasound (VH-IVUS);
integrated backscatter intravascular ultrasound (IB-IVUS); angioscopy;
optical coherence tomography (OCT)
ID OPTICAL COHERENCE TOMOGRAPHY; BACKSCATTER-INTRAVASCULAR ULTRASOUND;
ACUTE CORONARY SYNDROMES; THIN-CAP FIBROATHEROMA; RADIOFREQUENCY
DATA-ANALYSIS; ELECTIVE STENT IMPLANTATION; RISK-ASSESSMENT STRATEGIES;
IN-VIVO CHARACTERIZATION; VIRTUAL HISTOLOGY; MYOCARDIAL-INFARCTION
AB The concept of vulnerable plaque (VP) has been widely accepted as the primary cause of acute coronary syndrome (ACS) and sudden cardiac death. ACS is thought to result from sudden disruption of a VP with subsequent occlusive thrombosis. VP typically consists of several components; a large necrotic core, thin fibrous cap, increase in macrophage activity, increase in vaso vasorum, and positive remodeling.
In recent years, invasive or non-invasive diagnostic imaging modalities have been developed for indentifying VP. VP has been recognized in various modalities not only by visualization of cross sectional images by high-resolution imaging modalities, such as virtual histology intravascular ultrasound (VH-IVUS), integrated backscatter (TB) IVUS, and optical coherence tomography (OCT), but also by direct visualization by intracoronary angioscopy.
VH-IVUS uses advanced radiofrequency signal analysis of ultrasound signals and allows detailed qualitative and quantitative assessment of plaque composition, while IB-IVUS analyzes the radiofrequency signal by applying a fast Fourier transformation of the component of the backscattered signals. Different tissue components reflect the radiofrequency signaling at different power levels, which could be used to differentiate various tissue components. Angioscopy allows direct visualization of internal surface of the lumen, providing the detailed information of characteristics of plaque and thrombus. Optical coherence tomography (OCT) is an analog of IVUS, but uses light instead of sound. OCT has a 10-fold higher image resolution (10-15 mu m) compared to conventional IVUS, therefore it is able to provide superior image quality. The commercially available versions of the technology used time-domain (TD) OCT (M2, M3, Light lab, Westford, MA, USA) and fourier-domain (FD) OCT (C7XR, Light lab. Westford, MA, USA). OCT is the only imaging modality with high enough resolution to measure fibrous cap thickness and neovascularization. Moreover OCT has a unique ability of detecting macrophages.
In this review, we attempted to summarize the advantages and limitations of the currently available intravascular modalities. (J Nippon Med Sch 2011; 78: 340-351)
C1 [Kato, Koji; Yonetsu, Taishi; Kim, Soo Joong; Xing, Lei; Kratlian, Christina M.; Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Kato, Koji; Yonetsu, Taishi; Kim, Soo Joong; Xing, Lei; Kratlian, Christina M.; Jang, Ik-Kyung] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Yasutake, Masahiro; Mizuno, Kyoichi] Nippon Med Sch, Dept Internal Med, Div Cardiol Hepatol Geriatr & Integrated Med, Tokyo, Japan.
[Kim, Soo Joong] Kyung Hee Univ, Coll Med, Dept Cardiol, Seoul, South Korea.
[Takano, Masamichi] Chiba Hokusoh Hosp, Nippon Med Sch, Ctr Cardiovasc, Chiba, Japan.
RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St GRB 800, Boston, MA 02114 USA.
EM ijang@partners.org
NR 68
TC 5
Z9 5
U1 0
U2 3
PU MEDICAL ASSOC NIPPON MEDICAL SCH
PI TOKYO
PA 1-1-5, SENDAGI, TOKYO, 113-8602, JAPAN
SN 1345-4676
J9 J NIPPON MED SCH
JI J. Nippon Med. Sch.
PD DEC
PY 2011
VL 78
IS 6
BP 340
EP 351
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 888BQ
UT WOS:000299979200002
PM 22197866
ER
PT J
AU Lenders, CM
Gorman, K
Lim-Miller, A
Puklin, S
Pratt, J
AF Lenders, C. M.
Gorman, K.
Lim-Miller, A.
Puklin, S.
Pratt, J.
TI Practical Approaches to the Treatment of Severe Pediatric Obesity
SO PEDIATRIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Pediatrics; Severe obesity; Assessment; Pharmacotherapy; Weight loss
surgery; Behavior treatment
ID FAMILY-BASED TREATMENT; WEIGHT-LOSS SURGERY; CONTROLLED-TRIAL; CHILDHOOD
OVERWEIGHT; BARIATRIC SURGERY; SLEEP DURATION; RISK-FACTORS; CHILDREN;
ADOLESCENTS; INTERVENTIONS
AB Pediatric obesity is a major public health threat. Obese children and adolescents are at increased risk for many medical and surgical conditions. These conditions may affect their quality of life and life expectancy. The rapidly progressive nature of type 2 diabetes mellitus within the first 5 years of obesity diagnosis is particularly concerning. Because health risk increases with degree of obesity, adolescents who may be eligible for more aggressive obesity treatment should be identified and counseled.
C1 [Lenders, C. M.] Boston Univ, Sch Med, Dept Pediat,Boston Med Ctr, Nutr & Fitness Life Program Pediat Obes, Boston, MA 02118 USA.
[Lenders, C. M.; Pratt, J.] Harvard Univ, Sch Med, Boston, MA 02118 USA.
[Pratt, J.] Massachusetts Gen Hosp, Weight Loss Surg Program, Dept Surg, Boston, MA 02114 USA.
RP Lenders, CM (reprint author), Boston Univ, Sch Med, Dept Pediat,Boston Med Ctr, Nutr & Fitness Life Program Pediat Obes, Vose Hall 3,88 E Newton St, Boston, MA 02118 USA.
EM Carine.Lenders@bmc.org
RI DE SOUZA, AGLECIO/Q-4056-2016
NR 42
TC 7
Z9 8
U1 2
U2 9
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0031-3955
J9 PEDIATR CLIN N AM
JI Pediatr. Clin. N. Am.
PD DEC
PY 2011
VL 58
IS 6
BP 1425
EP +
DI 10.1016/j.pcl.2011.09.013
PG 16
WC Pediatrics
SC Pediatrics
GA 865LF
UT WOS:000298311700008
PM 22093860
ER
PT J
AU Tannock, LR
AF Tannock, Lisa R.
TI Ursolic acid effect on atherosclerosis: Apples and apples, or apples and
oranges?
SO ATHEROSCLEROSIS
LA English
DT Editorial Material
DE Ursolic acid; Atherosclerosis; Mouse models
ID RECEPTOR-DEFICIENT MICE; APOLIPOPROTEIN-E
C1 [Tannock, Lisa R.] Univ Kentucky, Div Endocrinol & Mol Med, Lexington, KY 40536 USA.
[Tannock, Lisa R.] US Dept Vet Affairs, Lexington, KY USA.
RP Tannock, LR (reprint author), Univ Kentucky, Div Endocrinol & Mol Med, Wethington Bldg,Room 567,900 S Limestone St, Lexington, KY 40536 USA.
EM Lisa.Tannock@uky.edu
NR 8
TC 5
Z9 5
U1 0
U2 12
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 DEC
PY 2011
VL 219
IS 2
BP 397
EP 398
DI 10.1016/j.atherosclerosis.2011.09.029
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 872MN
UT WOS:000298813900007
PM 21993411
ER
PT J
AU Prudente, S
Morini, E
Larmon, J
Andreozzi, F
Di Pietro, N
Nigro, A
Gervino, EV
Mannino, GC
Bacci, S
Hauser, TH
Bellacchio, E
Formoso, G
Pellegrini, F
Proto, V
Menzaghi, C
Frittitta, L
Pandolfi, A
Sesti, G
Doria, A
Trischitta, V
AF Prudente, Sabrina
Morini, Eleonora
Larmon, Jay
Andreozzi, Francesco
Di Pietro, Natalia
Nigro, Angela
Gervino, Ernest V.
Mannino, Gaia Chiara
Bacci, Simonetta
Hauser, Thomas H.
Bellacchio, Emanuele
Formoso, Gloria
Pellegrini, Fabio
Proto, Vittoria
Menzaghi, Claudia
Frittitta, Lucia
Pandolfi, Assunta
Sesti, Giorgio
Doria, Alessandro
Trischitta, Vincenzo
TI The SH2B1 obesity locus is associated with myocardial infarction in
diabetic patients and with NO synthase activity in endothelial cells
SO ATHEROSCLEROSIS
LA English
DT Article
DE Genetic risk factors; Polymorphisms; Coronary artery disease; Type 2
diabetes mellitus; Insulin resistance; Myocardial infarction
ID CORONARY-ARTERY-DISEASE; GENOME-WIDE ASSOCIATION; NITRIC-OXIDE SYNTHASE;
BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE;
IDENTIFICATION; RISK; SUSCEPTIBILITY; INDIVIDUALS
AB Objective: Obesity and cardiovascular disease recognize a common metabolic soil and may therefore share part of their genetic background. Genome-wide association studies have identified variability at the SH2B1 locus as a predictor of obesity. We investigated whether SNP rs4788102, which captures the entire SH2B1 variability, is associated with coronary artery disease (CAD) and/or myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM).
Design and setting: SNP rs4788102 was typed in 2015 White subjects with T2DM from three CAD case-control studies [n = 740 from the Gargano Hearth Study (GHS, Italy); n = 818 from the Joslin Hearth Study (JHS, Boston); n = 457 from the University of Catanzaro (CZ, Italy)].
Results: SNP rs4788102 (G/A) was not associated with CAD (overall allelic OR = 1.06, 95% CI = 0.93-1.21; p = 0.37). On the contrary, it was associated with MI in GHS (1.42, 1.12-1.81; p = 0.004) and in the three samples analyzed together (1.21, 1.04-1.41; p = 0.016). Insulin stimulated nitric oxide synthase (NOS) activity in human vein endothelial cells from G/G (n = 4, p = 0.03) but not the G/A (n = 5,p = 0.83) genotype. Of the SNPs in perfect LD with rs4788102, one (rs7498665) affects amino acid polarity (Ala484Thr) and falls into a highly conserved protein segment of SH2B1 containing a class II SH3 domain binding site.
Conclusions: Variability at the SH2B1 obesity locus is associated with MI in diabetic patients and with reduced insulin-stimulated NOS activity in human endothelial cells. Further studies are needed to replicate this association and dissect the biology underlying this finding. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Prudente, Sabrina; Bellacchio, Emanuele; Proto, Vittoria; Trischitta, Vincenzo] IRCSS Casa Sollievo Sofferenza, Mendel Lab, San Giovanni Rotondo, Italy.
[Morini, Eleonora; Menzaghi, Claudia; Trischitta, Vincenzo] IRCSS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy.
[Larmon, Jay; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.
[Andreozzi, Francesco; Mannino, Gaia Chiara; Sesti, Giorgio] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy.
[Di Pietro, Natalia; Pandolfi, Assunta] Univ G DAnnunzio, Aging Res Ctr, Dept Biomed Sci, G DAnnunzio Univ Fdn,CeSI, Chieti, Italy.
[Nigro, Angela; Frittitta, Lucia] Univ Catania, Sch Med, Garibaldi Hosp, Unit Endocrinol,Dept Internal & Specialist Med, Catania, Italy.
[Gervino, Ernest V.; Hauser, Thomas H.; Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Bacci, Simonetta] IRCCS Casa Sollievo Sofferenza, Unit Endocrinol, San Giovanni Rotondo, Italy.
[Formoso, Gloria] Univ G DAnnunzio, Aging Res Ctr, Dept Med & Aging Sci, CeSI,G DAnnunzio Univ Fdn, Chieti, Italy.
[Pellegrini, Fabio] IRCCS Casa Sollievo Sofferenza, Biostat Unit, San Giovanni Rotondo, Italy.
[Pellegrini, Fabio] Consorzio Mario Negri Sud, Dept Clin Pharmacol & Epidemiol, Chieti, Italy.
[Doria, Alessandro] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy.
RP Prudente, S (reprint author), CSS Mendel Inst, Viale Regina Margherita 261, I-00198 Rome, Italy.
EM s.prudente@css-mendel.it; vincenzo.trischitta@uniroma1.it
RI Sesti, Giorgio/B-1509-2012; Prudente, Sabrina/H-2886-2016; Mannino,
Gaia/K-1580-2016; Di Pietro, Natalia/K-1604-2016; Trischitta,
Vincenzo/K-1487-2016; pandolfi, assunta/K-4595-2016;
OI Menzaghi, Claudia/0000-0002-7438-8955; Sesti,
Giorgio/0000-0002-1618-7688; Prudente, Sabrina/0000-0001-9220-8981;
Mannino, Gaia/0000-0002-6341-4572; Di Pietro,
Natalia/0000-0001-9720-2116; Trischitta, Vincenzo/0000-0003-1174-127X;
pandolfi, assunta/0000-0003-4135-7631; Andreozzi,
Francesco/0000-0001-9375-1513
FU Italian Ministry of Health; Fondazione Roma; National Institutes of
Health [HL73168, DK36836]; European Union [LSHM-CT-2004-512013]
FX This work was partly supported by the Italian Ministry of Health
(Ricerca Corrente 2010 and 2011 to S.P and V.T), by the Fondazione Roma
("Sostegno alla ricerca scientifica biomedica 2008" to V.T), by the
National Institutes of Health (HL73168 to A.D. and DK36836 to the
Genetics Core of the Diabetes 82 Endocrinology Research Center at the
Joslin Diabetes Center), and by the European Union (FP6 EUGENE2 no.
LSHM-CT-2004-512013 to G.S.).
NR 36
TC 11
Z9 11
U1 0
U2 4
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 DEC
PY 2011
VL 219
IS 2
BP 667
EP 672
DI 10.1016/j.atherosclerosis.2011.08.019
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 872MN
UT WOS:000298813900047
PM 21907990
ER
PT J
AU Kaz, AM
Wong, CJ
Luo, YX
Virgin, JB
Washington, MK
Willis, JE
Leidner, RS
Chak, A
Grady, WM
AF Kaz, Andrew M.
Wong, Chao-Jen
Luo, Yanxin
Virgin, Jeffrey B.
Washington, M. Kay
Willis, Joseph E.
Leidner, Rom S.
Chak, Amitabh
Grady, William M.
TI DNA methylation profiling in Barrett's esophagus and esophageal
adenocarcinoma reveals unique methylation signatures and molecular
subclasses
SO EPIGENETICS
LA English
DT Article
DE Barrett's esophagus; esophageal adenocarcinoma; DNA methylation;
methylation microarray
ID HIGH-GRADE DYSPLASIA; NEOPLASTIC PROGRESSION; PREDICTS PROGRESSION;
CANCER; PHENOTYPE; RISK; HYPERMETHYLATION; OVEREXPRESSION; METAPLASIA;
BIOMARKERS
AB Barrett's esophagus (BE) is a metaplastic process whereby the normal stratified, squamous esophageal epithelium is replaced by specialized intestinal epithelium. Barrett's is the only accepted precursor lesion for esophageal adenocarcinoma (EAC), a solid tumor that is rapidly increasing in incidence in western countries. BE evolves into EAC through intermediate steps that involve increasing degrees of dysplasia. Current histologic criteria are quite subjective and the clinical behavior of BE is highly variable and difficult to predict using these standards. It is widely believed that molecular alterations present in BE and EAC will provide more precise prognostic and predictive markers for these conditions than the current clinical and histologic features in use. In order to further define molecular alterations that can classify unique groups of BE and EAC, we utilized methylation microarrays to compare the global gene methylation status of a collection of normal squamous, BE, BE+ high-grade dysplasia (HGD) and EAC cases. We found distinct global methylation signatures, as well as differential methylation of specific genes, that discriminated these histological groups. We also noted high and low methylation epigenotypes among the BE and EAC cases. Additional validation of those CpG sites that distinguished BE from BE + HGD and EAC may lead to the discovery of useful biomarkers with potential clinical applications in the diagnosis and prognosis of BE and EAC.
C1 [Kaz, Andrew M.; Luo, Yanxin; Grady, William M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Kaz, Andrew M.; Grady, William M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[Virgin, Jeffrey B.] VA Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA USA.
[Kaz, Andrew M.] VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA.
[Luo, Yanxin] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal Surg, Guangzhou 510275, Guangdong, Peoples R China.
[Luo, Yanxin] Sun Yat Sen Univ, Gastrointestinal Inst, Guangzhou 510275, Guangdong, Peoples R China.
[Washington, M. Kay] Vanderbilt Univ, Dept Pathol, Nashville, TN USA.
[Willis, Joseph E.] Case Western Reserve Univ, Sch Med, Dept Pathol, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
[Chak, Amitabh] Case Western Reserve Univ, Sch Med, Div Gastroenterol, Case Comprehens Canc Ctr, Cleveland, OH USA.
[Leidner, Rom S.; Chak, Amitabh] Case Western Reserve Univ, Sch Med, Div Oncol, Case Comprehens Canc Ctr, Cleveland, OH USA.
RP Grady, WM (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
EM akaz@fhcrc.org; wgrady@fhcrc.org
FU NIH/NIDDK [05K08-DK080630, K24DK002800]; NIH/NCI [CA135692]; Midcareer
Award in Patient Orient Research; Burroughs Wellcome Fund; [U54
CA163060-01]; [U01CA152756-01]
FX This research was supported by NIH/NIDDK grant 05K08-DK080630 (A.M.K.),
NIH/NCI CA135692 (A.C.), a Midcareer Award in Patient Orient Research,
NIH/NIDDK K24DK002800 (A.C.), U54 CA163060-01 (W.M.G, A.K., A.C.),
Burroughs Wellcome Fund (W.M.G.) and U01CA152756-01 (W.M.G).
NR 51
TC 22
Z9 24
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1559-2294
J9 EPIGENETICS-US
JI Epigenetics
PD DEC
PY 2011
VL 6
IS 12
BP 1403
EP 1412
DI 10.4161/epi.6.12.18199
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 886CI
UT WOS:000299828200001
PM 22139570
ER
PT J
AU Baron, JM
Higgins, JM
Dzik, WH
AF Baron, Jason M.
Higgins, John M.
Dzik, Walter H.
TI A Revised Timeline for the Origin of Plasmodium falciparum as a Human
Pathogen
SO JOURNAL OF MOLECULAR EVOLUTION
LA English
DT Article
DE Plasmodium falciparum; P. falciparum; Molecular clock; Malaria;
Evolution; Host switch; Malarial anthropophily
ID HUMAN MALARIA PARASITE; MOLECULAR CLOCK; EVOLUTIONARY; GENETICS; GENOME;
DIVERSIFICATION; SUSCEPTIBILITY; HYPOTHESIS; CHILDREN; DISEASES
AB While Plasmodium falciparum is known to have had a strong effect on human evolution, the time period when P. falciparum first infected ancestors of modern humans has remained uncertain. Recent advances demonstrated that P. falciparum evolved from ancestors of gorilla parasites via host switching. Here, we estimate the range of dates during which this host switch may have occurred. DNA sequences of portions of the mitochondrial cytochrome b gene obtained from gorilla parasites closely related to human P. falciparum were aligned and compared against similar sequences from human P. falciparum. Time estimates were calculated by applying a previously established parasite cytochrome b gene mutation rate (0.012 mutations per site per million years) and by modeling uncertainty in a Monte-Carlo simulation. We estimate a 95% confidence interval for when P. falciparum first infected ancestors of modern humans to be 112,000 and 1,036,000 years ago (median estimate, 365,000 years ago). This confidence interval suggests that P. falciparum first infected human ancestors much more recently than the previous recognized estimate of 2.5 million years ago. The revised estimate may inform our understanding of certain aspects of human-malaria co-evolution. For example, this revised date suggests a closer relationship between the entry of P. falciparum in humans and the appearance of many red blood cell polymorphisms considered to be genetic adaptations to malaria. In addition, the confidence interval lies within the timeframe dating the dawn of Homo sapiens, suggesting that P. falciparum may have undergone host switching as a Plasmodia adaptation specific for our species.
C1 [Baron, Jason M.; Higgins, John M.; Dzik, Walter H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Higgins, John M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Higgins, John M.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA.
RP Baron, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Room GRJ 235,55 Fruit St, Boston, MA 02114 USA.
EM jmbaron@partners.org
NR 34
TC 7
Z9 7
U1 4
U2 42
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0022-2844
J9 J MOL EVOL
JI J. Mol. Evol.
PD DEC
PY 2011
VL 73
IS 5-6
BP 297
EP 304
DI 10.1007/s00239-011-9476-x
PG 8
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 887OT
UT WOS:000299938500005
PM 22183792
ER
PT J
AU Linder, JA
Rigotti, NA
Schneider, LI
Kelley, JHK
Brawarsky, P
Schnipper, JL
Middleton, B
Haas, JS
AF Linder, Jeffrey A.
Rigotti, Nancy A.
Schneider, Louise I.
Kelley, Jennifer H. K.
Brawarsky, Phyllis
Schnipper, Jeffrey L.
Middleton, Blackford
Haas, Jennifer S.
TI Clinician characteristics and use of novel electronic health record
functionality in primary care
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID DECISION-SUPPORT-SYSTEMS; PATIENT OUTCOMES; AMBULATORY-CARE; QUALITY;
PERFORMANCE; IMPACT; TRIAL
AB Background Conventional wisdom holds that older, busier clinicians who see complex patients are less likely to adopt and use novel electronic health record (EHR) functionality.
Methods To compare the characteristics of clinicians who did and did not use novel EHR functionality, we conducted a retrospective analysis of the intervention arm of a randomized trial of new EHR-based tobacco treatment functionality.
Results The novel functionality was used by 103 of 207 (50%) clinicians. Staff physicians were more likely than trainees to use the functionality (64% vs 37%; p<0.001). Clinicians who graduated more than 10 years previously were more likely to use the functionality than those who graduated less than 10 years previously (64% vs 42%; p<0.01). Clinicians with higher patient volumes were more likely to use the functionality (lowest quartile of number of patient visits, 25%; 2nd quartile, 38%; 3rd quartile, 65%; highest quartile, 71%; p<0.001). Clinicians who saw patients with more documented problems were more likely to use the functionality (lowest tertile of documented patient problems, 38%; 2nd tertile, 58%; highest tertile, 54%; p=0.04). In multivariable modeling, independent predictors of use were the number of patient visits (OR 1.2 per 100 additional patients; 95% CI 1.1 to 1.4) and number of documented problems (OR 2.9 per average additional problem; 95% CI 1.4 to 6.1).
Conclusions Contrary to conventional wisdom, clinically busier physicians seeing patients with more documented problems were more likely to use novel EHR functionality.
C1 [Linder, Jeffrey A.; Schneider, Louise I.; Brawarsky, Phyllis; Schnipper, Jeffrey L.; Middleton, Blackford; Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02120 USA.
[Linder, Jeffrey A.; Rigotti, Nancy A.; Schneider, Louise I.; Schnipper, Jeffrey L.; Middleton, Blackford; Haas, Jennifer S.] Harvard Univ, Sch Med, Boston, MA USA.
[Rigotti, Nancy A.; Kelley, Jennifer H. K.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
[Rigotti, Nancy A.; Kelley, Jennifer H. K.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
RP Linder, JA (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, 1620 Tremont St,BC 3-2X, Boston, MA 02120 USA.
EM jlinder@partners.org
FU National Cancer Institute [R21 CA121906]; Agency for Healthcare Research
and Quality [R01 HS015169-01, K08 HS014563]; National Heart, Lung, and
Blood Institute [1K08 HL072806-01]
FX This study was supported by grants from the National Cancer Institute
(R21 CA121906) and the Agency for Healthcare Research and Quality (R01
HS015169-01). Dr Linder was supported by a career development award from
the Agency for Healthcare Research and Quality (K08 HS014563). Dr
Schnipper was supported by a mentored career development award from the
National Heart, Lung, and Blood Institute (1K08 HL072806-01).
NR 20
TC 3
Z9 3
U1 2
U2 9
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD DEC
PY 2011
VL 18
SU 1
BP I87
EP I90
DI 10.1136/amiajnl-2011-000330
PG 4
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Health Care Sciences & Services;
Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
Library Science; Medical Informatics
GA 886RJ
UT WOS:000299871300014
PM 21900702
ER
PT J
AU Miller, AM
Boro, MS
Korman, NE
Ben Davoren, J
AF Miller, Allison M.
Boro, Maureen S.
Korman, Nancy E.
Ben Davoren, J.
TI Provider and pharmacist responses to warfarin drug-drug interaction
alerts: a study of healthcare downstream of CPOE alerts
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID PHYSICIAN ORDER ENTRY; CLINICAL DECISION-SUPPORT; PLASMINOGEN-ACTIVATOR;
MYOCARDIAL-INFARCTION; PHASE-I; MEDICATION; SYSTEM; RATES; THROMBOLYSIS;
PRESCRIBERS
AB Objective To categorize the appropriateness of provider and pharmacist responses to warfarin critical drug-drug interaction (cDDI) alerts, assess responses and actions to the cDDI, and determine the occurrence of warfarin adverse drug events (ADE) after alerts.
Design An 18-month, retrospective study of acute care admissions at a single Veterans Affairs medical center using computerized provider order entry (CPOE).
Measurements Patients included had at least one warfarin cDDI alert. Chart reviews included baseline laboratory values and demographics, provider actions, patient outcomes, and associated factors, including other interacting medications and number of simultaneously processed alerts.
Results 137 admissions were included (133 unique patients). Amiodarone, vitamin E in a multivitamin, sulfamethoxazole, and levothyroxine accounted for 75% of warfarin cDDI. Provider responses were clinically appropriate in 19.7% of admissions and pharmacist responses were appropriate in 9.5% of admissions. There were 50 ADE (36.6% of admissions) with warfarin; 80% were rated as having no or mild clinical effect. An increased number of non-critical alerts at the time of the reference cDDI alert was the only variable associated with an inappropriate provider response (p=0.01).
Limitations This study was limited by being a retrospective review and the possibility of confounding variables, such as other interacting medications.
Conclusion The large number of CPOE alerts may lead to inappropriate responses by providers and pharmacists. The high rate of ADE suggests a need for improved medication management systems for patients on warfarin. This study highlights the possibility of alert fatigue contributing to the high prevalence of inappropriate alert over-ride text responses.
C1 [Miller, Allison M.] Univ Calif San Francisco, Dept Pharmaceut Serv, San Francisco, CA 94143 USA.
[Boro, Maureen S.; Korman, Nancy E.] San Francisco VA Med Ctr, Serv Pharm, San Francisco, CA USA.
[Ben Davoren, J.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA.
RP Miller, AM (reprint author), Univ Calif San Francisco, Dept Pharmaceut Serv, 505 Parnassus Ave,Rm M39C,Box 0622, San Francisco, CA 94143 USA.
EM allison.miller@ucsfmedctr.org
NR 31
TC 20
Z9 20
U1 2
U2 12
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD DEC
PY 2011
VL 18
SU 1
BP I45
EP I50
DI 10.1136/amiajnl-2011-000262
PG 6
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Health Care Sciences & Services;
Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
Library Science; Medical Informatics
GA 886RJ
UT WOS:000299871300009
PM 22037888
ER
PT J
AU Murphy, SN
Gainer, V
Mendis, M
Churchill, S
Kohane, I
AF Murphy, Shawn N.
Gainer, Vivian
Mendis, Michael
Churchill, Susanne
Kohane, Isaac
TI Strategies for maintaining patient privacy in i2b2
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID AUTOMATIC DE-IDENTIFICATION; INFORMATION; ENTERPRISE; DOCUMENTS; ACCESS
AB Background The re-use of patient data from electronic healthcare record systems can provide tremendous benefits for clinical research, but measures to protect patient privacy while utilizing these records have many challenges. Some of these challenges arise from a misperception that the problem should be solved technically when actually the problem needs a holistic solution.
Objective The authors' experience with informatics for integrating biology and the bedside (i2b2) use cases indicates that the privacy of the patient should be considered on three fronts: technical de-identification of the data, trust in the researcher and the research, and the security of the underlying technical platforms.
Methods The security structure of i2b2 is implemented based on consideration of all three fronts. It has been supported with several use cases across the USA, resulting in five privacy categories of users that serve to protect the data while supporting the use cases.
Results The i2b2 architecture is designed to provide consistency and faithfully implement these user privacy categories. These privacy categories help reflect the policy of both the Health Insurance Portability and Accountability Act and the provisions of the National Research Act of 1974, as embodied by current institutional review boards.
Conclusion By implementing a holistic approach to patient privacy solutions, i2b2 is able to help close the gap between principle and practice.
C1 [Murphy, Shawn N.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA.
[Murphy, Shawn N.; Kohane, Isaac] Harvard Univ, Sch Med, Boston, MA USA.
[Murphy, Shawn N.; Gainer, Vivian; Mendis, Michael; Churchill, Susanne] Partners HealthCare Syst Inc, Informat Syst, Wellesley, MA USA.
[Kohane, Isaac] Childrens Hosp, Boston, MA 02115 USA.
[Kohane, Isaac] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Murphy, SN (reprint author), Partners HealthCare Syst Inc, Informat Syst, Constitut Ctr 1, Charlestown, MA 02129 USA.
EM murphy.shawn@mgh.harvard.edu
RI Kohane, Isaac Kohane/K-3716-2012
OI Kohane, Isaac Kohane/0000-0003-2192-5160
FU National Institutes of Health through the NIH Roadmap for Medical
Research [U54LM008748]
FX This work was funded by the National Institutes of Health through the
NIH Roadmap for Medical Research, grant U54LM008748.
NR 19
TC 12
Z9 12
U1 0
U2 8
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD DEC
PY 2011
VL 18
SU 1
BP I103
EP I108
DI 10.1136/amiajnl-2011-000316
PG 6
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Health Care Sciences & Services;
Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
Library Science; Medical Informatics
GA 886RJ
UT WOS:000299871300017
PM 21984588
ER
PT J
AU Gutman, R
DeDe, G
Caplan, D
Liu, JS
AF Gutman, Roee
DeDe, Gayle
Caplan, David
Liu, Jun S.
TI Rasch Model and Its Extensions for Analysis of Aphasic Deficits in
Syntactic Comprehension
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE Bayesian analysis; GLMM; IRT; Mixture models; Similar tests
ID MAXIMUM-LIKELIHOOD; EM ALGORITHM; FIT; DISTRIBUTIONS; PARAMETERS
AB Aphasia is the loss of the ability to produce and/or comprehend language, due to injury to brain areas responsible for these functions. Aphasic patients' performance on comprehension tests has traditionally been related both to the patient's individual ability and to the difficulty of the test questions. The natural choice for analysis of these test results is the Rasch model. It assumes that the probability of a patient responding correctly to a question is the inverse-logit function of the difference between the individual patient's ability and the difficulty of the test question. This study first modeled the way aphasic patients process different sentence types, as well as their ability to accomplish tasks using Rasch models. However, several scientifically important features of the data, such as the correlation of correct responses between two different comprehension tasks, and the association between response patterns in control sentences and response patterns in experimental sentences, were found to be inadequately captured by such models. Alternatively, we used a full Bayesian approach, exploring a mixture of generalized linear mixed models that clustered patients into similar response patterns and abilities. The mixture model was found to better describe the experimental results than any other model examined. The mixture model also expresses the hypothesis that aphasic patients can be classified into different ability and response profile groups, and that patients utilize different cognitive resources in different comprehension tasks. These results are scientifically important and could not have been discovered by using the simple Rasch model. This article has supplementary material online.
C1 [Gutman, Roee] Brown Univ, Dept Biostat, Providence, RI 02912 USA.
[DeDe, Gayle] Univ Arizona, Speech Language & Hearing Sci Dept, Tucson, AZ 85721 USA.
[Caplan, David] Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA.
[Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA.
RP Gutman, R (reprint author), Brown Univ, Dept Biostat, Providence, RI 02912 USA.
EM rgutman@stat.brown.edu; gdede@email.arizona.edu; dcaplan@patners.org;
jliu@stat.harvard.edu
RI Gutman, Roee/J-2355-2014
OI Gutman, Roee/0000-0001-7095-3016
FU NSF [DMS-0907562, DMS-0906545]; NIDCD [DC00942]
FX Roee Gutman is Assistant Professor, Department of Biostatistics, Brown
University, Providence, RI 02912 (E-mail: rgutman@stat.brown.edu). Gayle
DeDe is Assistant Professor, Speech, Language, and Hearing Sciences
Department, The University of Arizona, Tucson, AZ 85721 (E-mail:
gdede@email.arizona.edu). David Caplan is Professor, Neuropsychology
Laboratory, Massachusetts General Hospital, Boston, MA 02114 (E-mail:
dcaplan@patners.org). Jun Liu is Professor of Statistics, Department of
Statistics, Harvard University, Cambridge, MA 02138 (E-mail:
jliu@stat.harvard.edu). This work was partially supported by NSF grants
DMS-0907562 and DMS-0906545, as well as by NIDCD grant DC00942. The
authors thank the editor, associate editor, and the referees for their
valuable comments.
NR 41
TC 2
Z9 2
U1 2
U2 4
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0162-1459
EI 1537-274X
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD DEC
PY 2011
VL 106
IS 496
BP 1304
EP 1316
DI 10.1198/jasa.2011.ap10017
PG 13
WC Statistics & Probability
SC Mathematics
GA 883VL
UT WOS:000299662900007
ER
PT J
AU Ding, P
Geng, Z
Yan, W
Zhou, XH
AF Ding, Peng
Geng, Zhi
Yan, Wei
Zhou, Xiao-Hua
TI Identifiability and Estimation of Causal Effects by Principal
Stratification With Outcomes Truncated by Death
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE Causal inference; Quality of life; Survivor average causal effect
ID INFERENCE; MODELS
AB In medical studies, there are many situations where the final outcomes are truncated by death, in which patients die before outcomes of interest are measured. In this article we consider identifiability and estimation of causal effects by principal stratification when some outcomes are truncated by death. Previous studies mostly focused on large sample bounds, Bayesian analysis, sensitivity analysis. In this article, we propose a new method for identifying the causal parameter of interest under a nonparametric and semiparametric model. We show that the causal parameter of interest is identifiable under some regularity assumptions and the assumption that there exists a pretreatment covariate whose conditional distributions among two principal strata are not the same, but our approach does not need the assumption of a mixture normal distribution for outcomes as required by Zhang, Rubin, and Mealli (2009). Hence, the proposed method is applicable not only to a continuous outcome but also to a binary outcome. When some of the assumptions are violated, we discuss biases of estimators and propose methods to reduce these biases. We conduct several simulation studies to evaluate the finite-sample performance of the proposed approach. Finally, we apply the proposed approach to a real dataset from a Southwest Oncology Group (SWOG) clinical trial.
C1 [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98105 USA.
[Ding, Peng; Geng, Zhi; Yan, Wei] Peking Univ, Sch Math Sci, Beijing 100871, Peoples R China.
[Ding, Peng; Geng, Zhi; Yan, Wei] Peking Univ, Ctr Stat Sci, Beijing 100871, Peoples R China.
[Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, Biostat Unit, HSR&D Ctr Excellence, Seattle, WA USA.
RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98105 USA.
EM pengdingpku@gmail.com; zgeng@math.pku.edu.cn; yanwei1982@pku.edu.cn;
azhou@u.washington.edu
FU NSFC [30728019, 11021463, 10931002]; NIH [R03 TW007197]; Department of
Veterans Affairs [05-196]
FX Peng Ding is Postgraduate Student (E-mail: pengdingpku@gmail.com), Zhi
Geng is Professor (E-mail: zgeng@math.pku.edu.cn), and Wei Yan is Ph.D.
Student (E-mail: yanwei1982@pku.edu.cn), School of Mathematical Sciences
and Center for Statistical Science, Peking University, Beijing 100871,
China. Xiao-Hua Zhou is Professor, Department of Biostatistics,
University of Washington, Seattle, WA 98105, and Director of
Biostatistics Unit, HSR&D Center of Excellence, VA Puget Sound Health
Care System (E-mail: azhou@u.washington.edu). This research was
supported by NSFC grants 30728019, 11021463, 10931002, NIH R03 TW007197,
and Department of Veterans Affairs HSR&D RCS Award 05-196. It does not
necessarily represent the views of VA HSR&D Service. We thank the
editor, the associate editor, and two anonymous referees for their
detailed comments and suggestions, which helped us greatly improve our
article. We also thank the Genitourinary Committee of the South Oncology
Group for providing data and scientific support.
NR 24
TC 11
Z9 11
U1 0
U2 16
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0162-1459
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD DEC
PY 2011
VL 106
IS 496
BP 1578
EP 1591
DI 10.1198/jasa.2011.tm10265
PG 14
WC Statistics & Probability
SC Mathematics
GA 883VL
UT WOS:000299662900028
ER
PT J
AU Ligorio, M
Izzotti, A
Pulliero, A
Arrigo, P
AF Ligorio, Matteo
Izzotti, Alberto
Pulliero, Alessandra
Arrigo, Patrizio
TI Mutagens interfere with microRNA maturation by inhibiting DICER. An in
silico biology analysis
SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
LA English
DT Article
DE DICER; microRNA; Bioinformatics; Mutagens; Epigenetic damage
ID DOUBLE-STRANDED-RNA; CIGARETTE-SMOKE; STRUCTURAL BASIS; DOWN-REGULATION;
HUMAN CANCERS; LUNG-CANCER; EXPRESSION; TRANSFORMATION; RECOGNITION;
TUMORIGENESIS
AB Exposure to environmental mutagens results in alteration of microRNA expression mainly oriented towards down-regulation, as typically observed in cigarette smoke. However, the molecular mechanism triggering this event is still unknown. To shed light on this issue, we developed an 'in silico' analysis testing 25 established environmental mutagens (polycyclic aromatic hydrocarbons, heterocyclic compounds, nitrosoamines, morpholine, ethylnitrosurea, benzene derivatives, hydroxyl amines, alkenes) for their potential to interfere with the function of DICER, the enzyme involved in the cytoplasmic phase of microRNA maturation. In order to analyse the binding affinity between DICER and each mutagen, the three-dimensional bioinformatic structures of DICER-RNase III domains and of mutagens have been constructed. The binding affinity of mutagens for each DICER's RNase III domain was estimated by calculating the global contact-energy and the number of intermolecular contacts. These two parameters reflect the stability of the DICER-mutagen complexes. All the 25 mutagens tested form stable complexes with DICER, 20 of which form a complex with DICER A domain, that is more stable than those formed by DICER with its natural substrate, i.e. double strand short RNAs. These mutagens are benzo(a)pyrene dial epoxide, nitroimidazoles, fluorenes, naphthalene, morpholine, stilbenes, hydroxylamines, fecapentenes. In the case of exposure to mutagen mixtures (benzo(a)pyrene-diolepoxide and 4-acetylaminostilbene), synergistic or less than addictive effects occur depending on the docking order of the compounds. A group of 8 mutagens with the highest ability to interfere with this DICER function, was identified by hierarchical cluster analysis. This group included 1-ethyl-1-nitrosourea and 4-nitrosomorpholine.
Herein, presented data support the view that mutagens interfere with microRNA maturation by binding DICER. This finding sheds light on a new epigenetic mechanism exerted by environmental mutagens in inducing cell damage. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Ligorio, Matteo; Izzotti, Alberto; Pulliero, Alessandra] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy.
[Ligorio, Matteo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA.
[Arrigo, Patrizio] CNR, Natl Res Council, Inst Macromol Res, ISMAC, Genoa, Italy.
RP Izzotti, A (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy.
EM izzotti@unige.it
OI izzotti, alberto/0000-0002-8588-0347
FU Italian Association for cancer research (AIRC) [8909]
FX This study was supported by Italian Association for cancer research
(AIRC), grant number 8909.
NR 50
TC 13
Z9 15
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0027-5107
J9 MUTAT RES-FUND MOL M
JI Mutat. Res.-Fundam. Mol. Mech. Mutagen.
PD DEC 1
PY 2011
VL 717
IS 1-2
SI SI
BP 116
EP 128
DI 10.1016/j.mrfmmm.2011.07.020
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 858FQ
UT WOS:000297781700015
PM 21889945
ER
PT J
AU van Vuurden, DG
Hulleman, E
Meijer, OLM
Wedekind, LE
Kool, M
Witt, H
Vandertop, PWP
Wurdinger, T
Noske, DP
Kaspers, GJL
Cloos, J
AF van Vuurden, Dannis G.
Hulleman, Esther
Meijer, Olga L. M.
Wedekind, Laurine E.
Kool, Marcel
Witt, Hendrik
Vandertop, Peter W. Peter
Wurdinger, Thomas
Noske, David P.
Kaspers, Gertjan J. L.
Cloos, Jacqueline
TI PARP inhibition sensitizes childhood high grade glioma, medulloblastoma
and ependymoma to radiation
SO ONCOTARGET
LA English
DT Article
DE PARP; radiation; medulloblastoma; ependymoma; glioma; pediatric
ID CENTRAL-NERVOUS-SYSTEM; DOUBLE-STRAND BREAKS; BRAIN-TUMORS; HOMOLOGOUS
RECOMBINATION; IN-VITRO; GENE-EXPRESSION; CELL-LINES; CHILDREN; PATHWAY;
PTEN
AB Poly ADP-ribose polymerase (PARP) is a protein involved in single strand break repair. Recently, PARP inhibitors have shown considerable promise in the treatment of several cancers, both in monotherapy and in combination with cytotoxic agents. Synthetic lethal action of PARP inhibitors has been observed in tumors with mutations in double strand break repair pathways. In addition, PARP inhibition potentially enhances sensitivity of tumor cells to DNA damaging agents, including radiotherapy. Aim of this study is to determine the radiosensitizing properties of the PARP inhibitor Olaparib in childhood medulloblastoma, ependymoma and high grade glioma (HGG). Increased PARP1 expression was observed in medulloblastoma, ependymoma and HGG, as compared to non-neoplastic brain tissue. Pediatric high grade glioma, medulloblastoma and ependymoma gene expression profiling revealed that high PARP1 expression is associated with poor prognosis. Cell growth inhibition assays with Olaparib resulted in differential sensitivity, with IC50 values ranging from 1.4 to 8.4 mu M, irrespective of tumor type and PARP1 protein expression. Sensitization to radiation was observed in medulloblastoma, ependymoma and HGG cell lines with subcytotoxic concentrations of Olaparib, which coincided with persistence of double strand breaks. Combining PARP inhibitors with radiotherapy in clinical studies in childhood high grade brain tumors may improve therapeutic outcome.
C1 [van Vuurden, Dannis G.; Hulleman, Esther; Meijer, Olga L. M.; Wedekind, Laurine E.] Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Dept Pediat Oncol Hematol,Neurooncol Res Grp, Amsterdam, Netherlands.
[Kool, Marcel; Witt, Hendrik] German Canc Res Ctr, Dept Mol Genet Childhood Brain Tumors, Heidelberg, Germany.
[Witt, Hendrik] Univ Heidelberg Hosp, Dept Pediat Hematol & Oncol, Heidelberg, Germany.
[Vandertop, Peter W. Peter; Wurdinger, Thomas; Noske, David P.] Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg,Neurooncol Res Grp, Amsterdam, Netherlands.
[Wurdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA.
[Wurdinger, Thomas] Harvard Univ, Sch Med, Boston, MA USA.
[Kaspers, Gertjan J. L.; Cloos, Jacqueline] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Oncol Hematol, Amsterdam, Netherlands.
[Cloos, Jacqueline] Vrije Univ Amsterdam, Med Ctr, Dept Hematol, Amsterdam, Netherlands.
RP van Vuurden, DG (reprint author), Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Dept Pediat Oncol Hematol,Neurooncol Res Grp, Amsterdam, Netherlands.
EM dg.vanvuurden@vumc.nl
RI Kool, Marcel/H-2541-2013; Witt, Hendrik/L-7810-2015;
OI Van Vuurden, Dannis/0000-0002-1364-9007
FU VUmc Cancer Center Amsterdam - VUmc Institute for Cancer and Immunology
(VUmc CCA/V-ICI)
FX This work was financially supported by VUmc Cancer Center Amsterdam -
VUmc Institute for Cancer and Immunology (VUmc CCA/V-ICI).
NR 55
TC 30
Z9 30
U1 1
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD DEC
PY 2011
VL 2
IS 12
BP 984
EP 996
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 880RI
UT WOS:000299424200012
PM 22184287
ER
PT J
AU Mancias, JD
Kimmelman, AC
AF Mancias, Joseph D.
Kimmelman, Alec C.
TI Targeting Autophagy Addiction in Cancer
SO ONCOTARGET
LA English
DT Article
DE Autophagy; Ras; Metabolism; Cancer; tumor; therapy
ID RHEUMATOID-ARTHRITIS; HYDROXYCHLOROQUINE; INHIBITION; MECHANISMS
AB Autophagy inhibition is a novel cancer therapeutic strategy in the early stages of clinical trial testing. The initial rationale for using autophagy inhibition was generated by research revealing that autophagy is upregulated in response to external stresses, including chemotherapy and radiotherapy. Combining autophagy inhibition with agents that induce autophagy as a pro-survival response may therefore increase their therapeutic efficacy. Recent research has shown that some cancer cells, particularly those driven by the K-Ras oncogene, also depend on elevated levels of autophagy for survival even in the absence of external stressors. In multiple in vitro as well as in vivo systems, oncogenic Ras-mediated transformation and tumor growth are dependent on autophagy to evade metabolic stress and cell death. These studies have subsequently led to further early phase clinical testing whether autophagy inhibition is a viable and effective strategy for targeting Ras-driven tumors. Even before the clinical results are available from these ongoing clinical trials, much work remains to optimally develop the approach of autophagy inhibition clinically; most notably reliably detecting levels of autophagy in human tumor samples, pharmacodynamics of currently available autophagy inhibitors (chloroquine and the derivative hydroxychloroquine), and new target identification and drug development.
C1 [Kimmelman, Alec C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02115 USA.
[Mancias, Joseph D.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA.
RP Kimmelman, AC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM Alec_Kimmelman@DFCI.HARVARD.EDU
FU Dana Farber Cancer Institute, National Cancer Institute [R01CA157490];
Kimmel Scholar Award; AACR-PanCAN
FX We apologize for any omission of primary citations. A. C. K is supported
by the Dana Farber Cancer Institute, National Cancer Institute Grant
R01CA157490, Kimmel Scholar Award, and AACR-PanCAN Career Development
Award.
NR 19
TC 79
Z9 82
U1 0
U2 6
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD DEC
PY 2011
VL 2
IS 12
BP 1302
EP 1306
PG 5
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 880RI
UT WOS:000299424200036
PM 22185891
ER
PT J
AU Hoh, BL
Kleinhenz, DT
Chi, YY
Mocco, J
Barker, FG
AF Hoh, Brian L.
Kleinhenz, Dominic T.
Chi, Yueh-Yun
Mocco, J.
Barker, Fred G., II
TI Incidence of Ventricular Shunt Placement for Hydrocephalus with Clipping
versus Coiling for Ruptured and Unruptured Cerebral Aneurysms in the
Nationwide Inpatient Sample Database: 2002 to 2007
SO WORLD NEUROSURGERY
LA English
DT Review
DE Cerebral aneurysm; Clipping; Coiling; Hydrocephalus; Ruptured; Shunt;
Unruptured
ID SPONTANEOUS SUBARACHNOID HEMORRHAGE; INTRACRANIAL ANEURYSMS; DEPENDENT
HYDROCEPHALUS; ENDOVASCULAR TREATMENT; LAMINA-TERMINALIS; UNITED-STATES;
ELDERLY-PATIENTS; EMBOLIZATION; FENESTRATION; OCCLUSION
AB BACKGROUND: Few studies have compared the incidence of ventricular shunt placement for hydrocephalus after clipping versus coiling of cerebral aneurysms.
OBJECTIVE: The Nationwide Inpatient Sample (NIS) database was used to compare, on a national level, the incidence of ventricular shunt placement after clipping versus coiling of ruptured and unruptured aneurysms.
METHODS: Hospitalizations for clipping and coiling of ruptured and unruptured aneurysms from 2002 to 2007 were collected from the NIS by cross-matching International Classification of Diseases-9 codes for diagnoses of subarachnoid hemorrhage or unruptured cerebral aneurysm with procedure codes for clipping or coiling. The incidence of ventricular shunt placement for hydrocephalus after clipping and coiling was compared using generalized linear models with generalized estimating equations (GEE) to adjust for patient-and hospital-specific factors and correlation between admissions.
RESULTS: Of 10,899 ruptured aneurysm patients (6593 clipping, 4306 coiling), clipping had a similar incidence of ventricular shunt placement (9.3%) compared to coiling (10.5%) (odds ratio = 0.984; 95% confidence interval = 0.85, -1.14; P value = 0.833 after adjustment for patient-specific and hospital-specific factors). Likewise, of 9686 unruptured aneurysm patients (4483 clipping, 5203 coiling), clipping had similar incidence of ventricular shunt placement (0.4%) compared to coiling (0.5%) (odds ratio = 0.763; 95% confidence interval = 0.37, -1.58; P value =0.465 after adjustment for patient-specific and hospital-specific factors). Predictors of shunt placement in ruptured aneurysm patients were age, comorbidity score, admission type, payer, and hospital aneurysm volume. Predictors of shunt placement in unruptured aneurysm patients were comorbidity score and admission type.
CONCLUSIONS: In an observational study, clipping and coiling of ruptured and unruptured cerebral aneurysms are associated with similar incidences of ventricular shunt placement for hydrocephalus.
C1 [Hoh, Brian L.; Kleinhenz, Dominic T.; Mocco, J.] Univ Florida, Dept Neurol Surg, Gainesville, FL 32610 USA.
[Chi, Yueh-Yun] Univ Florida, Dept Epidemiol & Hlth Policy Res, Gainesville, FL USA.
[Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA.
RP Hoh, BL (reprint author), Univ Florida, Dept Neurol Surg, Gainesville, FL 32610 USA.
EM brian.hoh@neurosurgery.ufl.edu
FU Boston Scientific; Codman Neurovascular
FX Conflict of interest statement: B.L.H. has received an honorarium from
Codman Neurovascular. J.M. has received an unrestricted educational
grant from Boston Scientific; an unrestricted educational grant from and
is a consultant for Codman Neurovascular; is a consultant for Actelion
Pharmaceuticals, Nfocus, and Lazarus Effect; and has received an
honorarium from Edge Therapeutics.
NR 45
TC 31
Z9 32
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1878-8750
J9 WORLD NEUROSURG
JI World Neurosurg.
PD DEC
PY 2011
VL 76
IS 6
BP 548
EP 554
DI 10.1016/j.wneu.2011.05.054
PG 7
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 885XL
UT WOS:000299814600015
PM 22251503
ER
PT J
AU Cheung, HW
Du, JY
Boehm, JS
He, F
Weir, BA
Wang, XX
Butaney, M
Sequist, LV
Luo, BA
Engelman, JA
Root, DE
Meyerson, M
Golub, TR
Janne, PA
Hahn, WC
AF Cheung, Hiu Wing
Du, Jinyan
Boehm, Jesse S.
He, Frank
Weir, Barbara A.
Wang, Xiaoxing
Butaney, Mohit
Sequist, Lecia V.
Luo, Biao
Engelman, Jeffrey A.
Root, David E.
Meyerson, Matthew
Golub, Todd R.
Jaenne, Pasi A.
Hahn, William C.
TI Amplification of CRKL Induces Transformation and Epidermal Growth Factor
Receptor Inhibitor Resistance in Human Non-Small Cell Lung Cancers
SO CANCER DISCOVERY
LA English
DT Article
ID CHRONIC MYELOGENOUS LEUKEMIA; ANAPLASTIC LYMPHOMA KINASE;
PROTEIN-KINASE; HEMATOPOIETIC-CELLS; SIGNALING PATHWAYS; INDUCED
ACTIVATION; ADAPTER PROTEIN; SH3 DOMAIN; MAP KINASE; FACTOR C3G
AB We previously identified a region of recurrent amplification on chromosome 22q11.21 in a subset of primary lung adenocarcinomas. Here we show that CRKL, encoding for an adaptor protein, is amplified and overexpressed in non-small cell lung cancer (NSCLC) cells that harbor 22q11.21 amplifications. Overexpression of CRKL in immortalized human airway epithelial cells promoted anchorage-independent growth and tumorigenicity. Oncogenic CRKL activates the SOS1-RAS-RAF-ERK and SRC-C3G-RAP1 pathways. Suppression of CRKL in NSCLC cells that harbor CRKL amplifications induced cell death. Overexpression of CRKL in epidermal growth factor receptor (EGFR)-mutant cells induces resistance to gefitinib by activating extracellular signal-regulated kinase and AKT signaling. We identified CRKL amplification in an EGFR inhibitor-treated lung adenocarcinoma that was not present before treatment. These observations demonstrate that CRKL overexpression induces cell transformation, credential CRKL as a therapeutic target for a subset of NSCLC that harbor CRKL amplifications, and implicate CRKL as an additional mechanism of resistance to EGFR-directed therapy.
SIGNIFICANCE: These studies credential CRKL as an oncogene in a subset of NSCLC. Overexpression of CRKL induces cell transformation and resistance to epidermal growth factor receptor inhibitor treatment and suggest that therapeutic interventions targeting CRKL may confer a clinical benefit in a defined subset of NSCLCs. Cancer Discovery; 1(7); 608-25. (C) 2011 AACR.
C1 [Cheung, Hiu Wing; Weir, Barbara A.; Wang, Xiaoxing; Butaney, Mohit; Meyerson, Matthew; Jaenne, Pasi A.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Du, Jinyan; He, Frank; Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Butaney, Mohit; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
[Meyerson, Matthew; Golub, Todd R.; Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Sequist, Lecia V.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Hahn, William C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Cheung, Hiu Wing; Du, Jinyan; Boehm, Jesse S.; He, Frank; Weir, Barbara A.; Wang, Xiaoxing; Luo, Biao; Root, David E.; Meyerson, Matthew; Golub, Todd R.; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA USA.
RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Dana 1538, Boston, MA 02115 USA.
EM William_Hahn@dfci.harvard.edu
RI Meyerson, Matthew/E-7123-2012;
OI Boehm, Jesse/0000-0002-6795-6336
FU National Institutes of Health [R33 CA128625, U54 CA112962, R01 CA135257,
R01 CA114465, P50 CA090578]
FX This work was supported in part by grants from the National Institutes
of Health (R33 CA128625, U54 CA112962, R01 CA135257, R01 CA114465, P50
CA090578).
NR 55
TC 56
Z9 58
U1 0
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD DEC
PY 2011
VL 1
IS 7
BP 608
EP 625
DI 10.1158/2159-8290.CD-11-0046
PG 18
WC Oncology
SC Oncology
GA 880MX
UT WOS:000299412300032
PM 22586683
ER
PT J
AU Teng, YD
Yu, D
Ropper, AE
Li, JX
Kabatas, S
Wakeman, DR
Wang, JM
Sullivan, MP
Redmond, DE
Langer, R
Snyder, EY
Sidman, RL
AF Teng Yang D
Yu Dou
Ropper, Alexander E.
Li Jianxue
Kabatas, Serdar
Wakeman, Dustin R.
Wang Junmei
Sullivan, Maryrose P.
Redmond, D. Eugene, Jr.
Langer, Robert
Snyder, Evan Y.
Sidman, Richard L.
TI Functional Multipotency of Stem Cells: A Conceptual Review of
Neurotrophic Factor-Based Evidence and Its Role in Translational
Research
SO CURRENT NEUROPHARMACOLOGY
LA English
DT Article
DE Stem cells; Neural stem cells; Multipotency; Neurotrophic factors;
Neural Repair; Spinal Cord Injury
ID SPINAL-CORD-INJURY; NERVE GROWTH-FACTOR; AMYOTROPHIC-LATERAL-SCLEROSIS;
NEURAL PROGENITOR CELLS; MILD COGNITIVE IMPAIRMENT; FOREBRAIN
CHOLINERGIC NEURONS; PROMOTES AXONAL REGENERATION; LONG-TERM
POTENTIATION; ADULT-RAT; ALZHEIMERS-DISEASE
AB We here propose an updated concept of stem cells (SCs), with an emphasis on neural stem cells (NSCs). The conventional view, which has touched principally on the essential property of lineage multipotency (e.g., the ability of NSCs to differentiate into all neural cells), should be broadened to include the emerging recognition of biofunctional multipotency of SCs to mediate systemic homeostasis, evidenced in NSCs in particular by the secretion of neurotrophic factors. Under this new conceptual context and taking the NSC as a leading example, one may begin to appreciate and seek the "logic" behind the wide range of molecular tactics the NSC appears to serve at successive developmental stages as it integrates into and prepares, modifies, and guides the surrounding CNS micro-and macro-environment towards the formation and self-maintenance of a functioning adult nervous system. We suggest that embracing this view of the "multipotency" of the SCs is pivotal for correctly, efficiently, and optimally exploiting stem cell biology for therapeutic applications, including reconstitution of a dysfunctional CNS.
C1 [Teng Yang D; Yu Dou; Ropper, Alexander E.; Kabatas, Serdar; Wang Junmei] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA.
[Teng Yang D; Yu Dou; Ropper, Alexander E.; Kabatas, Serdar; Wang Junmei] Childrens Hosp, Boston, MA 02115 USA.
[Teng Yang D] Vet Affairs Boston Healthcare Syst, Div SCI Res, Boston, MA USA.
[Teng Yang D] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA.
[Li Jianxue; Sidman, Richard L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA.
[Wakeman, Dustin R.; Snyder, Evan Y.] Sanford Burnham Med Res Inst, Stem Cell & Regenerat Program, La Jolla, CA USA.
[Sullivan, Maryrose P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Urol,VA Boston Hlth Care Syst, Boston, MA 02115 USA.
[Sullivan, Maryrose P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Redmond, D. Eugene, Jr.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Redmond, D. Eugene, Jr.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA.
[Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
RP Teng, YD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA.
EM yang_teng@hms.harvard.edu
FU VA Rehabilitation RD; VA Biomedical Laboratory RD; NIH; DOD; CIMIT;
HeadNorth Foundation; Department of Neurosurgery, Brigham & Women's
Hospital; Massachusetts SCI
FX Support was received from the VA Rehabilitation R&D, VA Biomedical
Laboratory R&D, NIH, DOD, CIMIT, HeadNorth Foundation, Department of
Neurosurgery, Brigham & Women's Hospital and Massachusetts SCI cure
research grant (Teng Lab).
NR 185
TC 17
Z9 19
U1 6
U2 14
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-159X
J9 CURR NEUROPHARMACOL
JI Curr. Neuropharmacol.
PD DEC
PY 2011
VL 9
IS 4
BP 574
EP 585
PG 12
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 883IE
UT WOS:000299626700006
PM 22654717
ER
PT J
AU Le Norcy, E
Kwak, SY
Allaire, M
Fratzl, P
Yamakoshi, Y
Simmer, JP
Margolis, HC
AF Le Norcy, Elvire
Kwak, Seo-Young
Allaire, Marc
Fratzl, Peter
Yamakoshi, Yasuo
Simmer, James P.
Margolis, Henry C.
TI Effect of phosphorylation on the interaction of calcium with
leucine-rich amelogenin peptide
SO EUROPEAN JOURNAL OF ORAL SCIENCES
LA English
DT Article; Proceedings Paper
CT 8th International Symposium on Development, Properties and Pathology of
Tooth Enamel
CY JUN 12-18, 2011
CL N Utica, IL
DE amelogenin; conformation; leucine-rich amelogenin peptide;
phosphorylation; small angle X-ray scattering
ID X-RAY-SCATTERING; IN-VITRO; HYDROXYAPATITE CRYSTALS; SECRETORY-STAGE;
ENAMEL MATRIX; AGGREGATION; PHOSPHATE; PROTEINS; BINDING; SYSTEM
AB Amelogenin undergoes self-assembly and plays an essential role in guiding enamel mineral formation. The leucine-rich amelogenin peptide (LRAP) is an alternative splice product of the amelogenin gene and is composed of the N terminus (containing the only phosphate group) and the C terminus of full-length amelogenin. This study was conducted to investigate further the role of phosphorylation in LRAP self-assembly in the presence and absence of calcium using small angle X-ray scattering (SAXS). Consistent with our previous dynamic light-scattering findings for phosphorylated (+P) and non-phosphorylated (-P) LRAP, SAXS analyses revealed radii of gyration (R(g)) for LRAP(-P) (46.3-48.0 angstrom) that were larger than those for LRAP(+P) (25.0-27.4 angstrom) at pH 7.4. However, added calcium (up to 2.5 mM) induced significant increases in the R(g) of LRAP(+P) (up to 46.4 angstrom), while it had relatively little effect on LRAP(-P) particle size. Furthermore, SAXS analyses suggested compact folded structures for LRAP(-P) in the presence and absence of calcium, whereas the conformation of LRAP(+P) changed from an unfolded structure to a more compact structure upon the addition of calcium. We conclude that the single phosphate group in LRAP(+P) induces functionally important conformational changes, suggesting that phosphorylation may also influence amelogenin conformation and protein-mineral interactions during the early stages of amelogenesis.
C1 [Le Norcy, Elvire; Kwak, Seo-Young; Margolis, Henry C.] Forsyth Inst, Dept Biomineralizat, Cambridge, MA 02142 USA.
[Le Norcy, Elvire; Kwak, Seo-Young; Margolis, Henry C.] Harvard Univ, Dept Dev Biol, Sch Dent Med, Boston, MA 02115 USA.
[Allaire, Marc] Brookhaven Natl Lab, Natl Synchrotron Light Source, Upton, NY 11973 USA.
[Fratzl, Peter] Max Planck Inst Colloids & Interfaces, Dept Biomat, Potsdam, Germany.
[Yamakoshi, Yasuo; Simmer, James P.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
RP Margolis, HC (reprint author), Forsyth Inst, Dept Biomineralizat, 245 1st St, Cambridge, MA 02142 USA.
EM hmargolis@forsyth.org
RI Fratzl, Peter/H-9095-2012
OI Fratzl, Peter/0000-0003-4437-7830
FU NIDCR NIH HHS [R56 DE016376, DE-016376, R01 DE016376, R01 DE016376-05]
NR 37
TC 5
Z9 5
U1 0
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0909-8836
J9 EUR J ORAL SCI
JI Eur. J. Oral Sci.
PD DEC
PY 2011
VL 119
SU 1
SI SI
BP 97
EP 102
DI 10.1111/j.1600-0722.2011.00900.x
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 875YB
UT WOS:000299070300018
PM 22243234
ER
PT J
AU Kwak, SY
Green, S
Wiedemann-Bidlack, FB
Beniash, E
Yamakoshi, Y
Simmer, JP
Margolis, HC
AF Kwak, Seo-Young
Green, Samantha
Wiedemann-Bidlack, Felicitas B.
Beniash, Elia
Yamakoshi, Yasuo
Simmer, James P.
Margolis, Henry C.
TI Regulation of calcium phosphate formation by amelogenins under
physiological conditions
SO EUROPEAN JOURNAL OF ORAL SCIENCES
LA English
DT Article; Proceedings Paper
CT 8th International Symposium on Development, Properties and Pathology of
Tooth Enamel
CY JUN 12-18, 2011
CL N Utica, IL
DE amelogenin; enamel; hydroxyapatite; ionic strength; mineralization
ID MINERALIZATION IN-VITRO; MOUSE AMELOGENINS; ENAMEL MATRIX; BONE;
CRYSTALS; PHASE; FLUID
AB Amelogenin is essential for proper enamel formation. The present in vitro study extends our previous work at low (10 mM) ionic strength (IS) by examining the effect of amelogenin on mineralization under higher (162 mM) IS conditions found in developing enamel. Full-length phosphorylated (P173) and non-phosphorylated (rP172) amelogenins were examined, along with P148 and rP147 that lack the hydrophilic C-terminus. Calcium phosphate formation was assessed by pH change, while the minerals formed were characterized using transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy. Amelogenin self-assembly was also studied using dynamic light scattering and TEM. The results indicate that IS does not influence the effects of rP147, rP172, and P173 on mineralization. However, in contrast to the findings for low IS, where both P173 and P148 stabilize initially formed amorphous calcium phosphate (ACP) nanoparticles for > 1 d, elongated hydroxyapatite crystals were observed after 24 h using P148 at high IS, unlike that seen with P173. Differences in self-assembly help explain these findings, which suggest that P173 and P148 may play different roles in regulating enamel mineral formation. The present data support the notion that proteolytic processing of P173 is required in vivo to induce the transformation of initial ACP phases to apatitic enamel crystals.
C1 [Kwak, Seo-Young; Wiedemann-Bidlack, Felicitas B.; Margolis, Henry C.] Forsyth Inst, Dept Biomineralizat, Cambridge, MA 02142 USA.
[Kwak, Seo-Young; Wiedemann-Bidlack, Felicitas B.; Margolis, Henry C.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
[Green, Samantha] Simmons Coll, Dept Biochem, Boston, MA 02115 USA.
[Beniash, Elia] Univ Pittsburgh, Dept Oral Biol, Pittsburgh, PA USA.
[Yamakoshi, Yasuo; Simmer, James P.] Univ Michigan, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
RP Margolis, HC (reprint author), Forsyth Inst, Dept Biomineralizat, 245 First St, Cambridge, MA 02142 USA.
EM hmargolis@forsyth.org
FU NIDCR NIH HHS [R01 DE016376, R01 DE016376-05, R01-DE016376,
T32-DE007327, T32 DE007327]
NR 32
TC 10
Z9 11
U1 1
U2 15
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0909-8836
J9 EUR J ORAL SCI
JI Eur. J. Oral Sci.
PD DEC
PY 2011
VL 119
SU 1
SI SI
BP 103
EP 111
DI 10.1111/j.1600-0722.2011.00911.x
PG 9
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 875YB
UT WOS:000299070300019
PM 22243235
ER
PT J
AU Smith, CE
Hu, YY
Richardson, AS
Bartlett, JD
Hu, JCC
Simmer, JP
AF Smith, Charles E.
Hu, Yuanyuan
Richardson, Amelia S.
Bartlett, John D.
Hu, Jan C. -C.
Simmer, James P.
TI Relationships between protein and mineral during enamel development in
normal and genetically altered mice
SO EUROPEAN JOURNAL OF ORAL SCIENCES
LA English
DT Article; Proceedings Paper
CT 8th International Symposium on Development, Properties and Pathology of
Tooth Enamel
CY JUN 12-18, 2011
CL N Utica, IL
DE ameloblastin; enamelin; KLK4; mineral; matrix metalloproteinase 20
(MMP20)
ID RAT INCISOR; AMELOGENESIS IMPERFECTA; MATURATION STAGE; MATRIX PROTEINS;
AMELOBLASTS; EXPRESSION; MOUSE; KLK4; DIFFERENTIATION; ORGANIZATION
AB The purpose of this study was to quantify and compare the amounts of volatiles (mostly protein) and mineral present in developing incisor enamel in normal mice and in those genetically engineered for absence of intact enamelin, ameloblastin, matrix metalloproteinase 20 (MMP20) or kallikrein-related peptidase 4 (KLK4). Data indicated that all mice showed peaks in the gross weight of volatiles and a similar weight of mineral at locations on incisors normally associated with early maturation. Thereafter, the content of volatiles on normal incisors declined rapidly by as much as 62%, but not by 100%, over 2 mm, accompanied by increases of similar to threefold in mineral weights. Enamelin heterozygous mice (lower incisors) showed a decrease in volatile content across the maturation stage, yet mineral failed to increase significantly. Mmp20 null mice showed no significant loss of volatiles from maturing enamel, yet the amount of mineral increased. Klk4 null mice showed normal mineral acquisition up to early maturation, but the input of new volatiles in mid to late maturation caused the final mineralization to slow below normal levels. These results suggest that it is not only the amount of protein but also the nature or type of protein or fragments present in the local crystallite environment that affects their volumetric expansion as they mature.
C1 [Smith, Charles E.] McGill Univ, Dept Anat & Cell Biol, Facil Elect Microscopy Res, Montreal, PQ H3A 2B2, Canada.
[Smith, Charles E.] McGill Univ, Fac Dent, Montreal, PQ H3A 2B2, Canada.
[Smith, Charles E.; Hu, Yuanyuan; Richardson, Amelia S.; Hu, Jan C. -C.; Simmer, James P.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Dent Res Lab, Ann Arbor, MI 48109 USA.
[Bartlett, John D.] Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Cambridge, MA 02138 USA.
[Bartlett, John D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Cambridge, MA 02138 USA.
RP Smith, CE (reprint author), McGill Univ, Dept Anat & Cell Biol, Facil Elect Microscopy Res, 3640 Univ St, Montreal, PQ H3A 2B2, Canada.
EM charles.smith@mcgill.ca
FU Canadian Institutes of Health Research; NIDCR NIH HHS [DE011301,
DE016276, DE019775, R01 DE011301, R01 DE016276, R01 DE016276-05, R01
DE019775, R01 DE019775-04, R29 DE011301, R56 DE011301, R56 DE016276]
NR 50
TC 16
Z9 17
U1 0
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0909-8836
J9 EUR J ORAL SCI
JI Eur. J. Oral Sci.
PD DEC
PY 2011
VL 119
SU 1
SI SI
BP 125
EP 135
DI 10.1111/j.1600-0722.2011.00871.x
PG 11
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 875YB
UT WOS:000299070300022
PM 22243238
ER
PT J
AU Bartlett, JD
Skobe, Z
Nanci, A
Smith, CE
AF Bartlett, John D.
Skobe, Ziedonis
Nanci, Antonio
Smith, Charles E.
TI Matrix metalloproteinase 20 promotes a smooth enamel surface, a strong
dentino-enamel junction, and a decussating enamel rod pattern
SO EUROPEAN JOURNAL OF ORAL SCIENCES
LA English
DT Article; Proceedings Paper
CT 8th International Symposium on Development, Properties and Pathology of
Tooth Enamel
CY JUN 12-18, 2011
CL N Utica, IL
DE ameloblast; enamel; enamel organ; enamelysin; matrix metalloproteinase
20
ID HYPOMATURATION AMELOGENESIS IMPERFECTA; NULL MOUSE ENAMEL; E-CADHERIN;
P-CADHERIN; MMP-20; EXPRESSION; TOOTH; AMELOBLASTIN; CLEAVAGE; PROTEIN
AB Mutations of the matrix metalloproteinase 20 (MMP20, enamelysin) gene cause autosomal-recessive amelogenesis imperfecta, and Mmp20 ablated mice also have malformed dental enamel. Here we showed that Mmp20 null mouse secretory-stage ameloblasts maintain a columnar shape and are present as a single layer of cells. However, the maturation-stage ameloblasts from null mouse cover extraneous nodules of ectopic calcified material formed at the enamel surface. Remarkably, nodule formation occurs in null mouse enamel when MMP20 is normally no longer expressed. The malformed enamel in Mmp20 null teeth was loosely attached to the dentin and the entire enamel layer tended to separate from the dentin, indicative of a faulty dentinoenamel junction (DEJ). The enamel rod pattern was also altered in Mmp20 null mice. Each enamel rod is formed by a single ameloblast and is a mineralized record of the migration path of the ameloblast that formed it. The enamel rods in Mmp20 null mice were grossly malformed or absent, indicating that the ameloblasts do not migrate properly when backing away from the DEJ. Thus, MMP20 is required for ameloblast cell movement necessary to form the decussating enamel rod patterns, for the prevention of ectopic mineral formation, and to maintain a functional DEJ.
C1 [Bartlett, John D.; Skobe, Ziedonis] Forsyth Inst, Dept Cytokine Biol, Cambridge, MA 02142 USA.
[Bartlett, John D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
[Nanci, Antonio] Univ Montreal, Fac Med Dent, Montreal, PQ H3C 3J7, Canada.
[Smith, Charles E.] McGill Univ, Dept Anat & Cell Biol, Facil Electron Microscopy Res, Montreal, PQ, Canada.
[Smith, Charles E.] McGill Univ, Fac Dent, Montreal, PQ, Canada.
RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, 245 1st St, Cambridge, MA 02142 USA.
EM jbartlett@forsyth.org
FU Canadian Institutes of Health Research; NIDCR NIH HHS [DE016276, R01
DE016276-05, R01 DE016276, R56 DE016276]
NR 42
TC 10
Z9 10
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0909-8836
J9 EUR J ORAL SCI
JI Eur. J. Oral Sci.
PD DEC
PY 2011
VL 119
SU 1
SI SI
BP 199
EP 205
DI 10.1111/j.1600-0722.2011.00864.x
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 875YB
UT WOS:000299070300031
PM 22243247
ER
PT J
AU Yamakoshi, Y
Richardson, AS
Nunez, SM
Yamakoshi, F
Milkovich, RN
Hu, JCC
Bartlett, JD
Simmer, JP
AF Yamakoshi, Yasuo
Richardson, Amelia S.
Nunez, Stephanie M.
Yamakoshi, Fumiko
Milkovich, Rachel N.
Hu, Jan C-C.
Bartlett, John D.
Simmer, James P.
TI Enamel proteins and proteases in Mmp20 and Klk4 null and double-null
mice
SO EUROPEAN JOURNAL OF ORAL SCIENCES
LA English
DT Article; Proceedings Paper
CT 8th International Symposium on Development, Properties and Pathology of
Tooth Enamel
CY JUN 12-18, 2011
CL N Utica, IL
DE enamel; enamel maturation; kallikrein 4; proteases; proteinases; teeth
ID HYPOMATURATION AMELOGENESIS-IMPERFECTA; SHEATH PROTEINS; DENTAL ENAMEL;
MATRIX METALLOPROTEINASE-20; MOUSE AMELOGENINS; MATURATION STAGE;
EXPRESSION; MMP-20; AMELOBLASTIN; CLONING
AB Matrix metalloproteinase 20 (MMP20) and kallikrein-related peptidase 4 (KLK4) are thought to be necessary to clear proteins from the enamel matrix of developing teeth. We characterized Mmp20 and Klk4 null mice to better understand their roles in matrix degradation and removal. Histological examination showed retained organic matrix in Mmp20, Klk4, and Mmp20/Klk4 double-null mouse enamel matrix, but not in the wild-type. X-gal histostaining of Mmp20 null mice heterozygous for the Klk4 knockout/lacZ knockin showed that Klk4 is expressed normally in the Mmp20 null background. This finding was corroborated by zymogram and western blotting, which discovered a 40-kDa protease induced in the maturation stage of Mmp20 null mice. Proteins were extracted from secretory-stage or maturation-stage maxillary first molars from wild-type, Mmp20 null, Klk4 null, and Mmp20/Klk4 double-null mice and were analyzed by SDS-PAGE and western blotting. Only intact amelogenins and ameloblastin were observed in secretory-stage enamel of Mmp20 null mice, whereas the secretory-stage matrix from Klk4 null mice was identical to the matrix from wildtype mice. More residual matrix was observed in the double-null mice compared with either of the single-null mice. These results support the importance of MMP20 during the secretory stage and of KLK4 during the maturation stage and show there is only limited functional redundancy for these enzymes.
C1 [Simmer, James P.] Univ Michigan, Dept Biol & Mat Sci, Dent Res Lab, Sch Dent, Ann Arbor, MI 48108 USA.
[Bartlett, John D.] Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Cambridge, MA 02138 USA.
[Bartlett, John D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Cambridge, MA 02138 USA.
RP Simmer, JP (reprint author), Univ Michigan, Dept Biol & Mat Sci, Dent Res Lab, Sch Dent, 1210 Eisenhower Pl, Ann Arbor, MI 48108 USA.
EM jsimmer@umich.edu
FU NIDCR NIH HHS [DE015846, DE016276, DE019775, R01 DE015846, R01
DE015846-09, R01 DE016276, R01 DE016276-04, R01 DE019775, R01
DE019775-04, R56 DE016276]
NR 56
TC 21
Z9 21
U1 0
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0909-8836
J9 EUR J ORAL SCI
JI Eur. J. Oral Sci.
PD DEC
PY 2011
VL 119
SU 1
SI SI
BP 206
EP 216
DI 10.1111/j.1600-0722.2011.00866.x
PG 11
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 875YB
UT WOS:000299070300032
PM 22243248
ER
PT J
AU Hu, YY
Hu, JCC
Smith, CE
Bartlett, JD
Simmer, JP
AF Hu, Yuanyuan
Hu, Jan C-C.
Smith, Charles E.
Bartlett, John D.
Simmer, James P.
TI Kallikrein-related peptidase 4, matrix metalloproteinase 20, and the
maturation of murine and porcine enamel
SO EUROPEAN JOURNAL OF ORAL SCIENCES
LA English
DT Article; Proceedings Paper
CT 8th International Symposium on Development, Properties and Pathology of
Tooth Enamel
CY JUN 12-18, 2011
CL N Utica, IL
DE backscatter scanning electron microscopy; energy-dispersive X-ray
analysis; proteases; proteinases; teeth
ID AMELOGENESIS IMPERFECTA PHENOTYPE; MICE DISPLAY; AMELOBLASTIN; MMP-20;
CLEAVAGE; CLONING; KLK4; EXPRESSION; SEQUENCE; DEFECTS
AB The crowns of matrix metalloproteinase 20 (Mmp20) null mice fracture at the dentino-enamel junction (DEJ), whereas the crowns of kallikrein-related peptidase 4 (Klk4) null mice fracture in the deep enamel just above the DEJ. We used backscatter scanning electron microscopy to assess enamel mineralization in incisors from 9-wk-old wild-type, Klk4 null, and Mmp20 null mice, and in developing pig molars. We observed a line of hypermineralization along the DEJ in developing wild-type mouse and pig teeth. This line was discernible from the early secretory stage until the enamel in the maturation stage reached a similar density. The line was apparent in Klk4 null mice, but absent in Mmp20 null mice. Enamel in the Klk4 null mice matured normally at the surface, but was progressively less mineralized with depth. Enamel in the Mmp20 null mice formed as a mineral bilayer, with neither layer looking like true enamel. The most superficial mineral layer expanded during the maturation stage and formed irregular surface nodules. A surprising finding was the observation of electron backscatter from mid-maturation wild-type ameloblasts, which we attributed to the accumulation and release of iron. We conclude that enamel breaks in the deep enamel of Klk4 null mice because of decreasing enamel maturation with depth, and at the DEJ in Mmp20 null mice because of hypomineralization at the DEJ.
C1 [Simmer, James P.] Univ Michigan, Dept Biol & Mat Sci, Dent Res Lab, Sch Dent, Ann Arbor, MI 48108 USA.
[Smith, Charles E.] McGill Univ, Dept Anat & Cell Biol, Facil Electron Microscopy Res, Montreal, PQ, Canada.
[Smith, Charles E.] McGill Univ, Fac Dent, Montreal, PQ, Canada.
[Bartlett, John D.] Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Cambridge, MA 02138 USA.
[Bartlett, John D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Cambridge, MA 02138 USA.
RP Simmer, JP (reprint author), Univ Michigan, Dept Biol & Mat Sci, Dent Res Lab, Sch Dent, 1210 Eisenhower Pl, Ann Arbor, MI 48108 USA.
EM jsimmer@umich.edu
FU NIDCR NIH HHS [R01 DE016276-05, R56 DE016276, R01 DE019775, R01
DE019775-04, R01 DE016276]
NR 25
TC 16
Z9 16
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0909-8836
J9 EUR J ORAL SCI
JI Eur. J. Oral Sci.
PD DEC
PY 2011
VL 119
SU 1
SI SI
BP 217
EP 225
DI 10.1111/j.1600-0722.2011.00859.x
PG 9
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 875YB
UT WOS:000299070300033
PM 22243249
ER
PT J
AU Walcott, BP
Nahed, BV
Redjal, N
Stein, TD
Kahle, KT
Coumans, JV
AF Walcott, Brian P.
Nahed, Brian V.
Redjal, Navid
Stein, Thor D.
Kahle, Kristopher T.
Coumans, Jean-Valery
TI Pathological mechanism of lumbar disc herniation resulting in neurogenic
muscle hypertrophy
SO JOURNAL OF CLINICAL NEUROSCIENCE
LA English
DT Article
DE Denervation; Disc; Hypertrophy; Muscle; Myopathy neurogenic
ID COMPLEX REPETITIVE DISCHARGES; BOTULINUM TOXIN; RADICULOPATHY;
DENERVATION; PATIENT
AB We present a 33-year-old man with 5-year history of low back pain who presented with an enlarging right calf. The patient underwent an extensive workup including biopsy without diagnosis. The patient's examination was significant for diminished pinprick sensation in the right L5/S1 dermatome. Reflexes were absent in the right ankle. The circumference of the right calf (58 cm) was twice that of the left. MRI revealed a herniated lumbar disc at the L5/S1 level. He then underwent a L5/S1 microdiscectomy. Following this surgery, the patient noted complete resolution of all sensory deficits in his lower extremity. His calf circumference had decreased by 5 cm at 4 months and by a total of 8 cm at his 2-year postoperative visit. Histological examination of the affected muscle demonstrated severe grouped atrophy of both type I and type II fibers. There was also evidence of compensatory fiber hypertrophy as well as fiber splitting. We concluded that the patient suffered from a herniated lumbar disc causing radiculopathy with calf hypertrophy (neurogenic hypertrophy). To our knowledge this is the first report of both grouped atrophy and compensatory hypertrophy of both muscle fiber types seen in this phenomenon. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Walcott, Brian P.; Nahed, Brian V.; Redjal, Navid; Kahle, Kristopher T.; Coumans, Jean-Valery] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Walcott, Brian P.; Nahed, Brian V.; Redjal, Navid; Stein, Thor D.; Kahle, Kristopher T.; Coumans, Jean-Valery] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Stein, Thor D.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA.
EM walcott.brian@mgh.harvard.edu
OI Stein, Thor/0000-0001-6954-4477
FU CSRD VA [I01 CX001038]
NR 18
TC 3
Z9 3
U1 1
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0967-5868
J9 J CLIN NEUROSCI
JI J. Clin. Neurosci.
PD DEC
PY 2011
VL 18
IS 12
BP 1682
EP 1684
DI 10.1016/j.jocn.2011.03.033
PG 3
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 881PG
UT WOS:000299498000020
PM 21985744
ER
PT J
AU Rubenstein, LZ
Vivrette, R
Harker, JO
Stevens, JA
Kramer, BJ
AF Rubenstein, Laurence Z.
Vivrette, Rebecca
Harker, Judith O.
Stevens, Judy A.
Kramer, B. Josea
TI Validating an evidence-based, self-rated fall risk questionnaire (FRQ)
for older adults
SO JOURNAL OF SAFETY RESEARCH
LA English
DT Article
DE Falls; Fall prevention; Geriatrics; Risk assessment
ID PREVENTION; PEOPLE; EPIDEMIOLOGY; METAANALYSIS
AB Background: Falls are a common, serious, and often unrecognized problem facing older adults. The objective of this study was to provide an initial clinical and statistical validation for a public health strategy of fall risk self-assessment by older adults using a Fall Risk Questionnaire (FRQ). Methods: Adults age 65+ (n = 40) were recruited at a Los Angeles Veterans Affairs (VA) medical facility and at a local assisted living facility. Participants completed the FRQ self-assessment and results were compared to a "gold standard" of a clinical evaluation of risks using the American/British Geriatrics Society guidelines to assess independent predictors of falls: history of previous falls, fear of falling, gait/balance, muscle weakness, incontinence, sensation and proprioception, depression, vision, and medications. For the comparison, we used an iterative statistical approach, weighing items based on relative risk. Results: There was strong agreement between the FRQ and clinical evaluation (kappa = .875, p < .0001). Individual item kappa values ranged from .305-832. After dropping one FRQ item (vision risk) because of inadequate agreement with the clinical evaluation (kappa = .139, p = .321), the final FRQ had good concurrent validity. Conclusions: The FRQ goes beyond existing screening tools in that it is based on both evidence and clinical acceptability and has been initially validated with clinical examination data. A larger validation with longitudinal follow-up should determine the actual strength of the FRQ in predicting future falls. (C) 2011 National Safety Council and Elsevier Ltd. All rights reserved.
C1 [Rubenstein, Laurence Z.] Univ Oklahoma, Coll Med, Donald W Reynolds Dept Geriatr Med, Oklahoma City, OK 73104 USA.
[Rubenstein, Laurence Z.; Vivrette, Rebecca; Harker, Judith O.] Greater Los Angeles VA Med Ctr 11E, GRECC, Sepulveda, CA 91343 USA.
[Stevens, Judy A.] Ctr Dis Control & Prevent, Natl Ctr Injury Prevent & Control, Atlanta, GA 30341 USA.
[Rubenstein, Laurence Z.; Kramer, B. Josea] Univ Calif Los Angeles, Sch Med, Sepulveda, CA 91343 USA.
[Rubenstein, Laurence Z.; Kramer, B. Josea] Greater Los Angeles VA Med Ctr, GRECC, Sepulveda, CA 91343 USA.
RP Rubenstein, LZ (reprint author), Univ Oklahoma, Coll Med, Donald W Reynolds Dept Geriatr Med, 921 NE 13th St,VAMC 11 G, Oklahoma City, OK 73104 USA.
EM Laurence-rubenstein@ouhsc.edu
NR 26
TC 7
Z9 7
U1 2
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-4375
J9 J SAFETY RES
JI J. Saf. Res.
PD DEC
PY 2011
VL 42
IS 6
BP 493
EP 499
DI 10.1016/j.jsr.2011.08.006
PG 7
WC Ergonomics; Public, Environmental & Occupational Health; Social
Sciences, Interdisciplinary; Transportation
SC Engineering; Public, Environmental & Occupational Health; Social
Sciences - Other Topics; Transportation
GA 876WQ
UT WOS:000299138900012
PM 22152267
ER
PT J
AU de Moya, MA
Manolakaki, D
Chang, YC
Amygdalos, I
Gao, FF
Alam, HB
Velmahos, GC
AF de Moya, Marc A.
Manolakaki, Dimitra
Chang, Yuchiao
Amygdalos, Iakovos
Gao, Fangfei
Alam, Hasan B.
Velmahos, George C.
TI Blunt Pulmonary Contusion: Admission Computed Tomography Scan Predicts
Mechanical Ventilation
SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
LA English
DT Article
DE Lung injury; Contusion; Mechanical ventilation
ID RESPIRATORY-DISTRESS-SYNDROME; TRAUMA PATIENTS; THORACIC TRAUMA; CHEST
TRAUMA; FLAIL CHEST; SCORING SYSTEM; MANAGEMENT; RISK; INJURY
AB Background: Blunt pulmonary contusion (BPC) evolves over 12 to 24 hours, and the initial plain radiographs fail to reliably identify patients at risk of clinical deterioration. Admission computed tomography (CT) may offer accurate characterization of BPC and early prediction of the need for mechanical ventilation (MV).
Methods: This was a combination of a 5-year retrospective study (January 2002 to April 2007) and a 6-month prospective study (September 2007 to February 2008) of adult blunt trauma (BT) patients with thoracic injuries and a chest CT upon hospital arrival. The primary outcome was MV due to thoracic trauma. To ensure that MV was required for BPC and not for associated injuries, all patients with significant extrathoracic injuries (Abbreviated Injury Scale score >2) were excluded. The extent of BPC was measured by two scoring systems.
Results: Of 392 patients (67% males; age, 48 years +/- 21 years; Abbreviated Injury Scale score chest, 3 +/- 1; and Injury Severity Score [ISS], 13 +/- 6), 243 (62%) had BPC. Twenty-five (6%) patients required MV and two (0.5%) died. The combination of Glasgow Coma Scale (GCS) score <14, BPC score >2, and >4 ribs fractured predicted MV in 100% of the cases, and the absence of all factors precluded MV in 100%. In the prospective period of 6 months, 55 patients had BPC and we confirmed our finding that the absence of the three factors precludes MV.
Conclusion: A simple score derived by the initial chest CT, in combination with GCS and the number of fractured ribs, can predict the need for MV early. In the presence of these predictors, patients should be admitted to a high level of monitoring.
C1 [de Moya, Marc A.; Manolakaki, Dimitra; Amygdalos, Iakovos; Gao, Fangfei; Alam, Hasan B.; Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
[Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP de Moya, MA (reprint author), 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
EM mdemoya@partners.org
NR 30
TC 10
Z9 10
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-5282
J9 J TRAUMA
JI J. Trauma-Injury Infect. Crit. Care
PD DEC
PY 2011
VL 71
IS 6
BP 1543
EP 1547
DI 10.1097/TA.0b013e31822c4a8b
PG 5
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 869RT
UT WOS:000298616400016
PM 21857256
ER
PT J
AU Fink, D
Romanowski, K
Valuckaite, V
Babrowski, T
Kim, M
Matthews, JB
Liu, D
Zaborina, O
Alverdy, JC
AF Fink, David
Romanowski, Kathleen
Valuckaite, Vesta
Babrowski, Trissa
Kim, Moses
Matthews, Jeffrey B.
Liu, Donald
Zaborina, Olga
Alverdy, John C.
TI Pseudomonas aeruginosa Potentiates the Lethal Effect of Intestinal
Ischemia-Reperfusion Injury: The Role of In Vivo Virulence Activation
SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
LA English
DT Article
DE Intestinal ischemia-reperfusion; Pseudomonas aeruginosa; Virulence
activation; Virulence transcription regulation; Small bowel bacterial
overgrowth
ID GUT-DERIVED SEPSIS; INFECTION; PATHOGEN; LECTINS; TRACT; BLOOD; HOST
AB Background: Experimental models of intestinal ischemia-reperfusion (IIR) injury are invariably performed in mice harboring their normal commensal flora, even though multiple IIR events occur in humans during prolonged intensive care confinement when they are colonized by a highly pathogenic hospital flora. The aims of this study were to determine whether the presence of the human pathogen Pseudomonas aeruginosa in the distal intestine potentiates the lethality of mice exposed to IIR and to determine what role any in vivo virulence activation plays in the observed mortality.
Methods: Seven-to 9-week-old C57/BL6 mice were exposed to 15 minutes of superior mesenteric artery occlusion (SMAO) followed by direct intestinal inoculation of 1.0 x 10(6) colony-forming unit of P. aeruginosa PAO1 into the ileum and observed for mortality. Reiterative studies were performed in separate groups of mice to evaluate both the migration/dissemination pattern and in vivo virulence activation of intestinally inoculated strains using live photon camera imaging of both a constitutive bioluminescent P. aeruginosa PAO1 derivative XEN41 and an inducible reporter derivative of PAO1, the PAO1/lecA:luxCDABE that conditionally expresses the quorum sensing-dependent epithelial disrupting virulence protein PA 1 Lectin (PA-IL).
Results: Mice exposed to 15 minutes of SMAO and reperfusion with intestinal inoculation of P. aeruginosa had a significantly increased mortality rate (p < 0.001) of 100% compared with <10% for sham-operated mice intestinally inoculated with P. aeruginosa without SMAO and IIR alone (<50%). Migration/dissemination patterns of P. aeruginosa in mice subjected to IIR demonstrated proximal migration of distally injected strains and translocation to mesenteric lymph nodes, liver, spleen, lung, and kidney. A key role for in vivo virulence expression of the barrier disrupting adhesin PA-IL during IIR was established since its expression was enhanced during IR and mutant strains lacking PA-IL displayed attenuated mortality.
Conclusions: The presence of intestinal P. aeruginosa potentiates the lethal effect of IIR in mice in part due to in vivo virulence activation of its epithelial barrier disrupting protein PA-IL.
C1 [Fink, David; Romanowski, Kathleen; Valuckaite, Vesta; Babrowski, Trissa; Matthews, Jeffrey B.; Liu, Donald; Zaborina, Olga; Alverdy, John C.] Univ Chicago, Dept Surg, Chicago, IL 60637 USA.
[Fink, David; Valuckaite, Vesta; Matthews, Jeffrey B.; Alverdy, John C.] Harvard Univ, Massachusetts Gen Hosp, BIASE, Boston, MA USA.
[Fink, David] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA.
[Kim, Moses] Univ Illinois, Metro Program, Chicago, IL 60680 USA.
RP Alverdy, JC (reprint author), Univ Chicago, Dept Surg, 5841 S Maryland,MC 6090, Chicago, IL 60637 USA.
EM jalverdy@surgery.bsd.uchicago.edu
RI Ji, Haofeng/G-6206-2012
FU NIH [5R01GM062344-11]; University of Chicago BSD Imagine Research
Institute
FX Supported by NIH grant 5R01GM062344-11 (to J.C.A.) and by the University
of Chicago BSD Imagine Research Institute for Pilot Research Projects
(to J.C.A.).
NR 23
TC 11
Z9 11
U1 1
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-5282
J9 J TRAUMA
JI J. Trauma-Injury Infect. Crit. Care
PD DEC
PY 2011
VL 71
IS 6
BP 1575
EP 1582
DI 10.1097/TA.0b013e31821cb7e5
PG 8
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 869RT
UT WOS:000298616400023
PM 22002612
ER
PT J
AU de Moya, M
Bramos, T
Agarwal, S
Fikry, K
Janjua, S
King, DR
Alam, HB
Velmahos, GC
Burke, P
Tobler, W
AF de Moya, Marc
Bramos, Thanos
Agarwal, Suresh
Fikry, Karim
Janjua, Sumbal
King, David R.
Alam, Hasan B.
Velmahos, George C.
Burke, Peter
Tobler, William
TI Pain as an Indication for Rib Fixation: A Bi-Institutional Pilot Study
SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
LA English
DT Article; Proceedings Paper
CT 40th Annual Meeting of the Western-Trauma-Association
CY FEB 28-MAR 07, 2010
CL Telluride, CO
SP Western Trauma Assoc, Novo Nordisk A/S
DE Chest trauma; Rib fractures; Rib fixation; Flail chest
ID CHEST-WALL FRACTURES; UNDERUSED PROCEDURE; OPERATIVE FIXATION; FLAIL
CHEST; STABILIZATION; MORTALITY; MANAGEMENT; MORBIDITY; OUTCOMES
AB Background: In trauma patients, open reduction and internal fixation of rib fractures remain controversial. We hypothesized that patients who have open reduction and internal fixation of rib fractures would experience less pain compared with controls and thus require fewer opiates. Further, we hypothesized that improved pain control would result in fewer pulmonary complications and decreased length of stay.
Methods: This is a retrospective bi-institutional matched case-control study. Cases were matched 1: 2 by age, injury severity Score, chest abbreviated injury severity score, head abbreviated injury severity score, pulmonary contusion score, and number of fractured ribs. The daily total doses of analgesic drugs were converted to equianalgesic intravenous morphine doses, and the primary outcome was inpatient narcotic administration.
Results: Sixteen patients between July 2005 and June 2009 underwent rib fixation in 5 +/- 3 days after injury using an average of 3 (1-5) metallic plates. Morphine requirements decreased from 110 mg +/- 98 mg preoperatively to 63 +/- 57 mg postoperatively (p = 0.01). There were no significant differences between cases and controls in the mean morphine dose (79 +/- 63 vs. 76 +/- 55 mg, p = 0.65), hospital stay (18 +/- 12 vs. 16 +/- 11 days, p = 0.67), intensive care unit stay (9 +/- 8 vs. 7 +/- 10 days, p = 0.75), ventilation days (7 +/- 8 vs. 6 +/- 10, p = 0.44), and pneumonia rates (31% vs. 38%, p = 0.76).
Conclusion: The need for analgesia was significantly reduced after rib fixation in patients with multiple rib fractures. However, no difference in outcomes was observed when these patients were compared with matched controls in this pilot study. Further study is required to investigate these preliminary findings.
C1 [de Moya, Marc] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
[de Moya, Marc] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Agarwal, Suresh] Div Trauma, Boston, MA USA.
[Burke, Peter; Tobler, William] Boston Med Ctr, Boston, MA USA.
RP de Moya, M (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
EM mdemoya@partners.org
OI Burke, Peter/0000-0002-0329-5436; King, David/0000-0003-1028-1478
NR 14
TC 18
Z9 19
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-5282
J9 J TRAUMA
JI J. Trauma-Injury Infect. Crit. Care
PD DEC
PY 2011
VL 71
IS 6
BP 1750
EP 1754
DI 10.1097/TA.0b013e31823c85e9
PG 5
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 869RT
UT WOS:000298616400055
PM 22182884
ER
PT J
AU King, DR
AF King, David R.
TI Thirty Consecutive Uses of a Hemostatic Bandage at a US Army Combat
Support Hospital and Forward Surgical Team in Operation Iraqi Freedom
SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
LA English
DT Article
DE MRDH; Combat; Hemostasis; Coagulopathy; Topical; Bandage
ID SEVERE LIVER-INJURY; REDUCES BLOOD-LOSS; COAGULOPATHIC PIGS; HEMORRHAGE
CONTROL; CASE SERIES; DRESSINGS; EXPERIENCE; MORTALITY; SWINE; MODEL
AB Background: Topical hemostatic agents have generated intense research interest in recent years, prompted in part by the demands of wartime medicine. Numerous animal studies demonstrate variable degrees of efficacy of a variety of agents; however, little clinical data are available in severely traumatized patients. This report describes 30 consecutive uses of the modified rapid deployment hemostat (MRDH) during combat operations in Operation Iraqi Freedom.
Methods: In a prospective observational fashion, traumatized patients presenting to a combat support hospital or a forward surgical team with difficult to control hemorrhage (due to anatomy, limited resources, or tactical environment) had the MRDH applied to severely bleeding wounds. Basic demographics, wounding mechanism, wound characteristics, circumstances, and efficacy were recorded. Presence of a clinical coagulopathy was also noted.
Results: Thirty hemostatic bandages were applied to 19 patients with a wide variety of wounds. All but one application occurred in the operating room. The demographics were mean age 27 years (range, 9-55 years), 95% male, 68% penetrating or fragmentation, and four casualties had a clinical coagulopathy. Hemostasis was achieved following application of the hemostatic agent in 16 of 19 wounds. Rebleeding occurred upon removal in three cases. In all cases, the patient failed conventional interventions at hemostasis before the hemostat was applied.
Conclusions: This is the single largest description of the clinical efficacy of the MRDH and the first description during combat operations. The MRDH bandage was an effective hemostat for temporarily controlling hemorrhage in difficult circumstances. Caution should be exercised when removing the dressing as rebleeding may occur.
C1 [King, David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02141 USA.
[King, David R.] Harvard Univ, Sch Med, Boston, MA 02141 USA.
RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA.
EM dking3@partners.org
OI King, David/0000-0003-1028-1478
NR 14
TC 14
Z9 14
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-5282
J9 J TRAUMA
JI J. Trauma-Injury Infect. Crit. Care
PD DEC
PY 2011
VL 71
IS 6
BP 1775
EP 1778
DI 10.1097/TA.0b013e3182231615
PG 4
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 869RT
UT WOS:000298616400061
PM 22182888
ER
PT J
AU Nickerson, A
Aderka, IM
Bryant, RA
Litz, BT
Hofmann, SG
AF Nickerson, Angela
Aderka, Idan M.
Bryant, Richard A.
Litz, Brett T.
Hofmann, Stefan G.
TI Accidental and Intentional Perpetration of Serious Injury or Death:
Correlates and Relationship to Trauma Exposure
SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
LA English
DT Article
DE Perpetration; Injury; Trauma; Psychopathology; Posttraumatic stress
disorder
ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-COMORBIDITY-SURVEY; INTIMATE
PARTNER VIOLENCE; MAJOR RAILWAY ACCIDENTS; REPLICATION NCS-R; TRAIN
DRIVERS; MENTAL-HEALTH; RISK-FACTORS; PSYCHOLOGICAL REACTIONS;
REPRESENTATIVE SAMPLE
AB Background: The pernicious individual and societal effects of exposure to violence highlight the importance of understanding factors related to trauma perpetration. Little research has investigated the phenomenon of accidental perpetration of serious injury and death, or considered the relationship between perpetration and trauma exposure.
Methods: This study uses data from the National Comorbidity Survey-Replication to examine the demographic correlates and characteristics of both intentional and accidental perpetration of trauma, as well as the relationship of these types of perpetration to exposure to traumatic events. Participants were 83 individuals who had accidentally perpetrated trauma and 120 individuals who had intentionally perpetrated trauma.
Results: Findings indicated that men were more likely than women to report having intentionally, compared to accidentally, perpetrated trauma. Intentional and accidental perpetration of trauma were both associated with high levels of psychologic disorders, although those who had intentionally perpetrated trauma were more likely to report symptoms of posttraumatic stress disorder compared with those who had accidentally perpetrated trauma. Intentional perpetrators were more likely to have experienced interpersonal trauma in adulthood and childhood compared to accidental perpetrators. Interpersonal and sexual trauma was likely to precede any kind of trauma perpetration.
Conclusions: Findings suggest that accidental, as well as intentional, perpetration of serious injury or death frequently occurs in the context of trauma and violence. Both types of perpetration are related to psychopathology. Potential mechanisms underlying the relationship between trauma exposure, psychopathology, and perpetration are discussed. Further research is needed to elucidate pathways from trauma exposure to perpetration and mental disorder.
C1 [Nickerson, Angela; Litz, Brett T.] Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA.
[Aderka, Idan M.; Hofmann, Stefan G.] Boston Univ, Psychotherapy & Emot Res Lab, Boston, MA 02215 USA.
[Nickerson, Angela; Bryant, Richard A.] Univ New S Wales, Sch Psychol, Sydney, NSW, Australia.
RP Nickerson, A (reprint author), Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, 150 S Huntington Ave, Boston, MA 02130 USA.
EM anickerson@psy.unsw.edu.au
RI Hofmann, Stefan/B-8769-2014;
OI Hofmann, Stefan/0000-0002-3548-9681; Bryant, Richard/0000-0002-9607-819X
NR 68
TC 2
Z9 2
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-5282
J9 J TRAUMA
JI J. Trauma-Injury Infect. Crit. Care
PD DEC
PY 2011
VL 71
IS 6
BP 1821
EP 1828
DI 10.1097/TA.0b013e318226ec53
PG 8
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 869RT
UT WOS:000298616400069
PM 22027880
ER
PT J
AU King, DR
AF King, David R.
TI Emergent Cricothyroidotomy in the Morbidly Obese: A Safe,
No-Visualization Technique
SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
LA English
DT Article
C1 [King, David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02141 USA.
[King, David R.] Harvard Univ, Sch Med, Boston, MA 02141 USA.
RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA.
EM dking3@partners.org
OI King, David/0000-0003-1028-1478
NR 2
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-5282
J9 J TRAUMA
JI J. Trauma-Injury Infect. Crit. Care
PD DEC
PY 2011
VL 71
IS 6
BP 1873
EP 1874
DI 10.1097/TA.0b013e318226fd92
PG 2
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 869RT
UT WOS:000298616400075
PM 22182897
ER
PT J
AU Kaiser, AP
Park, CL
King, LA
King, DW
Schuster, J
Spiro, A
Moore, JL
Kaloupek, DG
Keane, TM
AF Kaiser, Anica Pless
Park, Crystal L.
King, Lynda A.
King, Daniel W.
Schuster, Jennifer
Spiro, Avron, III
Moore, Jeffrey L.
Kaloupek, Danny G.
Keane, Terence M.
TI Long-term effects of coping with extreme stress: Longitudinal study of
Vietnam-era repatriated prisoners of war
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID GOODNESS-OF-FIT; FORMER PRISONERS; APPRAISALS; HYPOTHESIS; SURVIVORS;
VETERANS; OUTCOMES; TORTURE; TRAUMA; SCALE
AB Captivity stressors and coping strategies were assessed shortly after the repatriation of Vietnam-era prisoners of war, and physical and mental health were assessed almost three decades later. Given research on coping goodness-of-fit, specifically the extent to which coping effects depend on situational controllability, we proposed that endorsement of the usefulness of avoidance-based strategies in captivity would be predictive of better later-life health. Findings indicated that approach-based and avoidance-based coping both moderated the link between physical torture and later physical health functional status, whereas approach-based coping moderated the link between injuries at capture and later mental health. Specifically, greater endorsement of avoidance-based coping was associated with better long-term physical health for prisoners who experienced the most physical torture. Lower endorsement of approach-based coping was associated with better long-term mental health for prisoners who reported the most injuries at the time of capture.
C1 [Kaiser, Anica Pless; Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Massachusetts Vet Epidemiol Res & Informat Ctr, VA Boston Healthcare Syst,Dept Epidemiol, Boston, MA 02130 USA.
[Kaiser, Anica Pless; King, Lynda A.; King, Daniel W.; Schuster, Jennifer; Kaloupek, Danny G.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA.
[Kaiser, Anica Pless; King, Lynda A.; King, Daniel W.; Kaloupek, Danny G.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Park, Crystal L.] Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA.
[Spiro, Avron, III] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA.
[Moore, Jeffrey L.] RE Mitchell Ctr Repatriated Prisoner War Studies, Pensacola, FL USA.
RP Kaiser, AP (reprint author), Boston Univ, Sch Publ Hlth, Massachusetts Vet Epidemiol Res & Informat Ctr, VA Boston Healthcare Syst,Dept Epidemiol, 150 S Huntington Ave,116B-2, Boston, MA 02130 USA.
EM anica.plesskaiser@va.gov
RI Schueter, nicos/A-3625-2014;
OI Spiro III, Avron/0000-0003-4080-8621; Kaloupek,
Danny/0000-0002-0795-593X
NR 30
TC 3
Z9 3
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0894-9867
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD DEC
PY 2011
VL 24
IS 6
BP 680
EP 690
DI 10.1002/jts.20695
PG 11
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 869FF
UT WOS:000298581800008
PM 22147391
ER
PT J
AU Arifuzzaman, M
Ahmed, T
Rahman, MA
Chowdhury, F
Rashu, R
Khan, AI
LaRocque, RC
Harris, JB
Bhuiyan, TR
Ryan, ET
Calderwood, SB
Qadri, F
AF Arifuzzaman, Mohammad
Ahmed, Tanvir
Rahman, Mohammad Arif
Chowdhury, Fahima
Rashu, Rasheduzzaman
Khan, Ashraful I.
LaRocque, Regina C.
Harris, Jason B.
Bhuiyan, Taufiqur Rahman
Ryan, Edward T.
Calderwood, Stephen B.
Qadri, Firdausi
TI Individuals with Le(a plus b-) Blood Group Have Increased Susceptibility
to Symptomatic Vibrio cholerae O1 Infection
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID ENTEROTOXIGENIC ESCHERICHIA-COLI; HELICOBACTER-PYLORI; CELL RESPONSES;
GROUP ANTIGENS; HUMAN-MILK; BANGLADESH; LEWIS; ABO; ANTIBODY; DIARRHEA
AB Background: Human genetic factors such as blood group antigens may affect the severity of infectious diseases. Presence of specific ABO and Lewis blood group antigens has been shown previously to be associated with the risk of different enteric infections. The aim of this study was to determine the relationship of the Lewis blood group antigens with susceptibility to cholera, as well as severity of disease and immune responses to infection.
Methodology: We determined Lewis and ABO blood groups of a cohort of patients infected by Vibrio cholerae O1, their household contacts, and healthy controls, and analyzed the risk of symptomatic infection, severity of disease if infected and immune response following infection. Principal Findings: We found that more individuals with cholera expressed the Le(a+b-) phenotype than the asymptomatic household contacts (OR 1.91, 95% CI 1.03-3.56) or healthy controls (OR 1.90, 95% CI 1.13-3.21), as has been seen previously for the risk of symptomatic ETEC infection. Le(a-b+) individuals were less susceptible to cholera and if infected, required less intravenous fluid replacement in hospital, suggesting that this blood group may be associated with protection against V. cholerae O1. Individuals with Le(a-b-) blood group phenotype who had symptomatic cholera had a longer duration of diarrhea and required higher volumes of intravenous fluid replacement. In addition, individuals with Le(a-b-) phenotype also had lessened plasma IgA responses to V. cholerae O1 lipopolysaccharide on day 7 after infection compared to individuals in the other two Lewis blood group phenotypes.
Conclusion: Individuals with Lewis blood type Le(a+b-) are more susceptible and Le(a-b+) are less susceptible to V. cholerae O1 associated symptomatic disease. Presence of this histo-blood group antigen may be included in evaluating the risk for cholera in a population, as well as in vaccine efficacy studies, as is currently being done for the ABO blood group antigens.
C1 [Arifuzzaman, Mohammad; Ahmed, Tanvir; Rahman, Mohammad Arif; Chowdhury, Fahima; Rashu, Rasheduzzaman; Khan, Ashraful I.; Bhuiyan, Taufiqur Rahman; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res Bangladesh ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh.
[Arifuzzaman, Mohammad; LaRocque, Regina C.; Harris, Jason B.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Harris, Jason B.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
RP Arifuzzaman, M (reprint author), Int Ctr Diarrhoeal Dis Res Bangladesh ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh.
EM fqadri@icddrb.org
FU ICDDR,B; International Research Scientist Development Award [KO1
TW07144, KO1 TW07409]; Howard Hughes Medical Institute Physician
Scientist Early Career Award; Fogarty International Center [D43
TW05572]; Fogarty International Center at the National Institutes of
Health [D43 TW005572, R24 TW007988]; Swedish International Development
Cooperation Agency (SIDA); [U01 AI058935]; [RO3 AI063079]; [U01
AI077883]
FX This research was supported by the ICDDR,B and by the following grants:
U01 AI058935 (SBC), RO3 AI063079 (FQ), U01 AI077883 (ETR), International
Research Scientist Development Award KO1 TW07144 (RCL), Howard Hughes
Medical Institute Physician Scientist Early Career Award (RCL),
International Research Scientist Development Award KO1 TW07409 (JBH),
and a Fogarty International Center Global Infectious Disease Research
Training Program Award in Vaccine Development D43 TW05572 (MA). TRB and
FC are recipients of Fogarty International Clinical Research Scholars
Awards from the Fogarty International Center at the National Institutes
of Health (D43 TW005572 and R24 TW007988). FQ is a recipient of funds
from the Swedish International Development Cooperation Agency (SIDA).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 46
TC 6
Z9 6
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1935-2727
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD DEC
PY 2011
VL 5
IS 12
AR e1413
DI 10.1371/journal.pntd.0001413
PG 8
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 870KI
UT WOS:000298667700019
PM 22216364
ER
PT J
AU Sheikh, A
Charles, RC
Sharmeen, N
Rollins, SM
Harris, JB
Bhuiyan, MS
Arifuzzaman, M
Khanam, F
Bukka, A
Kalsy, A
Porwollik, S
Leung, DT
Brooks, WA
LaRocque, RC
Hohmann, EL
Cravioto, A
Logvinenko, T
Calderwood, SB
McClelland, M
Graham, JE
Qadri, F
Ryan, ET
AF Sheikh, Alaullah
Charles, Richelle C.
Sharmeen, Nusrat
Rollins, Sean M.
Harris, Jason B.
Bhuiyan, Md. Saruar
Arifuzzaman, Mohammad
Khanam, Farhana
Bukka, Archana
Kalsy, Anuj
Porwollik, Steffen
Leung, Daniel T.
Brooks, W. Abdullah
LaRocque, Regina C.
Hohmann, Elizabeth L.
Cravioto, Alejandro
Logvinenko, Tanya
Calderwood, Stephen B.
McClelland, Michael
Graham, James E.
Qadri, Firdausi
Ryan, Edward T.
TI In Vivo Expression of Salmonella enterica Serotype Typhi Genes in the
Blood of Patients with Typhoid Fever in Bangladesh
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID TRANSCRIBED SEQUENCES SCOTS; COMPLETE GENOME SEQUENCE; SEROVAR
TYPHIMURIUM; SELECTIVE CAPTURE; HOST-CELLS; PEPTIDE RESISTANCE;
ESCHERICHIA-COLI; IVB PILI; VIRULENCE; MACROPHAGES
AB Background: Salmonella enterica serotype Typhi is the cause of typhoid fever. It is a human-restricted pathogen, and few data exist on S. Typhi gene expression in humans.
Methodology/Principal Findings: We applied an RNA capture and amplification technique, Selective Capture of Transcribed Sequences (SCOTS), and microarray hybridization to identify S. Typhi transcripts expressed in the blood of five humans infected with S. Typhi in Bangladesh. In total, we detected the expression of mRNAs for 2,046 S. Typhi genes (44% of the S. Typhi genome) in human blood; expression of 912 genes was detected in all 5 patients, and expression of 1,100 genes was detected in 4 or more patients. Identified transcripts were associated with the virulence-associated PhoP regulon, Salmonella pathogenicity islands, the use of alternative carbon and energy sources, synthesis and transport of iron, thiamine, and biotin, and resistance to antimicrobial peptides and oxidative stress. The most highly represented group were genes currently annotated as encoding proteins designated as hypothetical, unknown, or unclassified. Of the 2,046 detected transcripts, 1,320 (29% of the S. Typhi genome) had significantly different levels of detection in human blood compared to in vitro cultures; detection of 141 transcripts was significantly different in all 5 patients, and detection of 331 transcripts varied in at least 4 patients. These mRNAs encode proteins of unknown function, those involved in energy metabolism, transport and binding, cell envelope, cellular processes, and pathogenesis. We confirmed increased expression of a subset of identified mRNAs by quantitative-PCR.
Conclusions/Significance: We report the first characterization of bacterial transcriptional profiles in the blood of patients with typhoid fever. S. Typhi is an important global pathogen whose restricted host range has greatly inhibited laboratory studies. Our results suggest that S. Typhi uses a largely uncharacterized genetic repertoire to survive within cells and utilize alternate energy sources during infection.
C1 [Sheikh, Alaullah; Charles, Richelle C.; Rollins, Sean M.; Harris, Jason B.; Bhuiyan, Md. Saruar; Kalsy, Anuj; Leung, Daniel T.; LaRocque, Regina C.; Hohmann, Elizabeth L.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Charles, Richelle C.; Rollins, Sean M.; Harris, Jason B.; Leung, Daniel T.; LaRocque, Regina C.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Sheikh, Alaullah; Sharmeen, Nusrat; Bhuiyan, Md. Saruar; Arifuzzaman, Mohammad; Khanam, Farhana; Brooks, W. Abdullah; Cravioto, Alejandro; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh.
[Bukka, Archana] Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA.
[Porwollik, Steffen; McClelland, Michael] Vaccine Res Inst San Diego, San Diego, CA USA.
[Logvinenko, Tanya] Tufts Med Ctr, Div Biostat, Inst Clin Res & Hlth Policy Studies ICRHPS, Boston, MA USA.
[Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
[Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Charles, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
EM rccharles@partners.org
OI Rollins, Sean/0000-0002-3724-1989; McClelland,
Michael/0000-0003-1788-9347; leung, daniel/0000-0001-8401-0801
FU ICDDR,B; National Institutes of Health, including the National Institute
of Allergy & Infectious Diseases [AI072599, AI077883, AI058935,
AI052237, AI073971, AI075093, AI083964, AI039557, AI077645, AI083646,
BARD IS-4267-09, A148635]; Johns Hopkins Bloomberg School of Public
Health; ICDDRB-US Centers for Disease Control and Prevention; Fogarty
International Center [TW05572, K01 TW007409, K01 TW07144]; American
Recovery and Reinvestment Act (ARRA) [TW005572-S1]; NIAID [K08
AI089721]; Howard Hughes Medical Institute
FX This work was supported by the ICDDR,B and grants from the National
Institutes of Health, including the National Institute of Allergy &
Infectious Diseases (AI072599, AI077883 [ETR]; AI058935 [SBC]; AI052237,
AI073971, AI075093, AI083964, AI039557, AI077645, AI083646, and BARD
IS-4267-09 [MMCC]; A148635 [JEG]; ICDDR, B core funds (FQ, WAB); the
PneumoADIP Project of the Johns Hopkins Bloomberg School of Public
Health (WAB); a ICDDRB-US Centers for Disease Control and Prevention
Cooperative Agreement (WAB); a Training Grant in Vaccine Development
from the Fogarty International Center (TW05572 [AS, MSB, FQ]); an
American Recovery and Reinvestment Act (ARRA) FIC Post-doctoral
Fellowship in Global Infectious Diseases (TW005572-S1 [RCC]); Career
Development Awards from the Fogarty International Center (K01 TW007409
[JBH], K01 TW07144 [RCL]), and NIAID (K08 AI089721 [RCC]); and a
Physician Scientist Early Career Award from the Howard Hughes Medical
Institute (RCL). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 48
TC 22
Z9 22
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1935-2727
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD DEC
PY 2011
VL 5
IS 12
AR e1419
DI 10.1371/journal.pntd.0001419
PG 8
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 870KI
UT WOS:000298667700024
PM 22180799
ER
PT J
AU Hellmann, I
Lim, SY
Gelman, RS
Letvin, NL
AF Hellmann, Ina
Lim, So-Yon
Gelman, Rebecca S.
Letvin, Norman L.
TI Association of Activating KIR Copy Number Variation of NK Cells with
Containment of SIV Replication in Rhesus Monkeys
SO PLOS PATHOGENS
LA English
DT Article
ID NATURAL-KILLER-CELLS; IMMUNODEFICIENCY VIRUS-INFECTION; EXPOSED
UNINFECTED INDIVIDUALS; SIMIAN IMMUNODEFICIENCY; HIV-1 INFECTION;
RECEPTOR REPERTOIRES; TYPE-1 INFECTION; VIRAL-INFECTIONS; HLA-B;
MACAQUES
AB While the contribution of CD8(+) cytotoxic T lymphocytes to early containment of HIV-1 spread is well established, a role for NK cells in controlling HIV-1 replication during primary infection has been uncertain. The highly polymorphic family of KIR molecules expressed on NK cells can inhibit or activate these effector cells and might therefore modulate their activity against HIV-1-infected cells. In the present study, we investigated copy number variation in KIR3DH loci encoding the only activating KIR receptor family in rhesus monkeys and its effect on simian immunodeficiency virus (SIV) replication during primary infection in rhesus monkeys. We observed an association between copy numbers of KIR3DH genes and control of SIV replication in Mamu-A*01(-) rhesus monkeys that express restrictive TRIM5 alleles. These findings provide further evidence for an association between NK cells and the early containment of SIV replication, and underscore the potential importance of activating KIRs in stimulating NK cell responses to control SIV spread.
C1 [Hellmann, Ina; Lim, So-Yon; Letvin, Norman L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, Boston, MA 02215 USA.
[Gelman, Rebecca S.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA.
[Gelman, Rebecca S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Hellmann, I (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, Boston, MA 02215 USA.
EM nletvin@bidmc.harvard.edu
FU NIAID Center for HIV/AIDS [AI067854]
FX This work was supported by the NIAID Center for HIV/AIDS Vaccine
Immunology grant AI067854. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 54
TC 13
Z9 14
U1 0
U2 0
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 DEC
PY 2011
VL 7
IS 12
AR e1002436
DI 10.1371/journal.ppat.1002436
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 876LH
UT WOS:000299108500047
PM 22194686
ER
PT J
AU McCulloch, L
Brown, KL
Bradford, BM
Hopkins, J
Bailey, M
Rajewsky, K
Manson, JC
Mabbott, NA
AF McCulloch, Laura
Brown, Karen L.
Bradford, Barry M.
Hopkins, John
Bailey, Mick
Rajewsky, Klaus
Manson, Jean C.
Mabbott, Neil A.
TI Follicular Dendritic Cell-Specific Prion Protein (PrPc) Expression Alone
Is Sufficient to Sustain Prion Infection in the Spleen
SO PLOS PATHOGENS
LA English
DT Article
ID SCRAPIE AGENT NEUROINVASION; TUMOR-NECROSIS-FACTOR; LYMPHOID-TISSUES;
STROMAL CELLS; B-LYMPHOCYTES; SPONGIFORM ENCEPHALOPATHY;
AUTOIMMUNE-DISEASE; MICE; PATHOGENESIS; REPLICATION
AB Prion diseases are characterised by the accumulation of PrPSc, an abnormally folded isoform of the cellular prion protein (PrPC), in affected tissues. Following peripheral exposure high levels of prion-specific PrPSc accumulate first upon follicular dendritic cells (FDC) in lymphoid tissues before spreading to the CNS. Expression of PrPC is mandatory for cells to sustain prion infection and FDC appear to express high levels. However, whether FDC actively replicate prions or simply acquire them from other infected cells is uncertain. In the attempts to-date to establish the role of FDC in prion pathogenesis it was not possible to dissociate the Prnp expression of FDC from that of the nervous system and all other non-haematopoietic lineages. This is important as FDC may simply acquire prions after synthesis by other infected cells. To establish the role of FDC in prion pathogenesis transgenic mice were created in which PrPC expression was specifically "switched on" or "off" only on FDC. We show that PrPC-expression only on FDC is sufficient to sustain prion replication in the spleen. Furthermore, prion replication is blocked in the spleen when PrPC-expression is specifically ablated only on FDC. These data definitively demonstrate that FDC are the essential sites of prion replication in lymphoid tissues. The demonstration that Prnp-ablation only on FDC blocked splenic prion accumulation without apparent consequences for FDC status represents a novel opportunity to prevent neuroinvasion by modulation of PrPC expression on FDC.
C1 [McCulloch, Laura; Brown, Karen L.; Bradford, Barry M.; Hopkins, John; Manson, Jean C.; Mabbott, Neil A.] Univ Edinburgh, Roslin Inst, Edinburgh EH8 9YL, Midlothian, Scotland.
[McCulloch, Laura; Brown, Karen L.; Bradford, Barry M.; Hopkins, John; Manson, Jean C.; Mabbott, Neil A.] Univ Edinburgh, Royal Dick Sch Vet Sci, Edinburgh EH8 9YL, Midlothian, Scotland.
[Bailey, Mick] Univ Bristol, Sch Clin Vet Sci, Div Vet Pathol Infect & Immun, Bristol BS8 1TH, Avon, England.
[Rajewsky, Klaus] Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA.
[Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA.
RP McCulloch, L (reprint author), Univ Edinburgh, Roslin Inst, Edinburgh EH8 9YL, Midlothian, Scotland.
EM neil.mabbott@roslin.ed.ac.uk
RI Bradford, Barry/B-3783-2013; Hopkins, John/C-7756-2013
OI Bradford, Barry/0000-0002-4007-1685; Hopkins, John/0000-0002-9530-8037
FU UK Biotechnology and Biological Sciences Research Council;
[BB/526741-1]; [BBS/E/R/00001813]
FX This work was supported by project (Grant numbers BB/526741-1 and
BBS/E/R/00001813) and Institute Strategic Grant funding from the UK
Biotechnology and Biological Sciences Research Council. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 68
TC 32
Z9 32
U1 1
U2 9
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 DEC
PY 2011
VL 7
IS 12
AR e1002402
DI 10.1371/journal.ppat.1002402
PG 20
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 876LH
UT WOS:000299108500016
PM 22144895
ER
PT J
AU van Diepen, JA
Vroegrijk, IOCM
Berbee, JFP
Shoelson, SE
Romijn, JA
Havekes, LM
Rensen, PCN
Voshol, PJ
AF van Diepen, Janna A.
Vroegrijk, Irene O. C. M.
Berbee, Jimmy F. P.
Shoelson, Steven E.
Romijn, Johannes A.
Havekes, Louis M.
Rensen, Patrick C. N.
Voshol, Peter J.
TI Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride
production in mice fed a high-fat diet
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE lipid metabolism; inflammation; very low-density lipoprotein
ID NF-KAPPA-B; LIPOPROTEIN-LIPASE; INSULIN-RESISTANCE; SODIUM-SALICYLATE;
ACETYLSALICYLIC-ACID; SERUM-LIPOPROTEINS; LIPID-METABOLISM; TRANSGENIC
MICE; IKK-BETA; ENDOTOXIN
AB van Diepen JA, Vroegrijk IO, Berbee JF, Shoelson SE, Romijn JA, Havekes LM, Rensen PC, Voshol PJ. Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet. Am J Physiol Endocrinol Metab 301: E1099-E1107, 2011. First published August 23, 2011; doi: 10.1152/ajpendo.00185.2011.-Systemic inflammation is strongly involved in the pathophysiology of the metabolic syndrome, a cluster of metabolic risk factors that includes hypertriglyceridemia. Aspirin treatment lowers inflammation via inhibition of NF-kappa B activity but also reduces hypertriglyceridemia in humans. The aim of this study was to investigate the mechanism by which aspirin improves hypertriglyceridemia. Human apolipoprotein CI (apoCI)-expressing mice (APOC1 mice), an animal model with elevated plasma triglyceride (TG) levels, as well as normolipidemic wild-type (WT) mice were fed a high-fat diet (HFD) and treated with aspirin. Aspirin treatment reduced hepatic NF-kappa B activity in HFD-fed APOC1 and WT mice, and in addition, aspirin decreased plasma TG levels (-32%, P < 0.05) in hypertriglyceridemic APOC1 mice. This TG-lowering effect could not be explained by enhanced VLDL-TG clearance, but aspirin selectively reduced hepatic production of VLDL-TG in both APOC1 (-28%, P < 0.05) and WT mice (-33%, P < 0.05) without affecting VLDL-apoB production. Aspirin did not alter hepatic expression of genes involved in FA oxidation, lipogenesis, and VLDL production but decreased the incorporation of plasma-derived FA by the liver into VLDL-TG (-24%, P < 0.05), which was independent of hepatic expression of genes involved in FA uptake and transport. We conclude that aspirin improves hypertriglyceridemia by decreasing VLDL-TG production without affecting VLDL particle production. Therefore, the inhibition of inflammatory pathways by aspirin could be an interesting target for the treatment of hypertriglyceridemia.
C1 [van Diepen, Janna A.; Vroegrijk, Irene O. C. M.; Berbee, Jimmy F. P.; Romijn, Johannes A.; Havekes, Louis M.; Rensen, Patrick C. N.; Voshol, Peter J.] Leiden Univ, Med Ctr, Dept Gen Internal Med, NL-2300 RC Leiden, Netherlands.
[van Diepen, Janna A.; Vroegrijk, Irene O. C. M.; Berbee, Jimmy F. P.; Romijn, Johannes A.; Havekes, Louis M.; Rensen, Patrick C. N.; Voshol, Peter J.] Leiden Univ, Med Ctr, Dept Endocrinol, NL-2300 RC Leiden, Netherlands.
[van Diepen, Janna A.; Vroegrijk, Irene O. C. M.; Berbee, Jimmy F. P.; Romijn, Johannes A.; Havekes, Louis M.; Rensen, Patrick C. N.; Voshol, Peter J.] Leiden Univ, Med Ctr, Dept Metab Dis, NL-2300 RC Leiden, Netherlands.
[Havekes, Louis M.] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands.
[Shoelson, Steven E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Shoelson, Steven E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Havekes, Louis M.] TNO, IVVO, Gaubius Lab, Netherlands Org Appl Sci Res Biosci, NL-2300 AK Leiden, Netherlands.
RP van Diepen, JA (reprint author), Leiden Univ, Med Ctr, Dept Endocrinol & Metab Dis, Albinusdreef 2,POB 9600, NL-2300 RC Leiden, Netherlands.
EM J.A.van_Diepen@lumc.nl
RI van Diepen, Janna/E-9485-2010
OI van Diepen, Janna/0000-0001-9091-1075
FU Netherlands Organization for Scientific Research (NWO Zon-MW)
[917.76.301]; Dutch Diabetes Research Foundation [2005.01.003]; European
Union [202272]; Netherlands Heart Foundation [2009T038]
FX This work was supported by grants from The Netherlands Organization for
Scientific Research (NWO Zon-MW; 917.76.301 to P. J. Voshol) and the
Dutch Diabetes Research Foundation (2005.01.003 to P. J. Voshol). I. O.
C. M. Vroegrijk is supported by the Seventh Framework Program of the
European Union-funded "LipidomicNet" (202272). P. C. N. Rensen is an
Established Investigator of The Netherlands Heart Foundation (2009T038).
NR 38
TC 10
Z9 10
U1 0
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD DEC
PY 2011
VL 301
IS 6
BP E1099
EP E1107
DI 10.1152/ajpendo.00185.2011
PG 9
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 863CT
UT WOS:000298141100007
PM 21862721
ER
PT J
AU Falvo, JV
Ranjbar, S
Jasenosky, LD
Goldfeld, AE
AF Falvo, James V.
Ranjbar, Shahin
Jasenosky, Luke D.
Goldfeld, Anne E.
TI Arc of a Vicious Circle Pathways Activated by Mycobacterium tuberculosis
That Target the HIV-1 Long Terminal Repeat
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Review
DE HIV/TB coinfection; transcription; signal transduction; innate immunity;
cytokines
ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; TOLL-LIKE RECEPTORS; FACTOR-ALPHA
GENE; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CREB-BINDING-PROTEIN;
GROWTH-FACTOR-BETA; INTERFERON-GAMMA; T-CELLS; PROINFLAMMATORY CYTOKINES
AB In this review, we examine how a subset of signal transduction cascades initiated by Mycobacterium tuberculosis (Mtb) infection modulates transcription mediated by the human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR). We describe two distinct phases of signaling that target transcription factors known to bind the HIV-1 LTR, and thus drive viral transcription and replication, in cells of the Mtb-infected host. First, Mtb-derived molecules, including cell wall components and DNA, interact with a number of host pattern recognition receptors. Second, cytokines and chemokines secreted in response to Mtb infection initiate signal transduction cascades through their cognate receptors. Given the variation in cell wall components among distinct clinical Mtb strains, the initial pattern recognition receptor interaction leading to direct LTR activation and differential cytokine and chemokine production is likely to be an important aspect of Mtb strain-specific regulation of HIV-1 transcription and replication. Improved understanding of these molecular mechanisms in the context of bacterial and host genetics should provide key insights into the accelerated viral replication and disease progression characteristic of HIV/TB coinfection.
C1 [Falvo, James V.] Harvard Univ, Sch Med, Dept Pediat, Immune Dis Inst, Boston, MA 02115 USA.
[Falvo, James V.; Ranjbar, Shahin; Jasenosky, Luke D.; Goldfeld, Anne E.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
[Falvo, James V.; Ranjbar, Shahin; Jasenosky, Luke D.; Goldfeld, Anne E.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Goldfeld, Anne E.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Falvo, JV (reprint author), Harvard Univ, Sch Med, Dept Pediat, Immune Dis Inst, Boston, MA 02115 USA.
EM falvo@idi.harvard.edu
FU NIH [R01GM076685, NHLBL 059838, AI065285, R21AI060433]; Division of
Intramural Research of the NIH (NIAID); Harvard Center for AIDS Research
[P30A060354]
FX This work was supported by NIH grants R01GM076685, NHLBL 059838,
AI065285, and R21AI060433, by the Division of Intramural Research of the
NIH (NIAID) (A.E.G.), and by the Harvard Center for AIDS Research
(P30A060354) (S.R.).
NR 107
TC 12
Z9 12
U1 0
U2 4
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 DEC
PY 2011
VL 45
IS 6
BP 1116
EP 1124
DI 10.1165/rcmb.2011-0186TR
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 884CM
UT WOS:000299682500002
PM 21852682
ER
PT J
AU McKay, JR
AF McKay, James R.
TI Negative Mood, Craving, and Alcohol Relapse: Can Treatment Interrupt the
Process?
SO CURRENT PSYCHIATRY REPORTS
LA English
DT Editorial Material
DE Alcohol dependence; Behavioral treatment; Moderation; Mediation;
Negative mood; Craving; Relapse; Coping with craving;
Cognitive-behavioral therapy; Mechanisms of action
ID SUBSTANCE USE; LAPSES
C1 [McKay, James R.] Univ Penn, Philadelphia, PA 19104 USA.
[McKay, James R.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA.
RP McKay, JR (reprint author), Univ Penn, 3900 Chestnut St, Philadelphia, PA 19104 USA.
EM mckay_j@mail.trc.upenn.edu
FU NIAAA NIH HHS [P01 AA016821, P01 AA016821-03]
NR 8
TC 3
Z9 4
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3812
J9 CURR PSYCHIAT REP
JI Curr. Psychiatry Rep.
PD DEC
PY 2011
VL 13
IS 6
BP 431
EP 433
DI 10.1007/s11920-011-0225-z
PG 3
WC Psychiatry
SC Psychiatry
GA 876FG
UT WOS:000299092300001
PM 21822936
ER
PT J
AU Thase, ME
AF Thase, Michael E.
TI Combined Antidepressant Strategies Are Not More Effective Than Vigorous
Escitalopram Monotherapy: Results of the CO-MED Study
SO CURRENT PSYCHIATRY REPORTS
LA English
DT Editorial Material
DE Major depressive disorder; MDD; Depression; Randomized controlled trial;
RCT; Antidepressants; Combination therapy; Monotherapy; Escitalopram;
Bupropion; Venlafaxine; Mirtazapine; STAR*D; Depression Treatment
Network
ID MAJOR DEPRESSIVE DISORDER; DOUBLE-BLIND
C1 [Thase, Michael E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Thase, Michael E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
RP Thase, ME (reprint author), Univ Penn, Perelman Sch Med, 3535 Market St,Suite 670, Philadelphia, PA 19104 USA.
EM thase@mail.med.upenn.edu
NR 9
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3812
J9 CURR PSYCHIAT REP
JI Curr. Psychiatry Rep.
PD DEC
PY 2011
VL 13
IS 6
BP 434
EP 436
DI 10.1007/s11920-011-0236-9
PG 3
WC Psychiatry
SC Psychiatry
GA 876FG
UT WOS:000299092300002
PM 21956831
ER
PT J
AU Thase, ME
AF Thase, Michael E.
TI The Small Specific Effects of Antidepressants in Clinical Trials: What
Do They Mean to Psychiatrists?
SO CURRENT PSYCHIATRY REPORTS
LA English
DT Article
DE Antidepressants; Placebo; Meta-analysis; Randomized controlled trials;
RCT; Clinical trials; Psychiatrists
ID SEROTONIN REUPTAKE INHIBITORS; NATIONAL PATTERNS; MAJOR DEPRESSION;
PLACEBO-RESPONSE; REMISSION RATES; METAANALYSIS; EFFICACY;
PSYCHOTHERAPY; PHARMACOTHERAPY; MEDICATION
AB Although antidepressants continue to be a mainstay for clinicians who treat people suffering from depressive disorders, there have recently been articles published in both the scientific literature and the popular press that have raised questions about the utility of this class of medications. This paper briefly examines recent meta-analyses that have reported small drug versus placebo differences in randomized controlled trials and, from the perspective of a prescribing psychiatrist, discusses the clinical significance of these findings. It is concluded that antidepressants do have relatively modest effects (as compared with placebo) in contemporary randomized controlled trials, and that the contribution of placebo-expectancy factors to individual outcomes is often underestimated. Nevertheless, it is also concluded that the modest benefits of antidepressants in grouped datasets obscure large, specific, and very meaningful therapeutic effects for 10% to 20% of those treated with antidepressants.
C1 Univ Penn, Med Ctr, Philadelphia Vet Affairs Med Ctr, Perelman Sch Med,Univ Pittsburgh, Philadelphia, PA 19104 USA.
RP Thase, ME (reprint author), Univ Penn, Med Ctr, Philadelphia Vet Affairs Med Ctr, Perelman Sch Med,Univ Pittsburgh, 3535 Market St,Suite 670, Philadelphia, PA 19104 USA.
EM thase@mail.med.upenn.edu
FU Agency for Healthcare Research and Quality; Eli Lilly and Company;
Forest Pharmaceuticals; GlaxoSmithKline; National Institute of Mental
Health; Otsuka Pharmaceutical Co.; Sepracor; American Psychiatric
Foundation; Guilford Publications; Herald House; W.W. Norton Company
FX Dr. Thase has served as a consultant for Alkermes, AstraZeneca,
Bristol-Myers Squibb, Eli Lilly and Company, Dey Pharma, Forest
Laboratories, Gerson Lehrman Group, GlaxoSmithKline, Guidepoint Global,
H. Lundbeck A/S, MedAvante, Merck & Co. (formerly Schering-Plough and
Organon Pharmaceuticals USA), Neuronetics, Novartis, Otsuka
Pharmaceutical Co., Ortho-McNeil Pharmaceuticals (Johnson & Johnson),
Pamlab, Pfizer (formerly Wyeth-Ayerst International), PGxHealth, Shire
US, Supernus Pharmaceuticals, Takeda Pharmaceuticals North America, and
Transcept Pharmaceuticals; has received grant support from the Agency
for Healthcare Research and Quality, Eli Lilly and Company, Forest
Pharmaceuticals, GlaxoSmithKline, the National Institute of Mental
Health, Otsuka Pharmaceutical Co., and Sepracor; has received honoraria
from AstraZeneca, Bristol-Myers Squibb, Dey Pharma, Eli Lilly and
Company, Merck & Co., Pfizer (formerly Wyeth-Ayerst International); has
received royalties from the American Psychiatric Foundation, Guilford
Publications, Herald House, and W.W. Norton & Company; has received
payment for development of educational presentations (including service
on speakers' bureaus) from Pfizer and Bristol-Myers Squibb; and has held
stock/stock options in MedAvante. His wife has been employed by Embryon
(formerly Advogent).
NR 39
TC 9
Z9 9
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3812
J9 CURR PSYCHIAT REP
JI Curr. Psychiatry Rep.
PD DEC
PY 2011
VL 13
IS 6
BP 476
EP 482
DI 10.1007/s11920-011-0235-x
PG 7
WC Psychiatry
SC Psychiatry
GA 876FG
UT WOS:000299092300008
PM 21964929
ER
PT J
AU Wang, ZW
Baker, DG
Harrer, J
Hamner, M
Price, M
Amstadter, A
AF Wang, Zhewu
Baker, Dewleen G.
Harrer, Judith
Hamner, Mark
Price, Matthew
Amstadter, Ananda
TI The relationship between combat-related posttraumatic stress disorder
and the 5-HTTLPR/rs25531 polymorphism
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE post traumatic stress disorder; 5-HTTLPR; combat trauma; genetic risk;
5-HTTLPR genotypes; combat veteran
ID ADMINISTERED PTSD SCALE; ENVIRONMENTAL-INFLUENCES; EXPOSED ADULTS;
RISK-FACTORS; SEROTONIN; GENE; SYMPTOMS; INJURY; SUSCEPTIBILITY;
POPULATION
AB Background: Empirical evidence suggests that there is a significant genetic influence in the development of posttraumatic stress disorder (PTSD). The serotonin transporter (5-HTT) gene (SLC6A4) has been identified as a prime candidate for the development of the disorder, as 5-HTT is a working target for selective serotonin reuptake inhibitors (SSRIs), first line treatment agents for PTSD. Several studies have reported associations between 5-HTT-linked promoter region (5-HTTLPR) polymorphism variants and increased rates of PTSD in civilian samples. This study investigated the role of the 5-HTTLPR polymorphism, triallelically classified, in a sample of combat veterans with and without PTSD. Methods: Rates of PTSD were examined across three genotypes in a sample of 388 combat veterans. The short/long polymorphism of 5-HTTLPR and the A-G polymorphism within the 5-HTTLPR (rs25531) were genotyped, and statistical analyses were conducted. Results: There were significant intergroup (PTSD versus non-PTSD) differences in the genotype frequencies of 5-HTTLPR/rs25531 (2[1, n = 388] = 16.23, P = 5.62 x 10-5). The 5- HTTLPR S'/S' (low transcriptionally efficient) genotype was also associated with the PTSD severity score in the 228 participants who had combat severity data (r = .15, P = 0.03). Conclusions: The findings are consistent with previous research among civilian populations that have indicated that the low transcriptionally efficient S'/S' genotype of 5-HTTLPR is a risk factor for the development of PTSD after trauma exposure. Our findings are the first to examine this polymorphism and PTSD in a military sample. Additional large-scale investigations are needed to replicate these findings. Depression and Anxiety, 2011. (C) 2011 Wiley Periodicals, Inc.
C1 [Wang, Zhewu; Hamner, Mark] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA.
[Wang, Zhewu; Hamner, Mark; Price, Matthew] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA.
[Baker, Dewleen G.] VA San Diego, VA Ctr Exellence Stress & Mental Hlth, San Diego, CA USA.
[Baker, Dewleen G.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Harrer, Judith] Cincinnati VA Med Ctr, Cincinnati, OH USA.
[Amstadter, Ananda] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA.
RP Wang, ZW (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA.
EM wanzh@musc.edu
RI Schueter, nicos/A-3625-2014
FU Ralph H. Johnson VA Medical Center; Department of Veterans Affairs;
NARSAD
FX The authors disclose the following financial relationships within the
past 3 years: Contract grant sponsors: Ralph H. Johnson VA Medical
Center; The Department of Veterans Affairs; NARSAD.
NR 33
TC 38
Z9 39
U1 2
U2 7
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 DEC
PY 2011
VL 28
IS 12
BP 1067
EP 1073
DI 10.1002/da.20872
PG 7
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 855GW
UT WOS:000297552900005
PM 21818827
ER
PT J
AU Kimbrell, T
Pyne, JM
Kunik, ME
Magruder, KM
Petersen, NJ
Yu, HJ
Hudson, TJ
Schulz, PE
Qureshi, SU
AF Kimbrell, Tim
Pyne, Jeffrey M.
Kunik, Mark E.
Magruder, Kathy M.
Petersen, Nancy J.
Yu, Hong-Jen
Hudson, Teresa J.
Schulz, Paul E.
Qureshi, Salah U.
TI The impact of Purple Heart commendation and PTSD on mortality rates in
older veterans
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE posttraumatic stress; combat; resilience; injury; mortality; veteran
ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; COMBAT; PREVALENCE;
RESILIENCE; EXPOSURE; HEALTH; CARE; MEN; COMORBIDITY
AB Background: To determine whether having received a Purple Heart (PH) or having been diagnosed with posttraumatic stress disorder (PTSD) affected mortality in older veterans. Methods: We compared mortality rates of older veterans with a PH but without PTSD (PH+/PTSD-) to veterans with a PH and PTSD (PH+/PTSD+), veterans without a PH but with PTSD (PH-/PTSD+), and a comparison group without a PH or PTSD (PH-/PTSD-). Administrative data from the Veterans Integrated Service Network 16 were collected between 10/01/97 and 09/30/99 for veterans who were 65 years or older. Proportional hazards regression was used to compare the survival times for the four groups (n = 10,255) from entry into the study until death or study termination (9/30/2008). The Charleson co-morbidity index was used to control for potential co-morbid illness burden differences between the groups. Results: Older veterans with a PH (PH+/PTSD- and PH+/PTSD+) had significantly lower mortality rates than PH-/PTSD- veterans (hazard ratio [HR] = 0.6, 95% confidence interval [CI] 0.5 to 0.6, P<.0001; and HR = 0.5, 95% CI 0.4 to 0.7, P<.0001). The PH-/PTSD+ group had a higher mortality rate than the PH-/PTSD- group (HR = 1.1, 95% CI 1.0 to 1.2, P<.01). Conclusions: Veterans who had PH citations and survived into their seventh decade had half the mortality rate of veterans without PH citations with or without PTSD. Veterans with PTSD but without a PH had a significantly higher mortality rate compared to (PH-/PTSD-). Veterans who suffer combat injury without developing PTSD may provide a useful study population for determining the factors that confer resilience. Depression and Anxiety, 2011. (C) 2011 Wiley Periodicals, Inc.
C1 [Kimbrell, Tim; Pyne, Jeffrey M.; Hudson, Teresa J.] Cent Arkansas Vet Healthcare Syst, Ctr Mental Hlth & Outcomes Res, Little Rock, AR USA.
[Kimbrell, Tim; Pyne, Jeffrey M.; Hudson, Teresa J.] Univ Arkansas Med Sci, Coll Med, Dept Psychiat, Little Rock, AR 72205 USA.
[Kimbrell, Tim; Pyne, Jeffrey M.; Kunik, Mark E.; Petersen, Nancy J.; Yu, Hong-Jen; Hudson, Teresa J.; Qureshi, Salah U.] VA S Cent Mental Illness Res Educ & Clin Ctr, Little Rock, AR USA.
[Kunik, Mark E.; Petersen, Nancy J.; Yu, Hong-Jen; Qureshi, Salah U.] Michael E DeBakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX USA.
[Kunik, Mark E.; Qureshi, Salah U.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Magruder, Kathy M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA.
[Schulz, Paul E.] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Schulz, Paul E.] Univ Texas Hlth Sci Ctr Houston, Dept Neurol, Houston, TX USA.
RP Kimbrell, T (reprint author), Eugene Towbin VA Med Ctr, 116A NLR,2N112 Bldg 170,2200 Ft Roots Dr, N Little Rock, AR 72114 USA.
EM timothy.kimbrell@va.gov
RI Schueter, nicos/A-3625-2014
FU Houston Center for Quality of Care & Utilization Studies; VA South
Central Mental Illness Research and Clinical Center; Central Arkansas
Veterans Healthcare System Center for Mental Healthcare and Outcomes
Research
FX The authors disclose the following financial relationships within the
past 3 years: Contract grant sponsors: Houston Center for Quality of
Care & Utilization Studies; VA South Central Mental Illness Research and
Clinical Center; Central Arkansas Veterans Healthcare System Center for
Mental Healthcare and Outcomes Research.
NR 29
TC 3
Z9 3
U1 4
U2 8
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 DEC
PY 2011
VL 28
IS 12
BP 1086
EP 1090
DI 10.1002/da.20850
PG 5
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 855GW
UT WOS:000297552900008
PM 21751302
ER
PT J
AU Weir, SK
Berg, G
Fram, J
Schechter-Perkins, EM
Mitchell, PM
Sulis, C
Gupta, K
AF Weir, Susan K.
Berg, Gretchen
Fram, Julia
Schechter-Perkins, Elissa M.
Mitchell, Patricia M.
Sulis, Carol
Gupta, Kalpana
TI Discordance in Colonizing Strains of Staphylococcus aureus Isolated from
Different Body Sites
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Editorial Material
ID FIELD GEL-ELECTROPHORESIS; POLYMORPHIC DNA; UNIT
C1 [Weir, Susan K.; Berg, Gretchen; Sulis, Carol; Gupta, Kalpana] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Schechter-Perkins, Elissa M.; Mitchell, Patricia M.] Boston Univ, Sch Med, Dept Emergency Med, Boston, MA 02118 USA.
[Fram, Julia; Gupta, Kalpana] Vet Affairs Boston Healthcare Syst, Boston, MA USA.
[Fram, Julia; Gupta, Kalpana] Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
RP Gupta, K (reprint author), VA Boston HCS, 1400 VFW Pkwy,111 Med, W Roxbury, MA 02132 USA.
EM kalpana.gupta@va.gov
OI Sulis, Carol/0000-0003-2543-9469
FU NCRR NIH HHS [UL1RR025771]
NR 8
TC 1
Z9 1
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD DEC
PY 2011
VL 32
IS 12
BP 1225
EP 1227
DI 10.1086/662713
PG 5
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 876CH
UT WOS:000299084200014
PM 22080665
ER
PT J
AU Baeuml, J
Bose-O'Reilly, S
Lettmeier, B
Maydl, A
Messerer, K
Roider, G
Drasch, G
Siebert, U
AF Baeuml, Jennifer
Bose-O'Reilly, Stephan
Lettmeier, Beate
Maydl, Alexandra
Messerer, Katalin
Roider, Gabriele
Drasch, Gustav
Siebert, Uwe
TI Applicability of two mobile analysers for mercury in urine in
small-scale gold mining areas
SO INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH
LA English
DT Article
DE Mercury; Urine; Lumex; Seefelder; PerkinElmer (R); Gold mining; Vapour
ID CONTAMINATION; PHILIPPINES; MINDANAO; FISH
AB Mercury is still used in developing countries to extract gold from the ore in small-scale gold mining areas. This is a major health hazard for people living in mining areas. The concentration of mercury in urine was analysed in different mining areas in Zimbabwe, Indonesia and Tanzania. First the urine samples were analysed by CV-AAS (cold vapour atomic absorption spectrometry) during the field projects with a mobile mercury analyser (Lumex (R) or Seefelder (R)) and secondly, in a laboratory with a stationary CV-AAS mercury analyser (PerkinElmer (R)). Caused by the different systems (reduction agent either SnCl(2) (Lumex (R) or Seefelder (R))) or NaBH(4) (PerkinElmer (R)), with the mobile analysers only the inorganic mercury was obtained and with the stationary system the total mercury concentration was measured. The aims of the study were whether the results obtained in field with the mobile equipments can be compared with the stationary reference method in the laboratory and allow the application of these mobile analysers in screening studies on concerned populations to select those, who are exposed to critical mercury levels. Overall, the concentrations obtained with the two mobile systems were approximately 25% lower than determined with the stationary system. Nevertheless, both mobile systems seem to be very useful for screening of volunteers in field. Moreover, regional staff may be trained on such analysers to perform screening tests by themselves. (C) 2011 Elsevier GmbH. All rights reserved.
C1 [Baeuml, Jennifer; Bose-O'Reilly, Stephan; Lettmeier, Beate; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth & Hlth Technol Assessment, A-6060 Hall In Tirol, Austria.
[Maydl, Alexandra; Messerer, Katalin; Roider, Gabriele; Drasch, Gustav] Univ Munich, Inst Forens Med, D-80336 Munich, Germany.
[Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Inst Technol Assessment, Dept Radiol,Cardiovasc Res Progrom, Boston, MA 02115 USA.
[Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Bose-O'Reilly, S (reprint author), UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth & Hlth Technol Assessment, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria.
EM stephan.boeseoreilly@umit.at
FU UNIDO (United Nations Industrial Development Organization); GEF (Global
Environment Facility)
FX The global mercury project of the UNIDO (United Nations Industrial
Development Organization) was funded by GEF (Global Environment
Facility). There was no further funding, especially not by the
manufacturers of the used mercury analysers.
NR 13
TC 5
Z9 5
U1 0
U2 10
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 1438-4639
J9 INT J HYG ENVIR HEAL
JI Int. J. Hyg. Environ. Health.
PD DEC
PY 2011
VL 215
IS 1
BP 64
EP 67
DI 10.1016/j.ijheh.2011.06.005
PG 4
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 876VA
UT WOS:000299134600008
PM 21813324
ER
PT J
AU Knapp, H
Anaya, HD
Feld, JE
Hoang, T
Goetz, MB
AF Knapp, H.
Anaya, H. D.
Feld, J. E.
Hoang, T.
Goetz, M. B.
TI Launching nurse-initiated HIV rapid testing in Veterans Affairs primary
care: a comprehensive overview of a self-sustaining implementation
SO INTERNATIONAL JOURNAL OF STD & AIDS
LA English
DT Article
DE HIV; AIDS; diagnostic; testing; primary care; rapid test; point-of-care
test; Veterans Affairs
AB Our objectives were to use foundational pilot findings to guide the implementation of an HIV rapid testing (RT) intervention at one Veterans Affairs outpatient clinic and to evaluate the success and sustainability of this intervention over the course of one year. Policy modifications were drafted and adopted to enable nurses to order, administer, interpret and document HIV RTs. Staff enrolled in a two-part training sessions designed to teach pre- and post-test counselling techniques and the mechanics of administering, interpreting and coding test results in the patients' medical records. They were subsequently evaluated on their efforts at: (1) increasing HIV RT, (2) sustaining this effort one year post-launch. Enabling nurses to carry out HIV RT resulted in a significant increase in not only HIV RT, but also HIV testing rates overall at this facility, measured over the first year of this implementation. Our findings indicate that targeted strategies, aimed at increasing HIV RT rates, worked to increase testing rates overall, and also, that our initial testing strategies were independently sustainable, which is in contrast to findings in the literature on implementation science.
C1 [Knapp, H.; Anaya, H. D.; Feld, J. E.; Hoang, T.; Goetz, M. B.] VA Greater Los Angeles Healthcare Syst, Vet Affairs Greater Los Angeles Hlth Serv Res & D, Vet Affairs Qual Enhancement Res Initiat HIV & He, Los Angeles, CA USA.
[Knapp, H.; Anaya, H. D.; Feld, J. E.; Hoang, T.; Goetz, M. B.] VA Greater Los Angeles Healthcare Syst, Vet Affairs Greater Los Angeles Hlth Serv Res & D, Ctr Study Healthcare Provider Behav, Los Angeles, CA USA.
[Anaya, H. D.; Goetz, M. B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90095 USA.
RP Knapp, H (reprint author), 11301 Wilshire Blvd,111G,Bldg 500,Off 4681, Los Angeles, CA 90073 USA.
EM Herschel.Knapp@va.gov
NR 6
TC 1
Z9 1
U1 0
U2 2
PU ROYAL SOC MEDICINE PRESS LTD
PI LONDON
PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND
SN 0956-4624
J9 INT J STD AIDS
JI Int. J. STD AIDS
PD DEC
PY 2011
VL 22
IS 12
SI SI
BP 734
EP 737
DI 10.1258/ijsa.2009.009252
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 876ZB
UT WOS:000299145200009
PM 22174056
ER
PT J
AU Siev, J
Baer, L
Minichiello, WE
AF Siev, Jedidiah
Baer, Lee
Minichiello, William E.
TI Obsessive-Compulsive Disorder With Predominantly Scrupulous Symptoms:
Clinical and Religious Characteristics
SO JOURNAL OF CLINICAL PSYCHOLOGY
LA English
DT Article
DE Obsessive-compulsive disorder; Religious obsessions; Religion;
Scrupulosity; Treatment-seeking
ID QUALITY-OF-LIFE; OCI-R; EPIDEMIOLOGY; VALIDATION; INVENTORY; SAMPLE;
TRIAL; JEWS
AB Objectives: Scrupulosity is a relatively common but understudied subtype of obsessive-compulsive disorder (OCD) characterized by religious or moral fears. It is difficult to treat and frequently disabling. We examined scrupulosity as it relates to (a) treatment-seeking behavior and perceived treatment gains, (b) the perceived effect of symptoms on religious experience, and (c) conceptions of God. Method: Seventy-two individuals with scrupulous OCD (mean age = 36; 70% women) and 75 individuals with nonscrupulous OCD (mean age = 38; 81% women) completed an internet-based survey. Results: The groups did not differ on demographic variables or overall OCD severity. Compared with the nonscrupulous group, the scrupulous group was (a) more religious, (b) more likely to seek pastoral counseling, (c) less likely to seek medication treatment, and (d) more likely to report that symptoms interfered with their religious experience. Indeed, most scrupulous individuals endorsed that their symptoms interfered with their religious experience. Scrupulous individuals with a more negative concept of God experienced more severe symptoms, whereas a positive description of God was unrelated to severity of scrupulosity in this group. Nearly one in five scrupulous participants reported no religious affiliation. Conclusions: Scrupulous individuals have unique treatment-seeking preferences. Moreover, most scrupulous individuals perceive their symptoms as interfering with their religious experience. Focusing on the religious costs and benefits of scrupulous rituals might have clinical utility. Finally, scrupulous individuals with a more negative concept of God experienced more severe symptoms. Future research is necessary to evaluate whether addressing such concepts can improve treatment outcome. (C) 2011 Wiley Periodicals, Inc. J Clin Psychol 67: 1188-1196, 2011.
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Siev, J (reprint author), Nova SE Univ, Ctr Psychol Studies, 3301 Coll Ave, Ft Lauderdale, FL 33314 USA.
EM jedidiah.siev@nova.edu
NR 27
TC 18
Z9 18
U1 2
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9762
J9 J CLIN PSYCHOL
JI J. Clin. Psychol.
PD DEC
PY 2011
VL 67
IS 12
BP 1188
EP 1196
DI 10.1002/jclp.20843
PG 9
WC Psychology, Clinical
SC Psychology
GA 855PJ
UT WOS:000297576400004
PM 22042580
ER
PT J
AU Malone, JC
Westen, D
Levendosky, AA
AF Malone, Johanna C.
Westen, Drew
Levendosky, Alytia A.
TI Personalities of Adults With Traumatic Childhood Separations
SO JOURNAL OF CLINICAL PSYCHOLOGY
LA English
DT Article
DE personality; subtypes; separations; attachment disruptions; SWAP-II;
emotional dysregulation
ID EARLY SEVERE DEPRIVATION; RESIDENTIAL GROUP CARE; ASSESSING AXIS II;
BORDERLINE PERSONALITY; SEXUAL-ABUSE; ATTACHMENT DISTURBANCES; ROMANIAN
ORPHANAGES; 2-PARENT FAMILIES; GREEK CHILDREN; PARENTAL LOSS
AB Objectives: This study examined personality characteristics and identified personality subtypes of adults with childhood histories of traumatic separations from a parent. Previous work from attachment theory and developmental psychopathology suggests that distinct developmental trajectories might lead to different styles of personality adaptation after an attachment disruption. Design: Randomly selected psychologists and psychiatrists provided data on 203 adults with histories of traumatic separations using a personality pathology instrument designed for use by clinically experienced observers, the Shedler-Westen Assessment Procedure (SWAP-II). Results: Using a Q-factor analysis, 5 distinct personality subtypes were identified: internalizing/avoidant, psychopathic, emotionally dysregulated, hostile/paranoid, and resilient. Initial support for the validity of the subtypes was established, based on Axis I and Axis II pathology, adaptive functioning, developmental history, and family history variables. Conclusions: Both therapeutic interventions and case formulation might be strengthened by considering an individual's personality features and match to one of the identified subtypes. (C) 2011 Wiley Periodicals, Inc. J Clin Psychol 67: 1259-1282, 2011.
C1 [Malone, Johanna C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Westen, Drew] Emory Univ, Atlanta, GA 30322 USA.
[Levendosky, Alytia A.] Michigan State Univ, E Lansing, MI 48824 USA.
RP Malone, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM johanna.malone@gmail.com
FU NIMH NIH HHS [R01-MH62377, R01-MH62378]
NR 96
TC 1
Z9 1
U1 1
U2 18
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9762
J9 J CLIN PSYCHOL
JI J. Clin. Psychol.
PD DEC
PY 2011
VL 67
IS 12
BP 1259
EP 1282
DI 10.1002/jclp.20844
PG 24
WC Psychology, Clinical
SC Psychology
GA 855PJ
UT WOS:000297576400009
PM 22072534
ER
PT J
AU Mehta, DD
Zanartu, M
Quatieri, TF
Deliyski, DD
Hillman, RE
AF Mehta, Daryush D.
Zanartu, Matias
Quatieri, Thomas F.
Deliyski, Dimitar D.
Hillman, Robert E.
TI Investigating acoustic correlates of human vocal fold vibratory phase
asymmetry through modeling and laryngeal high-speed videoendoscopy
SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA
LA English
DT Article
ID GLOTTAL AIR-FLOW; VOICE PRODUCTION; 2-MASS MODEL; PHONATION; AREA;
VIDEOKYMOGRAPHY; SPEAKERS; CLASSIFICATION; BIFURCATIONS; RECORDINGS
AB Vocal fold vibratory asymmetry is often associated with inefficient sound production through its impact on source spectral tilt. This association is investigated in both a computational voice production model and a group of 47 human subjects. The model provides indirect control over the degree of left-right phase asymmetry within a nonlinear source-filter framework, and high-speed videoendoscopy provides in vivo measures of vocal fold vibratory asymmetry. Source spectral tilt measures are estimated from the inverse-filtered spectrum of the simulated and recorded radiated acoustic pressure. As expected, model simulations indicate that increasing left-right phase asymmetry induces steeper spectral tilt. Subject data, however, reveal that none of the vibratory asymmetry measures correlates with spectral tilt measures. Probing further into physiological correlates of spectral tilt that might be affected by asymmetry, the glottal area waveform is parameterized to obtain measures of the open phase (open/plateau quotient) and closing phase (speed/closing quotient). Subjects' left-right phase asymmetry exhibits low, but statistically significant, correlations with speed quotient (r = 0.45) and closing quotient (r = -0.39). Results call for future studies into the effect of asymmetric vocal fold vibration on glottal airflow and the associated impact on voice source spectral properties and vocal efficiency. (C) 2011 Acoustical Society of America. [DOI: 10.1121/1.3658441]
C1 [Mehta, Daryush D.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
[Zanartu, Matias] Univ Tecn Federico Santa Maria, Dept Elect Engn, Valparaiso, Chile.
[Quatieri, Thomas F.] MIT, Lincoln Lab, Lexington, MA 02421 USA.
[Deliyski, Dimitar D.] Cincinnati Childrens Hosp, Commun Sci Res Ctr, Med Ctr, Cincinnati, OH 45229 USA.
[Hillman, Robert E.] Massachusetts Gen Hosp, MGH Inst Hlth Profess, Boston, MA 02114 USA.
[Mehta, Daryush D.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Deliyski, Dimitar D.] Univ Cincinnati, Dept Otolaryngol Head & Neck Surg, Cincinnati, OH 45229 USA.
[Deliyski, Dimitar D.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45229 USA.
[Deliyski, Dimitar D.] Univ Cincinnati, Dept Commun Sci & Disorders, Cincinnati, OH 45229 USA.
[Hillman, Robert E.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Mehta, DD (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
EM daryush.mehta@alum.mit.edu
RI Zanartu, Matias/I-3133-2012; researchers, ac3e/N-2008-2016
OI Zanartu, Matias/0000-0001-5581-4392;
FU Department of Defense under Air Force [FA8721-05-C-0002]; NIH National
Institute on Deafness and Other Communication Disorders [T32 DC00038,
R01 DC007640]; Institute of Laryngology and Voice Restoration
FX The work of T.F.Q. was supported by the Department of Defense under Air
Force Contract No. FA8721-05-C-0002. The opinions, interpretations,
conclusions, and recommendations are those of the author and are not
necessarily endorsed by the United States Government. The work of the
other authors was supported by grants from the NIH National Institute on
Deafness and Other Communication Disorders (T32 DC00038 and R01
DC007640) and by the Institute of Laryngology and Voice Restoration. The
paper's contents are solely the responsibility of the authors and do not
necessarily represent the official views of the NTH.
NR 54
TC 21
Z9 21
U1 0
U2 10
PU ACOUSTICAL SOC AMER AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0001-4966
J9 J ACOUST SOC AM
JI J. Acoust. Soc. Am.
PD DEC
PY 2011
VL 130
IS 6
BP 3999
EP 4009
DI 10.1121/1.3658441
PG 11
WC Acoustics; Audiology & Speech-Language Pathology
SC Acoustics; Audiology & Speech-Language Pathology
GA 869AX
UT WOS:000298569100054
PM 22225054
ER
PT J
AU Vitkin, E
Turzhitsky, V
Qiu, L
Guo, LY
Itzkan, I
Hanlon, EB
Perelman, LT
AF Vitkin, Edward
Turzhitsky, Vladimir
Qiu, Le
Guo, Lianyu
Itzkan, Irving
Hanlon, Eugene B.
Perelman, Lev T.
TI Photon diffusion near the point-of-entry in anisotropically scattering
turbid media
SO NATURE COMMUNICATIONS
LA English
DT Article
ID MONTE-CARLO-SIMULATION; CONFOCAL LIGHT-ABSORPTION; REFLECTANCE
SPECTROSCOPY; STEADY-STATE; RADIATIVE TRANSPORT; OPTICAL-PROPERTIES;
DENSITY WAVES; APPROXIMATION; TISSUE; MICROSCOPY
AB From astronomy to cell biology, the manner in which light propagates in turbid media has been of central importance for many decades. However, light propagation near the point-of-entry in turbid media has never been analytically described, until now. Here we report a straightforward and accurate method that overcomes this longstanding, unsolved problem in radiative transport. Our theory properly treats anisotropic photon scattering events and takes the specific form of the phase function into account. As a result, our method correctly predicts the spatially dependent diffuse reflectance of light near the point-of-entry for any arbitrary phase function. We demonstrate that the theory is in excellent agreement with both experimental results and Monte Carlo simulations for several commonly used phase functions.
C1 [Vitkin, Edward; Turzhitsky, Vladimir; Qiu, Le; Guo, Lianyu; Itzkan, Irving; Hanlon, Eugene B.; Perelman, Lev T.] Harvard Univ, Dept Obstet Gynecol & Reprod Biol, Ctr Adv Biomed Imaging & Photon, Boston, MA 02215 USA.
[Vitkin, Edward; Turzhitsky, Vladimir; Qiu, Le; Guo, Lianyu; Itzkan, Irving; Hanlon, Eugene B.; Perelman, Lev T.] Harvard Univ, Dept Med, Boston, MA 02215 USA.
[Vitkin, Edward; Turzhitsky, Vladimir; Qiu, Le; Guo, Lianyu; Itzkan, Irving; Hanlon, Eugene B.; Perelman, Lev T.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Hanlon, Eugene B.] Med Res Serv, US Dept Vet Affairs, Bedford, MA 01730 USA.
[Hanlon, Eugene B.] US Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, Bedford, MA 01730 USA.
RP Perelman, LT (reprint author), Harvard Univ, Dept Obstet Gynecol & Reprod Biol, Ctr Adv Biomed Imaging & Photon, Boston, MA 02215 USA.
EM ltperel@caregroup.harvard.edu
FU US National Science Foundation [CBET-0922876, CBET-0943180,
CBET-1144025]; US National Institutes of Health [R01 EB003472, R01
EB006462, R33 RR017361]; Department of Veterans Affairs, Office of
Research and Development
FX This work was supported by the US National Science Foundation grants
CBET-0922876, CBET-0943180 and CBET-1144025, US National Institutes of
Health grants R01 EB003472, R01 EB006462 and R33 RR017361 and in part by
the Department of Veterans Affairs, Office of Research and Development.
NR 41
TC 25
Z9 25
U1 1
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD DEC
PY 2011
VL 2
AR 587
DI 10.1038/ncomms1599
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877EM
UT WOS:000299159900019
PM 22158442
ER
PT J
AU Lyon, BR
Lee, PA
Bennett, JM
DiTullio, GR
Janech, MG
AF Lyon, Barbara R.
Lee, Peter A.
Bennett, Jennifer M.
DiTullio, Giacomo R.
Janech, Michael G.
TI Proteomic Analysis of a Sea-Ice Diatom: Salinity Acclimation Provides
New Insight into the Dimethylsulfoniopropionate Production Pathway
SO PLANT PHYSIOLOGY
LA English
DT Article
ID PHOTOSYNTHETIC ENERGY-CONVERSION; ALDEHYDE DEHYDROGENASE GENE; SALT
STRESS; MARINE-ALGAE; PHAEODACTYLUM-TRICORNUTUM; BINDING PROTEINS;
FRAGILARIOPSIS-CYLINDRUS; BIOSYNTHETIC-PATHWAY; ARABIDOPSIS-THALIANA;
LIPID-PEROXIDATION
AB Dimethylsulfoniopropionate (DMSP) plays important roles in oceanic carbon and sulfur cycling and may significantly impact climate. It is a biomolecule synthesized from the methionine (Met) pathway and proposed to serve various physiological functions to aid in environmental stress adaptation through its compatible solute, cryoprotectant, and antioxidant properties. Yet, the enzymes and mechanisms regulating DMSP production are poorly understood. This study utilized a proteomics approach to investigate protein changes associated with salinity-induced DMSP increases in the model sea-ice diatom Fragilariopsis cylindrus (CCMP 1102). We hypothesized proteins associated with the Met-DMSP biosynthesis pathway would increase in relative abundance when challenged with elevated salinity. To test this hypothesis axenic log-phase cultures initially grown at a salinity of 35 were gradually shifted to a final salinity of 70 over a 24-h period. Intracellular DMSP was measured and two-dimensional gel electrophoresis was used to identify protein changes at 48 h after the shift. Intracellular DMSP increased by approximately 85% in the hypersaline cultures. One-third of the proteins increased under high salinity were associated with amino acid pathways. Three protein isoforms of S-adenosylhomo-cysteine hydrolase, which synthesizes a Met precursor, increased 1.8- to 2.1-fold, two isoforms of S-adenosyl Met synthetase increased 1.9- to 2.5-fold, and S-adenosyl Met methyltransferase increased by 2.8-fold, suggesting active methyl cycle proteins are recruited in the synthesis of DMSP. Proteins from the four enzyme classes of the proposed algal Met transaminase DMSP pathway were among the elevated proteins, supporting our hypothesis and providing candidate genes for future characterization studies.
C1 [Janech, Michael G.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA.
[Lyon, Barbara R.; Lee, Peter A.; Bennett, Jennifer M.; DiTullio, Giacomo R.] Hollings Marine Lab, Charleston, SC 29412 USA.
[Lyon, Barbara R.] Med Univ S Carolina, Marine Biomed & Environm Sci Ctr, Charleston, SC 29412 USA.
[Lee, Peter A.; Bennett, Jennifer M.; DiTullio, Giacomo R.] Coll Charleston, Grice Marine Lab, Charleston, SC 29412 USA.
[Janech, Michael G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA.
RP Janech, MG (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA.
EM janechmg@musc.edu
OI Janech, Michael/0000-0002-3202-4811
FU National Science Foundation [ANT-0739597, ANT-0739446, OPP0338097]
FX This work was supported by the National Science Foundation (grant nos.
ANT-0739597 to M. G. J., ANT-0739446 to P. A. L. and G. R. D., and
OPP0338097 to G.R.D.).
NR 92
TC 17
Z9 19
U1 3
U2 40
PU AMER SOC PLANT BIOLOGISTS
PI ROCKVILLE
PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA
SN 0032-0889
EI 1532-2548
J9 PLANT PHYSIOL
JI Plant Physiol.
PD DEC
PY 2011
VL 157
IS 4
BP 1926
EP 1941
DI 10.1104/pp.111.185025
PG 16
WC Plant Sciences
SC Plant Sciences
GA 866JC
UT WOS:000298375600026
PM 22034629
ER
PT J
AU Khetarpal, SA
Edmondson, AC
Raghavan, A
Neeli, H
Jin, WJ
Badellino, KO
Demissie, S
Manning, AK
DerOhannessian, SL
Wolfe, ML
Cupples, LA
Li, MY
Kathiresan, S
Rader, DJ
AF Khetarpal, Sumeet A.
Edmondson, Andrew C.
Raghavan, Avanthi
Neeli, Hemanth
Jin, Weijun
Badellino, Karen O.
Demissie, Serkalem
Manning, Alisa K.
DerOhannessian, Stephanie L.
Wolfe, Megan L.
Cupples, L. Adrienne
Li, Mingyao
Kathiresan, Sekar
Rader, Daniel J.
TI Mining the LIPG Allelic Spectrum Reveals the Contribution of Rare and
Common Regulatory Variants to HDL Cholesterol
SO PLOS GENETICS
LA English
DT Article
ID DENSITY-LIPOPROTEIN-CHOLESTEROL; CORONARY-HEART-DISEASE; ENDOTHELIAL
LIPASE GENE; WIDE ASSOCIATION ANALYSIS; APOLIPOPROTEIN-A-I;
ARTERY-DISEASE; PLASMA-LEVELS; RISK-FACTORS; POPULATION; ATHEROSCLEROSIS
AB Genome-wide association studies (GWAS) have successfully identified loci associated with quantitative traits, such as blood lipids. Deep resequencing studies are being utilized to catalogue the allelic spectrum at GWAS loci. The goal of these studies is to identify causative variants and missing heritability, including heritability due to low frequency and rare alleles with large phenotypic impact. Whereas rare variant efforts have primarily focused on nonsynonymous coding variants, we hypothesized that noncoding variants in these loci are also functionally important. Using the HDL-C gene LIPG as an example, we explored the effect of regulatory variants identified through resequencing of subjects at HDL-C extremes on gene expression, protein levels, and phenotype. Resequencing a portion of the LIPG promoter and 59 UTR in human subjects with extreme HDL-C, we identified several rare variants in individuals from both extremes. Luciferase reporter assays were used to measure the effect of these rare variants on LIPG expression. Variants conferring opposing effects on gene expression were enriched in opposite extremes of the phenotypic distribution. Minor alleles of a common regulatory haplotype and noncoding GWAS SNPs were associated with reduced plasma levels of the LIPG gene product endothelial lipase (EL), consistent with its role in HDL-C catabolism. Additionally, we found that a common nonfunctional coding variant associated with HDL-C (rs2000813) is in linkage disequilibrium with a 5' UTR variant (rs34474737) that decreases LIPG promoter activity. We attribute the gene regulatory role of rs34474737 to the observed association of the coding variant with plasma EL levels and HDL-C. Taken together, the findings show that both rare and common noncoding regulatory variants are important contributors to the allelic spectrum in complex trait loci.
C1 [Khetarpal, Sumeet A.; Edmondson, Andrew C.; Raghavan, Avanthi; DerOhannessian, Stephanie L.; Wolfe, Megan L.; Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
[Khetarpal, Sumeet A.; Edmondson, Andrew C.; Raghavan, Avanthi; DerOhannessian, Stephanie L.; Wolfe, Megan L.; Rader, Daniel J.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Neeli, Hemanth] Temple Univ Hosp & Med Sch, Sect Hosp Med, Philadelphia, PA 19140 USA.
[Jin, Weijun] Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA.
[Badellino, Karen O.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA.
[Demissie, Serkalem; Manning, Alisa K.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Demissie, Serkalem; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Li, Mingyao] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar] Broad Inst MIT & Harvard, Cambridge, MA USA.
RP Khetarpal, SA (reprint author), Univ Penn, Sch Med, Inst Translat Med & Therapeut, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
EM rader@mail.med.upenn.edu
OI Cupples, L. Adrienne/0000-0003-0273-7965
FU NHLBI, National Institutes of Health [HL55323]; Doris Duke Charitable
Foundation; NHLBI [5F30HL094050-03]; National American Heart
Association; National Institutes of Health [DK195253, K23 HL74967-01A1];
National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]
FX This work was supported by National Institutes of Health Grant HL55323
from the NHLBI and Doris Duke Charitable Foundation Distinguished
Clinical Scientist Award (both to DJR). ACE was supported by an NHLBI
Ruth L. Kirschstein National Research Service Award for Individual
Predoctoral MD/PhD Fellows (5F30HL094050-03). KOB was supported by a
National American Heart Association Scientist Development Award and by
National Institutes of Health grants DK19525 and K23 HL74967-01A1. The
Framingham Heart Study of the NHLBI of the NIH and Boston University
School of Medicine is supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (N01-HC-25195). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 68
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Z9 17
U1 0
U2 2
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 DEC
PY 2011
VL 7
IS 12
AR e1002393
DI 10.1371/journal.pgen.1002393
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 877HI
UT WOS:000299167900011
PM 22174694
ER
PT J
AU Ziller, MJ
Muller, F
Liao, J
Zhang, YY
Gu, HC
Bock, C
Boyle, P
Epstein, CB
Bernstein, BE
Lengauer, T
Gnirke, A
Meissner, A
AF Ziller, Michael J.
Mueller, Fabian
Liao, Jing
Zhang, Yingying
Gu, Hongcang
Bock, Christoph
Boyle, Patrick
Epstein, Charles B.
Bernstein, Bradley E.
Lengauer, Thomas
Gnirke, Andreas
Meissner, Alexander
TI Genomic Distribution and Inter-Sample Variation of Non-CpG Methylation
across Human Cell Types
SO PLOS GENETICS
LA English
DT Article
ID EMBRYONIC STEM-CELLS; DNA METHYLATION; PLURIPOTENT; LINES; MAPS;
RESOLUTION; PATTERNS; METHYLTRANSFERASES; DIFFERENTIATION; ARABIDOPSIS
AB DNA methylation plays an important role in development and disease. The primary sites of DNA methylation in vertebrates are cytosines in the CpG dinucleotide context, which account for roughly three quarters of the total DNA methylation content in human and mouse cells. While the genomic distribution, inter-individual stability, and functional role of CpG methylation are reasonably well understood, little is known about DNA methylation targeting CpA, CpT, and CpC (non-CpG) dinucleotides. Here we report a comprehensive analysis of non-CpG methylation in 76 genome-scale DNA methylation maps across pluripotent and differentiated human cell types. We confirm non-CpG methylation to be predominantly present in pluripotent cell types and observe a decrease upon differentiation and near complete absence in various somatic cell types. Although no function has been assigned to it in pluripotency, our data highlight that non-CpG methylation patterns reappear upon iPS cell reprogramming. Intriguingly, the patterns are highly variable and show little conservation between different pluripotent cell lines. We find a strong correlation of non-CpG methylation and DNMT3 expression levels while showing statistical independence of non-CpG methylation from pluripotency associated gene expression. In line with these findings, we show that knockdown of DNMTA and DNMT3B in hESCs results in a global reduction of non-CpG methylation. Finally, non-CpG methylation appears to be spatially correlated with CpG methylation. In summary these results contribute further to our understanding of cytosine methylation patterns in human cells using a large representative sample set.
C1 [Ziller, Michael J.; Mueller, Fabian; Liao, Jing; Zhang, Yingying; Gu, Hongcang; Bock, Christoph; Boyle, Patrick; Epstein, Charles B.; Bernstein, Bradley E.; Gnirke, Andreas; Meissner, Alexander] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Ziller, Michael J.; Mueller, Fabian; Liao, Jing; Zhang, Yingying; Bock, Christoph; Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Ziller, Michael J.; Mueller, Fabian; Liao, Jing; Zhang, Yingying; Bock, Christoph; Meissner, Alexander] Harvard Stem Cell Inst, Cambridge, MA USA.
[Mueller, Fabian; Bock, Christoph; Lengauer, Thomas] Max Planck Inst Informat, Saarbrucken, Germany.
[Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA USA.
[Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
RP Ziller, MJ (reprint author), Broad Inst Harvard & MIT, Cambridge, MA USA.
EM alexander_meissner@harvard.edu
RI Bock, Christoph/B-6723-2008; Liao, Jing/J-4620-2014
OI Bock, Christoph/0000-0001-6091-3088;
FU NIH [U01ES017155]
FX This research was funded by an NIH Roadmap Epigenomics Program
(U01ES017155) grant. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 35
TC 140
Z9 141
U1 1
U2 24
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 DEC
PY 2011
VL 7
IS 12
AR e1002389
DI 10.1371/journal.pgen.1002389
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 877HI
UT WOS:000299167900009
PM 22174693
ER
PT J
AU Hebert, PL
Taylor, LT
Wang, JJ
Bergman, MA
AF Hebert, Paul L.
Taylor, Leslie T.
Wang, Jason J.
Bergman, Margo A.
TI Methods for Using Data Abstracted from Medical Charts to Impute
Longitudinal Missing Data in a Clinical Trial
SO VALUE IN HEALTH
LA English
DT Article
DE blood pressure; clinical trials; imputation; longitudinal data; missing
data
ID CARE OUTCOME ANALYSES; MULTIPLE IMPUTATION; VALUES; ATTRITION
AB Objective: To describe a method for imputing missing follow-up blood pressure data in a clinical hypertension trial using blood pressures abstracted from medical charts. Methods: We tested a two-step method. In the first, a longitudinal mixed-effects model was estimated on blood pressures abstracted from medical charts. In the second, the patient-specific fitted values from this model at follow-up were used to impute blood pressures missing at follow-up in the trial. Simulations that imposed alternative missing data mechanisms on observed trial data were used to compare this approach to imputation approaches that do not incorporate data from charts. Results: For data that are missing at random, incorporating the fitted values from chart-based longitudinal models leads to estimates of the trial-based blood pressures that are unbiased and have lower mean squared deviation than do blood pressures imputed without the chart-based data. For data that are missing not at random, incorporating fitted values ameliorates but does not eliminate the inherent missing data bias. Conclusions: Incorporating chart data into an imputation algorithm via the use of longitudinal mixed-effects model is an efficient way to impute longitudinal data that are missing from a randomized trial.
C1 [Hebert, Paul L.; Taylor, Leslie T.; Bergman, Margo A.] NW Ctr Outcomes Res Older Adults, VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA USA.
[Wang, Jason J.] Primary Care Informat Project, Dept Hlth & Mental Hyg, New York, NY USA.
[Hebert, Paul L.] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY USA.
RP Hebert, PL (reprint author), 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA.
EM Paul.Hebert2@va.gov
FU National Institutes of Health, National Center for Minority Health and
Health Disparities [1P60MD000270-01]
FX Source of financial support: This work was funded by a grant from the
National Institutes of Health, National Center for Minority Health and
Health Disparities (1P60MD000270-01). The views expressed herein are
those of the authors and do not necessarily represent the views of the
National Institutes of Health and other affiliated institutions.
NR 17
TC 2
Z9 2
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-3015
J9 VALUE HEALTH
JI Value Health
PD DEC
PY 2011
VL 14
IS 8
BP 1085
EP 1091
DI 10.1016/j.jval.2011.05.049
PG 7
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 876BM
UT WOS:000299081900015
PM 22152178
ER
PT J
AU Morrison, JB
Rudolph, JW
AF Morrison, J. Bradley
Rudolph, Jenny W.
TI Learning from Accident and Error: Avoiding the Hazards of Workload,
Stress, and Routine Interruptions in the Emergency Department
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
ID WORKPLACE INTERRUPTIONS; JOB-SATISFACTION
AB This article presents a model of how a build-up of interruptions can shift the dynamics of the emergency department (ED) from an adaptive, self-regulating system into a fragile, crisis-prone one. Drawing on case studies of organizational disasters and insights from the theory of high-reliability organizations, the authors use computer simulations to show how the accumulation of small interruptions could have disproportionately large effects in the ED. In the face of a mounting workload created by interruptions, EDs, like other organizational systems, have tipping points, thresholds beyond which a vicious cycle can lead rather quickly to the collapse of normal operating routines and in the extreme to a crisis of organizational paralysis. The authors discuss some possible implications for emergency medicine, emphasizing the potential threat from routine, non-novel demands on EDs and raising the concern that EDs are operating closer to the precipitous edge of crisis as ED crowding exacerbates the problem.
C1 [Morrison, J. Bradley] Brandeis Int Business Sch, Waltham, MA USA.
Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Dept Anaesthesia, Cambridge, MA 02138 USA.
[Rudolph, Jenny W.] Ctr Med Simulat, Cambridge, MA USA.
RP Morrison, JB (reprint author), Brandeis Int Business Sch, Waltham, MA USA.
EM bmorriso@brandeis.edu
FU Agency for Healthcare Research and Quality (AHRQ) [1R13HS020139-01];
Robert Wood Johnson Foundation
FX Funding for this conference was made possible (in part) by
1R13HS020139-01 from the Agency for Healthcare Research and Quality
(AHRQ). The views expressed in written conference materials or
publications and by speakers and moderators do not necessarily reflect
the official policies of the Department of Health and Human Services,
nor does mention of trade names, commercial practices, or organizations
imply endorsement by the U. S. Government. This issue of Academic
Emergency Medicine is funded by the Robert Wood Johnson Foundation.
NR 46
TC 4
Z9 4
U1 3
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1069-6563
EI 1553-2712
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD DEC
PY 2011
VL 18
IS 12
SI SI
BP 1246
EP 1254
DI 10.1111/j.1553-2712.2011.01231.x
PG 9
WC Emergency Medicine
SC Emergency Medicine
GA 861IQ
UT WOS:000298013000005
PM 22168187
ER
PT J
AU Fee, C
Hall, K
Morrison, JB
Stephens, R
Cosby, K
Fairbanks, RJ
Youngberg, B
Lenehan, G
Abualenain, J
O'Connor, K
Wears, R
AF Fee, Christopher
Hall, Kendall
Morrison, J. Bradley
Stephens, Robert
Cosby, Karen
Fairbanks, Rollin (Terry) J.
Youngberg, Barbara
Lenehan, Gail
Abualenain, Jameel
O'Connor, Kevin
Wears, Robert
TI Consensus-based Recommendations for Research Priorities Related to
Interventions to Safeguard Patient Safety in the Crowded Emergency
Department
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
ID LENGTH-OF-STAY; ASSOCIATION; PNEUMONIA; MORTALITY; VISITS; TIME; PAIN
AB This article describes the results of the Interventions to Safeguard Safety breakout session of the 2011 Academic Emergency Medicine (AEM) consensus conference entitled Interventions to Assure Quality in the Crowded Emergency Department. Using a multistep nominal group technique, experts in emergency department (ED) crowding, patient safety, and systems engineering defined knowledge gaps and priority research questions related to the maintenance of safety in the crowded ED. Consensus was reached for seven research priorities related to interventions to maintain safety in the setting of a crowded ED. Included among these are: 1) How do routine corrective processes and compensating mechanism change during crowding? 2) What metrics should be used to determine ED safety? 3) How can checklists ensure safer care and what factors contribute to their success or failure? 4) What constitutes safe staffing levels/ratios? 5) How can we align emergency medicine (EM)-specific patient safety issues with national patient safety issues? 6) How can we develop metrics and skills to recognize when an ED is getting close to catastrophic overload conditions? and 7) What can EM learn from experts and modeling from fields outside of medicine to develop innovative solutions? These priorities have the potential to inform future clinical and human factors research and extramural funding decisions related to this important topic.
C1 [Fee, Christopher] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA.
[Hall, Kendall] Agcy Healthcare Res & Qual, Rockville, MD USA.
[Morrison, J. Bradley] Brandeis Univ, Waltham, MA USA.
[Stephens, Robert; Fairbanks, Rollin (Terry) J.; Abualenain, Jameel] Georgetown Univ, Washington, DC USA.
[Stephens, Robert; Fairbanks, Rollin (Terry) J.] MedStar Hlth, Columbia, MD USA.
[Cosby, Karen] Rush Med Coll, Chicago, IL 60612 USA.
Loyola Univ, Chicago, IL 60611 USA.
[Lenehan, Gail] Emergency Nurses Assoc, Des Plaines, IL USA.
[Lenehan, Gail] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[O'Connor, Kevin] Emergency Med Phys, Gastonia, NC USA.
[Wears, Robert] Univ Florida, Gainesville, FL USA.
RP Fee, C (reprint author), Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA.
EM Christopher.Fee@ucsf.edu
OI Wears, Robert/0000-0001-9826-954X
FU Agency for Healthcare Research and Quality (AHRQ) [1R13HS020139-01];
Robert Wood Johnson Foundation
FX Funding for this conference was made possible (in part) by
1R13HS020139-01 from the Agency for Healthcare Research and Quality
(AHRQ). The views expressed in written conference materials or
publications and by speakers and moderators do not necessarily reflect
the official policies of the Department of Health and Human Services,
nor does mention of trade names, commercial practices, or organizations
imply endorsement by the U. S. Government. This issue of Academic
Emergency Medicine is funded by the Robert Wood Johnson Foundation.
NR 22
TC 8
Z9 8
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD DEC
PY 2011
VL 18
IS 12
SI SI
BP 1283
EP 1288
DI 10.1111/j.1553-2712.2011.01234.x
PG 6
WC Emergency Medicine
SC Emergency Medicine
GA 861IQ
UT WOS:000298013000010
PM 22168192
ER
PT J
AU Kocher, KE
Shane, SA
Venkatesh, AK
Aronsky, D
Asplin, BR
Rathlev, NK
AF Kocher, Keith E.
Shane, Steven A.
Venkatesh, Arjun K.
Aronsky, Dominik
Asplin, Brent R.
Rathlev, Niels K.
TI Interventions to Safeguard System Effectiveness During Periods of
Emergency Department Crowding
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
ID COMMUNITY-ACQUIRED PNEUMONIA; ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE;
AMBULATORY-CARE; PATIENT SAFETY; ASSOCIATION; IMPACT; MORTALITY; MODEL;
ANTIBIOTICS
AB This article summarizes the proceedings of a breakout session, Interventions to Safeguard System Effectiveness, at the 2011 Academic Emergency Medicine consensus conference, Interventions to Assure Quality in the Crowded Emergency Department. Key definitions fundamental to understanding the effectiveness of emergency care during periods of emergency department (ED) crowding are outlined. Next, a proposed research agenda to evaluate interventions directed at improving emergency care effectiveness is outlined, and the paper concludes with a prioritization of those interventions based on breakout session participant discussion and evaluation.
C1 [Kocher, Keith E.] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA.
[Shane, Steven A.] St Rose Dominican Hosp, Henderson, NV USA.
[Shane, Steven A.] Childrens Hosp Nevada, Las Vegas, NV USA.
[Venkatesh, Arjun K.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA.
[Aronsky, Dominik] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA.
[Aronsky, Dominik] Vanderbilt Univ, Sch Med, Dept Emergency Care, Nashville, TN 37212 USA.
[Asplin, Brent R.] Fairview Med Grp, St Paul, MN USA.
[Rathlev, Niels K.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA.
[Rathlev, Niels K.] Tufts Univ, Sch Med, Springfield, MA 01199 USA.
[Shane, Steven A.] Childrens Hosp Nevada, Henderson, NV USA.
[Shane, Steven A.] St Rose Dominican Hosp, Las Vegas, NV USA.
RP Kocher, KE (reprint author), Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA.
EM kkocher@umich.edu
RI Kocher, Keith/A-7834-2013
FU Agency for Healthcare Research and Quality (AHRQ) [1R13HS020139-01];
Robert Wood Johnson Foundation
FX Funding for this conference was made possible (in part) by
1R13HS020139-01 from the Agency for Healthcare Research and Quality
(AHRQ). The views expressed in written conference materials or
publications and by speakers and moderators do not necessarily reflect
the official policies of the Department of Health and Human Services,
nor does mention of trade names, commercial practices, or organizations
imply endorsement by the U. S. Government. This issue of Academic
Emergency Medicine is funded by the Robert Wood Johnson Foundation.
NR 34
TC 3
Z9 3
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD DEC
PY 2011
VL 18
IS 12
SI SI
BP 1313
EP 1317
DI 10.1111/j.1553-2712.2011.01219.x
PG 5
WC Emergency Medicine
SC Emergency Medicine
GA 861IQ
UT WOS:000298013000014
PM 22168196
ER
PT J
AU Hwang, U
Weber, EJ
Richardson, LD
Sweet, V
Todd, K
Abraham, G
Ankel, F
AF Hwang, Ula
Weber, Ellen J.
Richardson, Lynne D.
Sweet, Vicki
Todd, Knox
Abraham, Gallane
Ankel, Felix
TI A Research Agenda to Assure Equity During Periods of Emergency
Department Crowding
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
ID HEALTH-CARE DISPARITIES; UNITED-STATES; LANGUAGE BARRIERS; CHEST-PAIN;
RACIAL DISPARITIES; ETHNIC DISPARITIES; ELDERLY-PATIENTS; TRAUMA;
MANAGEMENT; ACCESS
AB The effect of emergency department (ED) crowding on equitable care is the least studied of the domains of quality as defined by the Institute of Medicine (IOM). Inequities in access and treatment throughout the health care system are well documented in all fields of medicine. While there is little evidence demonstrating that inequity is worsened by crowding, theory and evidence from social science disciplines, as well as known barriers to care for vulnerable populations, would suggest that crowding will worsen inequities. To design successful interventions, however, it is important to first understand how crowding can result in disparities and base interventions on these mechanisms. A research agenda is proposed to understand mechanisms that may threaten equity during periods of crowding and design and test potential interventions that may ensure the equitable aspect of quality of care.
C1 [Hwang, Ula; Richardson, Lynne D.; Abraham, Gallane] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA.
[Hwang, Ula] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA.
[Richardson, Lynne D.] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY USA.
[Hwang, Ula] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA.
[Weber, Ellen J.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA.
[Sweet, Vicki] Emergency Serv & PreHosp Care, St Jude Med Ctr, Fullerton, CA USA.
[Todd, Knox] Univ Texas MD Anderson Canc Ctr, Dept Emergency Med, Houston, TX 77030 USA.
[Ankel, Felix] Univ Minnesota, Sch Med, Dept Emergency Med, Minneapolis, MN 55455 USA.
RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA.
EM ula.hwang@mountsinai.org
OI Weber, Ellen/0000-0002-0094-1973
FU Agency for Healthcare Research and Quality (AHRQ) [1R13HS020139-01];
Robert Wood Johnson Foundation
FX Funding for this conference was made possible (in part) by
1R13HS020139-01 from the Agency for Healthcare Research and Quality
(AHRQ). The views expressed in written conference materials or
publications and by speakers and moderators do not necessarily reflect
the official policies of the Department of Health and Human Services,
nor does mention of trade names, commercial practices, or organizations
imply endorsement by the U. S. Government. This issue of Academic
Emergency Medicine is funded by the Robert Wood Johnson Foundation.
NR 53
TC 5
Z9 5
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD DEC
PY 2011
VL 18
IS 12
SI SI
BP 1318
EP 1323
DI 10.1111/j.1553-2712.2011.01233.x
PG 6
WC Emergency Medicine
SC Emergency Medicine
GA 861IQ
UT WOS:000298013000015
PM 22168197
ER
PT J
AU Liu, SW
Chang, YC
Weissman, JS
Griffey, RT
Thomas, J
Nergui, S
Hamedani, AG
Camargo, CA
Singer, S
AF Liu, Shan W.
Chang, Yuchiao
Weissman, Joel S.
Griffey, Richard T.
Thomas, James
Nergui, Suvd
Hamedani, Azita G.
Camargo, Carlos A., Jr.
Singer, Sara
TI An Empirical Assessment of Boarding and Quality of Care: Delays in Care
Among Chest Pain, Pneumonia, and Cellulitis Patients
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
ID COMMUNITY-ACQUIRED PNEUMONIA; ICD-9-CM ADMINISTRATIVE DATA; CLINICAL
COMORBIDITY INDEX; EMERGENCY-DEPARTMENT; ADVERSE EVENTS;
MYOCARDIAL-INFARCTION; AMBULANCE DIVERSION; ADMITTED PATIENTS; NEGLIGENT
CARE; GUIDELINES
AB Background: As hospital crowding has increased, more patients have ended up boarding in the emergency department (ED) awaiting their inpatient beds. To the best of our knowledge, no study has compared the quality of care of boarded and nonboarded patients. Objectives: This study sought to examine whether being a boarded patient and boarding longer were associated with more delays, medication errors, and adverse events among ED patients admitted with chest pain, pneumonia, or cellulitis. Methods: This study was a retrospective cohort design in which data collection was accomplished via medical record review from two urban teaching hospitals. Patients admitted with chest pain, pneumonia, or cellulitis between August 2004 and January 2005 were eligible for inclusion. Our outcomes measures were: 1) delays in administration of home medications, cardiac enzyme tests, partial thromboplastin time (PTT), and antibiotics; 2) medication errors; and 3) adverse events or near misses. Primary independent variables were boarded status, boarding time, and boarded time interval. Multiple logistic regression models controlling for patient, ED, and hospital characteristics were used. Results: A total of 1,431 patient charts were included: 811 with chest pain, 387 with pneumonia, and 233 with cellulitis. Boarding time was associated with an increased odds of home medication delays (adjusted odds ratio [AOR] = 1.07, 95% confidence interval [CI] = 1.05 to 1.10), as were boarded time intervals of 12, 18, and 24 hours. Boarding time also was associated with lower odds of having a late cardiac enzyme test (AOR = 0.93, 95% CI = 0.88 to 0.97). Conclusions: Boarding was associated with home medication delays, but fewer cardiac enzyme test delays. Boarding was not associated with delayed PTT checks, antibiotic administration, medication errors, or adverse events/near misses. These findings likely reflect the inherent resources of the ED and the inpatient units.
C1 [Liu, Shan W.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA.
[Chang, Yuchiao; Weissman, Joel S.; Singer, Sara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Griffey, Richard T.] Washington Univ, Sch Med, Div Emergency Med, St Louis, MO USA.
[Thomas, James] Good Samaritan Hosp, Dept Emergency Med, Brockton, MA USA.
[Nergui, Suvd] Tohoku Univ, Grad Sch Med, Dept Cardiovasc Med, Sendai, Miyagi 980, Japan.
[Hamedani, Azita G.] Univ Wisconsin, Div Emergency Med, Sch Med & Publ Hlth, Madison, WI USA.
RP Liu, SW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA.
EM sliu1@partners.org
FU Eleanor and Miles Shore Fellowship; Risk Management Foundation
FX Funded by the Eleanor and Miles Shore Fellowship and the Risk Management
Foundation.
NR 46
TC 11
Z9 11
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD DEC
PY 2011
VL 18
IS 12
SI SI
BP 1339
EP 1348
DI 10.1111/j.1553-2712.2011.01082.x
PG 10
WC Emergency Medicine
SC Emergency Medicine
GA 861IQ
UT WOS:000298013000018
PM 21692902
ER
PT J
AU Wakeman, SE
AF Wakeman, Sarah E.
TI The One Liner
SO ACADEMIC MEDICINE
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Wakeman, SE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM swakeman@partners.org
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD DEC
PY 2011
VL 86
IS 12
BP 1555
EP 1555
DI 10.1097/ACM.0b013e3182351dc9
PG 1
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 863BN
UT WOS:000298137900018
PM 22130261
ER
PT J
AU Pryor, L
Gordon, CR
Swanson, EW
Reish, RG
Horton-Beeman, K
Cohen, SR
AF Pryor, Landon
Gordon, Chad R.
Swanson, Edward W.
Reish, Richard G.
Horton-Beeman, Kelly
Cohen, Steven R.
TI Dermaplaning, Topical Oxygen, and Photodynamic Therapy: A Systematic
Review of the Literature
SO AESTHETIC PLASTIC SURGERY
LA English
DT Review
DE Aesthetician; Dermaplaning; Light therapy; Noninvasive cosmetic
modality; Nonsurgical procedures; Oxygen therapy
ID INTENSE PULSED-LIGHT; CLINICAL-EXPERIENCE; HYPERBARIC-OXYGEN; RED-LIGHT;
SKIN; REJUVENATION; PHOTOTHERAPY; ULCERS
AB Noninvasive procedures for facial rejuvenation are becoming an increasingly popular component of a comprehensive skin care regimen. Concurrently, many new treatment methods are now available to both the plastic surgeon and the aesthetician. Because these techniques have become an integral part of many cosmetic practices, this study aimed to assess the existing evidence-based literature as to their clinical efficacy; to provide an objective overview of some of the most popular noninvasive rejuvenation strategies such as dermaplaning, oxygen therapy, and light therapy; to discuss recent pertinent scientific evidence-based literature; and to provide treatment recommendations based on these findings.
A systematic review was performed in August 2009 using PubMed and the following keywords: "dermaplaning," "oxygen therapy," and "light therapy." All peer-reviewed articles then were screened independently by three plastic surgeons.
The search identified 42 English-written, peer-reviewed manuscripts. The overall amount of scientific data supporting these methods was found to be scarce, anecdotal, and not well documented. Nevertheless, all three noninvasive therapies have become increasingly popular in the cosmetic market because many patients and physicians or surgeons report being pleased with their results.
Although the evidence supporting these nonsurgical methods is suboptimal, their uses continue to expand. As with any plastic surgery procedure, providing patients with realistic expectations is essential to achieving optimal outcomes and patient satisfaction. Therefore, critical investigation is warranted. In addition, these methods are most effective when included within a comprehensive skin care regimen consisting of sunscreen, vitamin therapy, and lifestyle modification.
C1 [Horton-Beeman, Kelly; Cohen, Steven R.] FACES Plast Surg Skin & Laser Ctr, San Diego, CA 92121 USA.
[Pryor, Landon] Rockford Hlth Syst, Rockford, IL 61103 USA.
[Gordon, Chad R.] Cleveland Clin, Dept Plast Surg, Cleveland, OH 44106 USA.
[Gordon, Chad R.; Swanson, Edward W.; Reish, Richard G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA.
[Cohen, Steven R.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Cohen, Steven R.] Rady Childrens Hosp, San Diego, CA USA.
RP Cohen, SR (reprint author), FACES Plast Surg Skin & Laser Ctr, 4510 Execut Dr,Suite 200, San Diego, CA 92121 USA.
EM landonpryor98@hotmail.com; scohen@facesplus.com
NR 43
TC 1
Z9 1
U1 1
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-216X
J9 AESTHET PLAST SURG
JI Aesthet. Plast. Surg.
PD DEC
PY 2011
VL 35
IS 6
BP 1151
EP 1159
DI 10.1007/s00266-011-9730-z
PG 9
WC Surgery
SC Surgery
GA 861FR
UT WOS:000298005200030
PM 21533984
ER
PT J
AU Silverman, S
Cates, M
Saunders, G
AF Silverman, ShienPei
Cates, Megan
Saunders, Gabrielle
TI Is Measured Hearing Aid Benefit Affected by Seeing Baseline Outcome
Questionnaire Responses?
SO AMERICAN JOURNAL OF AUDIOLOGY
LA English
DT Article
DE outcomes; hearing aids; audiologic rehabilitation
ID TEST-RETEST RELIABILITY; QUALITY-OF-LIFE; HANDICAP INVENTORY;
SATISFACTION; DISEASE; ADULTS; TRIAL
AB Purpose: To determine whether hearing aid outcome measured by the Hearing Handicap Inventory (HHI) for the Elderly/Adults (Newman, Weinstein, Jacobson, & Hug, 1990; Ventry & Weinstein, 1982) is differentially affected by informed vs. blind administration of the postfitting questionnaire.
Method: Participants completed the HHI at their hearing aid evaluation and again at their hearing aid follow-up visit. At follow-up, half received a clean HHI form (blind administration), whereas the remainder responded on their original form (informed administration) and could thus base their follow-up responses on those they gave at the hearing aid evaluation.
Results: The data show that for the population examined here, informed administration of the follow-up HHI did not yield a different outcome to blind administration of the follow-up HHI. This was not influenced by past hearing aid use, age of the participant, or the duration of time between baseline questionnaire completion and follow-up completion.
Conclusion: These data suggest that completion of follow-up questionnaires in either informed or blind format will have little impact on HHI responses, most likely because of the many other factors that combined to influence hearing aid outcome.
C1 [Silverman, ShienPei; Saunders, Gabrielle] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR USA.
[Cates, Megan] Univ Arkansas, Univ Arkansas Med Sci, Little Rock, AR 72204 USA.
RP Saunders, G (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR USA.
EM gabrielle.saunders@va.gov
FU National Institutes of Health [T35 DC008764]; VA Rehabilitation Research
& Development Grant [C4844C]
FX Support was provided by National Institutes of Health Pre-doctoral
Training Grant T35 DC008764 and by VA Rehabilitation Research &
Development Grant C4844C awarded to the VA RR&D National Center for
Rehabilitative Auditory Research. We thank Portland VAMC Audiology
clinic staff for their participation and assistance with data
collection.
NR 36
TC 0
Z9 1
U1 0
U2 3
PU AMER SPEECH-LANGUAGE-HEARING ASSOC
PI ROCKVILLE
PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA
SN 1059-0889
J9 AM J AUDIOL
JI Am. J. Audiol.
PD DEC
PY 2011
VL 20
IS 2
BP 90
EP 99
DI 10.1044/1059-0889(2011/10-0003)
PG 10
WC Audiology & Speech-Language Pathology; Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Otorhinolaryngology
GA 865ZJ
UT WOS:000298349100003
PM 21940983
ER
PT J
AU Hoang, MP
AF Hoang, Mai P.
TI Role of Immunohistochemistry in Diagnosing Tumors of Cutaneous
Appendages
SO AMERICAN JOURNAL OF DERMATOPATHOLOGY
LA English
DT Article
DE immunohistochemistry; follicular neoplasm; eccrine neoplasm; apocrine
neoplasm
ID BASAL-CELL CARCINOMA; MICROCYSTIC ADNEXAL CARCINOMA; EPITHELIAL MEMBRANE
ANTIGEN; DISEASE FLUID PROTEIN-15; MUIR-TORRE-SYNDROME; MALIGNANT
ECCRINE POROMA; FOLLICLE STEM-CELLS; SQUAMOUS-CELL; SEBACEOUS-CARCINOMA;
DESMOPLASTIC TRICHOEPITHELIOMA
AB In recent years, there has been significant progress in immunohistochemistry as an ancillary tool in diagnostic dermatopathology. In most instances, the histologic diagnosis can be rendered with the routine histologic sections; however, immunohistochemistry can help to narrow the differential in diagnosing neoplasms of cutaneous appendages in some settings including adnexal versus epidermal origin, benign versus malignant adnexal neoplasms, and primary adnexal carcinoma versus cutaneous metastases as outlined in this review.
C1 [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Hoang, Mai P.] Harvard Univ, Sch Med, Boston, MA USA.
RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 820, Boston, MA 02114 USA.
EM mhoang@partners.org
NR 91
TC 8
Z9 8
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0193-1091
J9 AM J DERMATOPATH
JI Am. J. Dermatopathol.
PD DEC
PY 2011
VL 33
IS 8
BP 765
EP 771
DI 10.1097/DAD.0b013e31820a4837
PG 7
WC Dermatology
SC Dermatology
GA 862JT
UT WOS:000298087700005
PM 22112636
ER
PT J
AU Peron, EP
Gray, SL
Hanlon, JT
AF Peron, Emily P.
Gray, Shelly L.
Hanlon, Joseph T.
TI Medication Use and Functional Status Decline in Older Adults: A
Narrative Review
SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY
LA English
DT Review
DE activities of daily living; aged; drug use
ID RANDOMIZED CONTROLLED-TRIAL; DRUG BURDEN INDEX; FRAIL ELDERLY
POPULATION; LOWER-EXTREMITY FUNCTION; NURSING-HOME RESIDENTS; PHYSICAL
FUNCTION; VITAMIN-D; GROWTH-HORMONE; HIP-FRACTURE; CALCIUM
SUPPLEMENTATION
AB Background: Functional status is the cornerstone of geriatric care and serves as an indicator of general well-being. A decline in function can increase health care use, worsen quality of life, threaten independence, and increase the risk of mortality. One of several risk factors for decline in functional status is medication use.
Objective: Our aim was to critically review published articles that have examined the relationship between medication use and functional status decline in the elderly.
Methods: The MEDLINE and EMBASE databases were searched for English-language articles published from January 1986 to June 2011. Search terms included aged, humans, drug utilization, polypharmacy, inappropriate prescribing, anticholinergics, psychotropics, antihypertensives, drug burden index, functional status, function change or decline, activities of daily living, gait, mobility limitation, and disability. A manual search of the reference lists of the identified articles and the authors' article files, book chapters, and recent reviews was conducted to retrieve additional publications. Only articles that used rigorous observational or interventional designs were included. Cross-sectional studies and case series were excluded from this review.
Results: Nineteen studies met the inclusion criteria. Five studies addressed the impact of suboptimal prescribing on function, 3 of which found an increased risk of worse function in community-dwelling subjects receiving polypharmacy. Three of the 4 studies that assessed benzodiazepine use and functional status decline found a statistically significant association. One cohort study identified no relationship between antidepressant use and functional status, whereas a randomized trial found that amitriptyline, but not desipramine or paroxetine, impaired certain measures of gait. Two studies found that increasing anticholinergic burden was associated with worse functional status. In a study of hospitalized rehabilitation patients, users of hypnotics/anxiolytics (eg, phenobarbital, zolpidem) had lower relative Functional Independence Measure motor gains than nonusers. Use of multiple central nervous system (CNS) drugs (using different definitions) was linked to greater declines in self-reported mobility and Short Physical Performance Battery (SPPB) scores in 2 community-based studies. Another study of nursing home patients did not report a significant decrease in SPPB scores in those taking multiple CNS drugs. Finally, 2 studies found mixed effects between antihypertensive use and functional status in the elderly.
Conclusions: Benzodiazepines and anticholinergics have been consistently associated with impairments in functional status in the elderly. The relationships between suboptimal prescribing, antidepressants, and antihypertensives and functional status decline were mixed. Further research using established measures and methods is needed to better describe the impact of medication use on functional status in older adults. (Am J Geriatr Pharmacother. 2011;9: 378-391) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.
C1 [Peron, Emily P.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA.
[Gray, Shelly L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA.
[Hanlon, Joseph T.] Univ Pittsburgh, Dept Biomed Informat, 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.] VA Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
[Hanlon, Joseph T.] VA Pittsburgh Hlth Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
RP Peron, EP (reprint author), Univ Pittsburgh, Dept Geriatr Med, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA.
EM emp56@pitt.edu
FU National Institute on Aging [U01 AG00678121, R01 AG027017, P30 AG024827,
T32 AG021885, K07 AG033174, R56 AG027017, R01 AG034056]; National
Institute of Mental Health [R34 MH082682]; National Institute of Nursing
Research [R01 NR010135]; Agency for Healthcare Research and Quality [R01
HS017695, R01 HS018721, K12 HS019461]; VA Health Services [IIR-06-062]
FX This study was primarily supported by National Institute on Aging grants
and contracts (U01 AG00678121, R01 AG027017, P30 AG024827, T32 AG021885,
K07 AG033174, R56 AG027017, R01 AG034056), 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, R01 HS018721, K12 HS019461), and a VA
Health Services Research grant (IIR-06-062).
NR 97
TC 34
Z9 35
U1 3
U2 27
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 1543-5946
J9 AM J GERIATR PHARMAC
JI Am. J. Geriatr. Pharmacother.
PD DEC
PY 2011
VL 9
IS 6
BP 378
EP 391
DI 10.1016/j.amjopharm.2011.10.002
PG 14
WC Geriatrics & Gerontology; Pharmacology & Pharmacy
SC Geriatrics & Gerontology; Pharmacology & Pharmacy
GA 869BM
UT WOS:000298570700003
PM 22057096
ER
PT J
AU Linnebur, SA
Fish, DN
Ruscin, JM
Radcliff, TA
Oman, KS
Fink, R
Van Dorsten, B
Liebrecht, D
Fish, R
McNulty, M
Hutt, E
AF Linnebur, Sunny A.
Fish, Douglas N.
Ruscin, J. Mark
Radcliff, Tiffany A.
Oman, Kathy S.
Fink, Regina
Van Dorsten, Brent
Liebrecht, Debra
Fish, Ron
McNulty, Monica
Hutt, Evelyn
TI Impact of a Multidisciplinary Intervention on Antibiotic Use for Nursing
Home-Acquired Pneumonia
SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY
LA English
DT Article
DE academic detailing; antibacterial agents; guideline adherence; nursing
homes; physician practice patterns; pneumonia
ID RANDOMIZED CONTROLLED-TRIAL; TERM-CARE FACILITIES; GUIDELINES;
PREVENTION; MANAGEMENT; RESIDENTS; ADHERENCE; COMMUNITY; EDUCATION;
THERAPY
AB Background: Academic detailing in nursing homes (NHs) has been shown to improve drug use patterns and adherence to guidelines.
Objective: The purpose of this study was to evaluate the impact of a multidisciplinary intervention that included academic detailing on adherence to national nursing home acquired pneumonia (NHAP) guidelines related to use of antibiotics.
Methods: This quasi-experimental study evaluated the effects of a 2-year multifaceted and multidisciplinary intervention targeting implementation of national evidence-based guidelines for NHAP. Interventions took place in 8 NHs in Colorado; 8 NHs in Kansas and Missouri served as controls. Interventions included (1) educational sessions for nurses to improve recognition and timely treatment of NHAP symptoms and (2) academic detailing to clinicians by pharmacists regarding diagnostic and prescribing practices. Differences in antibiotic use between groups were compared after 2 intervention years relative to baseline.
Results: A total of 549 episodes of NHAP were evaluated in the intervention group and 574 in the control group. Compared with baseline, 1 facility in the intervention group significantly improved in guideline adherence for optimal antibiotic use (P = 0.007), whereas no facilities in the control group improved. The mean adherence score for optimal antibiotic use in intervention NHs increased from 60% to 66%, whereas the control NHs increased from 32% to 39% (P = 0.3). Mean adherence to guidelines recommending antibiotic use within 4 hours of NHAP diagnosis increased from 57% to 75% in intervention NHs but decreased from 38% to 31% in control NHs (P = 0.0003 for difference). There was no difference between intervention and control NHs for guideline adherence regarding optimal duration of antibiotic use.
Conclusions: The ability of this multifaceted study to repeatedly remind nursing staff of the importance of timely antibiotic administration contrasts with its limited academic detailing interaction with clinicians. This difference within the intervention may explain the differential impact of the intervention on antibiotic guideline adherence. (Am J Geriatr Pharmacother. 2011;9:442-450) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.
C1 [Linnebur, Sunny A.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO 80045 USA.
[Ruscin, J. Mark] So Illinois Univ, Sch Pharm, Edwardsville, IL 62026 USA.
[Radcliff, Tiffany A.; Hutt, Evelyn] Denver Vet Affairs Med Ctr, Denver, CO USA.
RP Linnebur, SA (reprint author), Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Anschutz Med Campus,12850 E Montview Blvd,Campus, Aurora, CO 80045 USA.
EM sunny.linnebur@ucdenver.edu
FU Agency for Health Care Research and Quality [RO1 HS13618-01A1]
FX This study was supported by an investigator-initiated research grant
from the Agency for Health Care Research and Quality (RO1 HS13618-01A1).
The authors have indicated that they have no other conflicts of interest
regarding the content of this article.
NR 30
TC 13
Z9 14
U1 2
U2 6
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 1543-5946
J9 AM J GERIATR PHARMAC
JI Am. J. Geriatr. Pharmacother.
PD DEC
PY 2011
VL 9
IS 6
BP 442
EP 450
DI 10.1016/j.amjopharm.2011.09.009
PG 9
WC Geriatrics & Gerontology; Pharmacology & Pharmacy
SC Geriatrics & Gerontology; Pharmacology & Pharmacy
GA 869BM
UT WOS:000298570700009
PM 22055208
ER
PT J
AU da Cruz, LCH
Rodriguez, I
Domingues, RC
Gasparetto, EL
Sorensen, AG
AF Hygino da Cruz, L. C., Jr.
Rodriguez, I.
Domingues, R. C.
Gasparetto, E. L.
Sorensen, A. G.
TI Pseudoprogression and Pseudoresponse: Imaging Challenges in the
Assessment of Posttreatment Glioma
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Review
ID PROMOTER METHYLATION STATUS; RECURRENT BRAIN-TUMOR; GLIOBLASTOMA
PATIENTS; MALIGNANT GLIOMAS; CONCOMITANT RADIOCHEMOTHERAPY;
PSEUDO-PROGRESSION; RADIATION NECROSIS; RESPONSE CRITERIA; TEMOZOLOMIDE;
RADIOTHERAPY
AB The current standard of care for newly diagnosed cases of high-grade glioma is surgical resection followed by RT with concurrent chemotherapy. The most widely used criteria for assessing treatment response are based on a 2D measurement of the enhancing area on MR imaging known as the Macdonald Criteria. Recently, nontumoral increases (pseudoprogression) and decreases (pseudoresponse) in enhancement have been found, and these can confuse outcome evaluation. Here we review pseudoprogression and pseudoresponse and describe how better understanding of these phenomena can aid interpretation.
C1 Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil.
[Hygino da Cruz, L. C., Jr.] Univ Fed Rio de Janeiro, Dept Radiol, Clin IRM, Clin Diagnost Imagen & Multiimagem, Rio De Janeiro, Brazil.
[Rodriguez, I.] Imagen Med Avanzada, Madrid, Spain.
[Domingues, R. C.] Clin Clin Diagnost Imagen & Multiimagem, Rio De Janeiro, Brazil.
[Gasparetto, E. L.] Univ Fed Rio de Janeiro, Dept Radiol, Clin Clin Diagnost Imagen & Multiimagem, Rio De Janeiro, Brazil.
[Sorensen, A. G.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
Harvard Univ, Sch Med, Charlestown, MA USA.
RP da Cruz, LCH (reprint author), Rua Almirante Saddock Sa 266, BR-22411040 Rio De Janeiro, RJ, Brazil.
EM celsohygino@hotmail.com
NR 35
TC 70
Z9 72
U1 0
U2 11
PU AMER SOC NEURORADIOLOGY
PI DENVILLE
PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA
SN 0195-6108
EI 1936-959X
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD DEC
PY 2011
VL 32
IS 11
BP 1978
EP 1985
DI 10.3174/ajnr.A2397
PG 8
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 871ZC
UT WOS:000298775200003
PM 21393407
ER
PT J
AU Wei, X
Yu, ZY
Cho, KS
Chen, HH
Malik, MTA
Chen, XM
Lo, EH
Wang, XY
Chen, DF
AF Wei, Xin
Yu, Zhanyang
Cho, Kin-Sang
Chen, Huihui
Malik, Muhammad Taimur A.
Chen, Xiaoming
Lo, Eng H.
Wang, Xiaoying
Chen, Dong F.
TI Neuroglobin Is an Endogenous Neuroprotectant for Retinal Ganglion Cells
against Glaucomatous Damage
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID FOCAL CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; INTRAOCULAR-PRESSURE; GLUCOSE
DEPRIVATION; AXON REGENERATION; OPTIC-NERVE; CYTOGLOBIN; OXYGEN; BRAIN;
NEURONS
AB Neuroglobin (NGB), a newly discovered member of the globin superfamily, may regulate neuronal survival under hypoxia or oxidative stress. Although NGB is greatly expressed in retinal neurons, the biological functions of NGB in retinal diseases remain largely unknown. We investigated the role of NGB in an experimental model of glaucoma, a neurodegenerative disorder that usually involves elevation of intraocular pressure (LOP). Elevated IOP is thought to induce oxidative stress in retinal ganglion cells (RGCs), thereby causing RGC death and, eventually, blindness. We found that NGB plays a critical role in increasing RGC resistance to ocular hypertension and glaucomatous damage. Elevation of IOP stimulated a transient up-regulation of endogenous NGB in RGCs. Constitutive overexpression of NGB in transgenic mice prevented RGC damage induced by glutamate cytotoxicity in vitro and/or by chronic IOP elevation in vivo. Moreover, overexpression of NGB attenuated ocular hypertension-induced superoxide production and the associated decrease in ATP levels in mice, suggesting that NGB acts as an endogenous neuroprotectant to reduce oxidative stress and improve mitochondrial function, thereby promoting RGC survival. Thus, NGB may modulate RGC susceptibility to glaucomatous neural damage. Manipulating the expression and bioactivity of NGB may represent a novel therapeutic strategy for glaucoma. (Am J Pathol 2011, 179:2788-2797; DOI: 10.1016/j.ajpath.2011.08.015)
C1 [Wei, Xin; Cho, Kin-Sang; Chen, Huihui; Malik, Muhammad Taimur A.; Chen, Dong F.] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA.
[Wei, Xin; Chen, Xiaoming] Sichuan Univ, W China Hosp, Dept Ophthalmol, Chengdu 610064, Peoples R China.
[Wei, Xin; Chen, Xiaoming] Sichuan Univ, W China Hosp, Ophthalm Labs, Chengdu 610064, Peoples R China.
[Yu, Zhanyang; Lo, Eng H.; Wang, Xiaoying] Massachusetts Gen Hosp, Dept Neurol & Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA.
[Chen, Dong F.] VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA USA.
RP Chen, DF (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM wangxi@helix.mgh.harvard.edu; dongfeng.chen@schepens.harvard.edu
FU NIH National Eye Institute [R01EY017641]; NIH National Institute of Drug
Abuse [R21DA024803]; Department of Veterans Affairs [5I01RX000110];
Department of Defense [W23RYX-9104-N603]; American Health Foundation
[G2007-058]; National Institute of Neurological Disorder and Stroke
[R01NS49476]
FX Supported in part by grants from the NIH National Eye Institute
(R01EY017641), the NIH National Institute of Drug Abuse (R21DA024803),
the Department of Veterans Affairs (5I01RX000110), the Department of
Defense (W23RYX-9104-N603), and the American Health Foundation
(G2007-058 to D.F.C.), and the National Institute of Neurological
Disorder and Stroke (R01NS49476 to X.W.).
NR 62
TC 18
Z9 19
U1 1
U2 8
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 DEC
PY 2011
VL 179
IS 6
BP 2788
EP 2797
DI 10.1016/j.ajpath.2011.08.015
PG 10
WC Pathology
SC Pathology
GA 865JR
UT WOS:000298307700012
PM 21967817
ER
PT J
AU Pennock, S
Rheaume, MA
Mukai, S
Kazlauskas, A
AF Pennock, Steven
Rheaume, Marc-Andre
Mukai, Shizuo
Kazlauskas, Andrius
TI A Novel Strategy to Develop Therapeutic Approaches to Prevent
Proliferative Vitreoretinopathy
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID TISSUE GROWTH-FACTOR; MASSIVE PERIRETINAL PROLIFERATION; PIGMENT
EPITHELIAL-CELLS; RETINAL-DETACHMENT; DIABETIC-RETINOPATHY; EPIRETINAL
MEMBRANES; EXPERIMENTAL-MODEL; FACTOR RECEPTOR; VITREOUS-HUMOR; RABBIT
MODEL
AB Proliferative vitreoretinopathy (PVR) thwarts the repair of rhegmatogenous retinal detachments. Currently, there is no effective prevention for PVR. Platelet-derived growth factor receptor a (PDGFRa) is associated with PVR in humans and strongly promotes experimental PVR driven by multiple vitreal growth factors outside the PDGF family. We sought to identify vitreal factors required for experimental P'VR and to establish a potential approach to prevent PVR. Vitreous was obtained from normal rabbits or those in which PVR was either developing or stabilized. Normal vitreous contained substantial levels of growth factors and cytokines, which changed quantitatively and/or qualitatively as PVR progressed and stabilized. Neutralizing a subset of these agents in rabbit vitreous eliminated their ability to induce PVRrelevant signaling and cellular responses. A single intravitreal injection of neutralizing reagents for this subset prevented experimental PVR. To identify growth factors and cytokines likely driving PVR in humans, we subjected vitreous from patients with or without PVR to a similar series of analyses. This analysis accurately identified those agents required for vitreousinduced contraction of cells from a patient PVR membrane. We conclude that combination therapy encompassing a subset of vitreal growth factors and cytokines is a potential approach to prevent PVR. (Am J Pathol 2011, 179:2931-2940; DOI: 10.1016/j.ajpath.2011.08.043)
C1 [Pennock, Steven; Kazlauskas, Andrius] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA.
[Pennock, Steven; Rheaume, Marc-Andre; Mukai, Shizuo; Kazlauskas, Andrius] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
[Pennock, Steven; Rheaume, Marc-Andre; Mukai, Shizuo] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Kazlauskas, A (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM ak@eri.harvard.edu
FU Department of Defense [WB1XWH-10-1-0392]; National Institutes of Health
[EY012509]; Massachusetts Eye and Ear Infirmary
FX Supported by grants from the Department of Defense (WB1XWH-10-1-0392)
and National Institutes of Health (EY012509) to A.K., M.-A.R. is an
Allergan Horizon Grant in Retina 2011 Fellow. S.M. is supported in part
by gifts to the Mukai Fund of the Massachusetts Eye and Ear Infirmary.
NR 50
TC 29
Z9 30
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 DEC
PY 2011
VL 179
IS 6
BP 2931
EP 2940
DI 10.1016/j.ajpath.2011.08.043
PG 10
WC Pathology
SC Pathology
GA 865JR
UT WOS:000298307700025
PM 22035642
ER
PT J
AU Stewart, AK
Shmukler, BE
Vandorpe, DH
Rivera, A
Heneghan, JF
Li, XJ
Hsu, A
Karpatkin, M
O'Neill, AF
Bauer, DE
Heeney, MM
John, K
Kuypers, FA
Gallagher, PG
Lux, SE
Brugnara, C
Westhoff, CM
Alper, SL
AF Stewart, Andrew K.
Shmukler, Boris E.
Vandorpe, David H.
Rivera, Alicia
Heneghan, John F.
Li, Xiaojin
Hsu, Ann
Karpatkin, Margaret
O'Neill, Allison F.
Bauer, Daniel E.
Heeney, Matthew M.
John, Kathryn
Kuypers, Frans A.
Gallagher, Patrick G.
Lux, Samuel E.
Brugnara, Carlo
Westhoff, Connie M.
Alper, Seth L.
TI Loss-of-function and gain-of-function phenotypes of stomatocytosis
mutant RhAG F65S
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE hemolytic anemia; Rh antigen, ammonium, lithium; rubidium;
methylammonium; Xenopus oocyte
ID AMINO-ACID SUBSTITUTIONS; RED-BLOOD-CELLS; AMMONIUM TRANSPORT;
HEREDITARY STOMATOCYTOSIS; ERYTHROCYTE-MEMBRANE; SICKLE ERYTHROCYTES;
MOUSE ERYTHROCYTES; ESCHERICHIA-COLI; INTRACELLULAR PH; XENOPUS OOCYTES
AB Stewart AK, Shmukler BE, Vandorpe DH, Rivera A, Heneghan JF, Li X, Hsu A, Karpatkin M, O'Neill AF, Bauer DE, Heeney MM, John K, Kuypers FA, Gallagher PG, Lux SE, Brugnara C, Westhoff CM, Alper SL. Loss-of-function and gain-of-function phenotypes of stomatocytosis mutant RhAG F65S. Am J Physiol Cell Physiol 301: C1325-C1343, 2011. First published August 17, 2011; doi:10.1152/ajpcell.00054.2011.-Four patients with overhydrated cation leak stomatocytosis (OHSt) exhibited the heterozygous RhAG missense mutation F65S. OHSt erythrocytes were osmotically fragile, with elevated Na and decreased K contents and increased cation channel-like activity. Xenopus oocytes expressing wild-type RhAG and RhAG F65S exhibited increased ouabain and bumetanide-resistant uptake of Li+ and Rb-86(+), with secondarily increased Rb-86(+) influx sensitive to ouabain and to bumetanide. Increased RhAG-associated C-14-methylammonium (MA) influx was severely reduced in RhAG F65S-expressing oocytes. RhAG-associated influxes of Li+, Rb-86(+), and C-14-MA were pharmacologically distinct, and Li+ up-takes associated with RhAG and RhAG F65S were differentially inhibited by NH4+ and Gd-3(+). RhAG-expressing oocytes were acidified and depolarized by 5 mM bath NH3/NH4+, but alkalinized and depolarized by subsequent bath exposure to 5 mM methylammonium chloride (MA/MA(+)). RhAG F65S-expressing oocytes exhibited near-wild-type responses to NH4Cl, but MA/MA(+) elicited attenuated alkalinization and strong hyperpolarization. Expression of RhAG or RhAG F65S increased steady-state cation currents unaltered by bath Li+ substitution or bath addition of 5 mM NH4Cl or MA/MA(+). These oocyte studies suggest that 1) RhAG expression increases oocyte transport of NH3/NH4+ and MA/MA(+); 2) RhAG F65S exhibits gain-of-function phenotypes of increased cation conductance/permeability, and loss-of-function phenotypes of decreased and modified MA/MA(+) transport, and decreased NH3/NH4+ -associated depolarization; and 3) RhAG transports NH3/NH4+ and MA/MA(+) by distinct mechanisms, and/or the substrates elicit distinct cellular responses. Thus, RhAG F65S is a loss-of-function mutation for amine transport. The altered oocyte intracellular pH, membrane potential, and currents associated with RhAG or RhAG F65S expression may reflect distinct transport mechanisms.
C1 [Stewart, Andrew K.; Shmukler, Boris E.; Vandorpe, David H.; Heneghan, John F.; Hsu, Ann; Alper, Seth L.] Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA.
[Stewart, Andrew K.; Shmukler, Boris E.; Vandorpe, David H.; Heneghan, John F.; Hsu, Ann; Alper, Seth L.] Beth Israel Deaconess Med Ctr, Mol & Vasc Med Div, Boston, MA 02215 USA.
[Rivera, Alicia; Brugnara, Carlo] Childrens Hosp Boston, Dept Lab Med, Boston, MA USA.
[O'Neill, Allison F.; Bauer, Daniel E.; Heeney, Matthew M.; John, Kathryn; Lux, Samuel E.] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA.
[O'Neill, Allison F.; Lux, Samuel E.] Dana Farber Canc Ctr, Dept Pediat Oncol, Boston, MA USA.
[Stewart, Andrew K.; Shmukler, Boris E.; Vandorpe, David H.; Heneghan, John F.; O'Neill, Allison F.; Alper, Seth L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Bauer, Daniel E.; Heeney, Matthew M.; Lux, Samuel E.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Rivera, Alicia; Brugnara, Carlo] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Karpatkin, Margaret] NYU, Dept Pediat, Sch Med, New York, NY 10016 USA.
[Kuypers, Frans A.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
[Gallagher, Patrick G.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Westhoff, Connie M.] Amer Red Cross, Philadelphia, PA USA.
[Li, Xiaojin; Westhoff, Connie M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Westhoff, Connie M.] New York Blood Ctr, New York, NY 10021 USA.
RP Alper, SL (reprint author), Beth Israel Deaconess Med Ctr, Div Renal, 330 Brookline Ave, Boston, MA 02215 USA.
EM cwestoff@nybloodcenter.org; salper@bidmc.harvard.edu
RI Heeney, Matthew/J-6838-2015
OI Heeney, Matthew/0000-0002-1104-6843
FU National Institutes of Health [HL077765, HL090632, HL092535, DK62039,
HL081608]; American Red Cross Holland Laboratory (Bethesda, MD)
FX This work was funded by National Institutes of Health Grants HL077765
(to S. L. Alper and C. Brugnara), HL090632 (to A. Rivera), HL092535 (to
F. A. Kuypers), DK62039 (to P. G. Gallagher), and HL081608 (to S. E.
Lux). C. M. Westhoff was supported by the American Red Cross Holland
Laboratory (Bethesda, MD).
NR 85
TC 9
Z9 10
U1 1
U2 6
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
EI 1522-1563
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD DEC
PY 2011
VL 301
IS 6
BP C1325
EP C1343
DI 10.1152/ajpcell.00054.2011
PG 19
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 863GM
UT WOS:000298150800007
PM 21849667
ER
PT J
AU Weng, M
Baron, DM
Bloch, KD
Luster, AD
Lee, JJ
Medoff, BD
AF Weng, M.
Baron, D. M.
Bloch, K. D.
Luster, A. D.
Lee, J. J.
Medoff, B. D.
TI Eosinophils are necessary for pulmonary arterial remodeling in a mouse
model of eosinophilic inflammation-induced pulmonary hypertension
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE pulmonary hypertension; eosinophils; pulmonary artery smooth muscle
cells; adiponectin; mouse model
ID ACTIVATED-RECEPTOR-GAMMA; SMOOTH-MUSCLE-CELLS; ALLERGIC AIRWAY
INFLAMMATION; NF-KAPPA-B; VASCULAR-DISEASE; EPITHELIAL-CELLS; EOTAXIN
EXPRESSION; MURINE MODEL; ADIPONECTIN; LUNG
AB Weng M, Baron DM, Bloch KD, Luster AD, Lee JJ, Medoff BD. Eosinophils are necessary for pulmonary arterial remodeling in a mouse model of eosinophilic inflammation-induced pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 301: L927-L936, 2011. First published September 9, 2011; doi: 10.1152/ajplung.00049.2011.-There is increasing evidence that inflammation plays a pivotal role in the pathogenesis of some forms of pulmonary hypertension (PH). We recently demonstrated that deficiency of adiponectin (APN) in a mouse model of PH induced by eosinophilic inflammation increases pulmonary arterial remodeling, pulmonary pressures, and the accumulation of eosinophils in the lung. Based on these data, we hypothesized that APN deficiency exacerbates PH indirectly by increasing eosinophil recruitment. Herein, we examined the role of eosinophils in the development of inflammation-induced PH. Elimination of eosinophils in APN-deficient mice by treatment with anti-interleukin-5 antibody attenuated pulmonary arterial muscularization and PH. In addition, we observed that transgenic mice that are devoid of eosinophils also do not develop pulmonary arterial muscularization in eosinophilic inflammation-induced PH. To investigate the mechanism by which APN deficiency increased eosinophil accumulation in response to an allergic inflammatory stimulus, we measured expression levels of the eosinophil-specific chemokines in alveolar macrophages isolated from the lungs of mice with eosinophilic inflammation-induced PH. In these experiments, the levels of CCL11 and CCL24 were higher in macrophages isolated from APN-deficient mice than in macrophages from wild-type mice. Finally, we demonstrate that the extracts of eosinophil granules promoted the proliferation of pulmonary arterial smooth muscle cells in vitro. These data suggest that APN deficiency may exacerbate PH, in part, by increasing eosinophil recruitment into the lung and that eosinophils could play an important role in the pathogenesis of inflammation-induced PH. These results may have implications for the pathogenesis and treatment of PH caused by vascular inflammation.
C1 [Weng, M.; Medoff, B. D.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Baron, D. M.; Bloch, K. D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA.
[Baron, D. M.; Bloch, K. D.] Harvard Univ, Sch Med, Boston, MA USA.
[Weng, M.; Luster, A. D.; Medoff, B. D.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA.
[Weng, M.; Luster, A. D.; Medoff, B. D.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Lee, J. J.] Mayo Clin, Dept Biochem & Mol Biol, Scottsdale, AZ USA.
RP Medoff, BD (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA.
EM bmedoff@partners.org
FU National Heart, Lung, and Blood Institute [HL-088297, T32 HL-07874,
HL-074352]; Foundation Leducq
FX This work was supported by National Heart, Lung, and Blood Institute
Grants HL-088297 to B. D. Medoff, T32 HL-07874 to B. D. Medoff in
support of M. Weng, and HL-074352 to K. D. Bloch and by a Foundation
Leducq award to K. D. Bloch.
NR 79
TC 8
Z9 9
U1 1
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD DEC
PY 2011
VL 301
IS 6
BP L927
EP L936
DI 10.1152/ajplung.00049.2011
PG 10
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 863JI
UT WOS:000298158200013
PM 21908591
ER
PT J
AU Graham, BM
Milad, MR
AF Graham, Bronwyn M.
Milad, Mohammed R.
TI The Study of Fear Extinction: Implications for Anxiety Disorders
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Review
ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY;
VENTROMEDIAL PREFRONTAL CORTEX; OBSESSIVE-COMPULSIVE DISORDER; CHILDHOOD
SEXUAL-ABUSE; CEREBRAL-BLOOD-FLOW; CONDITIONED FEAR; D-CYCLOSERINE;
EXPOSURE THERAPY; BRAIN ACTIVATION
AB In this review, the authors propose that the fear extinction model can be used as an experimental tool to cut across symptom dimensions of multiple anxiety disorders to enhance our understanding of the psychopathology of these disorders and potentially facilitate the detection of biomarkers for them. The authors evaluate evidence for this proposition from studies examining the neurocircuitry underlying fear extinction in rodents, healthy humans, and clinical populations. The authors also assess the potential use of the fear extinction model to predict vulnerability for anxiety and treatment response and to improve existing treatments or develop novel ones. Finally, the authors suggest potential directions for future research that will help to further validate extinction as a biomarker for anxiety across diagnostic categories and to bridge the gap between basic neuroscience and clinical practice.
C1 [Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Milad, MR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
EM milad@nmr.mgh.harvard.edu
FU Micro Transponder, Inc.; NIMH (Massachusetts General Hospital)
[K01MH080346, 1R01MH081975-01]; American Australian Association
FX Dr. Milad has received fees from Micro Transponder, Inc. Dr. Graham
reports no financial relationships with commercial interests.; Supported
by NIMH grants K01MH080346 and 1R01MH081975-01 (Massachusetts General
Hospital subcontract) to Dr. Milad and by an American Australian
Association Neurological Fellowship to Dr. Graham.
NR 95
TC 103
Z9 104
U1 12
U2 44
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 DEC
PY 2011
VL 168
IS 12
BP 1255
EP 1265
DI 10.1176/appi.ajp.2011.11040557
PG 11
WC Psychiatry
SC Psychiatry
GA 860KO
UT WOS:000297947400008
PM 21865528
ER
PT J
AU Chopra, P
Verma, P
Klaustermeyer, WB
AF Chopra, Preet
Verma, Prashant
Klaustermeyer, William B.
TI SUCCESSFUL USE OF PRASUGREL, AN ALTERNATIVE ANTIPLATELET AGENT, IN A
PATIENT WITH CLOPIDOGREL ALLERGY
SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY
LA English
DT Letter
C1 [Chopra, Preet; Verma, Prashant; Klaustermeyer, William B.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare, Dept Allergy Immunol, Los Angeles, CA 90095 USA.
RP Chopra, P (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare, Dept Allergy Immunol, Los Angeles, CA 90095 USA.
EM preetichopra14@gmail.com
NR 8
TC 5
Z9 5
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1081-1206
J9 ANN ALLERG ASTHMA IM
JI Ann. Allergy Asthma Immunol.
PD DEC
PY 2011
VL 107
IS 6
BP 541
EP 542
DI 10.1016/j.anai.2011.08.003
PG 2
WC Allergy; Immunology
SC Allergy; Immunology
GA 862EN
UT WOS:000298072700014
PM 22123386
ER
PT J
AU Pallin, DJ
Sullivan, AF
Espinola, JA
Landman, AB
Camargo, CA
AF Pallin, Daniel J.
Sullivan, Ashley F.
Espinola, Janice A.
Landman, Adam B.
Camargo, Carlos A., Jr.
TI Increasing Adoption of Computerized Provider Order Entry, and Persistent
Regional Disparities, in US Emergency Departments
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Article
ID ELECTRONIC HEALTH RECORDS; INFORMATION-TECHNOLOGY; UNITED-STATES;
HOSPITALS; SYSTEM; QUALITY; CARE
AB Study objective: The US government provides financial incentives for "meaningful use" of health information technology, including computerized provider order entry. We assess prevalence of emergency department (ED) computerized provider order entry in 4 states, identify characteristics predicting computerized provider order entry adoption, and assess adoption in 1 state over time, all before incentive programs.
Methods: We surveyed all nonfederal EDs in Massachusetts, Colorado, Georgia, and Oregon, assessing health information technology prevalence in 2008, focusing on computerized provider order entry, an enabler of other health information technology and a key element in itself. We use multivariable logistic regression to evaluate predictors of adoption. We compared the Massachusetts data with data from a similar survey we conducted for Massachusetts in 2005, using 95% confidence intervals (CIs) to assess the change in rate.
Results: We identified and surveyed 351 EDs, and 290 (83%) responded to the computerized provider order entry module. Of these, 30% had adopted computerized provider order entry. Odds of computerized provider order entry in rural EDs were 0.07 relative to urban (95% Cl 0.01 to 0.39). Oregon EDs had a higher likelihood of computerized provider order entry adoption than Georgia EDs, the state with the lowest adoption (odds ratio 2.9; 95% Cl 1.2 to 7.3). In 2005, 15% of Massachusetts EDs reported computerized provider order entry versus 44% in 2008 (29% difference; 95% Cl 26% to 32%).
Conclusion: Health information technology adoption varies by state and urbanicity, with less computerized provider order entry in rural EDs. ED computerized provider order entry adoption nearly tripled in Massachusetts from 2005 to 2008, before any financial inducements. Federal resources might be more effective if they helped providers select health information technology tools, improve health information technology design, and evaluate its influence on care delivery, versus simply calling for "more". [Ann Emerg Med. 2011;58:543-550.]
C1 [Pallin, Daniel J.; Landman, Adam B.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Pallin, Daniel J.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA.
[Sullivan, Ashley F.; Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Pallin, DJ (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA.
EM dpallin@partners.org
RI Pallin, Daniel/H-6382-2013;
OI Pallin, Daniel/0000-0002-8517-9702; Landman, Adam/0000-0002-2166-0521
NR 30
TC 4
Z9 4
U1 5
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD DEC
PY 2011
VL 58
IS 6
BP 543
EP 550
DI 10.1016/j.annemergmed.2011.05.015
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA 864GI
UT WOS:000298224600011
PM 21802779
ER
PT J
AU Gabayan, GZ
Derose, SF
Asch, SM
Yiu, S
Lancaster, EM
Poon, KT
Hoffman, JR
Sun, BC
AF Gabayan, Gelareh Z.
Derose, Stephen F.
Asch, Steven M.
Yiu, Sau
Lancaster, Elizabeth M.
Poon, K. Trudy
Hoffman, Jerome R.
Sun, Benjamin C.
TI Patterns and Predictors of Short-Term Death After Emergency Department
Discharge
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Article
ID STAGE RENAL-DISEASE; AFTER-DISCHARGE; CARDIOVASCULAR-DISEASE;
OLDER-ADULTS; DATA SYSTEM; ALL-CAUSE; MORTALITY; COMORBIDITY; DIAGNOSIS;
SURVIVAL
AB Study objective: The emergency department (ED) is an inherently high-risk setting. Early death after an ED evaluation is a rare and devastating outcome; understanding it can potentially help improve patient care and outcomes. Using administrative data from an integrated health system, we describe characteristics and predictors of patients who experienced 7-day death after ED discharge.
Methods: Administrative data from 12 hospitals were used to identify death after discharge in adults aged 18 year or older within 7 days of ED presentation from January 1, 2007, to December 31, 2008. Patients who were nonmembers of the health system, in hospice care, or treated at out-of-network EDs were excluded. Predictors of 7-day postdischarge death were identified with multivariable logistic regression.
Results: The study cohort contained a total of 475,829 members, with 728,312 discharges from Kaiser Permanente Southern California EDs in 2007 and 2008. Death within 7 days of discharge occurred in 357 cases (0.05%). Increasing age, male sex, and number of preexisting comorbidities were associated with increased risk of death. The top 3 primary discharge diagnoses predictive of 7-day death after discharge included noninfectious lung disease (odds ratio [OR] 7.1; 95% confidence interval [Cl] 2.9 to 17.4), renal disease (OR 5.6; 95% Cl 2.2 to 14.2), and ischemic heart disease (OR 3.8; 95% Cl 1.0 to 13.6).
Conclusion: Our study suggests that 50 in 100,000 patients in the United States die within 7 days of discharge from an ED. To our knowledge, our study is the first to identify potentially "high-risk" discharge diagnoses in patients who experience a short-term death after discharge. [Ann Emerg Med. 2011;58:551-558.]
C1 [Gabayan, Gelareh Z.; Asch, Steven M.; Sun, Benjamin C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Gabayan, Gelareh Z.; Asch, Steven M.; Sun, Benjamin C.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Med, Los Angeles, CA USA.
[Gabayan, Gelareh Z.; Lancaster, Elizabeth M.] Ronald Reagan UCLA, Ctr Emergency Med, Los Angeles, CA USA.
[Derose, Stephen F.; Yiu, Sau; Lancaster, Elizabeth M.; Poon, K. Trudy] Kaiser Permanente So Calif, Div Res & Evaluat, Pasadena, CA USA.
[Hoffman, Jerome R.] Univ So Calif, Dept Emergency Med, Los Angeles, CA USA.
RP Gabayan, GZ (reprint author), Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
EM gelareh@gabayan.com
FU Kaiser Permanente Southern California; UCLA Oppenheimer Foundation;
Greater Los Angeles Veterans Affairs Department of Health Services
Research and Development; UCLA Older Americans Independence Center,
NIH/NIA [P30-AG028748]; Emergency Medicine Foundation [59668]
FX By Annals policy, all authors are required to disclose any and all
commercial, financial, and other relationships in any way related to the
subject of this article as per ICMJE conflict of interest guidelines
(see www.icmje.org). The authors have stated that no such relationships
exist. This research was supported by Kaiser Permanente Southern
California and the UCLA Oppenheimer Foundation. During the initial phase
of this project Dr. Gabayan received support from the Greater Los
Angeles Veterans Affairs Department of Health Services Research and
Development. Continued support was obtained from the Emergency Medicine
Foundation Career Development Award (59668: G. Gabayan). Dr. Sun
received support from the UCLA Older Americans Independence Center,
NIH/NIA grant P30-AG028748, and the content does not necessarily
represent the official views of the National Institute on Aging or the
National Institutes of Health.
NR 34
TC 18
Z9 18
U1 2
U2 12
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD DEC
PY 2011
VL 58
IS 6
BP 551
EP 558
DI 10.1016/j.annemergmed.2011.07.001
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA 864GI
UT WOS:000298224600012
PM 21802775
ER
PT J
AU Viswanathan, A
Greenberg, SM
AF Viswanathan, Anand
Greenberg, Steven M.
TI Cerebral amyloid angiopathy in the elderly
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID BLOOD-BRAIN-BARRIER; TRANSGENIC MOUSE MODEL; PITTSBURGH COMPOUND-B;
RECURRENT INTRACEREBRAL HEMORRHAGE; APOLIPOPROTEIN-E EPSILON-2;
WHITE-MATTER LESIONS; ALZHEIMERS-DISEASE; BETA-PEPTIDE;
CEREBROSPINAL-FLUID; VASCULAR DEMENTIA
AB Cerebral amyloid angiopathy (CAA) results from deposition of beta-amyloid in the media and adventitia of small arteries and capillaries of the leptomeninges and cerebral cortex and is a major cause of lobar intracerebral hemorrhage and cognitive impairment in the elderly. CAA is associated with a high prevalence of magnetic resonance imaging markers of small vessel disease, including cerebral microbleeds and white matter hyperintensities. Although advanced CAA is present in approximately 1/4 of brains with Alzheimer disease (AD), fewer than half of CAA cases meet pathologic criteria for AD. This review will discuss the pathophysiology of CAA and focus on new imaging modalities and laboratory biomarkers that may aid in the clinical diagnosis of individuals with the disease. ANN NEUROL 2011;70:871880
C1 [Viswanathan, Anand] Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Stroke Serv, Dept Neurol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Viswanathan, A (reprint author), Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Stroke Serv, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA.
EM aviswanathan1@partners.org
FU NIA NIH HHS [K23 AG028726, P50 AG005134]
NR 141
TC 156
Z9 166
U1 10
U2 31
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 DEC
PY 2011
VL 70
IS 6
BP 871
EP 880
DI 10.1002/ana.22516
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 865TD
UT WOS:000298332300005
PM 22190361
ER
PT J
AU van Es, MA
Schelhaas, HJ
van Vught, PWJ
Ticozzi, N
Andersen, PM
Groen, EJN
Schulte, C
Blauw, HM
Koppers, M
Diekstra, FP
Fumoto, K
LeClerc, AL
Keagle, P
Bloem, BR
Scheffer, H
van Nuenen, BFL
van Blitterswijk, M
van Rheenen, W
Wills, AM
Lowe, PP
Hu, GF
Yu, WH
Kishikawa, H
Wu, D
Folkerth, RD
Mariani, C
Goldwurm, S
Pezzoli, G
Van Damme, P
Lemmens, R
Dahlberg, C
Birve, A
Fernandez-Santiago, R
Waibel, S
Klein, C
Weber, M
van der Kooi, AJ
de Visser, M
Verbaan, D
van Hilten, JJ
Heutink, P
Hennekam, EAM
Cuppen, E
Berg, D
Brown, RH
Silani, V
Gasser, T
Ludolph, AC
Robberecht, W
Ophoff, RA
Veldink, JH
Pasterkamp, RJ
de Bakker, PIW
Landers, JE
van de Warrenburg, BP
van den Berg, LH
AF van Es, Michael A.
Schelhaas, Helenius J.
van Vught, Paul W. J.
Ticozzi, Nicola
Andersen, Peter M.
Groen, Ewout J. N.
Schulte, Claudia
Blauw, Hylke M.
Koppers, Max
Diekstra, Frank P.
Fumoto, Katsumi
LeClerc, Ashley Lyn
Keagle, Pamela
Bloem, Bastiaan R.
Scheffer, Hans
van Nuenen, Bart F. L.
van Blitterswijk, Marka
van Rheenen, Wouter
Wills, Anne-Marie
Lowe, Patrick P.
Hu, Guo-fu
Yu, Wenhao
Kishikawa, Hiroko
Wu, David
Folkerth, Rebecca D.
Mariani, Claudio
Goldwurm, Stefano
Pezzoli, Gianni
Van Damme, Philip
Lemmens, Robin
Dahlberg, Caroline
Birve, Anna
Fernandez-Santiago, Ruben
Waibel, Stefan
Klein, Christine
Weber, Markus
van der Kooi, Anneke J.
de Visser, Marianne
Verbaan, Dagmar
van Hilten, Jacobus J.
Heutink, Peter
Hennekam, Eric A. M.
Cuppen, Edwin
Berg, Daniela
Brown, Robert H., Jr.
Silani, Vincenzo
Gasser, Thomas
Ludolph, Albert C.
Robberecht, Wim
Ophoff, Roel A.
Veldink, Jan H.
Pasterkamp, R. Jeroen
de Bakker, Paul I. W.
Landers, John E.
van de Warrenburg, Bart P.
van den Berg, Leonard H.
TI Angiogenin variants in Parkinson disease and amyotrophic lateral
sclerosis
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; K17I ANG MUTATION; PROTECTS MOTONEURONS;
GENE-MUTATIONS; ALS; DEMENTIA; SUSCEPTIBILITY; EPIDEMIOLOGY;
HERITABILITY; SURVIVAL
AB Objective: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.
Methods: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios.
Results: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects ( p = 9.3 x 10(-6) for ALS and p = 4.3 x 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD.
Interpretation: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD. ANN NEUROL 2011; 70: 964-973
C1 [van Es, Michael A.; van Vught, Paul W. J.; Groen, Ewout J. N.; Blauw, Hylke M.; Koppers, Max; Diekstra, Frank P.; van Blitterswijk, Marka; van Rheenen, Wouter; Veldink, Jan H.; van den Berg, Leonard H.] Univ Med Ctr Utrecht, Dept Neurol, Rudolf Magnus Inst Neurosci, NL-3584 CX Utrecht, Netherlands.
[Schelhaas, Helenius J.; Bloem, Bastiaan R.; van Nuenen, Bart F. L.; Cuppen, Edwin; van de Warrenburg, Bart P.] Radboud Univ Nijmegen, Med Ctr, Ctr Neurosci, Dept Neurol,Donders Instute Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands.
[Ticozzi, Nicola; LeClerc, Ashley Lyn; Keagle, Pamela; Lowe, Patrick P.; Brown, Robert H., Jr.; Landers, John E.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA.
[Ticozzi, Nicola; Silani, Vincenzo] IRCCS Ist Auxol Italiano, Dept Neurol, Milan, Italy.
[Ticozzi, Nicola; Silani, Vincenzo] IRCCS Ist Auxol Italiano, Neurosci Lab, Milan, Italy.
[Andersen, Peter M.; Dahlberg, Caroline; Birve, Anna; Cuppen, Edwin] Umea Univ Hosp, Inst Clin Neurosci, S-90185 Umea, Sweden.
[Schulte, Claudia; Gasser, Thomas] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany.
[Schulte, Claudia; Gasser, Thomas] German Ctr Neurodegenerat Dis, Tubingen, Germany.
[Fumoto, Katsumi; Fernandez-Santiago, Ruben; Berg, Daniela; Pasterkamp, R. Jeroen] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurosci & Pharmacol, NL-3584 CX Utrecht, Netherlands.
[Scheffer, Hans] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Wills, Anne-Marie] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Hu, Guo-fu; Kishikawa, Hiroko] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Yu, Wenhao; Wu, David; Folkerth, Rebecca D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Mariani, Claudio; Goldwurm, Stefano; Pezzoli, Gianni] Ist Clin Perfezionamento, Parkinson Inst, Milan, Italy.
[Van Damme, Philip; Lemmens, Robin; Robberecht, Wim] Univ Louvain, Louvain, Belgium.
[Van Damme, Philip; Lemmens, Robin; Robberecht, Wim] VIB, Vesalius Res Ctr, Louvain, Belgium.
[Van Damme, Philip; Lemmens, Robin; Robberecht, Wim] Univ Louvain, Univ Hosp Leuven, Dept Neurol, Louvain, Belgium.
[Fernandez-Santiago, Ruben] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer, Dept Clin & Expt Neurol, Barcelona, Spain.
[Fernandez-Santiago, Ruben] Univ Tubingen, Grad Training Ctr Neurosci, Int Max Planck Res Sch, Grad Sch Cellular & Mol Neurosci, Tubingen, Germany.
[Waibel, Stefan; Ludolph, Albert C.] Univ Ulm, Dept Neurol, D-7900 Ulm, Germany.
[Klein, Christine] Univ Lubeck, Dept Neurol, Sect Clin & Mol Neurogenet, Lubeck, Germany.
[Weber, Markus] Kantonsspital, Neuromuscular Dis Unit, St Gallen, Switzerland.
[van der Kooi, Anneke J.; de Visser, Marianne] Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands.
[Verbaan, Dagmar; van Hilten, Jacobus J.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands.
[Heutink, Peter] Vrije Univ Amsterdam Med Ctr, Sect Med Genom, Dept Clin Genet, Amsterdam, Netherlands.
[Hennekam, Eric A. M.; Cuppen, Edwin; Ophoff, Roel A.; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CX Utrecht, Netherlands.
Royal Netherlands Acad Sci, Canc Genom Ctr, Hubrecht Inst Dev Biol & Stem Cell Res, Utrecht, Netherlands.
[Silani, Vincenzo] Univ Milan, Sch Med, Dept Neurol, Dino Ferrari Ctr, Milan, Italy.
[Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA.
[de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA.
[de Bakker, Paul I. W.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA USA.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3584 CX Utrecht, Netherlands.
RP van den Berg, LH (reprint author), Univ Med Ctr Utrecht, Dept Neurol, Rudolf Magnus Inst Neurosci, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.
EM B.vandeWarrenburg@neuro.umcn.nl; l.h.vandenberg@umcutrecht.nl
RI Van Damme, Philip/A-6464-2009; Scheffer, Hans/E-4644-2012; Bloem,
Bastiaan/E-3812-2010; Ticozzi, Nicola/K-8094-2016; Groen,
Ewout/L-5081-2016; Goldwurm, Stefano/Q-8978-2016; van Blitterswijk,
Marka/H-7274-2012; Cuppen, Edwin/F-5696-2011; de Bakker,
Paul/B-8730-2009; Bloem, B.R./H-8013-2014; van de Warrenburg,
Bart/D-1935-2010; Fernandez-Santiago, Ruben/K-3808-2014; Cuppen,
Edwin/H-2389-2016
OI Koppers, Max/0000-0002-7751-1082; Ingre, Caroline/0000-0001-5327-7204;
Silani, Vincenzo/0000-0002-7698-3854; Schulte,
Claudia/0000-0003-4006-1265; Pasterkamp, Jeroen/0000-0003-1631-6440; Van
Damme, Philip/0000-0001-6384-0611; Scheffer, Hans/0000-0002-2986-0915;
Ticozzi, Nicola/0000-0001-5963-7426; Groen, Ewout/0000-0002-2330-9444;
Goldwurm, Stefano/0000-0002-1651-567X; van Blitterswijk,
Marka/0000-0002-3054-7053; Cuppen, Edwin/0000-0002-0400-9542; de Bakker,
Paul/0000-0001-7735-7858; Fernandez-Santiago, Ruben/0000-0002-4582-0702;
Cuppen, Edwin/0000-0002-0400-9542
FU NIA NIH HHS [5P50AG005134-27]; NIMH NIH HHS [R01MH084676]; NINDS NIH HHS
[5U10NS053369-05, R01 NS050557, 1R01NS065847]; Telethon [GTB07001]
NR 50
TC 72
Z9 75
U1 2
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
EI 1531-8249
J9 ANN NEUROL
JI Ann. Neurol.
PD DEC
PY 2011
VL 70
IS 6
BP 964
EP 973
DI 10.1002/ana.22611
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 865TD
UT WOS:000298332300014
PM 22190368
ER
PT J
AU Susarla, SM
Swanson, E
Gordon, CR
AF Susarla, Srinivas M.
Swanson, Edward
Gordon, Chad R.
TI Craniomaxillofacial Reconstruction Using Allotransplantation and Tissue
Engineering Challenges, Opportunities, and Potential Synergy
SO ANNALS OF PLASTIC SURGERY
LA English
DT Article
DE craniomaxillofacial reconstruction; composite tissue
allotransplantation; tissue engineering; maxillofacial allograft; face
transplant; craniofacial surgery
ID PERIPHERAL-NERVE REGENERATION; BONE-MARROW-TRANSPLANTATION;
SKELETAL-MUSCLE TISSUE; STEM-CELLS; FACE TRANSPLANTATION; FACIAL
TRANSPLANTATION; AURICULAR RECONSTRUCTION; MIXED CHIMERISM;
ADIPOSE-TISSUE; IN-VIVO
AB The face is composed of an intricate underlying bony/cartilaginous framework that supports muscle, secretory organs, and sophisticated skin/subcutaneous structures. These components are attached through numerous ligaments and interact dynamically with a vast neurovascular network. The most sophisticated autologous reconstructive techniques, utilizing composite free-tissue flaps, are often inadequate to restore extensive maxillofacial defects. Massive craniomaxillofacial (CMF) defects resulting from trauma, oncologic resection, or congenital deformity present a unique challenge to reconstructive surgeons. Therefore, recent advances in craniofacial surgery and immunotherapy spurred the innovation of composite tissue allotransplantation (CTA), which permits reconstruction with tissue composed of all necessary components. However, CMF allotransplantation carries with it side effects of lifelong immunosuppression. Furthermore, the donor skeletal framework may not provide an ideal match, resulting in less than ideal occlusion and soft-tissue anthropometrics. An alternative to transplantation, tissue engineering, has provided hope for regenerating missing tissue and avoiding the need for immunosuppression. Many tissue subtypes, including bone and cartilage, have been successfully created, with sparse reports of clinical application. Tissue-engineered composite tissue required for complete CMF reconstruction continues to elude development, with vascular supply and tissue interactions posing the largest remaining obstacles. We report herein the current status and limitations of CTA and tissue engineering. Furthermore, we describe for the first time our vision of hybridization of CTA and engineering, utilizing the strengths of each strategy.
C1 [Gordon, Chad R.] Johns Hopkins Univ, Dept Plast & Reconstruct Surg, Sch Med, Baltimore, MD 21287 USA.
[Swanson, Edward; Gordon, Chad R.] Harvard Univ, Div Plast & Reconstruct Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Susarla, Srinivas M.] Harvard Univ, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Gordon, CR (reprint author), Johns Hopkins Univ, Dept Plast & Reconstruct Surg, Sch Med, JHOC 8152F,601 N Caroline St, Baltimore, MD 21287 USA.
EM cgordon@hjmi.edu
OI Susarla, Srinivas/0000-0003-0155-8260
NR 85
TC 9
Z9 10
U1 0
U2 20
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-7043
J9 ANN PLAS SURG
JI Ann. Plast. Surg.
PD DEC
PY 2011
VL 67
IS 6
BP 655
EP 661
DI 10.1097/SAP.0b013e31822c00e6
PG 7
WC Surgery
SC Surgery
GA 862JB
UT WOS:000298085900031
PM 21825966
ER
PT J
AU Asgari, MM
Warton, EM
Neugebauer, R
Chren, MM
AF Asgari, Maryam M.
Warton, E. Margaret
Neugebauer, Romain
Chren, Mary-Margaret
TI Predictors of Patient Satisfaction With Mohs Surgery Analysis of
Preoperative, Intraoperative, and Postoperative Factors in a Prospective
Cohort
SO ARCHIVES OF DERMATOLOGY
LA English
DT Article
ID CAUSAL DIAGRAMS; BREAST-CANCER; SKIN-CANCER; LIFE; CARE; MORBIDITY;
KNOWLEDGE; OUTCOMES
AB Objective: To identify preoperative, intraoperative, and postoperative variables that predict higher short-and long-term patient satisfaction with Mohs surgery.
Design: Prospective cohort study.
Setting: A university-based dermatology practice and the affiliated Veterans Affairs medical center dermatology clinic.
Patients: A total of 339 consecutive patients treated with Mohs surgery in 1999 and 2000.
Main Outcome Measures: Short-term satisfaction at 1 week and long-term satisfaction at 1 year. We used directed acyclic graphs to determine appropriate confounding adjustment for preoperative, intraoperative, and postoperative variables that influence satisfaction with Mohs surgery in logistic regression models.
Results: Better preoperative skin-related quality of life (measured using Skindex) and more intraoperative Mohs stages were the most salient predictors of higher short-and long-term satisfaction; these odds ratios (ORs) were 2.33 (95% CI, 1.01-5.35) and 5.19 (1.66-16.29), respectively, for preoperative skin-related quality of life and 7.06 (2.02-24.67) and 5.30 (1.24-22.64), respectively, for more intraoperative Mohs stages. Patients not bothered by postoperative bleeding were more likely to be satisfied short term (OR, 2.25; 95% CI, 1.25-4.05), as were those who considered themselves involved in decision making about their treatment (3.05; 1.52-6.10). Higher long-term satisfaction with Mohs surgery was observed among patients who were married (2.36; 1.10-5.09).
Conclusions: Higher short-and long-term satisfaction with Mohs surgery is predicted by better preoperative skin-related quality of life and by more intraoperative Mohs stages. The effect of postoperative variables wanes over time, suggesting that factors influencing satisfaction can vary depending on the time frame when satisfaction is measured. Our results may help clinicians identify patients who are at higher risk of dissatisfaction following Mohs surgery.
C1 [Asgari, Maryam M.; Warton, E. Margaret; Neugebauer, Romain] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA.
[Asgari, Maryam M.; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Chren, Mary-Margaret] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA.
RP Asgari, MM (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA.
EM maryam.m.asgari@kp.org
RI Asgari, Maryam/O-4947-2016
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
[K23 AR 051037, K24 AR052667]; Health Services Research and Development
Service, Department of Veterans Affairs [IIR 04-043-3]
FX This study was supported in part by grants K23 AR 051037 (Dr Asgari) and
K24 AR052667 (Dr Chren) from the National Institute of Arthritis and
Musculoskeletal and Skin Diseases and by grant IIR 04-043-3 (Dr Chren)
from the Health Services Research and Development Service, Department of
Veterans Affairs.
NR 35
TC 5
Z9 5
U1 1
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-987X
J9 ARCH DERMATOL
JI Arch. Dermatol.
PD DEC
PY 2011
VL 147
IS 12
BP 1387
EP 1394
PG 8
WC Dermatology
SC Dermatology
GA 864QV
UT WOS:000298255800005
PM 22184760
ER
PT J
AU Shargorodsky, J
Curhan, SG
Henderson, E
Eavey, R
Curhan, GC
AF Shargorodsky, Josef
Curhan, Sharon G.
Henderson, Elisabeth
Eavey, Roland
Curhan, Gary C.
TI Heavy Metals Exposure and Hearing Loss in US Adolescents
SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; BLOOD LEAD LEVELS; 3RD NATIONAL-HEALTH;
UNITED-STATES; BRAIN-STEM; CHILDREN 6; PREVALENCE; IMPAIRMENT; RISK; AGE
AB Introduction: Hearing loss is common and, in young persons, can compromise social development and educational achievement. Exposure to heavy metals has been proposed as an important risk factor for hearing loss.
Methods: We evaluated the cross-sectional associations between blood lead, blood mercury, and urinary cadmium and arsenic levels and audiometrically determined hearing loss in participants aged 12 to 19 years in the 2005-2008 National Health and Nutrition Examination Survey after accounting for the complex survey design. There were 2535 individuals available for analysis of blood lead and mercury levels, 878 for urinary cadmium levels, and 875 for urinary arsenic levels. Multivariate logistic regression was used to calculate adjusted odds ratios (ORs) and 95% CIs.
Results: A blood lead level greater than or equal to 2 mu g/dL (to convert to micromoles per liter, multiply by 0.0483) compared with less than 1 rho g/dL was associated with increased odds of high-frequency hearing loss (OR, 2.22; 95% CI, 1.39-3.56). Individuals in the highest quartile of urinary cadmium levels had significantly higher odds of low-frequency hearing loss than those in the lowest quartile (OR, 3.08; 95% CI, 1.02-9.25). There was no overall association between quartiles of blood mercury or urinary arsenic levels and hearing loss.
Conclusion: Blood lead levels well below the current recommended action level are associated with substantially increased odds of high-frequency hearing loss.
C1 [Shargorodsky, Josef; Curhan, Sharon G.; Curhan, Gary C.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Curhan, Gary C.] Brigham & Womens Hosp, Div Renal, Dept Med, Boston, MA 02115 USA.
[Shargorodsky, Josef] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Henderson, Elisabeth] Harvard Univ, Sch Med, Boston, MA USA.
[Eavey, Roland] Vanderbilt Univ, Sch Med, Vanderbilt Bill Wilkerson Ctr Otolaryngol & Commu, Nashville, TN 37212 USA.
[Curhan, Gary C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Shargorodsky, J (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA.
EM Josef_Shargorodsky@meei.harvard.edu
FU Massachusetts Eye and Ear Infirmary Foundation; Vanderbilt University
School of Medicine
FX This work was supported in part by the Massachusetts Eye and Ear
Infirmary Foundation and by Vanderbilt University School of Medicine
Development Funds.
NR 39
TC 9
Z9 9
U1 0
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0886-4470
J9 ARCH OTOLARYNGOL
JI Arch. Otolaryngol. Head Neck Surg.
PD DEC
PY 2011
VL 137
IS 12
BP 1177
EP 1183
PG 7
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 864SN
UT WOS:000298260500001
ER
PT J
AU Kim, SW
Kauvanough, K
Orbach, DB
Alomari, AI
Mulliken, JB
Rahbar, R
AF Kim, Sang W.
Kauvanough, Katie
Orbach, Darren B.
Alomari, Ahmad I.
Mulliken, John B.
Rahbar, Reza
TI Long-term Outcome of Radiofrequency Ablation for Intraoral Microcystic
Lymphatic Malformation
SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article
ID LYMPHANGIOMAS; TONGUE; HEAD; NECK
AB Objective: To determine long-term outcome of radiofrequency (RF) ablation of microcystic lymphatic malformation (LM) of the oral cavity for control of recurrent infection and bleeding.
Design: Institutional review board-approved retrospective study,
Setting: Tertiary pediatric medical center,
Patients: Twenty-six patients with intraoral microcystic LM were treated with RF ablation from August 2002 through August 2010.
Intervention: Radiofrequency ablation of intraoral LM.
Main Outcome Measures: Postoperative stay, diet, pain; control of bleeding and/or infection; recurrence; and indication for retreatment.
Results: The most common complaints necessitating initial RF ablation were recurrent infection (n=10 [37%]) and bleeding (n=9 [33%]). The most common problems requiring further ablation were bleeding (n=11 [41%]) and cosmetic deformity not affecting function (n=8 [31%]). Fourteen patients (55%) were discharged home on postoperative day (POD) 3; the remaining 11 (45%) were discharged home on POD 4. Thirteen patients (52%) resumed oral diet immediately on the day of the procedure. Ten patients (38%) began eating on POD 1, and virtually every patient was on full oral intake at discharge. Fourteen patients (55%) required only acetaminophen for pain control, 11 (41%) required acetaminophen with codeine, and 1 (4%) required oxycodone. The mean follow-up time was 47 months after treatment. At the most recent clinic evaluation, 13 patients (50%) were symptom free, 8 (31%) were stable and improved without need for future treatment, and 5 (19%) required further treatment. One-half of patients in the study group underwent more than 1 RF procedure for recurrence. The number of RF ablations in this series were 1 procedure (n=13), 2 procedures (n=7), 3 procedures (n=2), 4 procedures (n=2), and 6 or 7 procedures (n=2).
Conclusions: Radiofrequency ablation is an effective treatment for localized, superficial microcystic LM in the oral cavity. Pediatric patients tolerate the treatment with rapid postoperative recovery and minimal complications. The majority of patients required a short hospital stay for observation of the airway. Virtually every patient resumed oral diet by the time of discharge. Radiofrequency ablation is the treatment of choice at Children's Hospital Boston (CHB) for patients who present with symptomatic, superficial, and localized intraoral microcystic LM. For lesions involving deeper structures, multimodal treatments including surgical and sclerotherapy may be necessary.
C1 [Kim, Sang W.; Kauvanough, Katie; Rahbar, Reza] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, Boston, MA 02115 USA.
[Orbach, Darren B.; Alomari, Ahmad I.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Vasc & Intervent Radiol, Boston, MA 02115 USA.
[Mulliken, John B.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Plast Surg, Boston, MA 02115 USA.
[Mulliken, John B.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Surg, Boston, MA 02115 USA.
[Kim, Sang W.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
RP Rahbar, R (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, 300 Longwood Ave,Ste LO367, Boston, MA 02115 USA.
EM reza.rahbar@childrens.harvard.edu
RI Orbach, Darren/M-5773-2013
OI Orbach, Darren/0000-0002-1793-3398
NR 14
TC 12
Z9 12
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0886-4470
J9 ARCH OTOLARYNGOL
JI Arch. Otolaryngol. Head Neck Surg.
PD DEC
PY 2011
VL 137
IS 12
BP 1247
EP 1250
PG 4
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 864SN
UT WOS:000298260500012
PM 22183906
ER
PT J
AU Maturo, SC
Braun, N
Brown, DJ
Chong, PST
Kerschner, JE
Hartnick, CJ
AF Maturo, Stephen C.
Braun, Nicole
Brown, David J.
Chong, Peter Siao Tick
Kerschner, Joseph E.
Hartnick, Christopher J.
TI Intraoperative Laryngeal Electromyography in Children With Vocal Fold
Immobility Results of a Multicenter Longitudinal Study
SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article
ID CORD PARALYSIS; THYROARYTENOID MUSCLES; CANINE MODEL; TRACHEOTOMY;
MANAGEMENT; RECOVERY
AB Objectives: To determine whether laryngeal electromyography (LEMG) can predict recurrent laryngeal nerve function return in children and whether LEMG can aid in the management of vocal fold immobility (VFI).
Design: Prospective case series.
Setting: Tertiary pediatric aerodigestive centers.
Patients: Twenty-five children aged 14 days to 7 years at the time of first LEMG (mean age, 21.4 months) with VFI who underwent flexible fiberoptic laryngeal examination, intraoperative LEMG of the thyroarytenoid muscles, and 12-month follow-up.
Main Outcome Measures: To compare results of LEMG with flexible fiberoptic laryngeal examination in children with vocal fold paresis and to determine if LEMG can predict vocal fold return.
Results: In children who had a patent ductus arteriosus ligation, the LEMG data suggest that if there is no activity 6 months after injury, then the nerve is unlikely to regain function. In 3 of 3 children with central causes of VFI, normal LEMG findings predicted return of nerve function 2 to 7 months before vocal fold movement on fiberoptic examination. Finally, in 3 of 3 children with idiopathic VFI, LEMG predicted return within 2 to 14 months of vocal folds with normal findings.
Conclusions: Intraoperative LEMG is a safe, easy-touse method for determining the likelihood of recurrent laryngeal nerve function return in children who have undergone patent ductus arteriosus ligation, in children with centrally correctable lesions, and in children with idiopathic VFI. More work is needed in the area of pediatric LEMG, but it is possible that LEMG data can be used to aid in management strategies and provide families with more information to make better informed decisions regarding their child's care.
C1 [Maturo, Stephen C.; Hartnick, Christopher J.] Harvard Univ, Dept Otolaryngol, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Brown, David J.; Kerschner, Joseph E.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Braun, Nicole; Brown, David J.; Kerschner, Joseph E.] Childrens Hosp Wisconsin, Dept Otolaryngol, Milwaukee, WI 53201 USA.
[Chong, Peter Siao Tick] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Hartnick, CJ (reprint author), Harvard Univ, Dept Otolaryngol, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM Christopher_hartnick@meei.harvard.edu
NR 29
TC 7
Z9 7
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0886-4470
J9 ARCH OTOLARYNGOL
JI Arch. Otolaryngol. Head Neck Surg.
PD DEC
PY 2011
VL 137
IS 12
BP 1251
EP 1257
PG 7
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 864SN
UT WOS:000298260500013
PM 22183907
ER
PT J
AU Rattner, DW
AF Rattner, David W.
TI The 0.9% Solution?
SO ARCHIVES OF SURGERY
LA English
DT Editorial Material
ID INTRAPERITONEAL NORMAL SALINE; LAPAROSCOPIC CHOLECYSTECTOMY;
POSTOPERATIVE PAIN; INFUSION
C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA.
EM drattner@partners.org
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0004-0010
J9 ARCH SURG-CHICAGO
JI Arch. Surg.
PD DEC
PY 2011
VL 146
IS 12
BP 1366
EP 1367
PG 2
WC Surgery
SC Surgery
GA 864RF
UT WOS:000298256900007
PM 22184294
ER
PT J
AU Lawson, EH
Gibbons, MM
Ingraham, AM
Shekelle, PG
Ko, CY
AF Lawson, Elise H.
Gibbons, Melinda Maggard
Ingraham, Angela M.
Shekelle, Paul G.
Ko, Clifford Y.
TI Appropriateness Criteria to Assess Variations in Surgical Procedure Use
in the United States
SO ARCHIVES OF SURGERY
LA English
DT Review
ID BYPASS GRAFT-SURGERY; UPPER GASTROINTESTINAL ENDOSCOPY; ACADEMIC
MEDICAL-CENTERS; HEALTH-CARE SERVICES; NEW-YORK-STATE;
CAROTID-ENDARTERECTOMY; CORONARY REVASCULARIZATION; PHYSICIAN RATINGS;
CARDIAC REVASCULARIZATION; PRACTICE GUIDELINES
AB Objectives: To systematically describe appropriateness criteria (AC) developed in the United States for surgical procedures and to summarize how these criteria have been applied to identify overuse and underuse of procedures in US populations.
Data Sources: MEDLINE literature search performed in February 2010 and May 2011.
Study Selection: Studies were included if they addressed the appropriateness of a surgical procedure using the RAND-UCLA Appropriateness Method. Non-US studies were excluded.
Data Extraction: Information was abstracted on study design, surgical procedure, and reported rates of appropriate use, overuse, and underuse. Identified AC were cross-referenced with lists of common procedures from the Nationwide Inpatient Sample and the State Ambulatory Surgery databases.
Data Synthesis: A total of 1601 titles were identified; 39 met the inclusion criteria. Of these, 17 developed AC and 27 applied AC to US populations. Appropriateness criteria have been developed for 16 surgical procedures. Underuse has only been studied for coronary artery bypass graft surgery, and rates range from 24% to 57%. Overuse has been more broadly studied, with rates ranging from 9% to 53% for carotid endarterectomy, 0% to 14% for coronary artery bypass graft, 11% to 24% for upper gastrointestinal tract endoscopy, and 16% to 70% for hysterectomy. Appropriateness criteria exist for 10 of the 25 most common inpatient procedures and 6 of the 15 top ambulatory procedures in the United States. Most studies are more than 5 years old.
Conclusions: Most existing AC are outdated, and AC have never been developed for most common surgical procedures. A broad and coordinated effort to develop and maintain AC would be required to implement this tool to address variation in the use of surgical procedures.
C1 [Lawson, Elise H.] Univ Calif Los Angeles, Med Ctr, Dept Surg, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Lawson, Elise H.; Ingraham, Angela M.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA.
[Gibbons, Melinda Maggard] Olive View UCLA Univ Calif Los Angeles, Dept Surg, Med Ctr, Sylmar, CA USA.
[Ingraham, Angela M.] Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45267 USA.
[Shekelle, Paul G.] RAND Hlth, Santa Monica, CA USA.
[Shekelle, Paul G.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Lawson, EH (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Surg, David Geffen Sch Med, CHS 72-215,10833 LeConte Ave, Los Angeles, CA 90095 USA.
EM elawson@mednet.ucla.edu
FU Robert Wood Johnson Foundation through the American College of Surgeons
FX Dr Lawson's time was supported by the Robert Wood Johnson Foundation
Clinical Scholars Program through the American College of Surgeons.
NR 60
TC 22
Z9 22
U1 1
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0004-0010
J9 ARCH SURG-CHICAGO
JI Arch. Surg.
PD DEC
PY 2011
VL 146
IS 12
BP 1433
EP 1440
PG 8
WC Surgery
SC Surgery
GA 864RF
UT WOS:000298256900025
PM 22184308
ER
PT J
AU Stone, RM
AF Stone, Richard M.
TI Should the presence of minimal residual disease (MRD) in morphologic
complete remission alter post-remission strategy in AML?
SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
LA English
DT Article
DE minimal residual disease; multiparameter flow (MPF); cytometry;
post-remission; acute myeloid leukemia; AML; FLT3-ITD
ID ACUTE MYELOID-LEUKEMIA; POLYMERASE-CHAIN-REACTION; ACUTE PROMYELOCYTIC
LEUKEMIA; STRATIFICATION
AB Minimal residual disease (MRD) monitoring, particularly via multiparameter flow (MPF) cytometry assessed after chemotherapy, has been very useful in the prognostic and therapeutic approach for children with acute lymphoblastic leukemia. While many studies suggest that MRD monitoring (using MPF or other techniques that are more sensitive than morphologic examination) might be able to accurately predict patient outcome, there is very little data suggesting that treatment decisions should be altered based on such measurements. Proving that MPF-defined MRD should prompt a change in treatment plan optimally requires a contemporaneous control group or at least a historical control treated in standard fashion. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Stone, Richard M.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Stone, Richard M.] Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02215 USA.
RP Stone, RM (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA.
EM rstone@partners.org
FU Novartis Pharmaceuticals Corporation
FX Contracted Research: Novartis Pharmaceuticals Corporation.
NR 16
TC 7
Z9 7
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1521-6926
J9 BEST PRACT RES CL HA
JI Best Pract. Res. Clin. Haematol.
PD DEC
PY 2011
VL 24
IS 4
BP 509
EP 514
DI 10.1016/j.beha.2011.09.006
PG 6
WC Hematology
SC Hematology
GA 867NV
UT WOS:000298462000004
PM 22127313
ER
PT J
AU Kuter, DJ
AF Kuter, David J.
TI What is the potential for thrombopoietic agents in acute leukemia?
SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
LA English
DT Article
DE thrombopoietin; leukemia; thrombocytopenia; chemotherapy
ID HUMAN MEGAKARYOCYTE GROWTH; ACUTE MYELOID-LEUKEMIA; DOSE-INTENSIVE
CHEMOTHERAPY; C-MPL LIGAND; DOUBLE-BLIND; PLATELET PRODUCTION; RECEPTOR
AGONIST; STIMULATION; ELTROMBOPAG; REGULATOR
AB In the 16 years since thrombopoietin was identified and cloned, much has been learned about its biochemistry, how it is regulated, and its involvement in a wide range of functions in a variety of cell lineages. The first generation of recombinant human thrombopoietins, rHuTPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), were shown to increase platelet counts in patients with immune thrombocytopenia, in platelet apheresis donors, and in patients receiving nonmyeloablative chemotherapy. Their effects in patients with acute myeloid leukemia (AML) showed no benefit at a wide range of doses and schedules. The two second-generation TPO mimetics approved by the US Food and Drug Administration (FDA) for the treatment of ITP, romiplostim and eltrombopag, are now being studied in a number of thrombocytopenic disorders including those due to chemotherapy and hepatitis C. Since romiplostim is comparable to the first-generation recombinant thrombopoietins, it may not be beneficial in AML treatment; however, given its novel mechanism of action, eltrombopag may be a TPO potentiator and if given at the proper time during chemotherapy, may enable AML patients to recover platelet counts sooner. (C) 2011 Elsevier Ltd. All rights reserved.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Kuter, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey 7940,55 Fruit St, Boston, MA 02114 USA.
EM kuter.david@mgh.harvard.edu
FU Amgen Inc.; GlaxoSmithKline; Ono Pharmaceutical Co. Ltd.; Shionogi Co.
Ltd.
FX Consulting Fees: Amgen Inc., GlaxoSmithKline, Ono Pharmaceutical Co.
Ltd., Shionogi & Co. Ltd.; Contracted Research: Amgen Inc.,
GlaxoSmithKline, Ono Pharmaceutical Co. Ltd., Shionogi & Co. Ltd.
NR 22
TC 8
Z9 8
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1521-6926
J9 BEST PRACT RES CL HA
JI Best Pract. Res. Clin. Haematol.
PD DEC
PY 2011
VL 24
IS 4
BP 553
EP 558
DI 10.1016/j.beha.2011.09.002
PG 6
WC Hematology
SC Hematology
GA 867NV
UT WOS:000298462000011
PM 22127320
ER
PT J
AU Keliher, EJ
Yoo, J
Nahrendorf, M
Lewis, JS
Marinelli, B
Newton, A
Pittet, MJ
Weissleder, R
AF Keliher, Edmund J.
Yoo, Jeongsoo
Nahrendorf, Matthias
Lewis, Jason S.
Marinelli, Brett
Newton, Andita
Pittet, Mikael J.
Weissleder, Ralph
TI Zr-89-Labeled Dextran Nanoparticles Allow in Vivo Macrophage Imaging
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID TUMOR-ASSOCIATED MACROPHAGES; BENZODIAZEPINE-RECEPTOR; CANCER; ANTIBODY;
BIODISTRIBUTION; INFLAMMATION; EXPRESSION; BEHAVIOR; TISSUES; CELLS
AB Tissue macrophages play a critical role both in normal physiology and in disease states. However, because of a lack of specific imaging agents, we continue to have a poor understanding of their absolute numbers, flux rates, and functional states in different tissues. Here, we describe a new macrophage specific positron emission tomography imaging agent, labeled with zirconium-89 (Zr-89), that was based on a cross-linked, short chain dextran nanoparticle (13 nm). Following systemic administration, the particle demonstrated a vascular half-life of 3.9 h and was found to be located primarily in tissue resident macrophages rather than other white blood cells. Subsequent imaging of the probe using a xenograft mouse model of cancer allowed for quantitation of tumor-associated macrophage numbers, which are of major interest in emerging molecular targeting strategies. It is likely that the material described, which allows the visualization of macrophage biology in vivo, will likewise be useful for a multitude of human applications.
C1 [Keliher, Edmund J.; Yoo, Jeongsoo; Nahrendorf, Matthias; Marinelli, Brett; Newton, Andita; Pittet, Mikael J.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Lewis, Jason S.] Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol & Chem, New York, NY 10065 USA.
[Lewis, Jason S.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA.
[Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Yoo, Jeongsoo] Kyungpook Natl Univ, Sch Med, Dept Mol Med, Taegu, South Korea.
RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA.
EM rweissleder@mgh.harvard.edu
FU National Institutes of Health [P50 CA86355, U54 CA126515, U54 CA151884,
HHSN268201000044C, U24 CA092782]
FX We acknowledge the help of Dr. Rainer Kohler for help with intravital
microscopy, Dr. Yvonne Fisher-Jeffes for review of the manuscript, and
Yoshiko Iwamoto for performing histology. We also thank Nicholas Ramos
(Memorial Sloan-Kettering Cancer Center) for 89Zr production.
This work was funded in part by National Institutes of Health Grants P50
CA86355, U54 CA126515, U54 CA151884, HHSN268201000044C, and U24
CA092782.
NR 37
TC 45
Z9 48
U1 1
U2 24
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD DEC
PY 2011
VL 22
IS 12
BP 2383
EP 2389
DI 10.1021/bc200405d
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 864FL
UT WOS:000298222300004
PM 22035047
ER
PT J
AU Liong, M
Fernandez-Suarez, M
Issadore, D
Min, C
Tassa, C
Reiner, T
Fortune, SM
Toner, M
Lee, H
Weissleder, R
AF Liong, Monty
Fernandez-Suarez, Marta
Issadore, David
Min, Changwook
Tassa, Carlos
Reiner, Thomas
Fortune, Sarah M.
Toner, Mehmet
Lee, Hakho
Weissleder, Ralph
TI Specific Pathogen Detection Using Bioorthogonal Chemistry and Diagnostic
Magnetic Resonance
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID IN-VIVO; CANCER-CELLS; COPPER-FREE; CYCLOADDITIONS; SENSITIVITY;
LIGATION
AB The development of faster and more sensitive detection methods capable of identifying specific bacterial species and strains has remained a longstanding clinical challenge. Thus to date, the diagnosis of bacterial infections continues to rely on the performance of time-consuming microbiological cultures. Here, we demonstrate the use of bioorthogonal chemistry for magnetically labeling specific pathogens to enable their subsequent detection by nuclear magnetic resonance. Antibodies against a bacterial target of interest were first modified with trans-cyclooctene and then coupled to tetrazine-modified magnetic nanoprobes, directly on the bacteria. This labeling method was verified by surface plasmon resonance as well as by highly specific detection of Staphylococcus aureus using a miniaturized diagnostic magnetic resonance system. Compared to other copper-free bioorthogonal chemistries, the cycloaddition reaction reported here displayed faster kinetics and yielded higher labeling efficiency. Considering the short assay times and the portability of the necessary instrumentation, it is feasible that this approach could be adapted for clinical use in resource-limited settings.
C1 [Liong, Monty; Issadore, David; Min, Changwook; Tassa, Carlos; Reiner, Thomas; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA.
[Fernandez-Suarez, Marta; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr, Boston, MA USA.
[Fernandez-Suarez, Marta; Fortune, Sarah M.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Lee, H (reprint author), Simches Res Ctr, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA.
EM hlee@mgh.harvard.edu; rweissleder@mgh.harvard.edu
RI Issadore, David/L-8451-2014;
OI Reiner, Thomas/0000-0002-7819-5480
FU NIBIB [R01-EB010011, R01-EB00462605A1, P41 EB002503]; NHLBI
[HHSN268201000044C]; NIH [T32CA79443]; United States Army Medical
Research Acquisition Activity [W81XWH-10-2-0161]; Massachusetts General
Hospital Executive Committee
FX We thank B. Akerley, M. Lipsitch, S. Lory, and C. Thompson for providing
the laboratory reference bacterial strains; S. Agasti, H. J. Chung, R
Gorbatov, J. B. Haun, M.}Carver, and N. Sergeyev for assistance with
experiments; Y. Fisher-Jeffes for reviewing the manuscript. This work
was supported in part by NIBIB grants R01-EB010011 (R.W.),
R01-EB00462605A1 (R.W.), P41 EB002503 (M.T.), NHLBI contract
HHSN268201000044C (R.W.), NIH grant T32CA79443 (R.W.), United States
Army Medical Research Acquisition Activity Grant W81XWH-10-2-0161
(S.M.F.), and the Massachusetts General Hospital Executive Committee on
Research fellowship (M.F.S.).
NR 25
TC 32
Z9 32
U1 2
U2 52
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD DEC
PY 2011
VL 22
IS 12
BP 2390
EP 2394
DI 10.1021/bc200490r
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 864FL
UT WOS:000298222300005
PM 22043803
ER
PT J
AU Uno, H
Cai, TX
Tian, L
Wei, LJ
AF Uno, Hajime
Cai, Tianxi
Tian, Lu
Wei, L. J.
TI Graphical Procedures for Evaluating Overall and Subject-Specific
Incremental Values from New Predictors with Censored Event Time Data
SO BIOMETRICS
LA English
DT Article
DE Discriminant analysis; Nonparametric function estimation; Prediction;
Receiver operating characteristic curve
ID GENE-EXPRESSION SIGNATURE; C-REACTIVE PROTEIN; BREAST-CANCER;
REGRESSION-MODELS; RISK PREDICTION; ROC CURVE; SURVIVAL; MARKER; AREA;
LIMITATIONS
AB Quantitative procedures for evaluating added values from new markers over a conventional risk scoring system for predicting event rates at specific time points have been extensively studied. However, a single summary statistic, for example, the area under the receiver operating characteristic curve or its derivatives, may not provide a clear picture about the relationship between the conventional and the new risk scoring systems. When there are no censored event time observations in the data, two simple scatterplots with individual conventional and new scores for cases and controls provide valuable information regarding the overall and the subject-specific level incremental values from the new markers. Unfortunately, in the presence of censoring, it is not clear how to construct such plots. In this article, we propose a nonparametric estimation procedure for the distributions of the differences between two risk scores conditional on the conventional score. The resulting quantile curves of these differences over the subject-specific conventional score provide extra information about the overall added value from the new marker. They also help us to identify a subgroup of future subjects who need the new predictors, especially when there is no unified utility function available for costriskbenefit decision making. The procedure is illustrated with two data sets. The first is from a well-known Mayo Clinic primary biliary cirrhosis liver study. The second is from a recent breast cancer study on evaluating the added value from a gene score, which is relatively expensive to measure compared with the routinely used clinical biomarkers for predicting the patients survival after surgery.
C1 [Uno, Hajime] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Uno, Hajime; Cai, Tianxi; Wei, L. J.] Harvard Univ, Dept Biostat, Boston, MA 02115 USA.
[Tian, Lu] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA.
RP Uno, H (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
EM wei@hsph.harvard.edu
FU National Institutes of Health [R01-AI052817, U54-LM008748, RC4-CA155940,
R01-GM079330]; Research Scientist Developmental Funds
FX The authors are grateful to the editor, associate editor, and the
reviewers for insightful comments on the article. This work was
supported in part by grants R01-AI052817, U54-LM008748, RC4-CA155940,
and R01-GM079330 from the National Institutes of Health. HU thanks the
Department of Biostatistics and Computational Biology, Dana Farber
Cancer Institute for the support from the Research Scientist
Developmental Funds.
NR 31
TC 6
Z9 6
U1 0
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD DEC
PY 2011
VL 67
IS 4
BP 1389
EP 1396
DI 10.1111/j.1541-0420.2011.01600.x
PG 8
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 862MN
UT WOS:000298095900022
PM 21504421
ER
PT J
AU Abou-Nassar, KE
Stevenson, KE
Antin, JH
McDermott, K
Ho, VT
Cutler, CS
LaCasce, AS
Jacobsen, ED
Fisher, DC
Soiffer, RJ
Alyea, EP
Koreth, J
Freedman, AS
AF Abou-Nassar, K. E.
Stevenson, K. E.
Antin, J. H.
McDermott, K.
Ho, V. T.
Cutler, C. S.
LaCasce, A. S.
Jacobsen, E. D.
Fisher, D. C.
Soiffer, R. J.
Alyea, E. P.
Koreth, J.
Freedman, A. S.
TI Y-90-ibritumomab tiuxetan followed by reduced-intensity conditioning and
allo-SCT in patients with advanced follicular lymphoma
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE follicular lymphoma; allogeneic hematopoietic SCT; radioimmunotherapy;
Y-90-ibritumomab tiuxetan
ID STEM-CELL TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; VERSUS-HOST-DISEASE;
BONE-MARROW-TRANSPLANTATION; IBRITUMOMAB TIUXETAN;
YTTRIUM-90-IBRITUMOMAB TIUXETAN; I-131 TOSITUMOMAB; RADIOIMMUNOTHERAPY;
SURVIVAL; BLOOD
AB Reduced-intensity conditioning (RIC) hematopoietic SCT (HSCT) is a potentially curative therapeutic option for patients with advanced follicular lymphoma (FL), but disease relapse remains the most common cause of failure. Radioimmunoconjugates administered before RIC allo-HSCT may enhance cytoreduction and allow more time for GVL effect to develop without the associated toxicity of a myeloablative HSCT. We performed a retrospective study to describe the outcomes of patients with relapsed, refractory or transformed FL who received yttrium-90 (Y-90)-ibritumomab tiuxetan followed by fludarabine and low-dose BU RIC allogeneic HSCT at the Dana-Farber Cancer Institute between 2006 and 2009, inclusively. Twelve patients were identified with a median age of 55 (40-66) years and a median number of lines of therapy of 5 (2-10). Two patients (17%) had transformed to a more aggressive histology and five (42%) had chemorefractory FL. Cumulative incidences of grade II-IV acute GVHD at 100 days were 17% (+/- 11%) and chronic GVHD at 12 months were 63% (+/- 19%). Two-year non-relapse mortality was 18% (+/- 12%). Two-year OS and PFS were 83% (+/- 11%) and 74% (+/- 13%), respectively. This treatment is associated with favorable outcomes including acceptable rates of GVHD and relapse in advanced FL patients, and warrants prospective studies. Bone Marrow Transplantation (2011) 46, 1503-1509; doi:10.1038/bmt.2010.339; published online 24 January 2011
C1 [Abou-Nassar, K. E.; Antin, J. H.; McDermott, K.; Ho, V. T.; Cutler, C. S.; LaCasce, A. S.; Jacobsen, E. D.; Fisher, D. C.; Soiffer, R. J.; Alyea, E. P.; Koreth, J.; Freedman, A. S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lymphoma Program, Boston, MA 02115 USA.
RP Freedman, AS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lymphoma Program, 44 Binney St, Boston, MA 02115 USA.
EM arnold_freedman@dfci.harvard.edu
FU NIH [CA142106]; Jock and Bunny Adams Research and Teaching Endowment;
NIH/NCI [CA92625]
FX This work was supported in part by NIH Grant CA142106 and the Jock and
Bunny Adams Research and Teaching Endowment. ASF is supported in part by
NIH/NCI P01 Grant CA92625.
NR 30
TC 8
Z9 8
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD DEC
PY 2011
VL 46
IS 12
BP 1503
EP 1509
DI 10.1038/bmt.2010.339
PG 7
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 865QX
UT WOS:000298326500002
PM 21258420
ER
PT J
AU Daly, KP
Colan, SD
Blume, ED
Margossian, R
Gauvreau, K
Duncan, C
Lehmann, LE
Chen, MH
AF Daly, K. P.
Colan, S. D.
Blume, E. D.
Margossian, R.
Gauvreau, K.
Duncan, C.
Lehmann, L. E.
Chen, M. H.
TI Changes in echocardiographic measures of systolic and diastolic function
in children 1 year after hematopoietic SCT
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE pediatrics; SCT; cardiac function; diastolic function
ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; TOTAL-BODY
IRRADIATION; VENTRICULAR EJECTION FRACTION; CARDIAC TOXICITY;
CARDIOVASCULAR-DISEASE; PREDICTIVE-VALUE; RISK-FACTORS; LEUKEMIA; GROWTH
AB Hematopoietic SCT (HSCT) is a life-saving therapy in children, but has been associated with heart failure. Little is known about subclinical changes in cardiac function. We examined changes in systolic and diastolic function from pre- to 1-year post HSCT by echocardiography. All patients (n = 74, 61% men, median age 9.1 years, mean left-ventricular (LV) ejection fraction 61.3 +/- 4.9%) who underwent HSCT at Children's Hospital Boston between 2005 and 2008, were <21 years at time of HSCT, and had routine pre- and 1-year post echocardiograms were included. Systolic function parameters, including LV ejection fraction, rate-corrected velocity of fiber shortening (Vcfc) and stress-velocity index and diastolic parameters, including tissue Doppler imaging (TDI)-derived velocities, and left-ventricular flow propagation, were compared before and after transplant. At 1-year post HSCT, systolic function, as measured by Vcfc (1.10 +/- 0.15 vs 1.04 +/- 0.12 circ/s; P = 0.03) and stress-velocity index (z-score 0.40 +/- 1.4 vs -0.20 +/- 1.1; P = 0.02), had worsened; diastolic function parameters, including mitral E' velocity (16.6 +/- 3.9 vs 15.0 +/- 3.4 cm/s; P - 0.01) and tricuspid E' velocity (14.3 +/- 3.6 vs 12.4 +/- 2.8 cm/s; P = 0.002) had also decreased. At 1-year post HSCT, children have subclinical declines in systolic and diastolic function. These small changes might become clinically important over time. Serial non-invasive assessment of cardiac function should be considered in all children following HSCT. Bone Marrow Transplantation (2011) 46, 1532-1539; doi:10.1038/bmt.2010.345; published online 31 January 2011
C1 [Daly, K. P.; Colan, S. D.; Blume, E. D.; Margossian, R.; Gauvreau, K.; Chen, M. H.] Childrens Hosp Boston, Dept Cardiol, Boston, MA 02115 USA.
[Daly, K. P.; Colan, S. D.; Blume, E. D.; Margossian, R.; Gauvreau, K.; Duncan, C.; Lehmann, L. E.; Chen, M. H.] Harvard Univ, Sch Med, Boston, MA USA.
[Duncan, C.; Lehmann, L. E.] Childrens Hosp Boston, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA.
[Duncan, C.; Lehmann, L. E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Daly, KP (reprint author), Childrens Hosp Boston, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA.
EM kevin.daly@childrens.harvard.edu
OI Daly, Kevin/0000-0003-4327-1532
FU NIH [T32 HL07572]; Children's Hospital Boston Department of Cardiology
FX Acknowledgment of research support: Dr Daly received salary support from
a NIH training grant (T32 HL07572) while working on this study. Dr Chen
is supported by the Children's Hospital Boston Department of Cardiology
Translational Fund for Research in Cardiac Oncology. Dr Blume is
supported by the Children's Hospital Boston Department of Cardiology
Heart Failure/Transplant Research Fund. Previously presented: Young
Investigator Oral Abstract Presentation, 2nd International Conference on
Cardiomyopathy in Children, 13 May, 2010 in Bethesda, MD, USA.
NR 34
TC 1
Z9 1
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD DEC
PY 2011
VL 46
IS 12
BP 1532
EP 1539
DI 10.1038/bmt.2010.345
PG 8
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 865QX
UT WOS:000298326500006
PM 21278798
ER
PT J
AU Garcia-Alloza, M
Gregory, J
Kuchibhotla, KV
Fine, S
Wei, Y
Ayata, C
Frosch, MP
Greenberg, SM
Bacskai, BJ
AF Garcia-Alloza, Monica
Gregory, Julia
Kuchibhotla, Kishore V.
Fine, Sara
Wei, Ying
Ayata, Cenk
Frosch, Matthew P.
Greenberg, Steven M.
Bacskai, Brian J.
TI Cerebrovascular lesions induce transient beta-amyloid deposition
SO BRAIN
LA English
DT Article
DE Alzheimer's disease pathology; stroke; amyloid
ID MILD COGNITIVE IMPAIRMENT; FOCAL CEREBRAL-ISCHEMIA; VASCULAR
RISK-FACTORS; BRAIN A-BETA; ALZHEIMERS-DISEASE; IN-VIVO;
APOLIPOPROTEIN-E; TRANSGENIC MICE; PRECURSOR PROTEIN; BLOOD-PRESSURE
AB Previous clinical studies have documented a close relationship between cerebrovascular disease and risk of Alzheimer's disease. We examined possible mechanistic interactions through use of experimental stroke models in a transgenic mouse model of beta-amyloid deposition (APPswe/PS1dE9). Following middle cerebral artery occlusion, we observed a rapid increase in amyloid plaque burden in the region surrounding the infarction. In human tissue samples, however, we were unable to detect a localized increase in amyloid burden adjacent to cerebral infarcts. To resolve this discrepancy, we generated cerebral microstrokes in amyloid precursor protein mouse models with the photosensitive dye Rose bengal, and monitored plaque formation in real time using multiphoton microscopy. We observed a striking increase in the number of new plaques and amyloid angiopathy in the area immediately surrounding the infarcted area; however, the effect was transient, potentially resolving the discord between mouse and human tissue. We did not detect changes in candidate proteins related to beta-amyloid generation or degradation such as beta-amyloid-converting enzyme, amyloid precursor protein, presenilin 1, neprylisin or insulin-degrading enzyme. Together, these results demonstrate that strokes can trigger accelerated amyloid deposition, most likely through interference with amyloid clearance pathways. Additionally, this study indicates that focal ischaemia provides an experimental paradigm in which to study the mechanisms of plaque seeding and growth.
C1 [Bacskai, Brian J.] Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Alzheimer Res Unit, Charlestown, MA 02129 USA.
[Garcia-Alloza, Monica; Gregory, Julia; Kuchibhotla, Kishore V.; Fine, Sara; Frosch, Matthew P.; Greenberg, Steven M.; Bacskai, Brian J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Garcia-Alloza, Monica] Univ Cadiz, Div Physiol, Sch Med, Cadiz 11003, Spain.
[Wei, Ying; Ayata, Cenk] Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Dept Radiol, Charlestown, MA 02129 USA.
[Ayata, Cenk] Massachusetts Gen Hosp, Intens Care Unit, Dept Neurol, Charlestown, MA 02129 USA.
[Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Dept Pathol, Boston, MA 02114 USA.
[Frosch, Matthew P.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Alzheimer Res Unit, 114 16th St,2010, Charlestown, MA 02129 USA.
EM bbacskai@partners.org
RI Gregory, Julia/K-8726-2012;
OI Garcia-Alloza, Monica/0000-0003-1610-4114
FU National Institutes of Health [EB00768, AG021084, AG005134];
L'oreal-UNESCO; PN I + D+ I; ISCIII Subdireccion General de Evaluacion y
Fomento de la Investigacion [PS09/00969]; [RYC-2008-02333]
FX National Institutes of Health (EB00768 to B.J.B.); (AG021084, AG005134
to M.P.F.); (RYC-2008-02333; L'oreal-UNESCO 2010; PN I + D+ I 2008-2011:
ISCIII Subdireccion General de Evaluacion y Fomento de la Investigacion
PS09/00969 to M.G.-A.).
NR 64
TC 14
Z9 14
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD DEC
PY 2011
VL 134
BP 3694
EP 3704
DI 10.1093/brain/awr300
PN 12
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 863TB
UT WOS:000298189800023
PM 22120142
ER
PT J
AU Thase, ME
Larsen, KG
Kennedy, SH
AF Thase, Michael E.
Larsen, Klaus G.
Kennedy, Sidney H.
TI Assessing the 'true' effect of active antidepressant therapy v. placebo
in major depressive disorder: use of a mixture model
SO BRITISH JOURNAL OF PSYCHIATRY
LA English
DT Article
ID ESCITALOPRAM; SEVERITY; TRIALS; TRAJECTORIES; METAANALYSIS; EFFICACY
AB Background
There is controversy about the implications of relatively small average drug-placebo differences observed in randomised controlled trials of antidepressant medications.
Aims
To investigate whether efficacy is better understood as a large effect in a subgroup of patients.
Method
The mixture model was used to identify patient subgroups (patients benefiting or not benefiting from treatment) to directly model the skewness of Montgomery-Asberg Depression Rating Scale (MADRS) scores at week 8.
Results
The MADRS scores improved by 15.9 points (95% CI 15.2-16.6) among patients who benefited from treatment. The proportion of patients who benefited from escitalopram and not from placebo treatment was 19.5%, corresponding to a number needed to treat of 5.
Conclusions
This model gave a considerably better fit to the data than the analysis of covariance model in which all patients were assumed to benefit from treatment. The small average antidepressant-placebo difference obscures a much larger effect in a clinically meaningful subgroup of patients.
C1 [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Larsen, Klaus G.] H Lundbeck & Co AS, Copenhagen, Denmark.
[Kennedy, Sidney H.] Univ Toronto, Toronto, ON, Canada.
RP Thase, ME (reprint author), Univ Penn, Sch Med, Suite 689,3535 Market St, Philadelphia, PA 19104 USA.
EM thase@mail.med.upenn.edu
FU Agency for Healthcare Research and Quality; Aldolor; Alkermes;
AstraZeneca; Bristol-Myers Squibb; Cephalon; Cyberonics; Dey
Pharmaceuticals; Eli Lilly; GlaxoSmithKline; Janssen Pharmaceutica;
MedAvante; Merck
FX M.E.T. is an advisor/consultant for H. Lundbeck A/S. During the past 5
years has been advisor/consultant for, and/or received research funding
and/or honoraria for talks from: the Agency for Healthcare Research and
Quality, Aldolor, Alkermes, AstraZeneca, Bristol-Myers Squibb, Cephalon,
Cyberonics, Dey Pharmaceuticals, Eli Lilly, Forest Laboratories
(including PGx), GlaxoSmithKline, Janssen Pharmaceutica, MedAvante,
Merck (including Organon and Schering-Plough), National Institute of
Mental Health, Neuronetics, Novartis, Otsuka, PamLab, Pfizer (including
Wyeth), Rexahn, Sanofi Aventis, Sepracor, Shire US, Takeda and
Transcept. He has equity holdings in MedAvante and has received income
from royalties from American Psychiatric Publishing, Guilford
Publications and Herald House. S.H.K has received grant funding and
consulting honoraria from H. Lundbeck A/S. In the past 5 years he has
also received grant funding or consulting honoraria from AstraZeneca,
Biovail, Boehringer-Ingelheim, Eli Lilly, GlaxoSmithKline,
Janssen-Ortho, Merck-Frosst, Organon, Pfizer, Servier and St Jude
Medical. K.G.L. is an employee of H. Lundbeck A/S.
NR 29
TC 27
Z9 27
U1 1
U2 7
PU ROYAL COLLEGE OF PSYCHIATRISTS
PI LONDON
PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG,
ENGLAND
SN 0007-1250
EI 1472-1465
J9 BRIT J PSYCHIAT
JI Br. J. Psychiatry
PD DEC
PY 2011
VL 199
IS 6
BP 501
EP 507
DI 10.1192/bjp.bp.111.093336
PG 7
WC Psychiatry
SC Psychiatry
GA 867FO
UT WOS:000298440500014
PM 22130749
ER
PT J
AU MacDonald, I
Miller, J
AF MacDonald, Ian
Miller, Joan
TI Genetic factors and AMD
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Editorial Material
ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION
C1 [MacDonald, Ian] Univ Alberta, Dept Ophthalmol, Edmonton, AB T6G 2M7, Canada.
[Miller, Joan] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Miller, Joan] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP MacDonald, I (reprint author), Royal Alexandra Hosp, Dept Ophthalmol, 10240 Kingsway Ave, Edmonton, AB T5H 3V9, Canada.
EM macdonal@ualberta.ca
OI MacDonald, Ian/0000-0001-7472-8385
NR 5
TC 1
Z9 1
U1 0
U2 2
PU CANADIAN OPHTHAL SOC
PI OTTAWA
PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA
SN 0008-4182
J9 CAN J OPHTHALMOL
JI Can. J. Opthalmol.-J. Can. Opthalmol.
PD DEC
PY 2011
VL 46
IS 6
BP 456
EP 456
DI 10.1016/j.jcjo.2011.09.024
PG 1
WC Ophthalmology
SC Ophthalmology
GA 875GE
UT WOS:000299017600002
PM 22153626
ER
PT J
AU Park, LS
Tate, JP
Justice, AC
Lo Re, V
Lim, JK
Brau, N
Brown, ST
Butt, AA
Gibert, C
Goetz, MB
Rimland, D
Rodriguez-Barradas, MC
Dubrow, R
AF Park, Lesley S.
Tate, Janet P.
Justice, Amy C.
Lo Re, Vincent, III
Lim, Joseph K.
Braeu, Norbert
Brown, Sheldon T.
Butt, Adeel A.
Gibert, Cynthia
Goetz, Matthew Bidwell
Rimland, David
Rodriguez-Barradas, Maria C.
Dubrow, Robert
TI FIB-4 Index Is Associated with Hepatocellular Carcinoma Risk in
HIV-Infected Patients
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID C VIRUS-INFECTION; DIABETES-MELLITUS; UNITED-STATES; HEPATITIS;
EPIDEMIOLOGY; COINFECTION; MORTALITY; CIRRHOSIS; FIBROSIS; OBESITY
AB Background: Chronic inflammation caused by hepatitis B virus infection, hepatitis Cvirus infection, and/or heavy alcohol use can lead to fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). FIB-4 is an index score calculated from platelet count, alanine transaminase, aspartate transaminase, and age that predicts fibrosis and cirrhosis. We hypothesized that high FIB-4 would be associated with development of HCC in HIV infected persons, who are at high risk due to high prevalence of viral hepatitis and alcohol consumption, and possibly due to HIV infection itself.
Methods: Using proportional hazards models, we tested this hypothesis among 22,980 HIV-infected men from the Veterans Aging Cohort Study. We identified incident HCC cases from the Veterans Affairs Central Cancer Registry.
Results: During follow-up, there were 112 incident HCC diagnoses. The age-and race/ethnic group adjusted HR was 4.2 [95% confidence interval (CI), 2.4-7.4] for intermediate FIB-4 and 13.0 (95% CI, 7.2-23.4) for high FIB-4, compared with low FIB-4. After further adjustment for enrollment year, CD4 count, HIV-1 RNA level, antiretroviral therapy use, hepatitis B and C virus infection, alcohol abuse/dependency, and diabetes, FIB-4 remained a strong, significant, independent risk factor for HCC. The multivariate-adjusted HR was 3.6 (95% CI, 2.1-6.4) for intermediate FIB-4 and 9.6 (95% CI, 5.2-17.4) for high FIB-4.
Conclusions: Calculated from routine, noninvasive laboratory tests, FIB-4 is a strong, independent HCC risk factor in HIV-infected patients. Impact: FIB-4 might prove valuable as an easily measured index to identify those at highest risk for HCC, even prior to development of clinical cirrhosis. Cancer Epidemiol Biomarkers Prev; 20(12); 2512-7. (C) 2011 AACR.
C1 [Park, Lesley S.; Tate, Janet P.; Justice, Amy C.; Lim, Joseph K.; Dubrow, Robert] Yale Univ, Sch Med, West Haven, CT 06516 USA.
[Dubrow, Robert] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Tate, Janet P.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA.
[Lo Re, Vincent, III] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Lo Re, Vincent, III] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Braeu, Norbert; Brown, Sheldon T.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
[Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA.
[Gibert, Cynthia] Washington DC Vet Affairs Med Ctr, Washington, DC USA.
[Goetz, Matthew Bidwell] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA.
[Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Rimland, David] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA.
[Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA.
[Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA.
RP Park, LS (reprint author), Yale Univ, Sch Med, 950 Campbell Ave,Bldg 35A, West Haven, CT 06516 USA.
EM lesley.park@yale.edu
RI Lo Re, Vincent/N-7817-2015;
OI Goetz, Matthew/0000-0003-4542-992X
FU NIH: National Institute on Alcohol Abuse and Alcoholism [U01-AA13566];
National Institute on Aging [R01-AG029154]; National Heart, Lung, and
Blood Institute [R01-HL095136, R01-HL090342, RCI-HL100347]; National
Institute of Allergy and Infectious Diseases [U01-AI069918]; National
Institute of Mental Health [P30-MH062294]; Veterans Health
Administration Office of Research and Development [VA REA 08-266];
Office of Academic Affiliations
FX This work was supported by NIH: National Institute on Alcohol Abuse and
Alcoholism (U01-AA13566); National Institute on Aging (R01-AG029154);
National Heart, Lung, and Blood Institute (R01-HL095136, R01-HL090342,
RCI-HL100347); National Institute of Allergy and Infectious Diseases
(U01-AI069918); National Institute of Mental Health (P30-MH062294); and
the Veterans Health Administration Office of Research and Development
(VA REA 08-266) and Office of Academic Affiliations (Medical Informatics
Fellowship).
NR 22
TC 21
Z9 21
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD DEC
PY 2011
VL 20
IS 12
BP 2512
EP 2517
DI 10.1158/1055-9965.EPI-11-0582
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 864JA
UT WOS:000298234900006
PM 22028407
ER
PT J
AU Dhillon, PK
Penney, KL
Schumacher, F
Rider, JR
Sesso, HD
Pollak, M
Fiorentino, M
Finn, S
Loda, M
Rifai, N
Mucci, LA
Giovannucci, E
Stampfer, MJ
Ma, J
AF Dhillon, Preet K.
Penney, Kathryn L.
Schumacher, Fredrick
Rider, Jennifer R.
Sesso, Howard D.
Pollak, Michael
Fiorentino, Michelangelo
Finn, Stephen
Loda, Massimo
Rifai, Nader
Mucci, Lorelei A.
Giovannucci, Edward
Stampfer, Meir J.
Ma, Jing
TI Common Polymorphisms in the Adiponectin and Its Receptor Genes,
Adiponectin Levels and the Risk of Prostate Cancer
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID PLASMA ADIPONECTIN; METABOLIC SYNDROME; SERUM ADIPONECTIN; PHYSICIANS
HEALTH; APM1 GENE; MACROPHAGES; POPULATION; OBESITY; ADIPOR1;
ASSOCIATION
AB Background: Adiponectin, an insulin-sensitizing adipokine, is inversely associated with adiposity and prostate cancer risk and progression. However, the role of genetic variation in the adiponectin (ADIPOQ) and receptor genes (ADIPOR1/R2) in prostate cancer is largely unknown.
Methods: In a nested case-control study of 1,286 cases and 1,267 controls within the Physicians' Health Study, we evaluated 29 common single-nucleotide polymorphisms (SNP) in ADIPOQ (n = 13), ADIPOR1 (n = 5), and ADIPOR2 (n = 11) in relation to the risk of prostate cancer. In subgroups, we also evaluated the association of genotype and circulating adiponectin levels (n 951) and prostate tumor expression of insulin receptor (IR) and insulin-like growth factor 1 (IGF-IR) receptor (n = 181).
Results: Among the 12 tagging polymorphisms in ADIPOQ, four (rs266729, rs182052, rs822391, and rs2082940) were significantly associated (P < 0.05) with overall prostate cancer risk, with no significant difference by tumor grade or clinical stage. Two of the risk SNPs (rs266729 and rs182052) plus four other SNPs (rs16861209, rs17366568, rs3774261, and rs7639352) were also associated with plasma adiponectin levels, and three of these (rs1686109, rs17366568, and rs3774261) were also significantly associated with IR expression in prostate tumor tissue. One additional SNP was associated with IGFI-R tumor tissue expression (rs16861205). None of the 16 variants in ADIPOR1/R2 were related to cancer risk or circulating adiponectin levels.
Conclusions: Common variants in the adiponectin gene were associated with prostate cancer risk, plasma adiponectin levels, and IR or IGF-IR expression in the prostate tumor.
Impact: These genotype-phenotype associations support the biological relevance of adiponectin for prostate carcinogenesis, particularly in earlier stages of development. Cancer Epidemiol Biomarkers Prev; 20(12); 2618-27. (C) 2011 AACR.
C1 [Dhillon, Preet K.; Penney, Kathryn L.; Schumacher, Fredrick; Rider, Jennifer R.; Mucci, Lorelei A.; Giovannucci, Edward; Stampfer, Meir J.; Ma, Jing] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Sesso, Howard D.] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA.
[Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA USA.
[Fiorentino, Michelangelo; Finn, Stephen; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Dhillon, Preet K.; Schumacher, Fredrick; Mucci, Lorelei A.; Giovannucci, Edward; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Pollak, Michael] McGill Univ, Jewish Gen Hosp, Canc Prevent Res Unit, Dept Med,Lady Davis Res Inst, Montreal, PQ H3T 1E2, Canada.
[Pollak, Michael] McGill Univ, Jewish Gen Hosp, Canc Prevent Res Unit, Dept Oncol,Lady Davis Res Inst, Montreal, PQ H3T 1E2, Canada.
[Pollak, Michael] McGill Univ, Montreal, PQ, Canada.
[Dhillon, Preet K.] Publ Hlth Fdn India, S Asia Network Chron Dis, New Delhi, India.
[Rifai, Nader] Harvard Univ, Childrens Hosp, Sch Med, Dept Lab Med, Boston, MA 02115 USA.
RP Ma, J (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA.
EM jing.ma@channing.harvard.edu
RI Pollak, Michael/G-9094-2011;
OI Pollak, Michael/0000-0003-3047-0604; Rider,
Jennifer/0000-0002-2637-6036; Finn, Stephen/0000-0002-8628-5814
FU Prostate Cancer Foundation; Department of Defense [W81XWH-01-1-0322,
PC073618]; NIH, Bethesda, MD [CA 42182, CA 097193, R01CA131945,
RO1CA141298]; NCIC-Canadian Breast Cancer Research Initiative [019894];
Cancer Epidemiology Training [NCI T32 CA009001]
FX This work was funded by the Prostate Cancer Foundation Award, "Obesity,
Adiponectin, Angiogenesis, and Prostate Cancer Survival" the Department
of Defense (W81XWH-01-1-0322), the NIH (CA 42182 and CA 097193,
R01CA131945, RO1CA141298 Bethesda, MD), Department of Defense
(PC073618), and the NCIC-Canadian Breast Cancer Research Initiative
(019894). P. K. Dhillon was supported by a Cancer Epidemiology Training
grant NCI T32 CA009001.
NR 35
TC 31
Z9 34
U1 1
U2 11
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD DEC
PY 2011
VL 20
IS 12
BP 2618
EP 2627
DI 10.1158/1055-9965.EPI-11-0434
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 864JA
UT WOS:000298234900018
PM 21960694
ER
PT J
AU Stott-Miller, M
Houck, JR
Lohavanichbutr, P
Mendez, E
Upton, MP
Futran, ND
Schwartz, SM
Chen, C
AF Stott-Miller, Marni
Houck, John R.
Lohavanichbutr, Pawadee
Mendez, Eduardo
Upton, Melissa P.
Futran, Neal D.
Schwartz, Stephen M.
Chen, Chu
TI Tumor and Salivary Matrix Metalloproteinase Levels Are Strong Diagnostic
Markers of Oral Squamous Cell Carcinoma
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID SINGLE NUCLEOTIDE POLYMORPHISM; GENE-EXPRESSION; HUMAN-PAPILLOMAVIRUS;
POTENTIAL BIOMARKERS; OROPHARYNGEAL CANCER; CDNA MICROARRAY;
RISK-FACTOR; HEAD; NECK; PROGRESSION
AB Background: The matrix metalloproteinases (MMP) cause degradation of the extracellular matrix and basement membranes, and thus may play a key role in cancer development.
Methods: In our search for biomarkers for oral squamous cell carcinomas (OSCC), we compared primary OSCC, oral dysplasia and control subjects with respect to: (i) expression of MMP1, MMP3, MMP10, and MMP12 in oral epithelial tissue using Affymetrix U133 2.0 Plus GeneChip arrays, followed by quantitative reverse transcription-PCR (qRT-PCR) for MMP1, and (ii) determination of MMP1 and MMP3 concentrations in saliva.
Results: MMP1 expression in primary OSCC (n = 119) was > 200-fold higher (P 7.16 x 10(-40)) compared with expression levels in nonneoplastic oral epithelium from controls (n 35). qRT-PCR results on 30 cases and 22 controls confirmed this substantial differential expression. The exceptional discriminatory power to separate OSCC from controls was validated in two independent testing sets (AUC% 100; 95% CI: 100-100 and AUC% 98.4; 95% CI: 95.6-100). Salivary concentrations of MMP1 and MMP3 in OSCC patients (33 stage I/II, 26 stage III/IV) were 6.2 times (95% CI: 3.32-11.73) and 14.8 times (95% CI: 6.75-32.56) higher, respectively, than in controls, and displayed an increasing trend with higher stage disease.
Conclusion: Tumor and salivary MMPs are robust diagnostic biomarkers of OSCC.
Impact: The capacity of MMP gene expression to identify OSCC provides support for further investigation into MMPs as potential markers for OSCC development. Detection of MMP proteins in saliva in particular may provide a promising means to detect and monitor OSCC noninvasively. Cancer Epidemiol Biomarkers Prev; 20(12); 2628-36. (C) 2011 AACR.
C1 [Stott-Miller, Marni; Houck, John R.; Lohavanichbutr, Pawadee; Mendez, Eduardo; Schwartz, Stephen M.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA.
[Stott-Miller, Marni; Schwartz, Stephen M.; Chen, Chu] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Mendez, Eduardo; Futran, Neal D.; Chen, Chu] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA.
[Upton, Melissa P.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA.
RP Chen, C (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, 1100 Fairview Ave N,M5-C800,POB 19024, Seattle, WA 98109 USA.
EM cchen@fhcrc.org
FU U.S. NIH (from the National Cancer Institute) [R01CA095419]; NIH
[5T32DE007132-28]; Fred Hutchinson Cancer Research Center
FX U.S. NIH (R01CA095419 from the National Cancer Institute), NIH
5T32DE007132-28 (Comprehensive training in inter-disciplinary oral
health research), and institutional funds from the Fred Hutchinson
Cancer Research Center.
NR 49
TC 15
Z9 15
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD DEC
PY 2011
VL 20
IS 12
BP 2628
EP 2636
DI 10.1158/1055-9965.EPI-11-0503
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 864JA
UT WOS:000298234900019
PM 21960692
ER
PT J
AU Sun, T
Oh, WK
Jacobus, S
Regan, M
Pomerantz, M
Freedman, ML
Lee, GSM
Kantoff, PW
AF Sun, Tong
Oh, William K.
Jacobus, Susanna
Regan, Meredith
Pomerantz, Mark
Freedman, Matthew L.
Lee, Gwo-Shu Mary
Kantoff, Philip W.
TI The Impact of Common Genetic Variations in Genes of the Sex Hormone
Metabolic Pathways on Steroid Hormone Levels and Prostate Cancer
Aggressiveness
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID SERUM TESTOSTERONE LEVELS; COHORT CONSORTIUM; ANDROGEN; RISK;
DEHYDROGENASES; ASSOCIATION; ESTROGEN; THERAPY; ENZYMES; BREAST
AB Our previous work suggested that there was no significant association between plasma steroid hormone levels and prostate cancer tumor grade at diagnosis. In this study, we systematically tested the hypothesis that inherited variations in the androgen and estrogen metabolic pathways may be associated with plasma levels of steroid hormones, or prostate cancer aggressiveness at diagnosis. Plasma hormone levels including total testosterone, total estradiol, and sex hormone-binding globulin were measured in a cohort of 508 patients identified with localized prostate cancer. D'Amico risk classification at diagnosis was also determined. A total of 143 single-nucleotide polymorphisms (SNPs) from 30 genes that are involved in androgen and estrogen metabolism were selected for analysis. The global association of genotypes with plasma hormone levels and prostate cancer aggressiveness (D'Amico risk classification) was statistically analyzed. Q values were estimated to account for multiple testing. We observed significant associations between plasma testosterone level and SNPs in HSD17B2 (rs1424151), HSD17B3 (rs9409407), and HSD17B1 (rs12602084), with P values of 0.002, 0.006, and 0.006, respectively. We also observed borderline significant associations between prostate aggressiveness at diagnosis and SNPs in AKR1C1 (rs11252845; P = 0.005), UGT2B15 (rs2045100; P = 0.007), and HSD17B12 (rs7932905; P = 0.008). No individual SNP was associated with both clinical variables. Genetic variants of genes in hormone metabolic pathways may influence plasma androgen levels or prostate cancer aggressiveness. However, it seems that the inherited variations affecting plasma hormone levels differ from those affecting disease aggressiveness. Cancer Prev Res; 4(12); 2044-50. (C) 2011 AACR.
C1 [Sun, Tong; Oh, William K.; Pomerantz, Mark; Freedman, Matthew L.; Lee, Gwo-Shu Mary; Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Jacobus, Susanna; Regan, Meredith] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Lee, GSM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Binney St, Boston, MA 02215 USA.
EM Gwo-shu_lee@dfci.harvard.edu; Philip_kantoff@dfci.harvard.edu
RI Oh, William/B-9163-2012
OI Oh, William/0000-0001-5113-8147
FU SPORE [2 P50 CA090381-06]; Prostate Cancer Foundation; DoD
[W81XWH-09-1-0372]
FX This work was supported by a SPORE in Prostate Cancer 2 P50 CA090381-06
and a Prostate Cancer Foundation Challenge grant. T. Sun is supported by
a DoD Prostate Cancer Training Award W81XWH-09-1-0372.
NR 41
TC 16
Z9 17
U1 0
U2 4
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 DEC
PY 2011
VL 4
IS 12
BP 2044
EP 2050
DI 10.1158/1940-6207.CAPR-11-0283
PG 7
WC Oncology
SC Oncology
GA 863PN
UT WOS:000298178000011
PM 21900597
ER
PT J
AU Sukhotinsky, I
Dilekoz, E
Wang, YM
Qin, T
Eikermann-Haerter, K
Waeber, C
Ayata, C
AF Sukhotinsky, Inna
Dilekoz, Ergin
Wang, Yumei
Qin, Tao
Eikermann-Haerter, Katharina
Waeber, Christian
Ayata, Cenk
TI Chronic daily cortical spreading depressions suppress spreading
depression susceptibility
SO CEPHALALGIA
LA English
DT Article
DE Spreading depression; chronic migraine; astrocyte
ID CHRONIC MIGRAINE; EPISODIC MIGRAINE; BRAIN-INJURY; SPECTRUM; MOUSE;
MICE; CLASSIFICATION; ASTROCYTES; GLUTAMATE; HEADACHE
AB Background: Migraine is a disabling chronic episodic disorder. Attack frequency progressively increases in some patients. Incremental cortical excitability has been implicated as a mechanism underlying progression. Cortical spreading depression (CSD) is the electrophysiological event underlying migraine aura, and a headache trigger. We hypothesized that CSD events during frequent migraine attacks condition the cortex to increase the susceptibility to further attacks.
Methods: A single daily CSD was induced for 1 or 2 weeks in mouse frontal cortex; contralateral hemisphere served as sham control. At the end of CSD conditioning, occipital CSD susceptibility was determined by measuring the frequency of CSDs evoked by topical KCl application.
Results: Sham hemispheres developed 8.4 +/- 0.3 CSDs/hour, and did not significantly differ from naive controls without prior cranial surgery (9.3 +/- 0.4 CSDs/hour). After 2 but not 1 week of daily CSD conditioning, CSD frequency (4.9 +/- 0.3 CSDs/hour) as well as the duration and propagation speed were reduced significantly in the conditioned hemispheres. Histopathological examination revealed marked reactive astrocytosis without neuronal injury throughout the conditioned cortex after 2 weeks, temporally associated with CSD susceptibility.
Conclusions: These data do not support the hypothesis that frequent migraine attacks predispose the brain to further attacks by enhancing tissue susceptibility to CSD.
C1 [Sukhotinsky, Inna; Dilekoz, Ergin; Wang, Yumei; Qin, Tao; Eikermann-Haerter, Katharina; Waeber, Christian; Ayata, Cenk] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Dilekoz, Ergin] Gazi Univ, Ankara, Turkey.
RP Ayata, C (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 6408, Charlestown, MA 02129 USA.
EM cayata@partners.org
RI Waeber, Christian/A-8333-2009
OI Waeber, Christian/0000-0001-6078-0027
FU National Institutes of Health [NS061505, NS055104]
FX Supported by the National Institutes of Health (NS061505, NS055104).
NR 38
TC 8
Z9 8
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0333-1024
J9 CEPHALALGIA
JI Cephalalgia
PD DEC
PY 2011
VL 31
IS 16
BP 1601
EP 1608
DI 10.1177/0333102411425865
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 863SL
UT WOS:000298188100002
PM 22013142
ER
PT J
AU Koruth, JS
Aryana, A
Dukkipati, SR
Pak, HN
Kim, YH
Sosa, EA
Scanavacca, M
Mahapatra, S
Ailawadi, G
Reddy, VY
d'Avila, A
AF Koruth, Jacob S.
Aryana, Arash
Dukkipati, Srinivas R.
Pak, Hui-Nam
Kim, Young-Hoon
Sosa, Eduardo A.
Scanavacca, Mauricio
Mahapatra, Srijoy
Ailawadi, Gorav
Reddy, Vivek Y.
d'Avila, Andre
TI Unusual Complications of Percutaneous Epicardial Access and Epicardial
Mapping and Ablation of Cardiac Arrhythmias
SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
LA English
DT Article
DE epicardium; pericardium; epicardial access; epicardial ablation;
complications
ID RIGHT-VENTRICULAR PSEUDOANEURYSM; CATHETER ABLATION; TACHYCARDIA
AB Background-Percutaneous epicardial access and mapping/ablation of cardiac arrhythmias are being increasingly performed. Although complications such as pericardial effusion are relatively common, other unusual complications may occur due to the complex anatomic architecture of the heart and surrounding tissues. In this report, we report a series of rare and unusual complications related to percutaneous epicardial procedures.
Methods and Results-Between 2006 and 2011, 334 patients underwent attempts at percutaneous, subxiphoid access for epicardial mapping/ablation at 5 experienced centers. Seven selected complications are highlighted in this case series. Patient 1 had a 1-cm right ventricular pseudoaneurysm after several unsuccessful attempts at epicardial access. This was successfully managed conservatively. Patient 2 had intra-abdominal bleeding related to puncture of the left lobe of the liver during access that required surgical repair. Patient 3 had a subcapsular hepatic hematoma that was probably related to percutaneous access and was successfully managed conservatively. Patient 4 had severe pericardial bleeding followed by ventricular fibrillation, immediately after obtaining percutaneous epicardial access. A lacerated middle cardiac vein was repaired surgically. However, the patient ultimately died of complications. Patient 5 had a history of cardiothoracic surgery and developed a right ventricle-abdominal fistula after multiple attempts at percutaneous access. This was surgically repaired without major sequelae. Patient 6 had cardiac tamponade caused by a lacerated coronary sinus branch during epicardial catheter ablation and required surgical repair. Patient 7 had severe left coronary vasospasm and ventricular fibrillation during catheter manipulation in the pericardium. This complication was successfully managed with intracoronary nitrates.
Conclusions-Though generally safe, percutaneous epicardial access and mapping/ablation can result in uncommon complications. Awareness of these rare complications may facilitate early detection and successful management. (Circ Arrhythm Electrophysiol. 2011;4:882-888.)
C1 [Koruth, Jacob S.; Dukkipati, Srinivas R.; Reddy, Vivek Y.; d'Avila, Andre] Mt Sinai Med Ctr, Helmsley Electrophysiol Ctr, New York, NY 10029 USA.
[Aryana, Arash] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Pak, Hui-Nam; Kim, Young-Hoon] Korea Univ, Arrhythmia & Cardiovasc Ctr, Seoul, South Korea.
[Sosa, Eduardo A.; Scanavacca, Mauricio] Univ Sao Paulo, Fac Med, Unidade Clin Arritmia, Inst Coracao, Sao Paulo, Brazil.
[Mahapatra, Srijoy] Univ Virginia, Div Cardiac Electrophysiol, Charlottesville, VA USA.
[Ailawadi, Gorav] Univ Virginia, Div Cardiac Surg, Charlottesville, VA USA.
RP d'Avila, A (reprint author), Mt Sinai Sch Med, Helmsley Cardiac Arrhythmia Serv, 1 Gustave L Levy Pl,Box 1030, New York, NY 10029 USA.
EM andre.d'avila@mountsinai.org
RI Scanavacca, Mauricio Ibrahim/F-7693-2012; Pak, Hui-Nam/C-4266-2015;
d'Avila, Andre/F-8009-2010
OI Scanavacca, Mauricio Ibrahim/0000-0001-7327-2275; Pak,
Hui-Nam/0000-0002-3256-3620; d'Avila, Andre/0000-0001-8769-1411
NR 16
TC 26
Z9 26
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3149
J9 CIRC-ARRHYTHMIA ELEC
JI Circ.-Arrhythmia Electrophysiol.
PD DEC
PY 2011
VL 4
IS 6
BP 882
EP U161
DI 10.1161/CIRCEP.111.965731
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 866WB
UT WOS:000298415800019
PM 22007036
ER
PT J
AU Newton-Cheh, C
AF Newton-Cheh, Christopher
TI What Can Genetic Studies of Left Ventricular Mass Tell Us?
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Editorial Material
DE Editorials; electrocardiography; genetics; hypertrophy; conduction
ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; HYPERTROPHY; DURATION;
INTERVAL; LOCI
C1 [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Newton-Cheh, Christopher] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
RP Newton-Cheh, C (reprint author), Harvard Univ, Sch Med, Cardiovasc Res Ctr, 185 Cambridge St,CPZN 5-242, Boston, MA 02114 USA.
EM cnewtoncheh@chgr.mgh.harvard.edu
FU NHLBI NIH HHS [R01 HL098283-02, R01 HL098283, R01 HL098283-03, R01
HL098283-01]
NR 16
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD DEC
PY 2011
VL 4
IS 6
BP 581
EP 584
DI 10.1161/CIRCGENETICS.111.961839
PG 4
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 866VR
UT WOS:000298414800003
PM 22187447
ER
PT J
AU Jones, JA
Stroud, RE
O'Quinn, EC
Black, LE
Barth, JL
Elefteriades, JA
Bavaria, JE
Gorman, JH
Gorman, RC
Spinale, FG
Ikonomidis, JS
AF Jones, Jeffrey A.
Stroud, Robert E.
O'Quinn, Elizabeth C.
Black, Laurel E.
Barth, Jeremy L.
Elefteriades, John A.
Bavaria, Joseph E.
Gorman, Joseph H., III
Gorman, Robert C.
Spinale, Francis G.
Ikonomidis, John S.
TI Selective MicroRNA Suppression in Human Thoracic Aneurysms Relationship
of miR-29a to Aortic Size and Proteolytic Induction
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE aneurysm; thoracic aorta; microRNA; MMP; remodeling
ID CARDIOVASCULAR-DISEASE ENTERPRISES; IN-SITU LOCALIZATION; MATRIX
METALLOPROTEINASES; ENDOGENOUS INHIBITORS; MAJOR SHAREHOLDERS;
MARFAN-SYNDROME; IV COLLAGENASE; MURINE MODEL; EXPRESSION;
MATRIX-METALLOPROTEINASE-9
AB Background-Increasing evidence points to a direct role for altered microRNA (miRNA or miR) expression levels in cardiovascular remodeling and disease progression. Although alterations in miR expression levels have been directly linked to cardiac hypertrophy, fibrosis, and remodeling, their role in regulating gene expression during thoracic aortic aneurysm (TAA) development has yet to be explored.
Methods and Results-The present study examined miR expression levels in aortic tissue specimens collected from patients with ascending TAAs by quantitative real-time PCR, and observed decreased miR expression (miRs -1, -21, -29a, -133a, and -486) as compared with normal aortic specimens. A significant relationship between miR expression levels (miRs -1, -21, -29a, and -133a) and aortic diameter was identified; as aortic diameter increased, miR expression decreased. Through the use of a bioinformatics approach, members of the matrix metalloproteinase (MMP) family, proteins involved in TAA development, were examined for putative miR binding sites. MMP-2 and MMP-9 were identified as potential targets for miR-29a and miR-133a, respectively, and MMP-2 was subsequently verified as a miR-29a target in vitro. A significant inverse relationship between miR-29a and total MMP-2 was then identified in the clinical TAA specimens.
Conclusions-These findings demonstrate altered miR expression patterns in clinical TAA specimens, suggesting that the loss of specific miR expression may allow for the elaboration of specific MMPs capable of driving aortic remodeling during TAA development. Importantly, these data suggest that these miRs have biological and clinical relevance to the behavior of TAAs and may provide significant targets for therapeutic and diagnostic applications. (Circ Cardiovasc Genet. 2011;4:605-613.)
C1 [Ikonomidis, John S.] Med Univ S Carolina, Div Cardiothorac Surg, S Carolina Heart Valve Ctr, Charleston, SC 29425 USA.
[Jones, Jeffrey A.; Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA.
[Barth, Jeremy L.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA.
[Elefteriades, John A.] Yale Univ, Sch Med, Dept Cardiothorac Surg, New Haven, CT USA.
[Bavaria, Joseph E.; Gorman, Joseph H., III; Gorman, Robert C.] Univ Penn, Gorman Cardiovasc Res Grp, Glenolden Res Lab, Glenolden, PA USA.
RP Ikonomidis, JS (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, S Carolina Heart Valve Ctr, 25 Courtenay Dr,Suite 7030, Charleston, SC 29425 USA.
EM ctsxresearch@musc.edu
FU Department of Veterans Affairs; National Institutes of Health; NIH/NCRR
[RR16434, RR16461]; [NHLBI/R01s HL057952-08]; [HL059165-09];
[NHLBI/R21 HL089170-01A1]; [R01 HL102121-01A1]
FX This work was supported by the Department of Veterans Affairs: Career
Development Award (CDA-2) and a Merit Award to Dr Jones and a Merit
Award to Dr Spinale; National Institutes of Health grants NIH/NCRR
RR16434 and RR16461 to Dr Barth; NHLBI/R01s HL057952-08 and HL059165-09
to Dr Spinale; and NHLBI/R21 HL089170-01A1 and R01 HL102121-01A1 to Dr
Ikonomidis.
NR 35
TC 41
Z9 43
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD DEC
PY 2011
VL 4
IS 6
BP 605
EP U264
DI 10.1161/CIRCGENETICS.111.960419
PG 15
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 866VR
UT WOS:000298414800006
PM 22010139
ER
EF