FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU McMillan, PJ
Kraemer, BC
Robinson, L
Leverenz, JB
Raskind, M
Schellenberg, G
AF McMillan, Pamela J.
Kraemer, Brian C.
Robinson, Linda
Leverenz, James B.
Raskind, Murray
Schellenberg, Gerard
TI Truncation of tau at E391 Promotes Early Pathologic Changes in
Transgenic Mice
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Aggregation; Alzheimer disease; Tau; Transgenic mice; Truncation
ID PAIRED HELICAL FILAMENTS; INDUCIBLE MOUSE MODELS; RAT DENTATE GYRUS;
ALZHEIMERS-DISEASE; PROTEIN-TAU; NEURODEGENERATIVE DISORDERS;
NEUROFIBRILLARY PATHOLOGY; DETERMINES AGGREGATION; NERVOUS-SYSTEM;
TAUOPATHY
AB Proteolytic cleavage of tau at glutamic acid 391 (E391) is linked to the pathogenesis of Alzheimer disease (AD). This C-terminal-truncated tau species exists in neurofibrillary tangles and abnormal neurites in the brains of AD patients and may potentiate tau polymerization. We generated a mouse model that expresses human tau truncated at E391 to begin to elucidate the role of this C-terminal-truncated tau species in the development of tau pathology. Our results show that truncated but otherwise wild-type human tau is sufficient to drive pretangle pathologic changes in tau, including accumulation of insoluble tau, somatodendritic redistribution, formation of pathologic conformations, and dual phosphorylation of tau at sites associated with AD pathology. In addition, these mice exhibit atypical neuritic tau immunoreactivity, including abnormal neuritic processes and dystrophic neurites. These results suggest that changes in tau proteolysis can initiate tauopathy.
C1 [McMillan, Pamela J.; Leverenz, James B.; Raskind, Murray] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA.
[Kraemer, Brian C.; Robinson, Linda] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA.
[Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA.
[McMillan, Pamela J.; Leverenz, James B.; Raskind, Murray] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Kraemer, Brian C.] Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98195 USA.
[Leverenz, James B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Schellenberg, Gerard] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
RP McMillan, PJ (reprint author), Seattle Vet Affairs Puget Sound Hlth Care Syst, Box 358280,S182 GRECC,1660 S Columbian Way, Seattle, WA 98108 USA.
EM pammcm@u.washington.edu
FU National Institute on Aging [AG17586, 2P50AG005136-27]; Department of
Veterans Affairs; Veterans Affairs National Institute of Neurological
Disorders and Stroke [5P50NS062684-02]
FX This work was supported by National Institute on Aging Grant AG17586 to
G.D.S., Department of Veterans Affairs Merit Review Grant to B.C.K., and
Veterans Affairs National Institute of Neurological Disorders and Stroke
5P50NS062684-02 and National Institute on Aging 2P50AG005136-27 to
J.B.L.
NR 53
TC 14
Z9 15
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD NOV
PY 2011
VL 70
IS 11
BP 1006
EP 1019
DI 10.1097/NEN.0b013e31823557fb
PG 14
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 842DB
UT WOS:000296567800006
PM 22002427
ER
PT J
AU Patenaude, AF
AF Patenaude, Andrea Farkas
TI Commentary: Save the Children: Direct-to-Consumer Testing of Children is
Premature, Even for Research
SO JOURNAL OF PEDIATRIC PSYCHOLOGY
LA English
DT Editorial Material
ID CANCER SUSCEPTIBILITY; MUTATION; MOTHERS; UPDATE; LEGAL
C1 [Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genet,Psychol Serv,Dept Psychosocial Onc, Boston, MA 02215 USA.
[Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
RP Patenaude, AF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genet,Psychol Serv,Dept Psychosocial Onc, 450 Brookline Ave, Boston, MA 02215 USA.
EM andrea_patenaude@dfci.harvard.edu
NR 25
TC 5
Z9 5
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0146-8693
J9 J PEDIATR PSYCHOL
JI J. Pediatr. Psychol.
PD NOV-DEC
PY 2011
VL 36
IS 10
BP 1122
EP 1127
DI 10.1093/jpepsy/jsr068
PG 6
WC Psychology, Developmental
SC Psychology
GA 839AE
UT WOS:000296335600007
PM 21994422
ER
PT J
AU Spector, J
AF Spector, J.
TI The evolution of neonatal resuscitation training
SO JOURNAL OF PERINATOLOGY
LA English
DT Letter
C1 Massachusetts Gen Hosp, Div Newborn Serv, Boston, MA 02114 USA.
RP Spector, J (reprint author), Massachusetts Gen Hosp, Div Newborn Serv, Boston, MA 02114 USA.
EM jmspector@partners.org
NR 1
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0743-8346
J9 J PERINATOL
JI J. Perinatol.
PD NOV
PY 2011
VL 31
IS 11
BP 744
EP 744
DI 10.1038/jp.2011.35
PG 1
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 842IH
UT WOS:000296590600010
PM 22037158
ER
PT J
AU Stark, S
Snetselaar, L
Piraino, B
Stone, RA
Kim, S
Hall, B
Burke, LE
Sevick, MA
AF Stark, Susan
Snetselaar, Linda
Piraino, Beth
Stone, Roslyn A.
Kim, Sunghee
Hall, Beth
Burke, Lora E.
Sevick, Mary Ann
TI Personal Digital Assistant-Based Self-Monitoring Adherence Rates in 2
Dialysis Dietary Intervention Pilot Studies: BalanceWise-HD and
BalanceWise-PD
SO JOURNAL OF RENAL NUTRITION
LA English
DT Article
ID HOME-BASED WALKING; WEIGHT-LOSS; PROGRAM
AB Objective: The dialysis dietary regimen is complicated, and computer-based dietary self-monitoring may be useful for helping dialysis patients manage their dietary regimen. In this report, we describe dietary self-monitoring rates among study participants randomized to the intervention arms of 2 pilot studies.
Methods: Both studies tested similar interventions involving dietary counseling paired with personal digital assistant-based self-monitoring. One study was performed in hemodialysis (HD) and one in peritoneal dialysis (PD) patients.
Results: HD intervention participants entered an average of 244.9 meals (median = 288; interquartile range [IQR]: 186 to 342) over the 16-week intervention, 2.2 meals per day (median = 2.6; IQR: 1.7 to 3.1), and 73% of expected meals (median = 86; IQR: 55 to 102), assuming intake of 3 meals per day. At least some meals were entered in 87% of the observed weeks (median = 100%; IQR: 81 to 100). PD intervention participants entered an average of 212.1 meals (median = 203; IQR: 110 to 312) over the 16-week intervention, 1.9 meals per day (median = 1.8; IQR: 1 to 2.8), and 63% of expected meals (median = 60; IQR: 33 to 93), assuming 3 meals per day. At least some meals were entered in 80% of the observed weeks (median = 94; IQR: 50 to 100).
Conclusion: These HD and PD patients demonstrated excellent rates of self-monitoring. Additional research with a larger sample is required to confirm these findings. (C) 2011 by the National Kidney Foundation, Inc. All rights reserved.
C1 [Stark, Susan] Univ Pittsburgh, Sch Med, Dept Med, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA.
[Snetselaar, Linda] Univ Iowa, Coll Publ Hlth, Dept Endocrinol, Iowa City, IA USA.
[Stone, Roslyn A.; Kim, Sunghee; Burke, Lora E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Stone, Roslyn A.; Kim, Sunghee; Sevick, Mary Ann] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Burke, Lora E.] Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15261 USA.
[Piraino, Beth] Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA.
[Burke, Lora E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Sevick, Mary Ann] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA.
[Sevick, Mary Ann] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
RP Stark, S (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Ctr Res Hlth Care, 3520 Forbes Ave,1st Floor, Pittsburgh, PA 15213 USA.
EM starsa2@upmc.edu
OI Piraino, Beth/0000-0001-5061-0841
FU Paul Teschan Research Foundation; [NIH/NIDDK/DK-R21DK067181];
[NIH/NCRR/CTSA-UL1-RR024153]; [NIH/NCRR/GCRC-M01- RR000056]
FX The work in this article was supported by the following grants: Paul
Teschan Research Foundation, NIH/NIDDK/DK-R21DK067181,
NIH/NCRR/CTSA-UL1-RR024153, and NIH/NCRR/GCRC-M01- RR000056. The authors
take full responsibility for the contents of this article, which do not
represent the views of the Department of Veterans Affairs or the United
States Government. The authors acknowledge the individual contributions
of: Rita Marsh, RN, MSN; Deborah Klinvex, BA; and Tienna Luster.
NR 18
TC 4
Z9 4
U1 1
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1051-2276
J9 J RENAL NUTR
JI J. Renal Nutr.
PD NOV
PY 2011
VL 21
IS 6
BP 492
EP 498
DI 10.1053/j.jrn.2010.10.026
PG 7
WC Nutrition & Dietetics; Urology & Nephrology
SC Nutrition & Dietetics; Urology & Nephrology
GA 841SJ
UT WOS:000296533100009
PM 21420316
ER
PT J
AU Marshall, CL
Balentine, CJ
Robinson, CN
Wilks, JA
Anaya, D
Artinyan, A
Awad, SS
Berger, DH
Albo, D
AF Marshall, Christy L.
Balentine, Courtney J.
Robinson, Celia N.
Wilks, Jonathan A.
Anaya, Daniel
Artinyan, Avo
Awad, Samir S.
Berger, David H.
Albo, Daniel
TI A Multidisciplinary Cancer Center Maximizes Surgeons' Impact
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE colorectal cancer center; specialty-trained surgeons; prognostic;
outcomes; colorectal cancer
ID COLORECTAL LIVER METASTASES; HOSPITAL PROCEDURE VOLUME; COLON-CANCER;
RECTAL-CANCER; COMBINED RESECTION/ABLATION; RADIOFREQUENCY ABLATION;
SURGICAL SPECIALITY; HEPATIC RESECTION; OUTCOMES; RECURRENCE
AB Background. Colorectal cancer patients require care across different disciplines. Integration of multidisciplinary care is critical to accomplish excellent oncologic results. We hypothesized that the establishment of a dedicated colorectal cancer center (CRCC) around specialty-trained surgeons will lead to increased multidisciplinary management and improved outcomes in colorectal cancer patients.
Methods. We analyzed data from three periods: a baseline group, a period after the recruitment of specialty-trained surgeons, and a period after the creation of a dedicated multidisciplinary cancer center. Data analyzed included surrogate markers of surgical oncologic care, multidisciplinary integration, and oncologic outcomes.
Results. Recruitment of specialized surgeons led to improvements in surgical oncologic care; the establishment of the CRCC resulted in further improvements in surgical oncologic care and multidisciplinary integration.
Conclusion. Our study suggests that although the recruitment of specialty-trained surgeons in a high volume center leads to improvement in surgical oncologic care, it is the establishment of a multidisciplinary center around the surgeons that leads to integrated care and improvements in oncologic outcomes. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Albo, Daniel] Baylor Coll Med, Div Surg Oncol, Michael E DeBakey Dept Surg, Houston, TX 77030 USA.
Baylor Coll Med, Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
RP Albo, D (reprint author), Baylor Coll Med, Div Surg Oncol, Michael E DeBakey Dept Surg, 1709 Dryden,Suite 1500, Houston, TX 77030 USA.
EM dalbo@bcm.edu
NR 29
TC 4
Z9 4
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
J9 J SURG RES
JI J. Surg. Res.
PD NOV
PY 2011
VL 171
IS 1
BP 15
EP 22
DI 10.1016/j.jss.2010.12.007
PG 8
WC Surgery
SC Surgery
GA 839LS
UT WOS:000296368000022
PM 21696763
ER
PT J
AU Nezami, BG
Rahimpour, S
Sadeghi, M
Sianati, S
Anaraki, DK
Ebrahimi, F
Ghasemi, M
Dehpour, AR
AF Nezami, Behtash Ghazi
Rahimpour, Sina
Sadeghi, Mahsa
Sianati, Setareh
Anaraki, Dina Kalbasi
Ebrahimi, Farzad
Ghasemi, Mehdi
Dehpour, Ahmad Reza
TI Chronic Lithium Impairs Skin Tolerance to Ischemia in Random-Pattern
Skin Flap of Rats
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
ID GLYCOGEN-SYNTHASE KINASE-3-BETA; NITRIC-OXIDE; CORPUS CAVERNOSUM; SEXUAL
FUNCTION; GRANULE CELLS; ANIMAL-MODELS; RELAXATION; PHOSPHORYLATION;
INHIBITION; NEURONS
AB Background. Despite its apparent anti-apoptotic effect, lithium impairs endothelium-dependent vasorelaxation in various tissues. In this study, we assessed the effect of lithium treatment on ischemic skin flap survival and its interaction with nitric oxide pathway.
Materials and Methods. Seventy-six male Sprague-Dawley rats were randomly assigned into 13 groups. For skin flap surgery, dorsal skin flap measuring 8 x 2 cm was elevated on the midline. After local injections (if needed), the cranial pedicle was cut and flap was sutured back. Flap survival was assessed after 7 d. Animals in the chronic lithium group received lithium chloride in tap water for 4 wk preoperatively and 7 d postoperatively. Acute lithium groups received 3 nmol, 10 nmol and 3 mu mol/flap lithium locally. In another experiment, interaction with nitric oxide synthase inhibitor L-NAME as well as nitric oxide precursor L-arginine was studied, and the effect of ischemic preconditioning on skin flap survival in lithium treated rats was investigated.
Results. Chronic lithium group had mean flap survival value of 32.6% +/- 5.2% (mean +/- SD), which was significantly lower than normal subjects (52.7% +/- 6.1%, P < 0.001), while acute local lithium treatment had no effect. In chronic lithium group, systemic L-NAME (10 mg/kg, 30 min before flap elevation) failed to significantly decrease the survival, while sub-effective systemic L-arginine (100 mg/kg) and ischemic preconditioning significantly increased flap survival (P < 0.001 and P < 0.01, respectively).
Conclusions. We conclude that long-term lithium treatment impairs the skin tolerance to ischemia in rats, which seems to be nitric oxide mediated. This effect is prevented by ischemic preconditioning or L-arginine treatment. The results suggest that skin-involving interventions should be applied more cautiously in patients who are on lithium treatment. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Nezami, Behtash Ghazi; Rahimpour, Sina; Sadeghi, Mahsa; Sianati, Setareh; Anaraki, Dina Kalbasi; Ghasemi, Mehdi; Dehpour, Ahmad Reza] Univ Tehran Med Sci, Dept Pharmacol, Sch Med, Tehran, Iran.
[Ebrahimi, Farzad] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Dehpour, AR (reprint author), Univ Tehran Med Sci, Dept Pharmacol, Sch Med, POB 13145-784, Tehran, Iran.
EM dehpour@yahoo.com
OI dehpour, ahmad reza/0000-0002-8001-5565
FU Tehran University of Medical Sciences
FX The authors acknowledge support for this work by a research grant
provided by the Tehran University of Medical Sciences Vice Chancellor of
Research.
NR 37
TC 2
Z9 2
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
J9 J SURG RES
JI J. Surg. Res.
PD NOV
PY 2011
VL 171
IS 1
BP 374
EP 378
DI 10.1016/j.jss.2010.03.048
PG 5
WC Surgery
SC Surgery
GA 839LS
UT WOS:000296368000073
PM 20605607
ER
PT J
AU Bichakjian, CK
Halpern, AC
Johnson, TM
Hood, AF
Grichnik, JM
Swetter, SM
Tsao, H
Barbosa, VH
Chuang, TY
Duvic, M
Ho, VC
Sober, AJ
Beutner, KR
Bhushan, R
Begolka, WS
AF Bichakjian, Christopher K.
Halpern, Allan C.
Johnson, Timothy M.
Hood, Antoinette Foote
Grichnik, James M.
Swetter, Susan M.
Tsao, Hensin
Barbosa, Victoria Holloway
Chuang, Tsu-Yi
Duvic, Madeleine
Ho, Vincent C.
Sober, Arthur J.
Beutner, Karl R.
Bhushan, Reva
Begolka, Wendy Smith
TI Guidelines of care for the management of primary cutaneous melanoma
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
DE biopsy; follow-up; melanoma; pathology report; sentinel lymph node
biopsy; surgical margins
ID SENTINEL LYMPH-NODE; LENTIGO MALIGNA MELANOMA; AMERICAN-JOINT-COMMITTEE;
MOHS MICROGRAPHIC SURGERY; UNDERGO COMPLETION LYMPHADENECTOMY;
PREDICTING 10-YEAR SURVIVAL; COOPERATIVE-ONCOLOGY-GROUP; RANDOMIZED
SURGICAL TRIAL; CANCER STAGING SYSTEM; MM PRIMARY MELANOMA
AB The incidence of primary cutaneous melanoma has been increasing dramatically for several decades. Melanoma accounts for the majority of skin cancer related deaths, but treatment is nearly always curative with early detection of disease. In this update of the guidelines of care, we will discuss the treatment of patients with primary cutaneous melanoma. We will discuss biopsy techniques of a lesion clinically suspicious for melanoma and offer recommendations for the histopathologic interpretation of cutaneous melanoma. We will offer recommendations for the use of laboratory and imaging tests in the initial workup of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, we will provide recommendations for surgical margins and briefly discuss nonsurgical treatments. Finally, we will discuss the value and limitations of sentinel lymph node biopsy and offer recommendations for its use in patients with primary cutaneous melanoma. (J Am Acad Dermatol 2011;65:1032-47.)
C1 [Bhushan, Reva; Begolka, Wendy Smith] Amer Acad Dermatol, Schaumburg, IL 60173 USA.
[Bichakjian, Christopher K.; Johnson, Timothy M.] Univ Michigan Hlth Syst, Dept Dermatol, Ann Arbor, MI USA.
[Halpern, Allan C.] Mem Sloan Kettering Canc Ctr, Dept Dermatol, New York, NY 10021 USA.
[Hood, Antoinette Foote] Eastern Virginia Med Sch, Dept Dermatol, Norfolk, VA USA.
[Grichnik, James M.] Univ Miami Hosp & Clin, Univ Miami Hlth Syst, Dept Dermatol, Sylvester Comprehens Canc Ctr,Melanoma Program, Miami, FL USA.
[Swetter, Susan M.] Stanford Univ, Dept Dermatol, Med Ctr, Stanford, CA 94305 USA.
[Swetter, Susan M.] Dept Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Tsao, Hensin; Sober, Arthur J.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Tsao, Hensin; Sober, Arthur J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Barbosa, Victoria Holloway] Rush Univ, Dept Dermatol, Med Ctr, Chicago, IL 60612 USA.
[Chuang, Tsu-Yi] Univ So Calif, Los Angeles, CA USA.
[Chuang, Tsu-Yi] Desert Oasis Healthcare, Palm Springs, CA USA.
[Duvic, Madeleine] Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX USA.
[Ho, Vincent C.] Univ British Columbia, Div Dermatol, Vancouver, BC V5Z 1M9, Canada.
[Beutner, Karl R.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Beutner, Karl R.] Solano Dermatol, Fairfield, CA USA.
RP Bhushan, R (reprint author), Amer Acad Dermatol, 930 E Woodfield Rd, Schaumburg, IL 60173 USA.
EM rbhushan@aad.org
NR 145
TC 121
Z9 125
U1 0
U2 12
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD NOV
PY 2011
VL 65
IS 5
BP 1032
EP 1047
DI 10.1016/j.jaad.2011.04.031
PG 16
WC Dermatology
SC Dermatology
GA 838DW
UT WOS:000296268000014
PM 21868127
ER
PT J
AU Wiviott, SD
Hochholzer, W
AF Wiviott, Stephen D.
Hochholzer, Willibald
TI On-Clopidogrel Platelet Reactivity A Target in Sight?
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE platelets; platelet inhibitor; P2Y(12); thienopyridine
ID ACUTE CORONARY SYNDROMES; ST-SEGMENT ELEVATION; RANDOMIZED-TRIALS;
METAANALYSIS; CHOLESTEROL; ASPIRIN; PARTICIPANTS; EFFICACY; THERAPY;
STATINS
C1 [Wiviott, Stephen D.; Hochholzer, Willibald] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA.
[Wiviott, Stephen D.; Hochholzer, Willibald] Harvard Univ, Sch Med, Boston, MA USA.
[Hochholzer, Willibald] Herz Zentrum Bad Krozingen, Bad Krozingen, Germany.
RP Wiviott, SD (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA.
EM swiviott@partners.org
NR 18
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 NOV 1
PY 2011
VL 58
IS 19
BP 1955
EP 1957
DI 10.1016/j.jacc.2011.08.016
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 841VC
UT WOS:000296542300004
PM 22032705
ER
PT J
AU Nanji, KC
Rothschild, JM
Salzberg, C
Keohane, CA
Zigmont, K
Devita, J
Gandhi, TK
Dalal, AK
Bates, DW
Poon, EG
AF Nanji, Karen C.
Rothschild, Jeffrey M.
Salzberg, Claudia
Keohane, Carol A.
Zigmont, Katherine
Devita, Jim
Gandhi, Tejal K.
Dalal, Anuj K.
Bates, David W.
Poon, Eric G.
TI Errors associated with outpatient computerized prescribing systems
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID PHYSICIAN ORDER ENTRY; CLINICAL DECISION-SUPPORT; ADVERSE DRUG EVENTS;
MEDICATION ERRORS; IMPLEMENTATION; IMPACT; SAFETY
AB Objective To report the frequency, types, and causes of errors associated with outpatient computer-generated prescriptions, and to develop a framework to classify these errors to determine which strategies have greatest potential for preventing them.
Materials and methods This is a retrospective cohort study of 3850 computer-generated prescriptions received by a commercial outpatient pharmacy chain across three states over 4 weeks in 2008. A clinician panel reviewed the prescriptions using a previously described method to identify and classify medication errors. Primary outcomes were the incidence of medication errors; potential adverse drug events, defined as errors with potential for harm; and rate of prescribing errors by error type and by prescribing system.
Results Of 3850 prescriptions, 452 (11.7%) contained 466 total errors, of which 163 (35.0%) were considered potential adverse drug events. Error rates varied by computerized prescribing system, from 5.1% to 37.5%. The most common error was omitted information (60.7% of all errors).
Discussion About one in 10 computer-generated prescriptions included at least one error, of which a third had potential for harm. This is consistent with the literature on manual handwritten prescription error rates. The number, type, and severity of errors varied by computerized prescribing system, suggesting that some systems may be better at preventing errors than others.
Conclusions Implementing a computerized prescribing system without comprehensive functionality and processes in place to ensure meaningful system use does not decrease medication errors. The authors offer targeted recommendations on improving computerized prescribing systems to prevent errors.
C1 [Nanji, Karen C.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Rothschild, Jeffrey M.; Dalal, Anuj K.; Bates, David W.; Poon, Eric G.] Harvard Univ, Sch Med, Boston, MA USA.
[Rothschild, Jeffrey M.; Salzberg, Claudia; Keohane, Carol A.; Zigmont, Katherine; Gandhi, Tejal K.; Dalal, Anuj K.; Bates, David W.; Poon, Eric G.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Devita, Jim] CVS Pharm, Woonsocket, RI USA.
[Gandhi, Tejal K.; Bates, David W.; Poon, Eric G.] Partners Healthcare, Boston, MA USA.
RP Nanji, KC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
EM knanji@partners.org
FU Agency for Healthcare Research and Quality (Rockville MD) [U18HS016970];
Harvard Risk Management Foundation, Cambridge, Massachusetts
FX This project was supported by grant number U18HS016970 from the Agency
for Healthcare Research and Quality (Rockville MD) and in part by a
grant from the Harvard Risk Management Foundation, Cambridge,
Massachusetts.
NR 29
TC 51
Z9 52
U1 1
U2 11
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 NOV
PY 2011
VL 18
IS 6
BP 767
EP 773
DI 10.1136/amiajnl-2011-000205
PG 7
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Information Science & Library Science;
Medical Informatics
SC Computer Science; Information Science & Library Science; Medical
Informatics
GA 841DB
UT WOS:000296491600008
PM 21715428
ER
PT J
AU Calboli, FCF
Cox, DG
Buring, JE
Gaziano, JM
Ma, J
Stampfer, M
Willett, WC
Tworoger, SS
Hunter, DJ
Camargo, CA
Michaud, DS
AF Calboli, Federico C. F.
Cox, David G.
Buring, Julie E.
Gaziano, J. Michael
Ma, Jing
Stampfer, Meir
Willett, Walter C.
Tworoger, Shelley S.
Hunter, David J.
Camargo, Carlos A., Jr.
Michaud, Dominique S.
TI Prediagnostic Plasma IgE Levels and Risk of Adult Glioma in Four
Prospective Cohort Studies
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID BRAIN-TUMORS; IMMUNOGLOBULIN-E; ALLERGY; DISEASE
AB Background Increased levels of serum immunoglobulin E (IgE) because of allergies have been inversely associated with risk of glioma in observational studies. Despite consistency across studies examining history of allergies and glioma, questions remain as to whether those are causal associations. An inverse association between serum IgE and risk of glioma was reported in a large case-control study, but reverse causality and treatment effects remain potential explanations for those findings.
Methods We combined data from four prospective cohort studies and used a nested case-control design to examine the association between allergy and glioma. We included glioma case subjects who were confirmed from medical or pathology records or from death certificates, and with prediagnostic blood available. We matched three control subjects per case subject, and the final numbers for analyses were 169 case subjects and 520 control subjects. Total IgE, food allergen-specific IgE, and respiratory allergen-specific IgE levels were measured using a highly sensitive fluorescent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression analysis. Stratified analyses were conducted by age and birth cohorts.
Results Borderline elevated total IgE levels (25-100 kU/L) showed a statistically significant inverse association with glioma (OR = 0.63, 95% CI = 0.42 to 0.93), but no association was noted between elevated IgE (>100 kU/L) and glioma (OR = 0.98, 95% CI = 0.61 to 1.56) compared with clinically normal IgE levels (<25 kU/L). The association between glioma and total IgE was consistent for both men and women. Non-statistically significant inverse associations were noted for elevated IgE levels among individuals born before year 1930 (OR = 0.67, 95% CI = 0.34 to 1.34) and when restricting analyses to highly fatal (deceased within 2 years of diagnosis) glioma case subjects (OR = 0.64, 95% CI = 0.34 to 1.19) compared with individuals with clinically normal IgE levels. No associations were observed for either food allergen-specific or respiratory allergen-specific IgE levels.
Conclusions Overall, our prospective findings are consistent with recent retrospective studies and support an association between total IgE levels and glioma. However, this association requires further elucidation.
C1 [Michaud, Dominique S.] Brown Univ, Dept Epidemiol, Div Biol & Med, Providence, RI 02912 USA.
[Calboli, Federico C. F.; Cox, David G.; Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.
[Cox, David G.] Ctr Leon Berard, INSERM, U1052, Lyon Canc Res Ctr, F-69373 Lyon, France.
[Buring, Julie E.; Gaziano, J. Michael] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Ma, Jing; Stampfer, Meir; Willett, Walter C.; Tworoger, Shelley S.; Hunter, David J.; Camargo, Carlos A., Jr.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Ma, Jing; Stampfer, Meir; Willett, Walter C.; Tworoger, Shelley S.; Hunter, David J.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA.
[Stampfer, Meir; Willett, Walter C.; Tworoger, Shelley S.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Stampfer, Meir; Willett, Walter C.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Michaud, DS (reprint author), Brown Univ, Dept Epidemiol, Div Biol & Med, Box G-S121-2,121 S Main St, Providence, RI 02912 USA.
EM dominique_michaud@brown.edu
RI Cox, David/A-2023-2009; Michaud, Dominique/I-5231-2014;
OI Cox, David/0000-0002-2152-9259; Tworoger, Shelley/0000-0002-6986-7046
FU National Institutes of Health [R01 CA114205, R01 CA047988, R01 HL043851,
P01 CA097193, P01 CA087969, P01 CA055075]
FX This work was supported by the National Institutes of Health (R01
CA114205 to DSM, R01 CA047988 and R01 HL043851 to JEB, P01 CA097193 to
JMG, P01 CA087969 to Dr Susan Hankinson, P01 CA055075 to WCW).
NR 20
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U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD NOV
PY 2011
VL 103
IS 21
BP 1588
EP 1595
DI 10.1093/jnci/djr361
PG 8
WC Oncology
SC Oncology
GA 843HK
UT WOS:000296662700007
PM 22010181
ER
PT J
AU McMahon, PM
Kong, CY
Bouzan, C
Weinstein, MC
Cipriano, LE
Tramontano, AC
Johnson, BE
Weeks, JC
Gazelle, GS
AF McMahon, Pamela M.
Kong, Chung Yin
Bouzan, Colleen
Weinstein, Milton C.
Cipriano, Lauren E.
Tramontano, Angela C.
Johnson, Bruce E.
Weeks, Jane C.
Gazelle, G. Scott
TI Cost-Effectiveness of Computed Tomography Screening for Lung Cancer in
the United States
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Lung cancer; Screening; Cost-utility analysis; Microsimulation model
ID QUALITY-OF-LIFE; SMOKING-CESSATION; MORTALITY REDUCTION;
CONTROLLED-TRIAL; NICOTINE PATCH; TASK-FORCE; HEALTH; BUPROPION;
OUTCOMES; INTERVENTION
AB Introduction: A randomized trial has demonstrated that lung cancer screening reduces mortality. Identifying participant and program characteristics that influence the cost-effectiveness of screening will help translate trial results into benefits at the population level.
Methods: Six U.S. cohorts (men and women aged 50, 60, or 70 years) were simulated in an existing patient-level lung cancer model. Smoking histories reflected observed U.S. patterns. We simulated lifetime histories of 500,000 identical individuals per cohort in each scenario. Costs per quality-adjusted life-year gained ($/QALY) were estimated for each program: computed tomography screening; stand-alone smoking cessation therapies (4-30% 1-year abstinence); and combined programs.
Results: Annual screening of current and former smokers aged 50 to 74 years costs between $126,000 and $169,000/QALY (minimum 20 pack-years of smoking) or $110,000 and $166,000/QALY (40 pack-year minimum), when compared with no screening and assuming background quit rates. Screening was beneficial but had a higher cost per QALY when the model included radiation-induced lung cancers. If screen participation doubled background quit rates, the cost of annual screening (at age 50 years, 20 pack-year minimum) was below $75,000/QALY. If screen participation halved background quit rates, benefits from screening were nearly erased. If screening had no effect on quit rates, annual screening costs more but provided fewer QALYs than annual cessation therapies. Annual combined screening/cessation therapy programs at age 50 years costs $130,500 to $159,700/QALY, when compared with annual stand-alone cessation.
Conclusions: The cost-effectiveness of computed tomography screening will likely be strongly linked to achievable smoking cessation rates. Trials and further modeling should explore the consequences of relationships between smoking behaviors and screen participation.
C1 [McMahon, Pamela M.; Kong, Chung Yin; Bouzan, Colleen; Cipriano, Lauren E.; Tramontano, Angela C.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[McMahon, Pamela M.; Kong, Chung Yin; Gazelle, G. Scott] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Weinstein, Milton C.; Johnson, Bruce E.; Weeks, Jane C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Weinstein, Milton C.; Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Cipriano, Lauren E.] Stanford Univ, Dept Management Sci & Engn, Stanford, CA 94305 USA.
[Johnson, Bruce E.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
[Weeks, Jane C.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
[Weeks, Jane C.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
RP McMahon, PM (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM pamela@mgh-ita.org
RI Cipriano, Lauren/C-3521-2017
OI Cipriano, Lauren/0000-0001-5568-4516
FU National Electrical Manufacturers Association; American Cancer Society
[RSG 2008A060554]; National Cancer Institute [R01CA97337, R00CA126147]
FX The National Electrical Manufacturers Association funded Tramontano and
Gazelle for an unrelated project. Gazelle is a consultant to GE
Healthcare. All other authors declare no conflicts of interest.;
Supported by American Cancer Society (RSG 2008A060554) and National
Cancer Institute (R01CA97337 [to G.S.G.] and R00CA126147 [to P.M.M.]).
NR 43
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U1 2
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD NOV
PY 2011
VL 6
IS 11
BP 1841
EP 1848
DI 10.1097/JTO.0b013e31822e59b3
PG 8
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 843UW
UT WOS:000296700400009
PM 21892105
ER
PT J
AU Caplin, DM
Nikolic, B
Kalva, SP
Ganguli, S
Saad, WEA
Zuckerman, DA
AF Caplin, Drew M.
Nikolic, Boris
Kalva, Sanjeeva P.
Ganguli, Suvranu
Saad, Wael E. A.
Zuckerman, Darryl A.
CA Soc Interventional Radiology Stand
TI Quality Improvement Guidelines for the Performance of Inferior Vena Cava
Filter Placement for the Prevention of Pulmonary Embolism
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID TITANIUM GREENFIELD FILTER; CLINICAL-EXPERIENCE; VENOUS THROMBOSIS;
FOLLOW-UP; COMPLICATIONS; MIGRATION; MULTICENTER; SAFETY; TEMPORARY;
INSERTION
C1 [Caplin, Drew M.] N Shore Univ Hosp, Dept Radiol, Div Intervent Radiol, Manhasset, NY USA.
[Nikolic, Boris] Albert Einstein Med Ctr, Dept Radiol, Philadelphia, PA 19141 USA.
[Kalva, Sanjeeva P.; Ganguli, Suvranu] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Saad, Wael E. A.] Univ Virginia Hlth Syst, Dept Radiol, Charlottesville, VA USA.
[Zuckerman, Darryl A.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
RP Caplin, DM (reprint author), SIR, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA.
EM dcaplin@nshs.edu
FU Siemens (Forchheim, Germany); Amirsys; Elsevier
FX S.P.K. receives royalties from book publishers Amirsys and Elsevier.
W.E.A.S. is a paid consultant for Boston Scientific (Natick,
Massachusetts), has research funded by Siemens (Forchheim, Germany), and
serves on the Speaker's Bureau for Atrium (Hudson, New Hampshire). None
of the other authors have identified a conflict of interest
NR 74
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U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD NOV
PY 2011
VL 22
IS 11
BP 1499
EP 1506
DI 10.1016/j.jvir.2011.07.012
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 843HB
UT WOS:000296661800001
PM 21890380
ER
PT J
AU Angel, LF
Tapson, V
Galgon, RE
Restrepo, MI
Kaufman, J
AF Angel, Luis F.
Tapson, Victor
Galgon, Richard E.
Restrepo, Marcos I.
Kaufman, John
TI Systematic Review of the Use of Retrievable Inferior Vena Cava Filters
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Review
ID DEEP-VEIN THROMBOSIS; PULMONARY-EMBOLISM; VENOUS THROMBOEMBOLISM;
LONG-TERM; FOLLOW-UP; CLINICAL-EXPERIENCE; TECHNICAL SUCCESS; TRAUMA
PATIENTS; OPTEASE FILTER; MULTICENTER
AB Purpose: To review the available literature on retrievable inferior vena cava (IVC) filters to examine the effectiveness and risks of these devices.
Materials and Methods: Investigators searched MEDLINE for clinical trials evaluating retrievable filters and reviewed the complications reported to the Manufacturer and User Facility Device Experience (MAUDE) database of the U.S. Food and Drug Administration (FDA).
Results: Eligibility criteria were met by 37 studies comprising 6,834 patients. All of the trials had limitations, and no studies were randomized. There were 11 prospective clinical trials; the rest were retrospective studies. Despite the limitations of the evidence, the IVC filters seemed to be effective in preventing pulmonary embolism (PE); the rate of PE after IVC placement was 1.7%. The mean retrieval rate was 34%. Most of the filters became permanent devices. Multiple complications associated with the use of IVC filters were described in the reviewed literature or were reported to the MAUDE database; most of these were associated with long-term use (> 30 days). At the present time, the objective comparison data of different filter designs do not support superiority of any particular design.
Conclusions: In high-risk patients for whom anticoagulation is not feasible, retrievable IVC filters seem to be effective in preventing PE. Long-term complications are a serious concern with the use of these filters. The evidence of the effectiveness and the risks was limited by the small number of prospective studies.
C1 [Angel, Luis F.; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA.
[Tapson, Victor] Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC USA.
[Galgon, Richard E.] Univ Wisconsin, Dept Anesthesiol, Madison, WI USA.
[Restrepo, Marcos I.] S Texas Vet Hlth Care Syst, VERDICT, Audie L Murphy Div, San Antonio, TX USA.
[Kaufman, John] Oregon Hlth & Sci Ctr, Dotter Intervent Inst, Portland, OR USA.
RP Angel, LF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM angel@uthscsa.edu
RI Restrepo, Marcos/H-4442-2014
FU Department of Medicine, Division of Pulmonary and Critical Care
Medicine, University of Texas Health Science Center at San Antonio;
BiO2 Medical
FX Funding was provided by the Department of Medicine, Division of
Pulmonary and Critical Care Medicine, University of Texas Health Science
Center at San Antonio.; L.F.A. has a financial relationship with
BiO2 Medical. J.K. has received research funding from
BiO2 Medical. None of the other authors have identified a
conflict of interest.
NR 66
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U1 3
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
EI 1535-7732
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD NOV
PY 2011
VL 22
IS 11
BP 1522
EP 1530
DI 10.1016/j.jvir.2011.08.024
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 843HB
UT WOS:000296661800006
PM 22024114
ER
PT J
AU Fishman, JA
AF Fishman, Jay A.
TI Infections in Immunocompromised Hosts and Organ Transplant Recipients:
Essentials
SO LIVER TRANSPLANTATION
LA English
DT Article
AB Key Points
(1) Why do we need to know anything about these patients? Regardless of their specialties, physicians are increasingly confronted with the side effects of therapies that cause varying degrees of immunosuppression: chemotherapy and stem cell transplantation for cancer, solid organ transplantation, and therapies for autoimmune and rheumatological diseases. The management of these patients is increasingly being returned to community-based physicians. The infectious disease clinician is faced with major challenges.
(2) The possible etiologies of infections are diverse; they range from common bacterial and viral pathogens that affect the entire community to opportunistic pathogens that are clinically significant only for immunocompromised hosts.
(3) Inflammatory responses are impaired by immunosuppressive therapy, and this results in diminished clinical and radiological findings. Thus, an early diagnosis is much more difficult, but it is the key to successful therapy. Invasive diagnostic procedures are often required.
(4) Antimicrobial therapies are often more complex in these patients versus other patients because of the urgency of empiric therapy and the frequency of drug toxicity and drug interactions.
(5) Drug interactions and drug toxicity are common. The initiation or cessation of antimicrobial therapies may alter the levels of calcineurin inhibitors, antifungal agents, and other drugs.
(6) Graft rejection and graft-versus-host disease may be confused with infections.
(7) New pathogens and new manifestations of infections in compromised hosts are also problems:
a. Pathogens common to individuals with prolonged defects in their cellular immune function (human immunodeficiency virus) and to neutropenic hosts [Rhodococcus, Cryptosporidium, and Penicillium species; Mycobacterium species (eg, Mycobacterium avium complex); and Scedosporium] have been identified in transplant recipients.
b. Antimicrobial resistance is a major problem [vancomycin-resistant Enterococcus; methicillin-resistant Staphylococcus aureus; Pseudomonas, Stenotrophomonas, and Burkholderia species; fungi (both yeasts and molds); and ganciclovir-resistant cytomegalovirus].
c. There are few therapies for newer viral pathogens (eg, human herpesvirus 6, human herpesvirus 8, and BK virus) and common respiratory viruses (eg, respiratory syncytial virus, adenoviruses, and Metapneumovirus).
d. Patients from endemic regions may have parasites (eg, Chagas disease and Leishmania).
C1 Harvard Univ, Transplant Infect Dis & Compromised Host Serv, Div Infect Dis, Massachusetts Gen Hosp,Sch Med,Transplant Ctr, Boston, MA 02114 USA.
RP Fishman, JA (reprint author), Harvard Univ, Transplant Infect Dis & Compromised Host Serv, Div Infect Dis, Massachusetts Gen Hosp,Sch Med,Transplant Ctr, 55 Fruit St,GRJ 05, Boston, MA 02114 USA.
EM jfishman@partners.org
NR 0
TC 43
Z9 43
U1 0
U2 12
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1527-6465
J9 LIVER TRANSPLANT
JI Liver Transplant.
PD NOV
PY 2011
VL 17
SU 3
BP S34
EP S37
DI 10.1002/lt.22378
PG 4
WC Gastroenterology & Hepatology; Surgery; Transplantation
SC Gastroenterology & Hepatology; Surgery; Transplantation
GA 843VH
UT WOS:000296702000007
PM 21748845
ER
PT J
AU Muir, ER
Duong, TQ
AF Muir, Eric R.
Duong, Timothy Q.
TI Layer-Specific Functional and Anatomical MRI of the Retina With Passband
Balanced SSFP
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE steady state free precession; SSFP; fMRI; retina; ophthalmology; hypoxia
ID MANGANESE-ENHANCED MRI; CHOROIDAL BLOOD-FLOW; RAT RETINA; DEGENERATION;
RESOLUTION; BRAIN; TESLA
AB The retina consists of multiple cellular and synaptic layers and is nourished by two distinct (retinal and choroidal) circulations bounding the retina, separated by an avascular layer. High spatiotemporal resolution, layer-specific MRI of the retina remains challenging due to magnetic inhomogeneity-induced artifacts. This study reports passband balanced steady-state free-precession (bSSFP) MRI at 45x45x500 mm and 1.6 s temporal resolution to image the mouse retina, overcoming geometric distortion and signal dropout while maintaining rapid acquisition and high signal-to-noise ratio. bSSFP images revealed multiple alternating dark-bright-dark-bright retinal layers. Hypoxic (10% O(2)) inhalation decreased bSSFP signals in the two layers bounding the retina, corresponding to the retinal and choroidal vasculatures. The layer in between showed no substantial response and was assigned the avascular photoreceptor layers. Choroidal responses (-25.9 +/- 6.4%, mean +/- SD, n=6) were significantly (P< 0.05) larger than retinal vascular responses (-11.6 +/- 2.4%). bSSFP offers very high spatiotemporal resolution and could have important applications in imaging layer-specific changes in retinal diseases. Magn Reson Med 66: 1416-1421, 2011. (C) 2011 Wiley Periodicals, Inc.
C1 [Muir, Eric R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA.
[Muir, Eric R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Radiol, San Antonio, TX 78229 USA.
[Muir, Eric R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Physiol, San Antonio, TX 78229 USA.
[Muir, Eric R.] Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA.
[Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA.
EM duongt@uthscsa.edu
RI Duong, Timothy/B-8525-2008; Muir, Eric/H-8830-2013
FU National Eye Institute/National Institutes of Health [R01 EY018855, R01
EY014211]; Department of Veterans Affairs
FX Grant sponsor: National Eye Institute/National Institutes of Health;
Grant numbers: R01 EY018855, R01 EY014211; Grant sponsor: Department of
Veterans Affairs (VA MERIT Award).
NR 27
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U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD NOV
PY 2011
VL 66
IS 5
BP 1416
EP 1421
DI 10.1002/mrm.22935
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 839SP
UT WOS:000296389800024
PM 21604296
ER
PT J
AU Tisdall, MD
Lockhart, RA
Atkins, MS
AF Tisdall, M. Dylan
Lockhart, Richard A.
Atkins, M. Stella
TI The Bias/Variance Trade-Off When Estimating the MR Signal Magnitude From
the Complex Average of Repeated Measurements
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE signal-to-noise ratio; image bias; maximum likelihood estimate;
denoising; nuisance parameters
ID MAGNETIC-RESONANCE IMAGES; MAXIMUM-LIKELIHOOD-ESTIMATION;
CONFIDENCE-INTERVALS; RICIAN DISTRIBUTION; LOW SNR; NOISE; PARAMETERS;
PERFORMANCE; VARIANCE; ENVELOPE
AB The signal-dependent bias of MR images has been considered a hindrance to visual interpretation almost since the beginning of clinical MRI. Over time, a variety of procedures have been suggested to produce less-biased images from the complex average of repeated measurements. In this work, we re-evaluate these approaches using first a survey of previous estimators in the MRI literature, then a survey of the methods statisticians employ for our specific problem. Our conclusions are substantially different from much of the previous work: first, removing bias completely is impossible if we demand the estimator have bounded variance; second, reducing bias may not be beneficial to image quality. Magn Reson Med 66:1456-1467, 2011. (C) 2011 Wiley Periodicals, Inc.
C1 [Tisdall, M. Dylan] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Tisdall, M. Dylan] Harvard Univ, Dept Radiol, Sch Med, Brookline, MA USA.
[Lockhart, Richard A.] Simon Fraser Univ, Dept Stat & Actuarial Sci, Burnaby, BC V5A 1S6, Canada.
[Atkins, M. Stella] Simon Fraser Univ, Sch Comp Sci, Burnaby, BC V5A 1S6, Canada.
RP Tisdall, MD (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA.
EM tisdall@nmr.mgh.harvard.edu
FU Natural Sciences and Engineering Research Council of Canada
FX Grant sponsor: Natural Sciences and Engineering Research Council of
Canada
NR 40
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U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD NOV
PY 2011
VL 66
IS 5
BP 1456
EP 1467
DI 10.1002/mrm.22910
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 839SP
UT WOS:000296389800028
PM 21469187
ER
PT J
AU Shifren, JL
AF Shifren, Jan L.
TI Increasing our understanding of women's sexuality at midlife and beyond
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Editorial Material
ID POSTMENOPAUSAL WOMEN; UNITED-STATES; HEALTH; NATION; LIFE
C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA.
RP Shifren, JL (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA.
NR 12
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD NOV
PY 2011
VL 18
IS 11
BP 1149
EP 1151
DI 10.1097/gme.0b013e31823161fe
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 842NF
UT WOS:000296605500001
PM 21993079
ER
PT J
AU Chan, K
Davis, J
Pai, SY
Bonilla, FA
Puck, JM
Apkon, M
AF Chan, Kee
Davis, Joie
Pai, Sung-Yun
Bonilla, Francisco A.
Puck, Jennifer M.
Apkon, Michael
TI A Markov model to analyze cost-effectiveness of screening for severe
combined immunodeficiency (SCID)
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Severe combined immunodeficiency (SCID); Newborn screening;
Cost-effectiveness; Markov models; T-cell receptor excision circle
(TREC); Hematopoietic cell transplant
ID STEM-CELL TRANSPLANTATION; MEDICAL DECISION-MAKING; QUALITY-OF-LIFE;
THYMIC OUTPUT; HEALTH; CHILDREN; DISEASE; DEFICIENCY; UNIVERSAL;
BENEFITS
AB Objective: To evaluate the cost-effectiveness of universal neonatal screening for T cell lymphocytopenia in enhancing quality of life and life expectancy for children with severe combined immunodeficiency (SCID).
Methods: Decision trees were created and analyzed to estimate the cost, life years, and quality adjusted life years (QALYs) across a population when universal screening for lack of T cells is used to detect SCID, as implemented in five states, compared to detection based on recognizing symptoms and signs of disease. Terminal values of each tree limb were derived through Markov models simulating the natural history of three cohorts: unaffected subjects; those diagnosed with SCID as neonates (early diagnosis); and those diagnosed after becoming symptomatic and arousing clinical suspicion (late diagnosis). Models considered the costs of screening and of care including hematopoietic cell transplantation for affected individuals. Key decision variables were derived from the literature and from a survey of families with children affected by SCID, which was used to describe the clinical history and healthcare utilization for affected subjects. Sensitivity analyses were conducted to explore the influence of these decision variables.
Results: Over a 70-year time horizon, the average cost per infant was $8.89 without screening and $14.33 with universal screening. The model predicted that universal screening in the U.S. would cost approximately $22.4 million/year with a gain of 880 life years and 802 QALYs. Sensitivity analyses showed that screening test specificity and disease incidence were critical driving forces affecting the incremental cost-effectiveness ratio (ICER). Assuming a SCID incidence of 1/75,000 births and test specificity and sensitivity each at 0.99, screening remained cost-effective up to a maximum cost of $15 per infant screened.
Conclusion: At our current estimated screening cost of $4.22/infant, universal screening for SCID would be a cost effective means to improve quality and duration of life for children with SCID. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Chan, Kee] Boston Univ, Coll Hlth & Rehabil Sci, Sargent Coll, Dept Hlth Sci, Boston, MA 02215 USA.
[Chan, Kee] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
[Davis, Joie] NIAID, NIH, Bethesda, MD 20892 USA.
[Pai, Sung-Yun; Bonilla, Francisco A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Pai, Sung-Yun] Childrens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA.
[Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Bonilla, Francisco A.] Childerns Hosp, Div Immunol, Dept Med, Boston, MA USA.
[Puck, Jennifer M.] Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA.
[Puck, Jennifer M.] Univ Calif San Francisco, Benioff Childrens Hosp, San Francisco, CA 94143 USA.
[Apkon, Michael] Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA.
[Apkon, Michael] Childrens Hosp Philadelphia, Philadelphia, PA USA.
[Chan, Kee; Davis, Joie; Puck, Jennifer M.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Chan, Kee] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Apkon, Michael] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Apkon, Michael] Yale Univ, Sch Management, New Haven, CT 06510 USA.
RP Chan, K (reprint author), Boston Univ, Coll Hlth & Rehabil Sci, Sargent Coll, Dept Hlth Sci, 635 Commonwealth Ave, Boston, MA 02215 USA.
EM keechan@bu.edu
FU NHGRI; NIH; Division of Intramural Research; USIDNET [NO1-AI-30070];
Jeffrey Modell Foundation
FX Funds for this work came from the NHGRI, NIH, Division of Intramural
Research, USIDNET grant NO1-AI-30070 to JMP and the Jeffrey Modell
Foundation. We are grateful to the Immune Deficiency Foundation SCID
Initiative and SCID.net for posting our survey online and to the parents
of SCID children who recounted and re-lived their experiences for us in
the hope that future SCID children would benefit.
NR 38
TC 41
Z9 43
U1 3
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD NOV
PY 2011
VL 104
IS 3
BP 383
EP 389
DI 10.1016/j.ymgme.2011.07.007
PG 7
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 843KN
UT WOS:000296670800027
PM 21810544
ER
PT J
AU Rivas, MA
Beaudoin, M
Gardet, A
Stevens, C
Sharma, Y
Zhang, CK
Boucher, G
Ripke, S
Ellinghaus, D
Burtt, N
Fennell, T
Kirby, A
Latiano, A
Goyette, P
Green, T
Halfvarson, J
Haritunians, T
Korn, JM
Kuruvilla, F
Lagace, C
Neale, B
Lo, KS
Schumm, P
Torkvist, L
Dubinsky, MC
Brant, SR
Silverberg, MS
Duerr, RH
Altshuler, D
Gabriel, S
Lettre, G
Franke, A
D'Amato, M
McGovern, DPB
Cho, JH
Rioux, JD
Xavier, RJ
Daly, MJ
AF Rivas, Manuel A.
Beaudoin, Melissa
Gardet, Agnes
Stevens, Christine
Sharma, Yashoda
Zhang, Clarence K.
Boucher, Gabrielle
Ripke, Stephan
Ellinghaus, David
Burtt, Noel
Fennell, Tim
Kirby, Andrew
Latiano, Anna
Goyette, Philippe
Green, Todd
Halfvarson, Jonas
Haritunians, Talin
Korn, Joshua M.
Kuruvilla, Finny
Lagace, Caroline
Neale, Benjamin
Lo, Ken Sin
Schumm, Phil
Torkvist, Leif
Dubinsky, Marla C.
Brant, Steven R.
Silverberg, Mark S.
Duerr, Richard H.
Altshuler, David
Gabriel, Stacey
Lettre, Guillaume
Franke, Andre
D'Amato, Mauro
McGovern, Dermot P. B.
Cho, Judy H.
Rioux, John D.
Xavier, Ramnik J.
Daly, Mark J.
CA Natl Inst Diabet Digestive Kidney
United Kingdom Inflammatory Bowel
Int Inflammatory Bowel Dis
TI Deep resequencing of GWAS loci identifies independent rare variants
associated with inflammatory bowel disease
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MURAMYL DIPEPTIDE RECOGNITION; SUSCEPTIBILITY
LOCI; CROHNS-DISEASE; CARD15 MUTATIONS; RISK LOCI; GENE; NOD2;
FREQUENCY; RECRUITMENT
AB More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 x 10(-16), odds ratio approximate to 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models.
C1 [Rivas, Manuel A.; Ripke, Stephan; Kirby, Andrew; Neale, Benjamin; Altshuler, David; Xavier, Ramnik J.; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Rivas, Manuel A.; Stevens, Christine; Ripke, Stephan; Burtt, Noel; Fennell, Tim; Kirby, Andrew; Green, Todd; Korn, Joshua M.; Kuruvilla, Finny; Neale, Benjamin; Altshuler, David; Gabriel, Stacey; Xavier, Ramnik J.; Daly, Mark J.] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Rivas, Manuel A.] Univ Oxford, Nuffield Dept Clin Med, Oxford, England.
[Beaudoin, Melissa; Boucher, Gabrielle; Goyette, Philippe; Lagace, Caroline; Lo, Ken Sin; Lettre, Guillaume; Rioux, John D.] Univ Montreal, Montreal, PQ, Canada.
[Beaudoin, Melissa; Boucher, Gabrielle; Goyette, Philippe; Lagace, Caroline; Lo, Ken Sin; Lettre, Guillaume; Rioux, John D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada.
[Gardet, Agnes; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Ctr Study Inflammatory Bowe, Boston, MA USA.
[Gardet, Agnes; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA.
[Sharma, Yashoda; Zhang, Clarence K.; Cho, Judy H.] Yale Univ, Sch Med, New Haven, CT USA.
[Ellinghaus, David; Franke, Andre] Inst Clin Mol Biol, Kiel, Germany.
[Latiano, Anna] Casa Sollievo Sofferenza Hosp, Ist Ricovero & Cura Carattere Sci, Gastroenterol Unit, San Giovanni Rotondo, Italy.
[Halfvarson, Jonas] Univ Orebro, Dept Med, Orebro Univ Hosp, Orebro, Sweden.
[Halfvarson, Jonas] Univ Orebro, Sch Hlth & Med Sci, Orebro, Sweden.
[Haritunians, Talin; McGovern, Dermot P. B.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Kuruvilla, Finny] Clarus Ventures, Cambridge, MA USA.
[Schumm, Phil] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Torkvist, Leif] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
[Dubinsky, Marla C.] Cedars Sinai Med Ctr, Pediat Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA.
[Brant, Steven R.] Johns Hopkins Univ, Sch Med, Dept Med, Meyerhoff Inflammatory Bowel Dis Ctr, Baltimore, MD 21205 USA.
[Brant, Steven R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Silverberg, Mark S.] Univ Toronto, Mt Sinai Hosp, Inflammatory Bowel Dis Grp, Toronto, ON M5G 1X5, Canada.
[Duerr, Richard H.] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.
[Duerr, Richard H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[D'Amato, Mauro] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
[McGovern, Dermot P. B.] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA.
RP Daly, MJ (reprint author), Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
EM rivas@broadinstitute.org; mjdaly@atgu.mgh.harvard.edu
RI D'Amato, Mauro/F-2450-2010; Ellinghaus, David/G-4467-2012; Anderson,
Carl/B-8327-2013; Silverberg, Mark/B-4183-2008; Altshuler,
David/A-4476-2009; Schreiber, Stefan/B-6748-2008; Rioux,
John/A-9599-2015; Palmieri, Orazio/J-7697-2012; Latiano,
Anna/R-1965-2016; Franke, Andre/B-2151-2010
OI Henderson, Paul/0000-0003-3634-6428; Panes, Julian/0000-0002-4971-6902;
Barrett, Jeffrey/0000-0002-1152-370X; Gearry,
Richard/0000-0002-2298-5141; Halfvarson, Jonas/0000-0003-0122-7234;
Newman, William/0000-0002-6382-4678; D'Amato, Mauro/0000-0003-2743-5197;
Duerr, Richard/0000-0001-6586-3905; Laukens, Debby/0000-0002-1984-5850;
Anderson, Carl/0000-0003-1719-7009; Altshuler,
David/0000-0002-7250-4107; Schreiber, Stefan/0000-0003-2254-7771; Rioux,
John/0000-0001-7560-8326; Palmieri, Orazio/0000-0002-0019-7929; Latiano,
Anna/0000-0003-3719-2061; Franke, Andre/0000-0003-1530-5811
FU US National Human Genome Research Institute [DK83756, AI062773,
DK060049, DK086502, HG005923, DK043351]; Helmsley Trust; La Fondation
pour la Recherche Medicale; CCFA; Canada Research Chair; US National
Institutes of Allergy and Infectious Diseases [AI065687, AI067152];
NIDDK [DK064869, DK062432]; CCFA [SRA512]; La Fondation de l'Institut de
Cardiologie de Montreal; Crohn's and Colitis Foundation of Canada
(CCFC); Fonds de Recherche en Sante du Quebec [17199]; Canadian
Institutes of Health Research [01038]; Italian Ministry for Health
[GR-2008-1144485]; Giuliani; NCRR [M01-RR00425, U01-DK062413,
P01-DK046763]; Southern California Diabetes Endocrinology Research
Center [DK063491, R21-DK84554-01, U01 DK062413]; German Ministry of
Education and Research through the National Genome Research Network;
Swedish Research Council; Bengt Ihre Foundation; rebro University
Hospital Research Foundation; [DK062431]; [DK062422]; [DK062420];
[DK062423]; [DK062413]; [DK062429]
FX We thank L. Solomon for designing figures, R. Onofrio for designing PCR
primers, K. Ardlie and S. Mahan for assistance in DNA sample
preparation, J. Wilkinson and L. Ambrogio for Illumina sequence project
management, B. Thomson, G. Crenshaw and A. Taylor for genotyping
assistance, E.S. Lander for helpful comments, the Broad Institute
Sequencing Platform for sequence data production, J. Flannick and J.
Maguire for assistance with pooled sequence analysis, and M. dePristo
and the Broad Institute Genome Sequence Analysis Group for sequencing
analysis help and useful discussions. The work was supported by US
National Human Genome Research Institute sequencing grant DK83756; Funds
from the Helmsley Trust to M.J.D. and R.J.X.; and US National Institutes
of Health grants AI062773, DK060049, DK086502, HG005923 and DK043351 (to
R.J.X.). A. G. was supported by fellowships from La Fondation pour la
Recherche Medicale and the CCFA. J.D.R. holds a Canada Research Chair
and is funded by grants from the US National Institutes of Allergy and
Infectious Diseases (AI065687; AI067152) from the NIDDK (DK064869;
DK062432), the CCFA (SRA512), La Fondation de l'Institut de Cardiologie
de Montreal, the Crohn's and Colitis Foundation of Canada (CCFC), the
Fonds de Recherche en Sante du Quebec (17199) and the Canadian
Institutes of Health Research (01038). Genotyping of the Italian samples
was supported by the Italian Ministry for Health GR-2008-1144485 and
unrestricted research grant of Giuliani, with case collections provided
by the Italian Group for IBD. The NIDDK IBDGC is funded by the following
grants: DK062431 (S.R.B.), DK062422 (J.H.C.), DK062420 (R.H.D.),
DK062432 (J.D.R.), DK062423 (M.S.), DK062413 (D.P.B.M.) and DK062429
(J.H.C.). D.P.B.M. is supported by NCRR grant M01-RR00425 to the
Cedars-Sinai General Research Center Genotyping Core, U01-DK062413 (IBD
Genetics Research Center), P01-DK046763 (IBD Program Project Grant) and
Southern California Diabetes Endocrinology Research Center grants
DK063491, R21-DK84554-01 and U01 DK062413. Genotyping of the German
samples was supported by the German Ministry of Education and Research
through the National Genome Research Network with infrastructure support
through the Deutsche Forschungsgemeinschaft cluster of excellence
Inflammation at Interfaces. Genotyping of the Swedish samples was
supported by the Swedish Research Council, the Bengt Ihre Foundation and
the rebro University Hospital Research Foundation.
NR 46
TC 327
Z9 335
U1 5
U2 40
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD NOV
PY 2011
VL 43
IS 11
BP 1066
EP U50
DI 10.1038/ng.952
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 842GS
UT WOS:000296584000009
PM 21983784
ER
PT J
AU Chambers, JC
Zhang, WH
Sehmi, J
Li, XZ
Wass, MN
Van der Harst, P
Holm, H
Sanna, S
Kavousi, M
Baumeister, SE
Coin, LJ
Deng, GH
Gieger, C
Heard-Costa, NL
Hottenga, JJ
Kuhnel, B
Kumar, V
Lagou, V
Liang, LM
Luan, JA
Vidal, PM
Leach, IM
O'Reilly, PF
Peden, JF
Rahmioglu, N
Soininen, P
Speliotes, EK
Yuan, X
Thorleifsson, G
Alizadeh, BZ
Atwood, LD
Borecki, IB
Brown, MJ
Charoen, P
Cucca, F
Das, D
de Geus, EJC
Dixon, AL
Doering, A
Ehret, G
Eyjolfsson, GI
Farrall, M
Forouhi, NG
Friedrich, N
Goessling, W
Gudbjartsson, DF
Harris, TB
Hartikainen, AL
Heath, S
Hirschfield, GM
Hofman, A
Homuth, G
Hypponen, E
Janssen, HLA
Johnson, T
Kangas, AJ
Kema, IP
Kuhn, JP
Lai, S
Lathrop, M
Lerch, MM
Li, Y
Liang, TJ
Lin, JP
Loos, RJF
Martin, NG
Moffatt, MF
Montgomery, GW
Munroe, PB
Musunuru, K
Nakamura, Y
O'Donnell, CJ
Olafsson, I
Penninx, BW
Pouta, A
Prins, BP
Prokopenko, I
Puls, R
Ruokonen, A
Savolainen, MJ
Schlessinger, D
Schouten, JNL
Seedorf, U
Sen-Chowdhry, S
Siminovitch, KA
Smit, JH
Spector, TD
Tan, WT
Teslovich, TM
Tukiainen, T
Uitterlinden, AG
Van der Klauw, MM
Vasan, RS
Wallace, C
Wallaschofski, H
Wichmann, HE
Willemsen, G
Wurtz, P
Xu, C
Yerges-Armstrong, LM
Abecasis, GR
Ahmadi, KR
Boomsma, DI
Caulfield, M
Cookson, WO
van Duijn, CM
Froguel, P
Matsuda, K
McCarthy, MI
Meisinger, C
Mooser, V
Pietilainen, KH
Schumann, G
Snieder, H
Sternberg, MJE
Stolk, RP
Thomas, HC
Thorsteinsdottir, U
Uda, M
Waeber, G
Wareham, NJ
Waterworth, DM
Watkins, H
Whitfield, JB
Witteman, JCM
Wolffenbuttel, BHR
Fox, CS
Ala-Korpela, M
Stefansson, K
Vollenweider, P
Volzke, H
Schadt, EE
Scott, J
Jarvelin, MR
Elliott, P
Kooner, JS
AF Chambers, John C.
Zhang, Weihua
Sehmi, Joban
Li, Xinzhong
Wass, Mark N.
Van der Harst, Pim
Holm, Hilma
Sanna, Serena
Kavousi, Maryam
Baumeister, Sebastian E.
Coin, Lachlan J.
Deng, Guohong
Gieger, Christian
Heard-Costa, Nancy L.
Hottenga, Jouke-Jan
Kuehnel, Brigitte
Kumar, Vinod
Lagou, Vasiliki
Liang, Liming
Luan, Jian'an
Vidal, Pedro Marques
Leach, Irene Mateo
O'Reilly, Paul F.
Peden, John F.
Rahmioglu, Nilufer
Soininen, Pasi
Speliotes, Elizabeth K.
Yuan, Xin
Thorleifsson, Gudmar
Alizadeh, Behrooz Z.
Atwood, Larry D.
Borecki, Ingrid B.
Brown, Morris J.
Charoen, Pimphen
Cucca, Francesco
Das, Debashish
de Geus, Eco J. C.
Dixon, Anna L.
Doering, Angela
Ehret, Georg
Eyjolfsson, Gudmundur I.
Farrall, Martin
Forouhi, Nita G.
Friedrich, Nele
Goessling, Wolfram
Gudbjartsson, Daniel F.
Harris, Tamara B.
Hartikainen, Anna-Liisa
Heath, Simon
Hirschfield, Gideon M.
Hofman, Albert
Homuth, Georg
Hyppoenen, Elina
Janssen, Harry L. A.
Johnson, Toby
Kangas, Antti J.
Kema, Ido P.
Kuehn, Jens P.
Lai, Sandra
Lathrop, Mark
Lerch, Markus M.
Li, Yun
Liang, T. Jake
Lin, Jing-Ping
Loos, Ruth J. F.
Martin, Nicholas G.
Moffatt, Miriam F.
Montgomery, Grant W.
Munroe, Patricia B.
Musunuru, Kiran
Nakamura, Yusuke
O'Donnell, Christopher J.
Olafsson, Isleifur
Penninx, Brenda W.
Pouta, Anneli
Prins, Bram P.
Prokopenko, Inga
Puls, Ralf
Ruokonen, Aimo
Savolainen, Markku J.
Schlessinger, David
Schouten, Jeoffrey N. L.
Seedorf, Udo
Sen-Chowdhry, Srijita
Siminovitch, Katherine A.
Smit, Johannes H.
Spector, Timothy D.
Tan, Wenting
Teslovich, Tanya M.
Tukiainen, Taru
Uitterlinden, Andre G.
Van der Klauw, Melanie M.
Vasan, Ramachandran S.
Wallace, Chris
Wallaschofski, Henri
Wichmann, H-Erich
Willemsen, Gonneke
Wuertz, Peter
Xu, Chun
Yerges-Armstrong, Laura M.
Abecasis, Goncalo R.
Ahmadi, Kourosh R.
Boomsma, Dorret I.
Caulfield, Mark
Cookson, William O.
van Duijn, Cornelia M.
Froguel, Philippe
Matsuda, Koichi
McCarthy, Mark I.
Meisinger, Christa
Mooser, Vincent
Pietilainen, Kirsi H.
Schumann, Gunter
Snieder, Harold
Sternberg, Michael J. E.
Stolk, Ronald P.
Thomas, Howard C.
Thorsteinsdottir, Unnur
Uda, Manuela
Waeber, Gerard
Wareham, Nicholas J.
Waterworth, Dawn M.
Watkins, Hugh
Whitfield, John B.
Witteman, Jacqueline C. M.
Wolffenbuttel, Bruce H. R.
Fox, Caroline S.
Ala-Korpela, Mika
Stefansson, Kari
Vollenweider, Peter
Voelzke, Henry
Schadt, Eric E.
Scott, James
Jarvelin, Marjo-Riitta
Elliott, Paul
Kooner, Jaspal S.
CA Alcohol Genome-wide Assoc AlcGen
Diabet Genetics Replication
Genetic Invest Anthropometric
Global Lipids Genetics Consortium
Genetics Liver Dis GOLD Consortium
Int Consortium Blood Pressure ICBP
Meta-Anal Glucose Insulin-Related
TI Genome-wide association study identifies loci influencing concentrations
of liver enzymes in plasma
SO NATURE GENETICS
LA English
DT Article
ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; SALT EXPORT PUMP; METABOLIC
SYNDROME; RISK-FACTORS; HEPATOCELLULAR-CARCINOMA; HEREDITARY
CHOLESTASIS; SUSCEPTIBILITY LOCI; GENETIC-VARIANTS; COMMON VARIANTS
AB Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.
C1 [Chambers, John C.; Zhang, Weihua; Coin, Lachlan J.; O'Reilly, Paul F.; Charoen, Pimphen; Sen-Chowdhry, Srijita; Tukiainen, Taru; Wuertz, Peter; Jarvelin, Marjo-Riitta; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, London, England.
[Chambers, John C.; Thomas, Howard C.; Kooner, Jaspal S.] Imperial Coll Healthcare Natl Hlth Serv NHS Trust, London, England.
[Chambers, John C.; Zhang, Weihua; Sehmi, Joban; Das, Debashish; Kooner, Jaspal S.] Ealing Hosp NHS Trust, Middlesex, England.
[Sehmi, Joban; Scott, James; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London, England.
[Li, Xinzhong] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, Inst Clin Sci, London, England.
[Wass, Mark N.; Sternberg, Michael J. E.] Univ London Imperial Coll Sci Technol & Med, Div Mol Biosci, Struct Bioinformat Grp, London, England.
[Van der Harst, Pim; Leach, Irene Mateo] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 AB Groningen, Netherlands.
[Holm, Hilma; Thorleifsson, Gudmar; Gudbjartsson, Daniel F.; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[Sanna, Serena; Cucca, Francesco; Lai, Sandra; Uda, Manuela] CNR, Ist Ric Genet & Biomed, Cagliari, Italy.
[Kavousi, Maryam; Hofman, Albert; Janssen, Harry L. A.; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Kavousi, Maryam; Hofman, Albert; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Netherlands Genom Initiat, Rotterdam, Netherlands.
[Baumeister, Sebastian E.; Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17487 Greifswald, Germany.
[Deng, Guohong; Tan, Wenting] Third Mil Med Univ, Southwest Hosp, Inst Infect Dis, Chongqing, Peoples R China.
[Gieger, Christian; Kuehnel, Brigitte] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Heard-Costa, Nancy L.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Hottenga, Jouke-Jan; de Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] VU Univ Amsterdam VUA, Dept Biol Psychol, Amsterdam, Netherlands.
[Kumar, Vinod; Nakamura, Yusuke; Matsuda, Koichi] Univ Tokyo, Inst Med Sci, Mol Med Lab, Tokyo, Japan.
[Lagou, Vasiliki; Alizadeh, Behrooz Z.; Prins, Bram P.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Unit Genet Epidemiol & Bioinformat, Groningen, Netherlands.
[Lagou, Vasiliki; Rahmioglu, Nilufer; Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Lagou, Vasiliki; Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Luan, Jian'an; Forouhi, Nita G.; Loos, Ruth J. F.; Wareham, Nicholas J.] Addenbrookes Hosp, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge, England.
[Vidal, Pedro Marques] Univ Lausanne Hosp, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland.
[Vidal, Pedro Marques; Ehret, Georg] Univ Lausanne, Lausanne, Switzerland.
[Peden, John F.; Farrall, Martin; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford, England.
[Soininen, Pasi; Kangas, Antti J.; Savolainen, Markku J.; Tukiainen, Taru; Wuertz, Peter; Ala-Korpela, Mika] Univ Oulu, Inst Clin Med, Computat Med Res Grp, Oulu, Finland.
[Soininen, Pasi; Kangas, Antti J.; Savolainen, Markku J.; Tukiainen, Taru; Wuertz, Peter; Ala-Korpela, Mika] Univ Oulu, Bioctr, Oulu, Finland.
[Soininen, Pasi; Ala-Korpela, Mika] Univ Eastern Finland, Dept Biosci, Nucl Magnet Resonance NMR Metabon Lab, Kuopio, Finland.
[Speliotes, Elizabeth K.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Speliotes, Elizabeth K.] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Yuan, Xin; Mooser, Vincent; Waterworth, Dawn M.] GlaxoSmithKline Inc, Genet, King Of Prussia, PA USA.
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[Charoen, Pimphen] Mahidol Univ, Fac Trop Med, Dept Trop Hyg, Bangkok, Thailand.
[de Geus, Eco J. C.] VUA, Amsterdam, Netherlands.
[de Geus, Eco J. C.] VUA Med Ctr, Amsterdam, Netherlands.
[Dixon, Anna L.; Moffatt, Miriam F.; Cookson, William O.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
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[Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
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[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Wichmann, H-Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Willemsen, Gonneke; Boomsma, Dorret I.] VUA Med Ctr, EMGO Inst, Amsterdam, Netherlands.
[Xu, Chun] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Xu, Chun] Toronto Gen Res Inst, Toronto, ON, Canada.
[Yerges-Armstrong, Laura M.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[van Duijn, Cornelia M.] Ctr Med Syst Biol, Rotterdam, Netherlands.
[Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Publ Hlth, London, England.
[McCarthy, Mark I.] Churchill Hosp, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford OX3 7LJ, England.
[Meisinger, Christa] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Pietilainen, Kirsi H.] Helsinki Univ Hosp, Div Internal Med, Dept Med, Obes Res Unit, Helsinki, Finland.
[Pietilainen, Kirsi H.] Inst Mol Med FIMM, Helsinki, Finland.
[Pietilainen, Kirsi H.] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland.
[Schumann, Gunter] Kings Coll London, Inst Psychiat, MRC Social Genet Dev Psychiat SGDP Ctr, London WC2R 2LS, England.
[Stolk, Ronald P.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
[Thomas, Howard C.] Univ London Imperial Coll Sci Technol & Med, Fac Med, London, England.
[Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Waeber, Gerard; Vollenweider, Peter] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA.
[Schadt, Eric E.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
[Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Jarvelin, Marjo-Riitta; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, MRC, HPA, Ctr Environm Hlth, London, England.
RP Chambers, JC (reprint author), Univ London Imperial Coll Sci Technol & Med, Norfolk Pl, London, England.
EM john.chambers@ic.ac.uk; p.elliott@ic.ac.uk; j.kooner@ic.ac.uk
RI Smith, Albert Vernon/K-5150-2015; Marques-Vidal, Pedro/C-9449-2009;
Kronenberg, Florian/B-1736-2008; Lucas, Gavin/D-4346-2012; Ridderstrale,
Martin/F-7678-2012; Elliott, Amanda/G-5120-2012; Rudan,
Igor/I-1467-2012; Heath, Simon/J-4138-2012; Laan, Maris/A-4100-2011;
Singleton, Andrew/C-3010-2009; Stolk, Ronald/B-2341-2013; Wolffenbuttel,
Bruce/A-8419-2011; Willems van Dijk, Ko/A-1798-2008; Soininen,
Pasi/B-9716-2008; EHRET, Georg/A-9532-2009; Knowles, Josh/C-9241-2013;
Marusic, Ana/E-7683-2013; Kuznetsova, Tatiana/I-6882-2013; Colaus,
PsyColaus/K-6607-2013; Lagou, Vasiliki/N-8451-2013; van der Klauw,
Melanie/A-2138-2014; Hypponen, Elina/B-2596-2014; Hernaez,
Ruben/C-4039-2014; Kiemeney, Lambertus/D-3357-2009; Meisinger,
Christine/B-5358-2014; Grobbee, Diederick/C-7651-2014; Siminovitch,
Katherine/K-1475-2013; Palmer, Lyle/K-3196-2014; Boehm,
Bernhard/F-8750-2015; Onland-Moret, N. Charlotte/G-9185-2011; Gudnason,
Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Mattace- Raso,
Francesco/L-2541-2015; Hirschfield, Gideon/M-2143-2015; Polasek,
Ozren/B-6002-2011; de Geus, Eco/M-9318-2015; Montgomery,
Grant/B-7148-2008; Meitinger, Thomas/O-1318-2015; Prokopenko,
Inga/H-3241-2014; Lerch, Markus M./E-2206-2016; Grarup,
Niels/K-2807-2015; Aben, Katja/G-9686-2016; Ejebe, Kenechi/I-9238-2016;
Kyvik, Kirsten /K-5680-2016; Matullo, Giuseppe/K-6383-2016;
Visvikis-Siest, Sophie/H-2324-2014; Bochud, Murielle/A-3981-2010; Coin,
Lachlan/A-9001-2014; Erdmann, Jeanette/A-4417-2009; Naitza,
Silvia/D-5620-2017; Feitosa, Mary/K-8044-2012;
OI Jorgensen, Torben/0000-0001-9453-2830; Watkins,
Hugh/0000-0002-5287-9016; Visscher, Peter/0000-0002-2143-8760; Marmot,
Michael/0000-0002-2431-6419; Prabhakaran, Dorairaj/0000-0002-3172-834X;
Ouwehand, Willem/0000-0002-7744-1790; Kaprio,
Jaakko/0000-0002-3716-2455; Lawlor, Debbie A/0000-0002-6793-2262;
Rivolta, Carlo/0000-0002-0733-9950; Johansson, Asa/0000-0002-2915-4498;
Arora, Pankaj/0000-0003-2420-3550; Matsuda, Koichi/0000-0001-7292-2686;
Kumari, Meena/0000-0001-9716-1035; Melzer, David/0000-0002-0170-3838;
Goessling, Wolfram/0000-0001-9972-1569; Forouhi,
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Heard-Costa, Nancy/0000-0001-9730-0306
FU European Commission; European Science Foundation; European Science
Council; US NIH; US National Institute of Mental Health; US NIDDK;
Genetic Association Information Network; US National Institute on Aging;
US National Human Genome Research Institute; US NHLBI; UK NIHR; NIHR
Comprehensive Biomedical Research Centre Imperial College Healthcare NHS
Trust; NIHR Comprehensive Biomedical Research Centre Guy's and St.
Thomas' NHS Trust; UK Biotechnology and Biological Sciences Research
Council; UK MRC; British Heart Foundation; Wellcome Trust; Swiss
National Science Foundation; Academy of Finland; Finnish Cardiovascular
Research Foundation; Swedish Research Council; Swedish Heart-Lung
Foundation; Helmholtz Zentrum Munchen; German Research Center for
Environmental Health; German Federal Ministry of Education and Research;
German National Genome Research Network; Netherlands Organization for
Scientific Research; Dutch Ministries of Economic Affairs, of Education,
Culture and Science, for Health, Welfare and Sports; Netherlands
Organization for Health Research and Development; Dutch government;
Dutch Kidney Foundation; Dutch Diabetes Research Foundation; Dutch Brain
Foundation; Dutch Research Institute for Diseases in the Elderly;
Netherlands Genomics Initiative; Canadian Institutes for Health
Research; Ontario Research Fund; Barts and the London Charity;
University Medical Center Groningen; University of Groningen; University
of Oulu, Biocenter Oulu; University Hospital Oulu; Biocentrum Helsinki;
Erasmus Medical Center and Erasmus University, Rotterdam; Karolinska
Institutet; Stockholm County Council; Municipality of Rotterdam; Federal
State of Mecklenburg-West Pomerania; AstraZeneca; GlaxoSmithKline;
Siemens Healthcare; Novo Nordisk Foundation; Yrjo Jahnsson Foundation;
Biomedicum Helsinki Foundation; Gyllenberg Foundation; Knut and Alice
Wallenberg Foundation; Torsten and Ragnar Soderberg Foundation; Boston
University School of Medicine; Instrumentarium Science Foundation; Jenny
and Antti Wihuri Foundation; Canadian Primary Biliary Cirrhosis Society
FX We thank the many colleagues who contributed to collection and
phenotypic characterization of the clinical samples, as well as
genotyping and analysis of data. We also thank the research participants
who took part in these studies. Major support for the work came from
European Commission (FP5, FP6 and FP7); European Science Foundation;
European Science Council; US NIH; US National Institute of Mental
Health; US NIDDK; Genetic Association Information Network; US National
Institute on Aging; US National Human Genome Research Institute; US
NHLBI; UK NIHR; NIHR Comprehensive Biomedical Research Centre Imperial
College Healthcare NHS Trust; NIHR Comprehensive Biomedical Research
Centre Guy's and St. Thomas' NHS Trust; UK Biotechnology and Biological
Sciences Research Council; UK MRC; British Heart Foundation; Wellcome
Trust; Swiss National Science Foundation; Academy of Finland; Finnish
Cardiovascular Research Foundation; Swedish Research Council; Swedish
Heart-Lung Foundation; Helmholtz Zentrum Munchen; German Research Center
for Environmental Health; German Federal Ministry of Education and
Research; German National Genome Research Network; Netherlands
Organization for Scientific Research; Dutch Ministries of Economic
Affairs, of Education, Culture and Science, for Health, Welfare and
Sports; Netherlands Organization for Health Research and Development;
Economic Structure Enhancing Fund of the Dutch government; Dutch Kidney
Foundation; Dutch Diabetes Research Foundation; Dutch Brain Foundation;
Dutch Research Institute for Diseases in the Elderly; Netherlands
Genomics Initiative; Canadian Institutes for Health Research; Ontario
Research Fund; The Barts and the London Charity; University Medical
Center Groningen; University of Groningen; University of Oulu, Biocenter
Oulu; University Hospital Oulu; Biocentrum Helsinki; Erasmus Medical
Center and Erasmus University, Rotterdam; Karolinska Institutet;
Stockholm County Council; Municipality of Rotterdam; Federal State of
Mecklenburg-West Pomerania; AstraZeneca; GlaxoSmithKline; Siemens
Healthcare; Novo Nordisk Foundation; Yrjo Jahnsson Foundation;
Biomedicum Helsinki Foundation; Gyllenberg Foundation; Knut and Alice
Wallenberg Foundation; Torsten and Ragnar Soderberg Foundation; Robert
Dawson Evans Endowment, Boston University School of Medicine;
Instrumentarium Science Foundation; Jenny and Antti Wihuri Foundation
and the Canadian Primary Biliary Cirrhosis Society. A full list of
acknowledgments is provided in the Supplementary Note.
NR 72
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U1 7
U2 76
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD NOV
PY 2011
VL 43
IS 11
BP 1131
EP U129
DI 10.1038/ng.970
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 842GS
UT WOS:000296584000019
PM 22001757
ER
PT J
AU Dvir, T
Timko, BP
Brigham, MD
Naik, SR
Karajanagi, SS
Levy, O
Jin, HW
Parker, KK
Langer, R
Kohane, DS
AF Dvir, Tal
Timko, Brian P.
Brigham, Mark D.
Naik, Shreesh R.
Karajanagi, Sandeep S.
Levy, Oren
Jin, Hongwei
Parker, Kevin K.
Langer, Robert
Kohane, Daniel S.
TI Nanowired three-dimensional cardiac patches
SO NATURE NANOTECHNOLOGY
LA English
DT Article
ID MYOCARDIAL-INFARCTION; GOLD NANORODS; DEVICE ARRAYS; TISSUE; SCAFFOLDS;
ALGINATE; REGENERATION; DELIVERY; HEARTS; REPAIR
AB Engineered cardiac patches for treating damaged heart tissues after a heart attack are normally produced by seeding heart cells within three-dimensional porous biomaterial scaffolds(1-3). These biomaterials, which are usually made of either biological polymers such as alginate(4) or synthetic polymers such as poly(lactic acid) (PLA)(5), help cells organize into functioning tissues, but poor conductivity of these materials limits the ability of the patch to contract strongly as a unit(6). Here, we show that incorporating gold nanowires within alginate scaffolds can bridge the electrically resistant pore walls of alginate and improve electrical communication between adjacent cardiac cells. Tissues grown on these composite matrices were thicker and better aligned than those grown on pristine alginate and when electrically stimulated, the cells in these tissues contracted synchronously. Furthermore, higher levels of the proteins involved in muscle contraction and electrical coupling are detected in the composite matrices. It is expected that the integration of conducting nanowires within three-dimensional scaffolds may improve the therapeutic value of current cardiac patches.
C1 [Dvir, Tal; Timko, Brian P.; Naik, Shreesh R.; Karajanagi, Sandeep S.; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Dvir, Tal; Timko, Brian P.; Kohane, Daniel S.] Harvard Univ, Childrens Hosp Boston, Lab Biomat & Drug Delivery, Dept Anesthesiol,Div Crit Care Med,Med Sch, Boston, MA 02115 USA.
[Brigham, Mark D.; Jin, Hongwei; Parker, Kevin K.] Harvard Univ, Sch Engn & Appl Sci, Wyss Inst Biol Inspired Engn, Dis Biophys Grp, Cambridge, MA 02138 USA.
[Karajanagi, Sandeep S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA.
[Levy, Oren] Harvard Massachusetts Inst Technol Div Hlth Sci &, Cambridge, MA 02139 USA.
[Levy, Oren] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Cambridge, MA 02139 USA.
RP Dvir, T (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
EM Daniel.Kohane@childrens.harvard.edu
FU National Institutes of Health (NIH) [GM073626, DE13023, DE016516];
American Heart Association; NIH Ruth L. Kirschstein National Research
Service [F32GM096546]
FX This research was funded by the National Institutes of Health (NIH,
grants GM073626 to D. S. K. and DE13023 and DE016516 to R. L.). T. D.
thanks the American Heart Association for a Postdoctoral Fellowship. B.
P. T. acknowledges an NIH Ruth L. Kirschstein National Research Service
Award (no. F32GM096546). The authors would like to thank H. Park, B.
Tian, D. Liu, A. Argun and L. Bellan for their assistance and
discussions.
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U1 20
U2 198
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1748-3387
J9 NAT NANOTECHNOL
JI Nat. Nanotechnol.
PD NOV
PY 2011
VL 6
IS 11
BP 720
EP 725
DI 10.1038/NNANO.2011.160
PG 6
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
SC Science & Technology - Other Topics; Materials Science
GA 844HC
UT WOS:000296737300010
PM 21946708
ER
PT J
AU Flaherty, KT
Yasothan, U
Kirkpatrick, P
AF Flaherty, Keith. T.
Yasothan, Uma
Kirkpatrick, Peter
TI Vemurafenib
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Article
ID MELANOMA; BRAF; INHIBITION
C1 [Flaherty, Keith. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Yasothan, Uma] IMS Hlth, London NW1 6JB, England.
RP Flaherty, KT (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM kflaherty@partners.org; UYasothan@imscg.com; p.kirkpatrick@nature.com
NR 9
TC 76
Z9 78
U1 1
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD NOV
PY 2011
VL 10
IS 11
BP 811
EP 812
DI 10.1038/nrd3579
PG 2
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA 842IR
UT WOS:000296592100015
PM 22037033
ER
PT J
AU Ginsburg, ES
Partridge, AH
AF Ginsburg, Elizabeth S.
Partridge, Ann H.
TI REPRODUCTIVE ENDOCRINOLOGY Triptorelin ovarian suppression during breast
cancer chemotherapy
SO NATURE REVIEWS ENDOCRINOLOGY
LA English
DT Editorial Material
ID WOMEN; PREMENOPAUSAL; MENOPAUSE
C1 [Ginsburg, Elizabeth S.; Partridge, Ann H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Ginsburg, ES (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 450 Longwood Ave, Boston, MA 02115 USA.
EM eginsburg@partners.org
NR 10
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5029
J9 NAT REV ENDOCRINOL
JI Nat. Rev. Endocrinol.
PD NOV
PY 2011
VL 7
IS 11
BP 637
EP 638
DI 10.1038/nrendo.2011.159
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 842CM
UT WOS:000296565200004
PM 21931373
ER
PT J
AU Kim, M
Sun, ZYJ
Rand, KD
Shi, XM
Song, LK
Cheng, YX
Fahmy, AF
Majumdar, S
Ofek, G
Yang, YP
Kwong, PD
Wang, JH
Engen, JR
Wagner, G
Reinherz, EL
AF Kim, Mikyung
Sun, Zhen-Yu J.
Rand, Kasper D.
Shi, Xiaomeng
Song, Likai
Cheng, Yuxing
Fahmy, Amr F.
Majumdar, Shreoshi
Ofek, Gilad
Yang, Yongping
Kwong, Peter D.
Wang, Jia-Huai
Engen, John R.
Wagner, Gerhard
Reinherz, Ellis L.
TI Antibody mechanics on a membrane-bound HIV segment essential for
GP41-targeted viral neutralization
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; EXCHANGE-MASS-SPECTROMETRY;
COMPLEMENTARITY-DETERMINING REGION; STRUCTURAL BASIS; GP41 ECTODOMAIN;
COMBINING SITE; HEAVY-CHAIN; EPITOPE; 2F5; 4E10
AB Broadly neutralizing antibodies such as 2F5 are directed against the membrane-proximal external region (MPER) of HIV-1 GP41 and recognize well-defined linear core sequences. These epitopes can be engrafted onto protein scaffolds to serve as immunogens with high structural fidelity. Although antibodies that bind to this core GP41 epitope can be elicited, they lack neutralizing activity. To understand this paradox, we used biophysical methods to investigate the binding of human 2F5 to the MPER in a membrane environment, where it resides in vivo. Recognition is stepwise, through a paratope more extensive than core binding site contacts alone, and dynamic rearrangement through an apparent scoop-like movement of heavy chain complementarity-determining region 3 (CDRH3) is essential for MPER extraction from the viral membrane. Core-epitope recognition on the virus requires the induction of conformational changes in both the MPER and the paratope. Hence, target neutralization through this lipid-embedded viral segment places stringent requirements on the plasticity of the antibody combining site.
C1 [Kim, Mikyung; Cheng, Yuxing; Majumdar, Shreoshi; Wang, Jia-Huai; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA.
[Kim, Mikyung; Song, Likai; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Sun, Zhen-Yu J.; Fahmy, Amr F.; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Rand, Kasper D.; Shi, Xiaomeng; Engen, John R.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA.
[Rand, Kasper D.; Shi, Xiaomeng; Engen, John R.] Northeastern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA.
[Song, Likai; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Song, Likai] Natl High Magnet Field Lab, Tallahassee, FL USA.
[Cheng, Yuxing] Harvard Univ, Sch Publ Hlth, PhD Program Biol Sci Publ Hlth, Boston, MA 02115 USA.
[Ofek, Gilad; Yang, Yongping; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Wang, Jia-Huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA.
EM ellis_reinherz@dfci.harvard.edu
OI Rand, Kasper/0000-0002-6337-5489
FU US National Institutes of Health (NIH) [RO1AI84785, U19AI91693]; Gates
Foundation; NIH [RO1-GM086507]; Waters Corporation; The Danish Council
for Independent Research in Natural Sciences [09-063876]; US National
High Magnetic Field Laboratory (NHMFL); US National Science Foundation
[DMR-0654118]; State of Florida; US Department of Energy; The
Collaboration for AIDS Vaccine Discovery (CAVD) Program
FX This work was supported by US National Institutes of Health (NIH) grants
RO1AI84785 and U19AI91693 to E.L.R. and G.W., and a grant from the Gates
Foundation, The Collaboration for AIDS Vaccine Discovery (CAVD) Program
to E.L.R., G.W. and J.R.E. J.R.E. was also supported by NIH grant
RO1-GM086507 and funding through a cooperative research agreement with
the Waters Corporation. K.D.R. was supported by The Danish Council for
Independent Research in Natural Sciences (FNU grant 09-063876). J.R.E.
would like to thank T.E. Wales for expert technical assistance. L.S. was
also supported by an US National High Magnetic Field Laboratory (NHMFL)
User Collaboration Grants Program award. The NHMFL is funded by the US
National Science Foundation through the Cooperative Agreement No.
DMR-0654118, the State of Florida, and the US Department of Energy.
NR 58
TC 51
Z9 51
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD NOV
PY 2011
VL 18
IS 11
BP 1235
EP U81
DI 10.1038/nsmb.2154
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 844FX
UT WOS:000296734200010
PM 22002224
ER
PT J
AU Middleton, LE
Grinberg, LT
Miller, B
Kawas, C
Yaffe, K
AF Middleton, L. E.
Grinberg, L. T.
Miller, B.
Kawas, C.
Yaffe, K.
TI Neuropathologic features associated with Alzheimer disease diagnosis Age
matters
SO NEUROLOGY
LA English
DT Article
ID CENTER NACC DATABASE; OLDEST-OLD; LEWY BODIES; DEMENTIA; CENTENARIANS;
POPULATION; NONAGENARIANS; PREVALENCE; AUTOPSY; COHORT
AB Objective: To examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age.
Methods: We conducted a cross-sectional analysis of 2,014 older adults (>= 70 years at death) from the National Alzheimer's Coordinating Center database with clinical diagnosis of normal cognition (made <= 1 year before death, n = 419) or AD (at >= 65 years, n = 1,595) and a postmortem neuropathologic examination evaluating AD pathology (neurofibrillary tangles, neuritic plaques) and non-AD pathology (diffuse plaques, amyloid angiopathy, Lewy bodies, macrovascular disease, microvascular disease). We used adjusted logistic regression to analyze the relationship between clinical AD diagnosis and neuropathologic features, area under the receiver operating characteristic curve (c statistic) to evaluate how precisely neuropathology differentiates between cognitive diagnoses, and an interaction to identify effect modification by age group.
Results: In a model controlling for coexisting neuropathologic features, the relationship between clinical AD diagnosis and neurofibrillary tangles was significantly weaker with increasing age (p < 0.001 for interaction). The aggregate of all neuropathologic features more strongly differentiated people with clinical AD from those without in younger age groups (70-74 years: c statistic, 95% confidence interval: 0.93, 0.89-0.96; 75-84 years: 0.95, 0.87-0.95; >= 85 years: 0.83, 0.80-0.87). Non-AD pathology significantly improved precision of differentiation across all age groups (p < 0.004).
Conclusion: Clinical AD diagnosis was more weakly associated with neurofibrillary tangles among the oldest old compared to younger age groups, possibly due to less accurate clinical diagnosis, better neurocompensation, or unaccounted pathology among the oldest old. Neurology (R) 2011;77:1737-1744
C1 [Middleton, L. E.] Univ Waterloo, Waterloo, ON N2L 3G1, Canada.
[Middleton, L. E.] Sunnybrook Hlth Sci Ctr, Heart & Stroke Fdn, Ctr Stroke Recovery, Toronto, ON M4N 3M5, Canada.
[Miller, B.; Yaffe, K.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA.
[Grinberg, L. T.; Miller, B.; Yaffe, K.] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA.
[Yaffe, K.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Middleton, LE (reprint author), 200 Univ Ave W,BMH 1114, Waterloo, ON N2L 3G1, Canada.
EM laura.middleton@uwaterloo.ca
RI Middleton, Laura/C-6024-2009;
OI Middleton, Laura/0000-0001-8624-3123; grinberg, lea/0000-0002-6809-0618
FU Canadian Institute of Health Research; Alzheimer's Association; John
Douglas French Alzheimer's Foundation; publication of Behavioral
Neurology of Dementia (Cambridge); Handbook of Neurology (Elsevier);
Human Frontal Lobes (Guilford); Novartis; NIH/NIA; State of California
Alzheimer's Center; NIH/ Alzheimer's Disease Research Centre; NIH (NIA,
NIDDK, NIMH); Department of Defense; American Health Assistance
Foundation; Anonymous Foundation; Alzheimer Association; NIH [U01
AG016976]
FX Dr. Middleton serves on the editorial board of the Journal of
Alzheimer's Disease and receives fellowship support from the Canadian
Institute of Health Research fellowship. Dr. Grinberg serves as an
Associate Editor for Frontiers in Dementia and Cell and Tissue Banking;
and receives research support from the Alzheimer's Association and the
John Douglas French Alzheimer's Foundation. Dr. Miller serves on a
scientific advisory board for the Alzheimer's Disease Clinical Study;
serves as an Editor for Neurocase and as an Associate Editor of ADAD;
receives royalties from the publication of Behavioral Neurology of
Dementia (Cambridge, 2009), Handbook of Neurology (Elsevier, 2009), and
The Human Frontal Lobes (Guilford, 2008); serves as a consultant for
Lundbeck Inc., Elan Corporation, and Allon Therapeutics, Inc.; serves on
speakers' bureaus for Novartis and Pfizer Inc.; and receives research
support from Novartis and the NIH/NIA and the State of California
Alzheimer's Center. Dr. Kawas serves on a scientific advisory board for
Quintiles and receives research support from the NIH/ Alzheimer's
Disease Research Centre. Dr. Yaffe has served on data safety monitoring
boards for Pfizer Inc, Medivation, Inc., and the NIH (NIMH and NIA
trials); and has received research support from the NIH (NIA, NIDDK,
NIMH), the Department of Defense, American Health Assistance Foundation,
Anonymous Foundation, and the Alzheimer Association.; The National
Alzheimer's Coordinating Centre is funded by NIH U01 AG016976. The NIA
approved the final manuscript but did not influence the analysis,
results, or interpretation.
NR 31
TC 24
Z9 24
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD NOV
PY 2011
VL 77
IS 19
BP 1737
EP 1744
DI 10.1212/WNL.0b013e318236f0cf
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 844SO
UT WOS:000296767800010
PM 22031532
ER
PT J
AU Seddon, JM
Reynolds, R
Yu, Y
Daly, MJ
Rosner, B
AF Seddon, Johanna M.
Reynolds, Robyn
Yu, Yi
Daly, Mark J.
Rosner, Bernard
TI Risk Models for Progression to Advanced Age-Related Macular Degeneration
Using Demographic, Environmental, Genetic, and Ocular Factors
SO OPHTHALMOLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; BODY-MASS INDEX; DIETARY-FAT; VITAMIN-C; VARIANT;
ASSOCIATION; SUSCEPTIBILITY; POLYMORPHISM; MACULOPATHY; HTRA1
AB Purpose: To expand our predictive models for progression to advanced stages of age-related macular degeneration (AMD) based on demographic, environmental, genetic, and ocular factors, using longer follow-up, time varying analyses, calculation of absolute risks, adjustment for competing risks, and detailed baseline AMD and drusen status.
Design: Prospective, longitudinal study.
Participants: We included 2937 individuals in the Age-Related Eye Disease Study, of which 819 subjects progressed to advanced AMD during 12 years of follow-up.
Methods: Cox proportional hazards regression analyses were performed to calculate hazard ratios for progression. Covariates included demographic and environmental factors, 6 variants in 5 genes, baseline macular drusen size, and presence and type of advanced AMD in 1 eye at baseline. To assess the ability of risk scores based on all covariates to discriminate between progressors and nonprogressors, an algorithm was developed and the area under the receiver operating characteristic curve (AUC) was calculated. To validate the overall model, the total sample was randomly subdivided into derivation and test samples. Another model was built based on the derivation sample and assessed for calibration and discrimination in the test sample. Sample sizes needed for testing new treatments in clinical trials were estimated based on models with and without genetic variables.
Main Outcome Measures: Progression to advanced AMD, including geographic atrophy and neovascular disease.
Results: In multivariate models, age, smoking, body mass index, single nucleotide polymorphisms in the CFH, ARMS2/HTRA1, C3, C2, and CFB genes, as well as presence of advanced AMD in 1 eye and drusen size in both eyes were all independently associated with progression. The AUC for progression at 10 years in the model with genetic factors, drusen size, and environmental covariates was 0.915 in the total sample. In the test sample, based on a model estimated from the derivation sample, the AUC was 0.908. The sample sizes needed for clinical trials were estimated to be lower when genetic susceptibility was considered.
Conclusions: Factors reflective of nature and nurture were incorporated into an expanded algorithm for risk prediction, which performed very well in both derivation and test samples. Risk scores and predicted progression rates will be useful for AMD surveillance and for designing clinical trials.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011;118:2203-2211 (C) 2011 by the American Academy of Ophthalmology.
C1 [Seddon, Johanna M.] New England Eye Ctr, Tufts Med Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA.
[Seddon, Johanna M.; Reynolds, Robyn; Yu, Yi] Tufts Univ, Sch Med, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA.
[Daly, Mark J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rosner, Bernard] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA.
RP Seddon, JM (reprint author), New England Eye Ctr, Tufts Med Ctr, Ophthalm Epidemiol & Genet Serv, 800 Washington St 450, Boston, MA 02111 USA.
EM jseddon@tuftsmedicalcenter.org
FU National Institutes of Health [RO1-EY11309]; Massachusetts Lions Eye
Research Fund Inc., New Bedford, MA; Research to Prevent Blindness Inc.,
New York, NY; American Macular Degeneration Foundation, Northampton, MA;
Tufts Medical Center; Ophthalmic Epidemiology and Genetics Service,
Tufts Medical Center, Tufts University School of Medicine
FX Supported by grant RO1-EY11309 from the National Institutes of Health;
the Massachusetts Lions Eye Research Fund Inc., New Bedford, MA;
unrestricted grants from Research to Prevent Blindness Inc., New York,
NY; the American Macular Degeneration Foundation, Northampton, MA;
Virginia B Smith Fund, Tufts Medical Center; and the Age-Related Macular
Degeneration Research Fund, Ophthalmic Epidemiology and Genetics
Service, Tufts Medical Center, Tufts University School of Medicine.
NR 34
TC 86
Z9 88
U1 3
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2011
VL 118
IS 11
BP 2203
EP 2211
DI 10.1016/j.ophtha.2011.04.029
PG 9
WC Ophthalmology
SC Ophthalmology
GA 842EG
UT WOS:000296573500016
PM 21959373
ER
PT J
AU Lee, J
Ferrucci, S
AF Lee, Jimin
Ferrucci, Steven
TI Peripapillary subretinal neovascular membranes: A review
SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION
LA English
DT Review
DE Peripapillary subretinal neovascularization; Juxtapapillary subretinal
neovascularization; Age-related macular degeneration; Choroidal
neovascular membrane
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; INTRAVITREAL BEVACIZUMAB; LASER
PHOTOCOAGULATION; OCULAR HISTOPLASMOSIS; PHOTODYNAMIC THERAPY;
SURGICAL-TREATMENT; NATURAL-HISTORY; VERTEPORFIN; SURGERY; REMOVAL
AB Peripapillary subretinal neovascular membranes (PSRNVM) are most commonly associated with age-related macular degeneration and idiopathic causes in older patients. In younger patients, the condition has been linked to a wide variety of other conditions. As with the more commonly occurring macular form of choroidal neovascular membranes, PSRNVM can also lead to severe vision loss. Therefore, clinicians must take care to avoid overlooking this event to provide appropriate management and treatment. Current knowledge of PSRNVM suggests the importance of regular examinations of the affected eye in both treated and untreated cases to watch for progression and recurrence, which are unpredictable, and also of the fellow eye because there is a high risk of bilateral involvement. Optometry 2011;82:681-688
C1 [Lee, Jimin; Ferrucci, Steven] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Lee, Jimin; Ferrucci, Steven] Sepulveda Vet Affairs Ambulatory Care Ctr Nursing, Sepulveda, CA USA.
[Ferrucci, Steven] So Calif Coll Optometry, Fullerton, CA USA.
RP Ferrucci, S (reprint author), Sepulveda Vet Affairs Ambulatory Care Ctr, Dept Optometry, 16111 Plummer St 112E, Sepulveda, CA 91343 USA.
EM steven.ferrucci@va.gov
NR 32
TC 1
Z9 1
U1 2
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1529-1839
J9 OPTOMETRY
JI Optometry
PD NOV
PY 2011
VL 82
IS 11
BP 681
EP 688
DI 10.1016/j.optm.2011.04.104
PG 8
WC Ophthalmology
SC Ophthalmology
GA 843QL
UT WOS:000296687200006
PM 21873121
ER
PT J
AU Zhang, LZ
Chari, S
Smyrk, TC
Deshpande, V
Kloppel, G
Kojima, M
Liu, XL
Longnecker, DS
Mino-Kenudson, M
Notohara, K
Rodriguez-Justo, M
Srivastava, A
Zamboni, G
Zen, Y
AF Zhang, Lizhi
Chari, Suresh
Smyrk, Thomas C.
Deshpande, Vikram
Kloeppel, Guenter
Kojima, Motohiro
Liu, Xiuli
Longnecker, Daniel S.
Mino-Kenudson, Mari
Notohara, Kenji
Rodriguez-Justo, Manuel
Srivastava, Amitabh
Zamboni, Giuseppe
Zen, Yoh
TI Autoimmune Pancreatitis (AIP) Type 1 and Type 2 An International
Consensus Study on Histopathologic Diagnostic Criteria
SO PANCREAS
LA English
DT Article
DE autoimmune pancreatitis; chronic pancreatitis; granulocytic epithelial
lesion; IgG4
ID LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; DISEASE; INFILTRATION;
CARCINOMA; FEATURES; CELL
AB Objectives: To develop and validate histologic diagnostic criteria for autoimmune pancreatitis (AIP) and its types.
Methods: Thirteen pathologists participated in this 2-phase study to develop diagnostic criteria for AIP types 1 and 2 (phase 1) and validate them (phase 2). A virtual library of 40 resected pancreata with AIP and other forms of chronic pancreatitis (CP) was constructed. Readers reviewed the slides online and filled out a questionnaire for histopathologic findings and diagnosis.
Results: Diagnostic criteria for AIP and its types were proposed according to the results from the top 5 reviewers in phase 1. The interobserver agreement was significantly improved in phase 2 by applying the proposed diagnostic criteria. Features distinguishing AIP from alcoholic and obstructive forms of CP were periductal lymphoplasmacytic infiltrate, inflamed cellular stroma with storiform fibrosis, obliterative phlebitis, and granulocytic epithelial lesions. Although there was overlap, 2 types of AIP were recognized. Type 1 had dense lymphoplasmacytic infiltrate with storiform fibrosis and obliterative phlebitis, whereas type 2 was distinguished from type 1 by the presence of granulocytic epithelial lesions.
Conclusions: Autoimmune pancreatitis can be distinguished from other forms of CP with substantial interobserver agreement. The 2 types of AIP can be distinguished by the proposed consensus histopathologic diagnostic criteria.
C1 [Zhang, Lizhi; Smyrk, Thomas C.] Mayo Clin, Dept Lab & Anat Pathol, Rochester, MN 55905 USA.
[Chari, Suresh] Mayo Clin, Div Gastroenterol, Rochester, MN 55905 USA.
[Chari, Suresh] Mayo Clin, Div Hepatol, Rochester, MN 55905 USA.
[Deshpande, Vikram; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kloeppel, Guenter] Univ Kiel, Dept Pathol, D-2300 Kiel, Germany.
[Kojima, Motohiro] Natl Canc Ctr Hosp E, Div Clin Pathol, Chiba, Japan.
[Liu, Xiuli] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44106 USA.
[Longnecker, Daniel S.] Dartmouth Med Sch, Dept Pathol, Lebanon, NH USA.
[Longnecker, Daniel S.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
[Notohara, Kenji] Kurashiki Cent Hosp, Dept Pathol, Kurashiki, Okayama, Japan.
[Rodriguez-Justo, Manuel] UCL, Dept Pathol, London, England.
[Srivastava, Amitabh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Zamboni, Giuseppe] Univ Verona, Dept Pathol, I-37100 Verona, Italy.
[Zen, Yoh] Kings Coll Hosp London, Inst Liver Studies, London SE5 8RX, England.
RP Zhang, LZ (reprint author), Mayo Clin, Dept Lab & Anat Pathol, 200 1st St SW, Rochester, MN 55905 USA.
EM zhang.lizhi@mayo.edu; chari.suresh@mayo.edu; smyrk.thomas@mayo.edu
RI Giuseppe, Zamboni/A-5991-2016;
OI Giuseppe, Zamboni/0000-0001-7428-4673; Kloppel,
Gunter/0000-0002-6688-086X; Rodriguez-Justo, Manuel/0000-0001-5007-1761
NR 29
TC 47
Z9 49
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2011
VL 40
IS 8
BP 1172
EP 1179
DI 10.1097/MPA.0b013e318233bec5
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 839VQ
UT WOS:000296398000003
PM 21975436
ER
PT J
AU Mareninova, OA
Yakubov, I
Gukovsky, I
Gukovskaya, AS
AF Mareninova, O. A.
Yakubov, I.
Gukovsky, I.
Gukovskaya, A. S.
TI Lysosomal Dysfunction in Pancreatitis
SO PANCREAS
LA English
DT Meeting Abstract
C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
Univ Calif Los Angeles, Los Angeles, CA USA.
So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2011
VL 40
IS 8
BP 1337
EP 1337
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 839VQ
UT WOS:000296398000155
ER
PT J
AU Michailidou, M
Chiou, G
Warshaw, A
Fernandez-del Castillo, C
Fagenholz, P
AF Michailidou, M.
Chiou, G.
Warshaw, A.
Fernandez-del Castillo, C.
Fagenholz, P.
TI Contemporary Retrospective Review of Open Pancreatic Debridements - How
Are We Doing?
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Michailidou, M.; Chiou, G.; Warshaw, A.; Fernandez-del Castillo, C.; Fagenholz, P.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2011
VL 40
IS 8
BP 1339
EP 1339
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 839VQ
UT WOS:000296398000163
ER
PT J
AU Morales-Oyarvide, V
Mino-Kenudson, M
Thayer, SP
Wargo, JA
Ferrone, CR
Lillemoe, KD
Warshaw, AL
Fernandez-del Castillo, C
AF Morales-Oyarvide, V.
Mino-Kenudson, M.
Thayer, S. P.
Wargo, J. A.
Ferrone, C. R.
Lillemoe, K. D.
Warshaw, A. L.
Fernandez-del Castillo, C.
TI IPMNs Presenting with Acute Pancreatitis are Associated with an
Intestinal Phenotype
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Morales-Oyarvide, V.; Thayer, S. P.; Wargo, J. A.; Ferrone, C. R.; Lillemoe, K. D.; Warshaw, A. L.; Fernandez-del Castillo, C.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Mino-Kenudson, M.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2011
VL 40
IS 8
BP 1340
EP 1340
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 839VQ
UT WOS:000296398000169
ER
PT J
AU Morales-Oyarvide, V
Ingkakul, T
Deshpande, V
Forcione, DG
Brugge, WR
Fernandez-del Castillo, C
Pitman, MB
AF Morales-Oyarvide, V.
Ingkakul, T.
Deshpande, V.
Forcione, D. G.
Brugge, W. R.
Fernandez-del Castillo, C.
Pitman, M. B.
TI Utility of EUS-FNAB in the Diagnosis of Cystic Pancreatic Endocrine
Neoplasms
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Morales-Oyarvide, V.; Ingkakul, T.; Fernandez-del Castillo, C.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Deshpande, V.; Pitman, M. B.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Forcione, D. G.; Brugge, W. R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2011
VL 40
IS 8
BP 1340
EP 1340
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 839VQ
UT WOS:000296398000168
ER
PT J
AU Morales-Oyarvide, V
Fernandez-del Castillo, C
Valsangkar, NP
Sahani, DV
Pitman, MB
Thayer, SP
Mino-Kenudson, M
AF Morales-Oyarvide, V.
Fernandez-del Castillo, C.
Valsangkar, N. P.
Sahani, D. V.
Pitman, M. B.
Thayer, S. P.
Mino-Kenudson, M.
TI PDAC with Tumor-Related Retention Cysts, a Mimicker of Invasive IPMN,
May Be Associated with Poor Prognosis
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Morales-Oyarvide, V.; Fernandez-del Castillo, C.; Valsangkar, N. P.; Thayer, S. P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Sahani, D. V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Pitman, M. B.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2011
VL 40
IS 8
BP 1341
EP 1341
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 839VQ
UT WOS:000296398000170
ER
PT J
AU Spofford, I
Conwell, D
Wu, B
Mortele, K
Khorasani, R
Yu, S
Banks, P
Thompson, C
AF Spofford, I.
Conwell, D.
Wu, B.
Mortele, K.
Khorasani, R.
Yu, S.
Banks, P.
Thompson, C.
TI Endoscopic Versus Surgical Necrosectomy for Patients with Symptomatic
Pancreatic Necrotic Collections: A Retrospective Cohort Study
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Spofford, I.] Massachusetts Gen Hosp, Div Pediat Gastroenterol, Boston, MA 02114 USA.
[Spofford, I.; Conwell, D.; Wu, B.; Yu, S.; Banks, P.; Thompson, C.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA.
[Mortele, K.; Khorasani, R.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2011
VL 40
IS 8
BP 1355
EP 1355
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 839VQ
UT WOS:000296398000229
ER
PT J
AU Valsangkar, NP
Ingkakul, T
Correa-Gallego, C
Warshaw, AL
Fernandez-del Castillo, C
Liss, AS
Thayer, SP
AF Valsangkar, N. P.
Ingkakul, T.
Correa-Gallego, C.
Warshaw, A. L.
Fernandez-del Castillo, C.
Liss, A. S.
Thayer, S. P.
TI The G12D Mutation of KRAS Predicts Early Recurrence and Poor Overall
Survival in Ampullary Adenocarcinoma
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Valsangkar, N. P.; Ingkakul, T.; Correa-Gallego, C.; Warshaw, A. L.; Fernandez-del Castillo, C.; Liss, A. S.; Thayer, S. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Warshaw Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2011
VL 40
IS 8
BP 1360
EP 1361
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 839VQ
UT WOS:000296398000252
ER
PT J
AU Yamaguchi, J
Mino-Kenudson, M
Liss, AS
Fernandez-del Castillo, C
Warshaw, AL
Thayer, SP
AF Yamaguchi, J.
Mino-Kenudson, M.
Liss, A. S.
Fernandez-del Castillo, C.
Warshaw, A. L.
Thayer, S. P.
TI Pancreatic Duct Glands (PDG) Are the Origin of Gastric-Type IPMN
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Yamaguchi, J.; Liss, A. S.; Fernandez-del Castillo, C.; Warshaw, A. L.; Thayer, S. P.] Massachusetts Gen Hosp, Warshaw Inst, Boston, MA 02114 USA.
[Yamaguchi, J.; Liss, A. S.; Fernandez-del Castillo, C.; Warshaw, A. L.; Thayer, S. P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Mino-Kenudson, M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Mino-Kenudson, M.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2011
VL 40
IS 8
BP 1364
EP 1364
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 839VQ
UT WOS:000296398000267
ER
PT J
AU Yamaguchi, J
Mino-Kenudson, M
Liss, AS
Fernandez-del Castillo, C
Warshaw, AL
Thayer, SP
AF Yamaguchi, J.
Mino-Kenudson, M.
Liss, A. S.
Fernandez-del Castillo, C.
Warshaw, A. L.
Thayer, S. P.
TI Pancreatic Duct Glands (PDG), a Progenitor Stem Cell Niche Responsible
For Pancreatic Epithelial Renewal and Repair in Response To Inflammatory
Injury
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Yamaguchi, J.; Liss, A. S.; Fernandez-del Castillo, C.; Warshaw, A. L.; Thayer, S. P.] Massachusetts Gen Hosp, Warshaw Inst, Boston, MA 02114 USA.
[Yamaguchi, J.; Liss, A. S.; Fernandez-del Castillo, C.; Warshaw, A. L.; Thayer, S. P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Mino-Kenudson, M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Mino-Kenudson, M.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2011
VL 40
IS 8
BP 1364
EP 1364
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 839VQ
UT WOS:000296398000268
ER
PT J
AU Gordon, CR
Susarla, SM
Peacock, ZS
Cetrulo, CL
Zins, JE
Papay, F
Kaban, LB
Yaremchuk, MJ
AF Gordon, Chad R.
Susarla, Srinivas M.
Peacock, Zachary S.
Cetrulo, Curtis L.
Zins, James E.
Papay, Frank
Kaban, Leonard B.
Yaremchuk, Michael J.
TI Osteocutaneous Maxillofacial Allotransplantation: Lessons Learned from a
Novel Cadaver Study Applying Orthognathic Principles and Practice
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID FACIAL ALLOGRAFT TRANSPLANTATION; TOTAL HUMAN FACE; MICROVASCULAR
RECONSTRUCTION; CLASSIFICATION-SYSTEM; SKELETAL; DEFECTS; MIDFACE;
APPEARANCE; PROGRESS; SURGERY
AB Background: Osteocutaneous maxillofacial allotransplantation is an encouraging technique for reconstruction of complex midfacial injuries (i.e., Gordon type III composite tissue allotransplantation). Although clinical results have been promising, there are no published guidelines, to date, on how to establish a functional occlusion and class I skeletal relation between the donor maxilla and recipient mandible. The purpose of this study was to use orthognathic principles and practice to improve occlusal and facial skeletal outcomes in osteocutaneous maxillofacial allotransplantation.
Methods: Three Le Fort III-based maxillofacial allotransplantations were performed, using six fresh cadavers. Each recipient was prepared bluntly simulating a massive, bilateral orbitozygomatic maxillofacial defect. The first transplant was completed according to published protocol. The second was planned using dental cast models, cephalometric analyses, model surgery, and occlusal splint fabrication. The third involved an edentulous scenario, with the donor alloflap fixated to the recipient's mandible using a mimic Gunning splint to establish the vertical dimension of occlusion.
Results: All three operations resulted in facial aesthetics comparable to those seen with autologous methods. Operative times ranged from 3.5 to 5.3 hours. The first allotransplant resulted in a class II malocclusion (overjet, 5 mm). The second recipient, with a preexisting class II skeleton, displayed a small anterior open bite of -1.7 mm, 1 mm of overjet, and a class I skeletal relationship (A-point-nasion-B-point angle, 2.3 degrees) following transplantation. The final transplant, consisting of an edentulous alloflap to an edentulous recipient, demonstrated an orthognathic profile.
Conclusion: Use of orthognathic principles and practice in osteocutaneous maxillofacial allotransplantation resulted in improved occlusion, skeletal projection, and facial harmony relative to standard technique. (Plast. Reconstr. Surg. 128: 465e, 2011.)
C1 Johns Hopkins Univ, Sch Med, Dept Plast Surg, Johns Hopkins Hosp, Baltimore, MD 21287 USA.
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Cambridge, MA 02138 USA.
Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Cambridge, MA 02138 USA.
Cleveland Clin, Inst Dermatol & Plast Surg, Dept Plast Surg, Cleveland, OH USA.
RP Gordon, CR (reprint author), Johns Hopkins Univ, Sch Med, Dept Plast & Reconstruct Surg, Johns Hopkins Hosp,JHOC, Suite 8161,601 N Caroline St, Baltimore, MD 21287 USA.
EM cgordon@jhmi.edu
OI Susarla, Srinivas/0000-0003-0155-8260
NR 46
TC 13
Z9 13
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0032-1052
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD NOV
PY 2011
VL 128
IS 5
BP 465E
EP 479E
DI 10.1097/PRS.0b013e31822b6949
PG 15
WC Surgery
SC Surgery
GA 842GQ
UT WOS:000296583600010
PM 22030506
ER
PT J
AU Nyame, TT
Lemon, KP
Kolter, R
Liao, EC
AF Nyame, Theodore T.
Lemon, Katherine P.
Kolter, Roberto
Liao, Eric C.
TI High-Throughput Assay for Bacterial Adhesion on Acellular Dermal
Matrices and Synthetic Surgical Materials
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID ABDOMINAL-WALL RECONSTRUCTION; INGUINAL-HERNIA REPAIR;
STAPHYLOCOCCUS-AUREUS; BREAST RECONSTRUCTION; BIOFILM FORMATION; MESH
REPAIR; INFECTION; ALLODERM; BIOMATERIALS; PATHOGENESIS
AB Background: There has been increasing use of synthetic and acellular dermal matrix materials in surgery, ranging from breast reconstruction to hernia repairs. There is a paucity of data on how acellular dermal matrix compares with other surgical materials as a substrate for bacterial adhesion, the first step in formation biofilm, which occurs in prosthetic wound infections. The authors have designed a high-throughput assay to evaluate Staphylococcus aureus adherence on various synthetic and biologically derived materials.
Methods: Clinical isolates of S. aureus (strains SC-1 and UAMS-1) were cultured with different materials, and bacterial adherence was measured using a resazurin cell vitality assay. Four materials that are commonly used in surgery were evaluated: Prolene mesh, Vicryl mesh, and two different acellular dermal matrix preparations (AlloDerm and FlexHD). The authors were able to develop a high-throughput and reliable assay for quantifying bacterial adhesion on synthetic and biologically derived materials.
Results: The resazurin vitality assay can be reliably used to quantify bacterial adherence to acellular dermal matrix material and synthetic material. S. aureus strains SC-1 and UAMS-1 both adhered better to acellular dermal matrix materials (AlloDerm versus FlexHD) than to the synthetic material Prolene. S. aureus also adhered better to Vicryl than to Prolene. Strain UAMS-1 adhered better to Vicryl and acellular dermal matrix materials than did strain SC-1.
Conclusions: The results show that S. aureus adheres more readily to acellular dermal matrix material than to synthetic material. The resazurin assay provides a standard method for evaluating surgical materials with regard to bacterial adherence and potential propensity for biofilm development. (Plast. Reconstr. Surg. 128: 1061, 2011.)
C1 [Liao, Eric C.] Harvard Univ, Ctr Regenerat Med, Div Plast & Reconstruct Surg, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Ctr Regenerat Med, Div Infect Dis,Harvard Stem Cell Inst,Childrens H, Cambridge, MA 02138 USA.
Harvard Univ, Dept Microbiol & Mol Genet, Cambridge, MA 02138 USA.
RP Liao, EC (reprint author), Harvard Univ, Ctr Regenerat Med, Div Plast & Reconstruct Surg, Massachusetts Gen Hosp,Sch Med, WACC 435,15 Parkman St, Boston, MA 02114 USA.
EM cliao@partners.org
FU Mentored Clinical Scientist Development Award [K08 AI070561]; American
Surgical Association; March of Dimes Basil O'Connor Starter Scholar
Research Award; Shriners Hospitals for Children; [GM58213]
FX This work was generously supported by the Plastic Surgery Foundation.
This work was also supported in part by Mentored Clinical Scientist
Development Award K08 AI070561 (to K.P.L.) and by grant GM58213 (to
R.K.). Strains of S. aureus were graciously donated by Dr. Mark S.
Smeltzer and his laboratory. Eric C. Liao, M.D., Ph.D., received funding
support from the American Surgical Association Research Fellowship, the
March of Dimes Basil O'Connor Starter Scholar Research Award, and the
Shriners Hospitals for Children.
NR 46
TC 13
Z9 13
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0032-1052
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD NOV
PY 2011
VL 128
IS 5
BP 1061
EP 1068
DI 10.1097/PRS.0b013e31822b65af
PG 8
WC Surgery
SC Surgery
GA 842GQ
UT WOS:000296583600045
PM 22030489
ER
PT J
AU Carpenter, LL
Tyrka, AR
Lee, JK
Tracy, AP
Wilkinson, CW
Price, LH
AF Carpenter, Linda L.
Tyrka, Audrey R.
Lee, Janet K.
Tracy, Aaron P.
Wilkinson, Charles W.
Price, Lawrence H.
TI A placebo-controlled study of sertraline's effect on cortisol response
to the dexamethasone/corticotropin-releasing hormone test in healthy
adults
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Sertraline; Dex/CRH test; Cortisol; HPA axis
ID PITUITARY-ADRENAL-SYSTEM; MAJOR DEPRESSIVE EPISODE; HPA-AXIS REACTIVITY;
CHILDHOOD TRAUMA; DEX/CRH TEST; ANTIDEPRESSANT TREATMENT; LITHIUM
AUGMENTATION; UNIPOLAR DEPRESSION; AFFECTIVE-DISORDERS; ACTH RESPONSES
AB Rationale The dexamethasone/corticotropin-releasing hormone (Dex/CRH) test is a neuroendocrine probe involving serial blood sampling of cortisol during a standardized pharmacological challenge without inducing psychological distress in humans. Some past studies in depressed patients have shown a "normalization" or decrease in cortisol response to the Dex/CRH test following successful treatment with an antidepressant. Studies in nondepressed healthy adult samples have also shown aberrant cortisol reactivity to be associated with depression risk factors. These findings prompted research into the use of the Dex/CRH test as a tool for developing antidepressant drugs.
Objectives In this study, the Dex/CRH test was evaluated with regard to its potential utility for drug development in nonclinical samples.
Methods The Dex/CRH test was administered before and after 6 weeks of blinded treatment with either sertraline 100 mg/day or matching placebo in 22 healthy adults ( 13 women, nine men).
Results Cortisol response to the Dex/CRH test increased following treatment with standard doses of sertraline, compared to placebo, after controlling for age and sex.
Conclusions The observed pattern of change contrasts with results from published studies in depressed patients and with our initial hypothesis.
C1 [Carpenter, Linda L.; Tyrka, Audrey R.; Lee, Janet K.; Tracy, Aaron P.; Price, Lawrence H.] Butler Hosp, Mood Disorders Res Program, Providence, RI 02906 USA.
[Carpenter, Linda L.; Tyrka, Audrey R.; Lee, Janet K.; Tracy, Aaron P.; Price, Lawrence H.] Butler Hosp, Lab Clin Neurosci, Brown Dept Psychiat & Human Behav, Providence, RI 02906 USA.
[Wilkinson, Charles W.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA.
[Wilkinson, Charles W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA.
RP Carpenter, LL (reprint author), Butler Hosp, Mood Disorders Res Program, 345 Blackstone Blvd, Providence, RI 02906 USA.
EM Linda_Carpenter_MD@brown.edu
RI Tyrka, Audrey/L-2504-2014
FU Pfizer Inc.; Department of Veterans Affairs
FX The authors thank Kelly Colombo, B. A. for her assistance with data
management, Ashley Clement for her research assistant support in
manuscript preparation, and Daniel Gonzalez for performance of the
cortisol assays. This work was supported by an investigator-initiated
grant from Pfizer Inc. (LLC) and by the Department of Veterans Affairs
(CWW).
NR 63
TC 2
Z9 2
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD NOV
PY 2011
VL 218
IS 2
BP 371
EP 379
DI 10.1007/s00213-011-2336-y
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 844EL
UT WOS:000296730400007
PM 21617914
ER
PT J
AU Geller, AC
Brooks, DR
Woodring, B
Oppenheimer, S
McCabe, M
Rogers, J
Timm, A
Resnick, EA
Winickoff, JP
AF Geller, Alan C.
Brooks, Daniel R.
Woodring, Barbara
Oppenheimer, Sarah
McCabe, Margaret
Rogers, Jayne
Timm, Alison
Resnick, Elissa A.
Winickoff, Jonathan P.
TI Smoking Cessation Counseling for Parents During Child Hospitalization: A
National Survey of Pediatric Nurses
SO PUBLIC HEALTH NURSING
LA English
DT Article
DE nursing education; patient education; smoking
ID RESPIRATORY ILLNESS; PREVENTIVE CARE; QUIT SMOKING; TOBACCO;
INTERVENTION; ATTITUDES
AB Objectives: Given the central role played by pediatric nurses in intake assessment, discharge planning, and education for families of hospitalized pediatric patients, a child's hospitalization may provide a unique opportunity for counseling parents about smoking. We sought to determine if hospital policies can support nurses in effectively counseling parents about smoking. Design and Sample: We conducted a national survey of pediatric staff nurses and administrators/educators who were members of the Society of Pediatric Nurses in 2008 (n = 5888) to explore counseling practices for tobacco control. Measures: Questionnaires included data on demographics, personal and work environment characteristics, hospital policy characteristics, work attitudes and barriers and the main outcome-5As for smoking cessation counseling-Ask, Advise, Assess, Assist, and Arrange. Results: Overall, routine screening for household smokers was most common (43%), followed by advice to quit (25%), assessing willingness to quit (19%), assisting with a quit plan (6%), and arranging follow-up contact (3%). Nurses working in hospitals with admission assessments specifically asking about household members who smoke were 7 times more likely than those without such assessments to routinely ask about smoking (OR: 7.2, 95% CI: 4.9-10.5). Conclusion: Future research should test the efficacy of developing comprehensive hospital-wide policies to deliver smoking cessation for parents during a child's hospitalization.
C1 [Geller, Alan C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Brooks, Daniel R.; Timm, Alison] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Woodring, Barbara] Georgia State Univ, Dept Nursing, Atlanta, GA 30303 USA.
[Oppenheimer, Sarah] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[McCabe, Margaret; Rogers, Jayne] Childrens Hosp, Boston, MA 02115 USA.
[Resnick, Elissa A.] Univ Chicago, Inst Hlth Res & Policy, Chicago, IL 60637 USA.
[Winickoff, Jonathan P.] MGH Ctr Child & Adolescent Hlth Policy, Boston, MA USA.
[Winickoff, Jonathan P.] Amer Acad Pediat Julius, B Richmond Ctr, Tobacco Consortium, Elk Grove Village, IL USA.
RP Geller, AC (reprint author), Kresge Bldg,677 Huntington Ave, Boston, MA 02215 USA.
EM ageller@hsph.harvard.edu
OI Brooks, Daniel/0000-0001-6220-6889
NR 23
TC 8
Z9 8
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0737-1209
J9 PUBLIC HEALTH NURS
JI Public Health Nurs.
PD NOV-DEC
PY 2011
VL 28
IS 6
BP 475
EP 484
DI 10.1111/j.1525-1446.2011.00954.x
PG 10
WC Public, Environmental & Occupational Health; Nursing
SC Public, Environmental & Occupational Health; Nursing
GA 839DN
UT WOS:000296345300002
PM 22092457
ER
PT J
AU Venkatesan, AM
Wood, BJ
Gervais, DA
AF Venkatesan, Aradhana M.
Wood, Bradford J.
Gervais, Debra A.
TI Percutaneous Ablation in the Kidney
SO RADIOLOGY
LA English
DT Editorial Material
ID RENAL-CELL CARCINOMA; RADIO-FREQUENCY ABLATION; GUIDED RADIOFREQUENCY
ABLATION; INTENSITY FOCUSED ULTRASOUND; TERM-FOLLOW-UP; THERMAL
ABLATION; TUMOR ABLATION; LAPAROSCOPIC CRYOABLATION;
HEPATOCELLULAR-CARCINOMA; HEPATIC CRYOSURGERY
C1 [Venkatesan, Aradhana M.; Wood, Bradford J.] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA.
RP Venkatesan, AM (reprint author), NIH, Ctr Clin, Dept Radiol & Imaging Sci, 10 Ctr Dr,Bldg 10,Room 1C369,MSC 1182, Bethesda, MD 20892 USA.
EM VenkatesanA@cc.nih.gov
NR 112
TC 32
Z9 33
U1 0
U2 4
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD NOV
PY 2011
VL 261
IS 2
BP 375
EP 391
DI 10.1148/radiol.11091207
PG 17
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 841PL
UT WOS:000296524600007
PM 22012904
ER
PT J
AU Vanness, DJ
Knudsen, AB
Lansdorp-Vogelaar, I
Rutter, CM
Gareen, IF
Herman, BA
Kuntz, KM
Zauber, AG
van Ballegooijen, M
Feuer, EJ
Chen, MH
Johnson, CD
AF Vanness, David J.
Knudsen, Amy B.
Lansdorp-Vogelaar, Iris
Rutter, Carolyn M.
Gareen, Ilana F.
Herman, Benjamin A.
Kuntz, Karen M.
Zauber, Ann G.
van Ballegooijen, Marjolein
Feuer, Eric J.
Chen, Mei-Hsiu
Johnson, C. Daniel
TI Comparative Economic Evaluation of Data from the ACRIN National CT
Colonography Trial with Three Cancer Intervention and Surveillance
Modeling Network Microsimulations
SO RADIOLOGY
LA English
DT Article
ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; SERVICES TASK-FORCE;
FECAL-OCCULT-BLOOD; COST-EFFECTIVENESS ANALYSIS; COLORECTAL-CANCER;
VIRTUAL COLONOSCOPY; LARGE-INTESTINE; LARGE-BOWEL; CONVENTIONAL
COLONOSCOPY; EXTRACOLONIC FINDINGS
AB Purpose: To estimate the cost-effectiveness of computed tomographic (CT) colonography for colorectal cancer (CRC) screening in average-risk asymptomatic subjects in the United States aged 50 years.
Materials and Methods: Enrollees in the American College of Radiology Imaging Network National CT Colonography Trial provided informed consent, and approval was obtained from the institutional review board at each site. CT colonography performance estimates from the trial were incorporated into three Cancer Intervention and Surveillance Modeling Network CRC microsimulations. Simulated survival and lifetime costs for screening 50-year-old subjects in the United States with CT colonography every 5 or 10 years were compared with those for guideline-concordant screening with colonoscopy, flexible sigmoidoscopy plus either sensitive unrehydrated fecal occult blood testing (FOBT) or fecal immunochemical testing (FIT), and no screening. Perfect and reduced screening adherence scenarios were considered. Incremental cost-effectiveness and net health benefits were estimated from the U. S. health care sector perspective, assuming a 3% discount rate.
Results: CT colonography at 5- and 10-year screening intervals was more costly and less effective than FOBT plus flexible sigmoidoscopy in all three models in both 100% and 50% adherence scenarios. Colonoscopy also was more costly and less effective than FOBT plus flexible sigmoidoscopy, except in the CRC-SPIN model assuming 100% adherence (incremental cost-effectiveness ratio: $26300 per life-year gained). CT colonography at 5- and 10-year screening intervals and colonoscopy were net beneficial compared with no screening in all model scenarios. The 5-year screening interval was net beneficial over the 10-year interval except in the MISCAN model when assuming 100% adherence and willingness to pay $50000 per life-year gained.
Conclusion: All three models predict CT colonography to be more costly and less effective than non-CT colonographic screening but net beneficial compared with no screening given model assumptions. (C) RSNA, 2011
C1 [Vanness, David J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53726 USA.
[Knudsen, Amy B.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein] Erasmus MC Univ Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands.
[Rutter, Carolyn M.] Grp Hlth Seattle, Ctr Hlth Studies, Seattle, WA USA.
[Gareen, Ilana F.; Herman, Benjamin A.; Chen, Mei-Hsiu] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA.
[Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA.
[Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Johnson, C. Daniel] Mayo Clin, Dept Radiol, Scottsdale, AZ USA.
RP Vanness, DJ (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, 610 Walnut St, Madison, WI 53726 USA.
EM dvanness@wisc.edu
RI Gareen, Ilana/I-2816-2014;
OI Gareen, Ilana/0000-0002-0457-5595; Herman, Benjamin/0000-0001-6649-0354
FU United BioSource
FX D.J.V. Financial activities related to the present article: none to
disclose. Financial activities not related to the present article:
received money for a consultancy from United BioSource; was employed by
United BioSource. Other relationships: none to disclose. A. B. K. No
potential conflicts of interest to disclose. I. L. V. No potential
conflicts of interest to disclose. C. M. R. No potential conflicts of
interest to disclose. I. F. G. No potential conflicts of interest to
disclose. B. A. H. No potential conflicts of interest to disclose. K. M.
K. No potential conflicts of interest to disclose. A.G.Z. No potential
conflicts of interest to disclose. M. v. B. No potential conflicts of
interest to disclose. E.J.F. No potential conflicts of interest to
disclose. M. H. C. No potential conflicts of interest to disclose.
C.D.J. Financial activities related to the present article: none to
disclose. Financial activities not related to the present article:
institution received money for a software license/patent; receives
royalties from GE Medical Systems; institution receives royalties from
GE Medical Systems. Other relationships: none to disclose.
NR 73
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PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD NOV
PY 2011
VL 261
IS 2
BP 487
EP 498
DI 10.1148/radiol.11102411
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 841PL
UT WOS:000296524600018
PM 21813740
ER
PT J
AU Pan, JD
Pialat, JB
Joseph, T
Kuo, D
Joseph, GB
Nevitt, MC
Link, TM
AF Pan, Judong
Pialat, Jean-Baptiste
Joseph, Tom
Kuo, Daniel
Joseph, Gabby B.
Nevitt, Michael C.
Link, Thomas M.
TI Knee Cartilage T2 Characteristics and Evolution in Relation to
Morphologic Abnormalities Detected at 3-T MR Imaging: A Longitudinal
Study of the Normal Control Cohort from the Osteoarthritis Initiative
SO RADIOLOGY
LA English
DT Article
ID HUMAN ARTICULAR-CARTILAGE; PHYSICAL-ACTIVITY; RELAXATION-TIMES;
VALIDATION; JOINT; PREVALENCE; PRECISION; ARTHRITIS; DISEASE; VALUES
AB Purpose: To determine the frequency of degenerative knee morphologic abnormalities in asymptomatic individuals by using 3-T magnetic resonance (MR) imaging and to investigate the characteristics and evolution of cartilage T2 values in relation to morphologic abnormalities with a longitudinal study.
Materials and Methods: The study was approved by the institutional review board and was compliant with HIPAA. Ninety-five asymptomatic subjects aged 45-78 years who were free of risk factors for osteoarthritis (OA) were selected from the Osteoarthritis Initiative normal control cohort and examined with radiography and 3-T MR imaging. Data obtained at both baseline and 2-year follow-up were analyzed. OA-related knee abnormalities were analyzed by using the whole-organ MR imaging score (WORMS). Cartilage T2 maps were generated by using sagittal two-dimensional multi-echo spin-echo images of the right knee. Statistical significance was determined with the Student t test, the paired t test, a mixed random effects model, one-way analysis of variance, and a multiple linear regression model.
Results: Knee abnormalities were identified with a high frequency (90% at baseline and 92 % at 2-year follow-up). The prevalence of hyaline cartilage lesions was particularly high (86% at baseline and 84% at follow-up). A significant longitudinal increase in T2 was detected in the tibiofemoral cartilage but not the patellofemoral cartilage (P = .0072). The longitudinal change in T2 was significantly associated with worsening of the cartilage WORMS (P = .038).
Conclusion: Asymptomatic subjects have a high frequency of OA-related morphologic abnormalities. A significant increase in tibiofemoral cartilage T2 was detected over the 2-year period. A greater increase in T2 was associated with increased progression of cartilage morphologic abnormalities. (C) RSNA, 2011
C1 [Joseph, Tom] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Pan, Judong; Pialat, Jean-Baptiste; Kuo, Daniel; Joseph, Gabby B.; Link, Thomas M.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Nevitt, Michael C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Pialat, Jean-Baptiste] INSERM, U831, F-69008 Lyon, France.
[Pialat, Jean-Baptiste] Univ Lyon, Lyon, France.
RP Pan, JD (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,YAW 6E, Boston, MA 02114 USA.
EM jpan4@partners.org
OI Kuo, Daniel/0000-0002-3505-0169
FU Merck Research Laboratories; Novartis Pharmaceuticals; GlaxoSmithKline;
Pfizer; Foundation for the National Institutes of Health; National
Institutes of Health, a branch of the Department of Health and Human
Services [N01-AR-2-2258, N01-AR-2-2259, N01-AR-2-2260, N01-AR-2-2261,
N01-AR-2-2262]
FX Supported in part by Merck Research Laboratories, Novartis
Pharmaceuticals, GlaxoSmithKline, and Pfizer. Private-sector
Osteoarthritis Initiative funding is managed by the Foundation for the
National Institutes of Health.; The OAI is a public-private partnership
comprised of five contracts (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, a branch of the Department of Health and Human
Services, and conducted by the OAI Study Investigators. Private funding
partners include Pfizer, Novartis Pharmaceuticals, 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.
NR 35
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U1 0
U2 7
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD NOV
PY 2011
VL 261
IS 2
BP 507
EP 515
DI 10.1148/radiol.11102234
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 841PL
UT WOS:000296524600020
PM 21900614
ER
PT J
AU Chen, L
Miller, JW
Vavvas, D
Kim, IK
AF Chen, Ling
Miller, Joan W.
Vavvas, Demetrios
Kim, Ivana K.
TI ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR MONOTHERAPY VERSUS COMBINATION
TREATMENT WITH PHOTODYNAMIC THERAPY FOR SUBFOVEAL CHOROIDAL
NEOVASCULARIZATION SECONDARY TO CAUSES OTHER THAN AGE-RELATED MACULAR
DEGENERATION
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE choroidal neovascularization; anti-VEGF; photodynamic therapy; non-AMD
ID RANDOMIZED CLINICAL-TRIAL; INTRAVITREAL BEVACIZUMAB; ANGIOID STREAKS;
PATHOLOGICAL MYOPIA; MULTIFOCAL CHOROIDITIS; VERTEPORFIN
AB Purpose: To compare the visual outcomes and retreatment rates of monotherapy with intravitreal bevacizumab versus combination with photodynamic therapy for choroidal neovascularization secondary to causes other than age-related macular degeneration.
Methods: Seventeen patients received intravitreal bevacizumab, and 6 patients underwent intravitreal bevacizumab combined with verteporfin photodynamic therapy within 3 days. Additional bevacizumab was administrated if there was persistent fluorescein leakage or subretinal fluid on optical coherence tomography.
Results: The mean change in visual acuity was vision gain of 1.7 lines in the monotherapy group compared with 2.8 lines in the combination therapy group at 12-month follow-up (P = 0.45). At 12 months, 93% in the monotherapy group and 100% in the combination group lost <2 lines of vision (P = 1.0); 36% gained >3 lines of vision in the monotherapy compared with 60% in the combination therapy group (P = 0.60). The monotherapy group received a mean of 4.8 reinjections, while the combination group received 2.6 reinjections over 12 months (P = 0.11). Subgroup analysis of cases of choroidal neovascularization caused by pathologic myopia demonstrated a mean change in visual acuity of vision gain of +2.0 lines in the monotherapy group versus +2.3 lines in the combination therapy group (P = 0.82) and a mean of 7.2 reinjections versus 2 in monotherapy and combination group, respectively (P = 0.0498) at 12 months.
Conclusion: The majority of patients had stabilization or improvement in vision in both treatment groups. Combination therapy with bevacizumab plus photodynamic therapy showed lower retreatment rates in patients with myopia. Randomized clinical trials are necessary to confirm these findings. RETINA 31:2078-2083, 2011
C1 [Chen, Ling; Miller, Joan W.; Vavvas, Demetrios; Kim, Ivana K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA.
[Chen, Ling] Fudan Univ, Shanghai Med Sch, Dept Ophthalmol & Vis Sci, Eye & ENT Hosp, Shanghai 200433, Peoples R China.
RP Kim, IK (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM ivana_kim@meei.harvard.edu
OI Vavvas, Demetrios/0000-0002-8622-6478
FU Research to Prevent Blindness; Pujiang Talent Fund [10PJ1401900]
FX Supported in part by Research to Prevent Blindness Physician-Scientist
Award (I.K. Kim) and Pujiang Talent Fund (10PJ1401900, L. Chen).
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD NOV
PY 2011
VL 31
IS 10
BP 2078
EP 2083
DI 10.1097/IAE.0b013e3182109074
PG 6
WC Ophthalmology
SC Ophthalmology
GA 842AS
UT WOS:000296558500017
PM 21691258
ER
PT J
AU Aiello, LP
Vignati, L
Sheetz, MJ
Zhi, X
Girach, A
Davis, MD
Wolka, AM
Shahri, N
Milton, RC
AF Aiello, Lloyd Paul
Vignati, Louis
Sheetz, Matthew J.
Zhi, Xin
Girach, Aniz
Davis, Matthew D.
Wolka, Anne M.
Shahri, Nazila
Milton, Roy C.
CA PKC-DRS Study Grp
PKC-DRS2 Study Grp
TI ORAL PROTEIN KINASE C beta INHIBITION USING RUBOXISTAURIN Efficacy,
Safety, and Causes of Vision Loss Among 813 Patients (1,392 Eyes) with
Diabetic Retinopathy in the Protein Kinase C beta Inhibitor-Diabetic
Retinopathy Study and the Protein kinase C beta Inhibitor-Diabetic
Retinopathy Study 2
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE clinical trial; diabetes; diabetic retinopathy; PKC-DRS; PKC-DRS2;
protein kinase C beta; ruboxistaurin; vision loss
ID PKC-BETA; CLINICAL-TRIAL; MACULAR EDEMA; GROWTH-FACTOR; VISUAL-LOSS;
COMPLICATIONS; LY333531; RATS
AB Purpose: To evaluate efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with moderately severe to very severe nonproliferative diabetic retinopathy from the Protein Kinase C beta Inhibitor-Diabetic Retinopathy Study and Protein Kinase C beta Inhibitor-Diabetic Retinopathy Study 2 ruboxistaurin (RBX) protein kinase C beta inhibitor trials.
Methods: Patients in these 3-year, randomized, placebo-controlled, double-masked, Phase 3 trials had best-corrected Early Treatment Diabetic Retinopathy Study visual acuity >= 45 letters (similar to 20/125 Snellen), Early Treatment Diabetic Retinopathy Study retinopathy level 47A/B-53E, and no previous panretinal photocoagulation in >= 1 eye. Patients received placebo (N = 401) or RBX 32 mg/day (N = 412). Data from the 2 studies were combined and masked evaluation of retinal photographs was performed for cause of visual decline in all patients experiencing sustained moderate visual loss (>= 15-letter loss sustained for the last 6 months of study).
Results: In the studies combined, sustained moderate visual loss occurred in 10.2% of placebo-treated patients versus 6.1% of RBX-treated patients (P = 0.011). A >= 15-letter gain occurred in 2.4% of placebo versus 4.7% of RBX eyes (P = 0.021) and a >= 15-letter loss occurred in 11.4% versus 7.4%, respectively (P = 0.012). Diabetic macular edema was the probable primary cause of vision loss. Among eyes without focal/grid photocoagulation at baseline, fewer RBX group eyes (26.7%) required initial focal/grid photocoagulation versus placebo (35.6%; P = 0.008). No safety concerns were identified.
Conclusion: Analysis of data combined from two similar studies adds further statistical significance to RBX's beneficial effects on visual loss, need for focal laser, and vision gain, most likely through effects on macular edema. RETINA 31:2084-2094, 2011
C1 [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, Boston, MA 02215 USA.
[Vignati, Louis; Sheetz, Matthew J.; Zhi, Xin; Wolka, Anne M.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Girach, Aniz] Eli Lilly & Co, Windlesham, Surrey, England.
[Davis, Matthew D.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Shahri, Nazila] i3 Corp, San Diego, CA USA.
[Milton, Roy C.] EMMES Corp, Rockville, MD USA.
RP Aiello, LP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, 1 Joslin Pl, Boston, MA 02215 USA.
EM lpaiello@joslin.harvard.edu
FU Eli Lilly and Company (Indianapolis, IN)
FX Supported by Eli Lilly and Company (Indianapolis, IN). Drs. L. P.
Aiello, M. D. Davis, and R. C. Milton are consultants for Eli Lilly and
Company. Drs. M. J. Sheetz, X. Zhi, A. Girach, and A. M. Wolka are or
were full-time employees and shareholders of Eli Lilly and Company.
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U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD NOV
PY 2011
VL 31
IS 10
BP 2084
EP 2094
DI 10.1097/IAE.0b013e3182111669
PG 11
WC Ophthalmology
SC Ophthalmology
GA 842AS
UT WOS:000296558500018
PM 21862954
ER
PT J
AU Krueger, PM
Saint Onge, JM
Chang, VW
AF Krueger, Patrick M.
Saint Onge, Jarron M.
Chang, Virginia W.
TI Race/ethnic differences in adult mortality: The role of perceived stress
and health behaviors
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE Race; Ethnicity; Mortality; Health behaviors; Stress; USA
ID UNITED-STATES; SOCIOECONOMIC-STATUS; RACIAL DISPARITIES;
ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; SLEEP
DURATION; BLACK; WHITE; RISK
AB We examine the role of perceived stress and health behaviors (i.e., cigarette smoking, alcohol consumption, physical inactivity, sleep duration) in shaping differential mortality among whites, blacks, and Hispanics. We use data from the 1990 National Health Interview Survey (N = 38,891), a nationally representative sample of United States adults, to model prospective mortality through 2006. Our first aim examines whether unhealthy behaviors and perceived stress mediate race/ethnic disparities in mortality. The black disadvantage in mortality, relative to whites, closes after adjusting for socioeconomic status (SES), but re-emerges after adjusting for the lower smoking levels among blacks. After adjusting for SES. Hispanics have slightly lower mortality than whites; that advantage increases after adjusting for the greater physical inactivity among Hispanics, but closes after adjusting for their lower smoking levels. Perceived stress, sleep duration, and alcohol consumption do not mediate race/ethnic disparities in mortality. Our second aim tests competing hypotheses about race/ethnic differences in the relationships among unhealthy behaviors, perceived stress, and mortality. The social vulnerability hypothesis predicts that unhealthy behaviors and high stress levels will be more harmful for race/ethnic minorities. In contrast, the Blaxter (1990) hypothesis predicts that unhealthy lifestyles will be less harmful for disadvantaged groups. Consistent with the social vulnerability perspective, smoking is more harmful for blacks than for whites. But consistent with the Blaxter hypothesis, compared to whites, current smoking has a weaker relationship with mortality for Hispanics, and low or high levels of alcohol consumption, high levels of physical inactivity, and short or long sleep hours have weaker relationships with mortality for blacks. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Krueger, Patrick M.] Univ Colorado Denver, Denver, CO USA.
[Krueger, Patrick M.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Saint Onge, Jarron M.] Univ Houston, Dept Sociol, Houston, TX USA.
[Chang, Virginia W.] Philadelphia VAMC, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Chang, Virginia W.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Chang, Virginia W.] Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA.
RP Krueger, PM (reprint author), Univ Colorado Denver, Denver, CO USA.
EM Patrick.Krueger@ucdenver.edu
OI Saint Onge, Jarron/0000-0002-0914-4882
FU University of Colorado [NICHD R21 HD51146]; University of Houston [NIDA
R24 DA019798]; National Institutes of Health [NICHD K12-HD043459]
FX This paper has benefited from presentation at the 2008 meetings of the
American Sociological Association in Boston, MA. We acknowledge
administrative support from the University of Colorado Population
Program (NICHD R21 HD51146), the University of Houston (NIDA R24
DA019798), and the Leonard Davis Institute of Health Economics at the
University of Pennsylvania, and research support from the National
Institutes of Health (NICHD K12-HD043459).
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD NOV
PY 2011
VL 73
IS 9
BP 1312
EP 1322
DI 10.1016/j.socscimed.2011.08.007
PG 11
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 843OF
UT WOS:000296680800005
PM 21920655
ER
PT J
AU Liu, L
Cohen, S
Schulz, MS
Waldinger, RJ
AF Liu, Liang
Cohen, Shiri
Schulz, Marc S.
Waldinger, Robert J.
TI Sources of somatization: Exploring the roles of insecurity in
relationships and styles of anger experience and expression
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE USA; Gender; Attachment; Somatization; Anger proneness; Anger
expression; Emotion regulation
ID HEALTH-CARE-UTILIZATION; ADULT ATTACHMENT; TRANSIENT HYPOCHONDRIASIS;
SOMATIC SYMPTOMS; PARTNER VIOLENCE; MODEL; SELF; PERSONALITY;
DEPRESSION; COMPLAINTS
AB Research in the U.S. has shown strong connections between insecure attachment in close relationships and somatization. In addition, studies have demonstrated connections between somatic symptoms and anger experience and expression. In this study, we integrate perspectives from these two literatures by testing the hypothesis that proneness to anger and suppression of anger mediate the link between insecurity in relationships and somatization. Between 2000 and 2003, a community-based sample of 101 couples in a large U.S. city completed self-report measures, including the Somatic Symptom Inventory, the Relationship Scales Questionnaire, the Multidimensional Anger Inventory, the Revised Conflict Tactics Scale, and the Beck Depression Inventory. Controlling for age, income, and recent intimate partner violence, analyses showed that the link between insecure attachment and somatization was partially mediated by anger proneness for men and by anger suppression for women. Findings are consistent with the hypothesis that men who are insecurely attached are more prone to experience anger that in turn fosters somatization. For women, findings suggest that insecure attachment may influence adult levels of somatization by fostering suppression of anger expression. Specific clinical interventions that help patients manage and express angry feelings more adaptively may reduce insecurely attached individuals' vulnerability to medically unexplained somatic symptoms. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Waldinger, Robert J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Liu, Liang] Tongji Univ, Sch Med, Shanghai 200092, Peoples R China.
[Liu, Liang] Tongji Univ, Shanghai E Hosp, Dept Psychosomat Med, Shanghai 200092, Peoples R China.
[Cohen, Shiri; Waldinger, Robert J.] Harvard Univ, Sch Med, Boston, MA USA.
[Schulz, Marc S.] Bryn Mawr Coll, Bryn Mawr, PA 19010 USA.
RP Waldinger, RJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA.
EM rwaldinger@partners.org
FU National Institute of Mental Health [K08 MH01555]; National Institute on
Aging [R01 AG034554]
FX Supported by grants from the National Institute of Mental Health (K08
MH01555, Waldinger, PI) and the National Institute on Aging (R01
AG034554, Waldinger, PI). The funding sources had no involvement in the
design, data collection or analysis of the research, nor were the
sponsors involved in the preparation and submission of the manuscript.
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD NOV
PY 2011
VL 73
IS 9
BP 1436
EP 1443
DI 10.1016/j.socscimed.2011.07.034
PG 8
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 843OF
UT WOS:000296680800021
PM 21907475
ER
PT J
AU Fidalgo, M
Shekar, PC
Ang, YS
Fujiwara, Y
Orkin, SH
Wang, JL
AF Fidalgo, Miguel
Shekar, P. Chandra
Ang, Yen-Sin
Fujiwara, Yuko
Orkin, Stuart H.
Wang, Jianlong
TI Zfp281 Functions as a Transcriptional Repressor for Pluripotency of
Mouse Embryonic Stem Cells
SO STEM CELLS
LA English
DT Article
DE Zfp281; Nanog; Embryonic stem cells; Transcriptional repressor;
Self-renewal; Pluripotency
ID PROTEIN-INTERACTION NETWORK; SELF-RENEWAL; SIGNALING NETWORKS; RNA
INTERFERENCE; ES CELLS; NANOG; OCT4; MYC; DIFFERENTIATION;
IDENTIFICATION
AB Embryonic stem cells (ESCs) derived from preimplantation blastocysts have unique self-renewal and multilineage differentiation properties that are controlled by key components of a core regulatory network including Oct4, Sox2, and Nanog. Understanding molecular underpinnings of these properties requires identification and characterization of additional factors that act in conjunction with these key factors in ESCs. We have previously identified Zfp281, a Kruppel-like zinc finger transcription factor, as an interaction partner of Nanog. We now present detailed functional analyses of Zfp281 using a genetically ablated null allele in mouse ESCs. Our data show that while Zfp281 is dispensable for establishment and maintenance of ESCs, it is required for their proper differentiation in vitro. We performed microarray profiling in combination with previously published datasets of Zfp281 global target gene occupancy and found that Zfp281 mainly functions as a repressor to restrict expression of many stem cell pluripotency genes. In particular, we demonstrated that deletion of Zfp281 resulted in upregulation of Nanog at both the transcript and protein levels with concomitant compromised differentiation of ESCs during embryoid body culture. Chromatin immunoprecipitation experiments demonstrated that Zfp281 is required for Nanog binding to its own promoter, suggesting that Nanog-associated repressive complex(es) involving Zfp281 may fine-tune Nanog expression for pluripotency of ESCs. STEM CELLS 2011;29:1705-1716
C1 [Fidalgo, Miguel; Shekar, P. Chandra; Ang, Yen-Sin; Wang, Jianlong] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, Black Family Stem Cell Inst, New York, NY 10029 USA.
[Fujiwara, Yuko; Orkin, Stuart H.] Childrens Hosp, Boston, MA 02115 USA.
[Fujiwara, Yuko; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Fujiwara, Yuko; Orkin, Stuart H.] Harvard Stem Cell Inst, Cambridge, MA USA.
[Fujiwara, Yuko; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Wang, JL (reprint author), Mt Sinai Sch Med, Dept Dev & Regenerat Biol, Black Family Stem Cell Inst, Atran Bldg,AB7-10D,1428 Madison Ave, New York, NY 10029 USA.
EM jianlong.wang@mssm.edu
OI Fidalgo, Miguel/0000-0003-1134-2674
FU Black Family Stem Cell Institute at Mount Sinai School of Medicine; New
York State Department of Health [N09G315]; NIH [1R01-GM095942-01A1]
FX We thank Francesco Faiola and Arven Saunders of the Wang laboratory for
critically reading the manuscript. Research in the Wang laboratory is
supported by the seed fund from Black Family Stem Cell Institute at
Mount Sinai School of Medicine, a New York State Stem Cell Science
(NYSTEM) grant through New York State Department of Health (N09G315),
and a grant from the NIH (1R01-GM095942-01A1).
NR 38
TC 18
Z9 20
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD NOV
PY 2011
VL 29
IS 11
BP 1705
EP 1716
DI 10.1002/stem.736
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 842CN
UT WOS:000296565500008
PM 21915945
ER
PT J
AU Sebastiano, V
Maeder, ML
Angstman, JF
Haddad, B
Khayter, C
Yeo, DT
Goodwin, MJ
Hawkins, JS
Ramirez, CL
Batista, LFZ
Artandi, SE
Wernig, M
Joung, JK
AF Sebastiano, Vittorio
Maeder, Morgan L.
Angstman, James F.
Haddad, Bahareh
Khayter, Cyd
Yeo, Dana T.
Goodwin, Mathew J.
Hawkins, John S.
Ramirez, Cherie L.
Batista, Luis F. Z.
Artandi, Steven E.
Wernig, Marius
Joung, J. Keith
TI In Situ Genetic Correction of the Sickle Cell Anemia Mutation in Human
Induced Pluripotent Stem Cells Using Engineered Zinc Finger Nucleases
SO STEM CELLS
LA English
DT Article
DE Induced pluripotency; Gene therapy; Gene targeting; Anemia; Zinc finger
nucleases
ID HUMAN SOMATIC-CELLS; HOMOLOGOUS RECOMBINATION; TRANSCRIPTION FACTORS;
DEFINED FACTORS; HUMAN ESCS; GENERATION; GENOME; DISEASE; PATIENT;
CONSTRUCTION
AB The combination of induced pluripotent stem cell (iPSC) technology and targeted gene modification by homologous recombination (HR) represents a promising new approach to generate genetically corrected, patient-derived cells that could be used for autologous transplantation therapies. This strategy has several potential advantages over conventional gene therapy including eliminating the need for immunosuppression, avoiding the risk of insertional mutagenesis by therapeutic vectors, and maintaining expression of the corrected gene by endogenous control elements rather than a constitutive promoter. However, gene targeting in human pluripotent cells has remained challenging and inefficient. Recently, engineered zinc finger nucleases (ZFNs) have been shown to substantially increase HR frequencies in human iPSCs, raising the prospect of using this technology to correct disease causing mutations. Here, we describe the generation of iPSC lines from sickle cell anemia patients and in situ correction of the disease causing mutation using three ZFN pairs made by the publicly available oligomerized pool engineering method (OPEN). Gene-corrected cells retained full pluripotency and a normal karyotype following removal of reprogramming factor and drug-resistance genes. By testing various conditions, we also demonstrated that HR events in human iPSCs can occur as far as 82 bps from a ZFN-induced break. Our approach delineates a roadmap for using ZFNs made by an open-source method to achieve efficient, transgene-free correction of monogenic disease mutations in patient-derived iPSCs. Our results provide an important proof of principle that ZFNs can be used to produce gene-corrected human iPSCs that could be used for therapeutic applications. STEM CELLS 2011;29:1717-1726
C1 [Sebastiano, Vittorio; Haddad, Bahareh; Yeo, Dana T.; Hawkins, John S.; Wernig, Marius] Stanford Univ, Dept Pathol, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
[Sebastiano, Vittorio] Stanford Univ, Dept Obstet & Gynecol, Sch Med, Stanford, CA 94305 USA.
[Batista, Luis F. Z.; Artandi, Steven E.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Maeder, Morgan L.; Angstman, James F.; Khayter, Cyd; Goodwin, Mathew J.; Ramirez, Cherie L.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA USA.
[Maeder, Morgan L.; Angstman, James F.; Khayter, Cyd; Goodwin, Mathew J.; Ramirez, Cherie L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA.
[Maeder, Morgan L.; Ramirez, Cherie L.; Joung, J. Keith] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA USA.
[Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Wernig, M (reprint author), Stanford Univ, Dept Pathol, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
EM wernig@stanford.edu; jjoung@partners.org
OI Batista, Luis/0000-0002-7538-3240
FU NIH [R01 GM069906, DP1 OD006862]; National Science Foundation; Institute
for Stem Cell Biology and Regenerative Medicine, Stanford University
School of Medicine; Donald E. and Delia B. Baxter Foundation; CIRM
Training Grant
FX We thank the patients who volunteered to donate a skin biopsy for this
project, Rob Cho for consenting the patients and collecting the
biopsies, Pei Wang for help with the Adeno-Cre infections and
fluorescence-activated cell sorting, Stacey Thibodeau-Beganny for help
with plasmid construction, Jeffry Sander for help with identification of
potential genomic off-target sites, and Gerlinde Wernig for providing
critical technical advice. This work was supported by NIH Grant R01
GM069906 and Pioneer Award DP1 OD006862 (to J.K.J.); National Science
Foundation Graduate Research Fellowships (to M. L. M. and C. L. R.);
Start-up funds of the Institute for Stem Cell Biology and Regenerative
Medicine, Stanford University School of Medicine and the Donald E. and
Delia B. Baxter Foundation (to M. W.); and the CIRM Training Grant for
postdoctoral fellows (to V. S.). M. W. is a New York Stem Cell
Foundation Robertson Investigator. J.K.J. is the Jim and Ann Orr
Massachusetts General Hospital Research Scholar.
NR 49
TC 156
Z9 163
U1 5
U2 43
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD NOV
PY 2011
VL 29
IS 11
BP 1717
EP 1726
DI 10.1002/stem.718
PG 10
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 842CN
UT WOS:000296565500009
PM 21898685
ER
PT J
AU Nelson, P
Young, HN
Knobloch, MJ
Griesbach, SA
AF Nelson, Philip
Young, Henry N.
Knobloch, Mary Jo
Griesbach, Sara A.
TI Telephonic Monitoring and Optimization of Inhaler Technique
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE asthma; asthma management; telephonic monitoring; inhaler; metered-dose
inhalers; MDI; diskus; dry powder inhalers,patient education as topic;
telemedicine
ID METERED-DOSE INHALER; RANDOMIZED CONTROLLED-TRIAL; INHALATION TECHNIQUE;
ASTHMA REVIEWS; CARE; ACCESSIBILITY; INSTRUCTION; MISUSE
AB Introduction: Improper inhaler technique is a common problem affecting asthma control and healthcare costs. Telephonic asthma management can increase access to care while reducing costs and hospitalizations. However, no reliable method has been established for telephonically evaluating and correcting inhaler technique. Objective: The purpose of this study was to pilot test a method for assessing and correcting patient inhaler technique via telephone. Methods: Participants (n = 30) were adults with asthma using metered-dose inhalers (MDIs) and diskus inhalers. A pharmacist was located in one room and communicated via telephone with a participant in another room. The pharmacist telephonically assessed and taught inhaler technique. Participants were videorecorded, and videos were later examined by a second pharmacist to visually evaluate inhaler technique. Participants were assigned pre- and posteducation inhaler technique scores for the telephonic and video assessments. Scores were based on summated scales for MDI (0-9) and diskus (0-11) inhalers. Paired samples t-tests were used to compare telephone and video assessments. Results: Findings indicated a significant difference between the telephone and video assessments of MDI technique (p < 0.05); however, no difference was found for the diskus inhaler. Comparing pre-and posteducation inhaler technique for MDI and diskus, mean scores significantly improved from 5.7 to 7.8 (p < 0.05) and from 8.5 to 10.4 (p < 0.05), respectively. Conclusions: The telephonic method was able to improve and detect some deficiencies in patients' inhaler technique. However, modifications and further investigation will more clearly determine the role and value of such a telephonic intervention.
C1 [Knobloch, Mary Jo; Griesbach, Sara A.] Marshfield Clin Fdn Med Res & Educ, Div Educ, Marshfield, WI 54449 USA.
[Nelson, Philip] S Texas Vet Hlth Care Syst, Ambulatory Care Pharm, San Antonio, TX USA.
[Young, Henry N.] Univ Wisconsin, Social & Adm Sci Div, Madison Sch Pharm, Sonderegger Res Ctr, Madison, WI USA.
[Knobloch, Mary Jo] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Partnership Program, Madison, WI USA.
RP Griesbach, SA (reprint author), Marshfield Clin Fdn Med Res & Educ, Div Educ, 1000 N Oak Ave,GQ4, Marshfield, WI 54449 USA.
EM griesbach.sara@marshfieldclinic.org
FU Marshfield Clinic's Division of Education; National Center for Research
Resources, National Institutes of Health [1UL1RR025011]
FX The authors are grateful to Andrea Mahnke, BIRC usability analyst, for
the wonderful technical support in utilizing the Marshfield Clinic
Research Foundation's BIRC lab. We also thank Nina M. Antoniotti, RN,
MBA, PhD; Elizabeth D. Cox, MD, PhD; and Megan A. Moreno, MD, MSEd, MPH,
for their review of the article. We further thank Marie Fleisner of the
Marshfield Clinic Research Foundation's Office of Scientific Publication
for editorial assistance in the preparation of this article. Funding for
this study was provided by Marshfield Clinic's Division of Education
Resident Research Program and supported by grant 1UL1RR025011 from the
Clinical and Translational Science Award program of the National Center
for Research Resources, National Institutes of Health.
NR 33
TC 6
Z9 6
U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-5627
J9 TELEMED E-HEALTH
JI Telemed. e-Health
PD NOV
PY 2011
VL 17
IS 9
BP 734
EP 740
DI 10.1089/tmj.2011.0047
PG 7
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 842HT
UT WOS:000296588400012
PM 21943162
ER
PT J
AU Reynolds, HN
Sheinfeld, G
Chang, J
Tabatabai, A
Simmons, D
AF Reynolds, H. Neal
Sheinfeld, Geoffrey
Chang, James
Tabatabai, Ali
Simmons, Dell
TI The Tele-Intensive Care Unit During a Disaster: Seamless Transition from
Routine Operations to Disaster Mode
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE disaster medicine; telemedicine; telehealth
AB Disaster plans, during the actual disaster, often do not function as conceived and designed. Disaster or emergency situations may not present as anticipated in planning sessions confounding the intent of disaster planners. Systems that are created and shelved awaiting the disaster may be dysfunctional when needed due to problems such as failed batteries, forgotten training, misplaced equipment, the retraining curve, or software that has not been updated. We report here the smooth and seamless transition to disaster mode from a system in daily use and therefore operational when needed.
C1 [Reynolds, H. Neal; Chang, James; Tabatabai, Ali; Simmons, Dell] Univ Maryland, R Adams Cowley Shock Trauma Ctr, Sch Med, Baltimore, MD 21201 USA.
[Sheinfeld, Geoffrey] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Reynolds, HN (reprint author), Univ Maryland, R Adams Cowley Shock Trauma Ctr, Sch Med, 22 S Greene St, Baltimore, MD 21201 USA.
EM hneal.reynolds@gmail.com
NR 13
TC 4
Z9 4
U1 1
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-5627
J9 TELEMED E-HEALTH
JI Telemed. e-Health
PD NOV
PY 2011
VL 17
IS 9
BP 746
EP 749
DI 10.1089/tmj.2011.0046
PG 4
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 842HT
UT WOS:000296588400014
PM 21943160
ER
PT J
AU Daniels, GH
AF Daniels, Gilbert H.
TI Screening for Medullary Thyroid Carcinoma with Serum Calcitonin
Measurements in Patients with Thyroid Nodules in the United States and
Canada
SO THYROID
LA English
DT Article
ID C-CELL HYPERPLASIA; ROUTINE MEASUREMENT; PREOPERATIVE DIAGNOSIS; PLASMA
CALCITONIN; PREDICTIVE-VALUE; HIGH PREVALENCE; DISEASE; AUTOPSY; CANCER;
MICROCARCINOMA
AB Background: Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy with the potential for aggressive behavior. Measurement of serum calcitonin (Ct) in the thyroid nodule population is the most sensitive way to detect occult MTC. An important and controversial question is whether all patients with thyroid nodules should undergo Ct measurements to detect occult MTC.
Summary: The prevalence of MTC detected by performing surgery on unselected individuals with thyroid nodules with elevated serum Ct is 0.4%. The central role of pentagastrin (PG) stimulation for triaging patients with minimally elevated serum Ct to prevent unnecessary surgery is reviewed. Data concerning a large reservoir of medullary thyroid microcarcinomas are discussed.
Conclusion: Given the unavailability of PG in the United States and Canada, the available data argue against routine Ct measurements in all individuals with thyroid nodules in these countries because of the potential for unnecessary surgery and the uncertain benefit in diagnosing medullary microcarcinoma.
C1 [Daniels, Gilbert H.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med,Thyroid Unit, Boston, MA 02114 USA.
[Daniels, Gilbert H.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA.
RP Daniels, GH (reprint author), Massachusetts Gen Hosp ACC 730, Thyroid Unit ACC 730, Ctr Canc, Boston, MA 02114 USA.
EM gdaniels@partners.org
NR 60
TC 19
Z9 20
U1 0
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD NOV
PY 2011
VL 21
IS 11
BP 1199
EP 1207
DI 10.1089/thy.2010.0297
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 844IU
UT WOS:000296741700006
PM 21936671
ER
PT J
AU Cristini, S
Alessandri, G
Acerbi, F
Ciusani, E
Colombo, A
Fascio, U
Nicosia, RF
Invernizzi, RW
Gelati, M
Parati, EA
Invernici, G
AF Cristini, Silvia
Alessandri, Giulio
Acerbi, Francesco
Ciusani, Emilio
Colombo, Augusto
Fascio, Umberto
Nicosia, Roberto F.
Invernizzi, Roberto W.
Gelati, Maurizio
Parati, Eugenio A.
Invernici, Gloria
TI Three-Dimensional Self-Organizing Neural Architectures: A Neural Stem
Cells Reservoir and a System for Neurodevelopmental Studies
SO TISSUE ENGINEERING PART C-METHODS
LA English
DT Article
ID EPIDERMAL-GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; ADULT HUMAN BRAIN;
PROGENITOR CELLS; IN-VITRO; NEURONAL PROGENITORS; RECEPTOR ACTIVATION;
GENE-EXPRESSION; PRECURSOR CELLS; SPINAL-CORD
AB Complex microenvironmental stimuli influence neural cell properties. To study this, we developed a three-dimensional (3-D) neural culture system, composed of different populations including neurons, astrocytes, and neural stem cells (NSCs). In particular, these last-mentioned cells represent a source potentially exploitable to test drugs, to study neurodevelopment and cell-therapies for neuroregenerations. On seeding on matrigel in a medium supplemented with serum and mitogens, cells obtained from human fetal brain tissue formed 3-D self-organizing neural architectures. Immunocytochemical analysis demonstrated the presence of undifferentiated nestin + and CD133+ cells, surrounded by beta-tub-III+ and GFAP + cells, suggesting the formation of niches containing potential human NSCs (hNSCs). The presence of hNSCs was confirmed by both neurosphere assay and RT-PCR, and their multipotentiality was demonstrated by both immunofluorescent staining and RT-PCR. Flow cytometry analysis revealed that neurosphere forming cells originating from at least two different subsets expressing, respectively, CD133 and CD146 markers were endowed with different proliferative and differentiation potential. Our data implicate that the complexity of environment within niches and aggregates of heterogeneous neural cell subsets may represent an innovative platform for neurobiological and neurodevelopmental investigations and a reservoir for a rapid expansion of hNSCs.
C1 [Cristini, Silvia; Alessandri, Giulio; Gelati, Maurizio; Parati, Eugenio A.; Invernici, Gloria] Fdn IRCCS Ist Neurol Carlo Besta, Lab Cellular Neurobiol, I-20133 Milan, Italy.
[Acerbi, Francesco] Fdn IRCCS Ist Neurol Carlo Besta, Dept Neurosurg, I-20133 Milan, Italy.
[Acerbi, Francesco] Univ Milan, Dept Neurol Sci, Milan, Italy.
[Ciusani, Emilio] Fdn IRCCS Ist Neurol Carlo Besta, Lab Clin Anal, I-20133 Milan, Italy.
[Colombo, Augusto] Fdn IRCCS Osped Maggiore Policlin Mangiagalli & R, Dept Obstet & Gynecol, Milan, Italy.
[Fascio, Umberto] Univ Milan, Interdept Ctr Adv Microscopy CIMA, Milan, Italy.
[Nicosia, Roberto F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Nicosia, Roberto F.] Univ Washington, Seattle, WA 98195 USA.
[Invernizzi, Roberto W.] Ist Ric Farmacol M Negri, Lab Neurochem & Behav, Milan, Italy.
RP Invernici, G (reprint author), Fdn IRCCS Ist Neurol Carlo Besta, Lab Cellular Neurobiol, Via Celoria 11, I-20133 Milan, Italy.
EM gloria.invernici@istituto-besta.it
RI Parati, Eugenio/G-8765-2011; Gelati, Maurizio/H-2110-2016
OI Gelati, Maurizio/0000-0002-4828-9849
FU Fondazione IRCCS Istituto Neurologico "Carlo Besta" [LR8]; Italian
Ministry of Health [RF2008.22]; National Heart, Lung, and Blood
Institute [HL52585]; Department of Veterans Affairs Medical Research
Service
FX The authors thank Dr. Andrea Smith for the English review of the
article. We thank Deborah Jones for her excellent technical assistance
with the electron microscopy studies. This work was supported by
Fondazione IRCCS Istituto Neurologico "Carlo Besta" (LR8); the Italian
Ministry of Health (RF2008.22); National Heart, Lung, and Blood
Institute (HL52585); and Merit Review Grant, Department of Veterans
Affairs Medical Research Service.
NR 65
TC 1
Z9 1
U1 0
U2 5
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3384
EI 1937-3392
J9 TISSUE ENG PART C-ME
JI Tissue Eng. Part C-Methods
PD NOV
PY 2011
VL 17
IS 11
BP 1109
EP 1120
DI 10.1089/ten.tec.2010.0622
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 844BB
UT WOS:000296721200008
PM 21721991
ER
PT J
AU Lee, DH
Chowdhury, D
AF Lee, Dong-Hyun
Chowdhury, Dipanjan
TI What goes on must come off: phosphatases gate-crash the DNA damage
response
SO TRENDS IN BIOCHEMICAL SCIENCES
LA English
DT Review
ID DOUBLE-STRAND BREAK; REPLICATION-PROTEIN-A; CHECKPOINT KINASE RAD53;
WIP1 PHOSPHATASE; DEPHOSPHORYLATES GAMMA-H2AX; REGULATORY SUBUNIT;
TUMOR-SUPPRESSOR; SACCHAROMYCES-CEREVISIAE; DOCKING MOTIF; FORK RESTART
AB DNA-damage-induced phospho-signaling has been studied for decades, with a focus mainly on initiation of the signaling cascade, and the kinases activated by DNA lesions. It is widely accepted that the balance of phosphorylation needs to be restored and/or maintained by phosphatases, yet there have only been sporadic efforts to investigate the impact of phosphatases on DNA repair. Recent advances in phosphoproteomic strategies and implementation of large genetic screens indicate that these enzymes play pivotal roles in these signaling networks. Dephosphorylation of repair proteins is crucial for efficient DNA repair, and the recommencement of cell division post-repair. Here, we focus on serine/threonine phosphatases implicated in dephosphorylation of DNA repair factors, summarizing recent findings and speculating on untested roles of phosphatases in the DNA damage response.
C1 [Lee, Dong-Hyun; Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
RP Chowdhury, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
EM dipanjan_chowdhury@dfci.harvard.edu
FU Barr Award; NIH [CA 009078-34]
FX DC is by R01CA142698 (NCI), JCRT and a Barr Award. DL was supported by
NIH-training grant (CA 009078-34). We apologize to our colleagues whose
work we could not discuss due to space constraints.
NR 100
TC 15
Z9 15
U1 0
U2 1
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0968-0004
J9 TRENDS BIOCHEM SCI
JI Trends Biochem.Sci.
PD NOV
PY 2011
VL 36
IS 11
BP 569
EP 577
DI 10.1016/j.tibs.2011.08.007
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 843MG
UT WOS:000296675300002
PM 21930385
ER
PT J
AU Ix, JH
Chonchol, M
Laughlin, GA
Shlipak, MG
Whooley, MA
AF Ix, Joachim H.
Chonchol, Michel
Laughlin, Gail A.
Shlipak, Michael G.
Whooley, Mary A.
TI Relation of Sex and Estrogen Therapy to Serum Fibroblast Growth Factor
23, Serum Phosphorus, and Urine Phosphorus: The Heart and Soul Study
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Menopause; fibroblast growth factor 23; phosphorus; estradiol; sex
hormones
ID CORONARY-ARTERY-DISEASE; NUTRITION EXAMINATION SURVEY; CHRONIC
KIDNEY-DISEASE; VITAMIN-D METABOLITES; 3RD NATIONAL-HEALTH;
POSTMENOPAUSAL WOMEN; MINERAL METABOLISM; OSTEOPOROTIC FRACTURES;
PHOSPHATE REABSORPTION; CARDIOVASCULAR-DISEASE
AB Background: Menopause is associated with urine phosphorus retention, which is mitigated by estrogen therapy. Fibroblast growth factor 23 (FGF-23) is a hormone originating from bone that regulates urine phosphorus excretion. Whether sex or estrogen therapy is associated with different FGF-23 levels is unknown.
Study Design & Setting: Cross-sectional study of ambulatory individuals with prevalent cardiovascular disease.
Predictors: Sex and, in women, use or nonuse of estrogen.
Outcomes: Serum phosphorus, tubular maximum reabsorption of phosphorus indexed to glomerular filtration rate (TMP/GFR), and plasma FGF-23 concentrations.
Results: For 987 participants, mean age was 67 +/- 11 years, 182 (18%) were women, and 46 (25%) were using estrogen. Mean estimated GFR was 71 +/- 23 (SD) mL/min/1.73 m(2). Compared with women who were not using estrogen, both women on estrogen therapy and men had significantly lower serum phosphorus concentrations, lower TMP/GFR values (indicating higher urine phosphorus excretion), and lower FGF-23 concentrations with adjustment for age, demographics, and kidney function (P < 0.001 for each). Mean FGF-23 levels were 68.7 (95% CI, 59.7-79.0) relative units (RU)/mL in non-estrogen-using women, 43.8 (95% CI, 41.2-46.5) RU/mL in men, and 45.1 (95% CI, 35.2-57.4) RU/mL in women using estrogen in adjusted analysis (P < 0.001).
Limitations: Most participants were men. Estrogen therapy was not randomly assigned.
Conclusions: Older women who are not using estrogen have higher FGF-23 levels than either men or women using estrogen. In the context of prior literature, these data suggest that postmenopausal phosphorus retention may stimulate higher FGF-23 concentrations after menopause. Am J Kidney Dis. 58(5): 737-745. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.
C1 [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92161 USA.
[Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92161 USA.
[Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA.
[Chonchol, Michel] Univ Colorado Denver, Dept Med, Div Renal Dis & Hypertens, Aurora, CO USA.
[Laughlin, Gail A.] Univ Calif San Diego, Dept Family & Prevent Med, Div Epidemiol, San Diego, CA 92103 USA.
[Shlipak, Michael G.; Whooley, Mary A.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA.
[Shlipak, Michael G.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Shlipak, Michael G.; Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA.
EM joeix@ucsd.edu
FU National Heart, Lung and Blood Institute [NHLBI: R01 HL096851, R01
HL079235]; American Heart Association (AHA) [0575021N]; Sandra Daugherty
Foundation; Department of Veterans; Department of Veterans Affairs
Health Services Research and Development service; American Federation
for Aging Research; Robert Wood Johnson Foundation; Ischemia Research
and Education Foundation
FX This study was supported by grants from the National Heart, Lung and
Blood Institute (NHLBI: R01 HL096851), American Heart Association (AHA
0575021N), and the Sandra Daugherty Foundation to Dr Ix. The Heart and
Soul Study was supported by the Department of Veterans Epidemiology
Merit Review Program, the Department of Veterans Affairs Health Services
Research and Development service, the NHLBI (R01 HL079235), the American
Federation for Aging Research (Paul Beeson Scholars Program), the Robert
Wood Johnson Foundation (Generalist Physician Faculty Scholars Program),
and the Ischemia Research and Education Foundation.
NR 51
TC 27
Z9 27
U1 0
U2 12
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD NOV
PY 2011
VL 58
IS 5
BP 737
EP 745
DI 10.1053/j.ajkd.2011.06.011
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 839RF
UT WOS:000296385700011
PM 21855188
ER
PT J
AU Diaz, MFP
Pichler, RH
Nicosia, RF
Alpers, CE
Smith, KD
AF Diaz, Miguel F. Palma
Pichler, Raimund H.
Nicosia, Roberto F.
Alpers, Charles E.
Smith, Kelly D.
TI Collapsing Glomerulopathy Associated With Natural Killer Cell Leukemia:
A Case Report and Review of the Literature
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Focal segmental glomerulosclerosis; collapsing glomerulopathy; natural
killer (NK) cell leukemia
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; NEPHROTIC SYNDROME;
AFRICAN-AMERICANS; HEMOPHAGOCYTIC SYNDROME; PATHOGENESIS; NEPHROPATHY;
APOL1; PODOCYTE; DISEASE; MYH9
AB We report a case of collapsing glomerulopathy associated with natural killer cell leukemia in a previously healthy 27-year-old African American man. An initial kidney biopsy showed findings concordant with the cellular variant of focal segmental glomerulosclerosis. A repeated biopsy 3 months later showed collapsing glomerulopathy, likely representing a morphologic evolution from a cellular variant into the collapsing glomerulopathy variant of focal segmental glomerulosclerosis. Collapsing glomerulopathy has been described in connection with a number of disparate disorders in which podocyte injury seems to be the common denominator. The close temporal association between clinical presentation and the development of nephropathy provides support for a direct pathogenic link between the underlying lymphoproliferative disorder and the glomerular lesions. We hypothesize that dysregulated cytokine production by the neoplastic cells led to podocyte alterations and eventually to the development of collapsing glomerulopathy. Am J Kidney Dis. 58(5):855-859. (C) 2011 by the National Kidney Foundation, Inc.
C1 [Diaz, Miguel F. Palma; Nicosia, Roberto F.; Alpers, Charles E.; Smith, Kelly D.] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA.
[Pichler, Raimund H.] Univ Washington, Med Ctr, Div Nephrol, Seattle, WA 98195 USA.
[Nicosia, Roberto F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Diaz, MFP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, 10833 Le Conte Ave,CHS 13-145, Los Angeles, CA 90095 USA.
EM fpalmadiaz@mednet.ucla.edu
NR 25
TC 3
Z9 3
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD NOV
PY 2011
VL 58
IS 5
BP 855
EP 859
DI 10.1053/j.ajkd.2011.07.011
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 839RF
UT WOS:000296385700025
ER
PT J
AU Rigotti, NA
Bitton, A
Kelley, JK
Hoeppner, BB
Levy, DE
Mort, E
AF Rigotti, Nancy A.
Bitton, Asaf
Kelley, Jennifer K.
Hoeppner, Bettina B.
Levy, Douglas E.
Mort, Elizabeth
TI Offering Population-Based Tobacco Treatment in a Healthcare Setting A
Randomized Controlled Trial
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID NICOTINE REPLACEMENT THERAPY; SMOKING-CESSATION; QUITLINE; SMOKERS;
SYSTEM; RATES
AB Background: The healthcare system is a key channel for delivering treatment to tobacco users. Brief clinic-based interventions are effective but not reliably offered. Population management strategies might improve tobacco treatment delivery in a healthcare system.
Purpose: To test the effectiveness of supplementing clinic-based care with a population-based direct-to-smoker (DTS) outreach offering easily accessible free tobacco treatment.
Design: Randomized controlled trial, conducted in 2009-2010, comparing usual clinical care to usual care plus DTS outreach.
Setting/participants: A total of 590 smokers registered for primary care at a community health center in Revere MA.
Interventions: Three monthly letters offering a free telephone consultation with a tobacco coordinator who provided free treatment including up to 8 weeks of nicotine patches (NRT) and proactive referral to the state quitline for multisession counseling.
Main outcome measures: Use of any tobacco treatment (primary outcome) and tobacco abstinence at the 3-month follow-up; cost per quit.
Results: Of 413 eligible smokers, 43 (10.4%) in the DTS group accepted the treatment offer; 42 (98%) requested NRT and 30 (70%) requested counseling. In intention-to-treat analyses adjusted by logistic regression for age, gender, race, insurance, diabetes, and coronary heart disease, a higher proportion of the DTS group, compared to controls, had used NRT (11.6% vs 3.9%, OR = 3.47; 95% CI = 1.52, 7.92) or any tobacco treatment (14.5% vs 7.3%, OR = 1.95, 95% CI = 1.04, 3.65) and reported being tobacco abstinent for the past 7 days (5.3% vs 1.1%, OR = 5.35, 95% CI = 1.23, 22.32) and past 30 days (4.1% vs 0.6%, OR = 8.25, 95% CI = 1.08, 63.01). The intervention did not increase smokers' use of counseling (1.7% vs 1.1%) or non-NRT medication (3.6% vs 3.9%). Estimated incremental cost per quit was $464.
Conclusions: A population-based outreach offering free tobacco treatment to smokers in a health center was a feasible, cost-effective way to increase the reach of treatment (primarily NRT) and to increase short-term quit rates.
Trial registration: This study is registered at Clinicaltrials.gov NCT01321944. (Am J Prev Med 2011;41(5):498-503) (C) 2011 American Journal of Preventive Medicine
C1 [Rigotti, Nancy A.; Mort, Elizabeth] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA.
[Rigotti, Nancy A.; Bitton, Asaf; Kelley, Jennifer K.; Hoeppner, Bettina B.; Levy, Douglas E.] Tobacco Res & Treatment Ctr, Boston, MA USA.
[Hoeppner, Bettina B.] Massachusetts Gen Hosp, Ctr Addict Med, Dept Psychiat, Boston, MA 02114 USA.
[Bitton, Asaf] Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Boston, MA 02115 USA.
[Kelley, Jennifer K.; Mort, Elizabeth] Partners HealthCare, Mongan Inst Hlth Policy, High Performance Med, Boston, MA USA.
[Rigotti, Nancy A.; Bitton, Asaf; Hoeppner, Bettina B.; Levy, Douglas E.; Mort, Elizabeth] Harvard Univ, Sch Med, Boston, MA USA.
RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM nrigotti@partners.org
FU DTS; Health Resources and Services Administration [T32HP10251];
[1K01DA027097-01A1]; [K24-HL08880]
FX Partners Health Care, Inc., funded the DTS program, study data
collection and data management. Data analysis was conducted by an
independently funded investigator (BBH). Study investigators' efforts on
the project were supported by grants T32HP10251 from the Health
Resources and Services Administration for the Harvard General Medicine
Fellowship (AB); 1K01DA027097-01A1 (BBH); and K24-HL08880 (NAR). The
funders of these grants had no role in study design or conduct; data
collection, analysis, or interpretation; or manuscript preparation,
review, or approval.
NR 20
TC 13
Z9 13
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD NOV
PY 2011
VL 41
IS 5
BP 498
EP 503
DI 10.1016/j.amepre.2011.07.022
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 839UI
UT WOS:000296394500007
PM 22011421
ER
PT J
AU Robertson, WJ
Griffith, MH
Carroll, K
O'Donnell, T
Gill, TJ
AF Robertson, William J.
Griffith, Matthew H.
Carroll, Kaitlin
O'Donnell, Thomas
Gill, Thomas J.
TI Arthroscopic Versus Open Distal Clavicle Excision A Comparative
Assessment at Intermediate-Term Follow-up
SO AMERICAN JOURNAL OF SPORTS MEDICINE
LA English
DT Article
DE acromioclavicular joint; excision; open; arthroscopic
ID ACROMIOCLAVICULAR JOINT; BIOMECHANICAL ANALYSIS; RESECTION; DISLOCATION;
END
AB Background: While few comparative studies exist, it has been suggested that open distal clavicle excisions (DCEs) provide inferior results when compared with the all-arthroscopic technique.
Purpose: The purpose of this study was to compare the intermediate-term (5-year follow-up) results of patients undergoing arthroscopic versus open DCE for the treatment of recalcitrant acromioclavicular joint pain.
Study Design: Cohort study; Level of evidence, 3.
Methods: All patients who underwent an arthroscopic or open DCE between January 1999 and September 2006 were reviewed. Forty-eight patients (49 shoulders; 32 arthroscopic, 17 open) following DCE without significant glenohumeral pathologic changes were included. The mean follow-up for group I (open) and group II (arthroscopic) was 5.3 years and 4.2 years, respectively. The American Shoulder and Elbow Surgeons (ASES) score, visual analog scale (VAS) pain score, surgical time, and minimum radiographic acromioclavicular joint distance were calculated. Each patient completed a questionnaire assessing their scar satisfaction, percentage of normal shoulder function, and willingness to have the surgery again. Risk factors for poor outcomes were analyzed.
Results: Arthroscopic patients had significantly less pain (P = .035) by VAS (0.61 +/- 1.02) compared with open (1.59 +/- 2.15) at final follow-up. There was no significant difference between group I and group II with regard to ASES (87.5 +/- 17.6 vs 94.6 +/- 8.6), percentage of normal shoulder function (89.7% +/- 12.5 vs 92.9% +/- 8.6), average operative time (53.1 minutes vs 48 minutes), or radiographic resection distance (12.8 +/- 2.1 mm vs 9.5 +/- 2.9 mm). In the open group, patients with 16 of 17 shoulders were satisfied with their scar and 100% would do it again. In the arthroscopic group, patients with 31 of 32 shoulders (97%) were both satisfied and would have the surgery again.
Conclusion: Open and arthroscopic DCE are both effective surgeries to treat recalcitrant acromioclavicular joint pain. At intermediate-term follow-up, they provide similarly good to excellent results with regard to patient satisfaction and shoulder function. Although both are effective treatments, less residual pain was found using the arthroscopic technique.
C1 [Robertson, William J.; Griffith, Matthew H.; Carroll, Kaitlin; O'Donnell, Thomas; Gill, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Robertson, WJ (reprint author), UT SW Med Ctr Dallas, 1801 Inwood Rd, Dallas, TX 75390 USA.
EM robertsonwj@gmail.com
NR 18
TC 12
Z9 12
U1 0
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0363-5465
J9 AM J SPORT MED
JI Am. J. Sports Med.
PD NOV
PY 2011
VL 39
IS 11
BP 2415
EP 2420
DI 10.1177/0363546511419633
PG 6
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA 838KG
UT WOS:000296287900018
PM 21900626
ER
PT J
AU Levesque, V
Bardwell, PD
Shimizu, I
Haspot, F
Benichou, G
Yeap, BY
Sykes, M
AF Levesque, V.
Bardwell, P. D.
Shimizu, I.
Haspot, F.
Benichou, G.
Yeap, B. Y.
Sykes, M.
TI B-Cell-Dependent Memory T Cells Impede Nonmyeloablative Mixed Chimerism
Induction in Presensitized Mice
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Alloantibodies; memory; mixed chimerism; presensitization; T-cell
memory; tolerance
ID BONE-MARROW ENGRAFTMENT; TRANSPLANTATION TOLERANCE; HEMATOPOIETIC
CHIMERISM; ALLOGRAFT-REJECTION; DEFICIENT MICE; IN-VIVO; RECIPIENTS;
PATHWAY; IMMUNOSUPPRESSION; IRRADIATION
AB Presensitization to HLA antigens limits the success of organ transplantation. The achievement of donor-specific tolerance via mixed chimerism could improve outcomes of transplantation in presensitized patients. In presensitized B-cell-deficient mu MT B6 mice, we developed nonmyeloablative bone marrow transplantation (BMT) regimens that successfully tolerized presensitized T cells, achieving long-term(LT) multilineage chimerism and tolerance to donor-type skin. To apply these regimens in wild-type (WT) animals while avoiding antibody-mediated destruction of donor bone marrow cells, presensitized WT B6 mice were rested >2 years to allow alloantibody clearance. However, chimerism and tolerance were not reliably achieved in LT presensitized WT B6 mice in which alloantibody had declined to minimal or undetectable levels before BMT. Strong antidonor memory T-cell responses were detected in LT presensitized WT B6 mice after rejection of donor bone marrow (BM) occurred, whereas levels of alloantibody remained consistently low. In contrast, presensitized mu MT B6 mice had diminished memory T-cell responses compared to WT B6 mice. These data implicate T-cell memory, but not alloantibody, in rejection of donor BM in LT presensitized WT mice.
C1 [Levesque, V.; Bardwell, P. D.; Shimizu, I.; Haspot, F.; Sykes, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA.
[Benichou, G.] Harvard Univ, Sch Med, Dept Surg, Transplantat Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Yeap, B. Y.] Harvard Univ, Sch Med, Dept Med, Biostat Unit,Massachusetts Gen Hosp, Boston, MA USA.
RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA.
EM Megan.Sykes@tbrc.mgh.harvard.edu
RI Bardwell, Philip/H-2219-2014
OI Bardwell, Philip/0000-0002-3835-255X
FU NHLBI NIH HHS [P01 HL018646, R01 HL049915]; NIAID NIH HHS [R01 AI054976]
NR 27
TC 6
Z9 6
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD NOV
PY 2011
VL 11
IS 11
BP 2322
EP 2331
DI 10.1111/j.1600-6143.2011.03683.x
PG 10
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 839AF
UT WOS:000296335800011
PM 21831158
ER
PT J
AU Tulsky, JA
Arnold, RM
Alexander, SC
Olsen, MK
Jeffreys, AS
Rodriguez, KL
Skinner, CS
Farrell, D
Abernethy, AP
Pollak, KI
AF Tulsky, James A.
Arnold, Robert M.
Alexander, Stewart C.
Olsen, Maren K.
Jeffreys, Amy S.
Rodriguez, Keri L.
Skinner, Celette Sugg
Farrell, David
Abernethy, Amy P.
Pollak, Kathryn I.
TI Enhancing Communication Between Oncologists and Patients With a
Computer-Based Training Program A Randomized Trial
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID ADVANCED CANCER; PRIMARY-CARE; SCOPE TRIAL; SKILLS; QUALITY; PHYSICIAN;
EFFICACY; MODEL; TRUST; LIFE
AB Background: Quality cancer care requires addressing patients' emotions, which oncologists infrequently do. Multiday courses can teach oncologists skills to handle emotion; however, such workshops are long and costly.
Objective: To test whether a brief, computerized intervention improves oncologist responses to patient expressions of negative emotion.
Design: Randomized, controlled, parallel-group trial stratified by site, sex, and oncologic specialty. Oncologists were randomly assigned to receive a communication lecture or the lecture plus a tailored CD-ROM. (ClinicalTrials. gov registration number: NCT00276627)
Setting: Oncology clinics at a comprehensive cancer center and Veterans Affairs Medical Center in Durham, North Carolina, and a comprehensive cancer center in Pittsburgh, Pennsylvania. Participants: 48 medical, gynecologic, and radiation oncologists and 264 patients with advanced cancer.
Intervention: Oncologists were randomly assigned in a 1: 1 ratio to receive an interactive CD-ROM about responding to patients' negative emotions. The CD-ROM included tailored feedback on the oncologists' own recorded conversations.
Measurements: Postintervention audio recordings were used to identify the number of empathic statements and responses to patients' expressions of negative emotion. Surveys evaluated patients' trust in their oncologists and perceptions of their oncologists' communication skills.
Results: Oncologists in the intervention group used more empathic statements (relative risk, 1.9 [95% Cl, 1.1 to 3.3]; P = 0.024) and were more likely to respond to negative emotions empathically (odds ratio, 2.1 [Cl, 1.1 to 4.2]; P = 0.028) than control oncologists. Patients of intervention oncologists reported greater trust in their oncologists than did patients of control oncologists (estimated mean difference, 0.1 [Cl, 0.0 to 0.2]; P = 0.036). There was no significant difference in perceptions of communication skills.
Limitations: Long-term effects were not examined. The findings may not be generalizable outside of academic medical centers.
Conclusion: A brief computerized intervention improves how oncologists respond to patients' expressions of negative emotions.
Primary Funding Source: National Cancer Institute.
C1 Duke Univ, Vet Affairs Med Ctr, Durham, NC 27705 USA.
People Designs, Durham, NC USA.
Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA.
Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
RP Tulsky, JA (reprint author), Duke Univ, Ctr Palliat Care, Hock Plaza,Suite 1105,2424 Erwin Rd,Box 2720, Durham, NC 27705 USA.
EM jtulsky@duke.edu
FU National Cancer Institute [R01 CA100387]
FX By grant R01 CA100387 from the National Cancer Institute.
NR 38
TC 69
Z9 69
U1 4
U2 18
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 NOV 1
PY 2011
VL 155
IS 9
BP 593
EP U64
DI 10.7326/0003-4819-155-9-201111010-00007
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 842PW
UT WOS:000296612400004
PM 22041948
ER
PT J
AU Qaseem, A
Chou, R
Humphrey, LL
Starkey, M
Shekelle, P
AF Qaseem, Amir
Chou, Roger
Humphrey, Linda L.
Starkey, Melissa
Shekelle, Paul
CA Amer Coll Phys
TI Venous Thromboembolism Prophylaxis in Hospitalized Patients: A Clinical
Practice Guideline From the American College of Physicians
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID DEEP-VEIN THROMBOSIS; MOLECULAR-WEIGHT HEPARIN; ACUTE ISCHEMIC-STROKE;
LOW-DOSE HEPARIN; PLACEBO-CONTROLLED TRIAL; ILL MEDICAL PATIENTS; FATAL
PULMONARY-EMBOLISM; DOUBLE-BLIND; UNFRACTIONATED HEPARIN;
RANDOMIZED-TRIAL
AB Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on prophylaxis of venous thromboembolism for hospitalized nonsurgical patients (medical patients and patients with acute stroke).
Methods: This guideline is based on published literature on the topic from 1950 through April 2011 that was identified by using MEDLINE, the Cochrane Library, and reference lists of pertinent randomized trials and systematic reviews to identify additional reports. Searches were limited to randomized trials and English-language publications. The primary outcome for this guideline was total mortality up to 120 days after randomization. Secondary outcomes included symptomatic deep venous thrombosis; all pulmonary embolisms; fatal pulmonary embolism; all bleeding events; major bleeding events; and, for mechanical prophylaxis, effects on skin. This guideline grades the evidence and recommendations by using the ACP's clinical practice guidelines grading system.
Recommendation 1: ACP recommends assessment of the risk for thromboembolism and bleeding in medical (including stroke) patients prior to initiation of prophylaxis of venous thromboembolism (Grade: strong recommendation, moderate-quality evidence).
Recommendation 2: ACP recommends pharmacologic prophylaxis with heparin or a related drug for venous thromboembolism in medical (including stroke) patients unless the assessed risk for bleeding outweighs the likely benefits (Grade: strong recommendation, moderate-quality evidence).
Recommendation 3: ACP recommends against the use of mechanical prophylaxis with graduated compression stockings for prevention of venous thromboembolism (Grade: strong recommendation, moderate-quality evidence).
Policy Implication: ACP does not support the application of performance measures in medical (including stroke) patients that promotes universal venous thromboembolism prophylaxis regardless of risk.
C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA.
RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19106 USA.
EM aqaseem@acponline.org
FU ACP
FX Financial support for the development of this guideline comes
exclusively from the ACP operating budget.
NR 50
TC 93
Z9 97
U1 0
U2 7
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 NOV 1
PY 2011
VL 155
IS 9
BP 625
EP U118
DI 10.7326/0003-4819-155-9-201111010-00011
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 842PW
UT WOS:000296612400007
PM 22041951
ER
PT J
AU Cheng, YW
Kaimal, AJ
Bruckner, TA
Hallaron, DR
Caughey, AB
AF Cheng, Y. W.
Kaimal, A. J.
Bruckner, T. A.
Hallaron, D. R.
Caughey, A. B.
TI Perinatal morbidity associated with late preterm deliveries compared
with deliveries between 37 and 40 weeks of gestation
SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
LA English
DT Article
DE Late preterm births; perinatal outcomes
ID NEAR-TERM INFANTS; CESAREAN DELIVERY; TEMPORAL TRENDS; UNITED-STATES;
OUTCOMES; BIRTH; AGE; RISK; MORTALITY; COHORT
AB Objective To estimate the risk of short-term complications in neonates born between 34 and 36 weeks of gestation.
Design This is a retrospective cohort study.
Setting Deliveries in 2005 in the USA.
Population Singleton live births between 34 and 40 weeks of gestation.
Methods Gestational age was subgrouped into 34, 35, 36 and 37-40 completed weeks of gestation. Statistical comparisons were performed using chi-square test and multivariable logistic regression models, with 37-40 weeks of gestation designated as referent.
Main outcome measures Perinatal morbidities, including 5-minute Apgar scores, hyaline membrane disease, neonatal sepsis/antibiotics use, and admission to the intensive care unit.
Results In all, 175 112 neonates were born between 34 and 36 weeks in 2005. Compared with neonates born between 37 and 40 weeks, neonates born at 34 weeks had higher odds of 5-minute Apgar <7 (adjusted odds ratio [aOR] 5.51, 95% CI 5.16-5.88), hyaline membrane disease (aOR 10.2, 95% CI 9.44-10.9), mechanical ventilation use >6 hours (aOR 9.78, 95% CI 8.99-10.6) and antibiotic use (aOR 9.00, 95% CI 8.43-9.60). Neonates born at 35 weeks were similarly at risk of morbidity, with higher odds of 5-minute Apgar <7 (aOR 3.42, 95% CI 3.23-3.63), surfactant use (aOR 3.74, 95% CI 3.21-4.22), ventilation use >6 hours (aOR 5.53, 95% CI 5.11-5.99) and neonatal intensive-care unit admission (aOR 11.3, 95% CI 11.0-11.7). Neonates born at 36 weeks remain at higher risk of morbidity compared with deliveries at 37-40 weeks of gestation.
Conclusions Although the risk of undesirable neonatal outcomes decreases with increasing gestational age, the risk of neonatal complications in late preterm births remains higher compared with infants delivered at 37-40 weeks of gestation.
C1 [Cheng, Y. W.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Div Maternal Fetal Med, San Francisco, CA 94143 USA.
[Kaimal, A. J.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA.
[Bruckner, T. A.] Univ Calif Irvine, Sch Social Ecol, Dept Publ Hlth & Planning Policy & Design, Irvine, CA USA.
[Hallaron, D. R.] St Louis Univ, Dept Pediat, St Louis, MO 63103 USA.
[Caughey, A. B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA.
RP Cheng, YW (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Div Maternal Fetal Med, 505 Parnassus Ave Box 0132, San Francisco, CA 94143 USA.
EM yvecheng@hotmail.com
FU UCSF; NIH; Eunice Kennedy Shriver National Institute of Child Health and
Human Development [K12 HD001262]; Washington University CTSA
[KL2RR024994-01]
FX YWC is supported by the UCSF Women's Reproductive Health Research Career
Development Award, NIH, the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (K12 HD001262) and DRH is supported
by the Washington University CTSA (KL2RR024994-01).
NR 35
TC 29
Z9 29
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1470-0328
J9 BJOG-INT J OBSTET GY
JI BJOG
PD NOV
PY 2011
VL 118
IS 12
BP 1446
EP 1454
DI 10.1111/j.1471-0528.2011.03045.x
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 837LG
UT WOS:000296203900005
PM 21883872
ER
PT J
AU Stockdale, SE
Sherin, JE
Chan, JA
Hermann, RC
AF Stockdale, Susan E.
Sherin, Jonathan E.
Chan, Jeffrey A.
Hermann, Richard C.
TI Barriers and strategies for improving communication between inpatient
and outpatient mental health clinicians
SO BMJ QUALITY & SAFETY
LA English
DT Article
ID HOSPITAL DISCHARGE; CARE; TRANSITIONS; CONTINUITY
AB Objectives: To explore hospital leaders' perceptions of organisational factors as barriers and/or facilitators in improving inpatient-outpatient (IP-OP) communication.
Design: Semistructured in-person interviews. Analysis: Constant comparative method of qualitative data.
Setting: Inpatient psychiatry units in 33 general medical/surgical and specialty psychiatric hospitals in California and Massachusetts (USA).
Participants: Psychiatry chair/chief, service director or medical director.
Variables: Importance to leadership, resources, organisational structure and culture.
Results: A majority of hospital leaders rated the IP-OP communication objective as highly or moderately important. Hospitals with good IP-OP communication had structures in place to support communication or had changed/implemented new procedures to enhance communication, and anticipated clinicians would 'buy in' to the goal of improved communication. Hospitals reporting no improvement efforts were less likely to have structures supporting IP-OP communication, anticipated resistance among clinicians and reported a need for technological resources such as electronic health records, integrated IT and secure online communication. Most leaders reported a need for additional staff time and information, knowledge or data.
Conclusions: For many hospitals, successfully improving communication will require overcoming organisational barriers such as cultures not conducive to change and lack of resources and infrastructure. Creating a culture that values communication at discharge may help improve outcomes following hospitalisation, but changes in healthcare delivery in the past few decades may necessitate new strategies or changes at the systems level to address barriers to effective communication.
C1 [Stockdale, Susan E.] VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Study Healthcare Provider Behav, Sepulveda, CA 91343 USA.
[Stockdale, Susan E.] Univ Calif Los Angeles, UCLA Semel Inst Ctr Hlth Serv & Soc, Los Angeles, CA USA.
[Sherin, Jonathan E.] Miami VA Healthcare Syst, Miami, FL USA.
[Sherin, Jonathan E.] Univ Miami, Miami, FL USA.
[Chan, Jeffrey A.; Hermann, Richard C.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA.
[Chan, Jeffrey A.; Hermann, Richard C.] VA Boston Healthcare Syst, COLMR, Boston, MA USA.
RP Stockdale, SE (reprint author), VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Study Healthcare Provider Behav, 16111 Plummer St,Bldg 25,Room A-103, Sepulveda, CA 91343 USA.
EM susan.stockdale@va.gov
FU National Institute of Mental Health [R34 MH074788, P30 MH082760, P30
MH068639]
FX This research was supported by grants from the National Institute of
Mental Health (R34 MH074788, PI: R. Hermann; P30 MH082760, PI: K. Wells;
P30 MH068639, PI: K. Wells).
NR 33
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U2 13
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-5415
J9 BMJ QUAL SAF
JI BMJ Qual. Saf.
PD NOV
PY 2011
VL 20
IS 11
BP 941
EP 946
DI 10.1136/bmjqs.2010.050450
PG 6
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 837KQ
UT WOS:000296201200005
PM 21606473
ER
PT J
AU Zhang, Y
Moriguchi, H
AF Zhang, Yue
Moriguchi, Hisashi
TI Chromatin remodeling system, cancer stem-like attractors, and cellular
reprogramming
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Article
DE Caenorhabditis elegans; Drosophila melanogaster; Carcinogenesis; Cell
attractors; Chromatin remodeling system; Cellular reprogramming
ID GENE-EXPRESSION; EMBRYONIC STEM; C-ELEGANS; EXTRACELLULAR-MATRIX; CELLS;
COMPLEX; DIFFERENTIATION; PROTEIN; HSP90; PLURIPOTENCY
AB The cancer cell attractors theory provides a next-generation understanding of carcinogenesis and natural explanation of punctuated clonal expansions of tumor progression. The impressive notion of atavism of cancer is now updated but more evidence is awaited. Besides, the mechanisms that the ectopic expression of some germline genes result in somatic tumors such as melanoma and brain tumors are emerging but are not well understood. Cancer could be triggered by cells undergoing abnormal cell attractor transitions, and may be reversible with "cyto-education''. From mammals to model organisms like Caenorhabditis elegans and Drosophila melanogaster, the versatile Mi-2 beta/nucleosome remodeling and histone deacetylation complexes along with their functionally related chromatin remodeling complexes (CRCs), i.e., the dREAM/Myb-MuvB complex and Polycomb group complex are likely master regulators of cell attractors. The trajectory that benign cells switch to cancerous could be the reverse of navigation of embryonic cells converging from a series of intermediate transcriptional states to a final adult state, which is supported by gene expression dynamics inspector assays and some cross-species genetic evidence. The involvement of CRCs in locking cancer attractors may help find the recipes of perturbing genes to achieve successful reprogramming such that the reprogrammed cancer cell function in the same way as the normal cells.
C1 [Zhang, Yue] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, Boston, MA 02215 USA.
[Moriguchi, Hisashi] Univ Tokyo, Sch Med, Dept Plast & Reconstruct Surg, Tokyo 113, Japan.
[Moriguchi, Hisashi] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Zhang, Y (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, 99 Brookline Ave, Boston, MA 02215 USA.
EM yzhang1@bidmc.harvard.edu; hisashi.moriguchi@gmail.com
NR 90
TC 5
Z9 7
U1 0
U2 8
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD NOV
PY 2011
VL 68
IS 21
BP 3557
EP 3571
DI 10.1007/s00018-011-0808-1
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 840VK
UT WOS:000296469200010
PM 21909785
ER
PT J
AU Upadhyay, GA
Singh, JP
AF Upadhyay, Gaurav A.
Singh, Jagmeet P.
TI Making a Splash? - Intrathoracic Impedance and the Prediction of
Arrhythmic Events
SO CIRCULATION JOURNAL
LA English
DT Editorial Material
ID CARDIAC RESYNCHRONIZATION THERAPY; HEART-FAILURE HOSPITALIZATIONS;
DEVICE DIAGNOSTICS; VOLUME OVERLOAD
C1 [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr, 55 Fruit St,Gray Bldg 109, Boston, MA 02114 USA.
EM jsingh@partners.org
NR 12
TC 0
Z9 1
U1 0
U2 1
PU JAPANESE CIRCULATION SOC
PI KYOTO
PA KINKI INVENTION CENTER, 14 YOSHIDA KAWAHARACHO, SAKYO-KU, KYOTO,
606-8305, JAPAN
SN 1346-9843
J9 CIRC J
JI Circ. J.
PD NOV
PY 2011
VL 75
IS 11
BP 2539
EP 2540
DI 10.1253/circj.CJ-11-1054
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 839XP
UT WOS:000296403100006
PM 21963573
ER
PT J
AU Koontz, AM
Kankipati, P
Lin, YS
Cooper, RA
Boninger, ML
AF Koontz, Alicia M.
Kankipati, Padmaja
Lin, Yen-Sheng
Cooper, Rory A.
Boninger, Michael L.
TI Upper limb kinetic analysis of three sitting pivot wheelchair transfer
techniques
SO CLINICAL BIOMECHANICS
LA English
DT Article
DE Biomechanics; Upper limb pain; Spinal cord injury; Activities of daily
living; Wheelchair
ID SPINAL-CORD-INJURY; UPPER EXTREMITY; BIOMECHANICAL ANALYSIS;
INDIVIDUALS; SHOULDER; USERS; PARAPLEGIA; SYSTEM; KINEMATICS; MANEUVER
AB Background: The objective of this study was to investigate differences in shoulder, elbow and hand kinetics while performing three different SPTs that varied in terms of hand and trunk positioning.
Methods: Fourteen unimpaired individuals (8 male and 6 female) performed three variations of sitting pivot transfers in a random order from a wheelchair to a level tub bench. Two transfers involved a forward flexed trunk (head-hips technique) and the third with the trunk remaining upright. The two transfers involving a head hips technique were performed with two different leading hand initial positions. Motion analysis equipment recorded upper body movements and force sensors recorded hand reaction forces. Shoulder and elbow joint and hand kinetics were computed for the lift phase of the transfer.
Findings: Transferring using either of the head hips techniques compared to the trunk upright style of transferring resulted in reduced superior forces at the shoulder (P<0.002), elbow (P<0.004) and hand (P<0.013). There was a significant increase in the medial forces in the leading elbow (P=0.049) for both head hip transfers and the trailing hand for the head hip technique with the arm further away from the body (P<0.028). The head hip techniques resulted in higher shoulder external rotation, flexion and extension moments compared to the trunk upright technique (P<0.021).
Interpretation: Varying the hand placement and trunk positioning during transfers changes the load distribution across all upper limb joints. The results of this study may be useful for determining a technique that helps preserve upper limb function overtime. Published by Elsevier Ltd.
C1 [Koontz, Alicia M.; Kankipati, Padmaja; Lin, Yen-Sheng; Cooper, Rory A.; Boninger, Michael L.] Dept Vet Affairs, Human Engn Res Labs, Pittsburgh, PA USA.
[Koontz, Alicia M.; Kankipati, Padmaja; Lin, Yen-Sheng; Cooper, Rory A.; Boninger, Michael L.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA.
[Cooper, Rory A.; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA.
RP Koontz, AM (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151R1 H, 7180 Highland Dr,151R1-H, Pittsburgh, PA 15206 USA.
EM akoontz@pitt.edu
OI Boninger, Michael/0000-0001-6966-919X
FU VA Rehabilitation Research RD Services; National Institute on Disability
and Rehabilitation Research; National Institute of Health, Center for
Injury Research Control [VA-RRD E3589V, B3079R NIDRR H133A011107, NIH
R49/CCR310285-06]
FX Funding for this study was provided by the VA Rehabilitation Research
R&D Services and the National Institute on Disability and Rehabilitation
Research and the National Institute of Health, Center for Injury
Research Control (VA-RR&D E3589V and B3079R NIDRR H133A011107, NIH
R49/CCR310285-06). The contents of this paper do not represent the views
of the Department of Veterans Affairs or the United States Government.
NR 27
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U1 3
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0268-0033
J9 CLIN BIOMECH
JI Clin. Biomech.
PD NOV
PY 2011
VL 26
IS 9
BP 923
EP 929
DI 10.1016/j.clinbiomech.2011.05.005
PG 7
WC Engineering, Biomedical; Orthopedics; Sport Sciences
SC Engineering; Orthopedics; Sport Sciences
GA 840AK
UT WOS:000296410400006
PM 21664733
ER
PT J
AU Kozanek, M
Hosseini, A
Van de Velde, SK
Moussa, ME
Li, JS
Gill, TJ
Li, GA
AF Kozanek, Michal
Hosseini, Ali
Van de Velde, Samuel K.
Moussa, Mohamed E.
Li, Jing Sheng
Gill, Thomas J.
Li, Guoan
TI Kinematic evaluation of the step-up exercise in anterior cruciate
ligament deficiency
SO CLINICAL BIOMECHANICS
LA English
DT Article
DE Anterior cruciate ligament; Injury; Rehabilitation; Kinematics; Knee;
Imaging
ID KINETIC-CHAIN EXERCISES; TIBIOFEMORAL JOINT FORCES; ELECTROMYOGRAPHIC
ACTIVITY; STAIR ASCENT; KNEE; COACTIVATION; TRANSLATION; WALKING;
MOTION; REHABILITATION
AB Background: Step-up exercise is one of the most commonly utilized exercises during rehabilitation of patients after both anterior cruciate ligament (ACL) injury and reconstruction. Currently, insurance providers increasingly required a trial of intensified rehabilitation before surgical reconstruction is attempted. The purpose of this study was to investigate whether this "safe" rehabilitation exercise in the setting of ACL deficiency can cause altered knee kinematics.
Methods: Thirty patients with unilateral ACL rupture were recruited for this study. The mean time from injury was 3.3 months. Tibiofemoral kinematics were determined during a step-up exercise using a combination of magnetic resonance imaging (MRI), dual fluoroscopy and advanced computer modeling.
Findings: The ACL-injured knee displayed an average 50 greater external tibial rotation than the uninjured knee (P<0.05), during the last 30% of step-up. The ACL-injured knee also demonstrated on average 2.5 mm greater anterior tibial shift during the last 40% of stance phase (P<0.01). In addition, during the last 30% of stance the tibia of the ACL-deficient knee tended to shift more medially (similar to 1 mm) as the knee approached full extension (P<0.01).
Interpretation: The data confirmed the initial hypothesis as it was found that ACL deficient knees demonstrated significantly increased anterior tibial translation, medial tibial translation and external tibial rotation toward the end of the step-up as the knee approached full extension. Intensive rehabilitation utilizing the step-up exercise in the setting of ACL deficiency can potentially introduce repetitive microtrauma by way of altered kinematics. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab,Sch Med,GRJ 1215, Boston, MA 02114 USA.
[Kozanek, Michal; Moussa, Mohamed E.; Gill, Thomas J.; Li, Guoan] Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, WHT 535, Boston, MA 02114 USA.
[Kozanek, Michal] Comenius Univ, Dept Orthopaed & Traumatol 1, Fac Med, Fac Hosp Ruzinov, Bratislava 82101, Slovakia.
RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab,Sch Med,GRJ 1215, 55 Fruit St, Boston, MA 02114 USA.
EM gli1@partners.org
FU National Institutes of Health (NIH) [R-01 AR055612, F-32 AR056451]
FX This investigation was made possible through the support of the National
Institutes of Health (NIH), grants R-01 AR055612 and F-32 AR056451.
NR 29
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U1 0
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0268-0033
J9 CLIN BIOMECH
JI Clin. Biomech.
PD NOV
PY 2011
VL 26
IS 9
BP 950
EP 954
DI 10.1016/j.clinbiomech.2011.05.003
PG 5
WC Engineering, Biomedical; Orthopedics; Sport Sciences
SC Engineering; Orthopedics; Sport Sciences
GA 840AK
UT WOS:000296410400010
PM 21652128
ER
PT J
AU Merchant, RM
Yang, L
Becker, LB
Berg, RA
Nadkarni, V
Nichol, G
Carr, BG
Mitra, N
Bradley, SM
Abella, BS
Groeneveld, PW
AF Merchant, Raina M.
Yang, Lin
Becker, Lance B.
Berg, Robert A.
Nadkarni, Vinay
Nichol, Graham
Carr, Brendan G.
Mitra, Nandita
Bradley, Steven M.
Abella, Benjamin S.
Groeneveld, Peter W.
CA American Heart Assoc Get Guideline
TI Incidence of treated cardiac arrest in hospitalized patients in the
United States
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE cardiopulmonary resuscitation; heart arrest; resuscitation
ID AMERICAN-HEART-ASSOCIATION; EMERGENCY CARDIOVASCULAR CARE;
CARDIOPULMONARY-RESUSCITATION; NATIONAL REGISTRY; SURVIVAL; GUIDELINES;
IMPLEMENTATION; DISPARITIES; COUNCIL; ORDERS
AB Objective: The incidence and incidence over time of cardiac arrest in hospitalized patients is unknown. We sought to estimate the event rate and temporal trends of adult inhospital cardiac arrest treated with a resuscitation response.
Design: Three approaches were used to estimate the inhospital cardiac arrest event rate. First approach: calculate the inhospital cardiac arrest event rate at hospitals (n = 433) in the Get With The Guidelines-Resuscitation registry, years 2003-2007, and multiply this by U. S. annual bed days. Second approach: use the Get With The Guidelines-Resuscitation inhospital cardiac arrest event rate to develop a regression model (including hospital demographic, geographic, and organizational factors), and use the model coefficients to calculate predicted event rates for acute care hospitals (n = 5445) responding to the American Hospital Association survey. Third approach: classify acute care hospitals into groups based on academic, urban, and bed size characteristics, and determine the average event rate for Get With The Guidelines-Resuscitation hospitals in each group, and use weighted averages to calculate the national inhospital cardiac arrest rate. Annual event rates were calculated to estimate temporal trends.
Setting: Get With The Guidelines-Resuscitation registry.
Patients: Adult inhospital cardiac arrest with a resuscitation response.
Measurements and Main Results: The mean adult treated inhospital cardiac arrest event rate at Get With The Guidelines-Resuscitation hospitals was 0.92/1000 bed days (interquartile range 0.58 to 1.2/1000). In hospitals (n = 150) contributing data for all years of the study period, the event rate increased from 2003 to 2007. With 2.09 million annual U. S. bed days, we estimated 192,000 inhospital cardiac arrests throughout the United States annually. Based on the regression model, extrapolating Get With The Guidelines-Resuscitation hospitals to hospitals participating in the American Hospital Association survey projected 211,000 annual inhospital cardiac arrests. Using weighted averages projected 209,000 annual U. S. inhospital cardiac arrests.
Conclusions: There are approximately 200,000 treated cardiac arrests among U. S. hospitalized patients annually, and this rate may be increasing. This is important for understanding the burden of inhospital cardiac arrest and developing strategies to improve care for hospitalized patients. (Crit Care Med 2011; 39: 2401-2406)
C1 [Merchant, Raina M.; Becker, Lance B.; Carr, Brendan G.; Abella, Benjamin S.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA.
[Berg, Robert A.; Nadkarni, Vinay] Univ Penn, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA.
[Mitra, Nandita] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Yang, Lin; Groeneveld, Peter W.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Berg, Robert A.; Nadkarni, Vinay] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Nichol, Graham; Bradley, Steven M.] Univ Washington, Seattle, WA 98195 USA.
[Groeneveld, Peter W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
RP Merchant, RM (reprint author), Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA.
EM raina.merchant@uphs.upenn.edu
OI Abella, Benjamin/0000-0003-2521-0891
FU Robert Wood Johnson Foundation at University of Pennsylvania; Institute
for Health Technology Studies (Washington, DC); National Heart, Lung,
and Blood Institute [1-R01-HL086919]; Pennsylvania Department of Health;
Department of Veterans Affairs' Health Services Research and Development
Service [RRP 09-117]; Philips Healthcare, Seattle, WA; Laerdal Medical,
Stavanger, Norway; NIH, Bethesda, MD; Cardiac Science, Bothell,
Washington; Laerdal Foundation for Acute Care Medicine, Stavanger,
Norway; NIH; Asmund S. Laerdal Foundation for Acute Medicine; NHLBI;
Medtronic Foundation; AHRQ; Medivance Corporation, Louisville, CO;
Philips Healthcare, Andover, MA; Doris Duke Foundation, New York City,
NY; American Heart Association, Dallas, TX
FX Supported, in part, by funding from the Robert Wood Johnson Foundation
Clinical Scholars program at the University of Pennsylvania (Merchant);
an unrestricted grant from the Institute for Health Technology Studies
(Washington, DC); grant 1-R01-HL086919 from the National Heart, Lung,
and Blood Institute; and a grant from the Pennsylvania Department of
Health, which specifically disclaims responsibility for any analyses,
interpretations, or conclusions. Dr. Groeneveld was additionally
supported by a Research Career Development Award (RRP 09-117) from the
Department of Veterans Affairs' Health Services Research and Development
Service.; Dr. Becker received speaker honoraria/consultant fees from
Philips Healthcare, Seattle, WA; institutional grant/research support
from Philips Healthcare, Seattle, WA, Laerdal Medical, Stavanger,
Norway, NIH, Bethesda, MD, and Cardiac Science, Bothell, Washington. Dr.
Nadkarni received institutional grant/research support from the Laerdal
Foundation for Acute Care Medicine, Stavanger, Norway, and NIH,
Bethesda, MD. Dr. Nichol received institutional grant/research support
from NIH, the Asmund S. Laerdal Foundation for Acute Medicine, the
NHLBI, the Medtronic Foundation, and has research collaborations with
Gambro Renal, Lakewood, CO, Sotera Wireless, San Diego, CA, Lifebridge
Medizintechnik AG, Ampfing, Germany. Dr. Carr received institutional
grant/research support from NIH, and AHRQ. Dr. Abella received speaker
honoraria/consultant fees from Philips Healthcare, Seattle, WA,
Medivance Corporation, Louisville, CO; and institutional grant/research
support: Philips Healthcare, Andover, MA, Doris Duke Foundation, New
York City, NY, American Heart Association, Dallas, TX, NIH, Bethesda,
MD. The remaining authors have not disclosed any potential conflict of
interests.
NR 36
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U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD NOV
PY 2011
VL 39
IS 11
BP 2401
EP 2406
DI 10.1097/CCM.0b013e3182257459
PG 6
WC Critical Care Medicine
SC General & Internal Medicine
GA 841JV
UT WOS:000296509500002
PM 21705896
ER
PT J
AU Cobb, JP
Hayden, DL
Schoenfeld, DA
AF Cobb, J. Perren
Hayden, Douglas L.
Schoenfeld, David A.
TI Novel diagnostics for sepsis: A decade of promise for gene expression
profiling
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE genomics; human; inflammation; microarray
ID CRITICAL ILLNESS; INJURY; RIBOLEUKOGRAM; PLASTICITY; DISEASE
C1 [Cobb, J. Perren] Massachusetts Gen Hosp, Crit Care Ctr, Boston, MA 02114 USA.
[Hayden, Douglas L.; Schoenfeld, David A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
RP Cobb, JP (reprint author), Massachusetts Gen Hosp, Crit Care Ctr, Boston, MA 02114 USA.
NR 21
TC 1
Z9 1
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD NOV
PY 2011
VL 39
IS 11
BP 2579
EP 2581
DI 10.1097/CCM.0b013e31822a5e36
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA 841JV
UT WOS:000296509500039
PM 22005238
ER
PT J
AU Ciuffreda, D
Kim, AY
AF Ciuffreda, Donatella
Kim, Arthur Y.
TI Update on hepatitis C virus-specific immunity
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Article
DE CD4 T cell; CD8 T cell; HLA; inhibitory markers
ID CD8(+) T-CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; PERSISTENT
VIRAL-INFECTION; NATURAL-KILLER-CELLS; ACUTE HCV INFECTION; ANTIGEN
CLASS-I; MHC CLASS-I; PD-1 EXPRESSION; DISEASE PROGRESSION;
HIV-INFECTION
AB Purpose of review
The goal of this study is to review key recent findings related to the immunopathogenesis of hepatitis C virus (HCV) infection, especially in regards to T lymphocytes. It aims to complement other reviews in this issue on the roles of host genetics (IL-28B), acute HCV infection (when disease outcome is determined) and other factors that may influence fibrosis progression (microbial translocation). The main focus is on specific immunity and T cells in the context of success and failure to control viral infection.
Recent findings
This review focuses on two areas of intense interest in the recent literature: the relationship between the human leukocyte antigen (HLA), class I-restricted T-cell responses and the evolution of the virus and the role of inhibitory markers on T cells in the immunopathogenesis of HCV. When appropriate, we compare findings from studies of HIV-specific immunity.
Summary
From examining the virus and the mutational changes associated with T-cell responses and from analyzing the markers on T cells, there have been numerous advances in the understanding of immune evasion mechanisms employed by HCV.
C1 [Kim, Arthur Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Ciuffreda, Donatella] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Kim, AY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA.
EM akim1@partners.org
FU Swiss National Science Foundation; National Institutes of
Health/National Institute of Allergy and Infectious Diseases [AI066345,
AI091649]
FX D. C. is supported by the Swiss National Science Foundation. A. Y. K. is
supported by the National Institutes of Health/National Institute of
Allergy and Infectious Diseases (AI066345 and AI091649). A. Y. K. serves
as a speaker for the New England AIDS Treatment and Education Center
(nonprofit) and is on an editorial board for FirstConsult.com.
NR 105
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD NOV
PY 2011
VL 6
IS 6
BP 559
EP 565
DI 10.1097/COH.0b013e32834b879e
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 839IX
UT WOS:000296360000017
PM 22001897
ER
PT J
AU Preffer, FI
Gratama, JW
AF Preffer, Frederic I.
Gratama, Jan W.
TI Clinical Cytometry on Both Sides of the Atlantic, 2011 Introduction to
ICCS and ESCCA/ICyS Abstracts
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Editorial Material
C1 [Preffer, Frederic I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Gratama, Jan W.] Erasmus MC, Dept Internal Oncol, NL-3075 EA Rotterdam, Netherlands.
RP Preffer, FI (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
EM preffer@helix.mgh.harvard.edu; j.w.gratama@erasmusmc.nl
NR 0
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2011
VL 80B
IS 6
BP 373
EP 374
DI 10.1002/cyto.b.20626
PG 2
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 838FT
UT WOS:000296273300006
PM 22002905
ER
PT J
AU Daley, J
Smith, R
Lazo-Kallanian, S
AF Daley, John, II
Smith, Robert
Lazo-Kallanian, Suzan
TI REMOTE FLOW CYTOMETRY: A REVIEW OF OPTIONS AVAILABLE AND SELECTED
APPLICATIONS
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 26th Annual Meeting of the International-Clinical-Cytometry-Society
CY OCT 14-18, 2011
CL Portland, OR
SP Int Clin Cytometry Soc
C1 [Daley, John, II; Smith, Robert; Lazo-Kallanian, Suzan] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2011
VL 80B
IS 6
BP 391
EP 392
PG 2
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 838FT
UT WOS:000296273300051
ER
PT J
AU Hansen, P
Dombkowski, D
DeLelys, M
Restell, A
Sylvia, D
Krauledat, P
Magnin, O
Preffer, F
AF Hansen, Peter
Dombkowski, David
DeLelys, Michelle
Restell, Amanda
Sylvia, Dorothy
Krauledat, Petra
Magnin, Olivier
Preffer, Frederic
TI ENABLING POINT-OF-CARE CD4 T-CELL COUNTING WITH A ONE MINUTE SAMPLE
PREPARATION METHOD AND HEAT STABLE ANTIBODY CONJUGATE
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 26th Annual Meeting of the International-Clinical-Cytometry-Society
CY OCT 14-18, 2011
CL Portland, OR
SP Int Clin Cytometry Soc
C1 [Hansen, Peter] Union Biometr Tech, Canaan, NY USA.
[Dombkowski, David; DeLelys, Michelle; Preffer, Frederic] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Restell, Amanda; Sylvia, Dorothy; Krauledat, Petra] PointCare Technol, Marlborough, MA USA.
[Magnin, Olivier] C2 Diagnost, Montpellier, France.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2011
VL 80B
IS 6
BP 404
EP 404
PG 1
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 838FT
UT WOS:000296273300086
ER
PT J
AU Ghillebert, R
Swinnen, E
Wen, J
Vandesteene, L
Ramon, M
Norga, K
Rolland, F
Winderickx, J
AF Ghillebert, Ruben
Swinnen, Erwin
Wen, Jing
Vandesteene, Lies
Ramon, Matthew
Norga, Koen
Rolland, Filip
Winderickx, Joris
TI The AMPK/SNF1/SnRK1 fuel gauge and energy regulator: structure, function
and regulation
SO FEBS JOURNAL
LA English
DT Review
DE allosteric regulation; AMP-activated kinase (AMPK); cross-species
conservation; energy signaling; function; phosphorylation; Snf1-related
kinase1 (SnRK1); stress response; structure; sucrose nonfermenting1
(SNF1)
ID ACTIVATED PROTEIN-KINASE; TREHALOSE-PHOSPHATE SYNTHASE;
SACCHAROMYCES-CEREVISIAE CELLS; MIG1 GLUCOSE REPRESSOR; ACETYL-COA
CARBOXYLASE; SNF1 KINASE; YEAST SNF1; CAENORHABDITIS-ELEGANS;
BETA-SUBUNITS; SUBCELLULAR-LOCALIZATION
AB All life forms on earth require a continuous input and monitoring of carbon and energy supplies. The AMP-activated kinase (AMPK)/sucrose nonfermenting1 (SNF1)/Snf1-related kinase1 (SnRK1) protein kinases are evolutionarily conserved metabolic sensors found in all eukaryotic organisms from simple unicellular fungi (yeast SNF1) to animals (AMPK) and plants (SnRK1). Activated by starvation and energy-depleting stress conditions, they enable energy homeostasis and survival by up-regulating energy-conserving and energy-producing catabolic processes, and by limiting energy-consuming anabolic metabolism. In addition, they control normal growth and development as well as metabolic homeostasis at the organismal level. As such, the AMPK/SNF1/SnRK1 kinases act in concert with other central signaling components to control carbohydrate uptake and metabolism, fatty acid and lipid biosynthesis and the storage of carbon energy reserves. Moreover, they have a tremendous impact on developmental processes that are triggered by environmental changes such as nutrient depletion or stress. Although intensive research by many groups has partly unveiled the factors that regulate AMPK/SNF1/SnRK1 kinase activity as well as the pathways and substrates they control, several fundamental issues still await to be clarified. In this review, we will highlight these issues and focus on the structure, function and regulation of the AMPK/SNF1/SnRK1 kinases.
C1 [Ghillebert, Ruben; Swinnen, Erwin; Wen, Jing; Vandesteene, Lies; Ramon, Matthew; Rolland, Filip; Winderickx, Joris] Katholieke Univ Leuven, Dept Biol, Lab Funct Biol, B-3001 Heverlee, Belgium.
[Ramon, Matthew] Harvard Univ, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA.
[Norga, Koen] Flanders Inst Biotechnol VIB, Lab Dev Genet, Louvain, Belgium.
[Norga, Koen] Katholieke Univ Leuven, Dept Woman & Child Pediat Hematol & Oncol, Louvain, Belgium.
RP Winderickx, J (reprint author), Katholieke Univ Leuven, Dept Biol, Lab Funct Biol, Kasteelpk Arenberg 31,POB 2433, B-3001 Heverlee, Belgium.
EM joris.winderickx@bio.kuleuven.be
OI Norga, Koenraad/0000-0002-9231-0350
FU Fonds voor Wetenschappelijk Onderzoek (FWO); Agentschap voor Innovatie
door Wetenschap en Technologie in Vlaanderen (IWT); K.U.Leuven (BOF,
Bijzonder Onderzoeksfonds); NSF [IOS-0843244]
FX Work on AMPK/SNF1/SnRK1 in the K.U.Leuven laboratories is funded by
Fonds voor Wetenschappelijk Onderzoek (FWO), Agentschap voor Innovatie
door Wetenschap en Technologie in Vlaanderen (IWT) and K.U.Leuven (BOF,
Bijzonder Onderzoeksfonds). Work on SnRK1 at MGH is funded by NSF grant
IOS-0843244.
NR 131
TC 83
Z9 86
U1 3
U2 67
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD NOV
PY 2011
VL 278
IS 21
BP 3978
EP 3990
DI 10.1111/j.1742-4658.2011.08315.x
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 837XT
UT WOS:000296245400002
PM 21883929
ER
PT J
AU Bakirtzi, K
Hatziapostolou, M
Karagiannides, I
Polytarchou, C
Jaeger, S
Iliopoulos, D
Pothoulakis, C
AF Bakirtzi, Kyriaki
Hatziapostolou, Maria
Karagiannides, Iordanes
Polytarchou, Christos
Jaeger, Savina
Iliopoulos, Dimitrios
Pothoulakis, Charalabos
TI Neurotensin Signaling Activates MicroRNAs-21 and-155 and Akt, Promotes
Tumor Growth in Mice, and Is Increased in Human Colon Tumors
SO GASTROENTEROLOGY
LA English
DT Article
DE Neuropeptide; Colorectal Cancer; Signal Transduction; Tumor Suppressor
ID INFLAMMATORY-BOWEL-DISEASE; PROTEIN-KINASE-B; CANCER-CELLS;
GASTRIC-CANCER; TARGET GENES; MAP-KINASE; EXPRESSION; IDENTIFICATION;
PATHWAY; RAT
AB BACKGROUND & AIMS: Neurotensin promotes inflammation and colon cancer via the neurotensin-1 receptor (NTR1). MicroRNAs (miR) regulate protein synthesis by degrading or preventing translation of mRNAs. We analyzed expression of 365 different microRNAs by human colonic epithelial cells (NCM460) after activation of NTR1. METHODS: We performed microarray analysis of mRNA expression by neurotensin-stimulated NCM460 cells that overexpressed NTR1. Nuclear factor-kappa B (NF-kappa B) binding sites were identified and tumorigenesis was assessed using soft agar assays and xenograft analysis of severe combined immunodeficiency mice. Targets of neurotensin-regulated microRNAs were identified via bioinformatic, real-time polymerase chain reaction, and immunoblot analyses. We analyzed RNA samples from human normal colon and tumor samples. RESULTS: Neurotensin stimulated differential expression of 38 microRNAs, including miR-21 and miR-155, which have been associated with tumor growth and contain NF-kappa B binding sites. Neurotensin expression increased colony formation by HCT-116 cells. Blocking miR-21 and/or miR-155 prevented colony formation (P<.001). In mice, intraperitoneal administration of neurotensin increased the growth rate of HCT-116 xenograft tumors; blocking miR-21 and/or miR-155 slowed this tumor growth. Neurotensin activated Akt in HCT-116 cells; this effect was inhibited by blocking miR-21 and/or miR-155 (P<.001). Neurotensin activated AKT through miR-155-mediated suppression of the phosphatase protein phosphatase 2A catalytic subunit alpha (PPP2CA). Levels of phosphatase and tensin homolog (PTEN) and suppressor of cytokine signaling 1 (SOCS1) mRNA, potential targets of miR-21 and miR-155, respectively, were down-regulated by these miRs. Levels of NTR1, miR-21, and miR-155 increased significantly in human colon tumor samples, compared with normal tissues, whereas PPP2CA, SOCS1, and PTEN mRNAs were reduced significantly. CONCLUSIONS: NTR1 activation stimulates expression of miR-21 and miR-155 in colonocytes, via Akt and NF-kappa B, to down-regulate PTEN and SOCS1 and promote growth of tumors in mice. Levels of NTR1, miR-21, and miR-155 increase in human colon tumor samples and correlate with tumor stage.
C1 [Bakirtzi, Kyriaki; Karagiannides, Iordanes; Pothoulakis, Charalabos] Univ Calif Los Angeles, Div Digest Dis, Ctr Inflammatory Bowel Dis, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Hatziapostolou, Maria; Iliopoulos, Dimitrios] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Hatziapostolou, Maria; Iliopoulos, Dimitrios] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Polytarchou, Christos] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA USA.
[Jaeger, Savina] Novartis Inst Biomed Res, Dept Dev Mol Pathways, Cambridge, MA USA.
RP Pothoulakis, C (reprint author), Univ Calif Los Angeles, Div Digest Dis, Ctr Inflammatory Bowel Dis, David Geffen Sch Med, 675 Charles E Young Dr,S MRL Bldg 1240, Los Angeles, CA 90095 USA.
EM cpothoulakis@mdenet.ucla.edu
RI Hatziapostolou, Maria/N-1820-2015
OI Hatziapostolou, Maria/0000-0003-2493-7028
FU US Public Health Service [RO1 DK60729]; Crohn's and Colitis Foundation
of America; Broad Foundation; Blinder Research Foundation for Crohn's
Disease; Eli and Edythe Broad Chair
FX Supported by US Public Health Service grant RO1 DK60729 (C. P.), a
Crohn's and Colitis Foundation of America Research Fellowship (I. K.), a
Medical Research Award from the Broad Foundation (I. K.), and by the
Blinder Research Foundation for Crohn's Disease and the Eli and Edythe
Broad Chair (C.P.).
NR 50
TC 53
Z9 59
U1 5
U2 22
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD NOV
PY 2011
VL 141
IS 5
BP 1749
EP U311
DI 10.1053/j.gastro.2011.07.038
PG 14
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 841KW
UT WOS:000296512200040
PM 21806946
ER
PT J
AU Paidassi, H
Acharya, M
Zhang, AL
Mukhopadhyay, S
Kwon, M
Chow, C
Stuart, LM
Savill, J
Lacy-Hulbert, A
AF Paidassi, Helena
Acharya, Mridu
Zhang, Ailiang
Mukhopadhyay, Subhankar
Kwon, Manjae
Chow, Camille
Stuart, Lynda M.
Savill, John
Lacy-Hulbert, Adam
TI Preferential Expression of Integrin alpha v beta 8 Promotes Generation
of Regulatory T Cells by Mouse CD103(+) Dendritic Cells
SO GASTROENTEROLOGY
LA English
DT Article
DE FoxP3; Signaling; Macrobiota; Immune Regulation
ID ALPHA-V INTEGRINS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;
RETINOIC-ACID; DIFFERENTIATION; MICE; TH17; COLITIS; T(H)17; ACTIVATION;
TOLERANCE
AB BACKGROUND & AIMS: Immune responses in the intestine are controlled by regulatory T cells (Tregs), which prevent inflammation in response to commensal bacteria. A specific population of intestinal dendritic cells (DCs), marked by expression of CD103, generate Tregs more efficiently than other DC populations through mechanisms that involve retinoic acid and transforming growth factor (TGF)-beta. However, it is not clear how CD103(+) DCs are specialized for this function. We investigated the ability of CD103(+) DCs to promote Treg generation through activation of TGF-beta and the role of integrins with the alpha v subunit in this process. METHODS: Nave T cells were cultured with purified DCs from mesenteric lymph nodes (MLNs) or intestines of wild-type and alpha v conditional knockout mice to assess generation of Tregs. Antigens were administered orally to mice, and antigen-specific generation of Tregs was measured in intestinal tissues. Expression of the integrin alpha v subunit was measured in purified subpopulations of DCs by quantitative polymerase chain reaction and immunoblot analyses. RESULTS: In vitro, CD103(+) DCs generated more Tregs in the presence of latent TGF-beta than other MLN DCs. Efficient generation of Tregs required expression of the integrin alpha v subunit by DCs; mice that lacked alpha v in immune cells did not convert nave T cells to intestinal Tregs in response to oral antigen. CD103(+) DCs derived from the MLNs selectively expressed high levels of integrin alpha v beta 8 compared with other populations of DCs. CONCLUSIONS: Expression of alpha v beta 8 is required for CD103(+) DCs to become specialized and activate latent TGF-beta and generate Tregs during the induction of tolerance to intestinal antigens in mice.
C1 [Paidassi, Helena; Acharya, Mridu; Mukhopadhyay, Subhankar; Kwon, Manjae; Chow, Camille; Stuart, Lynda M.; Lacy-Hulbert, Adam] Harvard Univ, Massachusetts Gen Hosp, Program Dev Immunol, Sch Med,Dept Pediat, Boston, MA 02114 USA.
[Paidassi, Helena; Zhang, Ailiang; Savill, John] Univ Edinburgh, Queens Med Res Inst, MRC Ctr Inflammat Res, Edinburgh, Midlothian, Scotland.
[Mukhopadhyay, Subhankar] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
RP Lacy-Hulbert, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Program Dev Immunol, Sch Med,Dept Pediat, GRJ1402,55 Fruit St, Boston, MA 02114 USA.
EM alacy-hulbert@partners.org
RI Paidassi, Helena/M-5739-2014;
OI Lacy-Hulbert, Adam/0000-0003-2162-0156
FU Crohn's and Colitis Foundation of America; Hood Pediatric Research
Foundation; National Institutes of Health [RO1AI79198]; UK Medical
Research Council [G0802069]; Wellcome Trust; Philippe Foundation;
Bettencourt-Schueller Foundation
FX Supported by grants from the Crohn's and Colitis Foundation of America
and the Hood Pediatric Research Foundation (to A. L.-H.), the National
Institutes of Health (grant RO1AI79198 to L. M. S.), the UK Medical
Research Council (grant G0802069 to J.S.), a Wellcome Trust traveling
fellowship (to S. M.), and the Philippe Foundation and the
Bettencourt-Schueller Foundation (Young Scientist Award to H.P.).
NR 30
TC 39
Z9 40
U1 0
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 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD NOV
PY 2011
VL 141
IS 5
BP 1813
EP 1820
DI 10.1053/j.gastro.2011.06.076
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 841KW
UT WOS:000296512200046
PM 21745448
ER
PT J
AU Corradini, E
Rozier, M
Meynard, D
Odhiambo, A
Lin, HY
Feng, Q
Migas, MC
Britton, RS
Babitt, JL
Fleming, RE
AF Corradini, Elena
Rozier, Molly
Meynard, Delphine
Odhiambo, Adam
Lin, Herbert Y.
Feng, Qi
Migas, Mary C.
Britton, Robert S.
Babitt, Jodie L.
Fleming, Robert E.
TI Iron Regulation of Hepcidin Despite Attenuated Smad1,5,8 Signaling in
Mice Without Transferrin Receptor 2 or Hfe
SO GASTROENTEROLOGY
LA English
DT Article
DE Bone Morphogenetic Protein 6; Id1
ID HEREDITARY HEMOCHROMATOSIS PROTEIN; MOUSE MODEL; IN-VIVO; JUVENILE
HEMOCHROMATOSIS; EXPRESSION; OVERLOAD; HEMOJUVELIN; METABOLISM; LIVER;
TFR2
AB BACKGROUND & AIMS: HFE and transferrin receptor 2 (TFR2) are each necessary for the normal relationship between body iron status and liver hepcidin expression. In murine Hfe and Tfr2 knockout models of hereditary hemochromatosis (HH), signal transduction to hepcidin via the bone morphogenetic protein 6 (Bmp6)/Smad1,5,8 pathway is attenuated. We examined the effect of dietary iron on regulation of hepcidin expression via the Bmp6/Smad1,5,8 pathway using mice with targeted disruption of Tfr2, Hfe, or both genes. METHODS: Hepatic iron concentrations and messenger RNA expression of Bmp6 and hepcidin were compared with wild-type mice in each of the HH models on standard or iron-loading diets. Liver phospho-Smad (P-Smad) 1,5,8 and Id1 messenger RNA levels were measured as markers of Bmp/Smad signaling. RESULTS: Whereas Bmp6 expression was increased, liver hepcidin and Id1 expression were decreased in each of the HH models compared with wild-type mice. Each of the HH models also showed attenuated P-Smad1,5,8 levels relative to liver iron status. Mice with combined Hfe/Tfr2 disruption were most affected. Dietary iron loading increased hepcidin and Id1 expression in each of the HH models. Compared with wild-type mice, HH mice demonstrated attenuated (Hfe knockout) or no increases in P-Smad1,5,8 levels in response to dietary iron loading. CONCLUSIONS: These observations show that Tfr2 and Hfe are each required for normal signaling of iron status to hepcidin via the Bmp6/Smad1,5,8 pathway. Mice with combined loss of Hfe and Tfr2 up-regulate hepcidin in response to dietary iron loading without increases in liver Bmp6 messenger RNA or steady-state P-Smad1,5,8 levels.
C1 [Rozier, Molly; Feng, Qi; Migas, Mary C.; Fleming, Robert E.] St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63104 USA.
[Britton, Robert S.] St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO 63104 USA.
[Fleming, Robert E.] St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA.
[Corradini, Elena; Meynard, Delphine; Odhiambo, Adam; Lin, Herbert Y.; Babitt, Jodie L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Div Nephrol,Program Membrane Biol, Boston, MA USA.
RP Fleming, RE (reprint author), St Louis Univ, Sch Med, Dept Pediat, 1465 S Grand Ave, St Louis, MO 63104 USA.
EM flemingr@slu.edu
RI Corradini, Elena/O-4167-2016; meynard, delphine/B-4236-2014
OI Corradini, Elena/0000-0001-9477-2164;
FU National Institutes of Health [R01 DK063016, K08 DK075846, R01 DK069533,
R01 DK071837]; Massachusetts General Hospital
FX Supported by National Institutes of Health grants (R01 DK063016 to R. E.
F., K08 DK075846 to J.L.B., and R01 DK069533 and R01 DK071837 to H.Y.L.)
and a Claflin Distinguished Scholar Award from the Massachusetts General
Hospital (to J.L.B).
NR 54
TC 34
Z9 37
U1 1
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD NOV
PY 2011
VL 141
IS 5
BP 1907
EP 1914
DI 10.1053/j.gastro.2011.06.077
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 841KW
UT WOS:000296512200055
PM 21745449
ER
PT J
AU Byrd, JB
Ho, PM
AF Byrd, James Brian
Ho, P. Michael
TI The possibility of unmeasured confounding variables in observational
studies: a forgotten fact?
SO HEART
LA English
DT Editorial Material
ID ACUTE MYOCARDIAL-INFARCTION; CLOPIDOGREL; OUTCOMES; DISEASE
C1 [Byrd, James Brian] Univ Colorado, Div Cardiol, Denver, CO 80202 USA.
[Ho, P. Michael] Denver VA Med Ctr, Cardiol Sect, Denver, CO USA.
RP Ho, PM (reprint author), 1055 Clermont St, Denver, CO 80220 USA.
EM michael.ho@coloradooutcomes.org
OI Byrd, J. Brian/0000-0002-0509-3520
NR 10
TC 3
Z9 3
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
J9 HEART
JI Heart
PD NOV
PY 2011
VL 97
IS 22
BP 1815
EP 1816
DI 10.1136/heartjnl-2011-300630
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 837LF
UT WOS:000296203800001
PM 21795300
ER
PT J
AU Murphy, K
van Ginneken, B
Reinhardt, JM
Kabus, S
Ding, K
Deng, X
Cao, KL
Du, KF
Christensen, GE
Garcia, V
Vercauteren, T
Ayache, N
Commowick, O
Malandain, G
Glocker, B
Paragios, N
Navab, N
Gorbunova, V
Sporring, J
de Bruijne, M
Han, X
Heinrich, MP
Schnabel, JA
Jenkinson, M
Lorenz, C
Modat, M
McClelland, JR
Ourselin, S
Muenzing, SEA
Viergever, MA
De Nigris, D
Collins, DL
Arbel, T
Peroni, M
Li, R
Sharp, GC
Schmidt-Richberg, A
Ehrhardt, J
Werner, R
Smeets, D
Loeckx, D
Song, G
Tustison, N
Avants, B
Gee, JC
Staring, M
Klein, S
Stoel, BC
Urschler, M
Werlberger, M
Vandemeulebroucke, J
Rit, S
Sarrut, D
Pluim, JPW
AF Murphy, Keelin
van Ginneken, Bram
Reinhardt, Joseph M.
Kabus, Sven
Ding, Kai
Deng, Xiang
Cao, Kunlin
Du, Kaifang
Christensen, Gary E.
Garcia, Vincent
Vercauteren, Tom
Ayache, Nicholas
Commowick, Olivier
Malandain, Gregoire
Glocker, Ben
Paragios, Nikos
Navab, Nassir
Gorbunova, Vladlena
Sporring, Jon
de Bruijne, Marleen
Han, Xiao
Heinrich, Mattias P.
Schnabel, Julia A.
Jenkinson, Mark
Lorenz, Cristian
Modat, Marc
McClelland, Jamie R.
Ourselin, Sebastien
Muenzing, Sascha E. A.
Viergever, Max A.
De Nigris, Dante
Collins, D. Louis
Arbel, Tal
Peroni, Marta
Li, Rui
Sharp, Gregory C.
Schmidt-Richberg, Alexander
Ehrhardt, Jan
Werner, Rene
Smeets, Dirk
Loeckx, Dirk
Song, Gang
Tustison, Nicholas
Avants, Brian
Gee, James C.
Staring, Marius
Klein, Stefan
Stoel, Berend C.
Urschler, Martin
Werlberger, Manuel
Vandemeulebroucke, Jef
Rit, Simon
Sarrut, David
Pluim, Josien P. W.
TI Evaluation of Registration Methods on Thoracic CT: The EMPIRE10
Challenge
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Chest; computed tomography; evaluation; registration
ID DEFORMABLE IMAGE REGISTRATION; LUNG MOTION; MULTI-INSTITUTION; MEDICAL
IMAGES; ACCURACY; ALGORITHMS; QUANTIFICATION; SEGMENTATION; VALIDATION;
FRAMEWORK
AB EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of intrapatient thoracic CT image pairs. Evaluation of nonrigid registration techniques is a nontrivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the configuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (http://empire10.isi.uu.nl). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This paper details the organization of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.
C1 [van Ginneken, Bram] Radboud Univ Nijmegen, Med Ctr, Dept Radiol, NL-6500 HB Nijmegen, Netherlands.
[Murphy, Keelin; van Ginneken, Bram; Muenzing, Sascha E. A.; Viergever, Max A.; Pluim, Josien P. W.] Univ Med Ctr, Image Sci Inst, NL-3584 CX Utrecht, Netherlands.
[Reinhardt, Joseph M.; Ding, Kai; Du, Kaifang] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA.
[Kabus, Sven; Lorenz, Cristian] Philips Res Labs, D-22335 Hamburg, Germany.
[Cao, Kunlin; Christensen, Gary E.] Univ Iowa, Dept Elect & Comp Engn, Iowa City, IA 52242 USA.
[Garcia, Vincent; Ayache, Nicholas; Malandain, Gregoire] INRIA Sophia Antipolis Mediterranee, F-06902 Sophia Antipolis, France.
[Vercauteren, Tom] Mauna Kea Technol, F-75010 Paris, France.
[Commowick, Olivier] INRIA Rennes Bretagne Atlantique, Rennes, France.
[Glocker, Ben; Navab, Nassir] Tech Univ Munich, D-85748 Garching, Germany.
[Paragios, Nikos] INRIA Saclay Ile de France, F-91893 Orsay, France.
[Paragios, Nikos] Ecole Cent Paris, Lab MAS, F-92295 Chatenay Malabry, France.
[Gorbunova, Vladlena; Sporring, Jon; de Bruijne, Marleen] Univ Copenhagen, Dept Comp Sci, DK-2100 Copenhagen, Denmark.
[de Bruijne, Marleen; Klein, Stefan] Erasmus MC, Biomed Imaging Grp Rotterdam, NL-3000 CA Rotterdam, Netherlands.
[Han, Xiao] Elekta Inc, CMS Software, Maryland Hts, MO 63043 USA.
[Heinrich, Mattias P.; Schnabel, Julia A.] Univ Oxford, Inst Biomed Engn, Dept Engn Sci, Oxford OX3 7DQ, England.
[Heinrich, Mattias P.; Jenkinson, Mark] Univ Oxford, Ctr Funct MRI Brain, Oxford OX3 9DU, England.
[Modat, Marc; McClelland, Jamie R.; Ourselin, Sebastien] UCL, Ctr Med Image Comp, London WC1E 6BT, England.
[De Nigris, Dante; Arbel, Tal] McGill Univ, Ctr Intelligent Machines, Montreal, PQ H3A 2T5, Canada.
[Collins, D. Louis] McGill Univ, Dept Biomed Engn, Montreal, PQ H3A 2T5, Canada.
[Peroni, Marta; Li, Rui; Sharp, Gregory C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Peroni, Marta] Politecn Milan, I-20133 Milan, Italy.
[Peroni, Marta] MIT, Cambridge, MA 02139 USA.
[Schmidt-Richberg, Alexander; Ehrhardt, Jan; Werner, Rene] Univ Lubeck, Inst Med Informat, D-23538 Lubeck, Germany.
[Smeets, Dirk; Loeckx, Dirk] Univ Hosp Gasthuisberg, KU Leuven, Fac Engn, ESAT PSI,Med Imaging Res Ctr, B-3000 Louvain, Belgium.
[Song, Gang; Avants, Brian; Gee, James C.] Univ Penn, Sch Med, PICSL, Dept Radiol, Philadelphia, PA 19104 USA.
[Tustison, Nicholas] Univ Virginia, Dept Radiol & Med Imaging, Charlottesville, VA 22908 USA.
[Staring, Marius; Stoel, Berend C.] Leiden Univ, Med Ctr, Div Image Proc, Dept Radiol, NL-2300 RC Leiden, Netherlands.
[Urschler, Martin; Werlberger, Manuel] Graz Univ Technol, Inst Comp Graph & Vis, A-8010 Graz, Austria.
[Urschler, Martin] Ludwig Boltzmann Inst Clin Forens Imaging, A-8010 Graz, Austria.
[Vandemeulebroucke, Jef; Rit, Simon; Sarrut, David] Univ Lyon 1, CREATIS, CNRS UMR5220, Inserm U1044,INSA Lyon,Ctr Leon Berard, F-69000 Lyon, France.
RP van Ginneken, B (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Radiol, NL-6500 HB Nijmegen, Netherlands.
EM b.vanginneken@rad.umcn.nl
RI Staring, Marius/A-9517-2009; Ding, Kai/E-1943-2013; Rit,
Simon/H-9410-2014; Viergever, Max/J-1215-2014; Vercauteren,
Tom/I-7290-2013; Sarrut, David/F-4849-2010; Schmidt-Richberg,
Alexander/G-1597-2015; van Ginneken, Bram/A-3728-2012;
Vandemeulebroucke, Jef/F-2596-2016; Malandain, Gregoire/J-8115-2015;
Sporring, Jon/L-4499-2016; de Bruijne, Marleen/G-2662-2010; Werner,
Rene/B-4989-2017
OI Jenkinson, Mark/0000-0001-6043-0166; avants, brian/0000-0002-4212-3362;
TUSTISON, NICHOLAS/0000-0001-9418-5103; Schnabel,
Julia/0000-0001-6107-3009; McClelland, Jamie/0000-0002-4922-0093;
Urschler, Martin/0000-0001-5792-3971; Glocker, Ben/0000-0002-4897-9356;
Vercauteren, Tom/0000-0003-1794-0456; Sarrut, David/0000-0002-4854-4141;
Schmidt-Richberg, Alexander/0000-0002-0633-4832; van Ginneken,
Bram/0000-0003-2028-8972; Vandemeulebroucke, Jef/0000-0001-5714-3254;
Malandain, Gregoire/0000-0002-4559-1575; Sporring,
Jon/0000-0003-1261-6702; de Bruijne, Marleen/0000-0002-6328-902X;
Werner, Rene/0000-0002-2296-3305
FU Roberto Rocca Foundation
FX The work of M. Peroni was supported by the Roberto Rocca Foundation.
Asterisk indicates corresponding author.
NR 63
TC 146
Z9 147
U1 3
U2 27
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD NOV
PY 2011
VL 30
IS 11
BP 1901
EP 1920
DI 10.1109/TMI.2011.2158349
PG 20
WC Computer Science, Interdisciplinary Applications; Engineering,
Biomedical; Engineering, Electrical & Electronic; Imaging Science &
Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 840QM
UT WOS:000296455500003
PM 21632295
ER
PT J
AU Balamayooran, T
Batra, S
Balamayooran, G
Cai, SS
Kobayashi, KS
Flavell, RA
Jeyaseelan, S
AF Balamayooran, Theivanthiran
Batra, Sanjay
Balamayooran, Gayathriy
Cai, Shanshan
Kobayashi, Koichi S.
Flavell, Richard A.
Jeyaseelan, Samithamby
TI Receptor-Interacting Protein 2 Controls Pulmonary Host Defense to
Escherichia coli Infection via the Regulation of Interleukin-17A
SO INFECTION AND IMMUNITY
LA English
DT Article
ID NF-KAPPA-B; CONTAINING ADAPTER PROTEIN; INNATE IMMUNE-RESPONSES;
NEUTROPHIL RECRUITMENT; KLEBSIELLA-PNEUMONIAE; INFLAMMATORY RESPONSE;
BACTERIAL PNEUMONIA; INHALED ENDOTOXIN; IL-17 PRODUCTION;
KINASE-ACTIVITY
AB Recognition of microbial patterns by host receptors is the first step in a multistep sequence leading to neutrophil-dependent host resistance. Although the role of membrane-bound sensors in bacterial recognition has been examined in detail, the importance of cytosolic sensors in the lungs is largely unexplored. In this context, there is a major lack of understanding related to the downstream signaling mediators, such as cells and/or molecules, during acute extracellular Gram-negative bacterial pneumonia. In order to determine the role of NOD-like receptors (NLRs), we used an experimental Escherichia coli infection model using mice deficient in the gene coding for the NLR adaptor, receptor-interacting protein 2 (RIP2). RIP2(-/-) mice with E. coli infection displayed higher bacterial burden and reduced neutrophil recruitment and tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), macrophage inflammatory protein 2 (MIP-2), and CXCL5/LIX expression, along with attenuated histopathological changes in the lungs. Decreased IL-17A levels were observed, along with lower numbers of IL-17A-producing T cells, in RIP2(-/-) mice after infection. RIP2(-/-) mice also show reduced IL-6 and IL-23 levels in the lungs, along with decreased activation of STAT3 after infection. Furthermore, activation of NF-kappa B and mitogen-activated protein kinases (MAPKs) and expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in the lungs of infected RIP2(-/-) mice were attenuated following infection. Although neutrophil mobilization to the blood was impaired in RIP2(-/-) mice following infection, the expression of CD62P, CD11a/18, CD11b, and CXCR2 on blood and lung neutrophils was not altered between infected wild-type (WT) and RIP2(-/-) mice. Thus, RIP2 contributes to neutrophil-dependent host defense against an extracellular Gram-negative pathogen via (i) IL-17A regulation and (ii) neutrophil mobilization to the blood.
C1 [Balamayooran, Theivanthiran; Batra, Sanjay; Balamayooran, Gayathriy; Cai, Shanshan; Jeyaseelan, Samithamby] Louisiana State Univ, Dept Pathobiol Sci, Lab Lung Biol, Baton Rouge, LA 70803 USA.
[Balamayooran, Theivanthiran; Batra, Sanjay; Balamayooran, Gayathriy; Cai, Shanshan; Jeyaseelan, Samithamby] Louisiana State Univ, Ctr Expt Infect Dis Res, Baton Rouge, LA 70803 USA.
[Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Flavell, Richard A.] Yale Univ, Howard Hughes Med Inst, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA.
[Jeyaseelan, Samithamby] LSU Hlth Sci Ctr, Sect Pulm & Crit Care Med, Dept Med, New Orleans, LA 70112 USA.
RP Jeyaseelan, S (reprint author), Louisiana State Univ, Dept Pathobiol Sci, Lab Lung Biol, Baton Rouge, LA 70803 USA.
EM jey@lsu.edu
FU FAMRI [YCSA-062466]; NIH via ARRA [R01 HL-091958, R01 HL-091958S1]
FX This work was supported by a Scientist Award from the FAMRI
(YCSA-062466); and grants from the NIH (R01 HL-091958 and R01
HL-091958S1 via ARRA) to S.J.
NR 60
TC 14
Z9 14
U1 1
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2011
VL 79
IS 11
BP 4588
EP 4599
DI 10.1128/IAI.05641-11
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 839GB
UT WOS:000296352400030
PM 21844230
ER
PT J
AU Nguyen, DD
AF Nguyen, Deanna D.
TI Thiopurines and Paternity: Is It Safe?
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Editorial Material
ID INFLAMMATORY-BOWEL-DISEASE; POPULATION-BASED COHORT; AZATHIOPRINE;
6-MERCAPTOPURINE; PREGNANCY; OUTCOMES; MERCAPTOPURINE; WOMEN
C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Crohns & Colitis Ctr, Boston, MA 02114 USA.
RP Nguyen, DD (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Crohns & Colitis Ctr, Boston, MA 02114 USA.
NR 13
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1078-0998
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD NOV
PY 2011
VL 17
IS 11
BP 2402
EP 2403
DI 10.1002/ibd.21718
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 840ED
UT WOS:000296420200025
PM 21484969
ER
PT J
AU Sajatovic, M
Al Jurdi, R
Gildengers, A
Greenberg, RL
Tenhave, T
Bruce, ML
Mulsant, B
Young, RC
AF Sajatovic, Martha
Al Jurdi, Rayan
Gildengers, Ariel
Greenberg, Rebecca L.
Tenhave, Thomas
Bruce, Martha L.
Mulsant, Benoit
Young, Robert C.
TI Depression symptom ratings in geriatric patients with bipolar mania
SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE bipolar disorder; geriatrics; older; depression; rating scales
ID OLDER-ADULTS; MIXED MANIA; CLINICAL-TRIALS; II DISORDERS; SCALE;
SENSITIVITY; DIAGNOSIS; SAMPLE; PURE
AB Objective: Given the paucity of information available regarding standardized ratings of depression symptoms in bipolar manic states, and in particular those in older adults, we explored depression ratings in symptomatic participants in a multicenter study of treatment of bipolar I disorder in late life.
Methods: Baseline data was obtained from the first 100 patients enrolled in an NIMH-funded, 9-week, randomized, double-blind RCT comparing treatment with lithium or valproate in patients of age 60 years and older with Type I Bipolar mania or hypomania. This multi-site study was conducted at six academic medical centers in the United States and enrolled inpatients and outpatients with a total Young Mania Rating Scale (YMRS) score of 18 or greater. Depressive symptoms were evaluated with the Hamilton Depression Rating Scale (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS). The criterion for at least moderate bipolar depressive symptoms was the European College of Neuropsychopharmacology (ECNP) Consensus Meeting definition of HAM-D 17 total score >20.
Results: Eleven percent of patients had mixed symptoms defined by depression scale severity according to ECNP criterion. In the overall sample, total scores on the two depression scales were highly correlated. Total YMRS scores of this mixed symptom group were similar to the remainder of the sample.
Conclusions: These preliminary findings suggest that moderate to severe depressive symptoms occur in about one in ten bipolar manic elders. Future studies are needed to further evaluate symptom profiles, clinical correlates, and treatments for bipolar older adults with combined manic and depressive symptoms. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Sajatovic, Martha] Case Western Reserve Univ, Sch Med, Dept Psychiat, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
[Al Jurdi, Rayan] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Psychiat, Menninger Dept Psychiat, Houston, TX 77030 USA.
[Gildengers, Ariel] Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA.
[Greenberg, Rebecca L.; Bruce, Martha L.; Young, Robert C.] Weill Cornell Med Coll, Dept Psychiat, White Plains, NY USA.
[Tenhave, Thomas] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Mulsant, Benoit] Univ Toronto, Geriatr Mental Hlth Program, Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Mulsant, Benoit] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
RP Sajatovic, M (reprint author), Case Western Reserve Univ, Sch Med, Dept Psychiat, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
EM martha.sajatovic@uhhospitals.org
RI Sajatovic, Martha/I-8001-2014;
OI Young, Robert/0000-0002-6380-6314
FU National Institute of Mental Health (NIMH) [U01 MH074091-01]; National
Center for Research Resources (NCRR), National Institutes of Health
(NIH) [M01 RR00080, UL1 RR024989]
FX This study was supported by National Institute of Mental Health (NIMH)
grant U01 MH074091-01 (all authors); the NIMH had no further role in
study design; in the collection, analysis and interpretation of data; in
the writing of the report and in the decision to submit the paper for
publication.; The project described was supported by Grant Number M01
RR00080 and UL1 RR024989 from the National Center for Research Resources
(NCRR), a component of the National Institutes of Health (NIH) and its
contents are solely the responsibility of the authors and do not
necessarily represent the official view of NCRR or NIH.
NR 36
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-6230
EI 1099-1166
J9 INT J GERIATR PSYCH
JI Int. J. Geriatr. Psychiatr.
PD NOV
PY 2011
VL 26
IS 11
BP 1201
EP 1208
DI 10.1002/gps.2664
PG 8
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 840NK
UT WOS:000296447300013
PM 21360754
ER
PT J
AU Charlton, BM
Corliss, HL
Missmer, SA
Frazier, AL
Rosario, M
Kahn, JA
Austin, SB
AF Charlton, Brittany M.
Corliss, Heather L.
Missmer, Stacey A.
Frazier, A. Lindsay
Rosario, Margaret
Kahn, Jessica A.
Austin, S. Bryn
TI Reproductive Health Screening Disparities and Sexual Orientation in a
Cohort Study of U.S. Adolescent and Young Adult Females
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Homosexuality; Female; Bisexuality; Heterosexuality; Sexuality; Sexual
behavior; Healthcare disparities; Papanicolaou test; Sexually
transmitted diseases; Papillomavirus infections
ID HUMAN-PAPILLOMAVIRUS INFECTION; GENITAL HUMAN-PAPILLOMAVIRUS;
CERVICAL-CANCER; WOMEN; LESBIANS; CARCINOGENESIS; MANAGEMENT; BEHAVIORS;
SERVICES; HISTORY
AB Purpose: To examine sexual orientation group disparities in the Papanicolaou (Pap) and sexually transmitted infection (STI)/human papillomavirus (HPV) tests among adolescents and young adult females.
Methods: Survey data from 4,224 adolescents and young adults aged 17-25 years who responded to the 2005 wave questionnaire of the Growing Up Today Study were cross-sectionally examined with multivariate generalized estimating equations regression. We examined associations between sexual orientation and reproductive healthcare utilization as well as abnormal results with completely heterosexual as the referent group, controlling for age, race/ethnicity, geographic region, and sexual history.
Results: After accounting for sociodemographics and sexual history, mostly heterosexual/bisexual females had 30% lower odds of having a Pap test within the last year and almost 40% higher odds of being diagnosed with an STI, as compared with the completely heterosexual group. Additionally, lesbians had very low odds of having a Pap test in their lifetime (odds ratio = .13, p <= .0001) and having a Pap test within the last year (odds ratio = .25, p = .0002), as compared with completely heterosexuals.
Conclusions: Our study demonstrates that sexual minority adolescent and young adult women underutilize routine reproductive health screenings, including Pap smears and STI tests. Providers and health educators should be aware of these disparities so that they can provide appropriate care to young women and their families and ensure that all young women receive reproductive health screening. Further research is needed to explore reasons sexual minority females are not accessing care as recommended because this may suggest opportunities to improve reproductive health screenings as well as broader healthcare access issues. (C) 2011 Society for Adolescent Health and Medicine. All rights reserved.
C1 [Charlton, Brittany M.; Missmer, Stacey A.; Frazier, A. Lindsay] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Corliss, Heather L.; Austin, S. Bryn] Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA 02115 USA.
[Corliss, Heather L.; Austin, S. Bryn] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Missmer, Stacey A.; Frazier, A. Lindsay; Austin, S. Bryn] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Missmer, Stacey A.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
[Frazier, A. Lindsay] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Rosario, Margaret] CUNY City Coll, Dept Psychol, New York, NY USA.
[Kahn, Jessica A.] Cincinnati Childrens Hosp, Med Ctr, Div Adolescent Med, Cincinnati, OH USA.
[Kahn, Jessica A.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA.
[Austin, S. Bryn] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Rosario, Margaret] CUNY, Grad Ctr, New York, NY USA.
RP Charlton, BM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,9th Floor, Boston, MA 02115 USA.
EM bcharlto@hsph.harvard.edu
FU National Institutes of Health [R01HD057368]; Maternal and Child Health
Bureau [T71 MC 00009-17]; National Institute on Drug Abuse [K01
DA023610]
FX This study was supported by research grant R01HD057368 from the National
Institutes of Health. HL Corliss and SB Austin are supported by the
Leadership Education in Adolescent Health Project grant T71 MC 00009-17
from the Maternal and Child Health Bureau. HL Corliss is also supported
by the National Institute on Drug Abuse grant K01 DA023610.
NR 34
TC 36
Z9 37
U1 1
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD NOV
PY 2011
VL 49
IS 5
BP 505
EP 510
DI 10.1016/j.jadohealth.2011.03.013
PG 6
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 839SR
UT WOS:000296390000010
PM 22018565
ER
PT J
AU Khullar, D
Oreskovic, NM
Perrin, JM
Goodman, E
AF Khullar, Dhruv
Oreskovic, Nicolas M.
Perrin, James M.
Goodman, Elizabeth
TI Optimism and the Socioeconomic Status Gradient in Adolescent Adiposity
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Socioeconomic status; Disparities; Dispositional optimism; Body mass
index; Adiposity
ID LIFE; OBESITY
AB Purpose: To assess whether dispositional optimism is associated with adiposity and to explore whether dispositional optimism mediates the relationship between parent education and adiposity (body mass index [BMI] z-score).
Methods: Multivariate regression analyses of data were collected from 1,298 non-Hispanic black and white adolescents aged 12-19 years from a single Midwestern public school district.
Results: Less optimistic adolescents had higher BMI z-scores (r = -.09, p < .001). Addition of dispositional optimism to the regression model caused an approximately 10% attenuation of the parent education and BMI z-score relationship. Sobel tests confirmed that this attenuation indicated partial mediation.
Conclusion: Lower dispositional optimism is associated with higher adiposity and this association accounts for some of the influence of parent education on adolescent adiposity. (C) 2011 Society for Adolescent Health and Medicine. All rights reserved.
C1 [Oreskovic, Nicolas M.; Perrin, James M.; Goodman, Elizabeth] MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA.
[Khullar, Dhruv] Yale Univ, Sch Med, New Haven, CT USA.
RP Goodman, E (reprint author), MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA.
EM egoodman3@partners.org
OI Oreskovic, Nicolas/0000-0001-8702-8636; Goodman,
Elizabeth/0000-0002-9640-9884
FU National Institutes of Health [HD041527, T35-HD007446]
FX The present study was supported by National Institutes of Health grants
HD041527 and T35-HD007446.
NR 10
TC 5
Z9 5
U1 2
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD NOV
PY 2011
VL 49
IS 5
BP 553
EP 555
DI 10.1016/j.jadohealth.2011.04.003
PG 3
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 839SR
UT WOS:000296390000019
PM 22018574
ER
PT J
AU Coumans, JVCE
Walcott, BP
AF Coumans, Jean-Valery C. E.
Walcott, Brian P.
TI Rapidly progressive lumbar subdural empyema following acromial bursal
injection
SO JOURNAL OF CLINICAL NEUROSCIENCE
LA English
DT Article
DE Complication; Infection; Spine; Staphylococcus aureus; Subdural empyema
ID DERMAL SINUS; ABSCESS
AB Spinal subdural empyemas are rare. We describe a 53-year-old male who presented with back pain, mental status changes, and sepsis. Five days prior he had undergone a triamcinolone and lidocaine injection of the acromial bursa. He also had a remote history of epidural steroid injection for thoracic back pain. Two lumbar MRI conducted 62 hours apart revealed a newly developed subdural empyema that was successfully treated with surgical evacuation and post-operative antibiotics. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, 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
NR 11
TC 8
Z9 8
U1 0
U2 1
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 NOV
PY 2011
VL 18
IS 11
BP 1562
EP 1563
DI 10.1016/j.jocn.2011.03.009
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 839XM
UT WOS:000296402800036
PM 21868236
ER
PT J
AU Sonnenberg, A
AF Sonnenberg, Amnon
TI Birth cohort patterns of gastric cancer and peptic ulcer among
non-whites in the USA
SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
LA English
DT Article
ID TIME TRENDS; HELICOBACTER-PYLORI; MORTALITY; SALT; INFECTION; GERMANY;
DISEASE; RATES; RISK
AB Background The aim of this study was to follow the long-term trends of mortality from gastric cancer, gastric ulcer and duodenal ulcer in the USA. It was hypothesised that the time trends among different ethnic groups would be shaped by similar birth cohort patterns.
Methods The US ulcer and cancer data were available from 1923 to 2006 and 1930 to 2006, respectively. Age-specific death rates were calculated for consecutive 10-year periods and 10-year age groups, stratified by sex and race. They were plotted against the period of death as period-age contours and against the period of birth as cohort-age contours. The time trends were also summarised as standardised cohort mortality ratios.
Results The occurrence of birth cohort patterns with an initial rise and a subsequent decline was observed in gastric cancer and both ulcer types. It occurred similarly in white and non-white population, as well as men and women. In all ethnic groups alike, the initial rise in mortality from gastric cancer and gastric ulcer preceded the rise of duodenal ulcer by 10-20 years. The two time lags between gastric cancer and gastric ulcer and between gastric and duodenal ulcer were most pronounced in white patients. In non-white patients, the rise of gastric cancer occurred later than in white patients and coincided with that of gastric ulcer. The initial rise in mortality from gastric cancer was more evident in non-white than in white patients.
Conclusion The birth cohort pattern has shaped the time trends of Helicobacter pylori-related disease similarly among different ethnic and socioeconomic groups. Its cause remains unknown and warrants further investigation.
C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Gastroenterol Sect, Portland, OR 97239 USA.
[Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA.
RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Gastroenterol Sect, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM sonnenbe@ohsu.edu
NR 31
TC 0
Z9 0
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0143-005X
J9 J EPIDEMIOL COMMUN H
JI J. Epidemiol. Community Health
PD NOV
PY 2011
VL 65
IS 11
BP 1059
EP 1064
DI 10.1136/jech.2010.121368
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 836VK
UT WOS:000296143300017
PM 21597103
ER
PT J
AU Joseph, J
AF Joseph, Jacob
TI Fattening by deprivation: methyl balance and perinatal cardiomyopathy
SO JOURNAL OF PATHOLOGY
LA English
DT Editorial Material
DE methylation; homocysteine; folate; B12; cardiomyopathy
ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; HYPERHOMOCYSTEINEMIA LEADS;
HYPERTENSIVE-RATS; HEART; HOMOCYSTEINE; METABOLISM; ACTIVATION;
MECHANISMS
AB Folate deficiency during pregnancy is associated with reduced birth weight, and a low birth weight is associated with increased cardiometabolic risk in adulthood. In the study by Moreno Garcia, Gueant-Rodriguez and colleagues reported in the current issue of the Journal of Pathology, the effect of methyl group deprivation in pregnancy on the neonatal myocardium was investigated. By utilizing a diet deficient in folate, vitamin B(12) and choline, the authors created a significant deficit of methyl groups in the fetus. During the weaning period and the concomitant shift from the relative hypoxia and glucose dependence of the gestational period to the aerobic, milk-derived high-fat metabolic environment of the weaning phase, the offspring developed a myocardial hypertrophy associated with disordered fatty acid oxidation and mitochondrial dysfunction. The functionality of PGC-1 alpha, a master regulator of metabolic pathways including mitochondrial energetics and fatty acid oxidation, was found to be reduced in the methyl-deprived group, due to an imbalance in the ratio of methylation to acetylation. This study demonstrates that maternal methyl deprivation could 'prime' the fetus by reducing its ability to oxidize fatty acids in the myocardium, thereby causing lipid accumulation and myocardial hypertrophy during exposure to high-fat diet in the weaning phase. This study has important implications for clinical perinatal cardiomyopathy and for the effect of maternal methyl group deprivation on the future risk of cardiovascular disease, and also potentially in enhancing the understanding of the elusive link between hyperhomocysteinaemic states in the adult and cardiovascular disease. Copyright. (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
C1 [Joseph, Jacob] VA Boston Healthcare Syst, Cardiol Sect 111, W Roxbury, MA 02132 USA.
[Joseph, Jacob] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
RP Joseph, J (reprint author), VA Boston Healthcare Syst, Cardiol Sect 111, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM jjoseph16@partners.org
FU NHLBI NIH HHS [HL89734]
NR 22
TC 7
Z9 8
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3417
J9 J PATHOL
JI J. Pathol.
PD NOV
PY 2011
VL 225
IS 3
BP 315
EP 317
DI 10.1002/path.2942
PG 3
WC Oncology; Pathology
SC Oncology; Pathology
GA 839ME
UT WOS:000296369900001
PM 21735445
ER
PT J
AU Prager, LM
AF Prager, Laura M.
TI Bipolar Disorder in the Book Forum
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Letter
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Prager, LM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM lmprager@partners.org
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD NOV
PY 2011
VL 50
IS 11
BP 1186
EP 1186
DI 10.1016/j.jaac.2011.07.023
PG 1
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 838PS
UT WOS:000296305300013
PM 22024006
ER
PT J
AU Wozniak, J
McDonnell, MA
Brenneman, JF
AF Wozniak, Janet
McDonnell, Mary Ann
Brenneman, Judy Fort
TI Bipolar Disorder in the Book Forum
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Letter
ID I DISORDER; ONSET; COMORBIDITY; ADOLESCENTS; CHILDREN; FAMILY
C1 [Wozniak, Janet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[McDonnell, Mary Ann] STEP Up Kids Inc, Marshfield, MA USA.
[Brenneman, Judy Fort] Greenfire Creat LLC, Ft Collins, CO USA.
RP Wozniak, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
EM jwozniak@partners.org
NR 9
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD NOV
PY 2011
VL 50
IS 11
BP 1186
EP 1187
PG 2
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 838PS
UT WOS:000296305300014
PM 22024007
ER
PT J
AU Okpokwasili, E
AF Okpokwasili, Ebele
TI Thirteen Reasons Why
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Book Review
ID ETHNOCULTURAL ASPECTS; YOUNG-PEOPLE; SUICIDE
C1 [Okpokwasili, Ebele] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Okpokwasili, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM eokpokwasili@partners.org
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD NOV
PY 2011
VL 50
IS 11
BP 1191
EP 1192
DI 10.1016/j.jaac.2011.09.004
PG 2
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 838PS
UT WOS:000296305300018
ER
PT J
AU Suri, RM
Burkhart, HM
Daly, RC
Dearani, JA
Park, SJ
Sundt, TM
Li, Z
Enriquez-Sarano, M
Schaff, HV
AF Suri, Rakesh M.
Burkhart, Harold M.
Daly, Richard C.
Dearani, Joseph A.
Park, Soon J.
Sundt, Thoralf M., III
Li, Zhuo
Enriquez-Sarano, Maurice
Schaff, Hartzell V.
TI Robotic mitral valve repair for all prolapse subsets using techniques
identical to open valvuloplasty: Establishing the benchmark against
which percutaneous interventions should be judged
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT 91st Annual Meeting of the American-Association-for-Thoracic-Surgery
CY MAY 07-11, 2011
CL Philadelphia, PA
SP Amer Assoc Thorac Surg
ID CARDIAC-SURGERY DATABASE; LEAFLET PROLAPSE; OPERATIONS TRENDS; OUTCOMES;
DURABILITY; REGURGITATION; ANNULOPLASTY; EXPERIENCE; SURVIVAL; SOCIETY
AB Objective: Recent reports have shown that robotic mitral valve repair is effective in treating posterior leaflet disease; however, comparison with trans-sternal (open) valvuloplasty for all prolapse categories has not been performed. Moreover, data from the recently published EVEREST II trial infer that adverse event rates after mitral valve repair for degenerative disease are high. We therefore compared early outcomes of robotic versus open mitral valve repair for patients with mitral valve prolapse.
Methods: Among 745 consecutive patients undergoing open or robotic mitral repair for degenerative disease, 95 propensity-matched pairs were identified. Leaflet prolapse categories were similar between groups. Complete mitral valve repair was performed using identical techniques.
Results: Median crossclamp and bypass times were longer in the robotic group but decreased significantly over time (P <.001). There were no conversions to open sternotomy, repair rate and early survival were 100%, dismissal mitral regurgitation grade was similar (P - 1.00), and all patients in the robotic group had mild or less mitral regurgitation at 1 month after repair. There were no differences in adverse events (5% open vs 4% robotic, P = 1.00). Patients in the robotic group had shorter postoperative ventilation time, intensive care unit stay, and hospital stay.
Conclusions: Robotic mitral valve repair allows complete anatomic correction of all categories of leaflet prolapse using techniques identical to open approaches. Robotic repair effectively corrects mitral regurgitation, offers excellent freedom from adverse events, and facilitates rapid weaning from ventilation, translating into earlier hospital dismissal. Safety and efficacy after both open and robotic mitral valve repair are higher than recently reported in the EVEREST II trial and establish a benchmark against which nonsurgical therapies should be evaluated. (J Thorac Cardiovasc Surg 2011;142:970-9)
C1 [Suri, Rakesh M.; Burkhart, Harold M.; Daly, Richard C.; Dearani, Joseph A.; Park, Soon J.; Schaff, Hartzell V.] Mayo Clin, Div Cardiovasc Surg, Rochester, MN 55905 USA.
[Li, Zhuo] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[Enriquez-Sarano, Maurice] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA.
[Sundt, Thoralf M., III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA.
RP Suri, RM (reprint author), Mayo Clin, Div Cardiovasc Surg, 200 1st St SW, Rochester, MN 55905 USA.
EM suri.rakesh@mayo.edu
OI Schaff, Hartzell/0000-0003-0994-027X
NR 34
TC 50
Z9 50
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD NOV
PY 2011
VL 142
IS 5
BP 970
EP 979
DI 10.1016/j.jtcvs.2011.07.027
PG 10
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 839AT
UT WOS:000296337500006
PM 21911231
ER
PT J
AU Dixon, JA
Goodman, AM
Gaillard, WF
Rivers, WT
McKinney, RA
Mukherjee, R
Baker, NL
Ikonomidis, JS
Spinale, FG
AF Dixon, Jennifer A.
Goodman, Amy M.
Gaillard, William F., II
Rivers, William T.
McKinney, Richard A.
Mukherjee, Rupak
Baker, Nathaniel L.
Ikonomidis, John S.
Spinale, Francis G.
TI Hemodynamics and myocardial blood flow patterns after placement of a
cardiac passive restraint device in a model of dilated cardiomyopathy
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID INDUCED HEART-FAILURE; TACHYCARDIA-INDUCED CARDIOMYOPATHY; FUNCTIONAL
MITRAL REGURGITATION; CONVERTING ENZYME-INHIBITION; ACORN
CLINICAL-TRIAL; SUPPORT DEVICE; COMBINATION THERAPY; INFARCTION;
REDUCTION; ADENOSINE
AB Background: The present study examined a cardiac passive restraint device which applies epicardial pressure (HeartNet Implant; Paracor Medical, Inc, Sunnyvale, Calif) in a clinically relevant model of dilated cardiomyopathy to determine effects on hemodynamic and myocardial blood flow patterns.
Methods: Dilated cardiomyopatht was established in 10 pigs (3 weeks of atrial pacing, 240 beats/min). Hemodynamic parameters and regional left ventricular blood flow were measured under baseline conditions and after acute placement of the HeartNet Implant. Measurements were repeated after adenosine infusion, allowing maximal coronary vasodilation and coronary flow reserve to be determined.
Results: Left ventricular dilation and systolic dysfunction occurred relative to baseline as measured by echocardiography. Left ventricular end-diastolic dimension increased and left ventricular fractional shortening decreased (3.8 +/- 0.1 vs 6.1 +/- 0.2 cm and 31.6% +/- 0.5% vs 16.2% +/- 2.1%, both P < .05, respectively), consistent with the dilated cardiomyopathy phenotype. The HeartNet Implant was successfully deployed without arrhythmias and a computed median mid-left ventricular epicardial pressure of 1.4 mm Hg was applied by the HeartNet Implant throughout the cardiac cycle. Acute HeartNet placement did not adversely affect steady state hemodynamics. With the HeartNet Implant in place, coronary reserve was significantly blunted.
Conclusions: In a large animal model of dilated cardiomyopathy, the cardiac passive restraint device did not appear to adversely affect basal resting myocardial blood flow. However, after acute HeartNet Implant placement, left ventricular maximal coronary reserve was blunted. These unique results suggest that cardiac passive restraint devices that apply epicardial transmural pressure can alter myocardial blood flow patterns in a model of dilated cardiomyopathy. Whether this blunting of coronary reserve holds clinical relevance with chronic passive restraint device placement remains unestablished. (J Thorac Cardiovasc Surg 2011;142:1038-45)
C1 [Dixon, Jennifer A.; Gaillard, William F., II; Rivers, William T.; McKinney, Richard A.; Mukherjee, Rupak; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA.
[Dixon, Jennifer A.; Gaillard, William F., II; Rivers, William T.; McKinney, Richard A.; Mukherjee, Rupak; Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
[Goodman, Amy M.; Ikonomidis, John S.] Paracor Med Inc, Sunnyvale, CA USA.
[Baker, Nathaniel L.] Med Univ S Carolina, Dept Biostat & Epidemiol, Charleston, SC 29425 USA.
RP Spinale, FG (reprint author), Strom Thurmond Res Ctr, 114 Doughty St,Suite 625, Charleston, SC 29425 USA.
EM wilburnm@musc.edu
FU Paracor Medical, Inc; National Institutes of Health [HL81692, HL87134];
Veterans' Affairs Health Administration
FX This research was supported by a grant from Paracor Medical, Inc, as
well as by National Institutes of Health grants HL81692 and HL87134 and
a Merit Award from the Veterans' Affairs Health Administration.
NR 26
TC 8
Z9 8
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD NOV
PY 2011
VL 142
IS 5
BP 1038
EP 1045
DI 10.1016/j.jtcvs.2010.09.065
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 839AT
UT WOS:000296337500015
PM 21397269
ER
PT J
AU Oniangue-Ndza, C
Kuntzen, T
Kemper, M
Berical, A
Wang, YYE
Neumann-Haefelin, C
Foote, PK
Hills-Evans, K
Reyor, LL
Kane, K
Gladden, AD
Bloom, AK
Power, KA
Thimme, R
Lauer, GM
Henn, MR
Kim, AY
Allen, TM
AF Oniangue-Ndza, Cesar
Kuntzen, Thomas
Kemper, Michael
Berical, Andrew
Wang, Yaoyu E.
Neumann-Haefelin, Christoph
Foote, Peter Kristian
Hills-Evans, Kelsey
Reyor, Laura L.
Kane, Katherine
Gladden, Adrianne D.
Bloom, Allyson K.
Power, Karen A.
Thimme, Robert
Lauer, Georg M.
Henn, Matthew R.
Kim, Arthur Y.
Allen, Todd M.
TI Compensatory Mutations Restore the Replication Defects Caused by
Cytotoxic T Lymphocyte Escape Mutations in Hepatitis C Virus Polymerase
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESTRICTED IMMUNE PRESSURE; LONG-TERM NONPROGRESSORS; RESISTANCE
MUTATIONS; CLASS-I; REPLICON VARIANTS; TYPE-1 INFECTION; RNA
REPLICATION; VIRAL FITNESS; CELL-CULTURE; GAG
AB While human leukocyte antigen B57 (HLA-B57) is associated with the spontaneous clearance of hepatitis C virus (HCV), the mechanisms behind this control remain unclear. Immunodominant CD8(+) T cell responses against the B57-restricted epitopes comprised of residues 2629 to 2637 of nonstructural protein 5B (NS5B(2629-2637)) (KSKKTPMGF) and E2(541-549) (NTRPPLGNW) were recently shown to be crucial in the control of HCV infection. Here, we investigated whether the selection of deleterious cytotoxic T lymphocyte (CTL) escape mutations in the NS5B KSKKTPMGF epitope might impair viral replication and contribute to the B57-mediated control of HCV. Common CTL escape mutations in this epitope were identified from a cohort of 374 HCV genotype 1a-infected subjects, and their impact on HCV replication assessed using a transient HCV replicon system. We demonstrate that while escape mutations at residue 2633 (position 5) of the epitope had little or no impact on HCV replication in vitro, mutations at residue 2629 (position 1) substantially impaired replication. Notably, the deleterious mutations at position 2629 were tightly linked in vivo to upstream mutations at residue 2626, which functioned to restore the replicative defects imparted by the deleterious escape mutations. These data suggest that the selection of costly escape mutations within the immunodominant NS5B KSKKTPMGF epitope may contribute in part to the control of HCV replication in B57-positive individuals and that persistence of HCV in B57-positive individuals may involve the development of specific secondary compensatory mutations. These findings are reminiscent of the selection of deleterious CTL escape and compensatory mutations by HLA-B57 in HIV-1 infection and, thus, may suggest a common mechanism by which alleles like HLA-B57 mediate protection against these highly variable pathogens.
C1 [Oniangue-Ndza, Cesar; Kuntzen, Thomas; Kemper, Michael; Berical, Andrew; Wang, Yaoyu E.; Neumann-Haefelin, Christoph; Kane, Katherine; Gladden, Adrianne D.; Bloom, Allyson K.; Power, Karen A.; Allen, Todd M.] Ragon Inst MGH MIT & Harvard, Boston, MA USA.
[Reyor, Laura L.; Lauer, Georg M.; Kim, Arthur Y.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Foote, Peter Kristian; Hills-Evans, Kelsey; Reyor, Laura L.; Lauer, Georg M.; Kim, Arthur Y.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Neumann-Haefelin, Christoph; Thimme, Robert] Univ Hosp Freiburg, Freiburg, Germany.
[Henn, Matthew R.] Broad Inst, Cambridge, MA USA.
RP Allen, TM (reprint author), Bldg 149,Rm 6625,13th St, Charlestown, MA 02129 USA.
EM tallen2@partners.org
RI Neumann-Haefelin, Christoph/E-5550-2011; Allen, Todd/F-5473-2011
FU National Institute of Allergy and Infectious Disease (NIAID)
[R01-AI067926, U19-AI066345, U19-AI082630]
FX This project was funded in part with federal funds from the National
Institute of Allergy and Infectious Disease (NIAID) under grants
R01-AI067926 (T. M. A.), U19-AI066345 (T. M. A. and G. M. L.), and
U19-AI082630 (T.M.A. and G.M.L.).
NR 53
TC 13
Z9 14
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD NOV
PY 2011
VL 85
IS 22
BP 11883
EP 11890
DI 10.1128/JVI.00779-11
PG 8
WC Virology
SC Virology
GA 840FB
UT WOS:000296422700031
PM 21880756
ER
PT J
AU Perlis, RH
AF Perlis, R. H.
TI Translating biomarkers to clinical practice
SO MOLECULAR PSYCHIATRY
LA English
DT Review
DE biomarker; test; diagnostic; genetic; cost-effectiveness; utility
ID STAR-ASTERISK-D; DEXAMETHASONE SUPPRESSION TEST; COST-EFFECTIVENESS
ANALYSIS; SERVICES TASK-FORCE; BREAST-CANCER; ANTIDEPRESSANT RESPONSE;
PREDICTION MODELS; BIPOLAR DISORDER; ROC CURVE; STEP-BD
AB Biomarkers are the measurable characteristics of an individual that may represent risk factors for a disease or outcome, or that may be indicators of disease progression or of treatment-associated changes. In general, the process by which biomarkers, once identified, might be translated into clinical practice has received scant attention in recent psychiatric literature. A body of work in diagnostic development suggests a framework for evaluating and validating novel biomarkers, but this work may be unfamiliar to clinical and translational researchers in psychiatry. Therefore, this review focuses on the steps that might follow the identification of putative biomarkers. It first addresses standard approaches to characterizing biomarker performance, followed by demonstrations of how a putative biomarker might be shown to have clinical relevance. Finally, it addresses ways in which a biomarker-based test might be validated for clinical application in terms of efficacy and cost-effectiveness. Molecular Psychiatry (2011) 16, 1076-1087; doi:10.1038/mp.2011.63; published online 28 June 2011
C1 [Perlis, R. H.] Massachusetts Gen Hosp, Dept Psychiat, Lab Psychiat Pharmacogen, Boston, MA 02114 USA.
[Perlis, R. H.] Harvard Univ, Sch Med, Boston, MA USA.
RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Lab Psychiat Pharmacogen, 185 Cambridge St,6th Floor, Boston, MA 02114 USA.
EM rperlis@partners.org
FU Stanley Center for Psychiatric Research; [R01 MH086026]
FX I thank Shaun Purcell, PhD, and Pamela Sklar, MD, PhD, for helpful
discussion. This work was supported by R01 MH086026 and by the Stanley
Center for Psychiatric Research.
NR 67
TC 42
Z9 42
U1 3
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD NOV
PY 2011
VL 16
IS 11
BP 1076
EP 1087
DI 10.1038/mp.2011.63
PG 12
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 840HD
UT WOS:000296429100007
PM 21709685
ER
PT J
AU Chen, X
Lee, G
Maher, BS
Fanous, AH
Chen, J
Zhao, Z
Guo, A
van den Oord, E
Sullivan, PF
Shi, J
Levinson, DF
Gejman, PV
Sanders, A
Duan, J
Owen, MJ
Craddock, NJ
O'Donovan, MC
Blackman, J
Lewis, D
Kirov, GK
Qin, W
Schwab, S
Wildenauer, D
Chowdari, K
Nimgaonkar, V
Straub, RE
Weinberger, DR
O'Neill, FA
Walsh, D
Bronstein, M
Darvasi, A
Lencz, T
Malhotra, AK
Rujescu, D
Giegling, I
Werge, T
Hansen, T
Ingason, A
Noethen, MM
Rietschel, M
Cichon, S
Djurovic, S
Andreassen, OA
Cantor, RM
Ophoff, R
Corvin, A
Morris, DW
Gill, M
Pato, CN
Pato, MT
Macedo, A
Gurling, HMD
McQuillin, A
Pimm, J
Hultman, C
Lichtenstein, P
Sklar, P
Purcell, SM
Scolnick, E
St Clair, D
Blackwood, DHR
Kendler, KS
AF Chen, X.
Lee, G.
Maher, B. S.
Fanous, A. H.
Chen, J.
Zhao, Z.
Guo, A.
van den Oord, E.
Sullivan, P. F.
Shi, J.
Levinson, D. F.
Gejman, P. V.
Sanders, A.
Duan, J.
Owen, M. J.
Craddock, N. J.
O'Donovan, M. C.
Blackman, J.
Lewis, D.
Kirov, G. K.
Qin, W.
Schwab, S.
Wildenauer, D.
Chowdari, K.
Nimgaonkar, V.
Straub, R. E.
Weinberger, D. R.
O'Neill, F. A.
Walsh, D.
Bronstein, M.
Darvasi, A.
Lencz, T.
Malhotra, A. K.
Rujescu, D.
Giegling, I.
Werge, T.
Hansen, T.
Ingason, A.
Noeethen, M. M.
Rietschel, M.
Cichon, S.
Djurovic, S.
Andreassen, O. A.
Cantor, R. M.
Ophoff, R.
Corvin, A.
Morris, D. W.
Gill, M.
Pato, C. N.
Pato, M. T.
Macedo, A.
Gurling, H. M. D.
McQuillin, A.
Pimm, J.
Hultman, C.
Lichtenstein, P.
Sklar, P.
Purcell, S. M.
Scolnick, E.
St Clair, D.
Blackwood, D. H. R.
Kendler, K. S.
CA Int Schizophrenia Consortium
TI GWA study data mining and independent replication identify
cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE association study; cardiomyopathy; GWA data mining; meta-analysis;
schizophrenia
ID GENOME-WIDE ASSOCIATION; SIB-PAIR FAMILIES; COMMON VARIANTS;
SUSCEPTIBILITY GENE; SAMPLES PROVIDES; PROTEIN MYOSPRYN; LINKAGE
ANALYSES; BINDING PARTNER; DYSBINDIN GENE; LUNG-CANCER
AB We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values <= 0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611-rs10043986, r(2) = 0.008; rs10043986-rs4704591, r(2) = 0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR) = 1.11, 95% confidence interval (CI) = 1.04-1.18, P = 8.2 x 10(-4) and rs4704591, OR = 1.07, 95% CI = 1.03-1.11, P = 3.0 x 10(-4)). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR = 1.11, 95% CI = 1.03-1.17, P = 0.0026 and rs4704591, OR = 1.07, 95% CI = 1.02-1.11, P = 0.0015). Furthermore, haplotype conditioned analyses indicated that the association signals observed at these two markers are independent. On the basis of these results, we concluded that CMYA5 is associated with schizophrenia and further investigation of the gene is warranted. Molecular Psychiatry (2011) 16, 1117-1129; doi:10.1038/mp.2010.96; published online 14 September 2010
C1 [Chen, X.; Lee, G.; Maher, B. S.; Fanous, A. H.; Chen, J.; van den Oord, E.; Kendler, K. S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA 23298 USA.
[Chen, X.; Kendler, K. S.] Virginia Commonwealth Univ, Dept Mol & Human Genet, Richmond, VA 23298 USA.
[Fanous, A. H.] Washington VA Med Ctr, Washington, DC USA.
[Fanous, A. H.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA.
[Zhao, Z.; Guo, A.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN USA.
[van den Oord, E.] Virginia Commonwealth Univ, Dept Pharm, Richmond, VA 23298 USA.
[Sullivan, P. F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Sullivan, P. F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Sullivan, P. F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Shi, J.; Levinson, D. F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Gejman, P. V.; Sanders, A.; Duan, J.] NorthShore Univ HealthSyst Res Inst, Ctr Psychiat Genet, Evanston, IL USA.
[Owen, M. J.; Craddock, N. J.; O'Donovan, M. C.; Blackman, J.; Lewis, D.; Kirov, G. K.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Dept Psychol Med, Cardiff, S Glam, Wales.
[Qin, W.; Schwab, S.; Wildenauer, D.] Univ Western Australia, Sch Psychiat, Perth, WA 6009, Australia.
[Qin, W.; Schwab, S.; Wildenauer, D.] Western Australian Inst Med Res, Perth, WA, Australia.
[Chowdari, K.; Nimgaonkar, V.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Chowdari, K.; Nimgaonkar, V.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Straub, R. E.; Weinberger, D. R.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[O'Neill, F. A.] Queens Univ Belfast, Dept Psychiat, Belfast, Antrim, North Ireland.
[Walsh, D.] Hlth Res Board, Dublin, Ireland.
[Bronstein, M.; Darvasi, A.] Hebrew Univ Jerusalem, Dept Genet, IL-91904 Jerusalem, Israel.
[Lencz, T.; Malhotra, A. K.] N Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Psychiat Res, Glen Oaks, NY USA.
[Rujescu, D.; Giegling, I.] Univ Munich, Div Mol & Clin Neurobiol, Munich, Germany.
[Werge, T.; Hansen, T.; Ingason, A.] Copenhagen Univ Hosp, Mental Hlth Ctr Sct Hans, Inst Psychiat, Roskilde, Denmark.
[Noeethen, M. M.; Cichon, S.] Univ Bonn, Inst Human Genet, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany.
[Rietschel, M.] Univ Heidelberg, Dept Genet Epidemiol Psychiat, Cent Inst Mental Hlth Mannheim, D-6800 Mannheim, Germany.
[Rietschel, M.] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany.
[Cichon, S.] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany.
[Djurovic, S.; Andreassen, O. A.] Oslo Univ Hosp, Oslo, Norway.
[Djurovic, S.; Andreassen, O. A.] Univ Oslo, Inst Psychiat, Oslo, Norway.
[Cantor, R. M.; Ophoff, R.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Dept Human Genet, Los Angeles, CA USA.
[Ophoff, R.] Univ Med Ctr Utrecht, Dept Med Genet, Cg Utrecht, Netherlands.
[Corvin, A.; Morris, D. W.; Gill, M.] Trinity Coll Dublin, Dept Psychiat, Dublin, Ireland.
[Corvin, A.; Morris, D. W.; Gill, M.] Trinity Coll Dublin, Inst Mol Med, Neuropsychiat Genet Res Grp, Dublin, Ireland.
[Pato, C. N.; Pato, M. T.] Univ So Calif, Ctr Genom Psychiat, Los Angeles, CA USA.
[Macedo, A.] Univ Coimbra, Dept Psychiat, Coimbra, Portugal.
[Gurling, H. M. D.; McQuillin, A.; Pimm, J.] UCL, Sch Med, Windeyer Inst Med Sci, Res Dept Mental Hlth Sci,Mol Psychiat Lab, London W1N 8AA, England.
[Hultman, C.; Lichtenstein, P.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Sklar, P.; Purcell, S. M.; Scolnick, E.] Psychiat & Neurodev Genet Unit, Boston, MA USA.
[Sklar, P.; Purcell, S. M.; Scolnick, E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[St Clair, D.] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland.
[Kendler, K. S.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland.
RP Chen, X (reprint author), Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, 800 E Leigh St,Suite 390, Richmond, VA 23298 USA.
EM xchen@vcu.edu
RI Ingason, Andres/G-6817-2012; Morley, Christopher P/K-1907-2014; Cahn ,
Wiepke /B-5743-2013; Gurling, Hugh/A-5029-2010; Maher,
Brion/F-9185-2010; macedo santos, antonio/M-5737-2013; Cichon,
Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Myin-Germeys, Inez
/L-5106-2014; Hansen, Thomas/O-5965-2014; Ruderfer, Douglas/M-5795-2016;
Lencz, Todd/J-3418-2014
OI McQuillin, Andrew/0000-0003-1567-2240; Andreassen, Ole
A./0000-0002-4461-3568; Visscher, Peter/0000-0002-2143-8760; Corvin,
Aiden/0000-0001-6717-4089; O'Donovan, Michael/0000-0001-7073-2379;
Morris, Derek/0000-0002-3413-570X; Myin-Germeys,
Inez/0000-0002-3731-4930; Gill, Michael/0000-0003-0206-5337;
lichtenstein, paul/0000-0003-3037-5287; Moran,
Jennifer/0000-0002-5664-4716; Bruggeman, Richard/0000-0002-3238-8471;
O'Neill, Francis Anthony/0000-0002-7531-7657; Morley, Christopher
P/0000-0003-0185-7148; de Oliveira Barreto Coimbra Carvalho, Celia
Maria/0000-0003-4453-8139; macedo santos, antonio/0000-0003-2180-2718;
Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X;
Hansen, Thomas/0000-0001-6703-7762; Ruderfer,
Douglas/0000-0002-2365-386X; Lencz, Todd/0000-0001-8586-338X
FU Stanley Medical Research Institute [07R-1770]; NARSAD; CATIE; GAIN;
international schizophrenia consortium; National Institutes of Health
[MH41953, MH63480, MH56242, MH078075]; Donald & Barbara Zucker
Foundation, USA; Medical Research Council; Wellcome Trust Foundation,
UK; Research Council of Norway [163070/V50, 167153/V50]; South-Eastern
Norway Health Authority [123/2004]; Science Foundation Ireland; Health
Research Board, Ireland; Lundbeck Foundation; Danish National Advanced
Technology Foundation, Denmark; National Institute of Mental Health [N01
MH900001, MH074027]; Eli Lilly and Company; National Alliance for
Research on Schizophrenia and Depression; National Center for Research
Resources
FX We thank the volunteers, patients and their family members for
participating in this study. This study was supported in part by a
research grant (07R-1770) from the Stanley Medical Research Institute
and an Independent Investigator Award from NARSAD to XC, and by grants
to investigators involved in the collection and analyses of the samples
from CATIE, GAIN, the international schizophrenia consortium and other
independent samples (National Institutes of Health (MH41953, MH63480,
MH56242, MH078075); NARSAD Young Investigator Award; Donald & Barbara
Zucker Foundation, USA; the Medical Research Council and the Wellcome
Trust Foundation, UK; the Research Council of Norway (Grant No.
163070/V50, 167153/V50); the South-Eastern Norway Health Authority
(123/2004); Science Foundation Ireland and Health Research Board,
Ireland; the Lundbeck Foundation and Danish National Advanced Technology
Foundation, Denmark). The Ashkenazi samples are part of the Hebrew
University Genetic Resource (HUGR). The principal investigators of the
CATIE trial were Jeffrey A Lieberman, T Scott Stroup and Joseph P
McEvoy. The CATIE trialwas funded by a grant from the National Institute
of Mental Health (N01 MH900001) along with MH074027 (PI PF Sullivan).
Genotyping was funded by Eli Lilly and Company. The principle
investigators for the MGS were Pablo Gejman and Douglas Levinson. MGS
study was supported by funding from the National Institute of Mental
Health and the National Alliance for Research on Schizophrenia and
Depression. Genotyping of part of the sample was supported by GAIN and
the Paul Michael Donovan Charitable Foundation. Genotyping was carried
out by the Center for Genotyping and Analysis at the Broad Institute of
Harvard and MIT with support from the National Center for Research
Resources.
NR 53
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U1 1
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD NOV
PY 2011
VL 16
IS 11
BP 1117
EP 1129
DI 10.1038/mp.2010.96
PG 13
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 840HD
UT WOS:000296429100011
PM 20838396
ER
PT J
AU Lukacs-Kornek, V
Malhotra, D
Fletcher, AL
Acton, SE
Elpek, KG
Tayalia, P
Collier, AR
Turley, SJ
AF Lukacs-Kornek, Veronika
Malhotra, Deepali
Fletcher, Anne L.
Acton, Sophie E.
Elpek, Kutlu G.
Tayalia, Prakriti
Collier, Ai-ris
Turley, Shannon J.
TI Regulated release of nitric oxide by nonhematopoietic stroma controls
expansion of the activated T cell pool in lymph nodes
SO NATURE IMMUNOLOGY
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; FIBROBLASTIC RETICULAR CELLS; INTERFERON-GAMMA;
IMMUNE-RESPONSES; ANTIGEN PRESENTATION; IFN-GAMMA; SYNTHASE; TOLERANCE;
HOMEOSTASIS; SELF
AB Fibroblastic reticular cells (FRCs) and lymphatic endothelial cells (LECs) are nonhematopoietic stromal cells of lymphoid organs. They influence the migration and homeostasis of naive T cells; however, their influence on activated T cells remains undescribed. Here we report that FRCs and LECs inhibited T cell proliferation through a tightly regulated mechanism dependent on nitric oxide synthase 2 (NOS2). Expression of NOS2 and production of nitric oxide paralleled the activation of T cells and required a tripartite synergism of interferon-gamma, tumor necrosis factor and direct contact with activated T cells. Notably, in vivo expression of NOS2 by FRCs and LECs regulated the size of the activated T cell pool. Our study elucidates an as-yet-unrecognized role for the lymph node stromal niche in controlling T cell responses.
C1 [Lukacs-Kornek, Veronika; Malhotra, Deepali; Fletcher, Anne L.; Acton, Sophie E.; Elpek, Kutlu G.; Collier, Ai-ris; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Malhotra, Deepali] Harvard Univ, Sch Med, Div Med Sci, Boston, MA USA.
[Tayalia, Prakriti] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Turley, Shannon J.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
RP Turley, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
EM shannon_turley@dfci.harvard.edu
RI Acton, Sophie/G-9784-2012;
OI Acton, Sophie/0000-0003-2704-716X; Malhotra, Deepali/0000-0002-8215-7639
FU US National Institutes of Health [R01 DK074500, P01 AI045757];
Dana-Farber Cancer Institute
FX We thank M. Curry for technical assistance at the Dana-Farber Cancer
Institute Flow Cytometry Core Facility; A. Sharpe (Harvard Medical
School) for PD-L1-deficient mice; L. Lefrancois (University of
Connecticut) for iFABP-tOVA mice; L.-H. Ang, Y. Zheng and S.J. Hagen for
technical assistance at the Imaging Microscopy Core of Beth Israel
Deaconess Medical Center; and J. Astarita and A. Bellemare-Pelletier for
critically reading the manuscript. Supported by the US National
Institutes of Health (R01 DK074500 and P01 AI045757 to S.J.T.) and the
Dana-Farber Cancer Institute (V.L.-K).
NR 50
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U1 5
U2 17
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD NOV
PY 2011
VL 12
IS 11
BP 1096
EP U105
DI 10.1038/ni.2112
PG 10
WC Immunology
SC Immunology
GA 841GG
UT WOS:000296500100015
PM 21926986
ER
PT J
AU Wesseling-Perry, K
Tsai, EW
Ettenger, RB
Juppner, H
Salusky, IB
AF Wesseling-Perry, Katherine
Tsai, Eileen W.
Ettenger, Robert B.
Jueppner, Harald
Salusky, Isidro B.
TI Mineral abnormalities and long-term graft function in pediatric renal
transplant recipients: a role for FGF-23?
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Article
DE acute rejection; FGF-23; indices of mineral metabolism; pediatric renal
transplantation; progression of renal failure
ID CHRONIC KIDNEY-DISEASE; VITAMIN-D STATUS; GLOMERULAR-FILTRATION-RATE;
GROWTH-HORMONE; CHILDREN; BONE; RATS; DEFICIENCY; FGF23
AB Background. Although current guidelines recommend the evaluation of mineral and bone metabolism in patients with all stages of chronic kidney disease (CKD), the prevalence of altered mineral ion homeostasis in the pediatric post-transplant population is unknown. Moreover, the contribution of abnormal mineral ion metabolism to graft outcomes in this population has not been evaluated.
Methods. Serum calcium, phosphorus, 25(OH) vitamin D, 1,25(OH)(2)vitamin D, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) levels were evaluated 4.9 +/- 0.5 years after transplantation in 68 stable pediatric renal allograft recipients. Patients were subsequently followed for 2 years.
Results. At baseline, mean estimated glomerular filtration rate (GFR) was 60 +/- 2 mL/min/1.73m(2). Serum calcium and phosphorus values were within the reference interval. PTH values were elevated but did not differ by CKD stage. 25(OH) vitamin D levels were low in nearly half of all subjects. Tubular reabsorption of phosphate and 1,25(OH)(2)vitamin D values were lower, while FGF-23 and PTH values were higher in more advanced stages of CKD. Thirty percent of patients with FGF-23 values >110 RU/mL had a decrease in GFR of >50% (P < 0.05) and FGF-23 values predicted future episodes of rejection.
Conclusions. Despite normal serum calcium and phosphorus levels in the majority of prevalent pediatric renal transplant recipients, abnormalities in PTH, 25(OH) vitamin D and FGF-23 are common. FGF-23 levels may be associated with increased risk for deterioration of kidney function and episodes of rejection.
C1 [Wesseling-Perry, Katherine; Tsai, Eileen W.; Ettenger, Robert B.; Salusky, Isidro B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Nephrol, Los Angeles, CA 90095 USA.
[Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA.
[Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA.
RP Wesseling-Perry, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Nephrol, Los Angeles, CA 90095 USA.
EM kwesseling@mednet.ucla.edu
FU USPHS [DK-67563, DK-35423, DK-51081, DK-073039, RR-00865]; National
Kidney Foundation; Casey Lee Ball Foundation
FX This work was supported in part by USPHS grants DK-67563, DK-35423,
DK-51081, DK-073039 and RR-00865; the National Kidney Foundation and
funds from the Casey Lee Ball Foundation.
NR 29
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Z9 19
U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD NOV
PY 2011
VL 26
IS 11
BP 3779
EP 3784
DI 10.1093/ndt/gfr126
PG 6
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA 839FH
UT WOS:000296350400057
PM 21441401
ER
PT J
AU Zuo, YT
Lu, HB
Vaupel, DB
Zhang, Y
Chefer, SI
Rea, WR
Moore, AV
Yang, YH
Stein, EA
AF Zuo, Yantao
Lu, Hanbing
Vaupel, D. Bruce
Zhang, Yi
Chefer, Svetlana I.
Rea, William R.
Moore, Anna V.
Yang, Yihong
Stein, Elliot A.
TI Acute Nicotine-Induced Tachyphylaxis Is Differentially Manifest in the
Limbic System
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE phMRI; nicotine; tolerance; relative cerebral blood volume
ID CEREBRAL-BLOOD-FLOW; ACETYLCHOLINE-RECEPTORS; RAT-BRAIN;
ALPHA-BUNGAROTOXIN; PHARMACOLOGICAL MRI; FUNCTIONAL MRI; CHOLINERGIC
MECHANISMS; DOPAMINE ANTAGONISTS; CIGARETTE-SMOKING; NEURONAL-ACTIVITY
AB Rapid tolerance develops to many of nicotine's behavioral and autonomic effects, A better understanding of the spatiotemporal patterns in neuronal activity as a consequence of acute nicotine tolerance (tachyphylaxis) may help explain its commonly found inverted 'U'-shaped biphasic dose-effect relationship on various behaviors. To this end, we employed high-resolution functional magnetic resonance imaging and relative cerebral blood volume (rCBV) as a marker of neuronal activity, to characterize the regional development of acute tolerance as a function of nicotine dose in naive, anesthetized rats. A single intravenous nicotine injection at 0.1 and 0.3, but not 0.03 mg/kg, significantly increased neuronal activity in many neocortical areas. In contrast, dose-dependent increases in rCBV were most pronounced in limbic regions, such that responses seen at 0.1 mg/kg nicotine in accumbens, hippocampus, amygdala, and several other limbic areas were not seen following 0.3 mg/kg nicotine. Finally, whereas profound tolerance was observed in many cortical regions after the second of two paired nicotine injections at either 0.1 or 0.3 mg/kg, subcortical limbic structures showed only a weak trend for tolerance. Lack of rCBV changes in animals receiving nicotine methiodide, a quaternary nicotine analog that does not cross the blood-brain barrier, supports a direct neuronal effect of nicotine rather than an action on the vasculature. These data provide pharmacodynamic insight into the regional heterogeneity of nicotine tachyphylaxis development, which may be relevant to behavioral and neurobiological mechanisms associated with repeated tobacco consumption. Neuropsychopharmacology (2011) 36, 2498-2512; doi:10.1038/npp.2011.139; published online 27 July 2011
C1 [Zuo, Yantao; Lu, Hanbing; Vaupel, D. Bruce; Chefer, Svetlana I.; Rea, William R.; Yang, Yihong; Stein, Elliot A.] NIDA, Intramural Res Program, Neuroimaging Res Branch, Baltimore, MD 21224 USA.
[Zhang, Yi] NIMH, Bethesda, MD 20892 USA.
[Moore, Anna V.] Massachusetts Gen Hosp, Dept Radiol, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA.
RP Stein, EA (reprint author), NIDA, Intramural Res Program, Neuroimaging Res Branch, 251 Bayview Blvd,Suite 200,Room 7A71 1A, Baltimore, MD 21224 USA.
EM estein@mail.nih.gov
FU US National Institutes of Health; National Institute on Drug Abuse;
Intramural Research Program
FX This research was funded by the US National Institutes of Health,
National Institute on Drug Abuse, and Intramural Research Program. We
thank Pradeep Kurup, MS and Tom Ross, PhD for their statistical
assistance.
NR 91
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U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD NOV
PY 2011
VL 36
IS 12
BP 2498
EP 2512
DI 10.1038/npp.2011.139
PG 15
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 835XS
UT WOS:000296070900014
PM 21796109
ER
PT J
AU Shen, Q
Duong, TQ
AF Shen, Qiang
Duong, Timothy Q.
TI Background suppression in arterial spin labeling MRI with a separate
neck labeling coil
SO NMR IN BIOMEDICINE
LA English
DT Article
DE arterial spin labeling; rodents; cerebral blood flow; cerebral
perfusion; high fields; inversion recovery
ID CEREBRAL-BLOOD-FLOW; TRANSIT-TIME; RAT-BRAIN; TISSUE WATER; PERFUSION;
DIFFUSION; INVERSION; ISCHEMIA; EXCHANGE; SIGNAL
AB In arterial spin labeling (ASL) MRI to measure cerebral blood flow (CBF), pair-wise subtraction of temporally adjacent non-labeled and labeled images often can not completely cancel the background static tissue signal because of temporally fluctuating physiological noise. While background suppression (BS) by inversion nulling improves CBF temporal stability, imperfect pulses compromise CBF contrast. Conventional BS techniques may not be applicable in small animals because the arterial transit time is short. This study presents a novel approach of BS to overcome these drawbacks using a separate 'neck' radiofrequency coil for ASL and a 'brain' radiofrequency coil for BS with the inversion pulse placed before spin labeling. The use of a separate 'neck' coil for ASL should also improve ASL contrast. This approach is referred to as the inversion-recovery BS with the two-coil continuous ASL (IR-cASL) technique. The temporal and spatial contrast-to-noise characteristics of basal CBF and CBF-based fMRI of hypercapnia and forepaw stimulation in rats at 7 Tesla were analyzed. IR-cASL yielded two times better temporal stability and 2.0-2.3 times higher functional contrast-to-noise ratios for hypercapnia and forepaw stimulation compared with cASL without BS in the same animals. The Bloch equations were modified to provide accurate CBF quantification at different levels of BS and for multislice acquisition where different slices have different degree of BS and residual degree of labeling. Improved basal CBF and CBF-based fMRI sensitivity should lead to more accurate CBF quantification and should prove useful for imaging low CBF conditions such as in white matter and stroke. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA.
[Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA.
[Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] Dept Vet Affairs, S Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Duong, TQ (reprint author), UTHSCSA, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM duongt@uthscsa.edu
RI Shen, Qiang/B-8784-2008; Duong, Timothy/B-8525-2008
OI Shen, Qiang/0000-0002-4287-3403;
FU NIH [R01-NS45879, R01EY014211, R01EY018855]; American Heart Association
[SDG-0430020N, SDG-0830293N]; VA MERIT award
FX This work was supported in part by the NIH (R01-NS45879, R01EY014211 and
R01EY018855), the American Heart Association (SDG-0430020N and
SDG-0830293N) and a VA MERIT award.
NR 33
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Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD NOV
PY 2011
VL 24
IS 9
BP 1111
EP 1118
DI 10.1002/nbm.1666
PG 8
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 840DT
UT WOS:000296419200011
PM 21294207
ER
PT J
AU Al-Safi, Z
Imudia, AN
Filetti, LC
Hobson, DT
Bahado-Singh, RO
Awonuga, AO
AF Al-Safi, Zain
Imudia, Anthony N.
Filetti, Lusia C.
Hobson, Deslyn T.
Bahado-Singh, Ray O.
Awonuga, Awoniyi O.
TI Delayed Postpartum Preeclampsia and Eclampsia Demographics, Clinical
Course, and Complications
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
AB OBJECTIVE: To estimate and evaluate the demographics, clinical course, and complications of delayed postpartum preeclampsia in patients with and without eclampsia.
METHODS: We conducted a retrospective cohort study of patients who were discharged and later readmitted with the diagnosis of delayed postpartum preeclampsia more than 2 days to 6 weeks or less after delivery between January 2003 and August 2009.
RESULTS: One hundred fifty-two patients met criteria for the diagnosis of delayed postpartum preeclampsia. Of these, 96 (63.2%) patients had no antecedent diagnosis of hypertensive disease in the current pregnancy, whereas seven (4.6%), 14 (9.2%), 28 (18.4%), and seven (4.6%) patients had gestational hypertension, chronic hypertension, preeclampsia, and preeclampsia superimposed on chronic hypertension, respectively, during the peripartum period. Twenty-two patients (14.5%) developed postpartum eclampsia, and more than 90% of these patients presented within 7 days after discharge from the hospital. The most common presenting symptom was headache in 105 (69.1%) patients. Patients who developed eclampsia were significantly younger than those who did not (mean +/- standard deviation, 23.2 +/- 6.2 compared with 28.3 +/- 6.7 years; adjusted odds ratio [OR] 1.13, 95% confidence interval [CI] 1.02-1.26, P=.03), and other demographic variables were no different. A lower readmission hemoglobin was associated with a lower odds of progression to eclampsia (10.7 +/- 1.7 compared with 11.6 +/- 2.2 g/dL, adjusted OR 0.75, 95% CI 0.57-0.98, P=.04).
CONCLUSION: One week after discharge appears to be a critical period for the development of postpartum eclampsia. Education about the possibility of delayed postpartum preeclampsia and eclampsia should occur after delivery, whether or not patients develop hypertensive disease before discharge from the hospital. (Obstet Gynecol 2011;118:1102-7) DOI: 10.1097/AOG.0b013e318231934c
C1 [Awonuga, Awoniyi O.] Wayne State Univ, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Sch Med,Detroit Med Ctr, Detroit, MI 48201 USA.
Massachusetts Gen Hosp, Div Reprod Med & Infertil, Boston, MA 02114 USA.
RP Awonuga, AO (reprint author), Wayne State Univ, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Sch Med,Detroit Med Ctr, 60 W Hancock, Detroit, MI 48201 USA.
EM aawonuga@med.wayne.edu
NR 14
TC 24
Z9 27
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD NOV
PY 2011
VL 118
IS 5
BP 1102
EP 1107
DI 10.1097/AOG.0b013e318231934c
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 838LK
UT WOS:000296292600019
PM 21979459
ER
PT J
AU Tracy, EE
AF Tracy, Erin E.
TI Three Is a Crowd The New Doctor-Patient-Policymaker Relationship
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID GAG RULE; POLITICS; VIOLENCE; SAFETY; FAMILY; WOMEN; RISK; HOME
AB A recent increase in legislative initiatives involving specific aspects of the practice of medicine is challenging traditional doctor-patient relationships. A Florida state law prohibiting physicians from asking patients about the presence of guns in the home could potentially result in real harm because of the risk of childhood injuries, domestic violence, suicide, and homicide. A number of states have specific language physicians are supposed to use when obtaining consent for pregnancy terminations. Some of these items required by law to be contained in the informed consent are not based on science, but instead on political beliefs. Other legislative initiatives involve issues as varied as hysterectomy consents, glomerular filtration rates, family planning, and palliative care. Laws that prohibit physicians from asking patients certain questions may be violating doctors' First Amendment rights. Laws mandating what information is contained in procedural consent forms and requiring certain scripts to be utilized may interfere with patients' ability to have accurate, unbiased, objective information to assist in their decision making. Physicians may be caught in the untenable position of balancing their professional and ethical obligations to their patients with their duty to obey the law as citizens. Physicians should be involved in legislative advocacy to try to prevent policy makers from legislating the practice of medicine. The American Congress of Obstetricians and Gynecologists' Committee on Ethics should consider review of this evolving issue. (Obstet Gynecol 2011;118:1164-8) DOI: 10.1097/AOG.0b013e31823188d6
C1 [Tracy, Erin E.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA.
RP Tracy, EE (reprint author), Gen Hosp, 55 Fruit St,406 Founders House, Boston, MA USA.
EM EETracy@partners.org
NR 27
TC 3
Z9 3
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD NOV
PY 2011
VL 118
IS 5
BP 1164
EP 1167
DI 10.1097/AOG.0b013e31823188d6
PG 4
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 838LK
UT WOS:000296292600028
PM 22015887
ER
PT J
AU Zimmermann, K
Lennerz, JK
Hein, A
Link, AS
Kaczmarek, JS
Delling, M
Uysal, S
Pfeifer, JD
Riccio, A
Clapham, DE
AF Zimmermann, Katharina
Lennerz, Jochen K.
Hein, Alexander
Link, Andrea S.
Kaczmarek, J. Stefan
Delling, Markus
Uysal, Serdar
Pfeifer, John D.
Riccio, Antonio
Clapham, David E.
TI Transient receptor potential cation channel, subfamily C, member 5
(TRPC5) is a cold-transducer in the peripheral nervous system
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE pain; single-fiber; thermo-transient receptor potential; nociception;
temperature sensing
ID ROOT GANGLION NEURONS; IN-VITRO; CAPSAICIN-RECEPTOR; NOXIOUS HEAT;
TRPM8; MOUSE; TEMPERATURES; MICE; STRAINS; DOMAIN
AB Detection and adaptation to cold temperature is crucial to survival. Cold sensing in the innocuous range of cold (> 10-15 degrees C) in the mammalian peripheral nervous system is thought to rely primarily on transient receptor potential (TRP) ion channels, most notably the menthol receptor, TRPM8. Here we report that TRP cation channel, subfamily C member 5 (TRPC5), but not TRPC1/TRPC5 heteromeric channels, are highly cold sensitive in the temperature range 37-25 degrees C. We found that TRPC5 is present in mouse and human sensory neurons of dorsal root ganglia, a substantial number of peripheral nerves including intraepithelial endings, and in the dorsal lamina of the spinal cord that receives sensory input from the skin, consistent with a potential TRPC5 function as an innocuous cold transducer in nociceptive and thermosensory nerve endings. Although deletion of TRPC5 in 129S1/SvImJ mice resulted in no temperature-sensitive behavioral changes, TRPM8 and/or other menthol-sensitive channels appear to underpin a much larger component of noxious cold sensing after TRPC5 deletion and a shift in mechanosensitive C-fiber subtypes. These findings demonstrate that highly cold-sensitive TRPC5 channels are a molecular component for detection and regional adaptation to cold temperatures in the peripheral nervous system that is distinct from noxious cold sensing.
C1 [Zimmermann, Katharina; Lennerz, Jochen K.; Hein, Alexander; Kaczmarek, J. Stefan; Delling, Markus; Uysal, Serdar; Riccio, Antonio; Clapham, David E.] Harvard Univ, Sch Med, Dept Cardiol, Manton Ctr Orphan Dis, Boston, MA 02115 USA.
[Zimmermann, Katharina; Kaczmarek, J. Stefan; Clapham, David E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Lennerz, Jochen K.; Pfeifer, John D.] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Lennerz, Jochen K.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02116 USA.
[Link, Andrea S.] Univ Erlangen Nurnberg, Dept Physiol & Pathophysiol, D-91054 Erlangen, Germany.
[Clapham, David E.] Harvard Univ, Howard Hughes Med Inst, Sch Med, Childrens Hosp, Boston, MA 02115 USA.
RP Clapham, DE (reprint author), Harvard Univ, Sch Med, Dept Cardiol, Manton Ctr Orphan Dis, Boston, MA 02115 USA.
EM dclapham@enders.tch.harvard.edu
RI Hein, Alexander/F-6999-2010;
OI Hein, Alexander/0000-0003-2601-3398; Zimmermann,
Katharina/0000-0003-2529-0692
FU National Institutes of Health [R01 MH090293-01, P30-HD18655]; German
Research Council [DFG Zi1172/1-1]
FX We thank B. Desai, P. Reeh, and J. N. Wood for discussions, D. Julius
and J. Siemens for TRPM8-deficient tissue samples, and H. Xu who first
noted that TRPC5 current decreases upon warming. We also thank A.
Watson, V. Layton, J. Hardges, O. Crisp, B. Henderson, K. Selle, D.
Leahart, K. Keith, and R. Brown for histotechnical assistance and G.
Krapivinsky, B. Zhou, J. Li, and C. Tyler for assistance with
immunohistochemistry. This work was funded by National Institutes of
Health Grant R01 MH090293-01. The Mental Retardation and Developmental
Disabilities Research Center Molecular Genetics Core Facility at
Children's Hospital Boston is supported by National Institutes of Health
Grant P30-HD18655. K.Z. was supported by German Research Council Grant
DFG Zi1172/1-1.
NR 47
TC 63
Z9 65
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 NOV 1
PY 2011
VL 108
IS 44
BP 18114
EP 18119
DI 10.1073/pnas.1115387108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 839NH
UT WOS:000296373400051
PM 22025699
ER
PT J
AU Sher, L
AF Sher, L.
TI Teaching medical professionals about suicide prevention: what's missing?
SO QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
LA English
DT Article
ID PSYCHIATRY RESIDENCY PROGRAMS; INPATIENT SUICIDE; CLINICAL-PSYCHOLOGY;
NATIONAL-SURVEY; DEPRESSION; PATIENT; RISK; HOSPITALIZATION;
INTERVENTION; ASSESSMENTS
C1 [Sher, L.] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA.
[Sher, L.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM leo.sher@mssm.edu
NR 43
TC 1
Z9 1
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1460-2725
EI 1460-2393
J9 QJM-INT J MED
JI QJM-An Int. J. Med.
PD NOV
PY 2011
VL 104
IS 11
BP 1005
EP 1008
DI 10.1093/qjmed/hcr125
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 839GX
UT WOS:000296354600018
PM 21824917
ER
PT J
AU Capitao, L
Sampaio, A
Sampaio, C
Vasconcelos, C
Fernandez, M
Garayzabal, E
Shenton, ME
Goncalves, OF
AF Capitao, Liliana
Sampaio, Adriana
Sampaio, Cassandra
Vasconcelos, Cristiana
Fernandez, Montse
Garayzabal, Elena
Shenton, Martha E.
Goncalves, Oscar F.
TI MRI amygdala volume in Williams Syndrome
SO RESEARCH IN DEVELOPMENTAL DISABILITIES
LA English
DT Article
DE Williams Syndrome; Hypersociability; Amygdala; Neurodevelopment
ID SOCIAL-BEHAVIOR; NEURAL BASIS; BRAIN; COGNITION; MEMORY; FEAR;
HYPERSOCIABILITY; APPROACHABILITY; ABNORMALITIES; HIPPOCAMPAL
AB One of the most intriguing characteristics of Williams Syndrome individuals is their hypersociability. The amygdala has been consistently implicated in the etiology of this social profile, particularly given its role in emotional and social behavior. This study examined amygdala volume and symmetry in WS individuals and in age and sex matched controls. Magnetic resonance imaging scans were obtained on a GE 1.5-T magnet with 1.5-mm contiguous slices and were used to measure whole gray matter, white matter and cerebrospinal fluid volumes, as well as amygdala volume (right and left). Results revealed significantly reduced intracranial volume in individuals with WS, compared with controls. There were no differences between groups in absolute amygdalae volume, although there was a relative increase in amygdalae volumes, when adjusted for total intracranial content. There were no inter-hemispheric differences in amygdalae volumes in both groups. These results suggest a relative increase in amygdala volume in WS compared with healthy controls that likely reflects abnormal neurodevelopmental processes of midline brain structures. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Capitao, Liliana; Sampaio, Adriana; Sampaio, Cassandra; Goncalves, Oscar F.] Univ Minho, Sch Psychol, Neuropsychophysiol Lab, CIPsi, P-4710057 Braga, Portugal.
[Vasconcelos, Cristiana] Hosp Geral Santo Antonio, Dept Neuroradiol, Oporto, Portugal.
[Fernandez, Montse] Univ Santiago de Compostela, Galician Publ Fdn Genom Med, Mol Genet Unit, Santiago De Compostela, Spain.
[Garayzabal, Elena] Univ Autonoma Madrid, Dept Linguist, Madrid, Spain.
[Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Dept Psychiat,Sch Med, Boston, MA 02115 USA.
[Shenton, Martha E.] Harvard Univ, Sch Med, Brockton, MA USA.
[Shenton, Martha E.] VA Boston Healthcare Syst, Dept Psychiat, Clin Neurosci Div, Lab Neurosci, Brockton, MA USA.
RP Sampaio, A (reprint author), Univ Minho, Sch Psychol, Neuropsychophysiol Lab, CIPsi, P-4710057 Braga, Portugal.
EM adriana.sampaio@psi.uminho.pt
RI Goncalves, Oscar/G-5278-2010; Sampaio, Adriana/C-8361-2011;
OI Goncalves, Oscar/0000-0003-2735-9155; Sampaio,
Adriana/0000-0001-7347-1282; , /0000-0002-7893-0289
NR 36
TC 13
Z9 14
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0891-4222
J9 RES DEV DISABIL
JI Res. Dev. Disabil.
PD NOV-DEC
PY 2011
VL 32
IS 6
BP 2767
EP 2772
DI 10.1016/j.ridd.2011.05.033
PG 6
WC Education, Special; Rehabilitation
SC Education & Educational Research; Rehabilitation
GA 838PF
UT WOS:000296304000086
PM 21752593
ER
PT J
AU Baker, JF
George, M
Baker, DG
Toedter, G
Von Feldt, JM
Leonard, MB
AF Baker, Joshua F.
George, Michael
Baker, Daniel G.
Toedter, Gary
Von Feldt, Joan M.
Leonard, Mary B.
TI Associations between body mass, radiographic joint damage, adipokines
and risk factors for bone loss in rheumatoid arthritis
SO RHEUMATOLOGY
LA English
DT Article
DE Rheumatoid arthritis; Body mass index; Erosion; Disease activity;
Adipokines; Adiponectin
ID SERUM CREATININE; PLASMA-LEVELS; ADIPONECTIN; INDEX; OSTEOPOROSIS;
DESTRUCTION; ANTIBODY; OBESITY; LEPTIN; WOMEN
AB Objective. To evaluate the association between BMI and radiographic joint damage (RJD) in RA.
Methods. van der Heijde-Sharp (vdHS) erosion scores were determined in 499 participants with RA, ages 18-85 years, while enrolled in a clinical trial of golimumab (GO-BEFORE trial). Subjects were MTX and biologic therapy naive. Multivariable logistic regressions determined the odds of prevalent RJD (defined as vdHS score > 10) according to BMI category. Longitudinal analyses evaluated the association between BMI category and progression of vdHS score over 52 weeks. Analyses in a subset of 100 participants examined the association between adipokines and vdHS scores.
Results. At enrolment and 52 weeks, 37.6 and 43.6% of participants had RJD. Compared with normal weight, obese subjects had lower odds of RJD [0.40 (95% CI 0.22, 0.74); P = 0.003], and underweight subjects had greater odds [3.86 (95% CI 1.66, 9.00); P = 0.002] at baseline, adjusted for demographic and disease characteristics. The baseline associations between BMI category and RJD were greater among participants with multiple risk factors for bone loss (female > 50 years, smoking, glucocorticoid exposure and vitamin D deficiency); test for interaction P = 0.05. Adjustment for adiponectin levels did not attenuate the association between BMI and vdHS scores. Baseline BMI and change in weight did not independently predict radiographic progression (P > 0.1).
Conclusions. Higher BMI was independently associated with less RJD and was greatest in participants with risk factors for bone loss. Future studies are needed to examine the associations between RJD, obesity, weight loss and osteoporosis.
C1 [Baker, Joshua F.; George, Michael] Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA.
[Baker, Daniel G.] Centocor Res & Dev, Clin Immunol, Malvern, PA USA.
[Leonard, Mary B.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Toedter, Gary] Centocor Res & Dev, Biomarker, Malvern, PA USA.
[Von Feldt, Joan M.] Vet Affairs Med Ctr, Div Rheumatol, Philadelphia, PA USA.
[Leonard, Mary B.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
RP Baker, JF (reprint author), Hosp Univ Penn, Dept Med, Div Rheumatol, 8 Penn Tower Bldg,34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM bakerjo@uphs.upenn.edu
NR 29
TC 20
Z9 20
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-0324
EI 1462-0332
J9 RHEUMATOLOGY
JI RHEUMATOLOGY
PD NOV
PY 2011
VL 50
IS 11
BP 2100
EP 2107
DI 10.1093/rheumatology/ker294
PG 8
WC Rheumatology
SC Rheumatology
GA 838MH
UT WOS:000296295800025
PM 21890621
ER
PT J
AU Kim, MC
Kim, KH
Jung, GJ
Rattner, DW
AF Kim, Min-Chan
Kim, Ki-Han
Jung, Ghap Joong
Rattner, David W.
TI Comparative Study of Complete and Partial Omentectomy in Radical
Subtotal Gastrectomy for Early Gastric Cancer
SO YONSEI MEDICAL JOURNAL
LA English
DT Article
DE Partial omentectomy; gastric cancer; post-operative outcome; comparative
study
ID LAPAROSCOPY-ASSISTED GASTRECTOMY; DISTAL GASTRECTOMY; MULTICENTER;
SURGERY; NODE; LYMPHADENECTOMY; COMPLICATIONS; GUIDELINES; MORBIDITY;
MORTALITY
AB Purpose: Curative surgery for patients with advanced or even early gastric cancer can be defined as resection of the stomach and dissection of the first and second level lymph nodes, including the greater omentum. The aim of this study was to evaluate the short- and long- term outcomes of partial omentectomy (PO) as compared with complete omentectomy (CO). Materials and Methods: Seventeen consecutive open distal gastrectomies with POs were initially performed between February and July in 2006. The patients' clinicopathologic data and post-operative outcomes were retrospectively compared with 20 patients who underwent open distal gastrectomies with COs for early gastric cancer in 2005. Results: The operation time in PO group was significantly shorter than that in CO group (142.4 minutes vs. 165.0 minutes, p=0.018). The serum albumin concentration on the first post-operative day in PO group was significantly higher than CO group (3.8 g/dL vs. 3.5 g/dL, p=0.018). Three postoperative minor complications were successfully managed with conservative treatment. Median follow-up period between PO and CO was 38.1 and 37.7 months. All patients were alive without recurrence until December 30, 2009. Conclusion: PO during open radical distal gastrectomy can be considered a more useful procedure than CO for treating early gastric cancer. To document the long-term technical and oncologic safety of this procedure, a large-scale prospective randomized trial will be needed.
C1 [Kim, Min-Chan; Kim, Ki-Han; Jung, Ghap Joong] Dong A Univ, Coll Med, Dept Surg, Pusan 602715, South Korea.
[Rattner, David W.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Kim, MC (reprint author), Dong A Univ, Coll Med, Dept Surg, 1 Dongdaesin Dong 3 Ga, Pusan 602715, South Korea.
EM mckim@donga.ac.kr
FU Dong-A University
FX This work was supported by the Dong-A University Research Fund in 2007.
NR 35
TC 10
Z9 12
U1 0
U2 3
PU YONSEI UNIV COLLEGE MEDICINE
PI SEOUL
PA IN-HONG CHOI, MD, PH D, 250 SEONGSAN-RO, SEODAEMUN-GU, SEOUL 120-752,
SOUTH KOREA
SN 0513-5796
J9 YONSEI MED J
JI Yonsei Med. J.
PD NOV 1
PY 2011
VL 52
IS 6
BP 961
EP 966
DI 10.3349/ymj.2011.52.6.961
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 838PQ
UT WOS:000296305100012
PM 22028160
ER
PT J
AU Bartosch, C
Lopes, JM
Oliva, E
AF Bartosch, Carla
Lopes, Jose Manuel
Oliva, Esther
TI Endometrial Carcinomas: A Review Emphasizing Overlapping and Distinctive
Morphological and Immunohistochemical Features
SO ADVANCES IN ANATOMIC PATHOLOGY
LA English
DT Review
DE uterus; endometrium; endometrial carcinoma; endometrioid; serous; clear
cell; dedifferentiated; malignant mixed mullerian; lynch-related
ID FEMALE GENITAL-TRACT; OF-THE-LITERATURE; UTERINE SEROUS CARCINOMA;
CLEAR-CELL CARCINOMA; GYNECOLOGIC-ONCOLOGY-GROUP; SMOOTH-MUSCLE TUMORS;
NONPOLYPOSIS COLORECTAL-CANCER; METASTATIC BREAST-CARCINOMA; MIXED
MULLERIAN TUMORS; E-CADHERIN EXPRESSION
AB This review focuses on the most common diagnostic pitfalls and helpful morphologic and immunohistochemical markers in the differential diagnosis between the different subtypes of endometrial carcinomas, including: (1) endometrioid versus serous glandular carcinoma, (2) papillary endometrioid (not otherwise specified, villoglandular and nonvillous variants) versus serous carcinoma, (3) endometrioid carcinoma with spindle cells, hyalinization, and heterologous components versus malignant mixed mullerian tumor, (4) high-grade endometrioid versus serous carcinoma, (5) high-grade endometrioid carcinoma versus dedifferentiated or undifferentiated carcinoma, (6) endometrioid carcinoma with clear cells versus clear cell carcinoma, (7) clear cell versus serous carcinoma, (8) undifferentiated versus neuroendocrine carcinoma, (9) carcinoma of mixed cell types versus carcinoma with ambiguous features or variant morphology, (10) Lynch syndrome-related endometrial carcinomas, (11) high-grade or undifferentiated carcinoma versus nonepithelial uterine tumors. As carcinomas in the endometrium are not always primary, this review also discusses the differential diagnosis between endometrial carcinomas and other gynecological malignancies such as endocervical (glandular) and ovarian/peritoneal serous carcinoma, as well as with extra-gynecologic metastases (mainly breast and colon).
C1 [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Oliva, Esther] Harvard Univ, Sch Med, Boston, MA USA.
[Bartosch, Carla; Lopes, Jose Manuel] Univ Porto IPATIMUP, Ctr Hosp S Joao, Oporto, Portugal.
[Lopes, Jose Manuel] Univ Porto IPATIMUP, Fac Med, Oporto, Portugal.
[Lopes, Jose Manuel] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Oporto, Portugal.
RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA.
EM eoliva@partners.org
RI Lopes, Jose Manuel/J-7428-2013;
OI Lopes, Jose Manuel/0000-0001-8597-3474; Bartosch,
Carla/0000-0003-0646-7667
NR 248
TC 28
Z9 31
U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-4109
J9 ADV ANAT PATHOL
JI Adv. Anat. Pathol.
PD NOV
PY 2011
VL 18
IS 6
BP 415
EP 437
DI 10.1097/PAP.0b013e318234ab18
PG 23
WC Pathology
SC Pathology
GA 836WO
UT WOS:000296148200001
PM 21993268
ER
PT J
AU Barcena, C
Oliva, E
AF Barcena, Carmen
Oliva, Esther
TI WT1 Expression in the Female Genital Tract
SO ADVANCES IN ANATOMIC PATHOLOGY
LA English
DT Review
DE WT1; female genital tract; differential diagnosis; immunohistochemistry
ID WILMS-TUMOR GENE; TRANSITIONAL-CELL-CARCINOMA; CORD-STROMAL TUMORS;
SMOOTH-MUSCLE TUMORS; INVASIVE MICROPAPILLARY CARCINOMA; EPITHELIAL
MEMBRANE ANTIGEN; OVARIAN SEROUS CARCINOMAS; ENDOMETRIOID GLANDULAR
DIFFERENTIATION; PRIMITIVE NEUROECTODERMAL TUMOR; MULLERIAN MIXED TUMORS
AB The Wilms tumor gene 1 (WT1) has been reported in normal tissues and many neoplasms of the female genital tract. This review discusses WT1 expression in the female genital tract and its potential utility in the differential diagnosis of neoplasms that occur at this location. WT1 is of value in the differential diagnosis of synchronous serous carcinomas arising in the ovary/fallopian tube/peritoneum and endometrium, as strong WT1 positivity in both tumors points toward an extrauterine origin. In addition, WT1 can be used to distinguish sex cord stromal tumors (WT1 positive) from endometrioid carcinomas (OECs). WT1 expression is not helpful in the differential diagnosis of ovarian serous carcinomas (OSCs) and transitional carcinomas, as both are typically positive and has limited value in the distinction of serous tumors arising in the ovary/fallopian tube/peritoneum from mesotheliomas. WT1 is also not helpful to differentiate small cell carcinoma of hypercalcemic type from juvenile granulosa cell tumor, a common diagnostic problem. Intra-abdominal desmoplastic round cell tumor reacts to WT1 (C-terminal) in contrast to all other tumors discussed which helps to separate this rare tumor from most other small round cell tumors that may involve, primarily or secondarily, the ovary with the exception of small cell carcinoma of hypercalcemic type that typically reacts with the N-terminal of WT1.
C1 [Barcena, Carmen; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA.
EM eoliva@partners.org
NR 205
TC 18
Z9 19
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-4109
J9 ADV ANAT PATHOL
JI Adv. Anat. Pathol.
PD NOV
PY 2011
VL 18
IS 6
BP 454
EP 465
DI 10.1097/PAP.0b013e318234aaed
PG 12
WC Pathology
SC Pathology
GA 836WO
UT WOS:000296148200005
PM 21993272
ER
PT J
AU Proeschold-Bell, RJ
Hoeppner, B
Taylor, B
Cohen, S
Blouin, R
Stringfield, B
Muir, AJ
AF Proeschold-Bell, Rae Jean
Hoeppner, Bettina
Taylor, Baishakhi
Cohen, Sarah
Blouin, Rachel
Stringfield, Beth
Muir, Andrew J.
TI An Interrupted Time Series Evaluation of a Hepatitis C Intervention for
Persons with HIV
SO AIDS AND BEHAVIOR
LA English
DT Article
DE HIV; Hepatitis C; Intervention research; Prevention; Interrupted Time
Series
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; SEXUAL
TRANSMISSION; INFECTED PATIENTS; NATURAL-HISTORY; LIVER-DISEASE;
UNITED-STATES; KNOWLEDGE; PREVALENCE; MORTALITY
AB Accurate HCV knowledge is lacking among high-risk groups, including people with HIV/AIDS (PLWHA). Liver disease primarily due to HCV has emerged as a serious cause of mortality among PLWHA. We used an Interrupted Time Series design to evaluate a social-ecologically based intervention for PLWHA, where an infectious disease clinic serving a six-county intervention area was monitored before (7 months) and after (17 months) intervention onset. The intervention included education of PLWHA and medical providers, HIV/HCV support groups, and adaptation of the patient chart top sheet to include HCV test information. Clinic-level outcomes were assessed prospectively every other week for 2 years by interviewing patients (n = 259) with clinic appointments on assessment days. Abrupt, gradual and delayed intervention effects were tested. Weighted regression analyses showed higher average HCV knowledge and a higher prevalence of patients reporting HCV discussion with their medical providers after intervention onset. A delayed effect was found for HCV awareness, and a gradually increasing effect was found for knowing one's HCV status. Other communities may consider adopting this intervention. Additional HCV interventions for PLWHA with HIV are needed.
C1 [Proeschold-Bell, Rae Jean] Duke Univ, Ctr Hlth Policy, Global Hlth Inst, Durham, NC 27708 USA.
[Hoeppner, Bettina] Harvard Univ, Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02115 USA.
[Taylor, Baishakhi] Duke Univ, N Carolina Consortium S Asian Studies, Durham, NC USA.
[Cohen, Sarah; Blouin, Rachel] Duke Univ, Duke Hlth Inequal Program, Durham, NC USA.
[Stringfield, Beth] Duke Univ, Ctr Hlth Policy, Piedmont HIV Hlth Care Consortium, Durham, NC USA.
[Muir, Andrew J.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
RP Proeschold-Bell, RJ (reprint author), Duke Univ, Ctr Hlth Policy, Global Hlth Inst, Box 90392, Durham, NC 27708 USA.
EM Rae.jean@duke.edu
FU NIDA NIH HHS [L30 DA025511, K01 DA027097]
NR 38
TC 5
Z9 5
U1 0
U2 7
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS Behav.
PD NOV
PY 2011
VL 15
IS 8
BP 1721
EP 1731
DI 10.1007/s10461-010-9870-1
PG 11
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 831MN
UT WOS:000295735200014
PM 21191643
ER
PT J
AU Becker, BW
Thames, AD
Woo, E
Castellon, SA
Hinkin, CH
AF Becker, Brian W.
Thames, April D.
Woo, Ellen
Castellon, Steven A.
Hinkin, Charles H.
TI Longitudinal Change in Cognitive Function and Medication Adherence in
HIV-Infected Adults
SO AIDS AND BEHAVIOR
LA English
DT Article
DE HIV; Medication adherence; HAART; Cognitive decline; Memory
ID ANTIRETROVIRAL THERAPY; NEUROPSYCHOLOGICAL PERFORMANCE; PROSPECTIVE
MEMORY; DRUG-RESISTANCE; VIRAL LOAD; COHORT; HAART; INDIVIDUALS;
IMPAIRMENT; PREDICTORS
AB Neuropsychological (NP) dysfunction has been linked to poor medication adherence among HIV-infected adults. However, there is a dearth of research examining longitudinal changes in the relationship between NP status and adherence rates. We hypothesized that declines in NP functioning would be associated with a corresponding decline in medication adherence while stable NP functioning would be associated with stable or improving adherence rates. Participants included 215 HIV-infected adults who underwent cognitive testing at study entry and six months later. Compared to the NP stable group, the NP decline group showed a greater drop in adherence rates. Further analysis revealed that, beyond global NP, learning and memory was significantly associated with changes in adherence rates. These findings further support the link between cognitive functioning and medication adherence and illustrates the importance of documenting changes in cognitive abilities for identifying individuals at risk for poor adherence.
C1 [Becker, Brian W.; Castellon, Steven A.; Hinkin, Charles H.] VA Greater Angeles Hlth Care Syst, Neuropsychol Lab 256, Los Angeles, CA 90073 USA.
[Becker, Brian W.; Thames, April D.; Woo, Ellen; Castellon, Steven A.; Hinkin, Charles H.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Becker, BW (reprint author), VA Greater Angeles Hlth Care Syst, Neuropsychol Lab 256, 11301 Wilshire, Los Angeles, CA 90073 USA.
EM brian.becker@va.gov
RI Thames, April/K-1964-2014
OI Thames, April/0000-0001-8414-7189
FU NIDA NIH HHS [R01 DA013799, R01 DA13799]; NIMH NIH HHS [R25 MH080663,
T32 MH019535, T32 MH19535]
NR 27
TC 30
Z9 30
U1 0
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS Behav.
PD NOV
PY 2011
VL 15
IS 8
BP 1888
EP 1894
DI 10.1007/s10461-011-9924-z
PG 7
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 831MN
UT WOS:000295735200030
PM 21437726
ER
PT J
AU Ix, JH
Biggs, ML
Kizer, JR
Mukamal, KJ
Djousse, L
Zieman, SJ
de Boer, IH
Nelson, TL
Newman, AB
Criqui, MH
Siscovick, DS
AF Ix, Joachim H.
Biggs, Mary L.
Kizer, Jorge R.
Mukamal, Kenneth J.
Djousse, Luc
Zieman, Susan J.
de Boer, Ian H.
Nelson, Tracy L.
Newman, Anne B.
Criqui, Michael H.
Siscovick, David S.
TI Association of Body Mass Index With Peripheral Arterial Disease in Older
Adults
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE ankle brachial index; body mass index; cardiovascular diseases;
peripheral arterial disease
ID CARDIOVASCULAR RISK-FACTORS; ANKLE BRACHIAL INDEX; INTERMITTENT
CLAUDICATION; ARM INDEX; PREVALENCE; HEALTH; MORTALITY; ATHEROSCLEROSIS;
POPULATION; SMOKING
AB The authors hypothesized that the absence of cross-sectional associations of body mass index (BMI; weight (kg)/height (m)(2)) with peripheral arterial disease (PAD) in prior studies may reflect lower weight among persons who smoke or have poor health status. They conducted an observational study among 5,419 noninstitutionalized residents of 4 US communities aged >= 65 years at baseline (1989-1990 or 1992-1993). Ankle brachial index was measured, and participants reported their history of PAD procedures. Participants were followed longitudinally for adjudicated incident PAD events. At baseline, mean BMI was 26.6 (standard deviation, 4.6), and 776 participants (14%) had prevalent PAD. During 13.2 (median) years of follow-up through June 30, 2007, 276 incident PAD events occurred. In cross-sectional analysis, each 5-unit increase in BMI was inversely associated with PAD (prevalence ratio (PR) = 0.92, 95% confidence interval (CI): 0.85, 1.00). However, among persons in good health who had never smoked, the direction of association was opposite (PR = 1.20, 95% CI: 0.94, 1.52). Similar results were observed between BMI calculated using weight at age 50 years and PAD prevalence (PR = 1.30, 95% CI: 1.11, 1.51) and between BMI at baseline and incident PAD events occurring during follow-up (hazard ratio = 1.32, 95% CI: 1.00, 1.76) among never smokers in good health. Greater BMI is associated with PAD in older persons who remain healthy and have never smoked. Normal weight maintenance may decrease PAD incidence and associated comorbidity in older age.
C1 [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA 92161 USA.
[Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, Dept Med, Sch Med, San Diego, CA 92161 USA.
[Ix, Joachim H.; Criqui, Michael H.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent Med, Sch Med, San Diego, CA 92161 USA.
[Biggs, Mary L.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Siscovick, David S.] Univ Washington, Sch Publ Hlth, Dept Med, Seattle, WA 98195 USA.
[Siscovick, David S.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Kizer, Jorge R.] Cornell Univ, Dept Med, Weill Med Coll, New York, NY 10021 USA.
[Kizer, Jorge R.] Cornell Univ, Dept Publ Hlth, Weill Med Coll, New York, NY 10021 USA.
[Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Mukamal, Kenneth J.] Harvard Univ, Sch Med, Boston, MA USA.
[Djousse, Luc] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging, Boston, MA USA.
[Djousse, Luc] Boston VA Healthcare Syst, Boston, MA USA.
[Zieman, Susan J.] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr, Baltimore, MD 21205 USA.
[Zieman, Susan J.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[de Boer, Ian H.] Univ Washington, Sch Med, Dept Med, Kidney Res Inst,Div Nephrol, Seattle, WA 98195 USA.
[Nelson, Tracy L.] Colorado State Univ, Colorado Sch Publ Hlth, Coll Appl Human Sci, Ft Collins, CO 80523 USA.
[Nelson, Tracy L.] Colorado State Univ, Dept Hlth & Exercise Sci, Coll Appl Human Sci, Ft Collins, CO 80523 USA.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Criqui, Michael H.] Univ Calif San Diego, Div Cardiol, Dept Med, Sch Med, San Diego, CA 92161 USA.
RP Ix, JH (reprint author), Univ Calif San Diego, Div Nephrol & Hypertens, Dept Med, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA.
EM joeix@ucsd.edu
RI Newman, Anne/C-6408-2013; Djousse, Luc/F-5033-2017
OI Newman, Anne/0000-0002-0106-1150; Djousse, Luc/0000-0002-9902-3047
FU National Heart, Lung, and Blood Institute [R01 HL094555, N01 HC-85079,
N01HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01 HC-75150, N01
HC-54133, N01-HC-80007, U01 HL080295]; National Institute of
Neurological Disorders and Stroke; VA San Diego Healthcare System
FX This publication was supported by grant R01 HL094555 from the National
Heart, Lung, and Blood Institute (to Drs. Ix, Kizer, Mukamal, Djousse,
and Zieman). The Cardiovascular Health Study was supported by contracts
N01 HC-85079 through N01HC-85086, N01-HC-35129, N01 HC-15103, N01
HC-55222, N01 HC-75150, N01 HC-54133, and N01-HC-80007 and grant U01
HL080295 from the National Heart, Lung, and Blood Institute, with
additional contributions from the National Institute of Neurological
Disorders and Stroke. The current study was partly supported by the VA
San Diego Healthcare System.
NR 31
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U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD NOV 1
PY 2011
VL 174
IS 9
BP 1036
EP 1043
DI 10.1093/aje/kwr228
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 836EW
UT WOS:000296093800006
PM 21920948
ER
PT J
AU Toosi, KK
Impink, BG
Baker, NA
Boninger, ML
AF Toosi, Kevin K.
Impink, Bradley G.
Baker, Nancy A.
Boninger, Michael L.
TI Effects of Computer Keyboarding on Ultrasonographic Measures of the
Median Nerve
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Article
DE carpal tunnel syndrome; computer keyboarding; median nerve;
ultrasonography; ultrasound
ID CARPAL-TUNNEL-SYNDROME; CUMULATIVE TRAUMA DISORDERS; MUSCULOSKELETAL
DISORDERS; RISK-FACTORS; GENERAL-POPULATION; UPPER EXTREMITY; OFFICE
WORKERS; SONOGRAPHY; DIAGNOSIS; WRIST
AB Background Keyboarding is a highly repetitive daily task and has been linked to musculoskeletal disorders of the upper extremity. However, the effect of keyboarding on median nerve injuries is not well understood. The purpose of this study was to use ultrasonographic measurements to determine whether continuous keyboarding can cause acute changes in the median nerve.
Methods Ultrasound images of the median nerve from 21 volunteers were captured at the levels of the pisiform and distal radius prior to and following a prolonged keyboarding task (i.e., 1 hr of continuous keyboarding). Images were analyzed by a blinded investigator to quantify the median nerve characteristics. Changes in the median nerve ultrasonographic measures as a result of continuous keyboarding task were evaluated.
Results Cross-sectional areas at the pisiform level were significantly larger in both dominant (P = 0.004) and non-dominant (P = 0.001) hands following the keyboarding task. Swelling ratio was significantly greater in the dominant hand (P = 0.020) after 60 min of keyboarding when compared to the baseline measures. Flattening ratios were not significantly different in either hand as a result of keyboarding.
Conclusion We were able to detect an acute increase in the area of the median nerve following 1 hr of keyboarding with a computer keyboard. This suggests that keyboarding has an impact on the median nerve. Further studies are required to understand this relationship, which would provide insight into the pathophysiology of median neuropathies such as carpal tunnel syndrome. Am. J. Ind. Med. 54:826-833, 2011. (C) 2011 Wiley Periodicals, Inc.
C1 [Toosi, Kevin K.; Impink, Bradley G.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Pittsburgh, PA 15206 USA.
[Toosi, Kevin K.; Impink, Bradley G.; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA.
[Toosi, Kevin K.; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA.
[Baker, Nancy A.] Univ Pittsburgh, Dept Occupat Therapy, Pittsburgh, PA USA.
RP Boninger, ML (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, 7180 Highland Dr 151R1-H,Bldg 4,2nd Floor,East Wi, Pittsburgh, PA 15206 USA.
EM boninger@pitt.edu
OI Boninger, Michael/0000-0001-6966-919X
FU U.S. Department of Veterans Affairs [B3142C]; National Institutes of
Health [T32HD049307]
FX This material is the result of work supported with resources and the use
of facilities at the Human Engineering Research Laboratories, VA
Pittsburgh Healthcare System. This study was supported by the U.S.
Department of Veterans Affairs (B3142C) and the National Institutes of
Health (T32HD049307). The contents of this paper do not represent the
views of the Department of Veterans Affairs or the United States
Government.
NR 40
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U1 0
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0271-3586
J9 AM J IND MED
JI Am. J. Ind. Med.
PD NOV
PY 2011
VL 54
IS 11
BP 826
EP 833
DI 10.1002/ajim.20983
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 837YF
UT WOS:000296248400003
PM 21739468
ER
PT J
AU van Blitterswijk, M
Gulati, S
Smoot, E
Jaffa, M
Maher, N
Hyman, BT
Ivinson, AJ
Scherzer, CR
Schoenfeld, DA
Cudkowicz, ME
Brown, RH
Bosco, DA
AF van Blitterswijk, Marka
Gulati, Sunita
Smoot, Elizabeth
Jaffa, Matthew
Maher, Nancy
Hyman, Bradley T.
Ivinson, Adrian J.
Scherzer, Clemens R.
Schoenfeld, David A.
Cudkowicz, Merit E.
Brown, Robert H., Jr.
Bosco, Daryl A.
TI Anti-superoxide dismutase antibodies are associated with survival in
patients with sporadic amyotrophic lateral sclerosis
SO AMYOTROPHIC LATERAL SCLEROSIS
LA English
DT Article
DE Sporadic amyotrophic lateral sclerosis; superoxide dismutase;
immunotherapy; Parkinson's disease; Alzheimer's disease
ID NEISSERIA-GONORRHOEAE; SPINAL-CORD; MUTANT SOD1; WILD-TYPE; MOTOR
CORTEX; ALS PATIENTS; IGG; IMMUNOGLOBULIN; MICE; QUANTITATION
AB Our objective was to test the hypothesis that aberrantly modified forms of superoxide dismutase (SOD1) influence the disease course for sporadic amyotrophic lateral sclerosis (SALS). We probed for anti-SOD1 antibodies (IgM and IgG) against both the normal and aberrantly oxidized-SOD1 (SODox) antigens in sera from patients with SALS, subjects diagnosed with other neurological disorders and healthy individuals, and correlated the levels of these antibodies to disease duration and/or severity. Anti-SOD1 antibodies were detected in all cohorts; however, a subset of similar to 5-10% of SALS cases exhibited elevated levels of anti-SOD1 antibodies. Those SALS cases with relatively high levels of IgM antibodies against SODox exhibit a longer survival of 6.4 years, compared to subjects lacking these antibodies. By contrast, SALS subjects expressing higher levels of IgG antibodies reactive for the normal WT-SOD1 antigen exhibit a shorter survival of 4.1 years. Anti-SOD1 antibody levels did not correlate with disease severity in either the Alzheimer's or Parkinson's disease cohorts. In conclusion, the association of longer survival with elevated levels of anti-SODox antibodies suggests that these antibodies may be protective. By extension, these data implicate aberrantly modified forms of WT-SOD1 (e. g. oxidized SOD1) in SALS pathogenesis. In contrast, an immune response against the normal WT-SOD1 appears to be disadvantageous in SALS, possibly because the anti-oxidizing activity of normal WT-SOD1 is beneficial to SALS individuals.
C1 [Bosco, Daryl A.] Univ Massachusetts, Med Ctr, Dept Neurol, LRB, Worcester, MA 01655 USA.
[Gulati, Sunita] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01655 USA.
[Smoot, Elizabeth; Schoenfeld, David A.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA.
[Jaffa, Matthew; Cudkowicz, Merit E.] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA USA.
[Maher, Nancy] Brigham & Womens Hosp, Harvard NeuroDiscovery Biomarker Program, Cambridge, MA USA.
[Hyman, Bradley T.; Ivinson, Adrian J.; Scherzer, Clemens R.] Harvard Univ, Sch Med, Harvard NeuroDiscovery Ctr Biomarker Program, Cambridge, MA 02138 USA.
[Scherzer, Clemens R.] Brigham & Womens Hosp, Ctr Neurol Dis, Cambridge, MA USA.
RP Bosco, DA (reprint author), Univ Massachusetts, Med Ctr, Dept Neurol, LRB, Room 603,364 Plantat Dr, Worcester, MA 01655 USA.
EM Daryl.Bosco@umassmed.edu
RI van Blitterswijk, Marka/H-7274-2012
OI van Blitterswijk, Marka/0000-0002-3054-7053
FU ALS Therapy Alliance-CVS Pharmacy; ALS Association; US National
Institutes of Health; National Institute on Neurological Disorders and
Stroke; Angel Fund; Project ALS
FX We thank Anne Hunt and the Eunice Kennedy Shriver Center at the
University of Massachusetts Medical School (UMMS) for statistical
analyses, the UMMS Proteomic and Mass spectrometry Core facility at
UMMS, the Northeast ALS Consortium and the Neurology Clinical Trial Unit
for contributing sera samples. We acknowledge financial support from the
ALS Therapy Alliance-CVS Pharmacy (D. A. B.), the ALS Association (D. A.
B., and R. H. B. Jr), the US National Institutes of Health (D. A. B.
(National Institute on Neurological Disorders and Stroke)), R. H. B. Jr
(National Institute on Neurological Disorders and Stroke), the Angel
Fund (R. H. B. Jr) and Project ALS (R.H.B. Jr).
NR 39
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U1 0
U2 7
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1748-2968
J9 AMYOTROPH LATERAL SC
JI Amyotroph. Lateral. Scler.
PD NOV
PY 2011
VL 12
IS 6
BP 430
EP 438
DI 10.3109/17482968.2011.585163
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 837AJ
UT WOS:000296162500006
PM 22023190
ER
PT J
AU Schneider, BC
Lichtenberg, PA
AF Schneider, Brooke C.
Lichtenberg, Peter A.
TI Influence of Reading Ability on Neuropsychological Performance in
African American Elders
SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY
LA English
DT Article
DE Assessment; Elderly; Geriatrics; Aging; Norms; Normative studies
ID NORMATIVE DATA; OLDER-ADULTS; LEVEL; EDUCATION; ACCULTURATION;
IMPAIRMENT; DEMENTIA; NORMS
AB Use of normative data stratified by education may result in misclassification of African American older adults because reading ability, an estimate of educational attainment, is lower than reported years of education for some African American elders. This study examined the contribution of reading ability versus education to neuropsychological test performance in 86 community-dwelling African American elders ages 56-91 with 8-18 years of education. Hierarchical multiple regression analyses revealed that reading ability, but not education, was significantly associated with performances on the Trail Making Test, Controlled Oral Word Association Test, Animal Naming, Digit Span, and the Stroop test. Reading ability was not significantly related to performances on measures of memory. Medium to large effect sizes (Cohen's d = 0.58-1.41) were found when comparing mean performances on neuropsychological measures in groups with low versus high reading scores. Results indicate that reading ability contributes beyond educational attainment to performances on some neuropsychological measures among African American elders. These findings have implications for reducing misclassification among minority populations through the use of appropriate normative data.
C1 [Schneider, Brooke C.] Greater Los Angeles VA Healthcare Ctr, Psychol Serv, W Los Angeles VA, Los Angeles, CA 90073 USA.
[Lichtenberg, Peter A.] Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA.
RP Schneider, BC (reprint author), Greater Los Angeles VA Healthcare Ctr, Psychol Serv, W Los Angeles VA, 11301 Wilshire Blvd,Room A206, Los Angeles, CA 90073 USA.
EM brooke.schneider@va.gov
FU NIH/NIA [T32 AG00275-06]
FX This work was supported by the NIH/NIA Aging and Urban Health
Pre-doctoral Research Training Grant (T32 AG00275-06).
NR 30
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Z9 2
U1 2
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0887-6177
J9 ARCH CLIN NEUROPSYCH
JI Arch. Clin. Neuropsychol.
PD NOV
PY 2011
VL 26
IS 7
BP 624
EP 631
DI 10.1093/arclin/acr062
PG 8
WC Psychology, Clinical; Psychology
SC Psychology
GA 836FF
UT WOS:000296094800006
PM 21835850
ER
PT J
AU Grenon, SM
Saary, J
AF Grenon, S. Marlene
Saary, Joan
TI Challenges in Aerospace Medicine Education
SO AVIATION SPACE AND ENVIRONMENTAL MEDICINE
LA English
DT Editorial Material
DE aerospace medicine; education
ID SPECIALTY
AB GRENON SM, SAARY J. Challenges in aerospace medicine education. Aviat Space Environ Med 2011; 82:1071-2.
Aerospace medicine training and research represents a dream for many and a challenge for most. In Canada, although some opportunities exist for the pursuit of education and research in the aerospace medicine field, they are limited despite the importance of this field for enabling safe human space exploration. In this commentary, we aim to identify some of the challenges facing individuals wishing to get involved in the field as well as the causal factors for these challenges. We also explore strategies to mitigate against these.
C1 [Grenon, S. Marlene] Univ Calif San Francisco, Dept Surg, Div Vasc & Endovasc Surg, Surg Serv,San Francisco VAMC, San Francisco, CA 94121 USA.
[Saary, Joan] Univ Toronto, Dept Occupat & Environm Hlth, Toronto, ON, Canada.
RP Grenon, SM (reprint author), Univ Calif San Francisco, Dept Surg, Div Vasc & Endovasc Surg, Surg Serv,San Francisco VAMC, Mail Code 112 G,4150 Clement St, San Francisco, CA 94121 USA.
EM marlene.grenon@ucsfmedctr.org
NR 8
TC 0
Z9 0
U1 0
U2 3
PU AEROSPACE MEDICAL ASSOC
PI ALEXANDRIA
PA 320 S HENRY ST, ALEXANDRIA, VA 22314-3579 USA
SN 0095-6562
J9 AVIAT SPACE ENVIR MD
JI Aviat. Space Environ. Med.
PD NOV
PY 2011
VL 82
IS 11
BP 1071
EP 1072
DI 10.3357/ASEM.3073.2011
PG 2
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Sport Sciences
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Sport Sciences
GA 837DZ
UT WOS:000296172600011
PM 22097645
ER
PT J
AU Malavia, NK
Zurakowski, D
Schroeder, A
Princiotto, AM
Laury, AR
Barash, HE
Sodroski, J
Langer, R
Madani, N
Kohane, DS
AF Malavia, Nikita K.
Zurakowski, David
Schroeder, Avi
Princiotto, Amy M.
Laury, Anna R.
Barash, Hila E.
Sodroski, Joseph
Langer, Robert
Madani, Navid
Kohane, Daniel S.
TI Liposomes for HIV prophylaxis
SO BIOMATERIALS
LA English
DT Article
DE Liposome; HIV; AIDS; Prophylaxis; Cardiolipin
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TOPICAL MICROBICIDES; PREVENTION; GP120;
TRANSMISSION; VACCINE; MODEL
AB There are approximately 33.4 million adults living with HIV worldwide of which an estimated 15.7 million are women. Although there has been enormous progress in the therapy of HIV/AIDS, treatment is not curative. Prevention is therefore of paramount importance, but vaccine-based and microbicidal approaches are still in their infancy. Since women acquire the virus largely through sexual intercourse, we developed liposomal systems potentially suitable for intra-vaginal use to prevent HIV-1 infection. We formulated liposomes from a range of naturally-occurring and synthetic lipids with varying physicochemical properties, and tested their ability to inhibit infection of transformed cells that express receptors specific to the virus. We identified formulations with the most favorable balance between decreasing HIV infection and causing cytotoxicity (i.e. therapeutic index). The therapeutic index improved with increasing cardiolipin content, and degree of unsaturation. Tissue reaction to these formulations was benign after intra-vaginal instillation in an in vivo female mouse model. These results support the potential use of cardiolipin-based liposomes enriched with synthetic lipids as microbicides for the prevention of HIV infection in women. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Malavia, Nikita K.; Barash, Hila E.; Kohane, Daniel S.] Harvard Univ, Sch Med, Lab Biomat & Drug Delivery, Dept Anesthesiol,Div Crit Care Med,Childrens Hosp, Boston, MA 02115 USA.
[Malavia, Nikita K.; Schroeder, Avi; Barash, Hila E.; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02142 USA.
[Princiotto, Amy M.; Sodroski, Joseph; Madani, Navid] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Princiotto, Amy M.; Sodroski, Joseph; Madani, Navid] Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA.
[Laury, Anna R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA.
RP Kohane, DS (reprint author), Harvard Univ, Sch Med, Lab Biomat & Drug Delivery, Dept Anesthesiol,Div Crit Care Med,Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA.
EM daniel.kohane@childrens.harvard.edu
OI Schroeder, Avi/0000-0003-2571-5937
FU Bill and Melinda Gates Foundation; NIH [GM073626]; Misrock Foundation;
American Foundation for AIDS Research [107431-45-RFRL]
FX This work was supported by Bill and Melinda Gates Foundation Grand
Challenges Explorations (GCE) Phase I grant (to R.L., D.S.K and N.K.
Malavia), and NIH GM073626 (D.S.K). A.S. thanks the Misrock Foundation
for a postdoctoral fellowship. N. Madani was supported by an American
Foundation for AIDS Research Mathilde Krim Fellowship in Basic
Biomedical Research # 107431-45-RFRL. JC53 cells were the generous gift
of Dr. David Kabat at Oregon Health Sciences University.
NR 27
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Z9 15
U1 0
U2 16
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
J9 BIOMATERIALS
JI Biomaterials
PD NOV
PY 2011
VL 32
IS 33
BP 8663
EP 8668
DI 10.1016/j.biomaterials.2011.07.068
PG 6
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 833CF
UT WOS:000295858700033
PM 21862123
ER
PT J
AU Walsh, MJ
Brimacombe, KR
Veith, H
Bougie, JM
Daniel, T
Leister, W
Cantley, LC
Israelsen, WJ
Vander Heiden, MG
Shen, M
Auld, DS
Thomas, CJ
Boxer, MB
AF Walsh, Martin J.
Brimacombe, Kyle R.
Veith, Henrike
Bougie, James M.
Daniel, Thomas
Leister, William
Cantley, Lewis C.
Israelsen, William J.
Vander Heiden, Matthew G.
Shen, Min
Auld, Douglas S.
Thomas, Craig J.
Boxer, Matthew B.
TI 2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators of
the tumor cell specific M2 isoform of pyruvate kinase
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE PKM2; Pyruvate kinase; Cellular metabolism; Anti-cancer strategies;
Small molecule activators
ID GENE; RAT; ISOZYMES; GROWTH; SYSTEM
AB Compared to normal differentiated cells, cancer cells have altered metabolic regulation to support biosynthesis and the expression of the M2 isozyme of pyruvate kinase (PKM2) plays an important role in this anabolic metabolism. While the M1 isoform is a highly active enzyme, the alternatively spliced M2 variant is considerably less active and expressed in tumors. While the exact mechanism by which decreased pyruvate kinase activity contributes to anabolic metabolism remains unclear, it is hypothesized that activation of PKM2 to levels seen with PKM1 may promote a metabolic program that is not conducive to cell proliferation. Here we report the third chemotype in a series of PKM2 activators based on the 2-oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamide scaffold. The synthesis, structure activity relationships, selectivity and notable physiochemical properties are described. Published by Elsevier Ltd.
C1 [Walsh, Martin J.; Brimacombe, Kyle R.; Veith, Henrike; Bougie, James M.; Daniel, Thomas; Leister, William; Shen, Min; Auld, Douglas S.; Thomas, Craig J.; Boxer, Matthew B.] NHGRI, NIH Chem Genom Ctr, NIH Ctr Translat Therapeut, NIH, Rockville, MD 20850 USA.
[Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA.
[Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Israelsen, William J.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Boxer, MB (reprint author), NHGRI, NIH Chem Genom Ctr, NIH Ctr Translat Therapeut, NIH, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM boxerm@mail.nih.gov
RI Cantley, Lewis/D-1800-2014
OI Cantley, Lewis/0000-0002-1298-7653
FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research;
National Human Genome Research Institute, National Institutes of Health
FX We thank Paul Shinn, Danielle VanLeer and Christopher LeClair for
assistance with compound management. This research was supported by the
Molecular Libraries Initiative of the NIH Roadmap for Medical Research
and the Intramural Research Program of the National Human Genome
Research Institute, National Institutes of Health.
NR 17
TC 29
Z9 30
U1 0
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD NOV 1
PY 2011
VL 21
IS 21
BP 6322
EP 6327
DI 10.1016/j.bmcl.2011.08.114
PG 6
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 835HA
UT WOS:000296025900021
PM 21958545
ER
PT J
AU Jacobus, SJ
Kumar, S
Uno, H
Van Wier, SA
Ahmann, GJ
Henderson, KJ
Callander, NS
Williams, ME
Siegel, DS
Greipp, PR
Rajkumar, SV
Fonseca, R
AF Jacobus, Susanna J.
Kumar, Shaji
Uno, Hajime
Van Wier, Scott A.
Ahmann, Greg J.
Henderson, Kimberly J.
Callander, Natalie S.
Williams, Michael E.
Siegel, David S.
Greipp, Philip R.
Rajkumar, S. Vincent
Fonseca, Rafael
TI Impact of high-risk classification by FISH: an Eastern Cooperative
Oncology Group (ECOG) study E4A03
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE myeloma; lenalidomide; dexamethasone; bortezomib; FISH
ID DIAGNOSED MULTIPLE-MYELOMA; LENALIDOMIDE PLUS DEXAMETHASONE; MOLECULAR
CLASSIFICATION; INTERGROUPE FRANCOPHONE; INDUCTION THERAPY;
PROGNOSTIC-FACTOR; BORTEZOMIB; STRATIFICATION; SURVIVAL; DELETION
AB Lenalidomide with dexamethasone is a standard induction treatment regimen for newly diagnosed myeloma (although a Federal Drug Administration indication is still absent). In the context of the Phase 3 clinical trial E4A03 (lenalidomide plus dexamethasone in low or high doses), we queried whether a fluorescence in situ hybridization (FISH)-based genetic classification into high risk (HR) and standard risk (SR) multiple myeloma (MM) would remain clinically significant. Of 445 E4A03 patients, 126 had FISH analysis; 21 were classified HR with t(4;14), t(14;16), or 17p13 deletions. Median survival follow-up approached 3 years. Patients with FISH data tended to be younger and healthier compared to the rest of the study population and, consequently, had superior overall survival (OS) results. Within the FISH cohort, shorter OS in the HR versus SR group (P = 0.004) corresponded to a hazard ratio of 3 48 [95% confidence interval: (1.42-8.53)], an effect also observed in multivariate analysis. Two-year OS rates were 91% for SR MM and 76% for HR MM. There was also evidence of interaction between risk status and treatment (P = 0.026). HR patients were less likely to attain good partial response (SR 46% and HR 30%, Odds Ratio = 2 0 [0.7-5.6]), but overall response rates were not different. FISH-based risk classification retained prognostic significance in patients receiving lenalidomide-based induction.
C1 [Van Wier, Scott A.; Ahmann, Greg J.; Fonseca, Rafael] Mayo Clin, Scottsdale, AZ 85259 USA.
[Jacobus, Susanna J.; Uno, Hajime] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kumar, Shaji; Henderson, Kimberly J.; Greipp, Philip R.; Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA.
[Callander, Natalie S.] Univ Wisconsin, Madison, WI USA.
[Williams, Michael E.] Univ Virginia, Med Ctr, Charlottesville, VA USA.
[Siegel, David S.] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
RP Fonseca, R (reprint author), Mayo Clin, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA.
EM fonseca.rafael@mayo.edu
RI Kumar, Shaji/A-9853-2008;
OI Kumar, Shaji/0000-0001-5392-9284; Fonseca, Rafael/0000-0002-5938-3769;
Rajkumar, S. Vincent/0000-0002-5862-1833
FU Celgene Clinical Trial Data Safety Committee; Cephalon; Genentech;
Millennium; Novartis; Celgene; Onyx; Public Health Service [CA23318,
CA66636, CA21115, CA13650]; National Cancer Institute, National
Institutes of Health; Department of Health and Human Services
FX S. K.: Clinical Trial Support - Celgene, Millennium, Genzyme, Novartis,
Cephalon; consultant in Merck. M. E. W.: Celgene Clinical Trial Research
funding; consultant and member of a Celgene Clinical Trial Data Safety
Committee (total compensation <$10 000); Cephalon, Genentech,
Millennium, Novartis: Clinical Trial Research funding. D. S. S.: Celgene
- Honoraria/Speakers Bureau/Research Support, Millennium -
Honoraria/Speakers Bureau; Onyx-Honoraria. R. F.: Patent for
prognostication of MM based on genetic categorization of the disease;
Consulting fees from Medtronic, Otsuka, Celgene, Genzyme, BMS and Amgen.
Research funding from Cylene, Onyx. All other authors have no conflicts
of interest to disclose.; This study was coordinated by the Eastern
Cooperative Oncology Group (Robert L. Comis, M. D., Chair) and supported
in part by Public Health Service Grants CA23318, CA66636, CA21115,
CA13650 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 28
TC 11
Z9 11
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD NOV
PY 2011
VL 155
IS 3
BP 340
EP 348
DI 10.1111/j.1365-2141.2011.08849.x
PG 9
WC Hematology
SC Hematology
GA 835VG
UT WOS:000296063700006
PM 21902684
ER
PT J
AU Bae, J
Tai, YT
Anderson, KC
Munshi, NC
AF Bae, Jooeun
Tai, Yu-Tzu
Anderson, Kenneth C.
Munshi, Nikhil C.
TI Novel epitope evoking CD138 antigen-specific cytotoxic T lymphocytes
targeting multiple myeloma and other plasma cell disorders
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE CD138 peptide; multiple myeloma; peptide vaccine; cytotoxic T
lymphocytes
ID BONE-MARROW BIOPSIES; HIGH-DOSE THERAPY; BREAST-CANCER; IDENTIFICATION;
SYNDECAN-1; EXPRESSION; LEUKEMIA; VACCINES; IMMUNOTHERAPY; MALIGNANCIES
AB The development of an immunotherapeutic strategy targeting CD138 antigen could potentially represent a new treatment option for multiple myeloma (MM). This study evaluated the immune function of CD138 peptide-specific cytotoxic T lymphocytes (CTL), generated ex vivo using an HLA-A2-specific CD138 epitope against MM cells. A novel immunogenic HLA-A2-specific CD138(260-268) (GLVGLIFAV) peptide was identified from the full-length protein sequence of the CD138 antigen, which induced CTL specific to primary CD138(+) MM cells. The peptide-induced CD138-CTL contained a high percentage of CD8(+) activated/memory T cells with a low percentage of CD4(+) T cell and naive CD8(+) T cell subsets. The CTL displayed HLA-A2-restricted and CD138 antigen-specific cytotoxicity against MM cell lines. In addition, CD138-CTL demonstrated increased degranulation, proliferation and gamma-interferon secretion to HLA-A2(+)/CD138(+) myeloma cells, but not HLA-A2)/CD138(+) or HLA-A2(+)/CD138) cells. The immune functional properties of the CD138-CTL were also demonstrated using primary HLA-A2(+)/CD138(+) cells isolated from myeloma patients. In conclusion, a novel immunogenic CD138(260-268) (GLVGLIFAV) peptide can induce antigen-specific CTL, which might be useful for the treatment of MM patients with peptide-based vaccine or cellular immunotherapy strategies.
C1 [Bae, Jooeun; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Bae, Jooeun; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Boston, MA USA.
[Munshi, Nikhil C.] VA Boston Healthcare Syst, Boston, MA USA.
RP Munshi, NC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM nikhil_munshi@dfci.harvard.edu
FU NIH [P50-100707, PO1-78378, RO1-129295, RO1-50947]; Multiple Myeloma
Research Foundation; Leukaemia and Lymphoma Society; Department of
Veteran's Affairs
FX This work is supported by: NIH grants; P50-100707, PO1-78378, (K. C. A.
and N.C.M.), RO1-129295 (N.C.M.) and RO1-50947 (K. C. A.), Multiple
Myeloma Research Foundation Awards, Leukaemia and Lymphoma Society
Scholar in Translational Research Award, and Department of Veteran's
Affairs merit review award.
NR 59
TC 14
Z9 15
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD NOV
PY 2011
VL 155
IS 3
BP 349
EP 361
DI 10.1111/j.1365-2141.2011.08850.x
PG 13
WC Hematology
SC Hematology
GA 835VG
UT WOS:000296063700007
PM 21902685
ER
PT J
AU Williams, SB
Gu, XM
Lipsitz, SR
Nguyen, PL
Choueiri, TK
Hu, JC
AF Williams, Stephen B.
Gu, Xiangmei
Lipsitz, Stuart R.
Nguyen, Paul L.
Choueiri, Toni K.
Hu, Jim C.
TI Utilization and Expense of Adjuvant Cancer Therapies Following Radical
Prostatectomy
SO CANCER
LA English
DT Article
DE prostatectomy; adjuvant therapy; utilization; expenditures; outcomes
ID POSITIVE SURGICAL MARGINS; BIOCHEMICAL RECURRENCE; PELVIC
LYMPHADENECTOMY; SALVAGE THERAPY; UNITED-STATES; OUTCOMES; MEN;
RADIOTHERAPY; FAILURE; PATTERNS
AB BACKGROUND: We sought to identify the costs of adjuvant therapies following radical prostatectomy (RP) and factors associated with their receipt. METHODS: We used SEER-Medicare data from 2004-2006 to identify 4247 men who underwent RP, of whom 600 subsequently received adjuvant therapies. We used Cox regression to identify factors associated with receipt of adjuvant therapies. Health care expenditures within 12 months of diagnosis were compared for RP alone versus RP with adjuvant therapies. RESULTS: Biopsy Gleason score, prostate-specific antigen, risk group, and SEER region were significantly associated with receipt of adjuvant treatments (all P < .001). Higher surgeon volume was associated with lower odds of receiving adjuvant therapies (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46-0.78 [P < .001]). Factors associated with increased receipt of adjuvant therapies were positive surgical margins (HR, 3.02; 95% CI, 2.55-3.57 [P < .001]), high-risk group versus low-risk group (HR, 7.65; 95% CI, 5.64-10.37 [P < .001]), lymph node-positive disease (HR, 5.36; 95% CI, 3.71-7.75 [P < .001]), and treatment in Iowa (HR, 1.93; 95% CI, 1.12-3.32 [P = .019]) and New Mexico/Georgia/Hawaii (HR, 1.92; 95% CI, 1.09-3.39 [P = .025]) versus San Francisco SEER regions (baseline). Age, race, comorbidities, and surgical approach were not associated with use of adjuvant therapies. The median expenditures attributable to postprostatectomy hormonal therapy, radiation therapy, and radiation with hormonal therapy versus were $1361, $12,040, and $23,487. CONCLUSIONS: Men treated by high-volume surgeons were less likely to receive adjuvant therapies. Regional variation and high-risk disease characteristics were associated with increased receipt of adjuvant therapies, which increased health care expenditures by 2-to 3-fold when radiotherapy was administered. Cancer 2011; 117: 4846-54. (C) 2011 American Cancer Society.
C1 [Williams, Stephen B.; Hu, Jim C.] Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA.
[Gu, Xiangmei; Lipsitz, Stuart R.; Hu, Jim C.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Nguyen, Paul L.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Radiat Oncol, Boston, MA 02115 USA.
RP Hu, JC (reprint author), ASBII 3, Div Urol, 45 Francis St, Boston, MA 02115 USA.
EM jhu2@partners.org
FU Department of Defense [W81XWH-08-1-0283]
FX This work was supported by a Department of Defense Prostate Cancer
Physician Training Award (W81XWH-08-1-0283) presented to J. C. Hu.
NR 40
TC 22
Z9 22
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 NOV 1
PY 2011
VL 117
IS 21
BP 4846
EP 4854
DI 10.1002/cncr.26012
PG 9
WC Oncology
SC Oncology
GA 836UR
UT WOS:000296139600007
PM 21365630
ER
PT J
AU Rhee, EP
Thadhani, R
AF Rhee, Eugene P.
Thadhani, Ravi
TI New insights into uremia-induced alterations in metabolic pathways
SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
LA English
DT Review
DE ESRD; metabolite profiling; metabolomics; uremia; uremic toxin
ID CHRONIC KIDNEY-DISEASE; INDOXYL SULFATE; ENDOTHELIAL DYSFUNCTION;
MASS-SPECTROMETRY; OXIDATIVE STRESS; KYNURENIC ACID; HEMODIALYSIS;
TOXINS; GUT; INFLAMMATION
AB Purpose of review
This article summarizes recent studies on uremia-induced alterations in metabolism, with particular emphasis on the application of emerging metabolomics technologies.
Recent findings
The plasma metabolome is estimated to include more than 4000 distinct metabolites. Because these metabolites can vary dramatically in size and polarity and are distributed across several orders of magnitude in relative abundance, no single analytical method is capable of comprehensive metabolomic profiling. Instead, a variety of analytical techniques, including targeted and nontargeted liquid chromatography-mass spectrometry, have been employed for metabolomic analysis of human plasma. Recent efforts to apply this technology to study uremia have reinforced the common view that end-stage renal disease is a state of generalized small molecule excess. However, the identification of precursor depletion and downstream metabolite excess - for example, with tryptophan and downstream kynurenine metabolites, with low molecular weight triglycerides and dicarboxylic acids, and with phosphatidylcholines, choline, and trimethylamine-N-oxide - suggest that uremia may directly modulate these metabolic pathways. Metabolomic studies have also begun to expand some of these findings to individuals with chronic kidney disease and in model systems.
Summary
Uremia is associated with diverse, but incompletely understood metabolic disturbances. Metabolomic approaches permit higher resolution phenotyping of these disturbances, but significant efforts will be required to understand the functional significance of select findings.
C1 [Rhee, Eugene P.; Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
[Thadhani, Ravi] Broad Inst, Cambridge, MA USA.
RP Rhee, EP (reprint author), Massachusetts Gen Hosp E, Div Nephrol, 149 13th St,8th Floor, Charlestown, MA 02129 USA.
EM eprhee@partners.org
FU NIH [F32-DK-085860-01]
FX E.P.R. received support from the NIH F32-DK-085860-01.
NR 39
TC 9
Z9 9
U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1062-4821
J9 CURR OPIN NEPHROL HY
JI Curr. Opin. Nephrol. Hypertens.
PD NOV
PY 2011
VL 20
IS 6
BP 593
EP 598
DI 10.1097/MNH.0b013e32834b8a1d
PG 6
WC Urology & Nephrology; Peripheral Vascular Disease
SC Urology & Nephrology; Cardiovascular System & Cardiology
GA 836VD
UT WOS:000296141700004
PM 21885966
ER
PT J
AU Liu, XW
Hamnvik, OPR
Petrou, M
Gong, HZ
Chamberland, JP
Christophi, CA
Kales, SN
Christiani, DC
Mantzoros, CS
AF Liu, Xiaowen
Hamnvik, Ole-Petter R.
Petrou, Michael
Gong, Huizhi
Chamberland, John P.
Christophi, Costas A.
Kales, Stefanos N.
Christiani, David C.
Mantzoros, Christos S.
TI Circulating lipocalin 2 is associated with body fat distribution at
baseline but is not an independent predictor of insulin resistance: the
prospective Cyprus Metabolism Study
SO EUROPEAN JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID GELATINASE-ASSOCIATED LIPOCALIN; NEUTROPHIL GELATINASE; PROTEIN;
OBESITY; LEPTIN; NGAL; IDENTIFICATION; MARKER
AB Objective: Lipocalin 2 (LCN2 or NGAL), a protein derived from neutrophils, macrophages, adipocytes, and other cells, has been proposed to be a link between obesity and insulin resistance (IR), but animal and cross-sectional human studies have revealed conflicting results. We studied the association of serum lipocalin 2 with anthropometric, metabolic, and cardiovascular risk markers in young healthy men cross-sectionally and, for the first time, prospectively after 2 years of follow-up, with and without adjustment for potential confounders including serum creatinine.
Design: Two hundred and seventy-two participants were randomly selected from the Cyprus Metabolism Study (1056 men, 18 years), of whom 93 subjects participated in the follow-up study 2 years after baseline assessment. Associations were also explored between total and free leptin levels (to serve as positive controls) and anthropometric metabolic variables.
Results: In the cross-sectional study, lipocalin 2 levels were marginally correlated in the unadjusted model with central fat distribution but not with body weight or total body fat mass. After adjusting for age, smoking, activity, body mass index, fat percentage, waist-to-hip ratio, and serum creatinine, no correlation was found with any cardiovascular risk factor. There was no correlation with the homeostasis model assessment of IR (HOMA-IR) at baseline. In the prospective analyses, baseline levels of lipocalin 2 were not predictive of any variables in unadjusted or adjusted models. As expected, total and free leptin were associated with anthropometric and metabolic variables both cross-sectionally and prospectively.
Conclusions: We demonstrate that lipocalin 2 is not an independent predictor of metabolic and cardiovascular risk factors in young men cross-sectionally or prospectively.
C1 [Liu, Xiaowen; Gong, Huizhi; Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Div Endocrinol Diabet & Metab, Dept Med, Med Sch,Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Hamnvik, Ole-Petter R.; Mantzoros, Christos S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA.
[Petrou, Michael; Christophi, Costas A.] Cyprus Univ Technol, Harvard Univ, Cyprus Int Inst Environm & Publ Hlth, Sch Publ Hlth, Limassol, Cyprus.
[Christophi, Costas A.; Kales, Stefanos N.; Christiani, David C.; Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA.
[Chamberland, John P.; Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA.
RP Mantzoros, CS (reprint author), Harvard Univ, Div Endocrinol Diabet & Metab, Dept Med, Med Sch,Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Feldberg 875, Boston, MA 02215 USA.
EM cmantzor@bidmc.harvard.edu
RI Hamnvik, Ole-Petter/D-1719-2011;
OI Chamberland, John/0000-0002-7862-1371
FU Cyprus Research Promotion Foundation [EPgammaEXi/0205/10]; Beth Israel
Deaconess Medical Center
FX The study was supported by the Cyprus Research Promotion Foundation (EP
gamma E Xi/0205/10). The Mantzoros Lab is supported by a discretionary
grant from Beth Israel Deaconess Medical Center.
NR 22
TC 16
Z9 17
U1 0
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0804-4643
J9 EUR J ENDOCRINOL
JI Eur. J. Endocrinol.
PD NOV
PY 2011
VL 165
IS 5
BP 805
EP 812
DI 10.1530/EJE-11-0660
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 836BN
UT WOS:000296082100015
PM 21885675
ER
PT J
AU Kelly, SK
Shire, DB
Chen, JH
Doyle, P
Gingerich, MD
Cogan, SF
Drohan, WA
Behan, S
Theogarajan, L
Wyatt, JL
Rizzo, JF
AF Kelly, Shawn K.
Shire, Douglas B.
Chen, Jinghua
Doyle, Patrick
Gingerich, Marcus D.
Cogan, Stuart F.
Drohan, William A.
Behan, Sonny
Theogarajan, Luke
Wyatt, John L.
Rizzo, Joseph F., III
TI A Hermetic Wireless Subretinal Neurostimulator for Vision Prostheses
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Biomedical electrodes; integrated circuit design; iridium oxide;
neuromuscular stimulation; retinal implant; retinal prosthesis;
telemetry
ID CHARGE-INJECTION LIMITS; IRIDIUM OXIDE AIROF; ELECTRICAL-STIMULATION;
VISUAL-CORTEX; HUMAN RETINA; IMPLANTATION; DEGENERATION; ELECTRODES;
RESPONSES; ARRAY
AB A miniaturized, hermetically encased, wirelessly operated retinal prosthesis has been developed for preclinical studies in the Yucatan minipig, and includes several design improvements over our previously reported device. The prosthesis attaches conformally to the outside of the eye and electrically drives a microfabricated thin-film polyimide array of sputtered iridium oxide film electrodes. This array is implanted into the subretinal space using a customized ab externo surgical technique. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip and discrete circuit components. Feedthroughs in the case connect the stimulator chip to secondary power and data receiving coils on the eye and to the electrode array under the retina. Long-term in vitro pulse testing of the electrodes projected a lifetime consistent with typical devices in industry. The final assembly was tested in vitro to verify wireless operation of the system in physiological saline using a custom RF transmitter and primary coils. Stimulation pulse strength, duration, and frequency were programmed wirelessly from a Peripheral Component Interconnect eXtensions for Instrumentation (PXI) computer. Operation of the retinal implant has been verified in two pigs for up to five and a half months by detecting stimulus artifacts generated by the implanted device.
C1 [Kelly, Shawn K.; Shire, Douglas B.; Doyle, Patrick; Gingerich, Marcus D.; Drohan, William A.; Rizzo, Joseph F., III] VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA.
[Kelly, Shawn K.; Doyle, Patrick; Drohan, William A.; Wyatt, John L.] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
[Shire, Douglas B.; Gingerich, Marcus D.] Cornell Univ, Ithaca, NY 14853 USA.
[Chen, Jinghua; Rizzo, Joseph F., III] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
[Chen, Jinghua; Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Cogan, Stuart F.] EIC Labs Inc, Norwood, MA 02062 USA.
[Behan, Sonny] Sonny Behan Consulting, Atlanta, GA 30096 USA.
[Theogarajan, Luke] Univ Calif Santa Barbara, Santa Barbara, CA 92106 USA.
RP Kelly, SK (reprint author), VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA.
EM skkelly@alum.mit.edu; dbs6@cornell.edu; jinghua_chen@meei.harvard.edu;
wpd@mit.edu; mdg37@cornell.edu; scogan@eiclabs.com; billd@mit.edu;
sbehan@bellsouth.net; ltheogar@ece.ucsb.edu; jlw@mit.edu;
joseph_rizzo@meei.harvard.edu
OI Kelly, Shawn/0000-0003-3533-5268
FU Department of Veterans Affairs Center for Innovative Visual
Rehabilitation; NIH [EY016674-01]; Department of Defense; Massachusetts
Lions Foundation; NSF
FX This work was supported in part by the Department of Veterans Affairs
Center for Innovative Visual Rehabilitation, the NIH under Grant
EY016674-01, the Department of Defense, NSF's support to the Cornell
NanoScale Science and Technology Facility, and the Massachusetts Lions
Foundation. MOSIS provided in-kind foundry services.
NR 28
TC 37
Z9 37
U1 3
U2 20
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD NOV
PY 2011
VL 58
IS 11
BP 3197
EP 3205
DI 10.1109/TBME.2011.2165713
PG 9
WC Engineering, Biomedical
SC Engineering
GA 835FA
UT WOS:000296019500018
PM 21859595
ER
PT J
AU Winters, M
Lloyd, R
Shahidi, A
Brown, S
Holodniy, M
AF Winters, Mark
Lloyd, Robert, Jr.
Shahidi, Azra
Brown, Sheldon
Holodniy, Mark
TI Use of dried clinical samples for storing and detecting influenza RNA
SO INFLUENZA AND OTHER RESPIRATORY VIRUSES
LA English
DT Article
DE Dried samples; influenza; real-time PCR
ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD SPOT ASSAY; DRUG-RESISTANCE; H1N1
VIRUS; A H1N1; SURVEILLANCE; COLLECTION; AMPLIFICATION; SENSITIVITY;
DIAGNOSIS
AB Background Most clinical samples collected for diagnostic influenza testing and monitoring require refrigerated or frozen storage or shipment, which imparts logistic and cost burdens. The ability to store and ship dried clinical specimens under ambient conditions for influenza testing would significantly reduce costs and protect samples from improper storage or equipment failure, especially in remote or resource-limited areas.
Objectives To evaluate the collection and storage of dried clinical samples on a transport matrix (ViveST (TM), ST) for influenza RNA testing by real-time reverse-transcription PCR (RT-PCR).
Methods Viral transport medium from swab or sputum samples was applied to ST, dried, and stored under ambient conditions from 2 days to 6 months. Additional aliquots of samples were frozen. Testing of frozen and ST-stored samples was performed using the WHO/CDC real-time influenza A (H1N1) RT-PCR protocol and compared to the Luminex xTAG RVP assay.
Results ST-stored samples yielded slightly higher threshold cycle values (median 2 54 cycles) compared to frozen samples tested in parallel. This difference was consistent regardless of viral input. There was no significant difference in signal recovery between samples stored for 1 week versus samples stored for 3 weeks, or from three samples stored for 6 months. Qualitatively, clinical specimens stored on ST were 100% concordant (36/36) with frozen samples for detecting the presence of influenza A RNA.
Conclusion ST-processed dried specimens produced similar rates of seasonal or novel 2009 HIN1 influenza RNA detection compared to conventional sample processing and thus presents a viable alternative to refrigerated or frozen samples.
C1 [Winters, Mark; Holodniy, Mark] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Winters, Mark; Holodniy, Mark] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Lloyd, Robert, Jr.] Res ThinkTank Inc, Buford, GA USA.
[Shahidi, Azra; Brown, Sheldon] James J Peters VA Med Ctr, Bronx, NY USA.
RP Winters, M (reprint author), AIDS Res Ctr, 3801 Miranda Ave 132, Palo Alto, CA 94304 USA.
EM mark.winters@stanford.edu
NR 33
TC 1
Z9 1
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1750-2640
J9 INFLUENZA OTHER RESP
JI Influenza Other Respir. Viruses
PD NOV
PY 2011
VL 5
IS 6
BP 413
EP 417
DI 10.1111/j.1750-2659.2011.00253.x
PG 5
WC Infectious Diseases; Virology
SC Infectious Diseases; Virology
GA 836BA
UT WOS:000296080300009
PM 21668673
ER
PT J
AU Bai, XY
Ovrutsky, AR
Kartalija, M
Chmura, K
Kamali, A
Honda, JR
Oberley-Deegan, RE
Dinarello, CA
Crapo, JD
Chang, LY
Chan, ED
AF Bai, Xiyuan
Ovrutsky, Alida R.
Kartalija, Marinka
Chmura, Kathryn
Kamali, Amanda
Honda, Jennifer R.
Oberley-Deegan, Rebecca E.
Dinarello, Charles A.
Crapo, James D.
Chang, Ling-Yi
Chan, Edward D.
TI IL-32 expression in the airway epithelial cells of patients with
Mycobacterium avium complex lung disease
SO INTERNATIONAL IMMUNOLOGY
LA English
DT Article
DE cytokine; immunohistochemistry; non-tuberculous mycobacteria
ID NECROSIS-FACTOR-ALPHA; A VIRUS-INFECTION; NONTUBERCULOUS MYCOBACTERIA;
PROINFLAMMATORY CYTOKINE; INTERFERON-GAMMA; TNF-ALPHA; MACROPHAGE
APOPTOSIS; TUBERCULOSIS; IMMUNITY; PREVALENCE
AB Lung disease due to Mycobacterium avium complex (MAC) organisms is increasing. A greater understanding of the host immune response to MAC organisms will provide a foundation to develop novel therapies for these recalcitrant infections. IL-32 is a newly described pro-inflammatory cytokine that enhances host immunity against various microbial pathogens. Cytokines that induce IL-32 such as interferon-gamma, IL-18, IL-12 and tumor necrosis factor-alpha are of considerable importance to mycobacterial immunity. We performed immunohistochemistry and morphometric analysis to quantify IL-32 expression in the lungs of 11 patients with MAC lung disease and 10 controls with normal lung tissues. After normalizing for basement membrane length, there was a profound increase in IL-32 expression in the airway epithelial cells of the MAC-infected lungs compared with controls. Following normalization for alveolar surface area, there was a trend toward increased IL-32 expression in type II alveolar cells and alveolar macrophages in the lungs of MAC patients. Human airway epithelial cells (BEAS-2B) infected with M. avium produced IL-32 by a nuclear factor-kappa B-dependent mechanism. In both BEAS-2B cells and human monocyte-derived macrophages, exogenous IL-32 gamma significantly reduced the growth of intracellular M. avium. This finding was corroborated by an increase in the number of intracellular M. avium recovered from THP-1 monocytes silenced for endogenous IL-32 expression. The anti-mycobacterial effect of IL-32 may be due, in part, to increased apoptosis of infected cells. These findings indicate that IL-32 facilitates host defense against MAC organisms but may also contribute to the airway inflammation associated with MAC pulmonary disease.
C1 [Bai, Xiyuan; Ovrutsky, Alida R.; Chmura, Kathryn; Oberley-Deegan, Rebecca E.; Crapo, James D.; Chang, Ling-Yi; Chan, Edward D.] Natl Jewish Hlth, Dept Acad Affairs, Denver, CO 80206 USA.
[Bai, Xiyuan; Ovrutsky, Alida R.; Kartalija, Marinka; Chan, Edward D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA.
[Bai, Xiyuan; Ovrutsky, Alida R.; Honda, Jennifer R.; Chan, Edward D.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA.
[Kartalija, Marinka; Dinarello, Charles A.] Univ Colorado Denver, Div Infect Dis, Aurora, CO 80045 USA.
[Kamali, Amanda; Honda, Jennifer R.; Chan, Edward D.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA.
[Chan, Edward D.] Natl Jewish Hlth, Dept Med, Cell Biol Program, Denver, CO 80206 USA.
RP Bai, XY (reprint author), Natl Jewish Hlth, Dept Acad Affairs, 1400 Jackson St, Denver, CO 80206 USA.
EM baix@njhealth.org
FU Department of Veterans Affairs Veterans Health Administration; Office of
Research and Development; National Institutes of Health [AI15614]
FX Department of Veterans Affairs Veterans Health Administration, Office of
Research and Development (E.D.C.) and National Institutes of Health
(AI15614 to C.A.D.).
NR 73
TC 11
Z9 12
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0953-8178
J9 INT IMMUNOL
JI Int. Immunol.
PD NOV
PY 2011
VL 23
IS 11
BP 679
EP 691
DI 10.1093/intimm/dxr075
PG 13
WC Immunology
SC Immunology
GA 838MG
UT WOS:000296295700003
PM 22033195
ER
PT J
AU Harries, AD
Lin, Y
Satyanarayana, S
Lonnroth, K
Li, L
Wilson, N
Chauhan, LS
Zachariah, R
Baker, MA
Jeon, CY
Murray, MB
Maher, D
Bygbjerg, IC
Enarson, DA
Billo, NE
Kapur, A
AF Harries, A. D.
Lin, Y.
Satyanarayana, S.
Loennroth, K.
Li, L.
Wilson, N.
Chauhan, L. S.
Zachariah, R.
Baker, M. A.
Jeon, C. Y.
Murray, M. B.
Maher, D.
Bygbjerg, I. C.
Enarson, D. A.
Billo, N. E.
Kapur, A.
TI The looming epidemic of diabetes-associated tuberculosis: learning
lessons from HIV-associated tuberculosis
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Review
DE diabetes mellitus; tuberculosis; screening; HIV; treatment outcomes;
framework
ID SUB-SAHARAN AFRICA; PULMONARY TUBERCULOSIS; ANTIRETROVIRAL THERAPY;
CHRONIC DISEASES; MELLITUS; PREVALENCE; INFECTION; WILL; RECURRENCE;
RELEVANCE
AB The prevalence of diabetes mellitus is increasing at a dramatic rate, and countries in Asia, particularly India and China, will bear the brunt of this epidemic. Persons with diabetes have a significantly increased risk of active tuberculosis (TB), which is two to three times higher than in persons without diabetes. In this article, we argue that the epidemiological interactions and the effects on clinical presentation and treatment resulting from the interaction between diabetes and TB are similar to those observed for human immunodeficiency virus (HIV) and TB. The lessons learned from approaches to reduce the dual burden of HIV and TB, and especially the modes of screening for the two diseases, can be adapted and applied to the screening, diagnosis, treatment and prevention of diabetes and TB. The new World Health Organization (WHO) and The Union Collaborative Framework for care and control of TB and diabetes has many similarities to the WHO Policy on Collaborative Activities to reduce the dual burden of TB and HIV, and aims to guide policy makers and implementers on how to move forward and combat this looming dual epidemic. The response to the growing HIV-associated TB epidemic in the 1980s and 1990s was slow and uncoordinated, despite clearly articulated warnings about the scale of the forthcoming problem. We must not make the same mistake with diabetes and TB. The Framework provides a template for action, and it is now up to donors, policy makers and implementers to apply the recommendations in the field and to 'learn by doing'.
C1 [Harries, A. D.; Enarson, D. A.; Billo, N. E.] Int Union TB & Lung Dis, Paris, France.
[Harries, A. D.; Maher, D.] London Sch Hyg & Trop Med, London WC1, England.
[Lin, Y.] China Off, Int Union TB & Lung Dis, Beijing, Peoples R China.
[Satyanarayana, S.; Wilson, N.] SE Asia Off, Int Union TB & Lung Dis, Delhi, India.
[Loennroth, K.] WHO, Stop TB Dept, CH-1211 Geneva, Switzerland.
[Li, L.] Chinese Ctr Dis Control & Prevent, Clin Ctr TB, Beijing, Peoples R China.
[Chauhan, L. S.] Govt India, Natl Ctr Dis Control, Minist Hlth & Family Welf, Delhi, India.
[Zachariah, R.] Brussels Operat Ctr, Dept Med, Operat Res Unit, Luxembourg, Luxembourg.
[Baker, M. A.; Murray, M. B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Baker, M. A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Jeon, C. Y.] Columbia Univ, New York, NY USA.
[Murray, M. B.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA.
[Bygbjerg, I. C.] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark.
[Kapur, A.] World Diabet Fdn, Gentofte, Denmark.
RP Harries, AD (reprint author), Vears Lane, Winchester SO21 1TQ, Hants, England.
EM adharries@theunion.org
RI Lonnroth, Knut/L-2339-2014
OI Lonnroth, Knut/0000-0001-5054-8240
NR 73
TC 35
Z9 36
U1 1
U2 10
PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
PI PARIS
PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE
SN 1027-3719
EI 1815-7920
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD NOV
PY 2011
VL 15
IS 11
BP 1436
EP 1444
DI 10.5588/ijtld.11.0503
PG 9
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA 837ER
UT WOS:000296174400007
PM 21902876
ER
PT J
AU Gruber, J
Miklowitz, DJ
Harvey, AG
Frank, E
Kupfer, D
Thase, ME
Sachs, GS
Ketter, TA
AF Gruber, June
Miklowitz, David J.
Harvey, Allison G.
Frank, Ellen
Kupfer, David
Thase, Michael E.
Sachs, Gary S.
Ketter, Terence A.
TI Sleep matters: Sleep functioning and course of illness in bipolar
disorder
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Bipolar disorder; Sleep; Mania; Depression; Functioning; STEP-BD
ID TREATMENT ENHANCEMENT PROGRAM; STEP-BD; MANIA; DEPRIVATION; DEPRESSION;
MOOD; EPISODE
AB Background: Few studies have prospectively examined the relationships of sleep with symptoms and functioning in bipolar disorder.
Methods: The present study examined concurrent and prospective associations between total sleep time (TST) and sleep variability (SV) with symptom severity and functioning in a cohort of DSM-IV bipolar patients (N = 468) participating in the National Institute of Mental Health Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), all of whom were recovered at study entry.
Results: Concurrent associations at study entry indicated that shorter TST was associated with increased mania severity, and greater SV was associated with increased mania and depression severity. Mixed-effects regression modeling was used to examine prospective associations in the 196 patients for whom follow-up data were available. Consistent with findings at study entry, shorter TST was associated with increased mania severity, and greater SV was associated with increased mania and depression severity over 12 months.
Discussion: These findings highlight the importance of disrupted sleep patterns in the course of bipolar illness. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Gruber, June] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[Miklowitz, David J.] Univ Calif Los Angeles, Div Child & Adolescent Psychiat, Semel Inst, Los Angeles, CA USA.
[Harvey, Allison G.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA.
[Frank, Ellen; Kupfer, David; Thase, Michael E.] Univ Pittsburgh, Dept Psychiat, Med Ctr, Pittsburgh, PA 15260 USA.
[Sachs, Gary S.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA.
[Sachs, Gary S.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA.
[Ketter, Terence A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
RP Gruber, J (reprint author), Yale Univ, Dept Psychol, POB 208205, New Haven, CT 06520 USA.
EM june.gruber@yale.edu
FU National Institute of Mental Health (NIMH) [N01MH80001]
FX The STEP-BD study was supported with Federal funds from the National
Institute of Mental Health (NIMH), under contract N01MH80001. Any
opinions, findings, and conclusions or recommendations expressed in this
publication are those of the authors and do not necessarily reflect the
views of the NIMH.
NR 26
TC 30
Z9 31
U1 3
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD NOV
PY 2011
VL 134
IS 1-3
BP 416
EP 420
DI 10.1016/j.jad.2011.05.016
PG 5
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 831TG
UT WOS:000295753400053
PM 21683450
ER
PT J
AU Sung, SC
Dryman, MT
Marks, E
Shear, MK
Ghesquiere, A
Fava, M
Simon, NM
AF Sung, Sharon C.
Dryman, M. Taylor
Marks, Elizabeth
Shear, M. Katherine
Ghesquiere, Angela
Fava, Maurizio
Simon, Naomi M.
TI Complicated grief among individuals with major depression: Prevalence,
comorbidity, and associated features
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Complicated grief; Bereavement; Traumatic grief; Prolonged grief; Major
depression
ID BEREAVEMENT-RELATED DEPRESSION; TRAUMATIC GRIEF; DIAGNOSTIC-CRITERIA;
PANIC DISORDER; ANXIETY; HEALTH; SCALE; LIFE; NORTRIPTYLINE;
PSYCHOTHERAPY
AB Background: Growing data suggest that complicated grief (CG) may be common in clinical care settings, but there are few prior reports about CG in outpatients presenting with primary mood disorders.
Methods: The present study examined rates of bereavement and threshold CG symptoms (defined as a score >= 25 on the Inventory of Complicated Grief scale) in 111 outpatients with major depressive disorder (MDD) and 142 healthy controls participating in a study of stress and depression. Clinical and demographic characteristics were also compared for bereaved individuals with CG (MDD + CG) to those without (MDD - CC). Participants completed structured diagnostic interviews as well as measures of CG, depression, anxiety, exposure to traumatic events, and perceived social support.
Results: Lifetime history of a significant loss did not differ for the MDD and control groups (79.3% vs. 76.1%), but bereaved participants with MDD had higher rates of threshold CG (25.0% vs. 2.8%). Among those with MDD, CG was associated with a higher prevalence of lifetime alcohol dependence, greater exposure to traumatic events, and lower perceived social support. Depressed women, but not men, with CG also had higher rates of panic disorder, social anxiety disorder, and posttraumatic stress disorder.
Limitations: Our findings are limited by the lack of a clinician confirmatory assessment of CG diagnosis, absence of complete information about the nature and timing of the loss, and relatively narrow generalizability.
Conclusions: We found high rates of CG in a group of psychiatric outpatients with chronic MDD, suggesting that patients with depression should be routinely screened for CG. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Sung, Sharon C.; Dryman, M. Taylor; Marks, Elizabeth; Simon, Naomi M.] Harvard Univ, Sch Med, Dept Psychiat, Ctr Anxiety & Traumat Stress Disorders,Massachuse, Boston, MA 02115 USA.
[Shear, M. Katherine; Ghesquiere, Angela] Columbia Univ, Sch Social Work, New York, NY USA.
[Shear, M. Katherine] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Fava, Maurizio] Harvard Univ, Sch Med, Dept Psychiat, Depress Clin & Res Program,Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Sung, SC (reprint author), Duke NUS Grad Med Sch Singapore, Off Clin Sci, 8 Coll Rd, Singapore 169857, Singapore.
EM sharon.sung@duke-nus.edu.sg
FU Massachusetts General Hospital
FX The authors wish to thank the staff of the Center for Anxiety and
Traumatic Stress Disorders and the Depression Clinical and Research
Program at Massachusetts General Hospital for their support and
assistance with this project
NR 41
TC 17
Z9 19
U1 3
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD NOV
PY 2011
VL 134
IS 1-3
BP 453
EP 458
DI 10.1016/j.jad.2011.05.017
PG 6
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 831TG
UT WOS:000295753400061
PM 21621849
ER
PT J
AU Shum, WWC
Ruan, YC
Da Silva, N
Breton, S
AF Shum, Winnie W. C.
Ruan, Ye Chun
Da Silva, Nicolas
Breton, Sylvie
TI Establishment of Cell-Cell Cross Talk in the Epididymis: Control of
Luminal Acidification
SO JOURNAL OF ANDROLOGY
LA English
DT Article
DE H(+)-ATPase; V-ATPase; pseudostratified epithelia; basal cells; clear
cells; principal cells
ID MALE REPRODUCTIVE-TRACT; TRANSMEMBRANE CONDUCTANCE REGULATOR; VACUOLAR
H+-ATPASE; ANGIOTENSIN-CONVERTING ENZYME; SOLUBLE ADENYLYL-CYCLASE;
TRANSCRIPTION FACTOR FOXI1; MOUSE SPERM CAPACITATION; VAS-DEFERENS
EPITHELIA; ACTIN-BINDING SITE; PROTEIN-KINASE-A
AB Male infertility is often caused by sperm that have low motility and interact poorly with the oocyte. Spermatozoa acquire these crucial functions in the epididymis. A low luminal bicarbonate (HCO(3)(-)) concentration and low pH keep sperm quiescent during their maturation and storage in this organ. This review describes how epididymal epithelial cells work in a concerted manner, together with spermatozoa, to establish and maintain this acidic luminal environment. Clear cells express the proton-pumping ATPase (V-ATPase) in their apical membrane and actively secrete protons. HCO(3)(-) induces V-ATPase accumulation in apical microvilli in clear cells via HCO(3)(-)-sensitive adenylyl cyclase-dependent cAMP production. HCO(3)(-) is secreted from principal cells following basolateral stimulation, to transiently "prime" spermatozoa before ejaculation. Luminal ATP and adenosine also induce V-ATPase apical accumulation in clear cells via activation of P2 and P1 receptors, respectively. ATP is released into the lumen from sperm and principal cells and is then metabolized into adenosine by local nucleotidases. In addition, the V-ATPase is regulated by luminal angiotensin II via activation of basal cells, which can extend narrow body projections that cross the tight junction barrier. Basal cells then secrete nitric oxide, which diffuses out to stimulate proton secretion in clear cells via activation of the cGMP pathway. Thus, an elaborate communication network is present between principal cells and clear cells, and between basal cells and clear cells, to control luminal acidification. Monitoring and decoding these "intercellular conversations" will help define pathophysiologic mechanisms underlying male infertility.
C1 Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Breton, S (reprint author), MGH Simches Res Ctr, Program Membrane Biol, 185 Cambridge St,CPZN 8-204, Boston, MA 02114 USA.
EM breton.sylvie@mgh.harvard.edu
FU NICHD NIH HHS [HD040793, HD045821, R01 HD040793, R01 HD045821]; NIDDK
NIH HHS [DK085715, DK038452, DK43351, DK57521, P01 DK038452, P30
DK043351, P30 DK057521, R01 DK085715]
NR 109
TC 35
Z9 38
U1 0
U2 7
PU AMER SOC ANDROLOGY, INC
PI LAWRENCE
PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA
SN 0196-3635
J9 J ANDROL
JI J. Androl.
PD NOV-DEC
PY 2011
VL 32
IS 6
BP 576
EP 586
DI 10.2164/jandrol.111.012971
PG 11
WC Andrology
SC Endocrinology & Metabolism
GA 835LH
UT WOS:000296037400004
PM 21441423
ER
PT J
AU Olson, RA
Brastianos, PK
Palma, DA
AF Olson, Robert A.
Brastianos, Priscilla K.
Palma, David A.
TI Prognostic and predictive value of epigenetic silencing of MGMT in
patients with high grade gliomas: a systematic review and meta-analysis
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Review
DE MGMT; Meta-analysis; Predictive markers; Prognostic markers; High-grade
glioma
ID NEWLY-DIAGNOSED GLIOBLASTOMA; O-6-METHYLGUANINE DNA METHYLTRANSFERASE;
PHASE-II TRIAL; PROMOTER METHYLATION; MALIGNANT GLIOMA; NCIC TRIAL;
TEMOZOLOMIDE; GENE; RADIOTHERAPY; SURVIVAL
AB Epigenetic silencing of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene is associated with improved survival in patients with high-grade gliomas (HGG), with varying estimates of magnitude. The objective of this meta-analysis is to determine the prognostic value of MGMT silencing, and assess its predictive value by treatment type. MEDLINE and EMBASE databases were searched for studies relating to gliomas and MGMT. Studies reporting overall survival (OS) by MGMT status in patients with HGG were considered potentially eligible. We excluded studies that did not control for potential confounding variables. A meta-analysis of studies was performed via random-effects modelling. Subgroup meta-analyses by treatment were performed according to a priori hypotheses. Twenty studies were ultimately eligible, including 2,018 patients. In the pooled analysis, MGMT silencing was associated with improved OS (HR = 0.436; 95% CI: 0.333-0.571; P < 0.001). The prognostic utility of MGMT status varies significantly by treatment type (P = 0.001): the HR for OS for MGMT silenced tumors is 0.190 (0.047-0.770), 0.403 (0.282-0.576), 0.743 (0.579-0.954), and 1.070 (0.722-1.585) for studies using surgery plus the addition of either: chemotherapy (CT), chemoradiotherapy (CRT), radiotherapy (RT), and nothing (surgery alone), respectively. Epigenetic silencing of MGMT is associated with markedly improved survival in patients with HGG who receive adjuvant therapy. MGMT silencing serves as a predictive marker, with the largest benefit seen in patients receiving CT as a component of adjuvant treatment, an intermediate benefit in patients receiving adjuvant RT, and no evidence to support benefit in those receiving surgery alone.
C1 [Olson, Robert A.] Univ British Columbia, Ctr North, Dept Radiat Oncol, Vancouver, BC V5Z 4E6, Canada.
[Olson, Robert A.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Olson, Robert A.; Brastianos, Priscilla K.; Palma, David A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Brastianos, Priscilla K.] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA.
[Brastianos, Priscilla K.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA.
[Brastianos, Priscilla K.] Massachusetts Gen Hosp, Ctr Canc, Dept Hematol & Oncol, Boston, MA 02114 USA.
[Palma, David A.] Univ Western Ontario, Div Radiat Oncol, London, ON N6A 4L6, Canada.
[Palma, David A.] London Reg Canc Program, London, ON N6A 4L6, Canada.
RP Olson, RA (reprint author), Univ British Columbia, Ctr North, Dept Radiat Oncol, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada.
EM rolson2@bccancer.bc.ca
OI Brastianos, Priscilla/0000-0003-4470-8425
NR 41
TC 37
Z9 38
U1 0
U2 8
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 NOV
PY 2011
VL 105
IS 2
BP 325
EP 335
DI 10.1007/s11060-011-0594-5
PG 11
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 835VK
UT WOS:000296064200023
PM 21523485
ER
PT J
AU Fernando, HN
Czamanski, J
Yuan, TY
Gu, WY
Salahadin, A
Huang, CYC
AF Fernando, Hanan N.
Czamanski, Jessica
Yuan, Tai-Yi
Gu, Weiyong
Salahadin, Abdi
Huang, Chun-Yuh Charles
TI Mechanical Loading Affects the Energy Metabolism of Intervertebral Disc
Cells
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE intervertebral disc; ATP; mechanical loading; energy production
ID REGULATES MITOCHONDRIAL RESPIRATION; BOVINE NUCLEUS PULPOSUS; DISCOGENIC
BACK-PAIN; DYNAMIC COMPRESSION; IN-VITRO; ISOLATED CHONDROCYTES; LUMBAR
RHIZOPATHIES; GLUCOSE-TRANSPORT; SYNTHESIS RATES; ATP
AB Research has shown that mechanical loading affects matrix biosynthesis of intervertebral disc (IVD) cells; however, the pathway(s) to this effect is currently unknown. Cellular matrix biosynthesis is an energy demanding process. The objective of this study was to investigate the effects of static and dynamic compressive loading on energy metabolism of IVD cells. Porcine annulus fibrosus (AF) and nucleus pulposus (NP) cells seeded in 2% agarose were used in this experiment. Experimental groups included 15% static compression and 0.1 and 1 Hz dynamic compression at 15% strain magnitude for 4 h. ATP, lactate, glucose, and nitric oxide (NO) contents in culture media, and ATP content in cell-agarose construct were measured using biochemical assays. While the total ATP content of AF cells was promoted by static and dynamic loading, only 1 Hz dynamic loading increased total ATP content of NP cells. Increases in lactate production and glucose consumption of AF cells suggest that ATP production via glycolysis is promoted by dynamic compression. ATP release and NO production of AF and NP cells were significantly increased by dynamic loading. Thus, this study clearly illustrates that static and dynamic compressive loading affect IVD cell energy production while cellular responses to mechanical loading were both cell type and compression type dependent. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1634-1641, 2011
C1 [Fernando, Hanan N.; Czamanski, Jessica; Yuan, Tai-Yi; Huang, Chun-Yuh Charles] Univ Miami, Stem Cell & Mechanobiol Lab, Dept Biomed Engn, Coll Engn, Coral Gables, FL 33146 USA.
[Yuan, Tai-Yi; Gu, Weiyong] Univ Miami, Tissue Biomech Lab, Dept Biomed Engn, Coral Gables, FL 33146 USA.
[Salahadin, Abdi] Harvard Univ, Sch Med, BIDMC, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA.
RP Huang, CYC (reprint author), Univ Miami, Stem Cell & Mechanobiol Lab, Dept Biomed Engn, Coll Engn, Coral Gables, FL 33146 USA.
EM c.huang@miami.edu
FU NIH [AR056101, EB008653]
FX This study was supported by the grants (AR056101 and EB008653) from the
NIH. The authors have no conflicts of interest in relation to the
presented material.
NR 50
TC 22
Z9 22
U1 2
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0736-0266
J9 J ORTHOP RES
JI J. Orthop. Res.
PD NOV
PY 2011
VL 29
IS 11
BP 1634
EP 1641
DI 10.1002/jor.21430
PG 8
WC Orthopedics
SC Orthopedics
GA 832KO
UT WOS:000295803900002
PM 21484859
ER
PT J
AU Lee, KB
Murray, SS
Duarte, MEL
Spitz, JF
Johnson, JS
Song, KJ
Brochmann, EJ
Taghavi, CE
Keorochana, G
Liao, JC
Wang, JC
AF Lee, Kwang-Bok
Murray, Samuel S.
Duarte, M. Eugenia L.
Spitz, Juliana F.
Johnson, Jared S.
Song, Kyung-Jin
Brochmann, Elsa J.
Taghavi, Cyrus E.
Keorochana, Gun
Liao, Jen-Chung
Wang, Jeffrey C.
TI Effects of the Bone Morphogenetic Protein Binding Protein spp24
(Secreted Phosphoprotein 24 kD) on the Growth of Human Lung Cancer Cells
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE spp24; bone morphogenetic proteins; lung cancer; bone tumors; A549 cell
line; metastases
ID METASTATIC PROSTATE-CANCER; OSTEOLYTIC LESIONS; TUMOR-GROWTH;
EXPRESSION; OVEREXPRESSION; ANTAGONISTS; CARCINOMAS; MOUSE
AB Bone morphogenetic proteins (BMPs) and transforming growth factor-beta (TGF-beta) contribute to the growth of some skeletal metastases through autocrine stimulation. Secreted phosphoprotein 24 kDa (spp24) has been shown to bind to both BMP-2 and TGF-beta and to markedly inhibit the osteogenic properties of rhBMP-2. We hypothesized that the addition of spp24 would sequester autocrine growth factors (especially BMP-2) and reduce tumor growth in a system (A549 human non-small cell lung cancer cell line) where autocrine stimulation by BMP-2 is known to be important. A549 cells were injected into two sites (subcutaneous and intraosseus) in SCID mice with and without the co-injection of BMP-2 and spp24. Tumor growth after 8 weeks was assessed through gross examination, radiological imaging, and histological analysis. Spp24 attenuated the tumor growth enhancing effects of rhBMP-2 and reduced the tumor growth when added to tumor cells that were not treated with BMP-2. We conclude that spp24 can reduce A549 cell tumor growth in both soft tissue and intraosseus environments. We hypothesize that the mechanism for this inhibition is interruption of autocrine stimulation through the sequestration of BMP-2. Spp24 can be developed into a therapeutic agent that can be employed in clinical situations where the inhibitions of BMPs and related proteins is advantageous. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:1712-1718, 2011
C1 [Lee, Kwang-Bok; Johnson, Jared S.; Taghavi, Cyrus E.; Keorochana, Gun; Liao, Jen-Chung; Wang, Jeffrey C.] Univ Calif Los Angeles, Dept Orthopaed Surg, UCLA Comprehens Spine Ctr, Los Angeles, CA 90095 USA.
[Lee, Kwang-Bok; Song, Kyung-Jin] Chonbuk Natl Univ, Sch Med, Chonbuk Natl Univ Hosp, Dept Orthopaed Surg,Res Inst Clin Med, Jonju, South Korea.
[Murray, Samuel S.; Brochmann, Elsa J.] VA Greater Los Angeles Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA.
[Murray, Samuel S.; Brochmann, Elsa J.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA.
[Murray, Samuel S.; Wang, Jeffrey C.] Univ Calif Los Angeles, Biomed Engn Interdept Program, Los Angeles, CA 90095 USA.
[Duarte, M. Eugenia L.; Spitz, Juliana F.] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil.
[Duarte, M. Eugenia L.; Spitz, Juliana F.] Natl Inst Traumatol & Orthopaed, Rio De Janeiro, Brazil.
RP Wang, JC (reprint author), Univ Calif Los Angeles, Dept Orthopaed Surg, UCLA Comprehens Spine Ctr, 1250 16th St,7th Floor,Tower 745, Los Angeles, CA 90095 USA.
EM jwang@mednet.ucla
FU Department of Veterans Affairs
FX Supported in part by the Department of Veterans Affairs.
NR 30
TC 9
Z9 9
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0736-0266
J9 J ORTHOP RES
JI J. Orthop. Res.
PD NOV
PY 2011
VL 29
IS 11
BP 1712
EP 1718
DI 10.1002/jor.21383
PG 7
WC Orthopedics
SC Orthopedics
GA 832KO
UT WOS:000295803900014
PM 21509819
ER
PT J
AU Wiggers, JK
Guitton, TG
Smith, RM
Vrahas, MS
Ring, D
AF Wiggers, Jimme K.
Guitton, Thierry G.
Smith, R. Malcolm
Vrahas, Mark S.
Ring, David
TI Observed and Expected Outcomes in Transfer and Nontransfer Patients With
a Hip Fracture
SO JOURNAL OF ORTHOPAEDIC TRAUMA
LA English
DT Article
DE hip fracture; mortality; complications; transfer status; operative
treatment
ID ACADEMIC-MEDICAL-CENTER; INTENSIVE-CARE-UNIT; INTERHOSPITAL TRANSFERS
AB Objectives: Hospitals and providers that accept transfer patients risk lower ratings on publically reported quality measures that are inadequately adjusted for infirmity and complexity. We compared the outcomes of transferred patients and nontransferred patients after treatment of a hip fracture and sought to determine if expected outcomes based on an expansion of All Patient Refined-Diagnosis Related Groups (APR-DRGs) norms are accurately adjusted for transfer status.
Design: Retrospective cohort study.
Setting: Tertiary care referral center.
Patients: Four hundred six consecutive patients 65 years and older who received operative treatment of an acute hip fracture.
Intervention: Patients who were transferred from another acute care hospital or a skilled nursing facility before treatment were classified as transfer patients (n = 123), and all other patients were nontransfer patients (n = 283).
Main Outcome: Groups were compared with respect to in-hospital mortality, length of stay (LOS), excess days over the geometric mean length of stay (GMLOS), and readmission rate as well as expected length of stay (Exp LOS) and expected mortality (Exp Mort) based on APR-DRG norms and additional adjustment for transfer status.
Results: Transfer patients had significantly greater LOS (10.2 vs 9.6 days; P < 0.05), Exp LOS (9.7 vs 7.7 days; P < 0.001), Exp Mort (0.07 vs 0.03; P = 0.004), and excess days over the GMLOS (4.1 vs 3.3 days; P = 0.025) than nontransfer patients, near-significant greater in-hospital mortality (9.8 vs 4.9%; P = 0.069), and similar readmission rates. The differences in LOS and Exp LOS were nonsignificant in both transfer (P = 0.49) and nontransfer patients (P = 0.10).
Conclusions: Patients 65 years and older transferred to a tertiary care facility for treatment of an acute hip fracture have worse outcome than nontransfer patients. Unadjusted data such as in-hospital mortality may be misleading, but risk adjustment using the APR-DRG methodology and additional correction for transfer status may provide meaningful benchmarks.
C1 [Ring, David] Harvard Univ, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Med Sch,Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Smith, R. Malcolm; Vrahas, Mark S.] Harvard Univ, Orthopaed Trauma Serv, Massachusetts Gen Hosp, Med Sch,Dept Orthopaed, Boston, MA 02114 USA.
RP Ring, D (reprint author), Harvard Univ, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Med Sch,Massachusetts Gen Hosp, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
OI Guitton, Thierry/0000-0002-2599-1985
NR 22
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-5339
J9 J ORTHOP TRAUMA
JI J. Orthop. Trauma
PD NOV
PY 2011
VL 25
IS 11
BP 666
EP 669
DI 10.1097/BOT.0b013e31821146b1
PG 4
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA 838BB
UT WOS:000296260300008
PM 21857540
ER
PT J
AU Dehghan, S
Seto, J
Hudson, NR
Robinson, CM
Jones, MS
Dyer, DW
Chodosh, J
Seto, D
AF Dehghan, Shoaleh
Seto, Jason
Hudson, Nolan R.
Robinson, Christopher M.
Jones, Morris S.
Dyer, David W.
Chodosh, James
Seto, Donald
TI Complete Genome Sequence of Human Adenovirus Prototype 17
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VECTOR DEVELOPMENT
AB As one of the first five human adenoviruses (HAdVs) to be sequenced, type 17 was important as a reference tool for comparative genomics of recently isolated HAdV pathogens in species D. HAdV-D17 was the first species D adenovirus to be sequenced and was deposited in GenBank in 1999. These genome data were not of high quality, and a redetermination of the same stock virus provides corrected data; among the differences are a length of 35,139 bp versus 35,100 bp in the original, and 160 mismatches to the original genome were found. Annotation of the coding sequences reveals 39 as opposed to 8, a finding which is important for phylogenomic studies.
C1 [Dehghan, Shoaleh; Seto, Jason; Seto, Donald] George Mason Univ, Sch Syst Biol, Manassas, VA 20110 USA.
[Hudson, Nolan R.; Jones, Morris S.] Calif Dept Publ Hlth, Viral & Rickettsial Dis Lab, Richmond, CA 94804 USA.
[Robinson, Christopher M.; Chodosh, James] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Howe Lab, Boston, MA 02114 USA.
[Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA.
RP Seto, D (reprint author), George Mason Univ, Sch Syst Biol, 10900 Univ Blvd,MSN 5B3, Manassas, VA 20110 USA.
EM dseto@gmu.edu
FU U.S. Public Health Service NIH [EY013124, P30EY014104]; Research to
Prevent Blindness, Inc.
FX This work was supported in part by U.S. Public Health Service NIH grants
EY013124 (D. S., M.S.J., D. W. D., and J.C.) and P30EY014104 (J.C.).
J.C. is also funded by an unrestricted grant to the Department of
Ophthalmology, Harvard Medical School, from Research to Prevent
Blindness, Inc.
NR 7
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD NOV
PY 2011
VL 85
IS 21
BP 11540
EP 11541
DI 10.1128/JVI.06051-11
PG 2
WC Virology
SC Virology
GA 837ZL
UT WOS:000296254400060
PM 21980031
ER
PT J
AU Chung, JH
Wu, CC
Gilman, MD
Palmer, EL
Hasserjian, RP
Shepard, JAO
AF Chung, Jonathan H.
Wu, Carol C.
Gilman, Matthew D.
Palmer, Edwin L.
Hasserjian, Robert P.
Shepard, Jo-Anne O.
TI Lymphomatoid Granulomatosis: CT and FDG-PET Findings
SO KOREAN JOURNAL OF RADIOLOGY
LA English
DT Article
DE Lymphomatoid granulomatosis; Cavitation; Pulmonary nodules; Pulmonary
masses; Halo sign; Air-bronchogram sign
ID RARE CAUSE; PROLIFERATION; NODULES; DISEASE; LUNG; SIGN
AB Objective: Lymphomatoid granulomatosis (LG) is a rare, aggressive extranodal Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disease. The purpose of our study was to analyze the CT and fluorodeoxyglucose positron emission tomography (FOG-PET) findings of pulmonary LG.
Materials and Methods: Between 2000 and 2009, four patients with pathologically proven pulmonary LG and chest CT were identified. Two of these patients also had FOG-PET. Imaging features of LG on CT and PET were reviewed.
Results: Pulmonary nodules or masses with peribronchovascular, subpleural, and lower lung zonal preponderance were present in all patients. Central low attenuation (4 of 4 patients), ground-glass halo (3 of 4 patients), and peripheral enhancement (4 of 4 patients) were observed in these nodules and masses. An air-bronchogram and cavitation were seen in three of four patients. FDG-PET scans demonstrated avid FOG uptake in the pulmonary nodules and masses.
Conclusion: Pulmonary LG presents with nodules and masses with a lymphatic distribution, as would be expected for a lymphoproliferative disease. However, central low attenuation, ground-glass halo and peripheral enhancement of the nodules/masses are likely related to the angioinvasive nature of this disease. Peripheral enhancement and ground-glass halo, in particular, are valuable characteristic not previously reported that can help radiologists suggest the diagnosis of pulmonary LG.
C1 [Chung, Jonathan H.] Natl Jewish Hlth, Inst Adv Biomed Imaging, Denver, CO 80206 USA.
[Wu, Carol C.; Gilman, Matthew D.; Palmer, Edwin L.; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Chung, JH (reprint author), Natl Jewish Hlth, Inst Adv Biomed Imaging, 1400 Jackson St, Denver, CO 80206 USA.
EM chungj@njhealth.org
FU Siemens AG; NIH
FX Jonathan H. Chung, MD receives salary support from Siemens AG and the
NIH.
NR 21
TC 8
Z9 9
U1 0
U2 5
PU KOREAN RADIOLOGICAL SOC
PI SEOUL
PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA
SN 1229-6929
J9 KOREAN J RADIOL
JI Korean J. Radiol.
PD NOV-DEC
PY 2011
VL 12
IS 6
BP 671
EP 678
DI 10.3348/kjr.2011.12.6.671
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 838TI
UT WOS:000296314700003
PM 22043148
ER
PT J
AU Mueller, T
Beutler, C
Pico, AH
Shibolet, O
Pratt, DS
Pascher, A
Neuhaus, P
Wiedenmann, B
Berg, T
Podolsky, DK
AF Mueller, Tobias
Beutler, Claudia
Pico, Almudena Hurtado
Shibolet, Oren
Pratt, Daniel S.
Pascher, Andreas
Neuhaus, Peter
Wiedenmann, Bertram
Berg, Thomas
Podolsky, Daniel K.
TI Enhanced innate immune responsiveness and intolerance to intestinal
endotoxins in human biliary epithelial cells contributes to chronic
cholangitis
SO LIVER INTERNATIONAL
LA English
DT Article
DE cholangiocyte; innate immune hypo-responsiveness; intestinal endotoxin;
nucleotide-binding oligomerization domain protein; primary sclerosing
cholangitis; toll-like receptor
ID PRIMARY SCLEROSING CHOLANGITIS; TOLL-LIKE RECEPTOR;
INFLAMMATORY-BOWEL-DISEASE; NECROSIS-FACTOR-ALPHA; KAPPA-B ACTIVATION;
SIGNALING PATHWAYS; UP-REGULATION; INCREASED EXPRESSION; LIPOTEICHOIC
ACID; GAMMA-INTERFERON
AB Background: Pattern recognition receptors (PRRs) orchestrate the innate immune defence in human biliary epithelial cells (BECs). Tight control of PRR signalling provides tolerance to physiological amounts of intestinal endotoxins in human bile to avoid constant innate immune activation in BECs. Aims: We wanted to determine whether inappropriate innate immune responses to intestinal endotoxins contribute to the development and perpetuation of chronic biliary inflammation. Methods: We examined PRR-mediated innate immune responses and protective endotoxin tolerance in primary BECs isolated from patients with primary sclerosing cholangitis (PSC), alcoholic liver disease and patients without chronic liver disease. Expression studies comprised northern blots, RT-PCR, Western blots and immunocytochemistry. Functional studies comprised immuno-precipitation Western blots, FACS for endotoxin uptake, and NF-kappa B activation assays and ELISA for secreted IL-8 and tumour necrosis factor (TNF)-alpha. Results: Primary BECs from explanted PSC livers showed reversibly increased TLR and NOD protein expression and activation of the MyD88/IRAK signalling complex. Consecutively, PSC BECs exhibited inappropriate innate immune responses to endotoxins and did not develop immune tolerance after repeated endotoxin exposures. This endotoxin hyper-responsiveness was probably because of the stimulatory effect of abundantly expressed IFN-gamma and TNF-alpha in PSC livers, which stimulated TLR4-mediated endotoxin signalling in BECs, leading to increased TLR4-mediated endotoxin incorporation and impaired inactivation of the TLR4 signalling cascade. As TNF-alpha inhibition partly restored protective innate immune tolerance, endogenous TNF-alpha secretion probably contributed to inappropriate endotoxin responses in BECs. Conclusion: Inappropriate innate immune responses to intestinal endotoxins and subsequent endotoxin intolerance because of enhanced PRR signalling in BECs probably contribute to chronic cholangitis.
C1 [Podolsky, Daniel K.] Univ Texas SW Med Ctr Dallas, Dallas, TX USA.
[Mueller, Tobias; Beutler, Claudia; Pico, Almudena Hurtado; Wiedenmann, Bertram] Charite, Med Klin Schwerpunkt Hepatol & Gastroenterol, Campus Virchow Klinikum, D-13353 Berlin, Germany.
[Shibolet, Oren] Hadassah Hebrew Univ, Dept Med, Liver Unit, Med Ctr Jerusalem, Jerusalem, Israel.
[Pratt, Daniel S.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA.
[Pratt, Daniel S.] Harvard Univ, Sch Med, Boston, MA USA.
[Pascher, Andreas; Neuhaus, Peter] Charite, Klin Allgemein Visceral & Transplantationschirurg, Campus Virchow Klinikum, D-13353 Berlin, Germany.
[Berg, Thomas] Univ Klinikum Leipzig, Klin Gastroenterol & Rheumatol, Sekt Hepatol, Leipzig, Germany.
RP Podolsky, DK (reprint author), UT SW Med Ctr, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM daniel.podolsky@utsouthwestern.edu
OI Berg, Thomas/0000-0003-0003-6241
FU NIDDK NIH HHS [P30 DK043351, R01 DK069344, T32 DK007191]
NR 57
TC 29
Z9 30
U1 0
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1478-3223
J9 LIVER INT
JI Liver Int.
PD NOV
PY 2011
VL 31
IS 10
BP 1574
EP 1588
DI 10.1111/j.1478-3231.2011.02635.x
PG 15
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 837YM
UT WOS:000296249800019
PM 22093333
ER
PT J
AU Gialamas, SP
Petridou, ET
Tseleni-Balafouta, S
Spyridopoulos, TN
Matsoukis, IL
Kondi-Pafiti, A
Zografos, G
Mantzoros, CS
AF Gialamas, Spyros P.
Petridou, Eleni Th.
Tseleni-Balafouta, Sofia
Spyridopoulos, Themistoklis N.
Matsoukis, Ioannis L.
Kondi-Pafiti, Agathi
Zografos, George
Mantzoros, Christos S.
TI Serum adiponectin levels and tissue expression of adiponectin receptors
are associated with risk, stage, and grade of colorectal cancer
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
ID PLASMA ADIPONECTIN; PROGNOSTIC-SIGNIFICANCE; LEPTIN CONCENTRATIONS;
METABOLIC SYNDROME; OBESITY; COLON; CARCINOMA; METAANALYSIS; ACTIVATION;
SURVIVAL
AB Adiponectin has been associated with colorectal cancer (CRC) risk This study aims to investigate the association of both adiponectin and tissue expression of its receptors with CRC risk as well as clinicopathological characteristics, notably stage and grade. Determination of serum adiponectin and immunohistochemical expression of adiponectin receptors in adenocarcinoma/normal colorectal tissue was performed in samples from 104 newly diagnosed CRC patients and 208 age- and sex-matched controls. Multiple logistic regression odds ratios and 95% confidence intervals for CRC risk were derived, controlling for a series of covariates. Serum adiponectin was negatively associated with CRC risk (odds ratio, 0.72; confidence interval, 0.53-0.99) and also with tumor grade (P = .05). Expression of both adiponectin receptors was stronger in adenocarcinoma vs normal tissue (P = .001). AdipoR1 expression was negatively associated with nodal stage (P = .03); AdipoR2 expression was positively associated with tumor, node, metastasis stage (P = .01). Established positive associations with red meat consumption and diabetes, and negative associations with physical exercise and plant food consumption were confirmed along with a more than 60% higher risk associated with central obesity. Adiponectin levels and tissue expression of hormonal receptors seem to be associated not only with CRC risk but also with components of clinicopathological characteristics; given power limitations, these results should be interpreted with caution. The exact nature of the association and the underlying pathophysiological mechanisms need to be further examined in large prospective studies assessing adiponectin and its receptors as novel targets for exploring CRC growth. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Gialamas, Spyros P.; Petridou, Eleni Th.; Spyridopoulos, Themistoklis N.; Matsoukis, Ioannis L.] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece.
[Tseleni-Balafouta, Sofia] Univ Athens, Sch Med, Dept Pathol, GR-11527 Athens, Greece.
[Spyridopoulos, Themistoklis N.] Univ Athens, Gen Univ Hosp Attikon, Dept Radiol 2, Athens 12462, Greece.
[Kondi-Pafiti, Agathi] Univ Athens, Aretaie Hosp, Dept Obstet & Gynecol 22, Athens 11528, Greece.
[Kondi-Pafiti, Agathi] Univ Athens, Aretaieion Hosp, Pathol Lab, Athens 11528, Greece.
[Zografos, George] Univ Athens, Sch Med, Hippokrat Hosp, Dept Propaedeut Surg 1, GR-11527 Athens, Greece.
[Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Internal Med, Boston, MA 02215 USA.
[Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02215 USA.
RP Petridou, ET (reprint author), Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece.
EM epetrid@med.uoa.gr
FU Medical School, National and Kapodistrian University of Athens, Greece;
Beth Israel Deaconess Medical Center; National Institute of Diabetes and
Digestive and Kidney Diseases [DK81913]
FX We thank Dr. D Korkolis; Vicky Kalampoki and Nick Dessypris,
statisticians; as well as M Flessa, health visitor, for their valuable
contribution to the study. Funding: The project was supported in part by
the Medical School, National and Kapodistrian University of Athens,
Greece; Beth Israel Deaconess Medical Center; and grant DK81913 from the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 52
TC 33
Z9 37
U1 1
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
J9 METABOLISM
JI Metab.-Clin. Exp.
PD NOV
PY 2011
VL 60
IS 11
BP 1530
EP 1538
DI 10.1016/j.metabol.2011.03.020
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 838RQ
UT WOS:000296310300006
PM 21632074
ER
PT J
AU Tam, CS
Berthoud, HR
Bueter, M
Chakravarthy, MV
Geliebter, A
Hajnal, A
Holst, J
Kaplan, L
Pories, W
Raybould, H
Seeley, R
Strader, A
Ravussin, E
AF Tam, C. S.
Berthoud, H. -R.
Bueter, M.
Chakravarthy, M. V.
Geliebter, A.
Hajnal, A.
Holst, J.
Kaplan, L.
Pories, W.
Raybould, H.
Seeley, R.
Strader, A.
Ravussin, E.
TI Could the mechanisms of bariatric surgery hold the key for novel
therapies?
SO OBESITY REVIEWS
LA English
DT Article
DE Bariatric surgery; gut hormones; weight loss
ID GLUCAGON-LIKE PEPTIDE-1; Y GASTRIC BYPASS; DIET-INDUCED OBESITY;
IMPROVES GLUCOSE-TOLERANCE; RESTING ENERGY-EXPENDITURE; WEIGHT-LOSS;
BODY-COMPOSITION; GUT MICROBIOTA; 7-36 AMIDE; RATS
AB Bariatric surgery is the most effective method for promoting dramatic and durable weight loss in morbidly obese subjects. Furthermore, type 2 diabetes is resolved in over 80% of patients. The mechanisms behind the amelioration in metabolic abnormalities are largely unknown but may be due to changes in energy metabolism, gut peptides and food preference. The goal of this meeting was to review the latest research to better understand the mechanisms behind the 'magic' of bariatric surgery. Replication of these effects in a non-surgical manner remains one of the ultimate challenges for the treatment of obesity and diabetes. Promising data on energy metabolism, gastrointestinal physiology, hedonic response and food intake were reviewed and discussed.
C1 [Tam, C. S.; Berthoud, H. -R.; Ravussin, E.] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
[Bueter, M.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England.
[Chakravarthy, M. V.] Merck Res Labs, Rahway, NJ USA.
[Geliebter, A.] Columbia Univ, New York, NY USA.
[Hajnal, A.] Penn State Univ, Hershey, PA USA.
[Holst, J.] Univ Copenhagen, Copenhagen, Denmark.
[Kaplan, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pories, W.] E Carolina Univ, Brody Sch Med, Greenville, NC USA.
[Raybould, H.] Univ Calif Davis, Davis, CA 95616 USA.
[Seeley, R.] Univ Cincinnati, Cincinnati, OH USA.
[Strader, A.] So Illinois Univ, Sch Med, Carbondale, IL 62901 USA.
RP Ravussin, E (reprint author), Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
EM eric.ravussin@pbrc.edu
FU Ajinomoto Co, Inc.; Amylin/Lilly Alliance; Covidien; Ethicon Endo
Surgery, Inc.; GlaxoSmithKline; PepsiCo; The Pennington Biomedical
Research Center Foundation
FX This meeting was sponsored by Ajinomoto Co, Inc., Amylin/Lilly Alliance,
Covidien, Ethicon Endo Surgery, Inc., GlaxoSmithKline, PepsiCo and The
Pennington Biomedical Research Center Foundation.
NR 50
TC 22
Z9 23
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1467-7881
J9 OBES REV
JI Obes. Rev.
PD NOV
PY 2011
VL 12
IS 11
BP 984
EP 994
DI 10.1111/j.1467-789X.2011.00902.x
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 835UC
UT WOS:000296060500007
PM 21729236
ER
PT J
AU Axelrod, FB
Liebes, L
Gold-von Simson, G
Mendoza, S
Mull, J
Leyne, M
Norcliffe-Kaufmann, L
Kaufmann, H
Slaugenhaupt, SA
AF Axelrod, Felicia B.
Liebes, Leonard
Gold-von Simson, Gabrielle
Mendoza, Sandra
Mull, James
Leyne, Maire
Norcliffe-Kaufmann, Lucy
Kaufmann, Horacio
Slaugenhaupt, Susan A.
TI Kinetin Improves IKBKAP mRNA Splicing in Patients With Familial
Dysautonomia
SO PEDIATRIC RESEARCH
LA English
DT Article
ID EXPRESSION; MUTATION; CELLS
AB Familial dysautonomia (FD) is caused by an intronic splice mutation in the IKBKAP gene that leads to partial skipping of exon 20 and tissue-specific reduction in I-kappa-B kinase complex-associated protein/elongation protein 1 (IKAP/ELP-1) expression. Kinetin (6-furfurylaminopurine) has been shown to improve splicing and increase WT IKBKAP mRNA and IKAP protein expression in FD cell lines and carriers. To determine whether oral kinetin treatment could alter mRNA splicing in FD subjects and was tolerable, we administered kinetin to eight FD individuals homozygous for the splice mutation. Subjects received 23.5 mg/Kg/d for 28 d. An increase in WT IKBKAP mRNA expression in leukocytes was noted after 8 d in six of eight individuals; after 28 d, the mean increase compared with baseline was significant (p = 0.002). We have demonstrated that kinetin is tolerable in this medically fragile population. Not only did kinetin produce the desired effect on splicing in FD patients but also that effect seems to improve with time despite lack of dose change. This is the first report of a drug that produces in vivo mRNA splicing changes in individuals with FD and supports future long-term trials to determine whether kinetin will prove therapeutic in FD patients. (Pediatr Res 70: 480-483, 2011)
C1 [Axelrod, Felicia B.] NYU, Dysauton Ctr, Langone Med Ctr, Dept Pediat,Sch Med, New York, NY 10016 USA.
[Axelrod, Felicia B.; Kaufmann, Horacio] NYU, Dept Neurol, Sch Med, New York, NY 10016 USA.
[Liebes, Leonard; Mendoza, Sandra] NYU, Dept Med, Sch Med, New York, NY 10016 USA.
[Norcliffe-Kaufmann, Lucy] NYU, Dept Physiol & Neurosci, Sch Med, New York, NY 10016 USA.
[Mull, James; Leyne, Maire; Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Dept Neurol Genet, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Axelrod, FB (reprint author), NYU, Dysauton Ctr, Langone Med Ctr, Dept Pediat,Sch Med, 530 1st Ave,Suite 9Q, New York, NY 10016 USA.
EM felicia.axelrod@nyumc.org
FU CTSI [1UL1RR029893]; NIH of the National Center for Research Resources
[M01 RR-00096, NIH NS058318, NS036326, U54NS065736, FDA FD-R-3731-01];
Dysautonomia Foundation, Inc, New York, NY
FX Supported by CTSI Grant 1UL1RR029893 and grants from the NIH General
Clinical Research Centers Program of the National Center for Research
Resources M01 RR-00096: NIH NS058318, NS036326, U54NS065736: FDA
FD-R-3731-01, and awards from the Dysautonomia Foundation, Inc, New
York, NY.
NR 17
TC 29
Z9 29
U1 1
U2 7
PU INT PEDIATRIC RESEARCH FOUNDATION, INC
PI BALTIMORE
PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA
SN 0031-3998
J9 PEDIATR RES
JI Pediatr. Res.
PD NOV
PY 2011
VL 70
IS 5
BP 480
EP 483
PG 4
WC Pediatrics
SC Pediatrics
GA 836ON
UT WOS:000296121100007
PM 21775922
ER
PT J
AU Holzel, BK
Lazar, SW
Gard, T
Schuman-Olivier, Z
Vago, DR
Ott, U
AF Hoelzel, Britta K.
Lazar, Sara W.
Gard, Tim
Schuman-Olivier, Zev
Vago, David R.
Ott, Ulrich
TI How Does Mindfulness Meditation Work? Proposing Mechanisms of Action
From a Conceptual and Neural Perspective
SO PERSPECTIVES ON PSYCHOLOGICAL SCIENCE
LA English
DT Article
DE anxiety disorders; attention; cognition; consciousness; neuroscience;
positive psychology; stress disorders
ID VENTROMEDIAL PREFRONTAL CORTEX; RANDOMIZED CONTROLLED-TRIAL; STRESS
REDUCTION PROGRAM; GENERALIZED ANXIETY DISORDER; SHORT-TERM MEDITATION;
HIPPOCAMPAL INACTIVATION DISRUPTS; FUNCTIONAL MAGNETIC-RESONANCE;
PEDIATRIC BIPOLAR DISORDER; TEMPORO-PARIETAL JUNCTION;
CEREBRAL-BLOOD-FLOW
AB Cultivation of mindfulness, the nonjudgmental awareness of experiences in the present moment, produces beneficial effects on well-being and ameliorates psychiatric and stress-related symptoms. Mindfulness meditation has therefore increasingly been incorporated into psychotherapeutic interventions. Although the number of publications in the field has sharply increased over the last two decades, there is a paucity of theoretical reviews that integrate the existing literature into a comprehensive theoretical framework. In this article, we explore several components through which mindfulness meditation exerts its effects: (a) attention regulation, (b) body awareness, (c) emotion regulation (including reappraisal and exposure, extinction, and reconsolidation), and (d) change in perspective on the self. Recent empirical research, including practitioners' self-reports and experimental data, provides evidence supporting these mechanisms. Functional and structural neuroimaging studies have begun to explore the neuroscientific processes underlying these components. Evidence suggests that mindfulness practice is associated with neuroplastic changes in the anterior cingulate cortex, insula, temporo-parietal junction, fronto-limbic network, and default mode network structures. The authors suggest that the mechanisms described here work synergistically, establishing a process of enhanced self-regulation. Differentiating between these components seems useful to guide future basic research and to specifically target areas of development in the treatment of psychological disorders.
C1 [Hoelzel, Britta K.; Gard, Tim; Ott, Ulrich] Univ Giessen, Bender Inst Neuroimaging, D-35394 Giessen, Germany.
[Hoelzel, Britta K.; Lazar, Sara W.; Gard, Tim; Schuman-Olivier, Zev] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Vago, David R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
RP Holzel, BK (reprint author), Univ Giessen, Bender Inst Neuroimaging, Otto Behaghel Str 10 H, D-35394 Giessen, Germany.
EM britta@nmr.mgh.harvard.edu
RI Lazar, Sara/G-3809-2012
OI Lazar, Sara/0000-0003-1126-8363
FU NCCIH NIH HHS [R01 AT006344, R21 AT003425]
NR 243
TC 407
Z9 415
U1 72
U2 372
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1745-6916
J9 PERSPECT PSYCHOL SCI
JI Perspect. Psychol. Sci.
PD NOV
PY 2011
VL 6
IS 6
BP 537
EP 559
DI 10.1177/1745691611419671
PG 23
WC Psychology, Multidisciplinary
SC Psychology
GA 833LV
UT WOS:000295887900003
PM 26168376
ER
PT J
AU Lee, J
Zaki, J
Harvey, PO
Ochsner, K
Green, MF
AF Lee, J.
Zaki, J.
Harvey, P. -O.
Ochsner, K.
Green, M. F.
TI Schizophrenia patients are impaired in empathic accuracy
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Empathic accuracy; expressivity; schizophrenia; social cognition
ID NATURALISTIC SOCIAL COGNITION; BASES; NEUROSCIENCE
AB Background. Empathy is crucial for successful social relationships. Despite its importance for social interactions, little is known about empathy in schizophrenia. This study investigated the degree to which schizophrenia patients can accurately infer the affective state of another person (i.e. empathic accuracy).
Method. A group of 30 schizophrenia patients and 22 healthy controls performed an empathic accuracy task on which they continuously rated the affective state of another person shown in a video (referred to as the 'target'). These ratings were compared with the target's own continuous self-rating of affective state; empathic accuracy was defined as the correlation between participants' ratings and the targets' self-ratings. A separate line-tracking task was administered to measure motoric/attentional factors that could account for group differences in performance. Participants' self-rated empathy was measured using the Interpersonal Reactivity Index, and targets' self-rated emotional expressivity was measured using the Berkeley Expressivity Questionnaire.
Results. Compared with controls, schizophrenia patients showed lower empathic accuracy although they performed the motoric tracking task at high accuracy. There was a significant group x target expressivity interaction such that patients showed a smaller increase in empathic accuracy with higher levels of emotional expressivity by the target, compared with controls. Patients' empathic accuracy was uncorrelated with self-reported empathy or clinical symptoms.
Conclusions. Schizophrenia patients showed lower empathic accuracy than controls, and their empathic accuracy was less influenced by the emotional expressivity of the target. These findings suggest that schizophrenia patients benefit less from social cues of another person when making an empathic judgement.
C1 [Lee, J.; Harvey, P. -O.; Green, M. F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
[Lee, J.; Harvey, P. -O.; Green, M. F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Zaki, J.; Ochsner, K.] Columbia Univ, Dept Psychol, New York, NY 10027 USA.
RP Lee, J (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 300 Med Plaza,Room 2261, Los Angeles, CA 90095 USA.
EM jungheelee@ucla.edu
RI Lee, Junghee/C-5226-2014
OI Lee, Junghee/0000-0001-9567-8700
FU National Institute of Mental Health (NIMH) [MH043292, MH076137];
National Institute on Drug Abuse (NIDA) [DA022541]; Autism Speaks Grant
[4787]
FX Support for this study came from a National Institute of Mental Health
(NIMH) grant (no. MH043292 to M. F. G.), a National Institute on Drug
Abuse (NIDA) grant (no. DA022541 to K.O.), a NIMH grant (no. MH076137 to
K.O.) and an Autism Speaks Grant (no. 4787 to J.Z.). The authors thank
Mark R. McGee, Shelly Crosby and Cory Tripp for assistance in data
collection.
NR 43
TC 38
Z9 38
U1 2
U2 14
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD NOV
PY 2011
VL 41
IS 11
BP 2297
EP 2304
DI 10.1017/S0033291711000614
PG 8
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 837XX
UT WOS:000296246300006
PM 21524334
ER
PT J
AU Loscalzo, J
Barabasi, AL
AF Loscalzo, Joseph
Barabasi, Albert-Laszlo
TI Systems biology and the future of medicine
SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE
LA English
DT Article
ID PROTEIN-INTERACTION NETWORK; HUMAN-DISEASE; COMPLEX NETWORKS; GENETIC
INTERACTIONS; METABOLIC NETWORKS; SMALL-WORLD; IDENTIFICATION;
ORGANIZATION; INTERACTOME; RESOURCE
AB Contemporary views of human disease are based on simple correlation between clinical syndromes and pathological analysis dating from the late 19th century. Although this approach to disease diagnosis, prognosis, and treatment has served the medical establishment and society well for many years, it has serious shortcomings for the modern era of the genomic medicine that stem from its reliance on reductionist principles of experimentation and analysis. Quantitative, holistic systems biology applied to human disease offers a unique approach for diagnosing established disease, defining disease predilection, and developing individualized ( personalized) treatment strategies that can take full advantage of modern molecular pathobiology and the comprehensive data sets that are rapidly becoming available for populations and individuals. In this way, systems pathobiology offers the promise of redefining our approach to disease and the field of medicine. (C) 2011 John Wiley & Sons, Inc. WIREs Syst Biol Med 2011 3 619-627 DOI: 10.1002/wsbm. 144
C1 [Loscalzo, Joseph; Barabasi, Albert-Laszlo] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Loscalzo, Joseph; Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Boston, MA USA.
[Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Ctr Canc Syst Biol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Barabasi, Albert-Laszlo] Northeastern Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Ctr Complex Networks Res, Boston, MA 02115 USA.
RP Loscalzo, J (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
EM jloscalzo@partners.org
FU NIH [HL61795, HL81587, HL70819, HL48743]
FX This work was supported in part by NIH grants HL61795, HL81587, HL70819,
and HL48743. The author wishes to thank Stephanie Tribuna for expert
technical assistance.
NR 68
TC 81
Z9 84
U1 2
U2 30
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1939-5094
J9 WIRES SYST BIOL MED
JI Wiley Interdiscip. Rev.-Syst. Biol
PD NOV-DEC
PY 2011
VL 3
IS 6
BP 619
EP 627
DI 10.1002/wsbm.144
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 838GQ
UT WOS:000296275800001
PM 21928407
ER
PT J
AU Sargent, DJ
Resnick, MB
Meyers, MO
Goldar-Najafi, A
Clancy, T
Gill, S
Siemons, GO
Shi, Q
Bot, BM
Wu, TT
Beaudry, G
Haince, JF
Fradet, Y
AF Sargent, Daniel J.
Resnick, Murray B.
Meyers, Michael O.
Goldar-Najafi, Atoussa
Clancy, Thomas
Gill, Sharlene
Siemons, Gary O.
Shi, Qian
Bot, Brian M.
Wu, Tsung-Teh
Beaudry, Guillaume
Haince, Jean-Francois
Fradet, Yves
TI Evaluation of Guanylyl Cyclase C Lymph Node Status for Colon Cancer
Staging and Prognosis
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT Gastrointestinal Cancers Symposium
CY 2011
CL San Francisco, CA
ID II COLORECTAL-CANCER; DEFECTIVE MISMATCH REPAIR;
POLYMERASE-CHAIN-REACTION; MICROSATELLITE-INSTABILITY; ADJUVANT
CHEMOTHERAPY; TUMOR-CELLS; SURVIVAL; MICROMETASTASES; EXPRESSION; NUMBER
AB Purpose. The prognostic significance of guanylyl cyclase C (GCC) gene expression in lymph nodes (LNs) was evaluated in patients with stage II colon cancer who were not treated with adjuvant chemotherapy. We report a planned analysis performed on 241 patients.
Methods. GCC mRNA was quantified by RT-qPCR using formalin-fixed LN tissues from patients with untreated stage II colon cancer who were diagnosed from 1999-2006 with at least ten LNs examined and blinded to clinical outcomes. Lymph node ratio (LNR) is the number of GCC-positive nodes divided by total number of informative LNs. Risk categories of low (0-0.1) and high (> 0.1) for LNR were chosen by significance using Cox regression models. The data were tested for association with time to recurrence.
Results. Twenty-nine patients (12%) had a disease recurrence or cancer death. The LNR significantly predicted higher recurrence risk for 84 patients (34.9%) classified as high risk (hazard ratio (HR), 2.38; P = 0.02). The estimated 5-year recurrence rates were 10% and 27% for the low- and high-risk groups, respectively. After adjusting for age, T stage, number of nodes assessed, and MMR status, a significant association remained (HR, 2.61; P = 0.02). In a subset of patients (n = 181) with T3 tumor, a parts per thousand yen 12 nodes examined and negative margins, a significant association between the GCC LNR and recurrence risk also was observed (HR, 5.06; P = 0.003).
Conclusions. Our preliminary results suggest that detection of GCC mRNA in LNs is associated with risk of disease recurrence in patients with untreated stage II colon cancer. A larger validation study is ongoing.
C1 [Sargent, Daniel J.; Shi, Qian; Bot, Brian M.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[Resnick, Murray B.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Resnick, Murray B.] Rhode Isl Hosp, Providence, RI USA.
[Meyers, Michael O.] Univ N Carolina, Div Surg Oncol, Chapel Hill, NC USA.
[Goldar-Najafi, Atoussa] Lahey Clin Gordon Canc Ctr, Dept Pathol, Burlington, MA USA.
[Clancy, Thomas] Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA.
[Clancy, Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Gill, Sharlene] Univ British Columbia, Div Med Oncol, BC Canc Agcy, Vancouver, BC V5Z 1M9, Canada.
[Siemons, Gary O.] Colon & Rectal Surg Associates S Jersey, Voorhees, NJ USA.
[Wu, Tsung-Teh] Mayo Clin, Dept Anat Pathol, Rochester, MN USA.
[Beaudry, Guillaume; Haince, Jean-Francois; Fradet, Yves] DiagnoCure Inc, Quebec City, PQ, Canada.
RP Sargent, DJ (reprint author), Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
EM sargent.daniel@mayo.edu
OI Bot, Brian/0000-0002-2412-6826; Sargent, Daniel/0000-0002-2684-4741
NR 40
TC 11
Z9 12
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD NOV
PY 2011
VL 18
IS 12
BP 3261
EP 3270
DI 10.1245/s10434-011-1731-2
PG 10
WC Oncology; Surgery
SC Oncology; Surgery
GA 832XQ
UT WOS:000295844400007
PM 21533822
ER
PT J
AU Biczo, G
Hegyi, P
Dosa, S
Shalbuyeva, N
Berczi, S
Sinervirta, R
Hracsko, Z
Siska, A
Kukor, Z
Jarmay, K
Venglovecz, V
Varga, IS
Ivanyi, B
Alhonen, L
Wittmann, T
Gukovskaya, A
Takacs, T
Rakonczay, Z
AF Biczo, Gyoergy
Hegyi, Peter
Dosa, Sandor
Shalbuyeva, Natalia
Berczi, Sandor
Sinervirta, Riitta
Hracsko, Zsuzsanna
Siska, Andrea
Kukor, Zoltan
Jarmay, Katalin
Venglovecz, Viktoria
Varga, Ilona S.
Ivanyi, Bela
Alhonen, Leena
Wittmann, Tibor
Gukovskaya, Anna
Takacs, Tamas
Rakonczay, Zoltan, Jr.
TI The Crucial Role of Early Mitochondrial Injury in L-Lysine-Induced Acute
Pancreatitis
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
ID KAPPA-B ACTIVATION; L-ARGININE; SUPEROXIDE-DISMUTASE; EXCESS LYSINE;
RATS; TRYPSINOGEN; PROTEIN; MODEL; MECHANISMS; ANALOGS
AB Aims: Large doses of intraperitoneally injected basic amino acids, L-arginine, or L-ornithine, induce acute pancreatitis in rodents, although the mechanisms mediating pancreatic toxicity remain unknown. Another basic amino acid, L-lysine, was also shown to cause pancreatic acinar cell injury. The aim of the study was to get insight into the mechanisms through which L-lysine damages the rat exocrine pancreas, in particular to characterize the kinetics of L-lysine-induced mitochondrial injury, as well as the pathologic responses (including alteration of antioxidant systems) characteristic of acute pancreatitis. Results: We showed that intraperitoneal administration of 2 g/kg L-lysine induced severe acute necrotizing pancreatitis. L-lysine administration caused early pancreatic mitochondrial damage that preceded the activation of trypsinogen and the proinflammatory transcription factor nuclear factor-kappa B (NF-kappa B), which are commonly thought to play an important role in the development of acute pancreatitis. Our data demonstrate that L-lysine impairs adenosine triphosphate synthase activity of isolated pancreatic, but not liver, mitochondria. Innovation and Conclusion: Taken together, early mitochondrial injury caused by large doses of L-lysine may lead to the development of acute pancreatitis independently of pancreatic trypsinogen and NF-kappa B activation. Antioxid. Redox Signal. 15, 2669-2681.
C1 [Biczo, Gyoergy; Hegyi, Peter; Jarmay, Katalin; Wittmann, Tibor; Takacs, Tamas; Rakonczay, Zoltan, Jr.] Univ Szeged, Dept Med 1, H-6701 Szeged, Hungary.
[Dosa, Sandor; Berczi, Sandor; Ivanyi, Bela] Univ Szeged, Dept Pathol, H-6701 Szeged, Hungary.
[Shalbuyeva, Natalia; Gukovskaya, Anna] Univ Calif Los Angeles, Los Angeles, CA USA.
[Shalbuyeva, Natalia; Gukovskaya, Anna] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Sinervirta, Riitta; Alhonen, Leena] Univ Eastern Finland, AI Virtanen Inst Mol Sci, Bioctr Kuopio, Kuopio, Finland.
[Hracsko, Zsuzsanna; Varga, Ilona S.] Univ Szeged, Dept Biochem & Mol Biol, H-6701 Szeged, Hungary.
[Siska, Andrea] Univ Szeged, Dept Clin Chem, H-6701 Szeged, Hungary.
[Kukor, Zoltan] Semmelweis Univ, Dept Med Chem Mol Biol & Pathobiochem, Budapest, Hungary.
[Venglovecz, Viktoria] Univ Szeged, Dept Pharmacol & Pharmacotherapy, H-6701 Szeged, Hungary.
RP Rakonczay, Z (reprint author), Univ Szeged, Dept Med 1, POB 427, H-6701 Szeged, Hungary.
EM raz@in1st.szote.u-szeged.hu
FU National Development Agency [TAMOP-4.2.2-08/1/2008-0002, 0013,
TAMOP-4.2.1.B-09/1/KONV-2010-0005]; Hungarian Scientific Research Fund
[K78311, NNF 78851, PD78087]; Hungarian Academy of Sciences [BO
00334/08/5, BO 00174/10/5]; Academy of Finland [130087]
FX This study was supported by National Development Agency grants
(TAMOP-4.2.2-08/1/2008-0002 and 0013;
TAMOP-4.2.1.B-09/1/KONV-2010-0005), the Hungarian Scientific Research
Fund (K78311 to Z.R., NNF 78851 to P.H., and PD78087 to V.V.), the
Hungarian Academy of Sciences (BO 00334/08/5 to P.H. and BO 00174/10/5
to Z.R.), and the Academy of Finland (130087 to L.A.). The authors would
like to thank Dr. Gizella Karacsony for her help with the TUNEL assay.
The rabbit anti-HSP72 antibody was a generous gift from Dr. Istvan
Kurucz.
NR 31
TC 12
Z9 13
U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD NOV
PY 2011
VL 15
IS 10
BP 2669
EP 2681
DI 10.1089/ars.2011.4065
PG 13
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 831MF
UT WOS:000295734400003
PM 21644850
ER
PT J
AU Gukovsky, I
Pandol, SJ
Gukovskaya, AS
AF Gukovsky, Ilya
Pandol, Stephen J.
Gukovskaya, Anna S.
TI Organellar Dysfunction in the Pathogenesis of Pancreatitis
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID MITOCHONDRIAL PERMEABILITY TRANSITION; CYTOCHROME-C RELEASE;
SMALL-MOLECULE INHIBITORS; BCL-X-L; CELL-DEATH; ACINAR-CELLS; OXIDATIVE
STRESS; MEMBRANE PERMEABILIZATION; TRYPSINOGEN ACTIVATION; CASPASE
ACTIVATION
AB Significance: Acute pancreatitis is an inflammatory disease of exocrine pancreas that carries considerable morbidity and mortality; its pathophysiology remains poorly understood. During the past decade, new insights have been gained into signaling pathways and molecules that mediate the inflammatory response of pancreatitis and death of acinar cells (the main exocrine pancreas cell type). By contrast, much less is known about the acinar cell organellar damage in pancreatitis and how it contributes to the disease pathogenesis. Recent Advances: This review summarizes recent findings from our group, obtained on experimental in vivo and ex vivo models, which reveal disordering of key cellular organelles, namely, mitochondria, autophagosomes, and lysosomes, in pancreatitis. Our results indicate a critical role for mitochondrial permeabilization in determining the balance between apoptosis and necrosis in pancreatitis, and thus the disease severity. We further investigate how the mitochondrial dysfunction (and hence acinar cell death) is regulated by Ca(2+), reactive oxygen species, and BclxL, in relation to specific properties of pancreatic mitochondria. Our results also reveal that autophagy, the principal cellular degradative, lysosome-driven pathway, is impaired in pancreatitis due to inefficient lysosomal function, and that impaired autophagy mediates two key pathological responses of pancreatitis-accumulation of vacuoles in acinar cells and the abnormal, intra-acinar activation of digestive enzymes such as trypsinogen. Critical Issues and Future Directions: The findings discussed in this review indicate critical roles for mitochondrial and autophagic/lysosomal dysfunctions in the pathogenesis of pancreatitis and delineate directions for detailed investigations into the molecular events that underlie acinar cell organellar damage. Antioxid. Redox Signal. 15, 2699-2710.
C1 [Gukovsky, Ilya; Pandol, Stephen J.; Gukovskaya, Anna S.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
RP Gukovsky, I (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
EM igukovsk@ucla.edu; agukovsk@ucla.edu
FU NIH [DK59936, AA19730]
FX Department of Veterans Affairs; NIH R01 grants DK59936 and AA19730;
Southern California Research Center for Alcoholic Liver and Pancreatic
Diseases and Cirrhosis (NIH P50AA11999).
NR 92
TC 23
Z9 24
U1 0
U2 10
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD NOV
PY 2011
VL 15
IS 10
BP 2699
EP 2710
DI 10.1089/ars.2011.4068
PG 12
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 831MF
UT WOS:000295734400005
PM 21834686
ER
PT J
AU Bigdeli, T
Neale, M
Neale, B
AF Bigdeli, Tim
Neale, Michael
Neale, Benjamin
TI Empirical significance for low-frequency common variants
SO BEHAVIOR GENETICS
LA English
DT Meeting Abstract
CT 41st Annual Meeting of the Behaviour-Genetics-Association
CY JUN 06-09, 2011
CL Newport, RI
SP Behav Genet Assoc
C1 [Neale, Michael] Virginia Commonwealth Univ, Richmond, VA 23284 USA.
[Neale, Benjamin] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-8244
J9 BEHAV GENET
JI Behav. Genet.
PD NOV
PY 2011
VL 41
IS 6
SI SI
BP 894
EP 894
PG 1
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA 826BO
UT WOS:000295326600024
ER
PT J
AU Neale, B
AF Neale, Benjamin
TI Analytic issues in next generation sequencing: Lessons from exome-wide
sequencing of autism
SO BEHAVIOR GENETICS
LA English
DT Meeting Abstract
CT 41st Annual Meeting of the Behaviour-Genetics-Association
CY JUN 06-09, 2011
CL Newport, RI
SP Behav Genet Assoc
C1 [Neale, Benjamin] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-8244
J9 BEHAV GENET
JI Behav. Genet.
PD NOV
PY 2011
VL 41
IS 6
SI SI
BP 927
EP 927
PG 1
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA 826BO
UT WOS:000295326600132
ER
PT J
AU Lee, J
Hwang, YJ
Boo, JH
Han, D
Kwon, OK
Todorova, K
Kowall, NW
Kim, Y
Ryu, H
AF Lee, J.
Hwang, Y. J.
Boo, J. H.
Han, D.
Kwon, O. K.
Todorova, K.
Kowall, N. W.
Kim, Y.
Ryu, H.
TI Dysregulation of upstream binding factor-1 acetylation at K352 is linked
to impaired ribosomal DNA transcription in Huntington's disease
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
DE UBF1; rDNA transcription; CBP; acetylation; Huntington's disease
ID RNA-POLYMERASE-I; GENE-EXPRESSION; CREB-BINDING; CAG REPEAT; FACTOR UBF;
POLYGLUTAMINE; NEURONS; CBP; PROTEIN; NEURODEGENERATION
AB Huntington's disease (HD) is an autosomal-dominant neurological disorder caused by expanded CAG repeats in the Huntingtin (Htt) gene, but it is not known how this mutation causes neurodegeneration. Herein, we found that dysfunction of upstream binding factor-1 (UBF-1) is linked to reduced ribosomal DNA (rDNA) transcription in HD. We identified that UBF1 acetylation at Lys (K) 352 by CREB binding protein (CBP) is crucial for the transcriptional activity of rDNA. UBF1 mutation (K352A, K352Q, and K352R) decreased rDNA transcriptional activity. Moreover, both CBP-dHAT mutant and knockdown of CBP by siRNA reduced acetylation of UBF1 and resulted in the decreased transcription of rDNA into rRNA. ChIP analysis showed a significant reduction of UBF1 occupancy in the promoter of rDNA in STHdh(Q111) cell line model of HD. These results demonstrate that abnormal activity of UBF1 and its acetylation by CBP are linked to impaired rDNA transcription in HD. This novel mechanism suggests that modulation of UBF-mediated rDNA synthesis by CBP may be a therapeutic target for improving neuronal rDNA transcription in HD. Cell Death and Differentiation (2011) 18, 1726-1735; doi: 10.1038/cdd.2011.38; published online 6 May 2011
C1 [Lee, J.; Todorova, K.; Kowall, N. W.; Ryu, H.] Boston Univ, Sch Med, Dept Neurol, Boston VA Healthcare Syst, Boston, MA 02130 USA.
[Hwang, Y. J.; Boo, J. H.; Ryu, H.] Seoul Natl Univ, Coll Med, Dept Biomed Sci, World Class Univ Neurocyt Grp, Seoul, South Korea.
RP Ryu, H (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston VA Healthcare Syst, Bldg 1A,Rm109,150 S Huntington Ave, Boston, MA 02130 USA.
EM hoonryu@bu.edu
RI Kowall, Neil/G-6364-2012; Kim, Youngsoo/D-6046-2012
OI Kowall, Neil/0000-0002-6624-0213;
FU WCU [800-20080848]; KOSEF [2010-0029-403]; NIH [NS52724]; Converging
Research Center through NRF of Korea [20090094081]
FX We thank Dr. Samson T. Jacob for pIRES-Luc and Human rRNA-luciferase
Vector and Dr. Marcy MacDonald for STHdhQ7/7 and
STHdhQ111/111 cells. We thank Dr. Byoung Yul Soh for his
technical assistance. This study was supported by WCU Neurocytomics
Program Grant (800-20080848) (H. R.) and SRC Grant (2010-0029-403) (H.
R.) from KOSEF and NIH NS52724 (H. R.). This work was also supported in
part by the Converging Research Center Program (20090094081) (Y.K.)
through NRF of Korea.
NR 36
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U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD NOV
PY 2011
VL 18
IS 11
BP 1726
EP 1735
DI 10.1038/cdd.2011.38
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 834AQ
UT WOS:000295929600005
PM 21546905
ER
PT J
AU Fish, KN
Sweet, RA
Lewis, DA
AF Fish, Kenneth N.
Sweet, Robert A.
Lewis, David A.
TI Differential Distribution of Proteins Regulating GABA Synthesis and
Reuptake in Axon Boutons of Subpopulations of Cortical Interneurons
SO CEREBRAL CORTEX
LA English
DT Article
DE cannabinoid 1 receptor; GABA; GABA membrane transporter 1; glutamic acid
decarboxylase; parvalbumin
ID GLUTAMIC-ACID DECARBOXYLASE; GAMMA-AMINOBUTYRIC-ACID; MONKEY PREFRONTAL
CORTEX; CANNABINOID CB1 RECEPTOR; GAD(67) MESSENGER-RNAS; RAT
SPINAL-CORD; POSTNATAL-DEVELOPMENT; 2 FORMS; MONOCLONAL-ANTIBODIES;
TRANSIENT INCREASE
AB Subclasses of gamma-aminobutyric acid (GABA) interneurons differentially influence cortical network activity. The contribution of differences in GABA synthesis and reuptake in axon boutons to cell type-specific functions is unknown. GABA is synthesized within boutons by glutamic acid decarboxylase 65 (GAD65) and GAD67, while GAT1 is responsible for GABA reuptake. Using an imaging methodology capable of determining the colocalization frequency of different immunocytochemical labels in the same bouton and the quantification of the fluorescence intensity of each label in these same structures, we assessed the bouton levels of GAD65, GAD67, and GAT1 in parvalbumin-expressing chandelier (PV(ch)) and basket (PV(b)) neurons and cannabinoid 1 receptor-expressing basket (CB1r(b)) neurons in the monkey prefrontal cortex. We show that PV(ch) boutons almost exclusively contained GAD67, relative to GAD65, whereas CB1r(b) boutons contained mostly GAD65. In contrast, both GAD65 and GAD67 were easily detected in PV(b) boutons. Furthermore, in comparison with PV(ch) boutons, CB1r(b) boutons expressed low to undetectable levels of GAT1. Our findings provide a new basis for the distinctive functional roles of these perisomatic-innervating interneurons in cortical circuits. In addition, they strongly suggest that altered levels of GAD67 or GAD65, as seen in some psychiatric diseases, would have cell type-specific consequences on the modulation of GABA neurotransmission.
C1 [Fish, Kenneth N.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Translat Neurosci Program, Pittsburgh, PA 15213 USA.
[Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA.
[Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN MIRECC 4, Pittsburgh, PA 15206 USA.
[Lewis, David A.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15213 USA.
RP Fish, KN (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Translat Neurosci Program, Biomed Sci Tower,Room E1652,3811 OHara St, Pittsburgh, PA 15213 USA.
EM fishkn@upmc.edu
RI Lewis, David/G-4053-2014
OI Lewis, David/0000-0002-3225-6778
FU National Institutes of Health [MH051234, MH084053, MH071533, MH085108];
BMS foundation; Bristol-Myers Squibb; Curridium Ltd; Pfizer
FX This work was supported by the National Institutes of Health (grant
numbers MH051234 and MH084053 to D. A. L., MH071533 to R. A. S.,
MH085108 to K.N.F.).; Conflict of Interest: D. A. L. currently receives
investigator-initiated research support from the BMS foundation,
Bristol-Myers Squibb, Curridium Ltd, and Pfizer and in 2007-2009 served
as a consultant in the areas of target identification and validation,
and new compound development to AstraZeneca, BioLine RX, Bristol-Myers
Squibb, Hoffman-Roche, Lilly, Merck, Neurogen, and SK Life Science. All
other authors report no competing interest.
NR 56
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U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD NOV
PY 2011
VL 21
IS 11
BP 2450
EP 2460
DI 10.1093/cercor/bhr007
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 827FK
UT WOS:000295413200003
PM 21422269
ER
PT J
AU Li, YX
Tafti, BA
Shaba, W
Berenji, GR
AF Li, Yuxin
Tafti, Bashir A.
Shaba, Wisam
Berenji, Gholam R.
TI Superscan Pattern of F-18 Sodium Fluoride PET/CT Study in a Case of
Prostate Cancer
SO CLINICAL NUCLEAR MEDICINE
LA English
DT Editorial Material
DE F-18 fluoride; superscan; positron emission tomography; bone scan;
prostate cancer
ID BONE-SCAN; DISEASE; ABSENT
AB A 63-year-old man with a history of prostate cancer (Gleason score, 9/10) received brachytherapy 2 years ago. The patient had been diagnosed with bone metastases 7 months ago and received treatment with dexamethasone and flutamide. Recently, the patient complained of worsening bone pain with rapid rising of prostate-specific antigen from 45 to 189. F-18 sodium fluoride PET/CT bone scan was conducted to evaluate for progression of bone metastases. Review of the PET/CT images demonstrated a "superscan" pattern of bone metastases with extensive sodium fluoride uptake in the axial skeleton, and poor visualization of distal appendicular skeleton and kidneys.
C1 [Berenji, Gholam R.] VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, Dept Nucl Med, Los Angeles, CA 90073 USA.
RP Berenji, GR (reprint author), VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, Dept Nucl Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM Gholam.Berenji@va.gov
NR 8
TC 5
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0363-9762
J9 CLIN NUCL MED
JI Clin. Nucl. Med.
PD NOV
PY 2011
VL 36
IS 11
BP 1046
EP 1048
DI 10.1097/RLU.0b013e3182291c3d
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 833GV
UT WOS:000295871900028
PM 21975402
ER
PT J
AU Wang, ZW
Olumi, AF
AF Wang, Zongwei
Olumi, Aria F.
TI Diabetes, growth hormone-insulin-like growth factor pathways and
association to benign prostatic hyperplasia
SO DIFFERENTIATION
LA English
DT Review
DE Diabetes; Hyperinsulinaemia; Benign prostatic hyperplasia; Insulin-like
growth factor; Insulin-like growth factor binding protein; c-Jun
ID FACTOR-BINDING PROTEIN-3; I IGF-I; MESSENGER-RNA LEVELS; IMPROVES
GLYCEMIC CONTROL; METABOLIC SYNDROME; GLUCOSE-TOLERANCE;
EPITHELIAL-CELLS; SKELETAL-MUSCLE; GENE-EXPRESSION; STROMAL CELLS
AB Diabetes significantly increases the risk of benign prostatic hyperplasia (BPH) and low urinary tract symptoms (LUTS). The major endocrine aberration in connection with the metabolic syndrome is hyperinsulinemia. Insulin is an independent risk factor and a promoter of BPH. Insulin resistance may change the risk of BPH through several biological pathways. Hyperinsulinemia stimulates the liver to produce more insulin-like growth factor (IGF), another mitogen and an anti-apoptotic agent which binds insulin receptor/IGF receptor and stimulates prostate growth. The levels of IGFs and IGF binding proteins (IGFBPs) in prostate tissue and in blood are associated with BPH risk, with the regulation of circulating androgen and growth hormone. Stromal-epithelial interactions play a critical role in the development and growth of the prostate gland and BPH. Previously, we have shown that the expression of c-Jun in the fibroblastic stroma can promote secretion of IGF-I, which stimulates prostate epithelial cell proliferation through activating specific target genes. Here, we will review the epidemiologic, clinical, and molecular findings which have evaluated the relation between diabetes and development of BPH. (C) 2011 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.
C1 [Wang, Zongwei; Olumi, Aria F.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[Wang, Zongwei; Olumi, Aria F.] Harvard Univ, Sch Med, Boston, MA USA.
RP Olumi, AF (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,Yawkey Bldg 7E, Boston, MA 02114 USA.
EM Olumi.Aria@mgh.harvard.edu
NR 147
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U1 1
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0301-4681
EI 1432-0436
J9 DIFFERENTIATION
JI Differentiation
PD NOV-DEC
PY 2011
VL 82
IS 4-5
SI SI
BP 261
EP 271
DI 10.1016/j.diff.2011.04.004
PG 11
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 832VO
UT WOS:000295837300011
PM 21536370
ER
PT J
AU Kim, S
Lewis, C
Nadel, JA
AF Kim, Suil
Lewis, Courtney
Nadel, Jay A.
TI Epidermal growth factor receptor reactivation induced by E-prostanoid-3
receptor- and tumor necrosis factor-alpha-converting enzyme-dependent
feedback exaggerates interleukin-8 production in airway cancer
(NCI-H292) cells
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Epidermal growth factor receptor; Cyclooxygenase-2; Prostaglandin E2;
E-prostanoid-3 receptor; Interleukin-8; Positive feedback
ID BRONCHIAL EPITHELIAL-CELLS; PROSTAGLANDIN E-2; HUMAN-LUNG; PROSTANOID
RECEPTORS; SIGNALING CASCADE; CIGARETTE-SMOKE; EGF RECEPTOR; EXPRESSION;
ACTIVATION; LINES
AB Airway epithelial cancer cells produce increased amounts of the chemokine interleukin-8 (IL-8), inducing pro-tumor responses. Multiple stimuli induce airway epithelial IL-8 production epidermal growth factor receptor (EGFR) dependently, but the mechanisms that exaggerate IL-8 production in airway cancers remain unknown. Here we show that direct activation of EGFR (EGFR-P) by its ligand transforming growth factor (TGF)-alpha induces a second EGFR-P in human airway (NCI-H292) cancer cells but not in normal human bronchial epithelial (NHBE) cells, exaggerating IL-8 production in these cancer cells. The second EGFR-P in NCI-H292 cells was caused by metalloprotease INF-alpha-converting enzyme (TACE)-dependent cleavage of EGFR pro-ligands and was responsible for most of the total IL-8 induced by TGF-alpha. In NCI-H292 cells, TGF-alpha induced cyclooxygenase (COX)-2-dependent prostaglandin (PG)E2 production and release. PGE2 increased the second EGFR-P and IL-8 production via binding to its Gi-protein-coupled E-prostanoid (EP)3 receptor. In NHBE cells, TGF-alpha-induced EGFR-P did not lead to PGE2 production or to a second EGFR-P, and less IL-8 was produced. Thus, we conclude that a positive feedback pathway involving COX-2/PGE2/EP3 receptor-dependent EGFR reactivation exaggerates IL-8 production in NCI-H292 cancer cells but not in NHBE (normal) cells. Published by Elsevier Inc.
C1 [Kim, Suil; Lewis, Courtney; Nadel, Jay A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
[Kim, Suil; Lewis, Courtney; Nadel, Jay A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Nadel, Jay A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
RP Kim, S (reprint author), Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,Mailcode R&D 6, Portland, OR 97239 USA.
EM kimsui@ohsu.edu; courtney.lewis@ucsf.edu; jay.nadel@ucsf.edu
FU National Institutes of Health [HL073906]; American Lung Association;
UCSF; Cystic Fibrosis Foundation; Cardiovascular Research Institute
FX We thank Dr. Jonathan Koff for his generous advice and for stimulating
discussions. This work was supported by National Institutes of Health
Grant HL073906 (SK), American Lung Association Biomedical Research Award
(SK), UCSF Clinical and Translational Sciences Pilot Research Award
(SK), Cystic Fibrosis Foundation Pilot Research Award (SK), and by
Cardiovascular Research Institute funding (JAN).
NR 44
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U1 0
U2 3
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD NOV 1
PY 2011
VL 317
IS 18
BP 2650
EP 2660
DI 10.1016/j.yexcr.2011.08.023
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 833UA
UT WOS:000295909200010
PM 21925169
ER
PT J
AU Kadakia, MB
Fox, CS
Scirica, BM
Murphy, SA
Bonaca, MP
Morrow, DA
AF Kadakia, Mitul B.
Fox, Caroline S.
Scirica, Benjamin M.
Murphy, Sabina A.
Bonaca, Marc P.
Morrow, David A.
TI Central obesity and cardiovascular outcomes in patients with acute
coronary syndrome: observations from the MERLIN-TIMI 36 trial
SO HEART
LA English
DT Article
ID BODY-MASS INDEX; ACUTE MYOCARDIAL-INFARCTION; META-REGRESSION ANALYSIS;
WAIST CIRCUMFERENCE; ABDOMINAL OBESITY; METABOLIC SYNDROME;
HEART-ASSOCIATION; UNSTABLE ANGINA; ARTERY-DISEASE; ADIPOSE-TISSUE
AB Objective Despite the association of obesity with incident cardiovascular disease, obese patients with acute coronary syndrome (ACS) appear to have more favourable short-term outcomes. A study was undertaken to determine whether this 'obesity paradox' persists in the long term and to examine the specific relationship of central obesity with outcomes after ACS.
Methods The relationship was investigated between two measures of obesity-body mass index (BMI) and waist circumference (WC)-and 30-day and 1-year outcomes after ACS. 6560 patients with non-ST elevation ACS in the MERLIN-TIMI 36 trial were followed for 1 year. Patients were stratified into three BMI groups (<25, 25-30, >= 30 kg/m(2)) and gender-specific tertiles of WC. The primary endpoint was cardiovascular death, myocardial infarction or recurrent ischaemia.
Results Patients with BMI >= 30 kg/m(2) had a significantly lower risk of the primary endpoint than those with BMI <25 kg/m(2) (HR 0.64; 95% CI 0.51 to 0.81, p<0.0001) at 30 days. However, after the 30-day acute phase, landmark analysis from 30 days to 1 year showed no difference in risk between BMI groups (HR 1.09; 95% CI 0.92 to 1.29, p=0.34). WC tertiles demonstrated a similar relationship. When BMI groups were stratified by WC there was a trend towards more adverse outcomes in higher WC groups among those in lower BMI groups. The group with the lowest BMI and highest WC had the highest risk (HR 2.8; 95% CI 0.93 to 8.3; p=0.067).
Conclusions Obesity is associated with more favourable short-term outcomes after ACS. However, in the longer term the obesity paradox is no longer present and may reverse. Those with WC out of proportion to BMI suggestive of significant central adiposity may be at highest risk following ACS.
C1 [Kadakia, Mitul B.] Hosp Univ Penn, Div Cardiovasc Med, Philadelphia, PA 19103 USA.
[Kadakia, Mitul B.; Scirica, Benjamin M.; Murphy, Sabina A.; Bonaca, Marc P.; Morrow, David A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
[Fox, Caroline S.] NHLBI, NHBLIs Framingham Heart Study, Framingham, MA USA.
[Kadakia, Mitul B.; Fox, Caroline S.; Scirica, Benjamin M.; Murphy, Sabina A.; Bonaca, Marc P.; Morrow, David A.] Harvard Univ, Sch Med, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Kadakia, MB (reprint author), Hosp Univ Penn, Div Cardiovasc Med, 3400 Spruce St, Philadelphia, PA 19103 USA.
EM kadakia@post.harvard.edu
FU CV Therapeutics (now Gilead Science Inc); Novartis Pharmaceuticals
Corporation; AstraZeneca Pharmaceuticals LP; Daiichi-Sankyo Inc; Merck
Co Inc; Johnson and Johnson Pharmaceutical Research & Development LLC;
Bayer HealthCare Pharmaceuticals; Bristol-Myers-Squibb Company; CV
Therapeutics
FX MERLIN-TIMI 36 was supported by CV Therapeutics (now Gilead Science
Inc).; BMS has received grants for clinical research via the TIMI Study
Group and Brigham and Women's Hospital from CV Therapeutics, Novartis
Pharmaceuticals Corporation, AstraZeneca Pharmaceuticals LP,
Daiichi-Sankyo Inc, Merck & Co Inc, Johnson and Johnson Pharmaceutical
Research & Development LLC, Bayer HealthCare Pharmaceuticals and
Bristol-Myers-Squibb Company and has served as a consultant for
AstraZeneca Pharmaceuticals LP, Novartis Pharmaceuticals Corporation, CV
Therapeutics, Cogentus, Shionogi & Co Ltd, Gilead Sciences Inc, Merck &
Co Inc and Schering-Plough Corporation. DAM has received grants for
clinical research via the TIMI Study Group and Brigham & Women's
Hospital from CV Therapeutics, served as a consultant for Menarini Group
and received honoraria for educational presentations from CV
Therapeutics. MBK, CSF, MPB and SAM do not report any potential
conflicts.
NR 33
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U1 0
U2 4
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
J9 HEART
JI Heart
PD NOV
PY 2011
VL 97
IS 21
BP 1782
EP 1787
DI 10.1136/heartjnl-2011-300231
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 829VK
UT WOS:000295612600013
PM 21865203
ER
PT J
AU Chiang, CWK
Gajdos, ZKZ
Korn, JM
Butler, JL
Hackett, R
Guiducci, C
Nguyen, TT
Wilks, R
Forrester, T
Henderson, KD
Le Marchand, L
Henderson, BE
Haiman, CA
Cooper, RS
Lyon, HN
Zhu, XF
McKenzie, CA
Palmert, MR
Hirschhorn, JN
AF Chiang, Charleston W. K.
Gajdos, Zofia K. Z.
Korn, Joshua M.
Butler, Johannah L.
Hackett, Rachel
Guiducci, Candace
Nguyen, Thutrang T.
Wilks, Rainford
Forrester, Terrence
Henderson, Katherine D.
Le Marchand, Loic
Henderson, Brian E.
Haiman, Christopher A.
Cooper, Richard S.
Lyon, Helen N.
Zhu, Xiaofeng
McKenzie, Colin A.
Palmert, Mark R.
Hirschhorn, Joel N.
TI The efficacy of detecting variants with small effects on the Affymetrix
6.0 platform using pooled DNA
SO HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MICROARRAYS; ABILITY; LOCI; EFFICIENT; TRAITS;
IDENTIFICATION; POPULATIONS; DISABILITY; CHILDREN
AB Genome-wide genotyping of a cohort using pools rather than individual samples has long been proposed as a cost-saving alternative for performing genome-wide association (GWA) studies. However, successful disease gene mapping using pooled genotyping has thus far been limited to detecting common variants with large effect sizes, which tend not to exist for many complex common diseases or traits. Therefore, for DNA pooling to be a viable strategy for conducting GWA studies, it is important to determine whether commonly used genome-wide SNP array platforms such as the Affymetrix 6.0 array can reliably detect common variants of small effect sizes using pooled DNA. Taking obesity and age at menarche as examples of human complex traits, we assessed the feasibility of genome-wide genotyping of pooled DNA as a single-stage design for phenotype association. By individually genotyping the top associations identified by pooling, we obtained a 14- to 16-fold enrichment of SNPs nominally associated with the phenotype, but we likely missed the top true associations. In addition, we assessed whether genotyping pooled DNA can serve as an inexpensive screen as the second stage of a multi-stage design with a large number of samples by comparing the most cost-effective 3-stage designs with 80% power to detect common variants with genotypic relative risk of 1.1, with and without pooling. Given the current state of the specific technology we employed and the associated genotyping costs, we showed through simulation that a design involving pooling would be 1.07 times more expensive than a design without pooling. Thus, while a significant amount of information exists within the data from pooled DNA, our analysis does not support genotyping pooled DNA as a means to efficiently identify common variants contributing small effects to phenotypes of interest. While our conclusions were based on the specific technology and study design we employed, the approach presented here will be useful for evaluating the utility of other or future genome-wide genotyping platforms in pooled DNA studies.
C1 [Chiang, Charleston W. K.; Gajdos, Zofia K. Z.; Butler, Johannah L.; Nguyen, Thutrang T.; Lyon, Helen N.; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Chiang, Charleston W. K.; Gajdos, Zofia K. Z.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Chiang, Charleston W. K.; Gajdos, Zofia K. Z.; Korn, Joshua M.; Hackett, Rachel; Guiducci, Candace; Lyon, Helen N.; Hirschhorn, Joel N.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Chiang, Charleston W. K.; Gajdos, Zofia K. Z.; Butler, Johannah L.; Nguyen, Thutrang T.; Lyon, Helen N.; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Chiang, Charleston W. K.; Gajdos, Zofia K. Z.; Butler, Johannah L.; Nguyen, Thutrang T.; Lyon, Helen N.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Korn, Joshua M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Korn, Joshua M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Wilks, Rainford] Univ W Indies, Epidemiol Res Unit, Res Inst Trop Med, Kingston 7, Jamaica.
[Forrester, Terrence; McKenzie, Colin A.] Univ W Indies, Trop Metab Res Unit, Res Inst Trop Med, Kingston 7, Jamaica.
[Henderson, Katherine D.] City Hope Natl Med Ctr, Div Canc Etiol, Dept Populat Sci, Duarte, CA 91010 USA.
[Le Marchand, Loic] Univ Hawaii, Canc Res Ctr Hawaii, Program Epidemiol, Honolulu, HI 96813 USA.
[Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cooper, Richard S.] Loyola Univ Chicago, Dept Prevent Med & Epidemiol, Stritch Sch Med, Maywood, IL USA.
[Zhu, Xiaofeng] Case Western Reserve Univ, Dept Biostat & Epidemiol, Cleveland, OH 44106 USA.
[Palmert, Mark R.] Hosp Sick Children, Div Endocrinol, Toronto, ON M5G 1X8, Canada.
[Palmert, Mark R.] Univ Toronto, Dept Pediat, Toronto, ON, Canada.
RP Hirschhorn, JN (reprint author), Childrens Hosp, Program Genom, CLS 16065,300 Longwood Ave, Boston, MA 02115 USA.
EM joelh@broadinstitute.org
OI Chiang, Charleston/0000-0002-0668-7865
FU National Science Foundation; National Institutes of Health [R01DK075787,
R37HL45508, R01HL53353, R01HL074166, R01HD048960]
FX The principal acknowledgement is to the participants who contributed
their time, biological samples, and phenotype data to the different
projects. The authors also thank P. I. de Bakker, P. Sklar, and past and
present members of the Hirschhorn laboratory for comments, ideas, and
discussions; the past and present team members and investigators at the
Tropical Medicine Research Institute and the Hawai'i and Los Angeles
Multi-Ethnic Cohort for collecting samples and data. This work was
supported by a graduate research fellowship from the National Science
Foundation to C. W. K. C. and grants from the National Institutes of
Health to J.N.H. (R01DK075787), to R. S. C. (R37HL45508 and R01HL53353),
to X.Z. (R01HL074166), and to M. R. P. (R01HD048960). The funders had no
role in study design, data collection, analysis, interpretation,
decision to publish, or preparation of the manuscript.
NR 37
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U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD NOV
PY 2011
VL 130
IS 5
BP 607
EP 621
DI 10.1007/s00439-011-0974-0
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 834DP
UT WOS:000295939900002
PM 21424828
ER
PT J
AU Im, KM
Kirchhoff, T
Wang, XS
Green, T
Chow, CY
Vijai, J
Korn, J
Gaudet, MM
Fredericksen, Z
Pankratz, VS
Guiducci, C
Crenshaw, A
McGuffog, L
Kartsonaki, C
Morrison, J
Healey, S
Sinilnikova, OM
Mai, PL
Greene, MH
Piedmonte, M
Rubinstein, WS
Hogervorst, FB
Rookus, MA
Collee, JM
Hoogerbrugge, N
van Asperen, CJ
Meijers-Heijboer, HEJ
van Roozendaal, CE
Caldes, T
Perez-Segura, P
Jakubowska, A
Lubinski, J
Huzarski, T
Blecharz, P
Nevanlinna, H
Aittomaki, K
Lazaro, C
Blanco, I
Barkardottir, RB
Montagna, M
D'Andrea, E
Devilee, P
Olopade, OI
Neuhausen, SL
Peissel, B
Bonanni, B
Peterlongo, P
Singer, CF
Rennert, G
Lejbkowicz, F
Andrulis, IL
Glendon, G
Ozcelik, H
Toland, AE
Caligo, MA
Beattie, MS
Chan, S
Domchek, SM
Nathanson, KL
Rebbeck, TR
Phelan, C
Narod, S
John, EM
Hopper, JL
Buys, SS
Daly, MB
Southey, MC
Terry, MB
Tung, N
Hansen, TVO
Osorio, A
Benitez, J
Duran, M
Weitzel, JN
Garber, J
Hamann, U
Peock, S
Cook, M
Oliver, CT
Frost, D
Platte, R
Evans, DG
Eeles, R
Izatt, L
Paterson, J
Brewer, C
Hodgson, S
Morrison, PJ
Porteous, M
Walker, L
Rogers, MT
Side, LE
Godwin, AK
Schmutzler, RK
Wappenschmidt, B
Laitman, Y
Meindl, A
Deissler, H
Varon-Mateeva, R
Preisler-Adams, S
Kast, K
Venat-Bouvet, L
Stoppa-Lyonnet, D
Chenevix-Trench, G
Easton, DF
Klein, RJ
Daly, MJ
Friedman, E
Dean, M
Clark, AG
Altshuler, DM
Antoniou, AC
Couch, FJ
Offit, K
Gold, B
AF Im, Kate M.
Kirchhoff, Tomas
Wang, Xianshu
Green, Todd
Chow, Clement Y.
Vijai, Joseph
Korn, Joshua
Gaudet, Mia M.
Fredericksen, Zachary
Pankratz, V. Shane
Guiducci, Candace
Crenshaw, Andrew
McGuffog, Lesley
Kartsonaki, Christiana
Morrison, Jonathan
Healey, Sue
Sinilnikova, Olga M.
Mai, Phuong L.
Greene, Mark H.
Piedmonte, Marion
Rubinstein, Wendy S.
Hogervorst, Frans B.
Rookus, Matti A.
Collee, J. Margriet
Hoogerbrugge, Nicoline
van Asperen, Christi J.
Meijers-Heijboer, Hanne E. J.
van Roozendaal, Cees E.
Caldes, Trinidad
Perez-Segura, Pedro
Jakubowska, Anna
Lubinski, Jan
Huzarski, Tomasz
Blecharz, Pawel
Nevanlinna, Heli
Aittomaki, Kristiina
Lazaro, Conxi
Blanco, Ignacio
Barkardottir, Rosa B.
Montagna, Marco
D'Andrea, Emma
Devilee, Peter
Olopade, Olufunmilayo I.
Neuhausen, Susan L.
Peissel, Bernard
Bonanni, Bernardo
Peterlongo, Paolo
Singer, Christian F.
Rennert, Gad
Lejbkowicz, Flavio
Andrulis, Irene L.
Glendon, Gord
Ozcelik, Hilmi
Toland, Amanda Ewart
Caligo, Maria Adelaide
Beattie, Mary S.
Chan, Salina
Domchek, Susan M.
Nathanson, Katherine L.
Rebbeck, Timothy R.
Phelan, Catherine
Narod, Steven
John, Esther M.
Hopper, John L.
Buys, Saundra S.
Daly, Mary B.
Southey, Melissa C.
Terry, Mary-Beth
Tung, Nadine
Hansen, Thomas V. O.
Osorio, Ana
Benitez, Javier
Duran, Mercedes
Weitzel, Jeffrey N.
Garber, Judy
Hamann, Ute
Peock, Susan
Cook, Margaret
Oliver, Clare T.
Frost, Debra
Platte, Radka
Evans, D. Gareth
Eeles, Ros
Izatt, Louise
Paterson, Joan
Brewer, Carole
Hodgson, Shirley
Morrison, Patrick J.
Porteous, Mary
Walker, Lisa
Rogers, Mark T.
Side, Lucy E.
Godwin, Andrew K.
Schmutzler, Rita K.
Wappenschmidt, Barbara
Laitman, Yael
Meindl, Alfons
Deissler, Helmut
Varon-Mateeva, Raymonda
Preisler-Adams, Sabine
Kast, Karin
Venat-Bouvet, Laurence
Stoppa-Lyonnet, Dominique
Chenevix-Trench, Georgia
Easton, Douglas F.
Klein, Robert J.
Daly, Mark J.
Friedman, Eitan
Dean, Michael
Clark, Andrew G.
Altshuler, David M.
Antoniou, Antonis C.
Couch, Fergus J.
Offit, Kenneth
Gold, Bert
TI Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation
carriers
SO HUMAN GENETICS
LA English
DT Article
ID TAY-SACHS DISEASE; BREAST-CANCER; POSITIVE SELECTION; GENETIC-VARIATION;
POPULATION; FREQUENCY; GENOME; JEWS; ASSOCIATION; SIGNATURES
AB Three founder mutations in BRCA1 and BRCA2 contribute to the risk of hereditary breast and ovarian cancer in Ashkenazi Jews (AJ). They are observed at increased frequency in the AJ compared to other BRCA mutations in Caucasian non-Jews (CNJ). Several authors have proposed that elevated allele frequencies in the surrounding genomic regions reflect adaptive or balancing selection. Such proposals predict long-range linkage disequilibrium (LD) resulting from a selective sweep, although genetic drift in a founder population may also act to create long-distance LD. To date, few studies have used the tools of statistical genomics to examine the likelihood of long-range LD at a deleterious locus in a population that faced a genetic bottleneck. We studied the genotypes of hundreds of women from a large international consortium of BRCA1 and BRCA2 mutation carriers and found that AJ women exhibited long-range haplotypes compared to CNJ women. More than 50% of the AJ chromosomes with the BRCA1 185delAG mutation share an identical 2.1 Mb haplotype and nearly 16% of AJ chromosomes carrying the BRCA2 6174delT mutation share a 1.4 Mb haplotype. Simulations based on the best inference of Ashkenazi population demography indicate that long-range haplotypes are expected in the context of a genome-wide survey. Our results are consistent with the hypothesis that a local bottleneck effect from population size constriction events could by chance have resulted in the large haplotype blocks observed at high frequency in the BRCA1 and BRCA2 regions of Ashkenazi Jews.
C1 [Gold, Bert] NCI, Frederick, MD 21702 USA.
[Im, Kate M.; Dean, Michael; Gold, Bert] NCI, Ctr Canc Res, Canc Inflammat Program, Human Genet Sect, Frederick, MD 21701 USA.
[Kirchhoff, Tomas; Vijai, Joseph; Klein, Robert J.; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, Dept Med, Program Canc Prevent & Populat Res,Program Canc P, New York, NY 10021 USA.
[Wang, Xianshu; Fredericksen, Zachary; Pankratz, V. Shane; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Green, Todd; Korn, Joshua; Guiducci, Candace; Crenshaw, Andrew; Collee, J. Margriet; Montagna, Marco] Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA USA.
[Green, Todd; Korn, Joshua; Guiducci, Candace; Crenshaw, Andrew; Daly, Mark J.; Altshuler, David M.] Harvard Univ, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02138 USA.
[Green, Todd; Korn, Joshua; Guiducci, Candace; Crenshaw, Andrew; Daly, Mark J.; Altshuler, David M.] Massachusetts Gen Hosp, Dept Mol Biol, Ctr Human Genet Res, Boston, MA 02114 USA.
[Chow, Clement Y.; Clark, Andrew G.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY USA.
[Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
[Healey, Sue; Chenevix-Trench, Georgia; Antoniou, Antonis C.] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia.
[Sinilnikova, Olga M.] Ctr Hosp Univ Lyon, Unite Mixte Genet Constitut Canc Frequents, Ctr Lyon Berard, Lyon, France.
[Sinilnikova, Olga M.] Univ Lyon, Ctr Leon Berard, Lyon, France.
[Mai, Phuong L.; Greene, Mark H.] NCI, Clin Genet Branch, Rockville, MD USA.
[Piedmonte, Marion] Roswell Pk Canc Inst, GOG Stat & Data Ctr, Buffalo, NY 14263 USA.
[Rubinstein, Wendy S.] NorthShore Univ Hlth Syst, Evanston, IL USA.
[Hogervorst, Frans B.] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands.
[Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands.
[Collee, J. Margriet] Erasmus Univ, Dept Clin Genet, Family Canc Clin, Med Ctr, NL-3000 DR Rotterdam, Netherlands.
[Hoogerbrugge, Nicoline] Radboud Univ Nijmegen, Hereditary Canc Clin, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Leiden, Netherlands.
[van Roozendaal, Cees E.] Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands.
[Caldes, Trinidad; Perez-Segura, Pedro] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain.
[Jakubowska, Anna; Lubinski, Jan; Huzarski, Tomasz] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland.
[Blecharz, Pawel] Maria Sklodowska Curie Mem Inst Oncol, Ctr Oncol, Krakow, Poland.
[Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland.
[Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, FIN-00290 Helsinki, Finland.
[Lazaro, Conxi; Blanco, Ignacio] Catalan Inst Oncol IDIBELL, Hereditary Canc Program, Barcelona, Spain.
[Barkardottir, Rosa B.] Landspitali LSH, Dept Pathol, Reykjavik, Iceland.
[Barkardottir, Rosa B.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Montagna, Marco; D'Andrea, Emma] IRCCS, Immunol & Mol Oncol Unit, Ist Oncol Veneto IOV, Padua, Italy.
[D'Andrea, Emma] Univ Padua, Dept Oncol & Surg Sci, Padua, Italy.
Peter MacCallum Canc Ctr, Kathleen Cuningham Fdn Consortium Res Familial Br, Melbourne, Vic, Australia.
[Devilee, Peter] Leiden Univ, Dept Human Genet & Pathol, Med Ctr, Leiden, Netherlands.
[Olopade, Olufunmilayo I.] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Dept Med, Chicago, IL 60637 USA.
[Neuhausen, Susan L.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA.
[Peissel, Bernard] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predict Med, Milan, Italy.
[Bonanni, Bernardo] IEO, Div Canc Prevent & Genet, Milan, Italy.
[Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Unit Genet Susceptibil Canc, Dept Expt Oncol & Mol Med, Milan, Italy.
[Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy.
[Singer, Christian F.] Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria.
[Singer, Christian F.] Univ Vienna, Comprehens Canc Med Ctr, Vienna, Austria.
[Rennert, Gad; Lejbkowicz, Flavio] Carmel Hosp, CHS Natl Canc Control Ctr, Haifa, Israel.
[Andrulis, Irene L.; Ozcelik, Hilmi] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel.
[Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi] Technion Israel Inst Technol, Fac Med, Haifa, Israel.
[Andrulis, Irene L.; Ozcelik, Hilmi] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Genet Network, Toronto, ON, Canada.
Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Toland, Amanda Ewart] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Caligo, Maria Adelaide] Univ Pisa, Sect Genet Oncol, Dept Lab Med, Pisa, Italy.
Santa Chiara Univ Hosp, Pisa, Italy.
Lund Univ, Dept Oncol, Lund, Sweden.
[Beattie, Mary S.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA.
[Chan, Salina] Univ Calif San Francisco, Canc Risk Program, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
Univ Cambridge, Dept Oncol, Cambridge, England.
[Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Phelan, Catherine] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
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[Hamann, Ute] Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany.
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[Izatt, Louise] Royal Marsden NHS Fdn Trust, Surrey, England.
[Paterson, Joan] Guys & St Thomas NHS Fdn Trust, London, England.
[Brewer, Carole] Addenbrookes Hosp, Dept Clin Genet, E Anglian Reg Genet Serv, Cambridge, England.
[Hodgson, Shirley] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England.
[Morrison, Patrick J.] Univ London, Dept Clin Genet, London, England.
[Porteous, Mary] Belfast City Hosp, No Ireland Reg Genet Ctr, Belfast BT9 7AD, Antrim, North Ireland.
[Walker, Lisa] Western Gen Hosp, SE Scotland Reg Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland.
[Rogers, Mark T.] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England.
[Side, Lucy E.] Univ Wales Hosp, All Wales Med Genet Serv, Cardiff CF4 4XW, S Glam, Wales.
[Godwin, Andrew K.] Great Ormond St Hosp Sick Children, NE Thames Reg Genet Serv, London WC1N 3JH, England.
[Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Kansas, Med Ctr, Dept Pathol & Lab, Kansas City, KS 66103 USA.
[Venat-Bouvet, Laurence] Univ Hosp Cologne, Cologne, Germany.
[Stoppa-Lyonnet, Dominique] Ctr Hosp Univ Dupuytren, Dept Med Oncol, Limoges, France.
[Laitman, Yael; Friedman, Eitan] Univ Paris 05, INSERM, U509, Serv Genet Oncol,Inst Curie, Paris, France.
[Meindl, Alfons] Chaim Sheba Med Ctr, Susan Levy Gertner Oncogenet Unit, Inst Genet, IL-52621 Tel Hashomer, Israel.
[Deissler, Helmut] Tech Univ Munich, Munich, Germany.
[Varon-Mateeva, Raymonda] Univ Hosp Ulm, Ulm, Germany.
[Preisler-Adams, Sabine] Charite Campus Virchow Klinikum, Inst Human Genet, Berlin, Germany.
[Kast, Karin] Univ Munster, Inst Human Genet, D-4400 Munster, Germany.
[Gold, Bert] Tech Univ Dresden, Dept Obstet & Gynaecol, Univ Hosp Carl Gustav, Dresden, Germany.
RP Gold, B (reprint author), NCI, Box B,Boyles St Ft Detrick, Frederick, MD 21702 USA.
EM golda@mail.nih.gov
RI Osorio, Ana/I-4324-2014; Bernard, Loris/K-5953-2014; Ehrencrona,
Hans/M-5619-2014; Jakubowska, Anna/O-8050-2014; GLADIEFF,
Laurence/O-5129-2014; Ligtenberg, Marjolijn/N-9666-2013; Ripamonti,
Carla Barbara/D-2247-2017; Peissel, Bernard/E-8187-2017; Oosterwijk, Jan
C./G-5770-2011; Hoogerbrugge, Nicoline/O-1016-2013; Radice,
Paolo/O-3119-2013; Blanco, Ignacio/D-2565-2013; Toland,
Amanda/E-4202-2011; montagna, marco/E-2225-2012; Dean,
Michael/G-8172-2012; D'Andrea, Emma/B-4374-2013; Andrulis,
Irene/E-7267-2013; Joseph, Vijai/J-9158-2013; Klein, Robert/K-1888-2013;
Altshuler, David/A-4476-2009
OI Evans, Gareth/0000-0002-8482-5784; Nevanlinna, Heli/0000-0002-0916-2976;
Kirchhoff, Tomas/0000-0002-9055-2364; Bossi, Paolo/0000-0003-0135-0224;
VENAT-BOUVET, Laurence/0000-0002-0716-2550; Osorio,
Ana/0000-0001-8124-3984; Ehrencrona, Hans/0000-0002-5589-3622; GLADIEFF,
Laurence/0000-0002-6980-9719; Ligtenberg, Marjolijn/0000-0003-1290-1474;
Ripamonti, Carla Barbara/0000-0002-2892-8164; Peissel,
Bernard/0000-0001-9233-3571; Nordling, Margareta/0000-0002-4047-4994;
Eeles, Rosalind/0000-0002-3698-6241; Nathanson,
Katherine/0000-0002-6740-0901; Blanco, Ignacio/0000-0002-7414-7481;
montagna, marco/0000-0002-4929-2150; Dean, Michael/0000-0003-2234-0631;
Joseph, Vijai/0000-0002-7933-151X; Klein, Robert/0000-0003-3539-5391;
Altshuler, David/0000-0002-7250-4107
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; Starr Foundation; Breast Cancer Research Foundation;
Sabin Family Fund; CRUK; Ligue National Contre le Cancer; Association
for International Cancer Research [AICR-07-0454]; Association "Le cancer
du sein, parlons-en"; NHMRC; National Breast Cancer Foundation; Cancer
Australia [628333]; Queensland Cancer Fund; Cancer Councils of New South
Wales, Victoria, Tasmania and South Australia; Cancer Foundation of
Western Australia; Italian citizens; Fondazione IRCCS Istituto Nazionale
Tumori; Komen Foundation; National Cancer Institute, National Institutes
of Health [RFA-CA-06-503]; ISCIII [RD06/0020/0021]; Dutch Cancer Society
[NKI1998-1854, NKI2004-3088, NKI2007-3756]; OSU Comprehensive Cancer
Center; Cancer Care Ontario; US National Cancer Institute, National
Institutes of Health [RFA CA-06-503]; Cancer Research UK [C1287/A10118,
C1287/A11990, C5047/A8385]; NIHR; Biomedical Research Centre,
Manchester; Biomedical Research Centre at The Institute of Cancer
Research; Royal Marsden NHS Foundation Trust; NEYE foundation;
[NIHCA116167]
FX This work was supported in part by federal funds from the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research. We also acknowledge the support
of the Starr Foundation, the Breast Cancer Research Foundation and the
Sabin Family Fund. The content of this publication does not necessarily
reflect the views of the Department of Health and Human Services nor
does its mention of trade names, commercial products or organizations
imply endorsement by the US government. The authors wish to thank Dr.
Colm O'hUigin, who provided valuable comments on an early version of
this manuscript.; UKFOCR was supported by a project grant from CRUK to
Paul Pharoah. We thank Paul Pharoah, Simon Gayther, Susan Ramus, Carole
Pye and Patricia Harrington for their contributions toward the UKFOCR.;
The GEMO study (Cancer Genetics Network "Groupe Genetique et Cancer'',
Federation Nationale des Centres de Lutte Contre le Cancer, France) is
supported by the Ligue National Contre le Cancer; Association for
International Cancer Research Grant (AICR-07-0454); and the Association
"Le cancer du sein, parlons-en!'' Award.; For kConFab, we wish to thank
Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and
staff, the heads and staff of the Family Cancer Clinic and the Clinical
Follow Up Study (funded 2001-2009 by NHMRC and currently by the National
Breast Cancer Foundation and Cancer Australia #628333) for their
contributions to this resource, and the many families who contributed to
kConFab. kConFab is supported by grants from the National Breast Cancer
Foundation, the National Health and Medical Research Council (NHMRC),
the Queensland Cancer Fund, the Cancer Councils of New South Wales,
Victoria, Tasmania and South Australia, and the Cancer Foundation of
Western Australia.; The CONSIT TEAM study (Consorzio degli Studi
Italiani Tumori Ereditari Alla Mammella), acknowledges Marco Pierotti,
Siranoush Manoukian, Daniela Zaffaroni, Carla B. Ripamonti and Paolo
Radice of the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan,
Italy; Monica Barile of the Istituto Europeo di Oncologia, Milan, Italy
and Loris Bernard of the Cogentech, Consortium for Genomic Technologies,
Milan, Italy. We thank all patients and families who participated in
this study. This study was supported by funds from Italian citizens who
allocated the 5 9 1,000 share of their tax payment in support of the
Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws
(INT-Institutional strategic projects '5 x 1,000').; For the Mayo Study,
the authors would like to acknowledge funding from the Breast Cancer
Research Foundation, Komen Foundation, and NIHCA116167.; The Cancer
Prevention Institute of California was supported by the National Cancer
Institute, National Institutes of Health under RFA-CA-06-503 and through
cooperative agreements with members of the Breast Cancer Family Registry
and P.I.s. 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 Cancer Family Registry (CFR), nor does
mention of trade names, commercial products or organizations imply
endorsement by the US government or the CFR.; The SWE-BRCA study
acknowledge the study collaborators: Per Karlsson, Margareta Nordling,
Annika Bergman and Zakaria Einbeigi, Gothenburg, Sahlgrenska University
Hospital; Marie StenmarkAskmalm and Sigrun Liedgren Linko "ping
University Hospital; A angstrom ke Borg, Niklas Loman, Hakan Olsson, Ulf
Kristoffersson, Helena Jernstrom, Katja Harbst and Karin Henriksson,
Lund University Hospital; Annika Lindblom, Brita Arver, Anna von
Wachenfeldt, Annelie Liljegren, Gisela Barbany-Bustinza and Johanna
Rantala, Stockholm, Karolinska University Hospital; Beatrice Melin,
Henrik Gronberg, Eva-Lena Stattin and Monica Emanuelsson, Umea
University Hospital; Hans Ehrencrona, Richard Rosenquist Brandell and
Niklas Dahl, Uppsala University Hospital. The HCSC study was supported
by RD06/0020/0021 from ISCIII.; The Hereditary Breast and Ovarian Cancer
Research Group Netherlands (HEBON) Collaborating Centers are
Coordinating center: Netherlands Cancer Institute, Amsterdam, NL: F.B.L.
Hogervorst, S. Verhoef, M. Verheus, L.J. van 't Veer, F.E. van Leeuwen,
M.A. Rookus; Erasmus Medical Center, Rotterdam, NL: M. Collee, A. M.W.
van den Ouweland, A. Jager, M.J. Hooning, M. M.A. Tilanus-Linthorst, C.
Seynaeve; Leiden University Medical Center, NL, Leiden: C.J. van
Asperen, J.T. Wijnen, M. P. Vreeswijk, R.A. Tollenaar, P. Devilee;
Radboud University Nijmegen Medical Center, Nijmegen, NL: M.J.
Ligtenberg, N. Hoogerbrugge; University Medical Center Utrecht, Utrecht,
NL: M.G. Ausems, R.B. van der Luijt; Amsterdam Medical Center, NL: C.M.
Aalfs, T.A. van Os; VU University Medical Center, Amsterdam, NL: J.J.P.
Gille, Q. Waisfisz, H.E.J. Meijers-Heijboer; University Hospital
Maastricht, Maastricht, NL: E. B. Gomez-Garcia, C.E. van Roozendaal,
Marinus J. Blok, B. Caanen; University Medical Center Groningen
University, NL: J.C. Oosterwijk, A. H. van der Hout, M.J. Mourits; The
Netherlands Foundation for the detection of hereditary tumours, Leiden,
NL: H.F. Vasen. The HEBON study is supported by the Dutch Cancer Society
grants NKI1998-1854, NKI2004-3088 and NKI2007-3756.; The Ohio State
University Clinical Cancer Genetics (OSU CCG) study is supported by the
OSU Comprehensive Cancer Center. We thank Leigha Senter and Kevin Sweet
for patient accrual, sample ascertainment and database management. The
Human Genetics Sample bank processed the samples.; This work was
supported by Cancer Care Ontario and the US National Cancer Institute,
National Institutes of Health under RFA #CA-06-503 and through
cooperative agreements with members of the Breast Cancer Family Registry
(BCFR) and principal investigators. 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 organizations imply
endorsement by the US government or the BCFR. We wish to thank Teresa
Selander, Nayana Weerasooriya and members of the Ontario Cancer Genetics
Network for their contributions to the study.; Douglas F. Easton is the
PI of the study. EMBRACE Collaborating Centers are Coordinating Centre,
Cambridge: Susan Peock, Margaret Cook, Clare T. Oliver, Debra Frost,
Radka Platte. North of Scotland Regional Genetics Service, Aberdeen:
Zosia Miedzybrodzka, Helen Gregory. Northern Ireland Regional Genetics
Service, Belfast: Patrick Morrison, Lisa Jeffers. West Midlands Regional
Clinical Genetics Service, Birmingham: Trevor Cole, Kai-ren Ong,
Jonathan Hoffman. South West Regional Genetics Service, Bristol: Alan
Donaldson, Margaret James. East Anglian Regional Genetics Service,
Cambridge: Joan Paterson, Sarah Downing, Amy Taylor. Medical Genetics
Services for Wales, Cardiff: Alexandra Murray, Mark T. Rogers, Emma
McCann. St James's Hospital, Dublin & National Centre for Medical
Genetics, Dublin: M. John Kennedy, David Barton. South East of Scotland
Regional Genetics Service, Edinburgh: Mary Porteous, Sarah Drummond.
Peninsula Clinical Genetics Service, Exeter: Carole Brewer, Emma Kivuva,
Anne Searle, Selina Goodman, Kathryn Hill. West of Scotland Regional
Genetics Service, Glasgow: Rosemarie Davidson, Victoria Murday, Nicola
Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt, Sarah Gibson,
Eshika Haque, Ed Tobias, Alexis Duncan. South East Thames Regional
Genetics Service, Guy's Hospital London: Louise Izatt, Chris Jacobs,
Caroline Langman, Anna Whaite. North West Thames Regional Genetics
Service, Harrow: Huw Dorkins, Kashmir Randhawa. Leicestershire Clinical
Genetics Service, Leicester: Julian Barwell, Nafisa Patel. Yorkshire
Regional Genetics Service, Leeds: Julian Adlard, Carol Chu, Julie
Miller. Merseyside & Cheshire Clinical Genetics Service, Liverpool: Ian
Ellis, Catherine Houghton. Manchester Regional Genetics Service,
Manchester: D Gareth Evans, Fiona Lalloo, Jane Taylor. North East Thames
Regional Genetics Service, NE Thames, London: Lucy Side, Alison Male,
Cheryl Berlin. Nottingham Centre for Medical Genetics, Nottingham:
Jacqueline Eason, Rebecca Collier. Northern Clinical Genetics Service,
Newcastle: Fiona Douglas, Oonagh Claber, Irene Jobson. Oxford Regional
Genetics Service, Oxford: Lisa Walker, Diane McLeod, Dorothy Halliday,
Sarah Durell, Barbara Stayner. The Institute of Cancer Research and
Royal Marsden NHS Foundation Trust: Ros Eeles, Susan Shanley, Nazneen
Rahman, Richard Houlston, Elizabeth Bancroft, Lucia D'Mello, Elizabeth
Page, Audrey Ardern-Jones, Kelly Kohut, Jennifer Wiggins, Elena Castro,
Anita Mitra, Lisa Robertson. North Trent Clinical Genetics Service,
Sheffield: Jackie Cook, Oliver Quarrell, Cathryn Bardsley. South West
Thames Regional Genetics Service, London: Shirley Hodgson, Glen Brice,
Lizzie Winchester, Charlotte Eddy, Vishakha Tripathi, Virginia Attard.
Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton:
Diana Eccles, Anneke Lucassen, Gillian Crawford, Donna McBride, Sarah
Smalley. EMBRACE is supported by Cancer Research UK Grants C1287/A10118
and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an
NIHR grant to the Biomedical Research Centre, Manchester. The
Investigators at The Institute of Cancer Research and The Royal Marsden
NHS Foundation Trust are supported by an NIHR grant to the Biomedical
Research Centre at The Institute of Cancer Research and The Royal
Marsden NHS Foundation Trust. Ros Eeles, Elizabeth Bancroft and Lucia
D'Mello are also supported by Cancer Research UK Grant C5047/A8385.;
CBCS: We thank Bent Ejlertsen, Mette K. Andersen, Anne-Marie Gerdes and
Susanne Kjaergaard for clinical data. Moreover, we thank the NEYE
foundation for financial support.
NR 38
TC 8
Z9 8
U1 2
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD NOV
PY 2011
VL 130
IS 5
BP 685
EP 699
DI 10.1007/s00439-011-1003-z
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 834DP
UT WOS:000295939900009
PM 21597964
ER
PT J
AU Fayaz, HC
Giannoudis, PV
Vrahas, MS
Smith, RM
Moran, C
Pape, HC
Krettek, C
Jupiter, JB
AF Fayaz, Hangama C.
Giannoudis, Peter V.
Vrahas, Mark S.
Smith, Raymond Malcolm
Moran, Christopher
Pape, Hans Christoph
Krettek, Christian
Jupiter, Jesse B.
TI The role of stem cells in fracture healing and nonunion
SO INTERNATIONAL ORTHOPAEDICS
LA English
DT Review
ID MARROW STROMAL CELLS; PROGENITOR CELLS; TIBIAL NONUNION; BONE DEFECTS;
REPAIR; RECONSTRUCTION; REGENERATION; DIFFERENTIATION; OSTEOGENESIS;
OSTEOBLASTS
AB Nonunion and large bone defects present a therapeutic challenge to the surgeon and are often associated with significant morbidity. These defects are expensive to both the health care system and society. However, several surgical procedures have been developed to maximise patient satisfaction and minimise health-care-associated and socioeconomic costs. Integrating recent evidence into the diamond concept leads to one simple conclusion that not only provides us with answers to the "open questions" but also simplifies our entire understanding of bone healing. It has been shown that a combination of neo-osteogenesis and neovascularisation will restore tissue deficits, and that the optimal approach includes a biomaterial scaffold, cell biology techniques, a growth factor and optimisation of the mechanical environment. Further prospective, controlled, randomised clinical studies will determine the effectiveness and economic benefits of treatment with mesenchymal stem cells, not in comparison to other conventional surgical approaches but in direct conjunction with them.
C1 [Giannoudis, Peter V.] Univ Leeds, Sch Med, Acad Dept Trauma & Orthopaed Surg, Leeds LS2 9JT, W Yorkshire, England.
[Smith, Raymond Malcolm] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Trauma Serv,Dept Orthopaed Surg, Boston, MA USA.
[Vrahas, Mark S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners Orthopaed Trauma Serv, Boston, MA USA.
[Moran, Christopher] Univ Hosp, Queens Med Ctr, Nottingham NG7 2UH, England.
[Pape, Hans Christoph] Univ Aachen, Med Ctr, Dept Orthopaed Trauma, D-5100 Aachen, Germany.
[Krettek, Christian] Hannover Med Sch, Dept Trauma Surg, D-3000 Hannover, Germany.
RP Giannoudis, PV (reprint author), Univ Leeds, Sch Med, Acad Dept Trauma & Orthopaed Surg, Leeds LS2 9JT, W Yorkshire, England.
EM dr.hana.fayaz@hotmail.de; pgiannoudi@aol.com; mvrahas@partners.org;
rmsmith1@partners.org; chris.moran1@me.com; hpape@ukaachen.de;
krettek.christian@mh-hannover.de; jjupiter1@partners.org
OI Krettek, Christian/0000-0001-9807-0020
NR 53
TC 40
Z9 42
U1 2
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0341-2695
J9 INT ORTHOP
JI Int. Orthop.
PD NOV
PY 2011
VL 35
IS 11
BP 1587
EP 1597
DI 10.1007/s00264-011-1338-z
PG 11
WC Orthopedics
SC Orthopedics
GA 834RW
UT WOS:000295982400001
PM 21863226
ER
PT J
AU Smith, MR
Klotz, L
van der Meulen, E
Colli, E
Tanko, LB
AF Smith, Matthew R.
Klotz, Laurence
van der Meulen, Egbert
Colli, Enrico
Tanko, Laszlo B.
TI Gonadotropin-Releasing Hormone Blockers and Cardiovascular Disease Risk:
Analysis of Prospective Clinical Trials of Degarelix
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostate; prostatic neoplasms; cardiovascular diseases; GnRH; risk
ID ANDROGEN-DEPRIVATION THERAPY; GROUP PHASE-III; PROSTATE-CANCER;
OPEN-LABEL; SUPPRESSION THERAPY; TESTOSTERONE SURGE; FREQUENCY;
12-MONTH; CORONARY; SAFETY
AB Purpose: We investigated associations of baseline cardiovascular disease risk profile, dosing regimen and treatment duration with incident cardiovascular disease events during androgen deprivation therapy with degarelix in patients with prostate cancer.
Materials and Methods: Data on 1,704 men who participated in a total of 9 clinical trials were pooled for analysis. Patients received treatment with 1-month (20 to 240 mg) or 3-month (240 to 480 mg) doses of degarelix for an average of 22 months. End points were ischemic heart disease, cerebrovascular disorders, arterial thrombotic/embolic events and intermittent claudication.
Results: First time cardiovascular disease events were reported in 92 men in the year before study entry and in 168 after degarelix treatment. Event rates were similar before and after degarelix treatment in the total population (5.5 vs 6.1/100 person-years, p = 0.45) and in men without cardiovascular disease (5.6 vs 4.3/100 person-years, p = 0.11). In contrast, event rates appeared higher after degarelix treatment in men with cardiovascular disease at baseline (5.3 to 10.5 events per 100 person-years, p = 0.0013). On multivariate analysis cardiovascular disease at baseline was the strongest independent predictor of events, followed by older age, alcohol abstinence and obesity (each p <0.05). Degarelix dose and schedule were not independently associated with cardiovascular disease events.
Conclusions: In men with prostate cancer observed rates of cardiovascular disease events were similar before and after degarelix treatment. Events were largely confined to men with preexisting cardiovascular disease and further modulated by age and modifiable risk factors. Randomized, controlled trials and longer followup are key to fully clarify the comparative safety of gonadotropin-releasing hormone antagonists vs agonists.
C1 [Smith, Matthew R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
[Klotz, Laurence] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada.
[van der Meulen, Egbert; Colli, Enrico; Tanko, Laszlo B.] Ferring Pharmaceut AS, Global Clin R&D, Copenhagen, Denmark.
RP Smith, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Yawkey 7030,55 Fruit St, Boston, MA 02114 USA.
EM smith.matthew@mgh.harvard.edu
FU National Institutes of Health [5K24CA121990]; Prostate Cancer Foundation
FX Supported by National Institutes of Health Midcareer Investigator Award
5K24CA121990 and Prostate Cancer Foundation competitive research awards.
NR 27
TC 28
Z9 29
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD NOV
PY 2011
VL 186
IS 5
BP 1835
EP 1842
DI 10.1016/j.juro.2011.07.035
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 835FX
UT WOS:000296022200027
PM 21944083
ER
PT J
AU Taylor, EN
Chan, AT
Giovannucci, EL
Curhan, GC
AF Taylor, Eric N.
Chan, Andrew T.
Giovannucci, Edward L.
Curhan, Gary C.
TI Cholelithiasis and the Risk of Nephrolithiasis
SO JOURNAL OF UROLOGY
LA English
DT Article
DE kidney calculi; gallstones; risk factors
ID SYMPTOMATIC GALLSTONE DISEASE; FOOD FREQUENCY QUESTIONNAIRE;
DIABETES-MELLITUS; PHYSICAL-ACTIVITY; KIDNEY-STONES; WOMEN; CONSUMPTION;
CALCIUM; MEN; CHOLESTEROL
AB Purpose: Existing data on the relation between gallstones and kidney stones are provocative but limited. Therefore, we determined whether symptomatic radio-graphically confirmed gallstones (and/or cholecystectomy) and symptomatic kidney stone disease are independently associated.
Materials and Methods: We conducted cross-sectional and prospective analyses in the Nurses' Health Studies I and II (older and younger women, respectively) and the Health Professionals Follow-Up Study (men) that included more than 240,000 participants followed for 14 to 24 years. Regression models adjusted for age, body size, thiazide use, diet and other factors.
Results: At baseline the multivariate odds ratio of kidney stone history in individuals with gallstone history compared to those without was 1.65 (95% CI 1.46-1.86) in older women, 1.85 (95% CI 1.65-2.07) in younger women and 1.61 (95% CI 1.41-1.85) in men. Prospectively, the multivariate relative risk of incident kidney stones in participants with gallstone history compared to those without was 1.26 (95% CI 1.09-1.44) in older women, 1.32 (95% CI 1.14-1.52) in younger women and 1.28 (95% CI 1.03-1.57) in men. The multivariate relative risk of incident gallstones in participants with kidney stone history compared to those without was 1.17 (95% CI 1.06-1.29) in older women, 1.31 (95% CI 1.19-1.45) in younger women and 1.51 (95% CI 1.35-1.68) in men. Prospective lag analyses instituting a delay of 4 years between the diagnoses of gallstones and kidney stones yielded similar results.
Conclusions: Gallstones and kidney stones are independently associated. Additional studies are needed to identify shared mechanisms underlying both diseases.
C1 [Taylor, Eric N.] Maine Med Ctr, Div Nephrol & Transplantat, Portland, ME 04102 USA.
[Taylor, Eric N.; Chan, Andrew T.; Curhan, Gary C.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Curhan, Gary C.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Giovannucci, Edward L.; Curhan, Gary C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward L.; Curhan, Gary C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
RP Taylor, EN (reprint author), Maine Med Ctr, Div Nephrol & Transplantat, 22 Bramhall St, Portland, ME 04102 USA.
EM entaylor@partners.org
FU National Institutes of Health [DK59583, DK70756, CA87969, CA55075,
CA50385]
FX Supported by Grants DK59583, DK70756, CA87969, CA55075 and CA50385 from
the National Institutes of Health.
NR 30
TC 7
Z9 7
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD NOV
PY 2011
VL 186
IS 5
BP 1882
EP 1887
DI 10.1016/j.juro.2011.06.067
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 835FX
UT WOS:000296022200044
PM 21944091
ER
PT J
AU Vadysirisack, DD
Baenke, F
Ory, B
Lei, K
Ellisen, LW
AF Vadysirisack, Douangsone D.
Baenke, Franziska
Ory, Benjamin
Lei, Kui
Ellisen, Leif W.
TI Feedback Control of p53 Translation by REDD1 and mTORC1 Limits the
p53-Dependent DNA Damage Response
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID TUMOR-SUPPRESSOR; IN-VIVO; HYPOXIA; CELLS; ACTIVATION; APOPTOSIS;
STRESS; IDENTIFICATION; RTP801; GROWTH
AB Exquisite control of the level and activity of p53 are required in order to preserve cellular homeostasis following DNA damage. How this regulation is integrated with other key metabolic pathways in vivo is poorly understood. Here, we describe an endogenous feedback circuit for regulation of p53 through its transcriptional target gene, Redd1, a stress-induced inhibitor of TOR complex 1 (TORC1) activity. Cells and tissues of Redd1(-/-) mice exhibit enhanced sensitivity to ionizing radiation and chemotherapy treatment, which we demonstrate is attributable to abnormally increased p53 protein level and activity in the absence of Redd1. We find that deregulation of p53 in this setting is not due to failed DNA repair or to increased p53 stabilization but, instead, to increased p53 translation. We show that Redd1 loss leads to elevated mammalian TORC1 (mTORC1) activity, which explains the increased p53 translation and protein levels. Together, these findings suggest that REDD1-mediated suppression of mTORC1 activity exerts feedback control on p53, thereby limiting the apoptotic response and contributing to cellular survival following DNA damage. This work therefore defines a role for REDD1 in the control of p53 in vivo, with potential therapeutic implications for cancer and for the variety of genetic diseases involving TOR pathway signaling components.
C1 [Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, GRJ-904,55 Fruit St, Boston, MA 02114 USA.
EM ellisen@helix.mgh.harvard.edu
RI ory, benjamin/K-8231-2015
FU NRSA [F32 CA150633]; [RO1 CA-122589]
FX This work was supported by RO1 CA-122589 to L.W.E. and by NRSA
postdoctoral fellowship award F32 CA150633 to D.D.V.
NR 37
TC 11
Z9 14
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD NOV
PY 2011
VL 31
IS 21
BP 4356
EP 4365
DI 10.1128/MCB.05541-11
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 834NQ
UT WOS:000295968900009
PM 21896779
ER
PT J
AU Pastor, R
Reed, C
Burkhart-Kasch, S
Li, N
Sharpe, AL
Coste, SC
Stenzel-Poore, MP
Phillips, TJ
AF Pastor, Raul
Reed, Cheryl
Burkhart-Kasch, Sue
Li, Na
Sharpe, Amanda L.
Coste, Sarah C.
Stenzel-Poore, Mary P.
Phillips, Tamara J.
TI Ethanol concentration-dependent effects and the role of stress on
ethanol drinking in corticotropin-releasing factor type 1 and double
type 1 and 2 receptor knockout mice
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE CRF; Stress; Knockout; Alcohol; Drinking; Swim stress
ID ALCOHOL-DRINKING; INDUCED INCREASES; CENTRAL NUCLEUS; ANIMAL-MODELS;
C57BL/6J MICE; RAT-BRAIN; CRF; ANTAGONIST; ANXIETY; WITHDRAWAL
AB Exposure to stressors promotes ethanol (EtOH) consumption and enhances drug craving during abstinence. Corticotropin-releasing factor (CRF), and in particular, CRF actions via type 1 CRF receptors (CRF(1)) are critical in behavioral responses to stressors. CRF(1) play a role in EtOH-induced behavioral neuroadaptation, in binge-like EtOH consumption, and in heightened EtOH consumption in dependent animals.
We investigated the involvement of CRF(1) in swim-stress-induced changes in EtOH consumption and in baseline consumption as a function of EtOH concentration. The role of CRF(2) in adapting to effects of the stressor was also examined.
Wild-type mice and knockout mice lacking CRF(1) were tested for two-bottle choice EtOH consumption at concentrations of 3-20%. Also, intake of 10% EtOH was examined in wild-type mice and knockout mice lacking CRF(1), or lacking both CRF(1) and CRF(2), before and after acute or repeated swim stress exposures.
EtOH intake was reduced in CRF(1) compared with wild-type mice when presented at a concentration of 20% but not when presented at lower concentrations. No genotype-dependent effects were found for saccharin or quinine drinking. Acute swim stress had no effect, but repeated swim stress resulted in higher levels of EtOH consumption in wild-type mice, compared with both types of knockout mice. Stress effects on EtOH drinking were longer lasting in double knockout mice.
These data suggest a prominent role of CRF(1) in stressor-induced changes in EtOH consumption, with involvement of CRF(2) in recovery from stressor effects.
C1 [Phillips, Tamara J.] Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA.
[Pastor, Raul; Reed, Cheryl; Burkhart-Kasch, Sue; Li, Na; Sharpe, Amanda L.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Behav Neurosci Dept, Portland, OR 97201 USA.
[Pastor, Raul; Reed, Cheryl; Burkhart-Kasch, Sue; Li, Na; Sharpe, Amanda L.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97201 USA.
[Coste, Sarah C.; Stenzel-Poore, Mary P.] Oregon Hlth & Sci Univ, Mol Microbiol & Immunol Dept, Portland, OR 97201 USA.
[Pastor, Raul] Univ Jaume 1, Area Psicobiol, Castellon de La Plana, Spain.
RP Phillips, TJ (reprint author), Portland VA Med Ctr, Res Serv, R&D32,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM phillipt@ohsu.edu
FU Department of Veterans Affairs; NIH from the National Institute of
Alcohol Abuse and Alcoholism [R01AA13331, P60AA010760]; NIH from Mental
Health [R01MH65689]
FX This work was supported by a grant from the Department of Veterans
Affairs and NIH grants from the National Institute of Alcohol Abuse and
Alcoholism (R01AA13331 and P60AA010760) and from Mental Health
(R01MH65689).
NR 47
TC 10
Z9 10
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD NOV
PY 2011
VL 218
IS 1
SI SI
BP 169
EP 177
DI 10.1007/s00213-011-2284-6
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 833EP
UT WOS:000295865000015
PM 21487655
ER
PT J
AU Clark, DG
AF Clark, David Glenn
CA Alzheimer Dis Neuroimaging Initiat
TI Residual vectors for Alzheimer disease diagnosis and prognostication
SO BRAIN AND BEHAVIOR
LA English
DT Article
DE ADNI; Alzheimer disease; Bioinformatics; Mild cognitive impairment; PET
scan
AB Alzheimer disease (AD) is an increasingly prevalent neurodegenerative condition and a looming socioeconomic threat. A biomarker for the disease could make the process of diagnosis easier and more accurate, and accelerate drug discovery. The current work describes amethod for scoring brain images that is inspired by fundamental principles from information retrieval (IR), a branch of computer science that includes the development of Internet search engines. For this research, a dataset of 254 baseline 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) scans was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). For a given contrast, a subset of scans (nine of every 10) was used to compute a residual vector that typified the difference, at each voxel, between the two groups being contrasted. Scans that were not used for computing the residual vector (the remaining one of 10 scans) were then compared to the residual vector using a cosine similarity metric. This process was repeated sequentially, each time generating cosine similarity scores on 10% of the FDG-PET scans for each contrast. Statistical analysis revealed that the scores were significant predictors of functional decline as measured by the Functional Activities Questionnaire (FAQ). When logistic regression models that incorporated these scores were evaluated with leave-one-out cross-validation, cognitively normal controls were discerned from AD with sensitivity and specificity of 94.4% and 84.8%, respectively. Patients who converted from mild cognitive impairment (MCI) to AD were discerned from MCI nonconverters with sensitivity and specificity of 89.7% and 62.9%, respectively, when FAQ scores were brought into the model. Residual vectors are easy to compute and provide a simple method for scoring the similarity between an FDG-PET scan and sets of examples from a given diagnostic group. The method is readily generalizable to any imaging modality. Further interdisciplinary work between IR and clinical neuroscience is warranted.
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), 1720 7th Ave South,SC 620C, Birmingham, AL 35294 USA.
EM dgclark@uab.edu
FU Department of Veterans Affairs [E6553W]; ADNI (National Institutes of
Health) [U01 AG024904]; National Institute on Aging; National Institute
of Biomedical Imaging and Bioengineering; NIH [P30 AG010129, K01
AG030514]; Dana Foundation
FX Dr. Clark is supported by a Career Development Award from the Department
of Veterans Affairs (E6553W), entitled "Semantic Memory, Financial
Capacity, and Brain Perfusion in MCI."; Data collection and sharing for
this project were funded by the ADNI (National Institutes of Health
Grant U01 AG024904). ADNI is funded by the National Institute on Aging,
the National Institute of Biomedical Imaging and Bioengineering, and
through generous contributions from the following: Abbott, AstraZeneca
AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global
Clinical Development, Elan Corporation, Genentech, GE Healthcare,
Glax-oSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co.,
Medpace Inc., Merck and Co. Inc., Novartis AG, Pfizer Inc., F.
Hoffman-La Roche, Schering-Plough, Synarc Inc., as well as nonprofit
partners the Alzheimer's Association and Alzheimer's Drug Discovery
Foundation, with participation from the US Food and Drug Administration.
Private sector contributions to ADNI are facilitated by the Foundation
for the National Institutes of Health (www. fnih. org). The grantee
organization is the Northern California Institute for Research and
Education, and the study is coordinated by the Alzheimer's Disease
Cooperative Study at the University of California, San Diego. ADNI data
are disseminated by the Laboratory for Neuro Imaging at the University
of California, Los Angeles. This research was also supported by NIH
grants P30 AG010129, K01 AG030514, and the Dana Foundation.
NR 23
TC 4
Z9 4
U1 3
U2 4
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 2162-3279
J9 BRAIN BEHAV
JI Brain Behav.
PD NOV
PY 2011
VL 1
IS 2
BP 142
EP 152
DI 10.1002/brb3.19
PG 11
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA V35UO
UT WOS:000209173700010
PM 22399094
ER
PT J
AU Podar, K
Anderson, KC
AF Podar, K.
Anderson, K. C.
TI Emerging Therapies Targeting Tumor Vasculature in Multiple Myeloma and
other Hematologic and Solid Malignancies
SO CURRENT CANCER DRUG TARGETS
LA English
DT Article
DE AMG-386; AVE8062; axitinib; bevacizumab; CDP860; CE-245677; CEP-11981;
cilengitide; combretastatin; CP-868,596; enzastaurin; exherin; HuMV833;
lenalidomide; metronomic chemotherapy; MN-029; OMP-21M18; pazopanib;
PF-4856884; pomalidomide; Reg421; semaxanib; sorafenib and sunitinib;
TB403; thalidomide; TZT-1027; vadimezan; vandetanib; vatalanib; VEGFR
antibodies; VEGF-trap; ZD6126
AB Research on the formation of new blood vessels (angiogenesis) in general and vascular endothelial growth factor (VEGF) in particular is a major focus in biomedicine and has led to the clinical approval of the monoclonal anti-VEGF antibody bevazicumab; and the second-generation multitargeted receptor kinase inhibitors (RTKIs) sorafenib, sunitinib, and pazopanib. Although these agents show significant preclinical and clinical anti-cancer activity, they prolong overall survival of cancer patients for only months, followed by a restoration of tumor growth and progression. Therefore, there is a clear need to increase our understanding of tumor angiogenesis and the development of resistance. In this review we discuss up-to-date knowledge on mechanisms of tumor angiogenesis, and summarize preclinical and clinical data on existing and potential future anti-angiogenic agents and treatment strategies for Multiple Myeloma (MM) and other hematologic and solid malignancies.
C1 [Podar, K.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Podar, K.] Heidelberg Univ, Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany.
[Podar, K.] German Canc Res Ctr, D-69120 Heidelberg, Germany.
RP Podar, K (reprint author), Heidelberg Univ, Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany.
EM klaus.podar@med.uni-heidelberg.de
FU MMRF Senior Research grant award; National Institutes of Health [RO
CA50947, PO-1 CA78378, P50 CA100707]; Doris Duke Distinguished Clinical
Research Scientist Award
FX This work was supported by a MMRF Senior Research grant award (to K.P.);
National Institutes of Health Grants RO CA50947, PO-1 CA78378, and P50
CA100707; and the Doris Duke Distinguished Clinical Research Scientist
Award (to K.C.A.)
NR 304
TC 15
Z9 15
U1 3
U2 8
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1568-0096
EI 1873-5576
J9 CURR CANCER DRUG TAR
JI Curr. Cancer Drug Targets
PD NOV
PY 2011
VL 11
IS 9
BP 1005
EP 1024
PG 20
WC Oncology
SC Oncology
GA V28BX
UT WOS:000208657400003
PM 21933109
ER
PT J
AU Sacco, A
Ghobrial, IM
Roccaro, AM
AF Sacco, A.
Ghobrial, I. M.
Roccaro, A. M.
TI Anti-Angiogenic Therapies in the Treatment of Waldenstrom's
Macroglobulinemia
SO CURRENT CANCER DRUG TARGETS
LA English
DT Article
DE Anti-angiogenic approach; Waldenstrom's Macroglobulinemia
AB Bone marrow microenvironment has been shown to play a crucial role in supporting the pathogenesis and the progression of several B-cell malignancies, including Waldenstrom's Macroglobulinemia (WM). Among the different cell types within the bone marrow milieu, endothelial cells have been proven to support WM cells growth. Based on the understanding of bone marrow neo-angiogenesis in plasma cell dyscrasias, a number of anti-angiogenic molecules are now available for the treatment of these diseases. Indeed, anti-angiogenic drugs, such as proteasome-, proteins kinase-C (PKC)-, phosphatidylinositol 3-kinase/mammalian target of rapamycin (mTOR)-, and histone deacetylase (HDAC)-inhibitors are now available, playing a key role in the treatment of WM both in the preclinical settings and as part of clinical trials.
C1 [Roccaro, A. M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Roccaro, A. M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Roccaro, AM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM aldo_roccaro@dfci.harvard.edu
NR 37
TC 0
Z9 0
U1 0
U2 2
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1568-0096
J9 CURR CANCER DRUG TAR
JI Curr. Cancer Drug Targets
PD NOV
PY 2011
VL 11
IS 9
BP 1025
EP 1029
PG 5
WC Oncology
SC Oncology
GA V28BX
UT WOS:000208657400004
PM 21933107
ER
PT J
AU Cheng, YC
O'Connell, JR
Cole, JW
Stine, OC
Dueker, N
McArdle, PF
Sparks, MJ
Shen, J
Laurie, CC
Nelson, S
Doheny, KF
Ling, H
Pugh, EW
Brott, TG
Brown, RD
Meschia, JF
Nalls, M
Rich, SS
Worrall, B
Anderson, CD
Biffi, A
Cortellini, L
Furie, KL
Rost, NS
Rosand, J
Manolio, TA
Kittner, SJ
Mitchell, BD
AF Cheng, Yu-Ching
O'Connell, Jeffrey R.
Cole, John W.
Stine, O. Colin
Dueker, Nicole
McArdle, Patrick F.
Sparks, Mary J.
Shen, Jess
Laurie, Cathy C.
Nelson, Sarah
Doheny, Kimberly F.
Ling, Hua
Pugh, Elizabeth W.
Brott, Thomas G.
Brown, Robert D., Jr.
Meschia, James F.
Nalls, Michael
Rich, Stephen S.
Worrall, Bradford
Anderson, Christopher D.
Biffi, Alessandro
Cortellini, Lynelle
Furie, Karen L.
Rost, Natalia S.
Rosand, Jonathan
Manolio, Teri A.
Kittner, Steven J.
Mitchell, Braxton D.
TI Genome-Wide Association Analysis of Ischemic Stroke in Young Adults
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE epidemiology; genetics; brain infarction; FMNL2
ID VARIANTS; RISK; CLASSIFICATION; DISEASE; IMPUTATION; INFARCTION;
SUBTYPE; LINKAGE; LOCI; TOOL
AB Ischemic stroke (IS) is among the leading causes of death in Western countries. There is a significant genetic component to IS susceptibility, especially among young adults. To date, research to identify genetic loci predisposing to stroke has met only with limited success. We performed a genome-wide association (GWA) analysis of early-onset IS to identify potential stroke susceptibility loci. The GWA analysis was conducted by genotyping 1 million SNPs in a biracial population of 889 IS cases and 927 controls, ages 15-49 years. Genotypes were imputed using the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic regression models adjusting for age, recruitment stages, and population structure were used to determine the association of IS with individual SNPs. Although no single SNP reached genome-wide significance (P < 5 x 10(-8)), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P = 1.2 x 10(-7)) and rs1986743 (in ARL6IP6; P = 2.7 x 10(-7)), strongly associated with early-onset stroke. These data suggest that a novel locus on human chromosome 2q23.3 may be associated with IS susceptibility among young adults.
C1 [Cheng, Yu-Ching; O'Connell, Jeffrey R.; McArdle, Patrick F.; Mitchell, Braxton D.] Univ Maryland, Dept Med, Sch Med, Baltimore, MD 21201 USA.
[Cole, John W.; Sparks, Mary J.; Kittner, Steven J.] Univ Maryland, Dept Neurol, Sch Med, Baltimore, MD 21201 USA.
[Stine, O. Colin; Dueker, Nicole] Univ Maryland, Dept Epidemiol & Publ Hlth, Sch Med, Baltimore, MD 21201 USA.
[Cole, John W.; Kittner, Steven J.] Vet Affairs Med Ctr, Dept Neurol, Baltimore, MD 21201 USA.
[Shen, Jess; Laurie, Cathy C.; Nelson, Sarah] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Doheny, Kimberly F.; Ling, Hua; Pugh, Elizabeth W.] Johns Hopkins Univ, Ctr Inherited Dis Res, Sch Med, Baltimore, MD 21224 USA.
[Brott, Thomas G.; Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Brown, Robert D., Jr.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA.
[Nalls, Michael] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Mitchell, Braxton D.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
[Rich, Stephen S.; Worrall, Bradford] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
[Worrall, Bradford] Univ Virginia, Dept Neurol, Charlottesville, VA 22908 USA.
[Anderson, Christopher D.; Biffi, Alessandro; Cortellini, Lynelle; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Anderson, Christopher D.; Biffi, Alessandro; Cortellini, Lynelle; Furie, Karen L.; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Anderson, Christopher D.; Biffi, Alessandro; Cortellini, Lynelle; Rost, Natalia S.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
RP Mitchell, BD (reprint author), Univ Maryland, Dept Med, Sch Med, 660 W Redwood St,Howard Hall,Room 492, Baltimore, MD 21201 USA.
EM bmitchel@medicine.umaryland.edu
OI Anderson, Christopher/0000-0002-0053-2002; Mitchell,
Braxton/0000-0003-4920-4744
FU National Institutes of Health (NIH) Genes, Environment and Health
Initiative (GEI) [U01 HG-004436]; Mid-Atlantic Nutrition and Obesity
Research Center [P30 DK-072488]; Office of Research and Development,
Medical Research Service; Baltimore Geriatrics Research, Education, and
Clinical Center of the Department of Veterans Affairs; GEI [U01
HG-004438-01]; Division of Adult and Community Health, Centers for
Disease Control; National Institute of Neurological Disorders and Stroke
(NINDS); NIH Office of Research on Women's Health [R01 NS-45012, U01
NS-069208-01]; National Institute on Aging, NIH [Z01 AG-000954-06, Z01
AG-000015-50]; NIH-NINDS [R01 NS-42733, R01 NS-39987, K23 NS-064052, R01
NS-063925, P50 NS-051343]; American Heart Association/Bugher Foundation
Centers for Stroke Prevention Research [0775010N]; Deane Institute for
Integrative Study of Atrial Fibrillation and Stroke; Keane Stroke
Genetics Research Fund; American Heart Association/Bugher Foundation
Centers for Stroke Prevention Research
FX GEOS was supported by the National Institutes of Health (NIH) Genes,
Environment and Health Initiative (GEI) Grant U01 HG-004436, as part of
the GENEVA consortium under GEI, with additional support provided by the
Mid-Atlantic Nutrition and Obesity Research Center (P30 DK-072488); and
by the Office of Research and Development, Medical Research Service, and
the Baltimore Geriatrics Research, Education, and Clinical Center of the
Department of Veterans Affairs. Genotyping services were provided by the
Johns Hopkins University Center for Inherited Disease Research (CIDR)
and funded by GEI Grant U01 HG-004438-01. Assistance with data cleaning
was provided by the GENEVA Coordinating Center (U01 HG-004446; Bruce S.
Weir, P. I.). Study recruitment and assembly of datasets were supported
by a Cooperative Agreement with the Division of Adult and Community
Health, Centers for Disease Control, and by National Institute of
Neurological Disorders and Stroke (NINDS) and NIH Office of Research on
Women's Health Grants R01 NS-45012 and U01 NS-069208-01. The ISGS/SWISS
study was supported in part by the Intramural Research Program of the
National Institute on Aging, NIH project Z01 AG-000954-06. ISGS/SWISS
used samples and clinical data from the NIH-NINDS Human Genetics
Resource Center DNA and Cell Line Repository
(http://ccr.coriell.org/ninds), human subjects protocol numbers 2003-081
and 2004-147. ISGS/SWISS used stroke-free participants from the
Baltimore Longitudinal Study of Aging (BLSA) as controls. The inclusion
of BLSA samples was supported in part by the Intramural Research Program
of the National Institute on Aging, NIH project Z01 AG-000015-50, human
subjects protocol number 2003-078. The ISGS study was funded by
NIH-NINDS Grant R01 NS-42733 (J. F. Meschia, P. I.). The SWISS study was
funded by NIH-NINDS Grant R01 NS-39987 (J. F. Meschia, P. I.). This
study utilized the high-performance computational capabilities of the
Biowulf Linux cluster at the NIH (http://biowulf.nih.gov). GASROS was
supported by American Heart Association/Bugher Foundation Centers for
Stroke Prevention Research Grant 0775010N; NIH-NINDS Grants K23
NS-064052 (N. S. Rost), R01 NS-063925 (J. Rosand), and P50 NS-051343 (J.
Rosand and K. L. Furie); the Deane Institute for Integrative Study of
Atrial Fibrillation and Stroke; and the Keane Stroke Genetics Research
Fund. Drs. A. Biffi, N. S. Rost, and C. D. Anderson were supported in
part by the American Heart Association/Bugher Foundation Centers for
Stroke Prevention Research.
NR 31
TC 12
Z9 12
U1 0
U2 0
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD NOV 1
PY 2011
VL 1
IS 6
BP 505
EP 513
DI 10.1534/g3.111.001164
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 055IP
UT WOS:000312409400011
PM 22384361
ER
PT J
AU Abi-Raad, R
Boutrus, R
Wang, R
Niemierko, A
Smith, B
Taghian, AG
AF Abi-Raad, Rita
Boutrus, Rimoun
Wang, Rui
Niemierko, Andrzej
Smith, Barbara
Taghian, Alphonse G.
TI PATTERNS AND RISK FACTORS OF LOCOREGIONAL RECURRENCE IN T1-T2 NODE
NEGATIVE BREAST CANCER PATIENTS TREATED WITH MASTECTOMY: IMPLICATIONS
FOR POSTMASTECTOMY RADIOTHERAPY
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Breast cancer; Mastectomy; Postmastectomy radiation; Risk factors;
Locoregional recurrence
AB Purpose: Postmastectomy radiation therapy (PMRT) can reduce locoregional recurrences (LRR) in high-risk patients, but its role in the treatment of lymph node negative (LN-) breast cancer remains unclear. The aim of this study was to identify a subgroup of T1-T2 breast cancer patients with LN-who might benefit from PMRT.
Methods and Materials: We retrospectively reviewed 1,136 node-negative T1-T2 breast cancer cases treated with mastectomy without PMRT at the Massachusetts General Hospital between 1980 and 2004. We estimated cumulative incidence rates for LRR overall and in specific subgroups, and used Cox proportional hazards models to identify potential risk factors.
Results: Median follow-up was 9 years. The 10-year cumulative incidence of LRR was 5.2% (95% CI: 3.9-6.7%). Chest wall was the most common (73%) site of LRR. Tumor size, margin, patient age, systemic therapy, and lymphovascular invasion (LVI) were significantly associated with LRR on multivariate analysis. These five variables were subsequently used as risk factors for stratified analysis. The 10-year cumulative incidence of LRR for patients with no risk factors was 2.0% (95% CI: 0.5-5.2%), whereas the incidence for patients with three or more risk factors was 19.7% (95% CI: 12.2-28.6%).
Conclusion: It has been suggested that patients with T1-T2N0 breast cancer who undergo mastectomy represent a favorable group for which PMRT renders little benefit. However, this study suggests that select patients with multiple risk factors including LVI, tumor size >= 2 cm, close or positive margin, age <= 50, and no systemic therapy are at higher risk of LRR and may benefit from PMRT. (c) 2011 Elsevier Inc.
C1 [Abi-Raad, Rita; Boutrus, Rimoun; Niemierko, Andrzej; Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA.
[Wang, Rui; Niemierko, Andrzej] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Biostat, Boston, MA USA.
[Smith, Barbara] Harvard Univ, Sch Med, Dept Surg, Div Surg Oncol,Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St Cox Bldg 302, Boston, MA 02114 USA.
EM ataghian@partners.org
FU National Cancer Institute [R01CA139118, P50CA089393]; National
Institutes of Health [CA50628]; Jane Mailloux Research Fund; Blanche
Montesi Fund; Tim Levy Fund
FX Supported in part by Award Number R01CA139118 (AGT) and Award Number
P50CA089393 (AGT) from the National Cancer Institute, in part by grant
CA50628 from the National Institutes of Health (AN). 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 study was also partially supported by
the Jane Mailloux Research Fund (AGT), the Blanche Montesi Fund (AGT),
Tim Levy Fund for breast cancer research (AGT).
NR 38
TC 14
Z9 14
U1 0
U2 0
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 NOV 1
PY 2011
VL 81
IS 3
BP E151
EP E157
DI 10.1016/j.ijrobp.2011.01.015
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA V33MZ
UT WOS:000209024200019
PM 21420245
ER
PT J
AU Ahern, RL
Corless, IB
Davis, SM
Kwong, JJ
AF Ahern, Richard L.
Corless, Inge B.
Davis, Sheila M.
Kwong, Jeffrey J.
TI Infusing Swanson's Theory of Caring into an Advanced Practice Nursing
Model for an Infectious Diseases Anal Dysplasia Clinic
SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE
LA English
DT Article
DE advanced practice nursing; anal dysplasia; HIV; theory of caring
AB The incidence of anal cancer is increasing among HIV-infected men and women. The process of screening for anal dysplasia and the management of abnormal findings are currently and most often based on a medical model. The needs of these patients, however, go well beyond medical care. A more comprehensive and holistic approach to health care is, therefore, required. Given the scope of practice of advanced practice nurses who are involved in the diagnosis and treatment of patients with anal dysplasia, it is appropriate for them to assume leadership roles in addressing the needs of these patients. This article describes the application of a theory of caring to create an advanced practice nursing model of care for HIV-infected men and women in infectious diseases anal dysplasia clinics. Copyright (C) 2011 Association of Nurses in AIDS Care
C1 [Ahern, Richard L.; Davis, Sheila M.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Corless, Inge B.] MGH Inst Hlth Profess, Sch Nursing, Boston, MA USA.
[Kwong, Jeffrey J.] Rutgers Coll Nursing, Newark, NJ USA.
RP Ahern, RL (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
OI Corless, Inge/0000-0003-0438-2037
NR 30
TC 1
Z9 1
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1055-3290
J9 J ASSOC NURSE AIDS C
JI J. Assoc. Nurses Aids Care
PD NOV-DEC
PY 2011
VL 22
IS 6
SI SI
BP 478
EP 488
DI 10.1016/j.jana.2011.06.010
PG 11
WC Nursing
SC Nursing
GA V28YQ
UT WOS:000208716500007
PM 22035527
ER
PT J
AU Bezerra, HG
Loureiro, R
Irlbeck, T
Bamberg, F
Schlett, CL
Rogers, I
Blankstein, R
Truong, QA
Brady, TJ
Cury, RC
Hoffmann, U
AF Bezerra, Hiram G.
Loureiro, Ricardo
Irlbeck, Thomas
Bamberg, Fabian
Schlett, Christopher L.
Rogers, Ian
Blankstein, Ron
Truong, Quynh A.
Brady, Thomas J.
Cury, Ricardo C.
Hoffmann, Udo
TI Incremental value of myocardial perfusion over regional left ventricular
function and coronary stenosis by cardiac CT for the detection of acute
coronary syndromes in high-risk patients: A subgroup analysis of the
ROMICAT trial
SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY
LA English
DT Article
DE Myocardial perfusion; Cardiac CT; Acute coronary syndrome
ID ACUTE CHEST-PAIN; MULTIDETECTOR COMPUTED-TOMOGRAPHY;
EMERGENCY-DEPARTMENT PATIENTS; DUAL-SOURCE CT; ARTERY-DISEASE;
INFARCTION; ANGIOGRAPHY; CARDIOLOGY; STATEMENT; MDCT
AB OBJECTIVES: To determine the incremental benefit of assessing myocardial perfusion defects (MPD) for acute coronary syndromes (ACS) over coronary and functional assessment by rest cardiac computed tomography (CT) in patients with acute chest pain.
BACKGROUND: Assessment of myocardial perfusion is feasible with cardiac CT; however, the diagnostic value of this assessment in patients at risk for ACS has not been demonstrated.
METHODS: The study included patients who presented to the emergency department with acute chest pain, nonischemic initial electrocardiogram (ECG), and negative cardiac biomarkers but had clinical suspicion for ACS and underwent invasive coronary angiography (ICA). Results were blinded to caregivers and patients. CT data sets were independently assessed for the presence of coronary plaque and stenosis, regional left ventricular function, and myocardial perfusion deficits by 2 blinded observers. Coronary angiography was assessed for the presence of stenosis, TIMI myocardial perfusion grade, and corrected TIMI frame count. The endpoint was ACS during index hospitalization.
RESULTS: We analyzed data from 35 subjects (69% male, mean age 58 +/- 9 years) of whom 22 (63%) had ACS. The sensitivity and specificity of MPD for ACS were 86% (95% CI: 64%-96%) and 62% (95% Cl: 32%-85%), respectively. Combined, MPD and RWMA assessment resulted in specificity and sensitivity of 86% (95% CI: 64%-96%) and 85% (95% CI: 54%-97%), respectively. Adding MPD and RWMA to the assessment for significant stenosis (>50%) resulted in a higher sensitivity of 91% (69-98%) and specificity of 85% (54-97%) and a significantly increased overall diagnostic accuracy when compared with assessment for stenosis (AUC: 0.88 vs 0.79; respectively, P = 0.02). Diagnostic accuracy of CT was not associated with impaired CTFC >40 or myocardial TIMI perfusion grade < 3.
CONCLUSIONS: Assessment of myocardial perfusion and regional wall motion abnormalities may enhance the ability of CT to detect ACS in patients with acute chest pain. (C) 2011 Society of Cardiovascular Computed Tomography. All rights reserved.
C1 [Bezerra, Hiram G.; Loureiro, Ricardo; Irlbeck, Thomas; Bamberg, Fabian; Schlett, Christopher L.; Rogers, Ian; Blankstein, Ron; Truong, Quynh A.; Brady, Thomas J.; Cury, Ricardo C.; Hoffmann, Udo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Bezerra, Hiram G.] Univ Hosp Case Med Ctr, Harrington McLaughlin Heart & Vasc Inst, Cleveland, OH USA.
[Loureiro, Ricardo; Irlbeck, Thomas; Bamberg, Fabian; Schlett, Christopher L.; Brady, Thomas J.; Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rogers, Ian; Blankstein, Ron; Truong, Quynh A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Cardiovasc MR & CT Program, Miami, FL USA.
RP Hoffmann, U (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM uhoffmann@partners.org
FU National Institutes of Health (NIH) [R01 HL080053, T32 HL076136]
FX This work was supported by National Institutes of Health (NIH) grant R01
HL080053. R.B., I.R., and Q.A.T. received salary support from NIH T32
HL076136.
NR 27
TC 16
Z9 16
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-5925
J9 J CARDIOVASC COMPUT
JI J. Cardiovasc. Comput. Tomogr.
PD NOV-DEC
PY 2011
VL 5
IS 6
BP 382
EP 391
DI 10.1016/j.jcct.2011.10.004
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 035HJ
UT WOS:000310933700005
PM 22146497
ER
PT J
AU Ghoshhajra, BB
Rogers, IS
Maurovich-Horvat, P
Techasith, T
Verdini, D
Sidhu, MS
Drzezga, NK
Medina, HM
Blankstein, R
Brady, TJ
Cury, RC
AF Ghoshhajra, Brian B.
Rogers, Ian S.
Maurovich-Horvat, Pal
Techasith, Tust
Verdini, Daniel
Sidhu, Manavjot S.
Drzezga, Nicola K.
Medina, Hector M.
Blankstein, Ron
Brady, Thomas J.
Cury, Ricardo C.
TI A comparison of reconstruction and viewing parameters on image quality
and accuracy of stress myocardial CT perfusion
SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY
LA English
DT Article
DE Optimal viewing parameters; Cardiac computed tomography; Perfusion
defects
ID COMPUTED-TOMOGRAPHY; MULTIDETECTOR CT; ANGIOGRAPHY; DEFECTS; EXTENT;
SPECT
AB BACKGROUND: Myocardial stress computed tomography perfusion (CTP) has similar diagnostic accuracy for detecting perfusion defects (PDs) versus single-photon emission computed tomography (SPECT). However, the optimal diagnostic viewing and image processing parameters for CTP are unknown.
OBJECTIVE: We sought to compare the diagnostic accuracy of different image processing techniques, cardiac phases, slice thicknesses, and viewing parameters for detection of PDs.
METHODS: A stress and rest dual-source CTP protocol was performed with adenosine. Twelve subjects with severe stenosis proven by quantitative coronary angiography (QCA), with corresponding territorial defects at SPECT, were selected as well as 7 controls (subjects with similar clinical suspicion but negative QCA and SPECT). Short-axis stress images were processed with 3 techniques: minimum intensity projection (MinIP), maximum intensity projection, and average intensity multiplanar reconstruction (MPR), 3 thicknesses (1, 3, 8 mm), and 2 phases (systolic, mid-diastolic). The resulting images (n = 1026) were randomized and interpreted by independent readers.
RESULTS: Diastolic reconstructions (8-mm MPR) showed the highest sensitivity (81%) to detect true PDs. The highest accuracy was achieved with the 8-mm (61%) and 1-mm (61%) MPR diastolic images. The most sensitive and accurate systolic reconstructions were 3-mm MinIP images. These findings related to viewing in relatively narrow window width and window level settings.
CONCLUSION: Viewing parameters for optimal accuracy in detection of perfusion defects on CTP differ for systolic and diastolic images. (C) 2011 Society of Cardiovascular Computed Tomography. All rights reserved.
C1 [Ghoshhajra, Brian B.; Rogers, Ian S.; Maurovich-Horvat, Pal; Techasith, Tust; Verdini, Daniel; Sidhu, Manavjot S.; Drzezga, Nicola K.; Medina, Hector M.; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02114 USA.
[Ghoshhajra, Brian B.; Rogers, Ian S.; Maurovich-Horvat, Pal; Techasith, Tust; Verdini, Daniel; Sidhu, Manavjot S.; Drzezga, Nicola K.; Medina, Hector M.; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Ghoshhajra, Brian B.; Rogers, Ian S.; Maurovich-Horvat, Pal; Techasith, Tust; Verdini, Daniel; Sidhu, Manavjot S.; Drzezga, Nicola K.; Medina, Hector M.; Brady, Thomas J.; Cury, Ricardo C.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Rogers, Ian S.] Stanford Univ, Falk Cardiovasc Res Ctr, Div Cardiovasc Med, Stanford, CA 94305 USA.
[Blankstein, Ron] Brigham & Womens Hosp, Div Cardiovasc, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA.
[Blankstein, Ron] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Cardiovasc MRI & CT Program, Miami, FL USA.
RP Ghoshhajra, BB (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM bghoshhajra@partners.org
RI Ghoshhajra, Brian/J-2114-2016;
OI Ghoshhajra, Brian/0000-0002-3865-3432; Maurovich-Horvat,
Pal/0000-0003-0885-736X
FU Astellas Pharmaceuticals Inc.
FX Astellas Pharmaceuticals Inc. provided grant support for the initial
study. The authors maintained full control over this study design and
data.
NR 15
TC 9
Z9 9
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-5925
J9 J CARDIOVASC COMPUT
JI J. Cardiovasc. Comput. Tomogr.
PD NOV-DEC
PY 2011
VL 5
IS 6
BP 459
EP 466
DI 10.1016/j.jcct.2011.10.011
PG 8
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 035HJ
UT WOS:000310933700013
PM 22146505
ER
PT J
AU Fortney, JC
Burgess, JF
Bosworth, HB
Booth, BM
Kaboli, PJ
AF Fortney, John C.
Burgess, James F., Jr.
Bosworth, Hayden B.
Booth, Brenda M.
Kaboli, Peter J.
TI A Re-conceptualization of Access for 21st Century Healthcare
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Review
DE access; e-health; digital; connectivity; veterans
AB Many e-health technologies are available to promote virtual patient-provider communication outside the context of face-to-face clinical encounters. Current digital communication modalities include cell phones, smartphones, interactive voice response, text messages, e-mails, clinic-based interactive video, home-based web-cams, mobile smartphone two-way cameras, personal monitoring devices, kiosks, dashboards, personal health records, web-based portals, social networking sites, secure chat rooms, and on-line forums. Improvements in digital access could drastically diminish the geographical, temporal, and cultural access problems faced by many patients. Conversely, a growing digital divide could create greater access disparities for some populations. As the paradigm of healthcare delivery evolves towards greater reliance on non-encounter-based digital communications between patients and their care teams, it is critical that our theoretical conceptualization of access undergoes a concurrent paradigm shift to make it more relevant for the digital age. The traditional conceptualizations and indicators of access are not well adapted to measure access to health services that are delivered digitally outside the context of face-to-face encounters with providers. This paper provides an overview of digital "encounterless" utilization, discusses the weaknesses of traditional conceptual frameworks of access, presents a new access framework, provides recommendations for how to measure access in the new framework, and discusses future directions for research on access.
C1 [Fortney, John C.; Booth, Brenda M.] Cent Arkansas Vet Healthcare Syst, Hlth Serv Res & Dev HSRD, Ctr Mental Hlth & Outcomes Res, North Little Rock, AR 72114 USA.
[Fortney, John C.] Cent Arkansas Vet Healthcare Syst, South Cent Mental Illness Res Educ & Clin Ctr, North Little Rock, AR 72114 USA.
[Fortney, John C.; Booth, Brenda M.] Univ Arkansas Med Sci, Div Hlth Serv Res, Dept Psychiat, Coll Med, North Little Rock, AR USA.
[Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA.
[Burgess, James F., Jr.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Bosworth, Hayden B.] Durham VA Med Ctr, Hlth Serv Res & Dev Serv HSR & D, Ctr Hlth Serv Res Primary Care, Durham, NC USA.
[Bosworth, Hayden B.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Bosworth, Hayden B.] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA.
[Bosworth, Hayden B.] Duke Univ, Med Ctr, Sch Nursing, Durham, NC 27710 USA.
[Kaboli, Peter J.] Vet Rural Hlth Resource Ctr Cent Reg, VA Off Rural Hlth ORH, Iowa City, IA USA.
[Kaboli, Peter J.] Iowa City VA Healthcare Syst, CRIISP, Iowa City, IA USA.
[Kaboli, Peter J.] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA.
RP Fortney, JC (reprint author), Cent Arkansas Vet Healthcare Syst, Hlth Serv Res & Dev HSRD, Ctr Mental Hlth & Outcomes Res, 2200 Ft Roots Dr, North Little Rock, AR 72114 USA.
EM fortneyjohnc@uams.edu
OI Burgess, James/0000-0002-6646-7071
FU Department of Veterans Affairs, South Central Mental Illness Research
Education and Clinical Center; Health Services Research and Development
Service Center for Mental Healthcare and Outcomes Research; Department
of Veterans Affairs, Health Services Research and Development Service
Career Scientist Award [08-027]; Department of Veterans Affairs Health
Services Research and Development Service Center for Mental Healthcare
and Outcomes Research; Department of Veterans Affairs, Office of Rural
Health, Veterans Rural Health Resource Center-Central Region
FX Dr. Fortney was funded by the Department of Veterans Affairs, South
Central Mental Illness Research Education and Clinical Center, and the
Health Services Research and Development Service Center for Mental
Healthcare and Outcomes Research. Dr. Bosworth was funded by the
Department of Veterans Affairs, Health Services Research and Development
Service Career Scientist Award 08-027. Dr. Booth was funded by the
Department of Veterans Affairs Health Services Research and Development
Service Center for Mental Healthcare and Outcomes Research. Dr. Kaboli
was supported by the Department of Veterans Affairs, Office of Rural
Health, Veterans Rural Health Resource Center-Central Region. The views
expressed in this paper are those of the authors and do not necessarily
represent the views of the Department of Veterans Affairs.
NR 56
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U1 2
U2 15
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2011
VL 26
SU 2
BP S639
EP S647
DI 10.1007/s11606-011-1806-6
PG 9
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V30JP
UT WOS:000208812600005
PM 21989616
ER
PT J
AU Hogan, TP
Wakefield, B
Nazi, KM
Houston, TK
Weaver, FM
AF Hogan, Timothy P.
Wakefield, Bonnie
Nazi, Kim M.
Houston, Thomas K.
Weaver, Frances M.
TI Promoting Access Through Complementary eHealth Technologies:
Recommendations for VA's Home Telehealth and Personal Health Record
Programs
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE eHealth; patient-centered medical home; telehealth; personal health
records; veteran
AB BACKGROUND: Many healthcare organizations have embraced eHealth technologies in their efforts to promote patient-centered care, increase access to services, and improve outcomes.
OBJECTIVE: Using the Department of Veterans Affairs (VA) as a case study, this paper presents two specific eHealth technologies, the Care Coordination Home Telehealth (CCHT) Program and the My HealtheVet (MHV) personal health record (PHR) portal with integrated secure messaging, and articulates a vision of how they might be implemented as part of a patient-centric healthcare model and used in a complementary manner to enhance access to care and to support patient-centered care.
METHODS: Based on our experience and ongoing work with both programs, we offer a series of recommendations for pursuing and ultimately achieving this vision.
CONCLUSION: VA's CCHT and MHV programs are examples of an expanding repertoire of eHealth applications available to patients and healthcare teams. VA's new patient-centric healthcare model represents a significant shift in the way that services are delivered and a profound opportunity to incorporate eHealth technologies like the CCHT and MHV programs into clinical practice to increase access to care, and to ensure the responsiveness of such technologies to the preferences and circumstances of patients.
C1 [Hogan, Timothy P.; Weaver, Frances M.] Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA.
[Hogan, Timothy P.; Weaver, Frances M.] Jr VA Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL 60141 USA.
[Hogan, Timothy P.; Wakefield, Bonnie; Houston, Thomas K.; Weaver, Frances M.] Edith Nourse Rogers Mem Vet Hosp, eHlth Qual Enhancement Res Initiat, Natl eHlth QUERI Coordinating Ctr, Bedford, MA USA.
[Hogan, Timothy P.; Weaver, Frances M.] Loyola Univ Chicago, Program Hlth Serv Res, Stritch Sch Med, Loyola Univ Hlth Syst, Maywood, IL USA.
[Wakefield, Bonnie] Iowa City VA Med Ctr, VA Hlth Serv Res & Dev, Ctr Comprehens Access & Delivery Res & Evaluat CA, Iowa City, IA USA.
[Nazi, Kim M.] US Dept Vet Affairs, Vet & Consumers Hlth Informat Off, Off Hlth Informat, Vet Hlth Adm, Washington, DC USA.
[Houston, Thomas K.] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res CHQOER, Bedford, MA USA.
[Houston, Thomas K.] Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, Worcester, MA USA.
RP Hogan, TP (reprint author), Jr VA Hosp, Ctr Management Complex Chron Care, Edward Hines, 5000 S 5th Ave, Hines, IL 60141 USA.
EM timothy.hogan@va.gov
NR 59
TC 19
Z9 19
U1 2
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2011
VL 26
SU 2
BP S628
EP S635
DI 10.1007/s11606-011-1765-y
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V30JP
UT WOS:000208812600003
PM 21989614
ER
PT J
AU Jackson, GL
Krein, SL
Alverson, DC
Darkins, AW
Gunnar, W
Harada, ND
Helfrich, CD
Houston, TK
Klobucar, TF
Nazi, KM
Poropatich, RK
Ralston, JD
Bosworth, HB
AF Jackson, George L.
Krein, Sarah L.
Alverson, Dale C.
Darkins, Adam W.
Gunnar, William
Harada, Nancy D.
Helfrich, Christian D.
Houston, Thomas K.
Klobucar, Thomas F.
Nazi, Kim M.
Poropatich, Ronald K.
Ralston, James D.
Bosworth, Hayden B.
TI Defining Core Issues in Utilizing Information Technology to Improve
Access: Evaluation and Research Agenda
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE access to care; medical informatics; veterans
AB The Department of Veterans Affairs (VA) has been at the vanguard of information technology (IT) and use of comprehensive electronic health records. Despite the widespread use of health IT in the VA, there are still a variety of key questions that need to be answered in order to maximize the utility of IT to improve patient access to quality services. This paper summarizes the potential of IT to enhance healthcare access, key gaps in current evidence linking IT and access, and methodologic challenges for related research. We also highlight four key issues to be addressed when implementing and evaluating the impact of IT interventions on improving access to quality care: 1) Understanding broader needs/perceptions of the Veteran population and their caregivers regarding use of IT to access healthcare services and related information. 2) Understanding individual provider/clinicianneeds/perceptions regarding use of IT for patient access to healthcare. 3) System/Organizational issues within the VA and other organizations related to the use of IT to improve access. 4) IT integration and information flow with non-VA entities. While the VA is used as an example, the issues are salient for healthcare systems that are beginning to take advantage of IT solutions.
C1 [Jackson, George L.; Bosworth, Hayden B.] Durham Vet Affairs Med Ctr, Hlth Serv Res & Dev HSR& D Ctr Hlth Serv Res Prim, Durham, NC 27705 USA.
[Jackson, George L.; Bosworth, Hayden B.] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA.
[Krein, Sarah L.] Ann Arbor Vet Affairs Med Ctr, HSR & D Ctr Clin Management Res, Ann Arbor, MI USA.
[Krein, Sarah L.] Univ Michigan, Sch Med, Div Gen Med, Ann Arbor, MI USA.
[Alverson, Dale C.] Univ New Mexico, Hlth Sci Ctr, Ctr Telehealth & Cybermed Res, Albuquerque, NM 87131 USA.
[Darkins, Adam W.] Vet Hlth Adm, Off Care Coordinat Serv, Washington, DC USA.
[Gunnar, William] Vet Hlth Adm, Off Patient Care Serv, Washington, DC USA.
[Harada, Nancy D.] Veteran Affairs Greater Los Angeles Healthcare Sy, Off Grad Med Educ & Geriatr Res, Educ & Clin Ctr, Los Angeles, CA USA.
[Harada, Nancy D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Helfrich, Christian D.] Vet Affairs Puget Sound Hlth Care Syst, HSR & D Northwest Outcomes Res Older Adults, Seattle, WA USA.
[Helfrich, Christian D.; Ralston, James D.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA.
[Houston, Thomas K.] Edith Nourse Rogers Mem Vet Hosp, HSR & D Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Houston, Thomas K.] Univ Massachusetts, Sch Med, Dept Qualitat Hlth Sci, Worcester, MA USA.
[Klobucar, Thomas F.] Cent Reg, Vet Rural Hlth Resource Ctr, Iowa City, IA USA.
[Nazi, Kim M.] Vet Hlth Adm, Vet & Consumers Hlth Informat Off, Off Hlth Informat, Washington, DC USA.
[Poropatich, Ronald K.] Telemed & Adv Technol Res Ctr, Ft Detrick, MD USA.
[Ralston, James D.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
RP Jackson, GL (reprint author), Durham Vet Affairs Med Ctr, Hlth Serv Res & Dev HSR& D Ctr Hlth Serv Res Prim, Durham, NC 27705 USA.
EM george.l.jackson@duke.edu
RI Krein, Sarah/E-2742-2014; Helfrich, Christian/D-2382-2016
OI Krein, Sarah/0000-0003-2111-8131; Helfrich,
Christian/0000-0002-9827-4768
FU VA HSR&D Career Scientist Award [08-027]
FX This paper summarizes deliberations of the Adoption and Implementation
of IT Workgroup at the VA Health Services Research & Development (HSR&D)
State of the Art Conference on Improving Access to VA Care held
September 21-22 2010 in Arlington, VA. In addition to the authors, the
following individuals were part of the workgroup: Leigh Anderson, MD;
David Atkins, MD, MPH; Nancy Maher, Ph.D.; Kevin Vigilante, MD, MPH; and
Kenneth R. Wingart, Ph.D. The last author was supported by a VA HSR&D
Career Scientist Award (08-027).
NR 50
TC 7
Z9 7
U1 4
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2011
VL 26
SU 2
BP S623
EP S627
DI 10.1007/s11606-011-1789-3
PG 5
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V30JP
UT WOS:000208812600002
PM 21989613
ER
PT J
AU Kramer, BJ
Jouldjian, S
Wang, MM
Dang, J
Mitchell, MN
Finke, B
Saliba, D
AF Kramer, B. Josea
Jouldjian, Stella
Wang, Mingming
Dang, Jeff
Mitchell, Michael N.
Finke, Bruce
Saliba, Debra
TI Do Correlates of Dual Use by American Indian and Alaska Native Veterans
Operate Uniformly Across the Veterans Health Administration and the
Indian Health Service?
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE access; underserved populations; health services research
AB OBJECTIVE: To determine if the combined effects of patient-level (demographic and clinical characteristics) and organizational-level (structure and strategies to improve access) factors are uniformly associated with utilization of Indian Health Service (IHS) and/or Veterans Health Administration (VHA) by American Indian and Alaska Native (AIAN) Veterans to inform policy which promotes dual use.
METHODS: We estimated correlates and compared two separate multilevel logistic regression models of VHA-IHS dual versus IHS-only and VHA-IHS dual versus VHA-only in a sample of 18,892 AIAN Veterans receiving care at 201 VHA and IHS facilities during FY02 and FY03. Demographic, diagnostic, eligibility, and utilization data were drawn from administrative records. A survey of VHA and IHS facilities defined availability of services and strategies to enhance access to healthcare for AIAN Veterans.
RESULTS: Facility level strategies that are generally associated with enhancing access to healthcare (e. g., population-based services and programs, transportation or co-location) were not significant factors associated with dual use. In both models the common variable of dual use was related to medical need, defined as the number of diagnoses per patient. Other significant demographic, medical need and organizational factors operated in opposing manners. For instance, age increased the likelihood of dual use versus IHS-only but decreased the likelihood of dual use versus VHA-only.
CONCLUSIONS: Efforts to enhance access through population-based and consumer-driven strategies may add value but be less important to utilization than availability of healthcare resources needed by this population. Sharing health records and co-management strategies would improve quality of care while policies allow and promote dual use.
C1 [Kramer, B. Josea; Jouldjian, Stella; Saliba, Debra] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, Sepulveda, CA 91343 USA.
[Kramer, B. Josea; Saliba, Debra] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr Med, Los Angeles, CA 90095 USA.
[Wang, Mingming; Mitchell, Michael N.; Saliba, Debra] VA Greater Los Angeles Healthcare Syst, Hlth Serv Res Ctr Excellence, Sepulveda, CA USA.
[Dang, Jeff] Consulting Measurement Grp Inc, Torrance, CA USA.
[Finke, Bruce] Indian Hlth Serv, Nashville, TN USA.
[Saliba, Debra] Univ Calif Los Angeles, Jewish Home Borun Ctr Gerontol Res, Los Angeles, CA USA.
[Saliba, Debra] RAND Corp, Santa Monica, CA USA.
RP Kramer, BJ (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, 16111 Plummer St 11E, Sepulveda, CA 91343 USA.
EM Josea.Kramer@va.gov
FU VA Health Services Research and Development [ACC 03-304]
FX This research was supported by a grant from the VA Health Services
Research and Development, ACC 03-304. This report presents findings and
conclusions of the authors; it does not necessarily reflect the opinions
or policies of the Department of Veterans Affairs or the Indian Health
Service. An earlier version of this paper was presented in a paper
session at the Gerontological Society of America, annual scientific
meetings in New Orleans, November 2010.
NR 23
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U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2011
VL 26
SU 2
BP S662
EP S668
DI 10.1007/s11606-011-1834-2
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V30JP
UT WOS:000208812600008
PM 21989619
ER
PT J
AU Pizer, SD
Prentice, JC
AF Pizer, Steven D.
Prentice, Julia C.
TI What Are the Consequences of Waiting for Health Care in the Veteran
Population?
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Review
DE wait times; health outcomes; chronic conditions; health care
utilization; VA
ID MEDICAL-CARE; MANAGEMENT; ACCESS; STRATEGIES; INSURANCE; MORTALITY;
OUTCOMES; QUALITY; DISEASE; PEOPLE
AB National health reform is expected to increase how long individuals have to wait between requests for appointments and when their appointment is scheduled. The increase in demand for care due to more widespread insurance will result in longer waits if there is not also a concomitant increase in supply of healthcare services. Long waits for healthcare are hypothesized to compromise health because less frequent outpatient visits result in delays in diagnosis and treatment. Research testing this hypothesis is scarce due to a paucity of data on how long individuals wait for healthcare in the United States. The main exception is the Veterans Health Administration (VA) that has been routinely collecting data on how long veterans wait for outpatient care for over a decade. This narrative review summarizes the results of studies using VA wait time data to answer two main questions: 1) How much do longer wait times decrease healthcare utilization and 2) Do longer wait times cause poorer health outcomes? Longer VA wait times lead to small, yet statistically significant decreases in utilization and are related to poorer health in elderly and vulnerable veteran populations. Both long-term outcomes (e. g. mortality, preventable hospitalizations) and intermediate outcomes such as hemoglobin A1C levels are worse for veterans who seek care at facilities with longer waits compared to veterans who visit facilities with shorter waits. Further research is needed on the mechanisms connecting longer wait times and poorer outcomes including identifying patient sub-populations whose risks are most sensitive to delayed access to care. If wait times increase for the general patient population with the implementation of national reform as expected, U.S. healthcare policymakers and clinicians will need to consider policies and interventions that minimize potential harms for all patients.
C1 [Pizer, Steven D.; Prentice, Julia C.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02130 USA.
RP Pizer, SD (reprint author), Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, VA Boston Hlth Care Syst, 150 South Huntington Ave,Mail Stop 152H, Boston, MA 02130 USA.
EM pizer@bu.edu
FU Health Services Research and Development Service, Department of Veterans
Affairs [IAD-06-112, IIR 04-233]; Health Care Financing and Organization
Initiative under the Robert Wood Johnson Foundation [62967]
FX Funding for this research was provided by Grant No: IAD-06-112 and IIR
04-233 from the Health Services Research and Development Service,
Department of Veterans Affairs and Grant No: 62967 from the Health Care
Financing and Organization Initiative under the Robert Wood Johnson
Foundation. Neither author has any conflicts of interest to report. The
authors are indebted to Matthew Neuman and John Gardner for programming
support. The views expressed in this article are those of the authors
and do not necessarily represent the views of the Department of Veterans
Affairs. This research was approved by the VA Boston Health Care System
institutional review board.
NR 40
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Z9 9
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2011
VL 26
SU 2
BP S676
EP S682
DI 10.1007/s11606-011-1819-1
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V30JP
UT WOS:000208812600010
PM 21989621
ER
PT J
AU Washington, DL
Bean-Mayberry, B
Riopelle, D
Yano, EM
AF Washington, Donna L.
Bean-Mayberry, Bevanne
Riopelle, Deborah
Yano, Elizabeth M.
TI Access to Care for Women Veterans: Delayed Healthcare and Unmet Need
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE access to care; women veterans; VA healthcare; health services need;
health services utilization
AB BACKGROUND: Timely access to healthcare is essential to ensuring optimal health outcomes, and not surprisingly, is at the heart of healthcare reform efforts. While the Veterans Health Administration (VA) has made improved access a priority, women veterans still under-utilize VA healthcare relative to men. Eliminating access disparities requires a better understanding of the barriers to care that women veterans' experience.
OBJECTIVE: We examined the association of general and veteran-specific barriers on access to healthcare among women veterans.
DESIGN AND PARTICIPANTS: Cross-sectional, population-based national telephone survey of 3,611 women veterans.
MAIN MEASURE: Delayed healthcare or unmet healthcare need in the prior 12 months.
KEY RESULTS: Of women veterans, 19% had delayed healthcare or unmet need, with higher rates in younger age groups (36%, 29%, 16%, 7%, respectively, in 18-34, 35-49, 50-64, and 65-plus age groups; p<0.001). Among those delaying or going without care, barriers that varied by age group were: unaffordable healthcare (63% of 18-34 versus 12% of 65-plus age groups); inability to take off from work (39% of those <50); and transportation difficulties (36% of 65-plus). Controlling for age, race/ethnicity, regular source of care, and health status, being uninsured (OR=6.5; confidence interval [CI] 3.0-14.0), knowledge gaps about VA care (OR=2.1; 95% CI 1.1-4.0), perception that VA providers are not gender-sensitive (OR=2.4; CI 1.2-4.7), and military sexual assault history (OR=2.1; CI 1.1-4.0) predicted delaying or foregoing care, whereas VA use and enrollment priority did not.
CONCLUSIONS: Both general and veteran-specific factors impact women veterans' access to needed services. Many of the identified access barriers are potentially modifiable through expanded VA healthcare and social services. Health reform efforts should address these barriers for VA nonusers. Efforts are also warranted to improve women veterans' knowledge of availability and affordability of VA healthcare, and to enhance the gender-sensitivity of this care.
C1 [Washington, Donna L.; Bean-Mayberry, Bevanne; Riopelle, Deborah; Yano, Elizabeth M.] VA Greater Los Angeles Hlth Serv Res & Dev HSR &, Sepulveda, CA USA.
[Washington, Donna L.; Bean-Mayberry, Bevanne] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA.
[Yano, Elizabeth M.] Univ Calif Los Angeles, Dept Hlth Serv, ServicesUCLA Sch Publ Hlth, Los Angeles, CA USA.
[Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA.
EM donna.washington@va.gov
FU Department of Veterans Affairs (VA) Office of Public Health and
Environmental Hazards, Women Veterans Health Strategic Healthcare Group;
VA Health Services Research and Development (HSRD) Service [SDR-08-270];
VA HSR&D Research Career Scientist award [RCS-05-195]; VA HSR&D Research
Career Development Transition award [RCD 02-039]
FX This study was funded by the Department of Veterans Affairs (VA) Office
of Public Health and Environmental Hazards, Women Veterans Health
Strategic Healthcare Group, and the VA Health Services Research and
Development (HSR&D) Service (#SDR-08-270). Dr. Yano is supported by a VA
HSR&D Research Career Scientist award (#RCS-05-195). Dr. Bean-Mayberry
was supported by a VA HSR&D Research Career Development Transition award
(#RCD 02-039) during this study. Dr. Washington had full access to all
the data in the study and takes responsibility for the integrity of the
data and the accuracy of the data analysis. The authors gratefully
acknowledge Mark Canning for project management, Julia Yosef, MA for
assistance with survey fieldwork, Su Sun, MPH for assistance with data
management, and Michael Mitchell, PhD, for statistical assistance. The
views expressed within are solely those of the authors, and do not
necessarily represent the views of the Department of Veterans Affairs or
the United States government.
NR 30
TC 51
Z9 51
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2011
VL 26
SU 2
BP S655
EP S661
DI 10.1007/s11606-011-1772-z
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V30JP
UT WOS:000208812600007
PM 21989618
ER
PT J
AU Dahlin, CM
Mazanec, P
AF Dahlin, Constance M.
Mazanec, Polly
TI Building From Our Past Celebrating 25 Years of Clinical Practice in
Hospice and Palliative Nursing
SO JOURNAL OF HOSPICE & PALLIATIVE NURSING
LA English
DT Article
DE 25 years; clinical practice; hospice and palliative nursing
AB Nursing has been leading the way to improve and advance care of patients struggling with life-limiting illnesses since hospice began. The growth and development of clinical hospice and palliative care nursing practice over the past 25 years have been tremendous. This article reviews the powerful legacy of hospice and palliative care, from the early beginnings in Connecticut, caring for patients with terminal cancer, to the development of palliative care nursing. Nurses have been meeting the needs of those with life-limiting illnesses and advocating for better care for patients and families by working at the bedside, working collaboratively within teams, developing practice guidelines, and shaping healthcare for those nearing end of life.
C1 [Dahlin, Constance M.] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA.
[Mazanec, Polly] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA.
[Mazanec, Polly] Univ Hosp Seidman Canc Ctr, Cleveland, OH USA.
RP Dahlin, CM (reprint author), 949 Hale St, Beverly, MA 01915 USA.
EM cdahlin@partners.org
NR 52
TC 0
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U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1522-2179
EI 1539-0705
J9 J HOSP PALLIAT NURS
JI J. Hosp. Palliat. Nurs.
PD NOV-DEC
PY 2011
VL 13
SU 6
BP S20
EP S28
DI 10.1097/NJH.0b013e3182331016
PG 9
WC Nursing
SC Nursing
GA V34HE
UT WOS:000209076700003
ER
PT J
AU McAndrew, EG
Dugast, AS
Licht, AF
Eusebio, JR
Alter, G
Ackerman, ME
AF McAndrew, Elizabeth G.
Dugast, Anne-Sophie
Licht, Anna F.
Eusebio, Justin R.
Alter, Galit
Ackerman, Margaret E.
TI Determining the Phagocytic Activity of Clinical Antibody Samples
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Immunology; Issue 57; Phagocytosis; Antibody; ADCC; Effector Function;
Fc receptor; antibody-dependent phagocytosis; monocytes
AB Antibody-driven phagocytosis is induced via the engagement of Fc receptors on professional phagocytes, and can contribute to both clearance as well as pathology of disease. While the properties of the variable domains of antibodies have long been considered critical to in vivo function, the ability of antibodies to recruit innate immune cells via their Fc domains has become increasingly appreciated as a major factor in their efficacy, both in the setting of recombinant monoclonal antibody therapy, as well as in the course of natural infection or vaccination(1-3).
Importantly, despite its nomenclature as a constant domain, the antibody Fc domain does not have constant function, and is strongly modulated by IgG subclass (IgG1-4) and glycosylation at Asparagine 297(4-6). Thus, this method to study functional differences of antigen-specific antibodies in clinical samples will facilitate correlation of the phagocytic potential of antibodies to disease state, susceptibility to infection, progression, or clinical outcome.
Furthermore, this effector function is particularly important in light of the documented ability of antibodies to enhance infection by providing pathogens access into host cells via Fc receptor-driven phagocytosis(7). Additionally, there is some evidence that phagocytic uptake of immune complexes can impact the Th1/Th2 polarization of the immune response(8).
Here, we describe an assay designed to detect differences in antibody-induced phagocytosis, which may be caused by differential IgG subclass, glycan structure at Asn297, as well as the ability to form immune complexes of antigen-specific antibodies in a high-throughput fashion. To this end, 1 mu m fluorescent beads are coated with antigen, then incubated with clinical antibody samples, generating fluorescent antigen specific immune complexes. These antibody-opsonized beads are then incubated with a monocytic cell line expressing multiple Fc gamma Rs, including both inhibitory and activating. Assay output can include phagocytic activity, cytokine secretion, and patterns of Fc gamma Rs usage, and are determined in a standardized manner, making this a highly useful system for parsing differences in this antibody-dependent effector function in both infection and vaccine-mediated protection(9).
C1 [McAndrew, Elizabeth G.; Dugast, Anne-Sophie; Licht, Anna F.; Eusebio, Justin R.; Alter, Galit] Ragon Inst MGH MIT & Harvard, Massachusetts Gen Hosp, Cambridge, MA USA.
[Ackerman, Margaret E.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.
RP Ackerman, ME (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.
EM margaret.e.ackerman@dartmouth.edu
RI Dugast, AnneSophie/L-9541-2015
FU NIH [3R01AI080289-02S1]; Harvard University Center for AIDS Research
Scholar Fellowship under NIH/NIAID [2P30AI060354-07]
FX The authors wish to acknowledge funding from NIH 3R01AI080289-02S1, and
a Harvard University Center for AIDS Research Scholar Fellowship under
NIH/NIAID 2P30AI060354-07.
NR 18
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Z9 4
U1 0
U2 0
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD NOV
PY 2011
IS 57
AR UNSP e3588
DI 10.3791/3588
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36OZ
UT WOS:000209222200047
PM 22143444
ER
PT J
AU Parsons, XH
Teng, YD
Parsons, JF
Snyder, EY
Smotrich, DB
Moore, DA
AF Parsons, Xuejun H.
Teng, Yang D.
Parsons, James F.
Snyder, Evan Y.
Smotrich, David B.
Moore, Dennis A.
TI Efficient Derivation of Human Cardiac Precursors and Cardiomyocytes from
Pluripotent Human Embryonic Stem Cells with Small Molecule Induction
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Developmental Biology; Issue 57; human embryonic stem cell; human;
cardiac progenitor; cardiomyocytes; human pluripotent cell; cardiac
differentiation; small molecule induction; cell culture; cell therapy
AB To date, the lack of a suitable human cardiac cell source has been the major setback in regenerating the human myocardium, either by cell-based transplantation or by cardiac tissue engineering(1-3). Cardiomyocytes become terminally-differentiated soon after birth and lose their ability to proliferate. There is no evidence that stem/progenitor cells derived from other sources, such as the bone marrow or the cord blood, are able to give rise to the contractile heart muscle cells following transplantation into the heart(1-3). The need to regenerate or repair the damaged heart muscle has not been met by adult stem cell therapy, either endogenous or via cell delivery(1-3). The genetically stable human embryonic stem cells hESCs) have unlimited expansion ability and unrestricted plasticity, proffering a pluripotent reservoir for in vitro derivation of large supplies of human somatic cells that are restricted to the lineage in need of repair and regeneration(4,5). Due to the prevalence of cardiovascular disease worldwide and acute shortage of donor organs, there is intense interest in developing hESC-based therapies as an alternative approach. However, how to channel the wide differentiation potential of pluripotent hESCs efficiently and predictably to a desired phenotype has been a major challenge for both developmental study and clinical translation. Conventional approaches rely on multi-lineage inclination of pluripotent cells through spontaneous germ layer differentiation, resulting in inefficient and uncontrollable lineage-commitment that is often followed by phenotypic heterogeneity and instability, hence, a high risk of tumorigenicity(6-8) see a schematic in Fig. 1A). In addition, undefined foreign/animal biological supplements and/or feeders that have typically been used for the isolation, expansion, and differentiation of hESCs may make direct use of such cell-specialized grafts in patients problematic(9-11). To overcome these obstacles, we have resolved the elements of a defined culture system necessary and sufficient for sustaining the epiblast pluripotence of hESCs, serving as a platform for de novo derivation of clinically-suitable hESCs and effectively directing such hESCs uniformly towards clinically-relevant lineages by small molecules(12) see a schematic in Fig. 1B). After screening a variety of small molecules and growth factors, we found that such defined conditions rendered nicotinamide (NAM) sufficient to induce the specification of cardiomesoderm direct from pluripotent hESCs that further progressed to cardioblasts that generated human beating cardiomyocytes with high efficiency Fig. 2). We defined conditions for induction of cardioblasts direct from pluripotent hESCs without an intervening multi-lineage embryoid body stage, enabling well-controlled efficient derivation of a large supply of human cardiac cells across the spectrum of developmental stages for cell-based therapeutics.
C1 [Parsons, Xuejun H.; Parsons, James F.; Snyder, Evan Y.; Smotrich, David B.; Moore, Dennis A.] San Diego Regenerat Med Inst, San Diego, CA 92109 USA.
[Parsons, Xuejun H.; Parsons, James F.; Snyder, Evan Y.; Smotrich, David B.; Moore, Dennis A.] Xcelthera, San Diego, CA USA.
[Teng, Yang D.] Harvard Univ, Sch Med, Dept Neurosurg, Cambridge, MA 02138 USA.
[Teng, Yang D.] VA Boston Healthcare Syst, Div SCI Res, Boston, MA USA.
[Snyder, Evan Y.] Sanford Burnham Med Res Inst, Program Stem Cell & Regenerat Biol, La Jolla, CA USA.
[Smotrich, David B.] La Jolla IVF, La Jolla, CA USA.
RP Parsons, XH (reprint author), San Diego Regenerat Med Inst, San Diego, CA 92109 USA.
EM parsons@SDRMI.org
FU National Institute of Health (NIH); National Institute on Aging
[NIHK01AG024496]; Eunice Kennedy Shriver National Institute of Child
Health and Human Development [NIHR21HD056530]
FX XHP has been supported by National Institute of Health (NIH) grants from
National Institute on Aging (NIHK01AG024496) and The Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NIHR21HD056530).
NR 23
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Z9 2
U1 0
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 NOV
PY 2011
IS 57
AR UNSP e3274
DI 10.3791/3274
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36OZ
UT WOS:000209222200019
PM 22083019
ER
PT J
AU Ficarro, SB
Zhang, Y
Carrasco-Alfonso, MJ
Garg, B
Adelmant, G
Webber, JT
Luckey, CJ
Marto, JA
AF Ficarro, Scott B.
Zhang, Yi
Carrasco-Alfonso, Marlene J.
Garg, Brijesh
Adelmant, Guillaume
Webber, James T.
Luckey, C. John
Marto, Jarrod A.
TI Online Nanoflow Multidimensional Fractionation for High Efficiency
Phosphopeptide Analysis
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID IONIZATION MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY;
HYDROPHILIC INTERACTION CHROMATOGRAPHY; EMBRYONIC STEM-CELLS;
LARGE-SCALE ANALYSIS; PROTEIN IDENTIFICATION TECHNOLOGY; CHRONIC
MYELOGENOUS LEUKEMIA; ION AFFINITY-CHROMATOGRAPHY; ACUTE
MYELOID-LEUKEMIA; PHOSPHOPROTEOME ANALYSIS
AB Despite intense, continued interest in global analyses of signaling cascades through mass spectrometry-based studies, the large-scale, systematic production of phosphoproteomics data has been hampered in-part by inefficient fractionation strategies subsequent to phosphopeptide enrichment. Here we explore two novel multidimensional fractionation strategies for analysis of phosphopeptides. In the first technique we utilize aliphatic ion pairing agents to improve retention of phosphopeptides at high pH in the first dimension of a two-dimensional RP-RP. The second approach is based on the addition of strong anion exchange as the second dimension in a three-dimensional reversed phase RP)-strong anion exchange (SAX)-RP configuration. Both techniques provide for automated, online data acquisition, with the 3-D platform providing the highest performance both in terms of separation peak capacity and the number of unique phosphopeptide sequences identified per mu g of cell lysate consumed. Our integrated RP-SAX-RP platform provides several analytical figures of merit, including: 1) orthogonal separation mechanisms in each dimension; 2) high separation peak capacity 3) efficient retention of singly-and multiply-phosphorylated peptides; 4) compatibility with automated, online LC-MS analysis. We demonstrate the reproducibility of RP-SAX-RP and apply it to the analysis of phosphopeptides derived from multiple biological contexts, including an in vitro model of acute myeloid leukemia in addition to primary polyclonal CD8(+) T-cells activated in vivo through bacterial infection and then purified from a single mouse. Molecular & Cellular Proteomics 10: 10.1074/mcp.O111.011064, 1-19, 2011.
C1 [Ficarro, Scott B.; Zhang, Yi; Garg, Brijesh; Adelmant, Guillaume; Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Ficarro, Scott B.; Zhang, Yi; Garg, Brijesh; Adelmant, Guillaume; Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA.
[Ficarro, Scott B.; Zhang, Yi; Adelmant, Guillaume; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Carrasco-Alfonso, Marlene J.; Luckey, C. John] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 1158A, Boston, MA 02115 USA.
EM jarrod_marto@dfci.harvard.edu
OI Webber, James/0000-0001-8594-9888
FU Brigham & Women's Hospital; Dana-Farber Cancer Institute; National
Institutes of Health; NHGRI [P50HG004233]; NINDS [P01NS047572]
FX This work was supported by the Brigham & Women's Hospital, the
Dana-Farber Cancer Institute, and the National Institutes of Health,
NHGRI (P50HG004233), and NINDS (P01NS047572).
NR 124
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U1 2
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
EI 1535-9484
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD NOV
PY 2011
VL 10
IS 11
AR O111.011064
DI 10.1074/mcp.O111.011064
PG 19
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 844PK
UT WOS:000296759400018
PM 21788404
ER
PT J
AU Brown, JK
Cooley, ME
Chernecky, C
Sarna, L
AF Brown, Jean K.
Cooley, Mary E.
Chernecky, Cynthia
Sarna, Linda
TI A Symptom Cluster and Sentinel Symptom Experienced by Women With Lung
Cancer
SO ONCOLOGY NURSING FORUM
LA English
DT Article
AB Purpose/Objectives: To determine the symptom experience and a sentinel symptom and to describe the relationship of participant characteristics with symptom clusters.
Design: Prospective, correlational study.
Setting: Clinical sites in five U.S. states.
Sample: 196 women six months to five years after non-small cell lung cancer diagnosis.
Methods: Symptoms were measured during the past day and past four weeks. Symptom clusters were described using a novel dummy coding approach.
Main Research Variables: Symptom occurrence and severity, demographic and clinical characteristics, health status factors, and meaning of illness.
Findings: About 98% of women experienced three or more symptoms in the past day. The most common symptoms reported by more than 80% of the women were fatigue, shortness of breath, anorexia, cough, and pain, with fatigue and shortness of breath rated as most severe. Sleep problems, concentration problems, and weight loss also were reported during the past four weeks. A five-symptom cluster including fatigue, shortness of breath, cough, pain, and anorexia was reported by 64% of women. Pain was identified as a sentinel symptom for that cluster.
Conclusions: Most women experienced at least three symptoms in the past day, and a five-symptom cluster occurred frequently and continued post-treatment.
Implications for Nursing: Women who participated in the study were, on average, two years postdiagnosis, but most experienced three or more symptoms well past treatment; therefore, vigilant ongoing clinical assessment of these women is essential. A co-occurring sentinel symptom used as a clinical indicator for the presence of a symptom cluster may be useful for clinical assessment.
C1 [Brown, Jean K.] SUNY Buffalo, Sch Nursing, Buffalo, NY 14260 USA.
[Cooley, Mary E.] Dana Farber Canc Inst, Ctr Res Nursing & Patient Care Serv, Boston, MA 02115 USA.
[Chernecky, Cynthia] Med Coll Georgia, Sch Nursing, Augusta, GA 30912 USA.
[Sarna, Linda] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA.
RP Brown, JK (reprint author), SUNY Buffalo, Sch Nursing, Buffalo, NY 14260 USA.
EM jebrown@buffalo.edu
FU ONS Foundation from Ortho Biotech, Inc. [018652]
FX Jean K. Brown, PhD, RN, FAAN, is a professor emeritus in the School of
Nursing at the University at Buffalo, the State University of New York;
Mary E. Cooley, PhD, RN, is a nurse scientist in the Phyllis F. Cantor
Center for Research in Nursing and Patient Care Services at Dana-Farber
Cancer Institute in Boston, MA; Cynthia Chernecky, PhD, RN, FAAN, is a
professor in the School of Nursing at the Medical College of Georgia in
Augusta; and Linda Sarna, DNSc, RN, FAAN, is a professor and the Lulu
Wolf-Hassenplug Endowed Chair in Nursing in the School of Nursing at the
University of California, Los Angeles. This research was funded by the
ONS Foundation through an unrestricted grant from Ortho Biotech, Inc.
(#018652). Brown can be reached at jebrown@buffalo.edu, with copy to
editor at ONFEditor@ons.org. (Submitted March 2009. Accepted for
publication December 3, 2010.)
NR 47
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U1 3
U2 3
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
EI 1538-0688
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD NOV
PY 2011
VL 38
IS 6
BP E425
EP E435
DI 10.1188/11.ONF.E425-E435
PG 11
WC Oncology; Nursing
SC Oncology; Nursing
GA V35IY
UT WOS:000209144600005
PM 22037342
ER
PT J
AU Patel, A
Borkar, J
Badhoniya, N
Pusdekar, Y
Hibberd, P
AF Patel, A.
Borkar, J.
Badhoniya, N.
Pusdekar, Y.
Hibberd, P.
TI USE OF BIOMASS FUEL FOR HOUSEHOLD COOKING IS ASSOCIATED WITH NEONATAL
MORTALITY IN INDIA
SO PEDIATRIC RESEARCH
LA English
DT Meeting Abstract
C1 [Patel, A.] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India.
[Patel, A.; Borkar, J.; Badhoniya, N.; Pusdekar, Y.] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Hibberd, P.] Massachusetts Gen Hosp, Div Global Hlth, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0031-3998
EI 1530-0447
J9 PEDIATR RES
JI Pediatr. Res.
PD NOV
PY 2011
VL 70
SU 5
MA 051
BP 51
EP 51
DI 10.1038/pr.2011.276
PG 1
WC Pediatrics
SC Pediatrics
GA V31FS
UT WOS:000208870100052
ER
PT J
AU Sinha, B
Balahara, B
Fujii, A
Ringer, SA
AF Sinha, B.
Balahara, B.
Fujii, A.
Ringer, S. A.
TI PATENT DUCTUS ARTERIOSUS LIGATION IN PREMATURE INFANTS: UNPROVEN LONG
TERM BENEFIT AT THE COST OF SHORT TERM MORBIDITIES?
SO PEDIATRIC RESEARCH
LA English
DT Meeting Abstract
C1 [Sinha, B.; Fujii, A.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Sinha, B.; Ringer, S. A.] Harvard Univ, Sch Med, Boston, MA USA.
[Balahara, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ringer, S. A.] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0031-3998
EI 1530-0447
J9 PEDIATR RES
JI Pediatr. Res.
PD NOV
PY 2011
VL 70
SU 5
MA 280
BP 280
EP 280
DI 10.1038/pr.2011.505
PG 1
WC Pediatrics
SC Pediatrics
GA V31FS
UT WOS:000208870100281
ER
PT J
AU Khodyakov, D
Stockdale, S
Jones, F
Ohito, E
Jones, A
Lizaola, E
Mango, J
AF Khodyakov, Dmitry
Stockdale, Susan
Jones, Felica
Ohito, Elizabeth
Jones, Andrea
Lizaola, Elizabeth
Mango, Joseph
TI An Exploration of the Effect of Community Engagement in Research on
Perceived Outcomes of Partnered Mental Health Services Projects
SO SOCIETY AND MENTAL HEALTH
LA English
DT Article
DE CBPR; community-based mental health; mental health; community engagement
in research; community-academic partnerships
AB Mental health research projects address sensitive issues for vulnerable populations and are implemented in complex environments. Community-based participatory research approaches are recommended for health research on vulnerable populations, but little is known about how variation in participation affects outcomes of partnered research projects. We developed a conceptual model demonstrating the impact of community engagement in research on outcomes of partnered projects. We collected data on key constructs from community and academic leaders of 21 sampled partnered research projects in two cycles of a research center funded by the National Institute of Mental Health. We conducted empirical analyses to test the model. Our findings suggest that community engagement in research is positively associated with perceived professional development as well as political and community impact.
C1 [Khodyakov, Dmitry] RAND Corp, Santa Monica, CA 90407 USA.
[Stockdale, Susan] US Dept Vet Affairs, Los Angeles, CA USA.
[Stockdale, Susan; Lizaola, Elizabeth; Mango, Joseph] Univ Calif Los Angeles, Los Angeles, CA USA.
[Jones, Felica; Jones, Andrea] Hlth African Amer Families, Los Angeles, CA USA.
[Ohito, Elizabeth] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Jones, Andrea] Charles Drew Univ Med & Sci, Los Angeles, CA USA.
RP Khodyakov, D (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA.
EM dkhodyak@rand.org
FU NIMH NIH HHS [P30 MH068639-05, P30 MH082760, P30 MH082760-01, P30
MH068639]
NR 45
TC 11
Z9 11
U1 1
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 2156-8693
EI 2156-8731
J9 SOC MENT HEALTH
JI Soc. Ment. Health
PD NOV
PY 2011
VL 1
IS 3
BP 185
EP 199
DI 10.1177/2156869311431613
PG 15
WC Sociology
SC Sociology
GA V36AA
UT WOS:000209184800004
PM 22582144
ER
PT J
AU Guanci, MM
AF Guanci, Mary McKenna
TI In order to maintain normothermia in a neuro patient what options can be
used besides connecting them to a temperature machine?
SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT
LA English
DT Letter
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Guanci, MM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2153-7658
EI 2153-7933
J9 THER HYPOTHERMIA TEM
JI Ther. Hypothermia Temp. Manag.
PD NOV 1
PY 2011
VL 1
IS 3
BP 169
EP 170
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA V38QI
UT WOS:000209357500009
ER
PT J
AU Li, M
Dickinson, CE
Finkelstein, EB
Neville, CM
Sundback, CA
AF Li, Mei
Dickinson, Caitlyn E.
Finkelstein, Eric B.
Neville, Craig M.
Sundback, Cathryn A.
TI The Role of Fibroblasts in Self-Assembled Skeletal Muscle
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID IN-VITRO; BASEMENT-MEMBRANE; CELL-CULTURES; BASAL LAMINA; COLLAGEN;
MYOSIN; MYOTUBES; STIMULATION; FIBRONECTIN; MYOGENESIS
AB Small facial skeletal muscles often have no autologous donor source to effect surgical reconstruction. Autologously derived muscles could be engineered for replacement tissue, but must be vascularized and innervated to be functional. As a critical step, engineered muscle must mimic the morphology, protein and gene expression, and function of native muscle. This study utilized a self-assembly process to engineer three-dimensional (3D) muscle from a statically strained muscle cell monolayer. Primary mouse myoblasts (PMMs) and mouse embryonic fibroblasts (MEFs) were separately proliferated and coseeded on a fibrin sheet with anchored sutures. Within 10 days of initiating PMM differentiation, the cell-gel layer contracted, lifted, and rolled into a cylindrical 3D structure around the tendon-like suture anchors; the myotubes longitudinally aligned along the lines of tensile force. The objectives of this study were to characterize these engineered muscles and to elucidate the role of the fibroblasts in the self-assembly process. Fibroblasts maintained myotube viability, mediated fibrin degradation, and assisted in muscle self-assembly. The optimal 1: 1 PMM:MEF ratio resulted in tissue morphology remarkably similar to native muscle. Through gene and protein expression assays, the development and maturation of the engineered muscle tissue was demonstrated to recapitulate normal skeletal muscle development.
C1 [Li, Mei; Dickinson, Caitlyn E.; Finkelstein, Eric B.; Neville, Craig M.; Sundback, Cathryn A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Finkelstein, Eric B.; Neville, Craig M.; Sundback, Cathryn A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Sundback, CA (reprint author), Massachusetts Gen Hosp, Dept Surg, CPZN 4809,185 Cambridge St, Boston, MA 02114 USA.
EM csundback@partners.org
FU Center for Military Biomaterials Research [W81XWH-04-2-0031]; U.S. Army
Telemedicine and Advanced Technology Research Center; Armed Forces
Institute of Regenerative Medicine [W81XWH-08-2-0034]; U.S. Army Medical
Research Acquisition Activity; administering acquisition office
FX This research was sponsored by the Center for Military Biomaterials
Research award number W81XWH-04-2-0031 funded by the U.S. Army
Telemedicine and Advanced Technology Research Center. This work was also
sponsored by the Armed Forces Institute of Regenerative Medicine award
number W81XWH-08-2-0034; the U.S. Army Medical Research Acquisition
Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014, is the
awarding and administering acquisition office. The content of the
article does not necessarily reflect the position or the policy of the
Government, and no official endorsement should be inferred.
NR 47
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U1 0
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD NOV
PY 2011
VL 17
IS 21-22
BP 2641
EP 2650
DI 10.1089/ten.tea.2010.0700
PG 10
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 842SD
UT WOS:000296619500006
PM 21657983
ER
PT J
AU Haas, JS
Liang, SY
Hassett, MJ
Shiboski, S
Elkin, EB
Phillips, KA
AF Haas, Jennifer S.
Liang, Su-Ying
Hassett, Michael J.
Shiboski, Stephen
Elkin, Elena B.
Phillips, Kathryn A.
TI Gene expression profile testing for breast cancer and the use of
chemotherapy, serious adverse effects, and costs of care
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Utilization; Genomics
ID RECURRENCE SCORE ASSAY; RT-PCR ASSAY; ECONOMIC-IMPLICATIONS; TREATMENT
SELECTION; PROPENSITY SCORE; THERAPY; RISK; MULTICENTER; SURVIVAL;
IMPACT
AB As gene expression profile (GEP) testing for breast cancer may provide additional prognostic information to guide the use of adjuvant chemotherapy, we examined the association between GEP testing and use of chemotherapy, serious chemotherapy-related adverse effects, and total charges during the 12 months following diagnosis. Medical record review was conducted for women age 30-64 years, with incident, non-metastatic, invasive breast cancer diagnosed 2006-2008 in a large, national health plan. Of 534 patients, 25.8% received GEP testing, 68.2% received chemotherapy, and 10.5% experienced a serious chemotherapy-related adverse effect. GEP testing was most commonly used in women at moderate clinical risk of recurrence (52.0 vs. 25.0% of low-risk women and 5.5% of high-risk). Controlling for the propensity to receive GEP testing, women who had GEP were less likely to receive chemotherapy (propensity adjusted odds ratio, 95% confidence interval 0.62, 0.39-0.99). Use of GEP was associated with more chemotherapy use among women at low risk based on clinical characteristics (OR = 42.19; CI 2.50-711.82), but less use among women with a high risk based on clinical characteristics (OR = 0.12; CI 0.03-0.47). Use of GEP was not associated with chemotherapy for the moderate risk group. There was no significant relationship between GEP use and either serious chemotherapy-associated adverse effects or total charges. While GEP testing was associated with an overall decrease in adjuvant chemotherapy, we did not find differences in serious chemotherapy-associated adverse events or charges during the 12 months following diagnosis.
C1 [Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02120 USA.
[Liang, Su-Ying; Shiboski, Stephen; Phillips, Kathryn A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hassett, Michael J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Elkin, Elena B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Haas, JS (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, 1620 Tremont St, Boston, MA 02120 USA.
EM jhaas@partners.org
FU National Cancer Institute [P01CA130818]; Aetna Foundation
FX The study was supported by a grant from the National Cancer Institute
(P01CA130818). Drs. Haas, Phillips, and Liang received funding from a
research grant from the Aetna Foundation for earlier related research.
NR 34
TC 7
Z9 7
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD NOV
PY 2011
VL 130
IS 2
BP 619
EP 626
DI 10.1007/s10549-011-1628-6
PG 8
WC Oncology
SC Oncology
GA 830RY
UT WOS:000295675700026
PM 21681446
ER
PT J
AU Holmes, MD
Chen, WY
Schnitt, SJ
Collins, L
Colditz, GA
Hankinson, SE
Tamimi, RM
AF Holmes, Michelle D.
Chen, Wendy Y.
Schnitt, Stuart J.
Collins, Laura
Colditz, Graham A.
Hankinson, Susan E.
Tamimi, Rulla M.
TI COX-2 expression predicts worse breast cancer prognosis and does not
modify the association with aspirin
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast neoplasms; Cyclooxygenase-2; Tumor markers; Prognosis; Survival;
Aspirin
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CYCLOOXYGENASE-2 EXPRESSION; TISSUE
MICROARRAY; SURVIVAL; RISK; OVEREXPRESSION; CARCINOMA; DIAGNOSIS; WOMEN
AB Some previous studies have found worse prognosis among cyclooxygenase-2 (COX-2)-expressing breast cancers. Aspirin and NSAIDs inhibit COX-2. Three studies, including ours, have reported a survival advantage among women with breast cancer who take either aspirin or NSAIDs. Through this study we hypothesized that in the Nurses' Health Study (NHS), COX-2 expression would be associated with worse prognosis, and aspirin use would be associated with better survival particularly among women with COX-2 positive tumors. In this study we investigated 2,001 women presenting with invasive breast cancers stained for COX-2 by immunohistochemistry. Tumor prognostic factors were from medical records. Aspirin use was assessed at least 12 months after diagnosis and updated. Cause of death was identified from death certificates. Statistical analyses included logistic regression of prognostic factors with COX-2 status as the outcome, and proportional hazards regression with breast cancer death as the outcome. Tumor COX-2 expression was associated with higher diagnostic stage. Compared with stage I, the RR(95% CI) for stages II-IV were 1.16 (0.93-1.45), 1.68 (1.27-2.22), and 1.76 (0.93-3.32). COX-2 expression was associated with lobular compared with ductal histology (1.40 [1.02-1.92]), and estrogen receptor positive compared with negative (2.22 [1.66-2.95]). The RR(95% CI) of breast cancer death for current aspirin use was similar for women with COX-2-positive and COX-2-negative tumors; 0.64 (0.43-0.96) and 0.57 (0.44-0.74), respectively. In the NHS, COX-2 breast cancer expression was associated with higher stage at diagnosis. The survival benefit associated with aspirin use did not differ by COX-2 status. COX-2 breast cancer expression is associated with worse prognosis. If aspirin truly impacts breast cancer survival, then it is not solely via COX-2.
C1 [Holmes, Michelle D.; Chen, Wendy Y.; Hankinson, Susan E.; Tamimi, Rulla M.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Holmes, Michelle D.; Chen, Wendy Y.; Hankinson, Susan E.; Tamimi, Rulla M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Holmes, Michelle D.; Colditz, Graham A.; Hankinson, Susan E.; Tamimi, Rulla M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Schnitt, Stuart J.; Collins, Laura] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
[Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
RP Holmes, MD (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA.
EM michelle.holmes@channing.harvard.edu
RI Colditz, Graham/A-3963-2009
OI Colditz, Graham/0000-0002-7307-0291
FU National Institutes of Health [CA87969]; Breast Cancer Research Fund;
GlaxoSmithKline [WE234 [EPI40307]]
FX This study was supported by the National Institutes of Health grant
CA87969 and a grant from the Breast Cancer Research Fund and
GlaxoSmithKline (WE234 [EPI40307]).
NR 21
TC 40
Z9 41
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD NOV
PY 2011
VL 130
IS 2
BP 657
EP 662
DI 10.1007/s10549-011-1651-7
PG 6
WC Oncology
SC Oncology
GA 830RY
UT WOS:000295675700030
PM 21728052
ER
PT J
AU Hoyer, D
Boyko, E
McNeely, M
Leonetti, D
Kahn, S
Fujimoto, W
AF Hoyer, D.
Boyko, E. J.
McNeely, M. J.
Leonetti, D. L.
Kahn, S. E.
Fujimoto, W. Y.
TI Subcutaneous thigh fat area is unrelated to risk of type 2 diabetes in a
prospective study of Japanese Americans
SO DIABETOLOGIA
LA English
DT Article
DE Adiposity; Computed tomography; Diabetes mellitus; Epidemiology;
Japanese American; Prospective study; Thigh circumference; Thigh
subcutaneous fat; Visceral fat; Waist circumference
ID ADIPOSE-TISSUE DISTRIBUTION; IMPAIRED GLUCOSE-TOLERANCE; BODY-FAT;
POSTMENOPAUSAL WOMEN; INSULIN-RESISTANCE; MEN; OBESE; MASS;
DYSLIPIDEMIA; ASSOCIATIONS
AB Cross-sectional research has reported a negative association between subcutaneous thigh fat (STF) and type 2 diabetes prevalence but no prospective research on this association exists using direct measurements of STF obtained from imaging studies while adjusting for other fat depots. We studied the independent associations of intra-abdominal fat (IAF), subcutaneous abdominal fat (SAF) and STF with future risk of diabetes.
We prospectively followed 489 non-diabetic Japanese Americans (BMI 25.0-29.9 kg/m(2) 32.7%, a parts per thousand yen30.0 kg/m(2) 5.4%) over 10 years for the development of diabetes defined by use of hypoglycaemic medication or a fasting plasma glucose a parts per thousand yen7.0 mmol/l or 2 h a parts per thousand yen11.1 mmol/l during an OGTT. STF, SAF and IAF area were measured by computed tomography scan and mid-thigh circumference (TC) by tape measure at baseline.
Over 10 years, 103 people developed diabetes. STF area was not independently associated with the odds of developing diabetes in a univariate or multiple logistic regression model (OR for a 1 SD increase 0.8 [95% CI 0.5, 1.2]) adjusted for age, sex, BMI, IAF and SAF. The only fat depot associated with diabetes odds in this model was IAF. TC was borderline significantly associated with a lower odds of developing diabetes (0.7 [95% CI 0.5, 1.0], p = 0.052).
Similar to other research, TC was negatively associated with diabetes risk, whereas STF was not, arguing that the negative association between TC and diabetes observed in other research is not due to STF mass. IAF area emerged as the only measured fat depot that was independently associated with type 2 diabetes risk.
C1 [Boyko, E. J.; Kahn, S. E.] VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA.
[Hoyer, D.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Boyko, E. J.; McNeely, M. J.; Kahn, S. E.; Fujimoto, W. Y.] Univ Washington, Dept Med, Seattle, WA USA.
[Leonetti, D. L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA.
RP Boyko, E (reprint author), VA Puget Sound Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA.
EM eboyko@uw.edu
OI Kahn, Steven/0000-0001-7307-9002
FU National Institutes of Health [DK-31170, HL-49293, DK-02654]; VA Puget
Sound Health Care System
FX This work was supported by National Institutes of Health Grants
DK-31170, HL-49293 and DK-02654; by facilities and services provided by
the Diabetes and Endocrinology Research Center (DK-17047), Clinical
Nutrition Research Unit (DK-35816), and the General Clinical Research
Center (RR-00037) at the University of Washington. VA Puget Sound Health
Care System provided support for the involvement of E.J. Boyko and S.E.
Kahn in this research. We are grateful to the King County
Japanese-American community for their support and cooperation.
NR 20
TC 7
Z9 7
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD NOV
PY 2011
VL 54
IS 11
BP 2795
EP 2800
DI 10.1007/s00125-011-2275-5
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 830TJ
UT WOS:000295679800008
PM 21837509
ER
PT J
AU Shetty, RS
Gallagher, CS
Chen, YT
Hims, MM
Mull, J
Leyne, M
Pickel, J
Kwok, D
Slaugenhaupt, SA
AF Shetty, Ranjit S.
Gallagher, Cary S.
Chen, Yei-Tsung
Hims, Matthew M.
Mull, James
Leyne, Maire
Pickel, James
Kwok, David
Slaugenhaupt, Susan A.
TI Specific correction of a splice defect in brain by nutritional
supplementation
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID B KINASE COMPLEX; FAMILIAL DYSAUTONOMIA; MESSENGER-RNA; ELONGATOR
COMPLEX; TRANSCRIPTIONAL ELONGATION; DISEASE; IKBKAP; PROTEIN; GENE;
EXPRESSION
AB Recent studies emphasize the importance of mRNA splicing in human genetic disease, as 20-30% of all disease-causing mutations are predicted to result in mRNA splicing defects. The plasticity of the mRNA splicing reaction has made these mutations attractive candidates for the development of therapeutics. Familial dysautonomia (FD) is a severe neurodegenerative disorder, and all patients have an intronic IVS2016T>C splice site mutation in the IKBKAP gene, which results in tissue-specific skipping of exon 20 and a corresponding reduction in ikappaB kinase complex associated protein (IKAP) levels. We created transgenic mouse lines using a human IKBKAP bacterial artificial chromosome (BAC) into which we inserted the IKBKAP splice mutation (FD BAC) and have shown that the transgenic mice exhibit the same tissue-specific aberrant splicing patterns as seen in FD patients. We have previously demonstrated that the plant cytokinin kinetin can significantly improve the production of wild-type IKBKAP transcripts in FD lymphoblast cell lines by improving exon inclusion. In this study, we tested the ability of kinetin to alter IKBKAP splicing in the transgenic mice carrying the FD BAC and show that it corrects IKBKAP splicing in all major tissues assayed, including the brain. The amount of wild-type IKBKAP mRNA and IKAP protein was significantly higher in the kinetin-treated mice. These exciting results prove that treatment of FD, as well as other mechanistically related splicing disorders, with kinetin holds great promise as a potential therapeutic aimed at increasing normal protein levels, which may, in turn, slow disease progression.
C1 [Shetty, Ranjit S.; Gallagher, Cary S.; Chen, Yei-Tsung; Hims, Matthew M.; Mull, James; Leyne, Maire; Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Shetty, Ranjit S.; Gallagher, Cary S.; Chen, Yei-Tsung; Hims, Matthew M.; Mull, James; Leyne, Maire; Slaugenhaupt, Susan A.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Pickel, James] NIMH, NIH, Bethesda, MD 20892 USA.
[Kwok, David] BRI Biopharmaceut Res Inc, Vancouver, BC V6P 3S8, Canada.
RP Slaugenhaupt, SA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5254, Boston, MA 02114 USA.
EM slaugenhaupt@chgr.mgh.harvard.edu
FU Dysautonomia Foundation, Inc; NIH [R01 NS36326, R21 NS R21NS058318];
Massachusetts General Hospital
FX This work was supported by a grant from the Dysautonomia Foundation,
Inc, and NIH (R01 NS36326 and R21 NS R21NS058318) to S. A. S. R. S. S.
was supported by a Massachusetts General Hospital ECOR Fund for Medical
Discovery Award.
NR 46
TC 8
Z9 8
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD NOV 1
PY 2011
VL 20
IS 21
BP 4093
EP 4101
DI 10.1093/hmg/ddr333
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 830VO
UT WOS:000295686000001
PM 21821670
ER
PT J
AU Takakura, A
Nelson, EA
Haque, N
Humphreys, BD
Zandi-Nejad, K
Frank, DA
Zhou, J
AF Takakura, Ayumi
Nelson, Erik A.
Haque, Nadeem
Humphreys, Benjamin D.
Zandi-Nejad, Kambiz
Frank, David A.
Zhou, Jing
TI Pyrimethamine inhibits adult polycystic kidney disease by modulating
STAT signaling pathways
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ACUTE-RENAL-FAILURE; CELL-CYCLE ARREST; JAK-STAT; TARGETED DISRUPTION;
EPITHELIAL-CELLS; CYST FORMATION; ACTIVATION; MTOR; PKD1; INACTIVATION
AB Autosomal dominant polycystic kidney disease (ADPKD) is a commonly inherited disorder mostly caused by mutations in PKD1, encoding polycystin-1 (PC1). The disease is characterized by development and growth of epithelium-lined cyst in both kidneys, often leading to renal failure. There is no specific treatment for this disease. Here, we report a sustained activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) in ischemic injured and uninjured Pkd1 knockout polycystic kidneys and in human ADPKD kidneys. Through a chemical library screen, we identified the anti-parasitic compound pyrimethamine as an inhibitor of STAT3 function. Treatment with pyrimethamine decreases cell proliferation in human ADPKD cells and blocks renal cyst formation in an adult and a neonatal PKD mouse model. Moreover, we demonstrated that a specific STAT3 inhibitor, S3I-201, reduces cyst formation and growth in a neonatal PKD mouse model. Our results suggest that PC1 acts as a negative regulator of STAT3 and that blocking STAT3 signaling with pyrimethamine or similar drugs may be an attractive therapy for human ADPKD.
C1 [Takakura, Ayumi; Haque, Nadeem; Humphreys, Benjamin D.; Zandi-Nejad, Kambiz; Zhou, Jing] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA.
[Nelson, Erik A.; Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Nelson, Erik A.; Frank, David A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Takakura, A (reprint author), Harvard Inst Med, Room 520,4 Blackfan Circle, Boston, MA 02115 USA.
EM atakakura@rics.bwh.harvard.edu; zhou@rics.bwh.harvard.edu
FU Zhou Lab; Harvard Center of Polycystic Kidney Disease Research
FX The authors would like to thank Ms C LaPierre for excellent technical
assistance and other members of Zhou Lab and the Harvard Center of
Polycystic Kidney Disease Research for scientific discussions and
support.
NR 44
TC 33
Z9 36
U1 2
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD NOV 1
PY 2011
VL 20
IS 21
BP 4143
EP 4154
DI 10.1093/hmg/ddr338
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 830VO
UT WOS:000295686000005
PM 21821671
ER
PT J
AU Fossale, E
Seong, IS
Coser, KR
Shioda, T
Kohane, IS
Wheeler, VC
Gusella, JF
MacDonald, ME
Lee, JM
AF Fossale, Elisa
Seong, Ihn Sik
Coser, Kathryn R.
Shioda, Toshi
Kohane, Isaac S.
Wheeler, Vanessa C.
Gusella, James F.
MacDonald, Marcy E.
Lee, Jong-Min
TI Differential effects of the Huntington's disease CAG mutation in
striatum and cerebellum are quantitative not qualitative
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ENERGY-METABOLISM; SPINOCEREBELLAR ATAXIA; IN-VIVO; REPEAT; IMPAIRMENT;
DEFECTS; ATROPHY; TYPE-1; SCAN
AB Huntington's disease (HD) involves marked early neurodegeneration in the striatum, whereas the cerebellum is relatively spared despite the ubiquitous expression of full-length mutant huntingtin, implying that inherent tissue-specific differences determine susceptibility to the HD CAG mutation. To understand this tissue specificity, we compared early mutant huntingtin-induced gene expression changes in striatum to those in cerebellum in young Hdh CAG knock-in mice, prior to onset of evident pathological alterations. Endogenous levels of full-length mutant huntingtin caused qualitatively similar, but quantitatively different gene expression changes in the two brain regions. Importantly, the quantitatively different responses in the striatum and cerebellum in mutant mice were well accounted for by the intrinsic molecular differences in gene expression between the striatum and cerebellum in wild-type animals. Tissue-specific gene expression changes in response to the HD mutation, therefore, appear to reflect the different inherent capacities of these tissues to buffer qualitatively similar effects of mutant huntingtin. These findings highlight a role for intrinsic quantitative tissue differences in contributing to HD pathogenesis, and likely to other neurodegenerative disorders exhibiting tissue-specificity, thereby guiding the search for effective therapeutic interventions.
C1 [Fossale, Elisa; Seong, Ihn Sik; Wheeler, Vanessa C.; Gusella, James F.; MacDonald, Marcy E.; Lee, Jong-Min] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Coser, Kathryn R.; Shioda, Toshi] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA 02129 USA.
[Kohane, Isaac S.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02114 USA.
[Kohane, Isaac S.] I2b2 Natl Ctr Biomed Comp, Boston, MA 02115 USA.
RP Lee, JM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM jlee51@partners.org
RI Kohane, Isaac Kohane/K-3716-2012
OI Kohane, Isaac Kohane/0000-0003-2192-5160
FU National Institutes of Health [NS32765, NS049206]; Massachusetts HD
Center Without Walls [NS16367]; i2b2 [LM008748-01]; Huntington's Disease
Society of America Coalition for the Cure Normal Function Team
FX This research was supported by National Institutes of Health (NS32765 to
M. E. M.; NS049206 to V. C. W.), The Massachusetts HD Center Without
Walls (NS16367 to M. E. M. and J.F.G.), i2b2 (LM008748-01 to I. S. K.),
the Huntington's Disease Society of America Coalition for the Cure
Normal Function Team (to M. E. M. and J.F.G.) and an Anonymous Donor.
NR 22
TC 11
Z9 11
U1 2
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD NOV 1
PY 2011
VL 20
IS 21
BP 4258
EP 4267
DI 10.1093/hmg/ddr355
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 830VO
UT WOS:000295686000015
PM 21840924
ER
PT J
AU de Lange, C
Brabrand, K
Emblem, KE
Bjornerud, A
Loberg, EM
Saugstad, OD
Munkeby, BH
AF de Lange, Charlotte
Brabrand, Knut
Emblem, Kyrre E.
Bjornerud, Atle
Loberg, Else Marit
Saugstad, Ola Didrik
Munkeby, Berit H.
TI Cerebral Perfusion in Perinatal Hypoxia and Resuscitation Assessed by
Transcranial Contrast-Enhanced Ultrasound and 3 T MRI in Newborn Pigs
SO INVESTIGATIVE RADIOLOGY
LA English
DT Article
DE cerebral perfusion; contrast-enhanced ultrasound; MRI; perfusion
weighted imaging; perinatal encephalopathy; piglet
ID BRAIN-INJURY; ISCHEMIC ENCEPHALOPATHY; BLOOD-FLOW; 100-PERCENT OXYGEN;
TERM INFANT; SPECTROSCOPY; ASPHYXIA; PIGLETS; STROKE; HYPOTENSION
AB Objective: Cerebrovascular factors are crucially involved in the early injury after perinatal asphyxia. With magnetic resonance imaging (MRI) and ultrasonography (US), this study aimed to quantify microvascular perfusion changes due to hypoxia and resuscitation, by comparing contrast-enhanced ultrasound (CEUS) to dynamic susceptibility contrast-enhanced (DSC)-MRI and diffusion-weighted MRI.
Material and Methods: Newborn piglets (n = 12/17) were reoxygenated with 21% (n = 6) or 100% O(2) (n = 6) after global hypoxia. Five piglets served as controls. CEUS and MRI were performed before, during, and up to 7 hours after hypoxia. Following are the perfusion parameters for CEUS: peak intensity (PI), area under the curve (AUC), time to peak (TTP), and upslope a and perfusion/diffusion parameters for MRI: relative cerebral blood volume, relative cerebral blood flow, mean transit time, and apparent diffusion coefficient were compared between different regions in the brain across time points and also compared with histology at the end.
Results: In CEUS, compared with the control group, perfusion changed significantly over time, in the hyperoxic group in all regions for PI, AUC in all regions of interests. The changes presented mainly as decreased perfusion during and shortly after resuscitation: for PI in the basal ganglia (BG), cortex, and the whole brain with 50 to 60% (P <= 0.001); for AUC in the BG and cortex with 90% (P <= 0.02) and in the whole brain with 70% (P = 0.004). In the injured brains (confirmed by histology), significant changes over time were seen in TTP and AUC with mainly increased perfusion during hypoxia: for TTP in the cortex, AUC in the BG and whole brain with 90 to 100% (P <= 0.04), and for TTP in the whole brain with 50% (P = 0.02). DSC-MRI showed the same trends in perfusion with regard to relative cerebral blood volume as CEUS. In all pigs exposed to hypoxia, perfusion returned toward baseline values at 7 hours after hypoxia in both methods. Apparent diffusion coefficient decreased significantly after 7 hours in the injured brains in the BG from 114.6 +/- 1.2 x 10(-5) mm(2)/s to 90.3 +/- 24 x 10(-5) mm(2)/s (P = 0.03).
Conclusions: CEUS and DSC-MRI can detect an early temporal evolution of cerebral perfusion in perinatal hypoxia and resuscitation, reversible after 7 hours. Hyperoxic resuscitation caused early decreased cerebral perfusion, not present in the normoxic group. The combined use of CEUS and DSC-MRI can provide important diagnostic information and give new insights into perinatal vascular hypoxia mechanisms.
C1 [de Lange, Charlotte] Oslo Univ Hosp, Rikshosp, Dept Paediat Res, N-0424 Oslo, Norway.
[de Lange, Charlotte; Brabrand, Knut] Oslo Univ Hosp, Dept Diagnost Imaging & Intervent, N-0424 Oslo, Norway.
[Emblem, Kyrre E.; Bjornerud, Atle] Oslo Univ Hosp, Intervent Ctr, N-0424 Oslo, Norway.
[Emblem, Kyrre E.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Bjornerud, Atle] Univ Oslo, Dept Phys, Oslo, Norway.
[Loberg, Else Marit] Oslo Univ Hosp, Dept Pathol, N-0424 Oslo, Norway.
[Saugstad, Ola Didrik] Univ Oslo, Dept Med, Oslo, Norway.
RP de Lange, C (reprint author), Oslo Univ Hosp, Rikshosp, Dept Paediat Res, Postboks 4950 Nydalen, N-0424 Oslo, Norway.
EM charlotte.de.lange@rr-research.no
RI Emblem, Kyrre/H-6691-2012
OI Emblem, Kyrre/0000-0002-6580-9519
FU Norwegian SIDS; Stillbirth Society; Child Foundation of Oslo University
Hospital
FX supported by the Norwegian SIDS and Stillbirth Society and the Child
Foundation of Oslo University Hospital. The authors declare nothing to
disclose.
NR 50
TC 8
Z9 8
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-9996
J9 INVEST RADIOL
JI Invest. Radiol.
PD NOV
PY 2011
VL 46
IS 11
BP 686
EP 696
DI 10.1097/RLI.0b013e3182266431
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 832TK
UT WOS:000295830600004
PM 21730873
ER
PT J
AU Ohta, K
Laborde, NJ
Kajiya, M
Shin, J
Zhu, T
Thondukolam, AK
Min, C
Kamata, N
Karimbux, NY
Stashenko, P
Kawai, T
AF Ohta, K.
Laborde, N. J.
Kajiya, M.
Shin, J.
Zhu, T.
Thondukolam, A. K.
Min, C.
Kamata, N.
Karimbux, N. Y.
Stashenko, P.
Kawai, T.
TI Expression and Possible Immune-regulatory Function of Ghrelin in Oral
Epithelium
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE ghrelin; gingival crevicular fluid; saliva; gingival epithelium; IL-8;
lipopolysaccharide
ID LOCALIZED AGGRESSIVE PERIODONTITIS; GINGIVAL CREVICULAR FLUID; CYTOKINE
EXPRESSION; CELLS; HORMONE; GROWTH; KERATINOCYTES; RELEASE; TISSUE;
PROLIFERATION
AB Originally found in stomach mucosa, ghrelin is a peptide appetite hormone that has been implicated as an immuno-modulatory factor. Ghrelin has also been found in salivary glands and saliva; however, its expression patterns and biological properties in the oral cavity remain unclear. Therefore, we investigated the expression patterns of ghrelin in saliva, gingival crevicular fluid (GCF), and gingival tissue, as well as its in vitro effects on IL-8 production by TNF-alpha or LPS-stimulated oral epithelial cells. In the clinical samples obtained from 12 healthy volunteers, the concentration of ghrelin in GCF remarkably exceeded that detected in saliva. The expression of ghrelin mRNAs and growth hormone secretagogue (GHS) receptors could be detected in human oral epithelial cells. Immunohistochemical analysis revealed the expression of ghrelin in gingival epithelium, as well as in fibroblasts in the lamina propria. Ghrelin increased intracellular calcium mobilization and cAMP levels in oral epithelial cells, suggesting that ghrelin acts on epithelial cells to induce cell signaling. Furthermore, synthetic ghrelin inhibited the production of IL-8 from TNF-alpha or LPS-stimulated oral epithelial cells. These results indicate that ghrelin produced in the oral cavity appears to play a regulatory role in innate immune responses to inflammatory infection.
C1 [Ohta, K.; Kajiya, M.; Shin, J.; Zhu, T.; Min, C.; Kawai, T.] Harvard Univ, Sch Dent Med, Dept Immunol, Boston, MA 02115 USA.
[Ohta, K.; Laborde, N. J.; Kajiya, M.; Zhu, T.; Thondukolam, A. K.; Karimbux, N. Y.; Kawai, T.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
[Ohta, K.; Kamata, N.] Hiroshima Univ, Dept Oral & Maxillofacial Surg, Div Cervicognathostomatol, Programs Appl Biomed,Grad Sch Biomed Sci, Hiroshima, Japan.
[Stashenko, P.] Forsyth Inst, Dept Cytokine Biol, Cambridge, MA 02142 USA.
RP Kawai, T (reprint author), Harvard Univ, Sch Dent Med, Dept Immunol, 188 Longwood Ave, Boston, MA 02115 USA.
EM tkawai@forsyth.org
FU NIH [DE-018310, DE-018499]; NIDCR; Harvard Catalyst; AADR
FX This study was supported by NIH grants DE-018310 and DE-018499 from the
NIDCR and by a Pilot Grant from Harvard Catalyst. Jane Shin was the
recipient of a 2010 Student Research Fellowship from the AADR. The
authors declare no potential conflicts of interest with respect to the
authorship and/or publication of this article.
NR 30
TC 12
Z9 12
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD NOV
PY 2011
VL 90
IS 11
BP 1286
EP 1292
DI 10.1177/0022034511420431
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 830XM
UT WOS:000295692600005
PM 21865591
ER
PT J
AU Tanner, ACR
Kent, RL
Holgerson, PL
Hughes, CV
Loo, CY
Kanasi, E
Chalmers, NI
Johansson, I
AF Tanner, A. C. R.
Kent, R. L., Jr.
Holgerson, P. Lif
Hughes, C. V.
Loo, C. Y.
Kanasi, E.
Chalmers, N. I.
Johansson, I.
TI Microbiota of Severe Early Childhood Caries before and after Therapy
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE pediatric dentistry; clinical outcomes; microbial ecology; Streptococcus
mutans; Scardovia wiggsiae
ID STREPTOCOCCUS-SOBRINUS; MOLECULAR ANALYSIS; MICROFLORA; CHILDREN;
BACTERIA; MUTANS
AB Severe early childhood caries (ECC) is difficult to treat successfully. This study aimed to characterize the microbiota of severe ECC and evaluate whether baseline or follow-up microbiotas are associated with new lesions post-treatment. Plaque samples from 2- to 6-year-old children were analyzed by a 16S rRNA-based microarray and by PCR for selected taxa. Severe-ECC children were monitored for 12 months post-therapy. By microarray, species associated with severe-ECC (n = 53) compared with caries-free (n = 32) children included Slackia exigua (p = 0.002), Streptococcus parasanguinis (p = 0.013), and Prevotella species (p < 0.02). By PCR, severe-ECC-associated taxa included Bifidobacteriaceae (p < 0.001), Scardovia wiggsiae (p = 0.003), Streptococcus mutans with bifidobacteria (p < 0.001), and S. mutans with S. wiggsiae (p = 0.001). In follow-up, children without new lesions (n = 36) showed lower detection of taxa including S. mutans, changes not observed in children with follow-up lesions (n = 17). Partial least-squares modeling separated the children into caries-free and two severe-ECC groups with either a stronger bacterial or a stronger dietary component. We conclude that several species, including S. wiggsiae and S. exigua, are associated with the ecology of advanced caries, that successful treatment is accompanied by a change in the microbiota, and that severe ECC is diverse, with influences from selected bacteria or from diet.
C1 [Tanner, A. C. R.; Holgerson, P. Lif; Kanasi, E.; Chalmers, N. I.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA.
[Kent, R. L., Jr.] Forsyth Inst, Dept Biostat, Cambridge, MA 02142 USA.
[Tanner, A. C. R.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
[Kent, R. L., Jr.; Kanasi, E.] Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA.
[Holgerson, P. Lif; Johansson, I.] Umea Univ, Dept Odontol, Cariol Sect, Fac Med, SE-90187 Umea, Sweden.
[Hughes, C. V.] Boston Univ, Goldman Sch Dent Med, Dept Pediat Dent, Boston, MA 02118 USA.
[Loo, C. Y.] Tufts Univ, Tufts Sch Dent Med, Dept Pediat Dent, Boston, MA 02111 USA.
RP Tanner, ACR (reprint author), Forsyth Inst, Dept Mol Genet, 245 1st St, Cambridge, MA 02142 USA.
EM annetanner@forsyth.org
RI Hughes, Christopher/E-1438-2014
FU USPHS from the NIDCR of NIH [DE-015847, DE-007327]; Colgate-Palmolive
Company; Henning and Johan Throne-Holst's Foundation
FX This investigation was supported by USPHS grants DE-015847 and DE-007327
from the NIDCR of NIH, the Colgate-Palmolive Company, and the Henning
and Johan Throne-Holst's Foundation.
NR 28
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U1 3
U2 15
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD NOV
PY 2011
VL 90
IS 11
BP 1298
EP 1305
DI 10.1177/0022034511421201
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 830XM
UT WOS:000295692600007
PM 21868693
ER
PT J
AU Mawardi, H
Giro, G
Kajiya, M
Ohta, K
Almazrooa, S
Alshwaimi, E
Woo, SB
Nishimura, I
Kawai, T
AF Mawardi, H.
Giro, G.
Kajiya, M.
Ohta, K.
Almazrooa, S.
Alshwaimi, E.
Woo, S-B.
Nishimura, I.
Kawai, T.
TI A Role of Oral Bacteria in Bisphosphonate-induced Osteonecrosis of the
Jaw
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE bisphosphonate-induced osteonecrosis of the jaw; pamidronate; gingival
fibroblast; KGF; wound healing; Fusobacterium nucleatum
ID INFECTED OSTEORADIONECROSIS; ZOLEDRONIC ACID; RECOGNITION; GROWTH;
TISSUE; CELLS; RATS
AB No consensus has yet been reached to associate oral bacteria conclusively with the etio-pathogenesis of bisphosphonate-induced osteonecrosis of the jaw (BONJ). Therefore, the present study examined the effects of oral bacteria on the development of BONJ-like lesions in a mouse model. In the pamidronate (Pam)-treated mice, but not control non-drug-treated mice, tooth extraction followed by oral infection with Fusobacterium nucleatum caused BONJ-like lesions and delayed epithelial healing, both of which were completely suppressed by a broad-spectrum antibiotic cocktail. Furthermore, in both in vitro and in vivo experiments, the combination of Pam and Fusobacterium nucleatum caused the death of gingival fibroblasts (GFs) and down-regulated their production of keratinocyte growth factor (KGF), which induces epithelial cell growth and migration. Therefore, in periodontal tissues pre-exposed to bisphosphonate, bacterial infection at tooth extraction sites caused diminished KGF expression in GFs, leading to a delay in the epithelial wound-healing process that was mitigated by antibiotics.
C1 [Mawardi, H.; Giro, G.; Kajiya, M.; Ohta, K.; Almazrooa, S.; Kawai, T.] Forsyth Inst, Dept Immunol, Cambridge, MA 02142 USA.
[Mawardi, H.; Kajiya, M.; Ohta, K.; Almazrooa, S.; Woo, S-B.; Kawai, T.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
[Mawardi, H.; Almazrooa, S.] King Abdulaziz Univ, Oral Med Div, Fac Dent, Jeddah 21589, Saudi Arabia.
[Giro, G.] UNESP Sao Paulo State Univ, Sch Dent Araraquara, Dept Oral Diag & Surg, BR-14801903 Sao Paulo, SP, Brazil.
[Alshwaimi, E.] Univ Dammam, Coll Dent, Restorat Dent Sci Dept, Dammam 31441, Saudi Arabia.
[Nishimura, I.] UCLA Sch Dent, Div Adv Prosthodont Biomat & Hosp Dent, Los Angeles, CA 90095 USA.
RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol, 245 1st St, Cambridge, MA 02142 USA.
EM tkawai@forsyth.org
RI AlShwaimi, Emad /F-4077-2012; Giro, Gabriela/D-2746-2009
OI Giro, Gabriela/0000-0002-7590-8158
FU NIH from the NIDCR [DE-18499, DE-19917]
FX This study was supported by NIH grants DE-18499 (TK) and DE-19917 (TK)
from the NIDCR. We acknowledge the assistance of Hajime Yamazaki in
taking x-rays. The authors declare no potential conflicts of interest
with respect to the authorship and/or publication of this article.
NR 25
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U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD NOV
PY 2011
VL 90
IS 11
BP 1339
EP 1345
DI 10.1177/0022034511420430
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 830XM
UT WOS:000295692600013
PM 21921248
ER
PT J
AU Pugach, MK
Ozer, F
Li, Y
Sheth, K
Beasley, R
Resnick, A
Daneshmehr, L
Kulkarni, AB
Bartlett, JD
Gibson, CW
Lindemeyer, RG
AF Pugach, M. K.
Ozer, F.
Li, Y.
Sheth, K.
Beasley, R.
Resnick, A.
Daneshmehr, L.
Kulkarni, A. B.
Bartlett, J. D.
Gibson, C. W.
Lindemeyer, R. G.
TI The Use of Mouse Models to Investigate Shear Bond Strength in
Amelogenesis Imperfecta
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE enamel; acid-etching; amelogenesis imperfecta; shear bond strength;
amelogenin; matrix metalloproteinase-20
ID CONSERVATIVE TREATMENT; MICE DISPLAY; PHENOTYPE; MUTATION; ENAMEL;
RESTORATIONS
AB Patients with amelogenesis imperfecta (AI) have defective enamel; therefore, bonded restorations of patients with AI have variable success rates. To distinguish which cases of AI may have good clinical outcomes with bonded materials, we evaluated etching characteristics and bond strength of enamel in mouse models, comparing wild-type (WT) with those having mutations in amelogenin (Amelx) and matrix metalloproteinase-20 (Mmp20), which mimic 2 forms of human AI. Etched enamel surfaces were compared for roughness by scanning electron microscopy (SEM) images. Bonding was compared through shear bond strength (SBS) studies with 2 different systems (etch-and-rinse and self-etch). Etched enamel surfaces of incisors from Amelx knockout (AmelxKO) mice appeared randomly organized and non-uniform compared with WT. Etching of Mmp20KO surfaces left little enamel, and the etching pattern was indistinguishable from unetched surfaces. SBS results were significantly different when AmelxKO and Mmp20KO enamel surfaces were compared. A significant increase in SBS was measured for all samples when the self-etch system was compared with the etch-and-rinse system. We have developed a novel system for testing shear bond strength of mouse incisors with AI variants, and analysis of these data may have important clinical implications for the treatment of patients with AI.
C1 [Lindemeyer, R. G.] Univ Penn, Sch Dent Med, Div Pediat Dent, Philadelphia, PA 19104 USA.
[Pugach, M. K.; Li, Y.; Sheth, K.; Beasley, R.; Resnick, A.; Gibson, C. W.] Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA.
[Ozer, F.; Daneshmehr, L.] Univ Penn, Sch Dent Med, Dept Prevent & Restorat Sci, Philadelphia, PA 19104 USA.
[Kulkarni, A. B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Cambridge, MA 02142 USA.
[Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Cambridge, MA 02142 USA.
RP Lindemeyer, RG (reprint author), Univ Penn, Sch Dent Med, Div Pediat Dent, 240 S 40th St, Philadelphia, PA 19104 USA.
EM lindemey@dental.upenn.edu
FU National Institute of Dental and Craniofacial Research (National
Institutes of Health) [DE011089, DE019968, DE016276]
FX The authors acknowledge Z. Nelson and A. Clark for assistance with
sample preparation, B. Winkelstein and Y. Shimada for technical
discussions, M. Blatz for clinical insights, and the National Institute
of Dental and Craniofacial Research (National Institutes of Health)
grants DE011089, DE019968, and DE016276 for supporting this study. The
authors declare no potential conflicts of interest with respect to the
authorship and/or publication of this article.
NR 29
TC 1
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U1 1
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD NOV
PY 2011
VL 90
IS 11
BP 1352
EP 1357
DI 10.1177/0022034511421929
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 830XM
UT WOS:000295692600015
PM 21917602
ER
PT J
AU Hochman, M
McCormick, D
AF Hochman, Michael
McCormick, Danny
TI Endpoint Selection and Relative (Versus Absolute) Risk Reporting in
Published Medication Trials
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE surrogate endpoints; composite endpoints; disease-specific mortality;
relative risk reduction
ID RANDOMIZED CONTROLLED-TRIALS; CLINICAL-TRIALS; COMPOSITE OUTCOMES; USERS
GUIDES; INTERVENTION; ASSOCIATION; CONCLUSIONS; PREVENTION; BENEFITS;
ARTICLE
AB The use of surrogate and composite endpoints, disease-specific mortality as an endpoint, and relative (rather than absolute) risk reporting in clinical trials may produce results that are misleading or difficult to interpret.
To describe the prevalence of these endpoints and of relative risk reporting in medication trials.
We analyzed all randomized medication trials published in the six highest impact general medicine journals between June 1, 2008 and September 30, 2010 and determined the percentage using these endpoints and the percentage reporting results in the abstract exclusively in relative terms.
We identified 316 medication trials, of which 116 (37%) used a surrogate primary endpoint and 106 (34%) used a composite primary endpoint. Among 118 trials in which the primary endpoint involved mortality, 32 (27%) used disease-specific mortality rather than all-cause mortality. Among 157 trials with positive results, 69 (44%) reported these results in the abstract exclusively in relative terms. Trials using surrogate endpoints and disease-specific mortality as an endpoint were more likely to be exclusively commercially funded (45% vs. 29%, difference 15% [95% CI 5%-26%], P = 0.004, and 39% vs. 16%, difference 22% [95% CI 6%-37%], P = 0.007, respectively). Trials using surrogate endpoints were more likely to report positive results (66% vs. 49%, difference 17% [95% CI 5%-28%], P = 0.006) while those using mortality endpoints were less likely to be positive (46% vs. 62%, difference -16% [95% CI -27%--4%], P = 0.01).
The use of surrogate and composite endpoints, endpoints involving disease-specific mortality, and relative risk reporting is common. Articles should highlight the limitations of these endpoints and should report results in absolute terms.
C1 [Hochman, Michael] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90024 USA.
[Hochman, Michael] US Dept Vet Affairs, Los Angeles, CA 90024 USA.
[McCormick, Danny] Cambridge Hlth Alliance, Dept Med, Cambridge, MA USA.
[McCormick, Danny] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Hochman, M (reprint author), Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, 911 Broxton Ave,3rd Floor, Los Angeles, CA 90024 USA.
EM Meh1979@gmail.com
NR 32
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U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2011
VL 26
IS 11
BP 1246
EP 1252
DI 10.1007/s11606-011-1813-7
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 830UU
UT WOS:000295683500007
PM 21842324
ER
PT J
AU Bass, MG
Korthuis, PT
Cofrancesco, J
Berkenblit, GV
Sullivan, LE
Asch, SM
Bashook, PG
Edison, M
Sosman, JM
Cook, RL
AF Bass, Michael G.
Korthuis, P. Todd
Cofrancesco, Joseph, Jr.
Berkenblit, Gail V.
Sullivan, Lynn E.
Asch, Steve M.
Bashook, Philip G.
Edison, Marcia
Sosman, James M.
Cook, Robert L.
TI Provider and Practice Characteristics Associated with Use of Rapid HIV
Testing by General Internists
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE testing; rapid HIV testing; HIV/AIDS; general internal medicine
physicians; HIV prevention; medical practice setting
ID HEALTH-CARE SETTINGS; EMERGENCY-DEPARTMENT; SCREENING-PROGRAM; ROUTINE;
PHYSICIANS; VIRUS; RECOMMENDATIONS; ADOLESCENTS; PREVALENCE
AB Rapid HIV testing could increase routine HIV testing. Most previous studies of rapid testing were conducted in acute care settings, and few described the primary care providers' perspective.
To identify characteristics of general internal medicine physicians with access to rapid HIV testing, and to determine whether such access is associated with differences in HIV-testing practices or perceived HIV-testing barriers.
Web-based cross-sectional survey conducted in 2009.
A total of 406 physician members of the Society of General Internal Medicine who supervise residents or provide care in outpatient settings.
Surveys assessed provider and practice characteristics, HIV-testing types, HIV-testing behavior, and potential barriers to HIV testing.
Among respondents, 15% had access to rapid HIV testing. In multivariable analysis, physicians were more likely to report access to rapid testing if they were non-white (OR 0.45, 95% CI 0.22, 0.91), had more years since completing training (OR 1.06, 95% CI 1.02, 1.10), practiced in the northeastern US (OR 2.35; 95% CI 1.28, 4.32), or their practice included a higher percentage of uninsured patients (OR 1.03; 95% CI 1.01, 1.04). Internists with access to rapid testing reported fewer barriers to HIV testing. More respondents with rapid than standard testing reported at least 25% of their patients received HIV testing (51% versus 35%, p = 0.02). However, access to rapid HIV testing was not significantly associated with the estimated proportion of patients receiving HIV testing within the previous 30 days (7.24% vs. 4.58%, p = 0.06).
Relatively few internists have access to rapid HIV testing in outpatient settings, with greater availability of rapid testing in community-based clinics and in the northeastern US. Future research may determine whether access to rapid testing in primary care settings will impact routinizing HIV testing.
C1 [Cook, Robert L.] Univ Florida, Dept Epidemiol, Gainesville, FL 32610 USA.
[Cook, Robert L.] Univ Florida, Dept Med, Gainesville, FL 32610 USA.
[Bass, Michael G.; Bashook, Philip G.; Edison, Marcia] Univ Illinois, Coll Med, Dept Med Educ, Chicago, IL USA.
[Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA.
[Cofrancesco, Joseph, Jr.; Berkenblit, Gail V.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Sullivan, Lynn E.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
[Asch, Steve M.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA.
[Sosman, James M.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA.
RP Cook, RL (reprint author), Univ Florida, Dept Epidemiol, CB 100231, Gainesville, FL 32610 USA.
EM cookrl@ufl.edu
FU Centers for Disease Control and Prevention; Centers for Disease Control
(CDC) [1 U22 PS00551-02]; Robert Wood Johnson Foundation; Health
Resources Services Administration for the Midwest AIDS Education and
Training Center; National Institutes of Health, National Institute on
Drug Abuse [K23 DA019809]
FX We want to thank our colleagues at the Society for General Internal
Medicine for responding to our survey, and providing thoughtful
feedback. We appreciate the funding we received from the Centers for
Disease Control and Prevention, and our respective agencies, which
allowed us to carry on this work. We wish to especially thank Leslie
Dunne, our SGIM project manager, who facilitated this effort to
completion.; This work was supported by a grant from the Centers for
Disease Control (CDC grant number 1 U22 PS00551-02 HIV Prevention with
National Medical Associations), in conjunction with the Society of
General Internal Medicine, HIV/AIDS Task Force. Dr. Sullivan was
supported by the Robert Wood Johnson Foundation Physician Faculty
Scholars Program during the conduct of this work. Drs. Bashook and
Edison were supported by a grant from the Health Resources Services
Administration for the Midwest AIDS Education and Training Center during
the conduct of this work. Dr. Korthuis was supported by the National
Institutes of Health, National Institute on Drug Abuse (K23 DA019809)
during the conduct of this work.
NR 36
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U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2011
VL 26
IS 11
BP 1258
EP 1264
DI 10.1007/s11606-011-1764-z
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 830UU
UT WOS:000295683500009
PM 21710314
ER
PT J
AU Joo, MJ
Au, DH
Fitzgibbon, ML
McKell, J
Lee, TA
AF Joo, Min J.
Au, David H.
Fitzgibbon, Marian L.
McKell, Joanne
Lee, Todd A.
TI Determinants of Spirometry Use and Accuracy of COPD Diagnosis in Primary
Care
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE chronic disease; diagnosis; health care delivery; chronic obstructive
pulmonary disease; spirometry; quality of care
ID OBSTRUCTIVE PULMONARY-DISEASE; INHALED CORTICOSTEROID USE;
LUNG-FUNCTION; SALMETEROL/FLUTICASONE PROPIONATE; FLUTICASONE
PROPIONATE; SALMETEROL; METAANALYSIS; TIOTROPIUM; FORMOTEROL; EFFICACY
AB It is unclear if primary care physicians are following guidelines or using other patient characteristics and factors to determine when to perform spirometry in patients at risk for COPD. It is also unclear to what degree a diagnosis of COPD is accurately reflected by spirometry results.
To examine characteristics associated with use of spirometry in primary care for patients with increased risk for COPD and to determine the accuracy of COPD diagnosis in patients with spirometry.
Retrospective cohort study.
A cohort that met the following criteria was identified: a parts per thousand yen35 years of age; a parts per thousand yen 2 primary care visits in internal medicine clinic in 2007; at least one respiratory or smoking cessation medication, or diagnosis of COPD or shortness of breath or dyspnea in 2007.
Medical records of all primary care physician visits prior to the time of inclusion in 2007 were reviewed. Data on patient demographics, co-morbidities, respiratory medication use, presence of symptoms, history of tobacco use, and pulmonary function tests were extracted.
A total 1052 patients were identified. Dyspnea on exertion (Adjusted odds ratio (AOR) 1.52 [95% CI 1.06-2.18]) and chronic cough (AOR 1.71 [1.07-2.72]) were the only chronic symptoms associated with use of spirometry. Current (AOR 1.54 [0.99-2.40]) or past smoking (AOR 1.09 [0.72-1.65]) status were not associated with use of spirometry. Of the 159 patients with a diagnosis of COPD, 93 (58.5%) met GOLD criteria and 81(50.9%) met lower limit of normal (LLN) criteria for COPD.
Clinicians use spirometry more often among patients with symptoms suggestive of COPD but not more often among patients with current or past tobacco use. For patients who had a spirometry and a diagnosis of COPD, primary care physicians were accurate in their diagnosis only half of the time.
C1 [Joo, Min J.; Fitzgibbon, Marian L.] Univ Illinois, Dept Med, Sect Hlth Promot Res, Chicago, IL 60612 USA.
[Joo, Min J.; McKell, Joanne] Univ Illinois, Dept Med, Sect Pulm Crit Care Sleep & Allergy Med, Chicago, IL 60612 USA.
[Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA.
[Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
[Lee, Todd A.] Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA.
[Lee, Todd A.] Univ Illinois, Dept Pharm Practice, Ctr Pharmacoecon Res, Chicago, IL 60612 USA.
RP Joo, MJ (reprint author), Univ Illinois, Dept Med, Sect Hlth Promot Res, 840 S Wood St,M-C 719, Chicago, IL 60612 USA.
EM joo@uic.edu
FU National Heart, Lung, and Blood Institute [K23HL094461]
FX This work was supported by the National Heart, Lung, and Blood Institute
[K23HL094461]. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the NHLBI, the
National Institutes. The views expressed in this manuscript reflect
those of the authors and not necessarily those of the Department of
Veterans Affairs.
NR 33
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U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2011
VL 26
IS 11
BP 1272
EP 1277
DI 10.1007/s11606-011-1770-1
PG 6
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 830UU
UT WOS:000295683500011
PM 21713542
ER
PT J
AU Axon, RN
Gebregziabher, M
Echols, C
Gilbert, G
Egede, LE
AF Axon, R. Neal
Gebregziabher, Mulugeta
Echols, Carrae
Gilbert, Gregory
Egede, Leonard E.
TI Racial and Ethnic Differences in Longitudinal Blood Pressure Control in
Veterans with Type 2 Diabetes Mellitus
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE blood pressure control; diabetes; epidemiology; race/ethnicity
ID CARDIOVASCULAR-DISEASE RISK; SYSTOLIC HYPERTENSION; AFRICAN-AMERICANS;
DISPARITIES; CARE; STROKE; RACE; PREVALENCE; MORTALITY; OUTCOMES
AB Few studies have examined racial/ethnic differences in blood pressure (BP) control over time, especially in an equal access system. We examined racial/ethnic differences in longitudinal BP control in Veterans with type 2 diabetes.
We collected data on a retrospective cohort of 5,319 Veterans with type 2 diabetes and initially uncontrolled BP followed from 1996 to 2006 at a Veterans Administration (VA) facility in the southeastern United States. The mean blood pressure value for each subject for each year was used for the analysis with BP control defined as < 140/< 90 mmHg. The primary outcome measure was proportion with controlled BP. The main predictor variable was race/ethnicity categorized as non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic/Other (H/O). Other covariates included age, gender, employment, marital status, service connectedness, and ICD-9 coded medical and psychiatric comorbidities. Generalized linear mixed models were used to assess the relationship between race/ethnicity and BP control after adjusting for covariates.
Mean follow-up was 5.0 years. The sample was 46% NHW, 26% NHB, 19% H/O, and 9% unknown. The average age was 68 years. In the final model, after adjusting for covariates, NHB race (OR = 1.38, 95%CI: 1.2, 1.6) and H/O race (OR = 1.57, 95% CI: 1.3, 1.8) were associated with increased likelihood of poor BP control (> 140/> 90 mmHg) over time compared to NHW patients.
Ethnic minority Veterans with type 2 diabetes have significantly increased odds of poor BP control over similar to 5 years of follow-up compared to their non-Hispanic White counterparts independent of sociodemographic factors and comorbidity patterns.
C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA.
[Axon, R. Neal; Gebregziabher, Mulugeta; Echols, Carrae; Gilbert, Gregory; Egede, Leonard E.] Ralph H Johnson VAMC, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA.
[Axon, R. Neal; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA.
[Gebregziabher, Mulugeta] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA.
RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA.
EM egedel@musc.edu
RI Gilbert, Gregory/C-7735-2016;
OI Gilbert, Gregory/0000-0003-0879-5496; Gebregziabher,
Mulugeta/0000-0002-4826-481X
FU Center for Disease Prevention and Health Interventions for Diverse
Populations [REA 08-261]; Veterans Affairs Health Services Research and
Development
FX This study was supported by Grant # REA 08-261, Center for Disease
Prevention and Health Interventions for Diverse Populations funded by
Veterans Affairs Health Services Research and Development (PI - Leonard
Egede).
NR 37
TC 10
Z9 10
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2011
VL 26
IS 11
BP 1278
EP 1283
DI 10.1007/s11606-011-1752-3
PG 6
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 830UU
UT WOS:000295683500012
PM 21671132
ER
PT J
AU Ly, DP
Jha, AK
Epstein, AM
AF Ly, Dan P.
Jha, Ashish K.
Epstein, Arnold M.
TI The Association Between Hospital Margins, Quality of Care, and Closure
or Other Change in Operating Status
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE margins; quality; closure
ID ACUTE MYOCARDIAL-INFARCTION; URBAN; MEDICARE; PERFORMANCE
AB Hospitals face increased pressure to improve their quality of care in an environment of dwindling hospital payments. It is unclear whether lower hospital margins are associated with worse quality of care or closure.
To determine the association of hospital margins with quality of care and changes in operating status.
We conducted an observational cross-sectional study analyzing hospitals' margin, quality of care (process quality, risk-adjusted readmission rates, and risk-adjusted mortality rates), and changes in operating status (rates of closure, merger and acquisition, and conversion to a critical access hospital) for 3,262 non-public U.S. hospitals with data from the Hospital Quality Alliance and Medicare Cost Reports.
Compared to those in the bottom 10% of operating margin, those in the top 10% had higher process quality (e.g. 95.3 vs. 93.7, p = 0.002 for acute myocardial infarction [AMI]) and lower readmission rates (e.g. 19.7% vs. 22.4%, p < 0.001 for AMI). We found no association between margins and mortality rates. Hospitals in the bottom 10% were more likely than those in the top 10% to close (5.7% vs. 2.0%), merge or become acquired (4.0% vs. 0.3%), or convert to a Critical Access Hospital (5.4% vs. 0.6%). Over 15% of hospitals in the lowest decile of hospital margin changed operating status in the subsequent year.
Low hospital margins are associated with worse processes of care and readmission rates and with changes in operating status. We should monitor low-margin hospitals closely for declining quality of care.
C1 [Ly, Dan P.] Weill Cornell Med Coll, New York, NY 10021 USA.
[Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA.
[Jha, Ashish K.; Epstein, Arnold M.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Epstein, Arnold M.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA.
RP Ly, DP (reprint author), Weill Cornell Med Coll, 420 E 70th St,Rm 11C, New York, NY 10021 USA.
EM dpl2001@med.cornell.edu
NR 23
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U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2011
VL 26
IS 11
BP 1291
EP 1296
DI 10.1007/s11606-011-1815-5
PG 6
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 830UU
UT WOS:000295683500014
PM 21837374
ER
PT J
AU Lee, CA
Chang, A
Chou, CL
Boscardin, C
Hauer, KE
AF Lee, Christina A.
Chang, Anna
Chou, Calvin L.
Boscardin, Christy
Hauer, Karen E.
TI Standardized Patient-Narrated Web-Based Learning Modules Improve
Students' Communication Skills on a High-stakes Clinical Skills
Examination
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE medical education; clinical skills; standardized patient; communication
ID MEDICAL-STUDENTS; HEALTH-PROFESSIONS; PERFORMANCE; SCORES; EDUCATION;
CARE; METAANALYSIS; STRATEGIES; MOTIVATION; RESIDENTS
AB BACKGROUND: Use of web-based standardized patient (SP) modules is associated with improved medical student history-taking and physical examination skills on clinical performance examinations (CPX), but a benefit for communication skills has not been shown.
AIM: We describe an innovative web-based SP module using detailed SP and faculty commentary to teach communication skills.
SETTING: A public medical school in 2008-2009.
PARTICIPANTS: Fourth-year medical students.
PROGRAM DESCRIPTION: A 90-minute web-based module with three simulated clinical encounters was narrated by an expert clinician and SP to explain expected history-taking, physical examination, and communication skills behaviors. All 147 students were encouraged to review the module one month before the CPX.
PROGRAME VALUATION: One hundred and six students (72%) viewed the web-based module. Students who watched the module performed significantly higher on the CPX communication score (+2.67%, p < 0.01) and overall score (+2.12%, p = 0.03), even after controlling for USMLE Step 1 and clerkship summary ratings. Use of the module did not significantly affect history/physical examination scores (+1.89%, p = 0.12).
DISCUSSION: Students who watched an optional web-based SP module prior to the CPX performed higher than those who did not on communication skills. The web-based module appears to be an effective CPX preparatory activity to enhance communication performance.
C1 [Lee, Christina A.] Palo Alto Med Fdn, Palo Alto, CA 94301 USA.
[Chang, Anna; Chou, Calvin L.; Boscardin, Christy; Hauer, Karen E.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Chang, Anna; Chou, Calvin L.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Lee, CA (reprint author), Palo Alto Med Fdn, 795 El Camino Real, Palo Alto, CA 94301 USA.
EM christinaaudreylee@gmail.com
OI Boscardin, Christy/0000-0002-9070-8859
FU University of California, San Francisco Academy of Medical Educators
FX We thank Bernie Miller and Jewel Smally for assistance with module
creation and examination administration and Christian Burke for
technical assistance. This study was supported by a University of
California, San Francisco Academy of Medical Educators Innovations
Grant.
NR 34
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U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2011
VL 26
IS 11
BP 1374
EP 1377
DI 10.1007/s11606-011-1809-3
PG 4
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 830UU
UT WOS:000295683500027
PM 21769506
ER
PT J
AU Shin, OS
Uddin, T
Citorik, R
Wang, JP
Della Pelle, P
Kradin, RL
Bingle, CD
Bingle, L
Camilli, A
Bhuiyan, TR
Shirin, T
Ryan, ET
Calderwood, SB
Finberg, RW
Qadri, F
LaRocque, RC
Harris, JB
AF Shin, Ok S.
Uddin, Taher
Citorik, Robert
Wang, Jennifer P.
Della Pelle, Patricia
Kradin, Richard L.
Bingle, Colin D.
Bingle, Lynne
Camilli, Andrew
Bhuiyan, Taufiqur R.
Shirin, Tahmina
Ryan, Edward T.
Calderwood, Stephen B.
Finberg, Robert W.
Qadri, Firdausi
LaRocque, Regina C.
Harris, Jason B.
TI LPLUNC1 Modulates Innate Immune Responses to Vibrio cholerae
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID PERMEABILITY-INCREASING PROTEIN; INFLAMMATORY MEDIATORS; HOST-DEFENSE;
LIPOPOLYSACCHARIDE; FAMILY; GENE; BINDING; CELLS; PLUNC;
BACTERICIDAL/PERMEABILITY
AB Metods. We investigated the role of LPLUNC1 in immune responses to V. cholerae, assessing its affect on bacterial growth and killing and on innate inflammatory responses to bacterial outer membrane components, including purified lipopolysaccharide (LPS) and outer membrane vesicles. We performed immunostaining for LPLUNC1 in duodenal biopsies from cholera patients and uninfected controls.
Results. LPLUNC1 decreased proinflammatory innate immune responses to V. cholerae and Escherichia coli LPS. The effect of LPLUNC1 was dose-dependent and occurred in a TLR4-dependent manner. LPLUNC1 did not affect lipoprotein-mediated TLR2 activation. Immunostaining demonstrated expression of LPLUNC1 in Paneth cells in cholera patients and controls.
Conclusions. Our results demonstrate that LPLUNC1 is expressed in Paneth cells and likely plays a role in modulating host inflammatory responses to V. cholerae infection. Attenuation of innate immune responses to LPS by LPLUNC1 may have implications for the maintenance of immune homeostasis in the intestine.
C1 [Shin, Ok S.; Citorik, Robert; Ryan, Edward T.; Calderwood, Stephen B.; LaRocque, Regina C.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Della Pelle, Patricia; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Shin, Ok S.; Ryan, Edward T.; Calderwood, Stephen B.; LaRocque, Regina C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Camilli, Andrew] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
[Wang, Jennifer P.; Finberg, Robert W.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[Uddin, Taher; Bhuiyan, Taufiqur R.; Shirin, Tahmina; Qadri, Firdausi] Int Ctr Diarrheal Dis Res, Lab Sci Div, Dhaka, Bangladesh.
[Bingle, Colin D.] Univ Sheffield, Dept Infect & Immun, Acad Unit Resp Med, Sheffield S10 2TN, S Yorkshire, England.
[Bingle, Colin D.] Univ Sheffield, Sch Clin Dent, Sheffield S10 2TN, S Yorkshire, England.
RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA.
EM jbharris@partners.org
OI wang, jennifer/0000-0002-2556-9100; Bingle, Colin/0000-0002-5405-6988;
Citorik, Robert/0000-0002-6397-5417
FU ICDDR, B: Centre for Health and Population Research; National Institute
of Allergy and Infectious Diseases, National Institutes of Health [U01
AI058935, RO3 AI063079, U01 AI077883]; International Research Scientist
Development Award [K01 TW07409, K01 TW07144]; Charles H. Hood
Foundation; Howard Hughes Medical Institute
FX This work was supported by the ICDDR, B: Centre for Health and
Population Research; the National Institute of Allergy and Infectious
Diseases, National Institutes of Health (U01 AI058935 to S. B. C., RO3
AI063079 to F. Q., and U01 AI077883 to E. T. R.); International Research
Scientist Development Award (K01 TW07409 to J. B. H.); Charles H. Hood
Foundation Child Health Research Award (J. B. H.); International
Research Scientist Development Award (K01 TW07144 to R. C. L.); and
Physician-Scientist Early Career Award from the Howard Hughes Medical
Institute (R. C. L.).
NR 36
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U1 1
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2011
VL 204
IS 9
BP 1349
EP 1357
DI 10.1093/infdis/jir544
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 828NS
UT WOS:000295509300008
PM 21900486
ER
PT J
AU Kopell, BH
Halverson, J
Butson, CR
Dickinson, M
Bobholz, J
Harsch, H
Rainey, C
Kondziolka, D
Howland, R
Eskandar, E
Evans, KC
Dougherty, DD
AF Kopell, Brian Harris
Halverson, Jerry
Butson, Christopher R.
Dickinson, Mercedes
Bobholz, Julie
Harsch, Harold
Rainey, Charles
Kondziolka, Douglas
Howland, Robert
Eskandar, Emad
Evans, Karleyton C.
Dougherty, Darin D.
TI Epidural Cortical Stimulation of the Left Dorsolateral Prefrontal Cortex
for Refractory Major Depressive Disorder
SO NEUROSURGERY
LA English
DT Article
DE Cortical stimulation; DLPFC; Major depressive disorder; Neuromodulation;
PET
ID TRANSCRANIAL MAGNETIC STIMULATION; TREATMENT-RESISTANT DEPRESSION; VAGUS
NERVE-STIMULATION; DEEP BRAIN-STIMULATION; RANDOMIZED CONTROLLED-TRIAL;
CEREBRAL-BLOOD-FLOW; ELECTROCONVULSIVE-THERAPY; MOTOR CORTEX; BURST
STIMULATION; LONG-TERM
AB BACKGROUND: A significant number of patients with major depressive disorder are unresponsive to conventional therapies. For these patients, neuromodulation approaches are being investigated.
OBJECTIVE: To determine whether epidural cortical stimulation at the left dorsolateral prefrontal cortex is safe and efficacious for major depressive disorder through a safety and feasibility study.
METHODS: Twelve patients were recruited in this randomized, single-blind, sham-controlled study with a 104-week follow-up period. The main outcome measures were Hamilton Depression Rating Scale-28 (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Function (GAF), and Quality of Life Enjoyment and Satisfaction (QLES) questionnaire. An electrode was implanted over Brodmann area 9/46 in the left hemisphere. The electrode provided long-term stimulation to this target via its connections to an implanted neurostimulator in the chest. RESULTS: During the sham-controlled phase, there was no statistical difference between sham and active stimulation, although a trend toward efficacy was seen with the active stimulation group. In the open-label phase, we observed a significant improvement in outcome scores for the HDRS, MADRS, and GAF but not the QLES (HDRS: df = 7, F = 7.72, P < .001; MADRS: df = 7, F = 8.2, P < .001; GAF: df = 5, F = 16.87, P < .001; QLES: df = 5, F = 1.32, P > .2; repeated measures ANOVA). With regard to the HDRS, 6 patients had >= 40% improvement, 5 patients had >= 50% improvement, and 4 subjects achieved remission (HDRS < 10) at some point during the study.
CONCLUSION: Epidural cortical stimulation of the left dorsolateral prefrontal cortex appears to be a safe and potentially efficacious neuromodulation approach for treatment-refractory major depressive disorder.
C1 [Kopell, Brian Harris; Butson, Christopher R.] Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA.
[Kopell, Brian Harris; Halverson, Jerry; Harsch, Harold; Rainey, Charles] Med Coll Wisconsin, Dept Psychiat, Milwaukee, WI 53226 USA.
[Butson, Christopher R.; Dickinson, Mercedes; Bobholz, Julie] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA.
[Kondziolka, Douglas] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA.
[Howland, Robert] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA.
[Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA.
[Evans, Karleyton C.; Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA.
RP Kopell, BH (reprint author), Med Coll Wisconsin, Dept Neurosurg, 9200 Wisconsin Ave, Milwaukee, WI 53226 USA.
EM bkopell@mcw.edu
RI Butson, Christopher/J-8034-2013; Howland, Robert/K-6937-2015
OI Butson, Christopher/0000-0002-2319-1263; Howland,
Robert/0000-0002-6533-6010
FU Pfizer; Takeda; Novartis; Cyberonics; St. Jude Medical Neuromodulation;
Sanofi-aventis; Otsuka; GlaxoSmithKline; Medtronic; Eli Lilly; McNeil;
Northstar Neuroscience (Seattle, Washington)
FX Dr Kopell was a consultant to Northstar Neuroscience, is on the
scientific advisory board of Prism Clinical Imaging, and is a consultant
and member of the clinical advisory board of Neurostream Technologies.
Dr Butson is a consultant and shareholder of Intelect Medical and a
consultant to NeuroPace and Advanced Bionics. Dr Harsch reports the
following conflicts of interest: Forest Lab (honorarium, speaker),
Pfizer (honorarium, grant, speaker, consultant, principal investigator),
Lilly (honorarium, speaker, consultant), AstraZeneca (honorarium,
speaker, consultant), Merck (honorarium, speaker), Takeda (educational
grant, teaching), e-Medicine (honorarium, editor), Novartis (grant,
principal investigator), Cyberonics (grant, principal investigator), St.
Jude Medical Neuromodulation (grant, principal investigator),
Sanofi-aventis (grant, principal investigator), Otsuka (grant, principal
investigator), and GlaxoSmithKline (grant, principal investigator). Dr
Kondziolka is a consultant to Elekta Instruments. Dr Eskandar has
received a consultant honorarium from Medtronic. Dr Evans has received
research support from Cyberonics, Medtronic, and Pfizer and has received
an honorarium from Medtronic. Dr Dougherty has the following conflicts
of interest to report: Medtronic (research support, consultant,
honorarium), Eli Lilly (research support, consultant, honorarium), Brand
Ideas (consultant, honorarium), McNeil (research support, consultant,
honorarium), Reed Elsevier (consultant, honorarium), and Cyberonics
(research support). This study was sponsored by Northstar Neuroscience
(Seattle, Washington). At the time of this publication, Northstar
Neuroscience has ceased operations. This trial, Assessment of the Safety
and Effectiveness of Cortical Stimulation in Subjects With Major
Depressive Disorder (PROSPECT), is registered at www.ClinicalTrials.gov;
unique identifier, NCT00380042. The authors have no personal financial
or institutional interest in any of the drugs, materials, or devices
described in this article.
NR 56
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U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD NOV
PY 2011
VL 69
IS 5
BP 1015
EP 1029
DI 10.1227/NEU.0b013e318229cfcd
PG 15
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 832UV
UT WOS:000295835300021
PM 21709597
ER
PT J
AU Houlahan, K
Temple, K
Young, M
AF Houlahan, Kathleen
Temple, Kendal
Young, Martha
TI CANCER PREVENTION EDUCATION FOR THE HEALTHY CHILD
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Houlahan, Kathleen] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2011
VL 57
IS 5
BP 716
EP 716
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 824ZB
UT WOS:000295239600036
ER
PT J
AU Steven, D
Shusterman, S
Reid, J
Ingle, A
Ahern, C
Baruchel, S
Glade-Bender, J
Ivy, P
Grier, H
Adamson, P
Blaney, S
AF Steven, DuBois
Shusterman, Suzanne
Reid, Joel
Ingle, Ashish
Ahern, Charlotte
Baruchel, Sylvain
Glade-Bender, Julie
Ivy, Percy
Grier, Holcombe
Adamson, Peter
Blaney, Susan
TI TOLERABILITY AND PHARMACOKINETIC PROFILE OF SUNITINIB GIVEN AS A POWDER
FORMULATION TO CHILDREN WITH REFRACTORY SOLID TUMORS: A CHILDREN'S
ONCOLOGY GROUP STUDY
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Steven, DuBois] UCSF Sch Med, Dept Pediat, San Francisco, CA USA.
[Shusterman, Suzanne; Grier, Holcombe] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Shusterman, Suzanne; Grier, Holcombe] Harvard Univ, Sch Med, Boston, MA USA.
[Reid, Joel] Mayo Coll Med, Rochester, NY USA.
[Ingle, Ashish] Childrens Oncol Grp, Arcadia, CA USA.
[Ahern, Charlotte; Blaney, Susan] Baylor Coll Med, Houston, TX 77030 USA.
[Baruchel, Sylvain] Univ Toronto, Toronto, ON, Canada.
[Baruchel, Sylvain] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Glade-Bender, Julie] Columbia Univ, New York, NY USA.
[Glade-Bender, Julie] Morgan Stanley Childrens Hosp, New York, NY USA.
[Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Adamson, Peter] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Blaney, Susan] Texas Childrens Canc Ctr, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2011
VL 57
IS 5
BP 717
EP 718
PG 2
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 824ZB
UT WOS:000295239600043
ER
PT J
AU Lindsay, F
Nicholson, J
Olson, T
Dang, H
Krailo, M
Billmire, D
Thornton, C
Hale, J
AF Lindsay, Frazier
Nicholson, James
Olson, Thomas
Dang, Ha
Krailo, Mark
Billmire, Deborah
Thornton, Claire
Hale, Juliet
TI PROGNOSTIC CLASSIFICATION OF PEDIATRIC GERM CELL TUMORS
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Lindsay, Frazier] DFCI, Boston, MA USA.
[Nicholson, James] Addenbrookes Hosp, Dept Paediat Haematol & Oncol, Cambridge, England.
[Olson, Thomas] Emory Univ, Atlanta, GA 30322 USA.
[Dang, Ha; Krailo, Mark] Childrens Oncol Grp, Arcadia, CA USA.
[Billmire, Deborah] Indiana Univ, James Whitcomb Riley Hosp Children, Bloomington, IN 47405 USA.
[Thornton, Claire] Royal Grp Hosp Trust, Belfast, Antrim, North Ireland.
[Hale, Juliet] Univ Nottingham Hosp, Natl Hlth Serv, Newcastle Upon Tyne, Tyne & Wear, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2011
VL 57
IS 5
BP 743
EP 743
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 824ZB
UT WOS:000295239600146
ER
PT J
AU Lai, JS
Zelko, F
Butt, Z
Krull, K
Manley, P
Goldman, S
AF Lai, Jin-Shei
Zelko, Frank
Butt, Zeeshan
Krull, Kevin
Manley, Peter
Goldman, Stewart
TI CAN PARENT-REPORTED PERCEIVED COGNITIVE FUNCTION BE USEFUL IN PEDIATRIC
ONCOLOGY CLINICS?
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Lai, Jin-Shei; Butt, Zeeshan] Northwestern Univ, Chicago, IL 60611 USA.
[Zelko, Frank] Childrens Mem Hosp, Pediat Neuropsychol Serv, Chicago, IL 60614 USA.
[Krull, Kevin] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA.
[Manley, Peter] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 NOV
PY 2011
VL 57
IS 5
BP 745
EP 745
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 824ZB
UT WOS:000295239600153
ER
PT J
AU Yagyu, S
Tanaka, S
Gotoh, T
London, W
Misawa-Furihata, A
Iehara, T
Hogarty, M
Teramukai, S
Sugimoto, T
Nakagawara, A
Hiyama, E
Maris, J
Hosoi, H
AF Yagyu, Shigeki
Tanaka, Shiro
Gotoh, Takahiro
London, Wendy
Misawa-Furihata, Akiko
Iehara, Tomoko
Hogarty, Michael
Teramukai, Satoshi
Sugimoto, Tohru
Nakagawara, Akira
Hiyama, Eiso
Maris, John
Hosoi, Hajime
TI PROGNOSIS OF NEUROBLASTOMA PATIENTS LESS THAN EIGHTEEN MONTHS OLD USING
SERUM-BASED QUANTIFICATION OF MYCN GENE AMPLIFICATION
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Yagyu, Shigeki; Gotoh, Takahiro; Misawa-Furihata, Akiko; Iehara, Tomoko; Sugimoto, Tohru; Hosoi, Hajime] Kyoto Prefectural Univ Med, Dept Pediat, Kyoto 602, Japan.
[Tanaka, Shiro; Teramukai, Satoshi] Kyoto Univ Hosp, Dept Clin Trial Design & Management, Kyoto 606, Japan.
[London, Wendy] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston,Div Hematol Oncol, Boston, MA 02115 USA.
[Hogarty, Michael; Maris, John] Childrens Hosp Philadelphia, Philadelphia, Japan.
[Hogarty, Michael; Maris, John] Univ Pennsylvania, Div Oncol, Philadelphia, Japan.
[Hogarty, Michael; Maris, John] Ctr Childhood Canc Res, Philadelphia, Japan.
[Nakagawara, Akira] Chiba Canc Ctr, Div Biochem & Innovat Canc Therapeut, Chiba 2608717, Japan.
[Hiyama, Eiso] Hiroshima Univ, Dept Pediat Surg, Hiroshima, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2011
VL 57
IS 5
BP 788
EP 788
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 824ZB
UT WOS:000295239600326
ER
PT J
AU Childs, S
Nguyen, P
Chi, S
Marcus, K
AF Childs, Stephanie
Nguyen, Paul
Chi, Susan
Marcus, Karen
TI INCIDENCE, OUTCOMES, AND PROGNOSTIC FACTORS IN CHILDREN WITH ATYPICAL
TERATOID RHABDOID TUMORS (ATRT) USING THE SURVEILLANCE EPIDEMIOLOGY AND
END RESULT (SEER) DATA-BASE
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Childs, Stephanie] Harvard Radiat Oncol Pmgram, Boston, MA USA.
[Nguyen, Paul] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Chi, Susan; Marcus, Karen] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2011
VL 57
IS 5
BP 802
EP 802
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 824ZB
UT WOS:000295239600386
ER
PT J
AU Slavc, I
Peyrl, A
Heinrich, M
Reismueller, B
Azizi, A
Kieran, M
Czech, T
Dieckmann, K
AF Slavc, Irene
Peyrl, Andreas
Heinrich, Monika
Reismueller, Bettina
Azizi, Amedeo
Kieran, Mark
Czech, Thomas
Dieckmann, Karin
TI METRONOMIC AND TARGETED ANTIANGIOGENESIS THERAPY FOR CHILDREN WITH
RECURRENT EMBRYONAL BRAIN TUMORS
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Slavc, Irene; Peyrl, Andreas; Heinrich, Monika; Reismueller, Bettina; Azizi, Amedeo] Med Univ Vienna, Dept Pediat, Vienna, Austria.
[Czech, Thomas] Med Univ Vienna, Dept Neurosurg, Vienna, Austria.
[Dieckmann, Karin] Med Univ Vienna, Dept Radiotherapy, Vienna, Austria.
[Kieran, Mark] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2011
VL 57
IS 5
BP 804
EP 804
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 824ZB
UT WOS:000295239600394
ER
PT J
AU Robison, N
Campigotta, F
Chi, SS
Manley, P
Turner, C
Zimmerman, MA
Chordas, C
Allen, J
Goldman, S
Rubin, J
Isakoff, M
Pan, W
Khatib, Z
Comito, M
Bendel, A
Pietrantonio, J
Kondrat, L
Hubbs, S
Neuberg, D
Kieran, M
AF Robison, Nathan
Campigotta, Federico
Chi, Susan
Manley, Peter
Turner, Christopher
Zimmerman, Mary Ann
Chordas, Christine
Allen, Jeffrey
Goldman, Stewart
Rubin, Joshua
Isakoff, Michael
Pan, Wilbur
Khatib, Ziad
Comito, Melanie
Bendel, Anne
Pietrantonio, Jay
Kondrat, Laura
Hubbs, Shannon
Neuberg, Donna
Kieran, Mark
TI A PHASE II TRIAL OF A MULTI-AGENT ORAL ANTIANGIOGENIC (METRONOMIC)
REGIMEN IN CHILDREN WITH RECURRENT OR PROGRESSIVE CANCER
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Campigotta, Federico; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA.
[Chi, Susan; Manley, Peter; Turner, Christopher; Zimmerman, Mary Ann; Chordas, Christine; Pietrantonio, Jay; Kondrat, Laura; Hubbs, Shannon; Kieran, Mark] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Allen, Jeffrey] NYU, Dept Pediat, Sch Med, New York, NY 10016 USA.
[Goldman, Stewart] Childrens Mem Hosp, Dept Pediat, Chicago, IL 60614 USA.
[Rubin, Joshua] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Isakoff, Michael] Connecticut Childrens Med Ctr, Dept Pediat, Hartford, CT USA.
[Pan, Wilbur] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pediat, New Brunswick, NJ 08903 USA.
[Khatib, Ziad] Miami Childrens Hosp, Dept Pediat, Miami, FL USA.
[Comito, Melanie] Penn State Hershey Childrens Hosp, Dept Pediat, Hershey, PA USA.
[Bendel, Anne] Childrens Hosp & Clin Minnesota, Dept Pediat Hematol Oncol, Minneapolis, MN USA.
NR 0
TC 2
Z9 2
U1 0
U2 1
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 NOV
PY 2011
VL 57
IS 5
BP 815
EP 815
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 824ZB
UT WOS:000295239600438
ER
PT J
AU Denburg, A
Sung, L
Joffe, S
Howard, S
AF Denburg, Avram
Sung, Lillian
Joffe, Steven
Howard, Scott
TI PEDIATRIC ONCOLOGY RESEARCH IN LOW INCOME COUNTRIES: ETHICAL CONCEPTS
AND CHALLENGES
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Denburg, Avram] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Joffe, Steven] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Howard, Scott] St Jude Childrens Hosp, Memphis, TN 38105 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2011
VL 57
IS 5
BP 835
EP 836
PG 2
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 824ZB
UT WOS:000295239600524
ER
PT J
AU Reilly, C
Porter, J
AF Reilly, Christine
Porter, Janet
TI PARENT ENGAGEMENT IN DESIGNING CARE AT DANA-FARBER CHILDREN'S HOSPITAL
CANCER CENTER
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Reilly, Christine] Dana Farber Childrens Hosp, Ctr Canc, Whitman, MA USA.
[Porter, Janet] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2011
VL 57
IS 5
BP 836
EP 836
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 824ZB
UT WOS:000295239600527
ER
PT J
AU Kunadian, V
Pride, YB
Buros, JL
Ciaglo, LN
Morrow, DA
Gibson, CM
AF Kunadian, Vijayalakshmi
Pride, Yuri B.
Buros, Jacqueline L.
Ciaglo, Lauren N.
Morrow, David A.
Gibson, C. Michael
TI Coronary flow reserve varies depending upon the location within the
artery it is assessed and the TIMI myocardial perfusion grade: a PROTECT
TIMI-30 analysis
SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS
LA English
DT Article
DE TIMI myocardial perfusion grade; Corrected TIMI frame count; Coronary
flow reserve; Adenosine; Myocardial perfusion
ID FRAME COUNT METHOD; INTRACORONARY DOPPLER; REACTIVE HYPEREMIA;
BLOOD-FLOW; ANGIOPLASTY; INFARCTION; MECHANISM; VELOCITY
AB Coronary flow reserve (CFR) is a measure of the capacity of the epicardial coronary artery and the microvasculature to achieve maximal blood flow in response to hyperemic stimulation. It is not known whether the CFR varies along the length of the artery. Likewise, the interaction between CFR and the thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade (TMPG) is unknown. CFR was measured using the number of cineframes required for the contrast to traverse the same length of the coronary artery before and following the administration of intracoronary adenosine. Following percutaneous coronary intervention (PCI), CFR was assessed both proximal and distal to the lesion in 192 consecutive patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) from the PROTECT TIMI-30 trial. TMPG was also assessed. The difference between the distal and proximal CFR for patients with TMPG 0/1 (n = 76) was 0.11 (95% CI 0.01-0.20, P = 0.026), while among those with TMPG 2/3 (n = 114) it was -0.02 (95% CI -0.09-0.06, P = 0.65). The difference in the CFR between the distal and proximal segments among patients with TMPG 0/1 and TMPG 2/3 was significant (P interaction = 0.044). Following PCI among patients with impaired TMPG (0/1) in the setting of NSTEACS, CFR varies significantly between the proximal and distal segment of coronary arteries and is associated with higher (greater) distal CFR.
C1 [Pride, Yuri B.; Buros, Jacqueline L.; Ciaglo, Lauren N.; Gibson, C. Michael] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cardiovasc Div,Dept Med,PERFUSE Study Grp, Boston, MA 02115 USA.
[Kunadian, Vijayalakshmi] Newcastle Univ, Inst Cellular Med, Fac Med Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Kunadian, Vijayalakshmi] Newcastle Upon Tyne Hosp NHS Fdn Trust, Freeman Hosp, Newcastle Upon Tyne, Tyne & Wear, England.
[Morrow, David A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Div,Dept Med,TIMI Study Grp, Boston, MA 02115 USA.
RP Gibson, CM (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cardiovasc Div,Dept Med,PERFUSE Study Grp, Boston, MA 02115 USA.
EM mgibson@perfuse.org
OI Buros, Jacqueline/0000-0001-9588-4889
FU Schering-Plough Research Institute in Kennilworth, NJ
FX PROTECT-TIMI 30 was supported in part by a grant from Schering-Plough
Research Institute in Kennilworth, NJ.
NR 13
TC 2
Z9 4
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0929-5305
J9 J THROMB THROMBOLYS
JI J. Thromb. Thrombolysis
PD NOV
PY 2011
VL 32
IS 4
BP 448
EP 452
DI 10.1007/s11239-011-0617-2
PG 5
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 826CW
UT WOS:000295330000009
PM 21713377
ER
PT J
AU Sarma, SV
Nguyen, DP
Czanner, G
Wirth, S
Wilson, MA
Suzuki, W
Brown, EN
AF Sarma, Sridevi V.
Nguyen, David P.
Czanner, Gabriela
Wirth, Sylvia
Wilson, Matthew A.
Suzuki, Wendy
Brown, Emery N.
TI Computing Confidence Intervals for Point Process Models
SO NEURAL COMPUTATION
LA English
DT Article
ID RECEPTIVE-FIELD PLASTICITY; CORTEX; HIPPOCAMPUS; MONKEYS; ADULT; MAP
AB Characterizing neural spiking activity as a function of intrinsic and extrinsic factors is important in neuroscience. Point process models are valuable for capturing such information; however, the process of fully applying these models is not always obvious. A complete model application has four broad steps: specification of the model, estimation of model parameters given observed data, verification of the model using goodness of fit, and characterization of the model using confidence bounds. Of these steps, only the first three have been applied widely in the literature, suggesting the need to dedicate a discussion to how the time-rescaling theorem, in combination with parametric bootstrap sampling, can be generally used to compute confidence bounds of point process models. In our first example, we use a generalized linear model of spiking propensity to demonstrate that confidence bounds derived from bootstrap simulations are consistent with those computed from closed-form analytic solutions. In our second example, we consider an adaptive point process model of hippocampal place field plasticity for which no analytical confidence bounds can be derived. We demonstrate how to simulate bootstrap samples from adaptive point process models, how to use these samples to generate confidence bounds, and how to statistically test the hypothesis that neural representations at two time points are significantly different. These examples have been designed as useful guides for performing scientific inference based on point process models.
C1 [Sarma, Sridevi V.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA.
[Nguyen, David P.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA.
[Nguyen, David P.; Wilson, Matthew A.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Czanner, Gabriela] Univ Warwick, Warwick Mfg Grp, Coventry CV4 7AL, W Midlands, England.
[Czanner, Gabriela] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
[Wirth, Sylvia] CNRS, Inst Cognit Sci, F-69675 Bron, France.
[Suzuki, Wendy] NYU, Ctr Neural Sci, New York, NY 10003 USA.
[Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Neurosci Stat Res Lab, Boston, MA 02114 USA.
[Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Sarma, SV (reprint author), Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA.
EM sree@jhu.edu; dpnguyen@alum.mit.edu; gabriela.czanner@warwick.ac.uk;
swirth@isc.cnrs.fr; mwilson@mit.edu; wendy@cns.nyu.edu;
enb@neurostat.mit.edu
FU Burrough's Wellcome Fund; L'Oreal for Women in Science fellowship; NIH
[MH59733, DP1 OD003646-01, DA015644, MH58847]; McKnight Foundation; John
Merck Scholars Award
FX We thank Uri Eden for valuable discussions. Support was provided by
Burrough's Wellcome Fund and L'Oreal for Women in Science fellowship to
S. V. S, NIH MH59733 and NIH Pioneer Award DP1 OD003646-01 to E.N.B, NIH
DA015644 to E.N.B. and W. A. S., NIH MH58847 to W. A. S., a McKnight
Foundation grant to W. A. S., and a John Merck Scholars Award to W.A.S.
NR 28
TC 4
Z9 4
U1 0
U2 4
PU MIT PRESS
PI CAMBRIDGE
PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA
SN 0899-7667
J9 NEURAL COMPUT
JI Neural Comput.
PD NOV
PY 2011
VL 23
IS 11
BP 2731
EP 2745
PG 15
WC Computer Science, Artificial Intelligence; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA 825ZO
UT WOS:000295321100001
PM 21851280
ER
PT J
AU Tantawy, MN
Peterson, TE
Jones, CK
Johnson, K
Rook, JM
Conn, PJ
Baldwin, RM
Ansari, MS
Kessler, RM
AF Tantawy, Mohammed N.
Peterson, Todd E.
Jones, Carrie K.
Johnson, Kari
Rook, Jerri M.
Conn, P. Jeffrey
Baldwin, Ronald M.
Ansari, M. Sib
Kessler, Robert M.
TI Impact of Isoflurane Anesthesia on D2 Receptor Occupancy by
[F-18]fallypride Measured by MicroPET With a Modified Logan Plot
SO SYNAPSE
LA English
DT Article
DE [F-18]fallypride; dopamine (DA) receptors; isoflurane; graphical
analysis; microPET
ID POSITRON-EMISSION-TOMOGRAPHY; DOPAMINE RELEASE; RAT-BRAIN;
NONHUMAN-PRIMATES; IN-VIVO; BINDING; PET; RADIOLIGAND; STRIATUM; REGIONS
AB In the previous work, we reported a method that utilized imaging data collected from 60 to 120 min following [F-18] fallypride administration to estimate the distribution volume ratio DVR' (DVR' proportional to DVR; DVR = 1 + BPND, where BPND is a measure of receptor density, DA D2 in this case). In this work, we use this method to assess the effects of isoflurane anesthesia on [F-18] fallypride DVR'. Methods: Rats were injected with [F-18] fallypride either unconsciously under similar to 1.5% isoflurane via the tail vein (Group 1) or consciously via a catheter inserted either in the jugular vein (Group 2) or the tail vein (Group 3). After about 1 h of free access to food and water the rats were anesthetized with 1.5% isoflurane and imaged in a microPET for 60 min. The rats that were injected consciously (Groups 2 and 3) were placed in a rat restrainer during [F-18]fallypride injection. They were habituated in that restrainer for 3 days prior to the experiment day to minimize restraint-related stress. For comparison, a control group of rats was imaged for 120 min simultaneously with the administration of [F-18]fallypride i.v. while under 1.5% isoflurane. The DVR' estimates from the 60 min acquisitions were compared with the DVR' from the last 60 min of the 120 min acquisitions (after neglecting the first 60 min). In addition, the striatal time-activity curves were fit with a 2-tissue + plasma compartment model using an arbitrary simulated plasma input function to obtain k(3)/k(4) (approximate to BPND) for the 60 and 120 min acquisitions. Results: Isoflurane anesthesia caused a significant reduction, up to 22%, in the DVR' estimates, which were 15.7 +/- 0.3 (mean +/- SE) for the controls, 17.7 +/- 0.3 for Group 1, 19.2 +/- 0.4 for Group 2, and 18.8 +/- 0.7 for Group 3. The compartmental model fit produced similar results, similar to 30% reduction in k(3)/k(4) for the 120-min acquisitions compared with the 60-min acquisitions (initial conscious uptake of the radiotracer). Conclusion: The results of this study demonstrate that isoflurane anesthesia significantly decreases striatal [F-18] fallypride BPND in rats. Of similar importance, this work demonstrates the effectiveness of delayed scans following radiotracer injection and the implication that different types of studies can be conducted simultaneously with this method, including studies of behavioral and environmental impact on brain receptors. Synapse 65:1173-1180, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Tantawy, Mohammed N.; Peterson, Todd E.; Baldwin, Ronald M.; Ansari, M. Sib; Kessler, Robert M.] Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA.
[Tantawy, Mohammed N.; Peterson, Todd E.; Baldwin, Ronald M.] Vanderbilt Univ, Med Ctr, Inst Imaging Sci, Nashville, TN 37232 USA.
[Jones, Carrie K.; Johnson, Kari; Rook, Jerri M.; Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA.
[Jones, Carrie K.; Johnson, Kari; Rook, Jerri M.; Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA.
[Jones, Carrie K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA.
EM n.tantawy@vanderbilt.edu
RI Conn, Peter/D-7848-2012
FU NCRR [1S10 RR17858]; Burroughs Welcome Fund
FX Contract grant sponsor: NCRR; Contract grant number: 1S10 RR17858; The
authors thank Jarrod True, Zou Yue, and Silvia Cambronero for their
assistance with the animal handling and injections. The research of Todd
E. Peterson, Ph.D. is supported by a Career Award at the Scientific
Interface from the Burroughs Welcome Fund.
NR 35
TC 5
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD NOV
PY 2011
VL 65
IS 11
BP 1173
EP 1180
DI 10.1002/syn.20955
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 827UU
UT WOS:000295455100007
PM 21584868
ER
PT J
AU Tran, HT
Barnich, N
Mizoguchi, E
AF Tran, Hoa T.
Barnich, Nicolas
Mizoguchi, Emiko
TI Potential role of chitinases and chitin-binding proteins in
host-microbial interactions during the development of intestinal
inflammation
SO HISTOLOGY AND HISTOPATHOLOGY
LA English
DT Review
DE Chitinase; Inflammatory bowel disease; Bacteria; Colonic epithelial
cells; CEACAM
ID INVASIVE ESCHERICHIA-COLI; BACILLUS-CIRCULANS WL-12; FIBROSIS EPIDEMIC
STRAIN; COLONIC EPITHELIAL-CELLS; CROHNS-DISEASE;
PSEUDOMONAS-AERUGINOSA; VIBRIO-CHOLERAE; GENE-EXPRESSION; ILEAL MUCOSA;
SERRATIA-MARCESCENS
AB The small and large intestines contain an abundance of luminal antigens derived from food products and enteric microorganisms. The function of intestinal epithelial cells is tightly regulated by several factors produced by enteric bacteria and the epithelial cells themselves. Epithelial cells actively participate in regulating the homeostasis of intestine, and failure of this function leads to abnormal and host-microbial interactions resulting in the development of intestinal inflammation. Major determinants of host susceptibility against luminal commensal bacteria include genes regulating mucosal immune responses, intestinal barrier function and microbial defense. Of note, it has been postulated that commensal bacterial adhesion and invasion on/into host cells may be strongly involved in the pathogenesis of inflammatory bowel disease (IBD). During the intestinal inflammation, the composition of the commensal flora is altered, with increased population of aggressive and detrimental bacteria and decreased populations of protective bacteria. In fact, some pathogenic bacteria, including Adherent-Invasive Escherichia coli, Listeria monocytogenes and Vibrio cholerae are likely to initiate their adhesion to the host cells by expressing accessory molecules such as chitinases and/or chitin-binding proteins on themselves. In addition, several inducible molecules (e.g., chitinase 3-like 1, CEACAM6) are also induced on the host cells (e.g. epithelial cells, lamina proprial macrophages) under inflammatory conditions, and are actively participated in the host-microbial interactions. In this review, we will summarize and discuss the potential roles of these important molecules during the development of acute and chronic inflammatory conditions.
C1 [Tran, Hoa T.; Mizoguchi, Emiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA.
[Barnich, Nicolas] Univ Clermont 1, Inst Natl Rech Agnom 2018, JE2526, Unite Contrat, Clermont Ferrand, France.
[Barnich, Nicolas] Inst Univ Technol Genie Biol, Aubiere, France.
[Mizoguchi, Emiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
RP Mizoguchi, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, GRJ 825D,55 Fruit St, Boston, MA 02114 USA.
EM emizoguchi@partners.org
FU National Institute of Health [DK 80070, DK74454, DK64289, DK43351]; Eli
and Edythe L. Broad Medical Foundation; American Gastroenterological
Association Foundation
FX We would like to thank Mr. Terry Danford Lott and Ms. Cindy W. Lau for
their excellent assistance in preparing this manuscript. This work has
been supported by National Institute of Health (DK 80070, DK74454,
DK64289 and DK43351), and grants from the Eli and Edythe L. Broad
Medical Foundation and American Gastroenterological Association
Foundation to EM.
NR 91
TC 18
Z9 20
U1 0
U2 13
PU F HERNANDEZ
PI MURCIA
PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN
SN 0213-3911
J9 HISTOL HISTOPATHOL
JI Histol. Histopath.
PD NOV
PY 2011
VL 26
IS 11
BP 1453
EP 1464
PG 12
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 823LN
UT WOS:000295123900010
PM 21938682
ER
PT J
AU Ng, KK
Thatte, HS
Spector, M
AF Ng, Karen K.
Thatte, Hemant S.
Spector, Myron
TI Chondrogenic differentiation of adult mesenchymal stem cells and
embryonic cells in collagen scaffolds
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
LA English
DT Article
DE cartilage tissue engineering; mesenchymal stem cell; embryonic cell;
collagen scaffold
ID SMOOTH-MUSCLE ACTIN; CARCINOMA-CELLS; IN-VITRO; CROSS-LINKING;
PROGENITOR CELLS; RETINOIC ACID; GAG SCAFFOLDS; MARROW; MODEL;
CONTRACTION
AB Many cell types and cellular microenvironments have been explored for articular cartilage tissue engineering. We compared the potential of bone marrow-derived mesenchymal stem cells (MSCs) and P19 embryonic carcinoma cells (ECCs), a pluripotent derivative of embryonic stem cells (ESCs), for cartilage histogenesis in porous collagen scaffolds in vitro. We found that while both MSCs and ECCs express alpha-smooth muscle actin (alpha-SMA), only MSCs exhibit condensation and contraction necessary for cartilage histogenesis. Furthermore, histology confirmed that only MSCs exhibited sulfated glycosaminoglycans and collagen type II formation after 14 days in culture. We conclude that MSCs appear to be superior over ECCs for cartilage regeneration under particular culture conditions. The alpha-SMA-expressing ECCs may not have contracted due to the absence of actin unit polymerization or the absence of myosin molecules. Our observations may explain the absence of a contractile scar in fetal wound healing. 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A: 275-282, 2011.
C1 [Ng, Karen K.; Spector, Myron] MIT, Cambridge, MA 02139 USA.
[Ng, Karen K.; Thatte, Hemant S.; Spector, Myron] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Thatte, Hemant S.; Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Spector, M (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM mspector@rics.bwh.harvard.edu
FU Department of Veterans Affairs; Veterans Health Administration;
Rehabilitation Research and Development Service
FX Contract grant sponsors: Department of Veterans Affairs, Veterans Health
Administration, Rehabilitation Research and Development Service
NR 34
TC 14
Z9 14
U1 1
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1549-3296
J9 J BIOMED MATER RES A
JI J. Biomed. Mater. Res. Part A
PD NOV
PY 2011
VL 99A
IS 2
BP 275
EP 282
DI 10.1002/jbm.a.33163
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 823RQ
UT WOS:000295142400015
PM 21858916
ER
PT J
AU Ticozzi, N
LeClerc, AL
van Blitterswijk, M
Keagle, P
McKenna-Yasek, DM
Sapp, PC
Silani, V
Wills, AM
Brown, RH
Landers, JE
AF Ticozzi, Nicola
LeClerc, Ashley Lyn
van Blitterswijk, Marka
Keagle, Pamela
McKenna-Yasek, Diane M.
Sapp, Peter C.
Silani, Vincenzo
Wills, Anne-Marie
Brown, Robert H., Jr.
Landers, John E.
TI Mutational analysis of TARDBP in neurodegenerative diseases
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE ALS; PD; AD; Genetics; TARDBP; TDP-43
ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; TDP-43
IMMUNOREACTIVITY; ALZHEIMERS-DISEASE; CLINICAL-DIAGNOSIS
AB Neurodegenerative diseases are often characterized by the presence of aggregates of misfolded proteins. TDP-43 is a major component of these aggregates in amyotrophic lateral sclerosis (ALS), but has also been observed in Alzheimer's (AD) and Parkinson's Diseases (PD). In addition, mutations in the TARDBP gene, encoding TDP-43, have been found to be a significant cause of familial ALS (FALS). All mutations, except for one, have been found in exon 6. To confirm this observation in ALS and to investigate whether TARDBP may play a role in the pathogenesis of AD and PD, we screened for mutations in exon 6 of the TARDBP gene in three cohorts composed of 376 AD, 463 PD (18% familial PD) and 376 ALS patients (50% FALS). We found mutations in similar to 7% of FALS and similar to 0.5% of sporadic ALS (SALS) patients, including two novel mutations, p.N352T and p.G384R. In contrast, we did not find TARDBP mutations in our cohort of AD and PD patients. These results suggest that mutations in TARDBP are not a significant cause of AD and PD. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Ticozzi, Nicola; LeClerc, Ashley Lyn; van Blitterswijk, Marka; Keagle, Pamela; McKenna-Yasek, Diane M.; Sapp, Peter C.; Brown, Robert H., Jr.; Landers, John E.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA.
[Ticozzi, Nicola; Silani, Vincenzo] Univ Milan, IRCCS Ist Auxol Italiano, Dino Ferrari Ctr, Dept Neurol, I-20149 Milan, Italy.
[Ticozzi, Nicola; Silani, Vincenzo] Univ Milan, IRCCS Ist Auxol Italiano, Dino Ferrari Ctr, Neurosci Lab, I-20149 Milan, Italy.
[Sapp, Peter C.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
[Sapp, Peter C.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Wills, Anne-Marie] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA.
RP Landers, JE (reprint author), LRB604,364 Plantat St, Worcester, MA 01605 USA.
EM n.ticozzi@fastwebnet.it; ashley.leclerc@umassmed.edu;
marka.van-blitterswijk@umassmed.edu; pamela.keagle@umassmed.edu;
diane.mckenna-yasek@umassmed.edu; peter.sapp@umassmed.edu;
vincenzo@silani.com; awills@partners.org; brownrhjr@aol.com;
john.landers@umassmed.edu
RI van Blitterswijk, Marka/H-7274-2012; Ticozzi, Nicola/K-8094-2016;
OI van Blitterswijk, Marka/0000-0002-3054-7053; Ticozzi,
Nicola/0000-0001-5963-7426; Silani, Vincenzo/0000-0002-7698-3854
FU ALS Therapy Alliance; Angel Fund; Pierre L. de Bourgknecht ALS Research
Foundation; Al-Athel ALS Research Foundation; ALS Family Charitable
Foundation; NINDS [NS050557]; Italian Ministry of Health [Art.56,
533F/N1]; Howard Hughes Medical Institute (HHMI); National Parkinson
Foundation; NIH [5P50NS038372-10]; Project ALS
FX A special thanks to the patients and their caregivers. Generous support
was provided by the ALS Therapy Alliance, Project ALS, the Angel Fund,
the Pierre L. de Bourgknecht ALS Research Foundation, the Al-Athel ALS
Research Foundation, the ALS Family Charitable Foundation and the NINDS
(NS050557). NT and VS were supported by the Italian Ministry of Health
(Malattie Neurodegenerative, ex Art.56, n.533F/N1). PS was supported by
the Howard Hughes Medical Institute (HHMI) through the auspices of Prof.
H. Robert Horvitz, an Investigator in the HHMI. The MGH PD DNA Bank is
supported by the National Parkinson Foundation and the NIH
(5P50NS038372-10).
NR 20
TC 18
Z9 19
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD NOV
PY 2011
VL 32
IS 11
BP 2096
EP 2099
DI 10.1016/j.neurobiolaging.2009.11.018
PG 4
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 824RV
UT WOS:000295220700017
PM 20031275
ER
PT J
AU Klein, AA
Slaymaker, VJ
Kelly, JF
AF Klein, Audrey A.
Slaymaker, Valerie J.
Kelly, John F.
TI The 12 Step Affiliation and Practices Scale: Development and initial
validation of a measure assessing 12 step affiliation
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE 12 Step affiliation; Psychometric; Alcohol dependence
ID CHEMICAL DEPENDENCY TREATMENT; 12-STEP PARTICIPATION; INPATIENT
TREATMENT; RELIABILITY; ABSTINENCE; MODEL; QUESTIONNAIRE; ADOLESCENTS;
ATTENDANCE; MEDIATORS
AB Objective: Research on instruments designed to measure endorsement of 12 step beliefs and practices among individuals with substance use disorders is virtually nonexistent. The goal of this study was to examine the psychometric properties of a novel instrument called the 12 Step Affiliation and Practices Scale (TSAPS) using a sample of young adults receiving 12 step-based residential treatment for alcohol and drug dependence.
Method: As part of a naturalistic treatment outcome study, 300 young adults receiving residential treatment completed the TSAPS and several other assessments during and after treatment. Analyses of the TSAPS examined its factor structure, internal consistency, sensitivity to change over time, and convergent and predictive validity.
Results: A maximum likelihood estimation factor analysis using oblique rotation produced 4 factors accounting for 61.16% of the variance. Internal consistency was very high and scores on the TSAPS significantly increased across the course of treatment. Convergent validity was demonstrated by relationships with scales of treatment attitudes, twelve step expectancies and commitment to sobriety. Predictive validity was also found, as evidenced by a relationship between total TSAPS score at 3 months post-treatment and percent of abstinent days at 6 months post-treatment.
Conclusions: The TSAPS shows promise as a psychometrically sound, internally reliable measure of 12 step affiliation and practices among individuals with substance dependence. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Klein, Audrey A.; Slaymaker, Valerie J.] Hazelden Fdn, Hazelden Butler Ctr Res, Center City, MN USA.
[Kelly, John F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Addict Med,Dept Psychiat, Cambridge, MA 02138 USA.
RP Klein, AA (reprint author), 15251 Pleasant Valley Rd,BC4, Center City, MN 55012 USA.
EM aklein@hazelden.org
FU NIAAA NIH HHS [R21 AA018185]
NR 27
TC 2
Z9 2
U1 1
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD NOV
PY 2011
VL 36
IS 11
BP 1045
EP 1051
DI 10.1016/j.addbeh.2011.06.011
PG 7
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 821OM
UT WOS:000294984300004
PM 21764222
ER
PT J
AU Doyle, SR
Donovan, DM
Simpson, TL
AF Doyle, Suzanne R.
Donovan, Dennis M.
Simpson, Tracy L.
TI Validation of a nine-dimensional measure of drinking motives for use in
clinical applications: The desired effects of drinking scale
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Drinking motives; Confirmatory factor analysis; Concurrent validity;
Predictive validity
ID ALCOHOL-RELATED PROBLEMS; COLLEGE-STUDENTS; YOUNG-PEOPLE; REASONS;
EXPECTANCIES; SAMPLE; QUESTIONNAIRE; DRINKERS; BEHAVIOR; INSTRUMENT
AB The Desired Effects of Drinking (DEOD) is a 36-item, 9-subscale, self-report measure assessing reasons for drinking, concerning three general motives for alcohol use: Coping, Social, and Enhancement. These subscales include Negative Feelings, Self-esteem, Relief, Positive Feelings, Social Facilitation, Assertion, Drug Effects, Sexual Enhancement, and Mental effects. As part of the COMBINE study, scores from the nine DEOD subscales, along with additional information about alcohol consumption and consequences, were incorporated into personalized client feedback as part of a motivational enhancement intervention and as a guide for the development of a plan for treatment and change. With responses from a clinical sample of 572 individuals seeking alcohol treatment, the 9-subscale structure of the instrument was substantiated through a second-order confirmatory factor analysis, revealing moderately large to large factor loadings and good indices of model fit. A third-order factor analysis indicated these nine subscales adequately represented the three drinking motives. It is suggested these three general motives for alcohol use, which may be more distinctly delineated into the nine dimensions reflected in the DEOD structure, can be used clinically to help plan appropriate interventions and facilitate behavior change. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Doyle, Suzanne R.; Donovan, Dennis M.] Univ Washington, Alcohol & Drug Abuse Inst, Seattle, WA 98105 USA.
[Donovan, Dennis M.; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
RP Doyle, SR (reprint author), Univ Washington, Alcohol & Drug Abuse Inst, 1107 NE 45th St,Suite 120, Seattle, WA 98105 USA.
EM srdoyle@u.washington.edu
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U10AA11715,
11716, 11721, 11727, 11756, 11768, 11773, 11776, 11777, 11783, 11787,
11799]; Combine Study Research Group; [U10AA011799]
FX The authors gratefully acknowledge support of the COMBINE study by the
National Institute on Alcohol Abuse and Alcoholism (NIAAA) through
Cooperative Agreements U10AA11715, 11716, 11721, 11727, 11756, 11768,
11773, 11776, 11777, 11783, 11787, 11799, and 11773.; Data presented in
this report were collected as part of the multisite COMBINE trial
Sponsored by the National Institute on Alcohol Abuse and Alcoholism, in
collaboration with the Combine Study Research Group. Preparation of this
report was supported in part by grant U10AA011799. A full listing of the
staff of the COMBINE study can be found at
http://www.cscc.unc.edu/combine/.
NR 64
TC 12
Z9 12
U1 2
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD NOV
PY 2011
VL 36
IS 11
BP 1052
EP 1060
DI 10.1016/j.addbeh.2011.06.012
PG 9
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 821OM
UT WOS:000294984300005
PM 21782346
ER
PT J
AU Furuno, JP
Johnson, JK
Schweizer, ML
Uche, A
Stine, OC
Shurland, SM
Forrest, GN
AF Furuno, Jon P.
Johnson, Jennifer K.
Schweizer, Marin L.
Uche, Anayochukwu
Stine, Oscar C.
Shurland, Simone M.
Forrest, Graeme N.
TI Community-associated Methicillin-resistant Staphylococcus aureus
Bacteremia and Endocarditis among HIV Patients: A cohort study
SO BMC INFECTIOUS DISEASES
LA English
DT Article
ID INJECTION-DRUG USERS; INFECTIVE ENDOCARDITIS; RISK-FACTORS;
ANTIRETROVIRAL THERAPY; ANTIBIOTIC-THERAPY; MRSA BACTEREMIA;
UNITED-STATES; MORTALITY; USA300; STRAINS
AB Background: HIV patients are at increased risk of development of infections and infection-associated poor health outcomes. We aimed to 1) assess the prevalence of USA300 community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) among HIV-infected patients with S. aureus bloodstream infections and. 2) determine risk factors for infective endocarditis and in-hospital mortality among patients in this population.
Methods: All adult HIV-infected patients with documented S. aureus bacteremia admitted to the University of Maryland Medical Center between January 1, 2003 and December 31, 2005 were included. CA-MRSA was defined as a USA300 MRSA isolate with the MBQBLO spa-type motif and positive for both the arginine catabolic mobile element and Panton-Valentin Leukocidin. Risk factors for S. aureus-associated infective endocarditis and mortality were determined using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Potential risk factors included demographic variables, comorbid illnesses, and intravenous drug use.
Results: Among 131 episodes of S. aureus bacteremia, 85 (66%) were MRSA of which 47 (54%) were CA-MRSA. Sixty-three patients (48%) developed endocarditis and 10 patients (8%) died in the hospital on the index admission Patients with CA-MRSA were significantly more likely to develop endocarditis (OR = 2.73, 95% CI = 1.30, 5.71). No other variables including comorbid conditions, current receipt of antiretroviral therapy, pre-culture severity of illness, or CD4 count were significantly associated with endocarditis and none were associated with in-hospital mortality.
Conclusions: CA-MRSA was significantly associated with an increased incidence of endocarditis in this cohort of HIV patients with MRSA bacteremia. In populations such as these, in which the prevalence of intravenous drug use and probability of endocarditis are both high, efforts must be made for early detection, which may improve treatment outcomes.
C1 [Forrest, Graeme N.] Portland VA Med Ctr, Div Infect Dis, Portland, OR USA.
[Forrest, Graeme N.] Oregon Hlth & Sci Univ, Portland, OR USA.
[Furuno, Jon P.] Oregon State Univ, Oregon Hlth & Sci Coll Pharm, Dept Pharm Practice, Portland, OR USA.
[Johnson, Jennifer K.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Schweizer, Marin L.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA.
[Furuno, Jon P.; Stine, Oscar C.; Shurland, Simone M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Uche, Anayochukwu] Oro Valley Hosp, Oro Valley, AZ USA.
[Shurland, Simone M.] US FDA, Silver Spring, MD USA.
RP Forrest, GN (reprint author), Portland VA Med Ctr, Div Infect Dis, Portland, OR USA.
EM forrestg@ohsu.edu
FU National Institutes of Health [M01 RR16500]; University of Maryland
General Clinical Research Center [1K01AI071015-03, 1K12RR023250-04];
Southern Medical Association; Cubist Pharmaceuticals, Inc.; Pfizer Inc.
FX National Institutes of Health Grants M01 RR16500, University of Maryland
General Clinical Research Center, 1K01AI071015-03 (J.P.F.) and
1K12RR023250-04 (J.K.J.) and a grant from the Southern Medical
Association (A.U.).; In the past 5 years J.P.F. and M.L.S. have served
as consults for Cubist Pharmaceuticals, Inc. Also, G.N.F. has received
research funding and honoraria from Cubist Pharmaceuticals, Inc. and
Pfizer Inc. M.L.S. has received research funding from Pfizer, Inc.
NR 43
TC 20
Z9 21
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD OCT 31
PY 2011
VL 11
AR 298
DI 10.1186/1471-2334-11-298
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA 846MX
UT WOS:000296909000001
PM 22040268
ER
PT J
AU Brunet, A
Ashbaugh, AR
Saumier, D
Nelson, M
Pitman, RK
Tremblay, J
Roullet, P
Birmes, P
AF Brunet, Alain
Ashbaugh, Andrea R.
Saumier, Daniel
Nelson, Marina
Pitman, Roger K.
Tremblay, Jacques
Roullet, Pascal
Birmes, Philippe
TI Does reconsolidation occur in humans: a reply
SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE
LA English
DT Editorial Material
ID FEAR; PROPRANOLOL; EXTINCTION; MEMORIES; REACTIVATION; ATTENUATION;
DISORDER; RETURN
C1 [Brunet, Alain; Ashbaugh, Andrea R.; Saumier, Daniel; Nelson, Marina; Tremblay, Jacques] McGill Univ, Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada.
[Pitman, Roger K.] Massachusetts Gen Hosp, Charlestown, MA USA.
[Pitman, Roger K.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Roullet, Pascal] Univ Toulouse 3, CRCA, F-31062 Toulouse, France.
[Birmes, Philippe] Univ Toulouse UPS, Toulouse, France.
[Birmes, Philippe] CHU Toulouse, Toulouse, France.
RP Brunet, A (reprint author), McGill Univ, Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada.
EM alain.brunet@mcgill.ca
NR 10
TC 13
Z9 13
U1 3
U2 18
PU FRONTIERS RES FOUND
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5153
J9 FRONT BEHAV NEUROSCI
JI Front. Behav. Neurosci.
PD OCT 31
PY 2011
VL 5
AR 74
DI 10.3389/fnbeh.2011.00074
PG 2
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 844EQ
UT WOS:000296730900001
PM 22065414
ER
PT J
AU Poulin, SP
Dautoff, R
Morris, JC
Barrett, LF
Dickerson, BC
AF Poulin, Stephane P.
Dautoff, Rebecca
Morris, John C.
Barrett, Lisa Feldman
Dickerson, Bradford C.
CA Alzheimers Dis Neuroimaging Initia
TI Amygdala atrophy is prominent in early Alzheimer's disease and relates
to symptom severity
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Hippocampus; Magnetic resonance imaging; Neuropsychiatric symptoms
ID MILD COGNITIVE IMPAIRMENT; MEDIAL TEMPORAL ATROPHY; MEMORY IMPAIRMENT;
INTRACRANIAL VOLUME; EARLY-STAGE; MRI; HIPPOCAMPUS; DISORDERS; DEMENTIA;
PLAQUES
AB Despite numerous studies on the role of medial temporal lobe structures in Alzheimer's disease (AD), the magnitude and clinical significance of amygdala atrophy have been relatively sparsely investigated. In this study, we used magnetic resonance imaging (MRI) to compare the level of amygdala atrophy to that of the hippocampus in very mild and mild AD subjects in two large samples (Sample 1 n = 90; Sample 2 n = 174). Using a series of linear regression analyses, we investigated whether amygdala atrophy is related to global cognitive functioning (Clinical Dementia Rating Sum of Boxes: CDR-SB: Mini Mental State Examination: MMSE) and neuropsychiatric status. Results indicated that amygdala atrophy was comparable to hippocampal atrophy in both samples. MMSE and CDR-SB were strongly related to amygdala atrophy, with amygdala atrophy predicting MMSE scores as well as hippocampal atrophy, but predicting CDR-SB scores less robustly. Amygdala atrophy was related to aberrant motor behavior, with potential relationships to anxiety and irritability. These results suggest that the magnitude of amygdala atrophy is comparable to that of the hippocampus in the earliest clinical stages of AD, and is related to global illness severity. There also appear to be specific relationships between the level of amygdala atrophy and neuropsychiatric symptoms that deserve further investigation. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Poulin, Stephane P.; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Dautoff, Rebecca; Barrett, Lisa Feldman; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Dickerson, Bradford C.] Massachusetts Gen Hosp, Frontotemporal Dementia Unit, Boston, MA 02114 USA.
[Dickerson, Bradford C.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA.
[Poulin, Stephane P.; Barrett, Lisa Feldman; Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Poulin, Stephane P.; Dautoff, Rebecca; Barrett, Lisa Feldman; Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA.
[Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA.
[Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Morris, John C.] Washington Univ, Sch Med, Alzheimers Dis Res Ctr, St Louis, MO USA.
RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
EM spoulin@nmr.mgh.harvard.edu; dautoff@nmr.mgh.harvard.edu;
morrisj@abraxas.wustl.edu; lisa@affective-science.org;
bradd@nmr.mgh.harvard.edu
RI Morris, John/A-1686-2012
FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes
of Health) [U01 AG024904]; National Institute on Aging; National
Institute of Biomedical Imaging and Bioengineering; NIH [P30 AG010129,
K01 AG030514]; Dana Foundation; Laval University, Quebec City, Canada;
[R01-AG029411]; [R21-AG029840]; [P50-AG05134]; [P50-AG05681];
[P01-AG003991]; [U24-RR021382]; [R01-MH56584]; [R01-AG030311];
[DP1OD003312]
FX Data collection and sharing for this project was funded by the
Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes
of Health Grant U01 AG024904). ADNI is funded by the National Institute
on Aging, the National Institute of Biomedical Imaging and
Bioengineering, and through generous contributions from the following:
Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb,
Eisai Global Clinical Development, Elan Corporation, Genentech, GE
Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli
Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer
Inc, F: Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as
non-profit partners the Alzheimer's Association and Alzheimer's Drug
Discovery Foundation, with participation from the U.S. Food and Drug
Administration. Private sector contributions to ADNI are facilitated by
the Foundation for the National Institutes of Health (www.fnih.org). The
grantee organization is the Northern California Institute for Research
and Education, and the study is coordinated by the Alzheimer's Disease
Cooperative Study at the University of California, San Diego. ADNI data
are disseminated by the Laboratory for Neuro Imaging at the University
of California, Los Angeles. This research was also supported by NIH
grants P30 AG010129, K01 AG030514, and the Dana Foundation. This work
was also supported by R01-AG029411, R21-AG029840, P50-AG05134,
P50-AG05681, and P01-AG003991, U24-RR021382, R01-MH56584, R01-AG030311,
and DP1OD003312. This work was supported in part by the McLaughlin
Dean's grant, Laval University, Quebec City, Canada.
NR 45
TC 73
Z9 76
U1 3
U2 23
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD OCT 31
PY 2011
VL 194
IS 1
BP 7
EP 13
DI 10.1016/j.pscychresns.2011.06.014
PG 7
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 841VW
UT WOS:000296544300002
PM 21920712
ER
PT J
AU Milane, L
Ganesh, S
Shah, S
Duan, ZF
Amiji, M
AF Milane, Lara
Ganesh, Shanthi
Shah, Shruti
Duan, Zhen-feng
Amiji, Mansoor
TI Multi-modal strategies for overcoming tumor drug resistance: Hypoxia,
the Warburg effect, stem cells, and multifunctional nanotechnology
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article; Proceedings Paper
CT 15th International Symposium on Recent Advances in Drug Delivery Systems
CY FEB 13-16, 2011
CL Salt Lake City, UT
SP Samyang Co, Abbott Vasc, Watson Pharmaceut, CibaVis, NOF, Boryung Pharmaceut, Green Cross, Kanarb, Univ Utah Coll Pharm, Teikoku Seiyako, Shiseido
DE Tumor hypoxia; Warburg's effect; Multidrug resistance; Cancer-initiating
(stem) cells; Multifunctional nanoparticles
ID IN-VIVO REVERSAL; MULTIDRUG-RESISTANCE; CANCER-CELLS; P-GLYCOPROTEIN;
BREAST-CANCER; TARGETED DELIVERY; RNA INTERFERENCE; GENE DELIVERY; SOLID
TUMOR; GLUCOSYLCERAMIDE SYNTHASE
AB Inefficiencies in systemic drug delivery and tumor residence as well as micro-environmental selection pressures contribute to the development of multidrug resistance (MDR) in cancer. Characteristics of MDR include abnormal vasculature, regions of hypoxia, up-regulation of ABC-transporters, aerobic glycolysis, and an elevated apoptotic threshold. Nano-sized delivery vehicles are ideal for treating MDR cancer as they can improve the therapeutic index of drugs and they can be engineered to achieve multifunctional parameters. The multifunctional ability of nanocarriers makes them more adept at treating heterogeneous tumor mass than traditional chemotherapy. Nanocarriers also have preferential tumor accumulation via the EPR effect; this accumulation can be further enhanced by actively targeting the biological profile of MDR cells. Perhaps the most significant benefit of using nanocarrier drug delivery to treat MDR cancer is that nanocarrier delivery diverts the effects of ABC-transporter mediated drug efflux; which is the primary mechanism of MDR. This review discusses the capabilities, applications, and examples of multifunctional nanocarriers for the treatment of MDR. This review emphasizes multifunctional nanocarriers that enhance drug delivery efficiency, the application of RNAi, modulation of the tumor apoptotic threshold, and physical approaches to overcome MDR. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Milane, Lara; Ganesh, Shanthi; Shah, Shruti; Amiji, Mansoor] Northeastern Univ, Sch Pharm, Dept Pharmaceut Sci, Boston, MA 02115 USA.
[Duan, Zhen-feng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA.
RP Amiji, M (reprint author), Northeastern Univ, Sch Pharm, Dept Pharmaceut Sci, 360 Huntington Ave, Boston, MA 02115 USA.
EM m.amiji@neu.edu
RI Amiji, Mansoor/A-4365-2014
OI Amiji, Mansoor/0000-0001-6170-881X
FU NCI NIH HHS [R01-CA119617, R01 CA119617, R01 CA119617-01, R01
CA119617-02, R01 CA119617-03, R01 CA119617-04, R01 CA119617-04S1,
R01-CA119617S1, R21 CA135594, R21 CA135594-01A2, R21 CA135594-02, U01
CA151452, U01-CA151452]
NR 125
TC 57
Z9 59
U1 3
U2 62
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
J9 J CONTROL RELEASE
JI J. Control. Release
PD OCT 30
PY 2011
VL 155
IS 2
BP 237
EP 247
DI 10.1016/j.jconrel.2011.03.032
PG 11
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 849CD
UT WOS:000297102200017
PM 21497176
ER
PT J
AU Steinbicker, AU
Liu, HL
Jiramongkolchai, K
Malhotra, R
Choe, EY
Busch, CJ
Graveline, AR
Kao, SM
Nagasaka, Y
Ichinose, F
Buys, ES
Brouckaert, P
Zapol, WM
Bloch, KD
AF Steinbicker, Andrea U.
Liu, Heling
Jiramongkolchai, Kim
Malhotra, Rajeev
Choe, Elizabeth Y.
Busch, Cornelius J.
Graveline, Amanda R.
Kao, Sonya M.
Nagasaka, Yasuko
Ichinose, Fumito
Buys, Emmanuel S.
Brouckaert, Peter
Zapol, Warren M.
Bloch, Kenneth D.
TI Nitric oxide regulates pulmonary vascular smooth muscle cell expression
of the inducible cAMP early repressor gene
SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY
LA English
DT Article
DE Nitric oxide; Vascular smooth muscle; cAMP-response element; Cyclic GMP;
Protein kinase A
ID DEPENDENT PROTEIN-KINASE; ELEMENT-BINDING PROTEIN; CYCLIC-GMP;
TRANSCRIPTION FACTOR; CREB PHOSPHORYLATION; SIGNAL-TRANSDUCTION; CGMP;
ACTIVATION; CALCIUM; MECHANISMS
AB Nitric oxide (NO) regulates vascular smooth muscle cell (VSMC) structure and function, in part by activating soluble guanylate cyclase (sGC) to synthesize cGMP. The objective of this study was to further characterize the signaling mechanisms by which NO regulates VSMC gene expression using transcription profiling. DNA microarrays were hybridized with RNA extracted from rat pulmonary artery smooth muscle cells (RPaSMC) exposed to the NO donor compound, S-nitroso-glutathione (GSNO). Many of the genes, whose expression was induced by GSNO, contain a cAMP-response element (CRE), of which one encoded the inducible cAMP early repressor (ICER). sGC and cAMP-dependent protein kinase, but not cGMP-dependent protein kinase, were required for NO-mediated phosphorylation of CRE-binding protein (CREB) and induction of ICER gene expression. Expression of a dominant-negative CREB in RPaSMC prevented the NO-mediated induction of CRE-dependent gene transcription and ICER gene expression. Pre-treatment of RPaSMC with the intracellular calcium (Ca(2+)) chelator, BAPTA-AM, blocked the induction of ICER gene expression by GSNO. The store-operated Ca(2+) channel inhibitors, 2-ABP, and SKF-96365, reduced the GSNO-mediated increase in ICER mRNA levels, while 2-ABP did not inhibit GSNO-induced CREB phosphorylation. Our results suggest that induction of ICER gene expression by NO requires both CREB phosphorylation and Ca(2+) signaling. Transcription profiling of RPaSMC exposed to GSNO revealed important roles for sGC, PKA, CREB, and Ca(2+) in the regulation of gene expression by NO. The induction of ICER in GSNO-treated RPaSMC highlights a novel crosstalk mechanism between cGMP and cAMP signaling pathways. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Steinbicker, Andrea U.; Jiramongkolchai, Kim; Graveline, Amanda R.; Nagasaka, Yasuko; Ichinose, Fumito; Buys, Emmanuel S.; Zapol, Warren M.; Bloch, Kenneth D.] Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Liu, Heling; Malhotra, Rajeev; Choe, Elizabeth Y.; Busch, Cornelius J.; Kao, Sonya M.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Liu, Heling; Malhotra, Rajeev; Choe, Elizabeth Y.; Busch, Cornelius J.; Kao, Sonya M.; Bloch, Kenneth D.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Brouckaert, Peter] Univ Ghent VIB, Dept Mol Biomed Res, B-9052 Ghent, Belgium.
RP Steinbicker, AU (reprint author), Univ Munster, Dept Anesthesiol & Intens Care Med, D-48149 Munster, Germany.
EM andrea.steinbicker@ukmuenster.de
OI Malhotra, Rajeev/0000-0003-0120-4630
FU German DFG [SW 119-3/1]; American Heart Association [9930085N,
10SDG2610313]; Howard Hughes Medical Institute [NHLBI T32HL007208];
FWO-Vlaanderen; UGent-GOA programs; Department of Anesthesia; NHLBI
[HL-57172, R01 HL074352]; INOTherapeutics; Massachusetts General
Hospital; Massachusetts General Hospital to Linde Corp (Munich,
Germany); Ikaria (Clinton, New Jersey)
FX This work was supported by the German DFG grant SW 119-3/1 (AUS), a
Scientist Development Grant 9930085N from the American Heart Association
(HL), a Research Training Fellowship for Medical Students from the
Howard Hughes Medical Institute (KJ), NHLBI T32HL007208 (RM), a
Scientist Development Grant 10SDG2610313 from the American Heart
Association (ESB), grants from the FWO-Vlaanderen and the UGent-GOA
programs (PB), as well as grants from the Department of Anesthesia at
MGH (WMZ) and grants from the NHLBI, HL-57172 and R01 HL074352 (KDB).;
KDB receives research Grant support via a sponsored research agreement
with INOTherapeutics and the Massachusetts General Hospital. WMZ
receives royalties on patents licensed by Massachusetts General Hospital
to Linde Corp (Munich, Germany) and Ikaria (Clinton, New Jersey) on
inhaled NO.
NR 43
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U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1089-8603
J9 NITRIC OXIDE-BIOL CH
JI Nitric Oxide-Biol. Chem.
PD OCT 30
PY 2011
VL 25
IS 3
BP 294
EP 302
DI 10.1016/j.niox.2011.05.006
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 837FZ
UT WOS:000296177800007
PM 21642009
ER
PT J
AU Houston, JP
Kohler, J
Ostbye, KM
Heinloth, A
Perlis, RH
AF Houston, John P.
Kohler, Jared
Ostbye, Katherine M.
Heinloth, Alexandra
Perlis, Roy H.
TI Association of catechol-O-methyltransferase variants with duloxetine
response in major depressive disorder
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Single nucleotide polymorphisms; Diplotype; rs165737
AB Single-nucleotide and diplotype associations with 17-item Hamilton Depression Rating Scale (HAMD(17)) total score changes were examined, based on catechol-O-methyltransferase (COMT) rs165599 status in duloxetine-treated, self-identified white patients with major depressive disorder. COMT rs165737 and a diplotype containing COMT rs165599 and COMT rs165737 were associated with HAMD17 total score changes. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Houston, John P.] Eli Lilly & Co, LLC, Dept Neurosci, Indianapolis, IN 46285 USA.
[Houston, John P.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA.
[Kohler, Jared; Ostbye, Katherine M.] BioStat Solut Inc, Pharmacogen, Mt Airy, MD USA.
[Heinloth, Alexandra] i3, Sci Commun, Ann Arbor, MI USA.
[Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Pharmacogen Lab, Boston, MA 02114 USA.
[Perlis, Roy H.] Harvard Univ, Sch Med, Boston, MA USA.
RP Houston, JP (reprint author), Eli Lilly & Co, LLC, Dept Neurosci, Mail Code 4103, Indianapolis, IN 46285 USA.
EM houston_john_p@lilly.com
NR 9
TC 3
Z9 5
U1 1
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD OCT 30
PY 2011
VL 189
IS 3
BP 475
EP 477
DI 10.1016/j.psychres.2011.07.002
PG 3
WC Psychiatry
SC Psychiatry
GA 836QM
UT WOS:000296126200027
PM 21788083
ER
PT J
AU Fayad, ZA
Mani, V
Woodward, M
Kallend, D
Abt, M
Burgess, T
Fuster, V
Ballantyne, CM
Stein, EA
Tardif, JC
Rudd, JHF
Farkouh, ME
Tawakol, A
AF Fayad, Zahi A.
Mani, Venkatesh
Woodward, Mark
Kallend, David
Abt, Markus
Burgess, Tracy
Fuster, Valentin
Ballantyne, Christie M.
Stein, Evan A.
Tardif, Jean-Claude
Rudd, James H. F.
Farkouh, Michael E.
Tawakol, Ahmed
CA Dal-PLAQUE Investigators
TI Safety and efficacy of dalcetrapib on atherosclerotic disease using
novel non-invasive multimodality imaging (dal-PLAQUE): a randomised
clinical trial
SO LANCET
LA English
DT Article
ID ESTER TRANSFER PROTEIN; HIGH-DENSITY-LIPOPROTEIN;
POSITRON-EMISSION-TOMOGRAPHY; CORONARY-HEART-DISEASE; RAPID EXTENDED
COVERAGE; CARDIOVASCULAR EVENTS; CHOLESTEROL LEVELS; HIGH-RESOLUTION;
STATIN THERAPY; BLOOD-PRESSURE
AB Background Dalcetrapib modulates cholesteryl ester transfer protein (CETP) activity to raise high-density lipoprotein cholesterol (HDL-C). After the failure of torcetrapib it was unknown if HDL produced by interaction with CETP had pro-atherogenic or pro-inflammatory properties. dal-PLAQUE is the first multicentre study using novel non-invasive multimodality imaging to assess structural and inflammatory indices of atherosclerosis as primary endpoints.
Methods In this phase 2b, double-blind, multicentre trial, patients (aged 18-75 years) with, or with high risk of, coronary heart disease were randomly assigned (1:1) to dalcetrapib 600 mg/day or placebo for 24 months. Randomisation was done with a computer-generated randomisation code and was stratified by centre. Patients and investigators were masked to treatment. Coprimary endpoints were MRI-assessed indices (total vessel area, wall area, wall thickness, and normalised wall index [average carotid]) after 24 months and (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT assessment of arterial inflammation within an index vessel (right carotid, left carotid, or ascending thoracic aorta) after 6 months, with no-harm boundaries established before unblinding of the trial. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00655473.
Findings 189 patients were screened and 130 randomly assigned to placebo (66 patients) or dalcetrapib (64 patients). For the coprimary MRI and PET/CT endpoints, CIs were below the no-harm boundary or the adverse change was numerically lower in the dalcetrapib group than in the placebo group. MRI-derived change in total vessel area was reduced in patients given dalcetrapib compared with those given placebo after 24 months; absolute change from baseline relative to placebo was -4.01 mm(2) (90% CI -7.23 to -0.80; nominal p=0.04). The PET/CT measure of index vessel most-diseased-segment target-to-background ratio (TBR) was not different between groups, but carotid artery analysis showed a 7% reduction in most-diseased-segment TBR in the dalcetrapib group compared with the placebo group (-7.3 [90% CI -13.5 to -0.8]; nominal p=0.07). Dalcetrapib did not increase office blood pressure and the frequency of adverse events was similar between groups.
Interpretation Dalcetrapib showed no evidence of a pathological effect related to the arterial wall over 24 months. Moreover, this trial suggests possible beneficial vascular effects of dalcetrapib, including the reduction in total vessel enlargement over 24 months, but long-term safety and clinical outcomes efficacy of dalcetrapib need to be analysed.
C1 [Fayad, Zahi A.; Mani, Venkatesh] Mt Sinai Sch Med, Dept Radiol, Translat & Mol Imaging Inst, New York, NY 10029 USA.
[Fayad, Zahi A.; Fuster, Valentin; Farkouh, Michael E.] Mt Sinai Sch Med, Cardiovasc Inst, New York, NY 10029 USA.
[Woodward, Mark] Univ Sydney, George Inst, Sydney, NSW 2006, Australia.
[Kallend, David] F Hoffmann La Roche Ltd, Basel, Switzerland.
[Burgess, Tracy] Hoffmann La Roche Inc, Nutley, NJ 07110 USA.
[Fuster, Valentin] CNIC, Madrid, Spain.
[Ballantyne, Christie M.] Baylor Coll Med, Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA.
[Stein, Evan A.] Metab & Atherosclerosis Res Ctr, Cincinnati, OH USA.
[Tardif, Jean-Claude] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.
[Rudd, James H. F.] Univ Cambridge, Div Cardiovasc Med, Cambridge, England.
[Farkouh, Michael E.] Peter Munk Cardiac Ctr, Toronto, ON, Canada.
[Farkouh, Michael E.] Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
[Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA USA.
[Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Fayad, ZA (reprint author), Mt Sinai Sch Med, Dept Radiol, Translat & Mol Imaging Inst, 1 Gustave L Levy Pl,Box 1234, New York, NY 10029 USA.
EM zahi.fayad@mssm.edu
RI Mani, Venkatesh/B-8939-2011; Woodward, Mark/D-8492-2015; Fuster,
Valentin/H-4319-2015;
OI Fuster, Valentin/0000-0002-9043-9986; Rudd, James/0000-0003-2243-3117;
Mani, Venkatesh/0000-0002-0432-2918
FU F Hoffmann-La Roche Ltd.; Roche; GlaxoSmithKline; Merck; VBL
Therapeutics; Novartis; Bristol-Myers Squibb; Via Pharmaceuticals;
Abbott; AstraZeneca; diaDexus; Kowa; Sanofi-Synthelabo; Takeda; National
Institutes of Health; American Diabetes Association; American Heart
Association; Amarin; F Hoffmann-La Roche Inc; Sanofi-Aventis;
Schering-Plough; National Institute for Health Research Cambridge
Biomedical Research Centre; BMS; Genentech; VBL
FX F Hoffmann-La Roche Ltd.; ZAF has received research grants from Roche,
GlaxoSmithKline, Merck, VBL Therapeutics, Novartis, Bristol-Myers
Squibb, and Via Pharmaceuticals, and honoraria from Roche. MW has
received honoraria from Roche. DK and MA are employees of F Hoffmann-La
Roche Ltd and receive share options. TB is an employee of F Hoffmann-La
Roche Inc. CMB has received grant or research support (paid to
institution, not individual) from Abbott, AstraZeneca, Bristol-Myers
Squibb, diaDexus, GlaxoSmithKline, Kowa, Merck, Novartis, Roche,
Sanofi-Synthelabo, Takeda, National Institutes of Health, American
Diabetes Association, and American Heart Association; is a consultant
for Abbott, Adnexus, Amylin, AstraZeneca, Bristol-Myers Squibb,
Esperion, Genentech, GlaxoSmithKline, Idera Pharma, Kowa, Merck,
Novartis, Omthera, Resverlogix, Roche, Sanofi-Synthelabo, and Takeda;
serves on the speaker's bureau of Abbott, AstraZeneca, GlaxoSmithKline,
and Merck; and has received honoraria from Abbott, AstraZeneca,
GlaxoSmithKline, Merck, Sanofi-Synthelabo, and Takeda. EAS has received
grant support (paid to institution, not individual) from AstraZeneca,
Abbott, GlaxoSmithKline, Amarin, F Hoffmann-La Roche Inc,
Sanofi-Aventis, Schering-Plough; serves on the speakers' bureau of
AstraZeneca; is a consultant or served on advisory board for F
Hoffmann-La Roche Inc, Sanofi-Aventis, and Schering-Plough. J-CT has
received research grants and honoraria from Roche. JHFR has received
honoraria from Roche and is part-supported by the National Institute for
Health Research Cambridge Biomedical Research Centre. MEF has received
honoraria from Roche. AT has received honoraria from Roche, BMS, and
Novartis; and research grants from Merck, BMS, Genentech,
GlaxoSmithKline, and VBL. VM and VF declare that they have no conflicts
of interest.
NR 64
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U1 1
U2 19
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 OCT 29
PY 2011
VL 378
IS 9802
BP 1547
EP 1559
DI 10.1016/S0140-6736(11)61383-4
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 844SL
UT WOS:000296767500020
PM 21908036
ER
PT J
AU Ellis, LZ
Liu, WM
Luo, YC
Okamoto, M
Qu, D
Dunn, JH
Fujita, M
AF Ellis, Lixia Z.
Liu, Weimin
Luo, Yuchun
Okamoto, Miyako
Qu, Dovina
Dunn, Jeffrey H.
Fujita, Mayumi
TI Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma
growth by inhibiting inflammasome and IL-1 beta secretion
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Green tea; Epigallocatechin-3-gallate; Melanoma; IL-1; Inflammasome;
NLRP1
ID NF-KAPPA-B; CELLS; (-)-EPIGALLOCATECHIN-3-GALLATE; ACTIVATION; MICE;
CANCER; PHARMACOKINETICS; METABOLITES; APOPTOSIS; CATECHINS
AB Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has been demonstrated to possess anti-inflammatory, antioxidant, anti-mutagenic and anti-carcinogenic properties. The anti-melanoma effect of EGCG has been previously suggested, but no clear mechanism of action has been established. In this study, we demonstrated that EGCG inhibits melanoma cell growth at physiological doses (0.1-1 mu M). In the search for mechanisms of EGCG-mediated melanoma cell suppression, we found that NF-kappa B was inhibited, and that reduced NF-kappa B activity was associated with decreased IL-1 beta secretion from melanoma cells. Since inflammasomes are involved in IL-1 beta secretion, we investigated whether IL-1 beta suppression was mediated by inflammasomes, and found that EGCG treatment led to downregulation of the inflammasome component, NLRP1, and reduced caspase-1 activation. Furthermore, silencing the expression of NLRP1 abolished EGCG-induced inhibition of tumor cell proliferation both in vitro and in vivo, suggesting a key role of inflammasomes in EGCG efficacy. This paper provides a novel mechanism for EGCG-induced melanoma inhibition: inflammasome downregulation -> decreased IL-1 beta secretion -> decreased NF-kappa B activities -> decreased cell growth. In addition, it suggests inflammasomes and IL-1 beta could be potential targets for future melanoma therapeutics. Published by Elsevier Inc.
C1 [Ellis, Lixia Z.; Liu, Weimin; Luo, Yuchun; Okamoto, Miyako; Qu, Dovina; Dunn, Jeffrey H.; Fujita, Mayumi] Univ Colorado, Sch Med, Dept Dermatol, Aurora, CO 80045 USA.
[Fujita, Mayumi] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA.
RP Fujita, M (reprint author), Univ Colorado, Sch Med, Dept Dermatol, Mail Stop 8127,12801 E 17th Ave,Room 4124, Aurora, CO 80045 USA.
EM mayumi.fujita@ucdenver.edu
RI Luo, Yuchun/B-8683-2014
FU Dermatology Foundation; Tadamitsu Cancer Research Fund; NIH [CA125833,
5T32AR007411]; Wendy Will Cancer Center
FX This work was supported by Grants from the Dermatology Foundation (to
M.F.), the Tadamitsu Cancer Research Fund (to M.F.), NIH Grants CA125833
(to M.F.), and the Wendy Will Cancer Center Fund (to M.F.). W.L. and
M.O. were supported by a training grant from NIH (5T32AR007411).
NR 32
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U2 16
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 OCT 28
PY 2011
VL 414
IS 3
BP 551
EP 556
DI 10.1016/j.bbrc.2011.09.115
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 868JL
UT WOS:000298519500019
PM 21982776
ER
PT J
AU Sarkar, A
Hochedlinger, K
AF Sarkar, Abby
Hochedlinger, Konrad
TI A Gutsy Way to Grow: Intestinal Stem Cells as Nutrient Sensors
SO CELL
LA English
DT Editorial Material
ID BEHAVIOR
AB Adult tissues can rapidly and reversibly change size to adapt to environmental and behavioral influences. In this issue, O'Brien et al. (2011) demonstrate that fly intestinal stem cells alter their division patterns in response to food availability to drive organ growth.
C1 [Sarkar, Abby; Hochedlinger, Konrad] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
[Sarkar, Abby; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Sarkar, Abby; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Sarkar, Abby; Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA 02114 USA.
[Sarkar, Abby; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Hochedlinger, K (reprint author), Harvard Univ, Howard Hughes Med Inst, 7 Divin Ave, Cambridge, MA 02138 USA.
EM khochedlinger@helix.mgh.harvard.edu
NR 10
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Z9 2
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 28
PY 2011
VL 147
IS 3
BP 483
EP 486
DI 10.1016/j.cell.2011.10.006
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 842EH
UT WOS:000296573700002
PM 22036555
ER
PT J
AU Trompouki, E
Bowman, TV
Lawton, LN
Fan, ZP
Wu, DC
DiBiase, A
Martin, CS
Cech, JN
Sessa, AK
Leblanc, JL
Li, PL
Durand, EM
Mosimann, C
Heffner, GC
Daley, GQ
Paulson, RF
Young, RA
Zon, LI
AF Trompouki, Eirini
Bowman, Teresa V.
Lawton, Lee N.
Fan, Zi Peng
Wu, Dai-Chen
DiBiase, Anthony
Martin, Corey S.
Cech, Jennifer N.
Sessa, Anna K.
Leblanc, Jocelyn L.
Li, Pulin
Durand, Ellen M.
Mosimann, Christian
Heffner, Garrett C.
Daley, George Q.
Paulson, Robert F.
Young, Richard A.
Zon, Leonard I.
TI Lineage Regulators Direct BMP and Wnt Pathways to Cell-Specific Programs
during Differentiation and Regeneration
SO CELL
LA English
DT Article
ID EMBRYONIC STEM-CELLS; UCSC GENOME BROWSER; TRANSCRIPTION FACTORS;
BETA-CATENIN; MEGAKARYOCYTIC DIFFERENTIATION; HEMATOPOIETIC PROGENITORS;
SIGNALING PATHWAYS; GENE ACTIVATION; GAMMA-CATENIN; PROTEIN
AB BMP and Wnt signaling pathways control essential cellular responses through activation of the transcription factors SMAD (BMP) and TCF (Wnt). Here, we show that regeneration of hematopoietic lineages following acute injury depends on the activation of each of these signaling pathways to induce expression of key blood genes. Both SMAD1 and TCF7L2 co-occupy sites with master regulators adjacent to hematopoietic genes. In addition, both SMAD1 and TCF7L2 follow the binding of the predominant lineage regulator during differentiation from multipotent hematopoietic progenitor cells to erythroid cells. Furthermore, induction of the myeloid lineage regulator C/EBP alpha in erythroid cells shifts binding of SMAD1 to sites newly occupied by C/EBP alpha, whereas expression of the erythroid regulator GATA1 directs SMAD1 loss on nonerythroid targets. We conclude that the regenerative response mediated by BMP and Wnt signaling pathways is coupled with the lineage master regulators to control the gene programs defining cellular identity.
C1 [Trompouki, Eirini; Bowman, Teresa V.; DiBiase, Anthony; Martin, Corey S.; Cech, Jennifer N.; Sessa, Anna K.; Leblanc, Jocelyn L.; Li, Pulin; Durand, Ellen M.; Mosimann, Christian; Zon, Leonard I.] Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA.
[Trompouki, Eirini; Bowman, Teresa V.; DiBiase, Anthony; Martin, Corey S.; Cech, Jennifer N.; Sessa, Anna K.; Leblanc, Jocelyn L.; Li, Pulin; Durand, Ellen M.; Mosimann, Christian; Zon, Leonard I.] Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp Boston,Harvard Stem Cell Inst, Boston, MA 02115 USA.
[Trompouki, Eirini; Bowman, Teresa V.; DiBiase, Anthony; Martin, Corey S.; Cech, Jennifer N.; Sessa, Anna K.; Leblanc, Jocelyn L.; Li, Pulin; Durand, Ellen M.; Mosimann, Christian; Zon, Leonard I.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Lawton, Lee N.; Fan, Zi Peng; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Wu, Dai-Chen; Paulson, Robert F.] Penn State Univ, Grad Program Biochem Microbiol & Mol Biol, University Pk, PA 16802 USA.
[Wu, Dai-Chen; Paulson, Robert F.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Heffner, Garrett C.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Heffner, Garrett C.; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Heffner, Garrett C.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Fan, Zi Peng] MIT, Computat & Syst Biol Program, Cambridge, MA 02142 USA.
RP Zon, LI (reprint author), Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
RI Young, Richard/F-6495-2012; cheng, yong/I-4270-2012;
OI Young, Richard/0000-0001-8855-8647; Trompouki,
Eirini/0000-0002-7242-8810
FU NIH [P50-NS40828, NIH-P30-HD18655, 5PO1HL32262-29, 5R01HL048801-18,
1R01DK080040-01, R01-HG002668, K01 DK085270-02, U01 HL100001, 1
RC2HL102815, T32HL007623]; ROFAR; HHMI; EMBO; Jane Coffin Childs
Memorial Fund
FX We would like to acknowledge A. Mullen and D. Orlando for helpful
discussions and sharing critical insights prior to publication and G.
Frampton for analytical advice and development of the ChIP-seq analysis
platform. We thank F. Rentzsch and M. Hammerschmidt for the Hs: BMP
zebrafish line, J. Tucker and M. Mullins for the Hs: Chordin zebrafish
line, and T. Schlaeger for the GATA2 expression plasmid. We are grateful
to X. Bai and R. White for critical reviews of the manuscript and O.
Tamplin for computational advice. The Whitehead Genome Technology Core
was instrumental in timely data production and analysis support,
especially S. Gupta. Microarray studies were performed by the Molecular
Genetics Core Facility at Children's Hospital Boston, supported by
NIH-P50-NS40828 and NIH-P30-HD18655. This work was supported by NIH #
5PO1HL32262-29 and # 5R01HL048801-18 (to L.I.Z), NIH 1R01DK080040-01 (to
R. F. P.), R01-HG002668 (to R. A. Y.), NIH K01 DK085270-02 (to T. V.
B.), NIH U01 HL100001, NIH 1 RC2HL102815, and ROFAR (to G. Q. D.), NIH
T32HL007623 (to G. C. H.), HHMI (to L.I.Z. and G. Q. D.), and EMBO
fellowship and Jane Coffin Childs Memorial Fund (to E. T.). L.I.Z. is a
founder and stock holder of Fate, Inc. and a scientific advisor for
Stemgent. G. Q. D. is a member of the Scientific Advisory Boards of MPM
Capital, Inc., Epizyme, Inc., and iPierian, Inc.
NR 60
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U1 2
U2 30
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 28
PY 2011
VL 147
IS 3
BP 577
EP 589
DI 10.1016/j.cell.2011.09.044
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 842EH
UT WOS:000296573700013
PM 22036566
ER
PT J
AU Boyer, L
Magoc, L
Dejardin, S
Cappillino, M
Paquette, N
Hinault, C
Charriere, GM
Ip, WKE
Fracchia, S
Hennessy, E
Erturk-Hasdemir, D
Reichhart, JM
Silverman, N
Lacy-Hulbert, A
Stuart, LM
AF Boyer, Laurent
Magoc, Lorin
Dejardin, Stephanie
Cappillino, Michael
Paquette, Nicholas
Hinault, Charlotte
Charriere, Guillaume M.
Ip, W. K. Eddie
Fracchia, Shannon
Hennessy, Elizabeth
Erturk-Hasdemir, Deniz
Reichhart, Jean-Marc
Silverman, Neal
Lacy-Hulbert, Adam
Stuart, Lynda M.
TI Pathogen-Derived Effectors Trigger Protective Immunity via Activation of
the Rac2 Enzyme and the IMD or Rip Kinase Signaling Pathway
SO IMMUNITY
LA English
DT Article
ID NECROTIZING FACTOR-I; INNATE IMMUNITY; RHO-GTPASES;
DROSOPHILA-MELANOGASTER; BACTERIAL EFFECTORS; FUNGAL-INFECTIONS;
ESCHERICHIA-COLI; TOXINS; SYSTEM; COMPLEX
AB Although infections with virulent pathogens often induce a strong inflammatory reaction, what drives the increased immune response to pathogens compared to nonpathogenic microbes is poorly understood. One possibility is that the immune system senses the level of threat from a microorganism and augments the response accordingly. Here, focusing on cytotoxic necrotizing factor 1 (CNF1), an Escherichia coli-derived effector molecule, we showed the host indirectly sensed the pathogen by monitoring for the effector that modified RhoGTPases. CNF1 modified Rac2, which then interacted with the innate immune adaptors IMD and Rip1-Rip2 in flies and mammalian cells, respectively, to drive an immune response. This response was protective and increased the ability of the host to restrict pathogen growth, thus defining a mechanism of effector-triggered immunity that contributes to how metazoans defend against microbes with pathogenic potential.
C1 [Boyer, Laurent; Magoc, Lorin; Dejardin, Stephanie; Cappillino, Michael; Paquette, Nicholas; Charriere, Guillaume M.; Ip, W. K. Eddie; Fracchia, Shannon; Hennessy, Elizabeth; Lacy-Hulbert, Adam; Stuart, Lynda M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hinault, Charlotte] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
[Hinault, Charlotte] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.
[Erturk-Hasdemir, Deniz; Silverman, Neal] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis, Worcester, MA 01605 USA.
[Reichhart, Jean-Marc] Univ Strasbourg, IBMC, UPR 9022, CNRS, F-67084 Strasbourg, France.
[Stuart, Lynda M.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
RP Boyer, L (reprint author), Ctr Mediterraneen Med Mol, INSERM, U895, C3M, F-06204 Nice 3, France.
EM boyerl@unice.fr; lstuart@partners.org
RI Ip, Eddie/C-3042-2012; Boyer, laurent/F-8921-2015; Charriere,
Guillaume/O-8317-2014;
OI Boyer, laurent/0000-0002-1375-1706; Charriere,
Guillaume/0000-0002-4796-1488; Lacy-Hulbert, Adam/0000-0003-2162-0156;
Silverman, Neal/0000-0002-4259-456X; hinault,
charlotte/0000-0002-3588-039X
FU Fondation Recherche Medical; MGH ECOR Fund for Medical Discovery; Ligue
Nationale Contre le Cancer; NIH/NIAID [PO1: A104420, RO1: A160025]; MGH
ECOR; NIH/NIAID
FX We would like to thank D. Ferrandon, J.L. Imler, and C. Kocks for
sharing fly stocks, K. Fitzgerald, J. Tschopp, G. Gacon, and the
Drosophila Genomics Resource Center for plasmids and E. Lemichez and G.
Flatau for providing CNF1 and CNF1 mutant purified proteins and cDNA and
anti-CNF1 antibody. We thank J. Dejardin, O. Visvikis, P. Leopold, M.
Maddugoda, A. Mettouchi, B. Ferrua, P. Munro, and A. Doye for technical
suggestions and F. Ausubel, A Ezekowitz, and E. Lemichez for critical
discussion and reading the manuscript. Technical support was provided by
the C3M Cell Imaging Facility (Francois Prodon) and the Taplin Mass
Spectrometric Facility (Ross Tomaino). L.B. was supported by Fondation
Recherche Medical, MGH ECOR Fund for Medical Discovery and Ligue
Nationale Contre le Cancer. This work was supported by NIH/NIAID grants
to J-M.R. (PO1: A104420) and N.S (RO1: A160025) and grants to L.S from
MGH ECOR and NIH/NIAID. All experiments were designed and interpreted by
L.B. and L.M.S. L.M.S. supervised the work with assistance from A.L-H.
L.B. and L.M.S. wrote the manuscript with input from A.L.-H. and N.S. In
vitro experiments were performed by L.B., S.D., C.H., G.M.C., EN., and
W.K.I. Flies were generated and maintained by L.B., M.C., and L.M. In
vivo experiments were performed by L.B., L.M., M.C., N.P., and S.F. IMD,
Relish, Dorsal and PGRP-LC reagents (constructs antibodies, etc.) were
generated and supplied by D.E.-H., J.M.R., and N.S.
NR 39
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U1 1
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD OCT 28
PY 2011
VL 35
IS 4
BP 536
EP 549
DI 10.1016/j.immuni.2011.08.015
PG 14
WC Immunology
SC Immunology
GA 843FM
UT WOS:000296657700013
PM 22018470
ER
PT J
AU Chauhan, D
Anderson, KC
AF Chauhan, Dharminder
Anderson, Kenneth C.
TI Proteasome inhibition, the pursuit of new cancer therapeutics, and the
adaptor molecule p130Cas
SO BMC BIOLOGY
LA English
DT Editorial Material
ID MULTIPLE-MYELOMA; DEGRADATION; AUTOPHAGY
AB Current interest in proteasome inhibitors for cancer therapy has stimulated considerable research efforts to identify the molecular pathway to their cytotoxicity with a view to identifying the mechanisms of sensitivity and resistance as well as informing the development of new drugs. Zhao and Vuori describe this month in BMC Biology experiments indicating a novel role of the adaptor protein p130Cas in sensitivity to apoptosis induced not only by proteasome inhibitors but also by the unrelated drug doxorubicin.
C1 [Chauhan, Dharminder] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA.
RP Chauhan, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, 44 Binney St, Boston, MA 02115 USA.
EM Dharminder_Chauhan@dfci.harvard.edu
FU NCI NIH HHS [R01CA050947, P01-CA078378]; PHS HHS [SPORE-P50100707]
NR 12
TC 2
Z9 2
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7007
J9 BMC BIOL
JI BMC Biol.
PD OCT 28
PY 2011
VL 9
AR 72
DI 10.1186/1741-7007-9-72
PG 4
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 838GY
UT WOS:000296276600002
PM 22034840
ER
PT J
AU Chaney, EF
Rubenstein, LV
Liu, CF
Yano, EM
Bolkan, C
Lee, M
Simon, B
Lanto, A
Felker, B
Uman, J
AF Chaney, Edmund F.
Rubenstein, Lisa V.
Liu, Chuan-Fen
Yano, Elizabeth M.
Bolkan, Cory
Lee, Martin
Simon, Barbara
Lanto, Andy
Felker, Bradford
Uman, Jane
TI Implementing collaborative care for depression treatment in primary
care: A cluster randomized evaluation of a quality improvement practice
redesign
SO IMPLEMENTATION SCIENCE
LA English
DT Article
ID MENTAL-HEALTH; QUERI SERIES; VETERANS; OUTCOMES; INTERVENTIONS;
MANAGEMENT; PROGRAMS; IMPACT; ORGANIZATIONS; GUIDELINES
AB Background: Meta-analyses show collaborative care models (CCMs) with nurse care management are effective for improving primary care for depression. This study aimed to develop CCM approaches that could be sustained and spread within Veterans Affairs (VA). Evidence-based quality improvement (EBQI) uses QI approaches within a research/clinical partnership to redesign care. The study used EBQI methods for CCM redesign, tested the effectiveness of the locally adapted model as implemented, and assessed the contextual factors shaping intervention effectiveness.
Methods: The study intervention is EBQI as applied to CCM implementation. The study uses a cluster randomized design as a formative evaluation tool to test and improve the effectiveness of the redesign process, with seven intervention and three non-intervention VA primary care practices in five different states. The primary study outcome is patient antidepressant use. The context evaluation is descriptive and uses subgroup analysis. The primary context evaluation measure is naturalistic primary care clinician (PCC) predilection to adopt CCM. For the randomized evaluation, trained telephone research interviewers enrolled consecutive primary care patients with major depression in the evaluation, referred enrolled patients in intervention practices to the implemented CCM, and re-surveyed at seven months.
Results: Interviewers enrolled 288 CCM site and 258 non-CCM site patients. Enrolled intervention site patients were more likely to receive appropriate antidepressant care (66% versus 43%, p = 0.01), but showed no significant difference in symptom improvement compared to usual care. In terms of context, only 40% of enrolled patients received complete care management per protocol. PCC predilection to adopt CCM had substantial effects on patient participation, with patients belonging to early adopter clinicians completing adequate care manager follow-up significantly more often than patients of clinicians with low predilection to adopt CCM (74% versus 48%%, p = 0.003).
Conclusions: Depression CCM designed and implemented by primary care practices using EBQI improved antidepressant initiation. Combining QI methods with a randomized evaluation proved challenging, but enabled new insights into the process of translating research-based CCM into practice. Future research on the effects of PCC attitudes and skills on CCM results, as well as on enhancing the link between improved antidepressant use and symptom outcomes, is needed.
C1 [Chaney, Edmund F.; Liu, Chuan-Fen; Felker, Bradford] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Rubenstein, Lisa V.; Yano, Elizabeth M.; Lee, Martin; Simon, Barbara; Lanto, Andy] VA Greater Los Angeles Healthcare Syst, VA Ctr Study Healthcare Provider Behav, Los Angeles, CA USA.
[Rubenstein, Lisa V.] RAND Hlth Program, Santa Monica, CA USA.
[Rubenstein, Lisa V.; Yano, Elizabeth M.; Lee, Martin] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Rubenstein, Lisa V.; Yano, Elizabeth M.; Lee, Martin] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Liu, Chuan-Fen; Uman, Jane] VA Puget Sound Hlth Care Syst, HSR&D NW Ctr Excellence Outcomes Res Older Adults, Seattle, WA USA.
[Bolkan, Cory] Washington State Univ, Dept Human Dev, Vancouver, WA USA.
RP Chaney, EF (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
EM chaney@u.washington.edu
FU Department of Veterans Affairs (VA) Health Services Research and
Development (HSRD) Service [MHI-99-375]; VA HSR&D Research Career
Scientist award [RCS 09-095]
FX Funding was provided by Department of Veterans Affairs (VA) Health
Services Research and Development (HSR&D) Service (grant number
MHI-99-375). The VA HSR&D Mental Health Quality Enhancement Research
Initiative (QUERI) staff provided critical assistance and oversight. Dr.
Yano's salary support during a portion of this work was provided by a VA
HSR&D Research Career Scientist award (grant number RCS 09-095). We
would like to specifically acknowledge the contributions of Laura
Bonner, Duncan Campbell, Jonathan Kanter, Debbie Mittman, Carol Oken,
Carol Simons, Susan Vivell and all other WAVES project research staff.
The study would not have been possible without the active partnership
and leadership of Randy Petzel, Scott Ober, Kathy Henderson, Joanne
Kirchner, Mike Davies, and all other participating administrators and
clinicians of VA VISNs 10, 16, and 23. Finally we thank VA Nursing
Service and more specifically Karen Vollen and Barbara Revay, pioneering
TIDES DCMs and the first TIDES nurse trainers. There are no contractual
rights to review the manuscript before submission, but there is a
requirement that Health Services Research and Development, Department of
Veterans Affairs, be given a copy of the accepted manuscript
NR 61
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U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD OCT 27
PY 2011
VL 6
AR 121
DI 10.1186/1748-5908-6-121
PG 15
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 849LX
UT WOS:000297128100001
PM 22032247
ER
PT J
AU Kumar, MS
Narla, A
Nonami, A
Mullally, A
Dimitrova, N
Ball, B
McAuley, JR
Poveromo, L
Kutok, JL
Galili, N
Raza, A
Attar, E
Gilliland, DG
Jacks, T
Ebert, BL
AF Kumar, Madhu S.
Narla, Anupama
Nonami, Atsushi
Mullally, Ann
Dimitrova, Nadya
Ball, Brian
McAuley, J. Randall
Poveromo, Luke
Kutok, Jeffrey L.
Galili, Naomi
Raza, Azra
Attar, Eyal
Gilliland, D. Gary
Jacks, Tyler
Ebert, Benjamin L.
TI Coordinate loss of a microRNA and protein-coding gene cooperate in the
pathogenesis of 5q(-) syndrome
SO BLOOD
LA English
DT Article
ID MESSENGER-RNAS; HUMAN CANCERS; STEM-CELLS; EXPRESSION; SUPPRESSOR;
MIR-145; FLI-1; IDENTIFICATION; 5Q-SYNDROME; PHENOTYPE
AB Large chromosomal deletions are among the most common molecular abnormalities in cancer, yet the identification of relevant genes has proven difficult. The 5q(-) syndrome, a subtype of myelodysplastic syndrome (MDS), is a chromosomal deletion syndrome characterized by anemia and thrombocytosis. Although we have previously shown that hemizygous loss of RPS14 recapitulates the failed erythroid differentiation seen in 5q(-) syndrome, it does not affect thrombocytosis. Here we show that a microRNA located in the common deletion region of 5q(-) syndrome, miR-145, affects megakaryocyte and erythroid differentiation. We find that miR-145 functions through repression of Fli-1, a megakaryocyte and erythroid regulatory transcription factor. Patients with del(5q) MDS have decreased expression of miR-145 and increased expression of Fli-1. Overexpression of miR-145 or inhibition of Fli-1 decreases the production of megakaryocytic cells relative to erythroid cells, whereas inhibition of miR-145 or overexpression of Fli-1 has a reciprocal effect. Moreover, combined loss of miR-145 and RPS14 cooperates to alter erythroid-megakaryocytic differentiation in a manner similar to the 5q(-) syndrome. Taken together, these findings demonstrate that coordinate deletion of a miRNA and a protein-coding gene contributes to the phenotype of a human malignancy, the 5q(-) syndrome. (Blood. 2011; 118(17): 4666-4673)
C1 [Narla, Anupama; Nonami, Atsushi; Mullally, Ann; Ball, Brian; McAuley, J. Randall; Poveromo, Luke; Gilliland, D. Gary; Ebert, Benjamin L.] Harvard Univ, Dept Med, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Kumar, Madhu S.; Dimitrova, Nadya; Jacks, Tyler] MIT, Dept Biol, Koch Inst Integrat Canc Res, Cambridge, MA USA.
[Kumar, Madhu S.; Dimitrova, Nadya; Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA USA.
[Narla, Anupama; Mullally, Ann; McAuley, J. Randall; Gilliland, D. Gary; Ebert, Benjamin L.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA.
[Narla, Anupama] Childrens Hosp, Dept Med, Boston, MA 02115 USA.
[Kutok, Jeffrey L.] Harvard Univ, Dept Pathol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Galili, Naomi; Raza, Azra] St Vincents Comprehens Canc Ctr, New York, NY USA.
[Attar, Eyal] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA.
[Gilliland, D. Gary; Ebert, Benjamin L.] Harvard Stem Cell Inst, Cambridge, MA USA.
[Gilliland, D. Gary] Harvard Univ, Howard Hughes Med Inst, Sch Med, Boston, MA 02115 USA.
RP Ebert, BL (reprint author), Harvard Univ, Dept Med, Brigham & Womens Hosp, Sch Med, Karp Res Bldg,1 Blackfan Circle,5th Fl,CHRB 05-21, Boston, MA 02115 USA.
EM benjamin_ebert@dfci.harvard.edu
FU National Cancer Institute [2-PO1-CA42063]; National Cancer Institute
(Cancer Center) [P30-CA14051]; National Heart, Lung, and Blood Institute
[R01-HL082945]; Burroughs Wellcome Fund Career Award in the Medical
Sciences
FX This work was supported by the National Cancer Institute (grant
2-PO1-CA42063), in part by the National Cancer Institute (Cancer Center
Support grant P30-CA14051), and in part by the National Heart, Lung, and
Blood Institute (grant R01-HL082945). B. L. E. was supported by a
Burroughs Wellcome Fund Career Award in the Medical Sciences. Animal
research was approved by Animal Welfare Assurance (A33033-01). M. S. K.
was an NSF Graduate Research Fellow. D. G. G. and T.J. are investigators
of the Howard Hughes Medical Institute. T.J. is a Ludwig Scholar.
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U1 0
U2 8
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 27
PY 2011
VL 118
IS 17
BP 4666
EP 4673
DI 10.1182/blood-2010-12-324715
PG 8
WC Hematology
SC Hematology
GA 839LY
UT WOS:000296368700029
PM 21873545
ER
PT J
AU Cheng, G
Liao, S
Wong, HK
Lacorre, DA
di Tomaso, E
Au, P
Fukumura, D
Jain, RK
Munn, LL
AF Cheng, Gang
Liao, Shan
Wong, Hon Kit
Lacorre, Delphine A.
di Tomaso, Emmanuelle
Au, Patrick
Fukumura, Dai
Jain, Rakesh K.
Munn, Lance L.
TI Engineered blood vessel networks connect to host vasculature via
wrapping-and-tapping anastomosis
SO BLOOD
LA English
DT Article
ID IN-VIVO; ENDOTHELIAL-CELLS; PROGENITOR CELLS; CORD BLOOD; TISSUE;
ANGIOGENESIS; MICROCIRCULATION; VASCULOGENESIS; GLIOBLASTOMA;
PERMEABILITY
AB Rapid blood perfusion is critical for postimplantation survival of thick, prevascularized bioartificial tissues. Yet the mechanism by which implanted vascular networks inosculate, or anastomose, with the host vasculature has been unknown, making it difficult to develop optimized strategies for facilitating perfusion. Here we show that implanted vascular networks anastomose with host vessels through a previously unidentified process of "wrapping and tapping" between the engrafted endothelial cells (ECs) and the host vasculature. At the host-implant interface, implanted ECs first wrap around nearby host vessels and then cause basement membrane and pericyte reorganization and localized displacement of the underlying host endothelium. In this way, the implanted ECs replace segments of host vessels to divert blood flow to the developing implanted vascular network. The process is facilitated by high levels of matrix metalloproteinase-14 and matrix metalloproteinase-9 expressed by the wrapping ECs. These findings open the door to new strategies for improving perfusion of tissue grafts and may have implications for other physiologic and pathologic processes involving postnatal vasculogenesis. (Blood. 2011; 118(17): 4740-4749)
C1 [Cheng, Gang; Liao, Shan; Wong, Hon Kit; Lacorre, Delphine A.; di Tomaso, Emmanuelle; Au, Patrick; Fukumura, Dai; Jain, Rakesh K.; Munn, Lance L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Cheng, Gang; Liao, Shan; Wong, Hon Kit; Lacorre, Delphine A.; di Tomaso, Emmanuelle; Au, Patrick; Fukumura, Dai; Jain, Rakesh K.; Munn, Lance L.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA.
EM munn@steele.mgh.harvard.edu
RI Munn, Lance/L-3950-2016; Wong, Hon-Kit/G-3944-2014
OI Munn, Lance/0000-0003-0698-7232; Wong, Hon-Kit/0000-0003-0049-8454
FU National Institutes of Health [HL64240, PO1 CA80124, R01-CA126642];
Federal Share/National Cancer Institute [R01-CA096915]
FX This work was supported by the National Institutes of Health (grant
HL64240, L. L. M.; grant PO1 CA80124, R.K.J., L. L. M., and D. F.; and
grant R01-CA126642, L. L. M.) and Federal Share/National Cancer
Institute (Proton Beam Program Income Grants, R.K.J., L. L. M., and D.
F.; and grant R01-CA096915, D.F.).
NR 34
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U1 0
U2 11
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 27
PY 2011
VL 118
IS 17
BP 4740
EP 4749
DI 10.1182/blood-2011-02-338426
PG 10
WC Hematology
SC Hematology
GA 839LY
UT WOS:000296368700039
PM 21835951
ER
PT J
AU Zuber, J
Shi, JW
Wang, E
Rappaport, AR
Herrmann, H
Sison, EA
Magoon, D
Qi, J
Blatt, K
Wunderlich, M
Taylor, MJ
Johns, C
Chicas, A
Mulloy, JC
Kogan, SC
Brown, P
Valent, P
Bradner, JE
Lowe, SW
Vakoc, CR
AF Zuber, Johannes
Shi, Junwei
Wang, Eric
Rappaport, Amy R.
Herrmann, Harald
Sison, Edward A.
Magoon, Daniel
Qi, Jun
Blatt, Katharina
Wunderlich, Mark
Taylor, Meredith J.
Johns, Christopher
Chicas, Agustin
Mulloy, James C.
Kogan, Scott C.
Brown, Patrick
Valent, Peter
Bradner, James E.
Lowe, Scott W.
Vakoc, Christopher R.
TI RNAi screen identifies Brd4 as a therapeutic target in acute myeloid
leukaemia
SO NATURE
LA English
DT Article
ID TRANSCRIPTIONAL PROGRAM; H3K79 METHYLATION; STEM-CELLS; IN-VIVO; C-MYC;
CLASSIFICATION; LEUKEMOGENESIS; EXPRESSION; MLL-AF9; INHIBITION
AB Epigenetic pathways can regulate gene expression by controlling and interpreting chromatin modifications. Cancer cells are characterized by altered epigenetic landscapes, and commonly exploit the chromatin regulatory machinery to enforce oncogenic gene expression programs(1). Although chromatin alterations are, in principle, reversible and often amenable to drug intervention, the promise of targeting such pathways therapeutically has been limited by an incomplete understanding of cancer-specific dependencies on epigenetic regulators. Here we describe a non-biased approach to probe epigenetic vulnerabilities in acute myeloid leukaemia (AML), an aggressive haematopoietic malignancy that is often associated with aberrant chromatin states(2). By screening a custom library of small hairpin RNAs (shRNAs) targeting known chromatin regulators in a genetically defined AML mouse model, we identify the protein bromodomain-containing 4 (Brd4) as being critically required for disease maintenance. Suppression of Brd4 using shRNAs or the small-molecule inhibitor JQ1 led to robust antileukaemic effects in vitro and in vivo, accompanied by terminal myeloid differentiation and elimination of leukaemia stem cells. Similar sensitivities were observed in a variety of human AML cell lines and primary patient samples, revealing that JQ1 has broad activity in diverse AML subtypes. The effects of Brd4 suppression are, at least in part, due to its role in sustaining Myc expression to promote aberrant self-renewal, which implicates JQ1 as a pharmacological means to suppress MYC in cancer. Our results establish small-molecule inhibition of Brd4 as a promising therapeutic strategy in AML and, potentially, other cancers, and highlight the utility of RNA interference (RNAi) screening for revealing epigenetic vulnerabilities that can be exploited for direct pharmacological intervention.
C1 [Lowe, Scott W.; Vakoc, Christopher R.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA.
[Zuber, Johannes] Res Inst Mol Pathol IMP, A-1030 Vienna, Austria.
[Shi, Junwei] SUNY Stony Brook, Mol & Cellular Biol Program, Stony Brook, NY 11794 USA.
[Rappaport, Amy R.; Lowe, Scott W.] Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
[Sison, Edward A.; Magoon, Daniel; Brown, Patrick] Johns Hopkins Univ, Sch Med, Div Pediat Oncol, Baltimore, MD 21231 USA.
[Qi, Jun; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Blatt, Katharina; Valent, Peter] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, A-1090 Vienna, Austria.
[Wunderlich, Mark; Mulloy, James C.] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
[Kogan, Scott C.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
RP Vakoc, CR (reprint author), Cold Spring Harbor Lab, Howard Hughes Med Inst, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM lowe@cshl.edu; vakoc@cshl.edu
RI Clovis, Jeff/C-1020-2009;
OI Vakoc, Christopher/0000-0002-1158-7180
FU Don Monti Memorial Research Foundation; Laurie Strauss Leukemia
Foundation; German Research Foundation (DFG); CSHL; NIH; Barbara
McClintock fellowship; Damon-Runyon Cancer Research Foundation; Smith
Family Foundation; Damon Runyon-Lilly Clinical Investigator Award;
Leukemia and Lymphoma Society (LLS); Leukemia and Lymphoma Society of
America; National Cancer Institute; Howard Hughes Medical Institute;
CSHL President's Council; SASS Foundation for Medical Research
FX We thank B. Ma, S. Muller and M. Weissenboeck for technical assistance;
J. Simon, E. Earl and L. Bianco for support with mouse work; C. dos
Santos for assistance with LSK FACS analysis; S. Hearn for microscopy
support; G. Hannon, K. Chang, and E. Hodges for shRNA technology
support; A. Gordon and M. Hammell for bioinformatics support; L. Dow for
assistance with mouse pathology sample preparation; and G. Blobel for
comments on the manuscript. We thank the Don Monti Memorial Research
Foundation and Laurie Strauss Leukemia Foundation for research support.
J.Z. was supported by a research fellowship from the German Research
Foundation (DFG) and by the Andrew Seligson Memorial Clinical Fellowship
at CSHL; A. R. R. was supported by an NIH traineeship and the Barbara
McClintock fellowship; J. E. B and J. Q. are supported by the
Damon-Runyon Cancer Research Foundation and Smith Family Foundation. P.
B. is supported by a Damon Runyon-Lilly Clinical Investigator Award and
a Leukemia and Lymphoma Society (LLS) Translational Research Program
Grant, and is an LLS Scholar in Clinical Research. S. W. L. is supported
by a Specialized Center of Research (SCOR) grant from the Leukemia and
Lymphoma Society of America, a Cancer Target Discovery and Development
(CTD2) grant from the National Cancer Institute, and by the Howard
Hughes Medical Institute; C. R. V., J. S. and E. W. are supported by the
CSHL President's Council and the SASS Foundation for Medical Research.
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 27
PY 2011
VL 478
IS 7370
BP 524
EP U124
DI 10.1038/nature10334
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200045
PM 21814200
ER
PT J
AU Bergwitz, C
Collins, MT
Kamath, RS
Rosenberg, AE
AF Bergwitz, Clemens
Collins, Michael T.
Kamath, Ravi S.
Rosenberg, Andrew E.
TI Case 33-2011: A 56-Year-Old Man with Hypophosphatemia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID TUMOR-INDUCED OSTEOMALACIA; OF-THE-LITERATURE; ONCOGENIC OSTEOMALACIA;
MESENCHYMAL TUMORS; AMELOBLASTIC FIBROSARCOMA; PHOSPHATE HOMEOSTASIS;
CALCIUM-METABOLISM; VITAMIN-D; FIBROBLAST-GROWTH-FACTOR-23; LOCALIZATION
C1 [Bergwitz, Clemens] Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA.
[Kamath, Ravi S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Bergwitz, Clemens] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Kamath, Ravi S.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Rosenberg, Andrew E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA.
FU Genzyme
FX Dr. Rosenberg reports receiving consulting fees from Genzyme. No other
potential conflict of interest relevant to this article was reported.
NR 27
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Z9 9
U1 0
U2 4
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 27
PY 2011
VL 365
IS 17
BP 1625
EP 1635
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 837HI
UT WOS:000296181800009
PM 22029985
ER
PT J
AU Szostak, JW
AF Szostak, Jack W.
TI An optimal degree of physical and chemical heterogeneity for the origin
of life?
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE origin of life; protocell; vesicle; fatty acids; genetic polymer
ID FATTY-ACID VESICLES; MODEL PROTOCELL; GENETIC SYSTEM; NUCLEIC-ACID;
MEMBRANES; GROWTH; LIGATION
AB The accumulation of pure, concentrated chemical building blocks, from which the essential components of protocells could be assembled, has long been viewed as a necessary, but extremely difficult step on the pathway to the origin of life. However, recent experiments have shown that moderately increasing the complexity of a set of chemical inputs can in some cases lead to a dramatic simplification of the resulting reaction products. Similarly, model protocell membranes composed of certain mixtures of amphiphilic molecules have superior physical properties than membranes composed of single amphiphiles. Moreover, membrane self-assembly under simple and natural conditions gives rise to heterogeneous mixtures of large multi-lamellar vesicles, which are predisposed to a robust pathway of growth and division that simpler and more homogeneous small unilamellar vesicles cannot undergo. Might a similar relaxation of the constraints on building block purity and homogeneity actually facilitate the difficult process of nucleic acid replication? Several arguments suggest that mixtures of monomers and short oligonucleotides may enable the chemical copying of polynucleotides of sufficient length and sequence complexity to allow for the emergence of the first nucleic acid catalysts. The question of the origin of life may become less daunting once the constraints of overly well-defined laboratory experiments are appropriately relaxed.
C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
EM szostak@molbio.mgh.harvard.edu
FU NASA; NSF
FX I thank Ting Zhu for help with figures, Ting Zhu and Itay Budin for
helpful comments on the manuscript, and the many current and past
members of my laboratory who have contributed to the development of the
protocell model. This work was supported in part by grants from NASA and
the NSF. The author is an Investigator of the Howard Hughes Medical
Institute.
NR 26
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U1 5
U2 39
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD OCT 27
PY 2011
VL 366
IS 1580
BP 2894
EP 2901
DI 10.1098/rstb.2011.0140
PG 8
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 821RW
UT WOS:000294993100006
PM 21930580
ER
PT J
AU Blagrove, M
Fouquet, NC
Henley-Einion, JA
Pace-Schott, EF
Davies, AC
Neuschaffer, JL
Turnbull, OH
AF Blagrove, Mark
Fouquet, Nathalie C.
Henley-Einion, Josephine A.
Pace-Schott, Edward F.
Davies, Anna C.
Neuschaffer, Jennifer L.
Turnbull, Oliver H.
TI Assessing the Dream-Lag Effect for REM and NREM Stage 2 Dreams
SO PLOS ONE
LA English
DT Article
ID MEMORY CONSOLIDATION; SLEEP; EVENTS; REPLICATION; MENTATION; STATES
AB This study investigates evidence, from dream reports, for memory consolidation during sleep. It is well-known that events and memories from waking life can be incorporated into dreams. These incorporations can be a literal replication of what occurred in waking life, or, more often, they can be partial or indirect. Two types of temporal relationship have been found to characterize the time of occurrence of a daytime event and the reappearance or incorporation of its features in a dream. These temporal relationships are referred to as the day-residue or immediate incorporation effect, where there is the reappearance of features from events occurring on the immediately preceding day, and the dream-lag effect, where there is the reappearance of features from events occurring 5-7 days prior to the dream. Previous work on the dream-lag effect has used spontaneous home recalled dream reports, which can be from Rapid Eye Movement Sleep (REM) and from non-Rapid Eye Movement Sleep (NREM). This study addresses whether the dream-lag effect occurs only for REM sleep dreams, or for both REM and NREM stage 2 (N2) dreams. 20 participants kept a daily diary for over a week before sleeping in the sleep laboratory for 2 nights. REM and N2 dreams collected in the laboratory were transcribed and each participant rated the level of correspondence between every dream report and every diary record. The dream-lag effect was found for REM but not N2 dreams. Further analysis indicated that this result was not due to N2 dream reports being shorter, in terms of number of words, than the REM dream reports. These results provide evidence for a 7-day sleep-dependent non-linear memory consolidation process that is specific to REM sleep, and accord with proposals for the importance of REM sleep to emotional memory consolidation.
C1 [Blagrove, Mark; Fouquet, Nathalie C.; Henley-Einion, Josephine A.; Davies, Anna C.; Neuschaffer, Jennifer L.] Swansea Univ, Dept Psychol, Swansea, W Glam, Wales.
[Pace-Schott, Edward F.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Pace-Schott, Edward F.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA.
[Turnbull, Oliver H.] Bangor Univ, Sch Psychol, Bangor, Gwynedd, Wales.
RP Blagrove, M (reprint author), Swansea Univ, Dept Psychol, Swansea, W Glam, Wales.
EM m.t.blagrove@swansea.ac.uk
FU Wales Institute of Cognitive Neuroscience [WBS066]
FX This study was funded by the Wales Institute of Cognitive Neuroscience,
grant WBS066 (http://www.wicn.ac.uk/). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 43
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U1 4
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 OCT 26
PY 2011
VL 6
IS 10
AR e26708
DI 10.1371/journal.pone.0026708
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 841NR
UT WOS:000296519600046
PM 22046336
ER
PT J
AU McGregor, R
Wu, MF
Barber, G
Ramanathan, L
Siegel, JM
AF McGregor, Ronald
Wu, Ming-Fung
Barber, Grace
Ramanathan, Lalini
Siegel, Jerome M.
TI Highly Specific Role of Hypocretin (Orexin) Neurons: Differential
Activation as a Function of Diurnal Phase, Operant Reinforcement versus
Operant Avoidance and Light Level
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID PARKINSONS-DISEASE; SLEEP-DEPRIVATION; HUMAN NARCOLEPSY; FOS EXPRESSION;
KNOCKOUT MICE; MUSCLE TONE; RATS; CATAPLEXY; AROUSAL; LESIONS
AB Hypocretin (Hcrt) cell loss is responsible for narcolepsy, but Hcrt's role in normal behavior is unclear. We found that Hcrt knock-out mice were unable to work for food or water reward during the light phase. However, they were unimpaired relative to wild-type (WT) mice when working for reward during the dark phase or when working to avoid shock in the light or dark phase. In WT mice, expression of Fos in Hcrt neurons occurs only in the light phase when working for positive reinforcement. Expression was seen throughout the mediolateral extent of the Hcrt field. Fos was not expressed when expected or unexpected unearned rewards were presented, when working to avoid negative reinforcement, or when given or expecting shock, even though these conditions elicit maximal electroencephalogram (EEG) arousal. Fos was not expressed in the light phase when light was removed. This may explain the lack of light-induced arousal in narcoleptics and its presence in normal individuals. This is the first demonstration of such specificity of arousal system function and has implications for understanding the motivational and circadian consequences of arousal system dysfunction. The current results also indicate that comparable and complementary specificities must exist in other arousal systems.
C1 [McGregor, Ronald; Wu, Ming-Fung; Barber, Grace; Ramanathan, Lalini; Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[McGregor, Ronald; Wu, Ming-Fung; Barber, Grace; Ramanathan, Lalini; Siegel, Jerome M.] Vet Adm Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA.
[McGregor, Ronald; Wu, Ming-Fung; Barber, Grace; Ramanathan, Lalini; Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA.
RP Siegel, JM (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
EM JSiegel@ucla.edu
FU National Institutes of Health [NS14610, MH64109, NS069640]; Medical
Research Service of the Department of Veteran Affairs
FX This work was supported by Grants NS14610, MH64109, and NS069640 from
the National Institutes of Health and the Medical Research Service of
the Department of Veteran Affairs. We thank Masashi Yanagisawa for
providing us with the orexin KO mice, and Lisa Boehmer and Krystal
Abordo for genotyping the mice. A preliminary report of some of these
data was previously presented in abstract form (McGregor et al., 2007).
NR 62
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U1 2
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 OCT 26
PY 2011
VL 31
IS 43
BP 15455
EP 15467
DI 10.1523/JNEUROSCI.4017-11.2011
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 840MZ
UT WOS:000296446200025
PM 22031892
ER
PT J
AU Campanha, C
Minati, L
Fregni, F
Boggio, PS
AF Campanha, Camila
Minati, Ludovico
Fregni, Felipe
Boggio, Paulo S.
TI Responding to Unfair Offers Made by a Friend: Neuroelectrical Activity
Changes in the Anterior Medial Prefrontal Cortex
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID FRONTAL-CORTEX; ALTRUISTIC PUNISHMENT; DECISION-MAKING; SOCIAL
COGNITION; REGRET AVERSION; FEEDBACK; BRAIN; NEGATIVITY; REWARD;
CONSEQUENCES
AB When receiving unfair monetary offers from another person, the most common response is punishment. Existing literature on the Ultimatum Game indicates that individuals frequently refuse unfair offers even when this results in a loss for themselves. Here, we present behavioral and neurophysiological evidence demonstrating that friendship substantially modifies this response. When the proposer was a friend rather than an unknown person, unfair offers were less frequently rejected and the medial frontal negativity (MFN) typically associated with unfair offers was reversed to positive polarity. The underlying generators were located in inferior-mesial and right inferior-and medial-lateral frontal regions (BA10 and BA11). These findings highlight the fundamental role of the anterior prefrontal cortex in interpersonal economic interaction and, particularly, present new evidence on the effects of social distance on the MFN.
C1 [Campanha, Camila; Boggio, Paulo S.] Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Social & Cognit Neurosci Lab, BR-01241001 Sao Paulo, Brazil.
[Campanha, Camila; Boggio, Paulo S.] Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Dev Disorders Program, BR-01241001 Sao Paulo, Brazil.
[Minati, Ludovico] Fdn IRCCS Ist Neurol Carlo Besta, Dept Sci, I-20133 Milan, Italy.
[Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil,Lab Neuromodulat, Boston, MA 02114 USA.
[Fregni, Felipe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fregni, Felipe] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA.
RP Boggio, PS (reprint author), Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Social & Cognit Neurosci Lab, Rua Piaui,181,10 Andar, BR-01241001 Sao Paulo, Brazil.
EM boggio@mackenzie.br
RI Boggio, Paulo/K-6272-2012
OI Boggio, Paulo/0000-0002-6109-0447
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2009/04694-1];
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
[305718/2009-6]; Mack Pesquisa
FX C.C. was supported by Fundacao de Amparo a Pesquisa do Estado de Sao
Paulo (2009/04694-1). P.S.B. was supported by Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (305718/2009-6) and by Mack
Pesquisa. We acknowledge Kayleen Weaver for proofreading of this
manuscript, Nathalia I. Baptista for picture design, and two anonymous
reviewers for insightful feedback on an earlier version.
NR 35
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U1 2
U2 19
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 26
PY 2011
VL 31
IS 43
BP 15569
EP 15574
DI 10.1523/JNEUROSCI.1253-11.2011
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 840MZ
UT WOS:000296446200035
PM 22031902
ER
PT J
AU Covinsky, KE
Pierluissi, E
Johnston, CB
AF Covinsky, Kenneth E.
Pierluissi, Edgar
Johnston, C. Bree
TI Hospitalization-Associated Disability "She Was Probably Able to
Ambulate, but I'm Not Sure"
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID PREDICTS FUNCTIONAL DECLINE; ACUTE MEDICAL ILLNESS; ILL OLDER PATIENTS;
LONG-TERM-CARE; RANDOMIZED-TRIAL; LOW MOBILITY; MULTICOMPONENT
INTERVENTION; GERIATRIC ASSESSMENT; RESTRICTED ACTIVITY; ELDERLY
PATIENTS
AB In older patients, acute medical illness that requires hospitalization is a sentinel event that often precipitates disability. This results in the subsequent inability to live independently and complete basic activities of daily living (ADLs). This hospitalization-associated disability occurs in approximately one-third of patients older than 70 years of age and may be triggered even when the illness that necessitated the hospitalization is successfully treated. In this article, we describe risk factors and risk stratification tools that identify older adults at highest risk of hospitalization-associated disability. We describe hospital processes that may promote hospitalization-associated disability and models of care that have been developed to prevent it. Since recognition of functional status problems is an essential prerequisite to preventing and managing disability, we also describe a pragmatic approach toward functional status assessment in the hospital focused on evaluation of ADLs, mobility, and cognition. Based on studies of acute geriatric units, we describe interventions hospitals and clinicians can consider to prevent hospitalization-associated disability in patients. Finally, we describe approaches clinicians can implement to improve the quality of life of older adults who develop hospitalization-associated disability and that of their caregivers. JAMA. 2011;306(16):1782-1793
C1 [Covinsky, Kenneth E.; Pierluissi, Edgar; Johnston, C. Bree] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA.
[Covinsky, Kenneth E.; Pierluissi, Edgar; Johnston, C. Bree] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA.
[Pierluissi, Edgar] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA.
[Pierluissi, Edgar] San Francisco Gen Hosp, Div Hosp Med, San Francisco, CA 94110 USA.
[Covinsky, Kenneth E.; Johnston, C. Bree] San Francisco VA Med Ctr, Sect Geriatr & Palliat Care, San Francisco, CA USA.
RP Covinsky, KE (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St 181G, San Francisco, CA 94121 USA.
EM ken.covinsky@ucsf.edu
FU National Institute on Aging; SCAN Foundation
FX This work was supported in part by a K24 midcareer investigator award
from the National Institute on Aging (Covinsky). The Care of the Aging
Patient series is made possible by funding from The SCAN Foundation.
NR 72
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U1 3
U2 24
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 26
PY 2011
VL 306
IS 16
BP 1782
EP 1793
DI 10.1001/jama.2011.1556
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 837HH
UT WOS:000296181600023
PM 22028354
ER
PT J
AU Kangovi, S
Grande, D
AF Kangovi, Shreya
Grande, David
TI Hospital Readmissions-Not Just a Measure of Quality
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID INSURANCE STATUS; FOLLOW-UP; CARE; ACCESS; IMPACT
C1 [Kangovi, Shreya] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA.
[Grande, David] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Kangovi, Shreya; Grande, David] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Kangovi, Shreya] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
RP Kangovi, S (reprint author), Univ Penn, Robert Wood Johnson Clin Scholars Program, 423 Guardian Dr,13th Floor,Blockley Hall, Philadelphia, PA 19104 USA.
EM kangovi@mail.med.upenn.edu
NR 10
TC 62
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U1 0
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 26
PY 2011
VL 306
IS 16
BP 1796
EP 1797
DI 10.1001/jama.2011.1562
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 837HH
UT WOS:000296181600025
PM 22028356
ER
PT J
AU Piller, LB
Baraniuk, S
Simpson, LM
Cushman, WC
Massie, BM
Einhorn, PT
Oparil, S
Ford, CE
Graumlich, JF
Dart, RA
Parish, DC
Retta, TM
Cuyjet, AB
Jafri, SZ
Furberg, CD
Saklayen, MG
Thadani, U
Probstfield, JL
Davis, BR
AF Piller, Linda B.
Baraniuk, Sarah
Simpson, Lara M.
Cushman, William C.
Massie, Barry M.
Einhorn, Paula T.
Oparil, Suzanne
Ford, Charles E.
Graumlich, James F.
Dart, Richard A.
Parish, David C.
Retta, Tamrat M.
Cuyjet, Aloysius B.
Jafri, Syed Z.
Furberg, Curt D.
Saklayen, Mohammad G.
Thadani, Udho
Probstfield, Jeffrey L.
Davis, Barry R.
CA ALLHAT Collaborative Res Grp
TI Long-Term Follow-Up of Participants With Heart Failure in the
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
Trial (ALLHAT)
SO CIRCULATION
LA English
DT Article
DE heart failure; hypertension; diuretics; mortality; ejection fraction
ID CONVERTING-ENZYME-INHIBITOR; CARDIOVASCULAR EVENTS; SURVIVAL;
HYPERTENSION; RISK; BLOCKER; TRENDS; OLDER
AB Background-In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in high-risk hypertensive participants, risk of new-onset heart failure (HF) was higher in the amlodipine (2.5-10 mg/d) and lisinopril (10-40 mg/d) arms compared with the chlorthalidone (12.5-25 mg/d) arm. Similar to other studies, mortality rates following new-onset HF were very high (>= 50% at 5 years), and were similar across randomized treatment arms. After the randomized phase of the trial ended in 2002, outcomes were determined from administrative databases.
Methods and Results-With the use of national databases, posttrial follow-up mortality through 2006 was obtained on participants who developed new-onset HF during the randomized (in-trial) phase of ALLHAT. Mean follow-up for the entire period was 8.9 years. Of 1761 participants with incident HF in-trial, 1348 died. Post-HF all-cause mortality was similar across treatment groups, with adjusted hazard ratios (95% confidence intervals) of 0.95 (0.81-1.12) and 1.05 (0.89-1.25), respectively, for amlodipine and lisinopril compared with chlorthalidone, and 10-year adjusted rates of 86%, 87%, and 83%, respectively. All-cause mortality rates were also similar among those with reduced ejection fractions (84%) and preserved ejection fractions (81%), with no significant differences by randomized treatment arm.
Conclusions-Once HF develops, risk of death is high and consistent across randomized treatment groups. Measures to prevent the development of HF, especially blood pressure control, must be a priority if mortality associated with the development of HF is to be addressed.
C1 [Piller, Linda B.; Baraniuk, Sarah; Simpson, Lara M.; Ford, Charles E.; Davis, Barry R.] Univ Texas Sch Publ Hlth, Houston, TX 77030 USA.
[Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA.
[Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Einhorn, Paula T.] NHLBI, Bethesda, MD 20892 USA.
[Oparil, Suzanne] Univ Alabama Birmingham, Birmingham, AL USA.
[Graumlich, James F.] Univ Illinois, Coll Med, Peoria, IL 61656 USA.
[Dart, Richard A.] Marshfield Clin Res Fdn, Marshfield, WI USA.
[Parish, David C.] Mercer Univ, Sch Med, Macon, GA 31207 USA.
[Retta, Tamrat M.] Howard Univ, Coll Med, Washington, DC USA.
[Cuyjet, Aloysius B.] Nassau Univ, Med Ctr, E Meadow, NY USA.
[Jafri, Syed Z.] Fargo Vet Affairs Med Ctr, Fargo, ND USA.
[Furberg, Curt D.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Saklayen, Mohammad G.] Vet Affairs Med Ctr, Dayton, OH USA.
[Saklayen, Mohammad G.] Wright State Univ, Dayton, OH 45435 USA.
[Thadani, Udho] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Thadani, Udho] Dept Vet Affairs Med Ctr, Oklahoma City, OK USA.
[Probstfield, Jeffrey L.] Univ Washington, Seattle, WA 98195 USA.
RP Piller, LB (reprint author), Univ Texas Sch Publ Hlth, 1200 Pressler St,W-906, Houston, TX 77030 USA.
EM Linda.B.Piller@uth.tmc.edu
FU National Heart, Lung, and Blood Institute [NO1-HC-35130]; Pfizer, Inc.;
GlaxoSmithKline; Merck; Novartis; Corthera; Takeda; Amgen; Daiichi
Sankyo; Gilead; Omron Healthcare; Pfizer; Schering Plough; Abbot
Laboratories; Boehringer Ingelheim; Sanofi-aventis; Bristol-Myers
Squibb; Eisai Medical Research; Eli Lilly; NIH; Schering-Plough
FX This study was supported by contract NO1-HC-35130 with the National
Heart, Lung, and Blood Institute. The ALLHAT investigators acknowledge
study medications contributed by Pfizer, Inc. (amlodipine and
doxazosin), AstraZeneca (atenolol and lisinopril), and Bristol-Myers
Squibb (pravastatin), and financial support provided by Pfizer, Inc.; Dr
Cushman has consulted for Daiichi Sankyo, Novartis, Noven,
Sanofi-aventis, Takeda, and Theravance; has received honoraria from
Bristol-Myers Squibb, and has received research grants from
GlaxoSmithKline, Merck, and Novartis. Dr Davis has consulted for Amgen
and Takeda. Dr. Massie has consulted for Averion, Bristol-Myers Squibb,
Gilead, Merck, Nile Therapeutics, Novartis, and Sanofi-aventis, and has
received payments for serving on the DSMB from Corthera and Takeda. Dr
Oparil has consulted for Boehringer Ingelheim, Daiichi Sankyo, Eli
Lilly, Forest Pharmaceuticals, NicOx, and Novartis, and has received
research grants from Amgen, Daiichi Sankyo, Gilead, Omron Healthcare,
Pfizer, Schering Plough, and Takeda. Dr Probstfield has received
research grants from Abbot Laboratories, Boehringer Ingelheim,
GlaxoSmithKline, and Sanofi-aventis. Dr Thadani has consulted for Forest
Laboratories, Gilead Colorado, Lilly/ICOS, and Merck; has received
honoraria from Daiichi Sankyo and Eli Lilly; and has received research
grants from Bristol-Myers Squibb, Eisai Medical Research, Eli Lilly,
NIH, Novartis, Pfizer, and Schering-Plough. The other authors report no
conflicts.
NR 29
TC 17
Z9 19
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD OCT 25
PY 2011
VL 124
IS 17
BP 1811
EP U88
DI 10.1161/CIRCULATIONAHA.110.012575
PG 14
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 842EY
UT WOS:000296576500012
PM 21969009
ER
PT J
AU Bangalore, S
Bhatt, DL
AF Bangalore, Sripal
Bhatt, Deepak L.
TI Right Heart Catheterization, Coronary Angiography, and Percutaneous
Coronary Intervention
SO CIRCULATION
LA English
DT Article
ID ASSOCIATION TASK-FORCE; PRACTICE GUIDELINES; ACC/AHA GUIDELINES; TRIAL;
GRADE; FLOW
C1 [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Integrated Intervent Cardiovasc Program, Boston, MA 02132 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA 02132 USA.
[Bangalore, Sripal] NYU, Sch Med, New York, NY USA.
RP Bhatt, DL (reprint author), Brigham & Womens Hosp, VA Boston Healthcare Syst, Integrated Intervent Cardiovasc Program, 1400 VFW Pkwy, Boston, MA 02132 USA.
EM dlbhattmd@post.harvard.edu
RI Bangalore, Sripal/B-6246-2013;
OI Bangalore, Sripal/0000-0001-9485-0652
NR 11
TC 5
Z9 5
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 25
PY 2011
VL 124
IS 17
BP E428
EP E433
DI 10.1161/CIRCULATIONAHA.111.065219
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 842EY
UT WOS:000296576500001
PM 22025641
ER
PT J
AU Tsai, TT
Messenger, JC
Brennan, M
Patel, UD
Dai, D
Piana, RN
Anstrom, KJ
Eisenstein, EL
Dokholyan, RS
Peterson, ED
Douglas, PS
AF Tsai, Thomas T.
Messenger, John C.
Brennan, Matthew
Patel, Uptal D.
Dai, David
Piana, Robert N.
Anstrom, Kevin J.
Eisenstein, Eric L.
Dokholyan, Rachel S.
Peterson, Eric D.
Douglas, Pamela S.
TI Safety and Efficacy of Drug-Eluting Stents in Older Patients With
Chronic Kidney Disease A Report From the Linked CathPCI Registry-CMS
Claims Database
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE comparative effectiveness research; drug-eluting stent(s); renal
insufficiency
ID CHRONIC RENAL-INSUFFICIENCY; BARE-METAL STENTS; PERCUTANEOUS CORONARY
REVASCULARIZATION; CARDIOVASCULAR DATA REGISTRY; LONG-TERM OUTCOMES;
TAXUS-IV TRIAL; OFF-LABEL USE; AMERICAN-COLLEGE; MYOCARDIAL-INFARCTION;
CLINICAL-OUTCOMES
AB Objectives The purpose of this study was to determine the safety and efficacy of drug-eluting stents (DES) compared with bare-metal stents (BMS) in older patients with chronic kidney disease (CKD).
Background DES may be associated with late death and myocardial infarction (MI) secondary to stent thrombosis. However, data on outcomes in older patients with CKD are limited.
Methods We estimated the glomerular filtration rate (GFR) of 283,593 patients 65 years of age and older who underwent stent implantation between 2004 and 2007. In propensity-matched cohorts grouped by GFR, the association between DES and BMS and the risk of death, MI, revascularization, and major bleeding was examined.
Results A total of 121,446 patients (42.8%) had CKD (GFR <60 ml/min/1.73 m(2)). The 30-month mortality rate for patients on long-term dialysis was 52.0%. In propensity-matched pairs, placement of a DES compared with a BMS in patients with normal renal function was associated with significant reductions in 30-month revascularization (hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.86 to 0.95), MI (HR: 0.77; 95% CI: 0.71 to 0.83), and death (HR: 0.73; 95% CI: 0.69 to 0.77), but no difference in bleeding (HR: 0.89; 95% CI: 0.79 to 1.00). Lower MI and mortality rates were also observed after DES compared with BMS implantation in all CKD subgroups with the exception of MI in the long-term dialysis group. Decreased rates of revascularization did not extend to any subgroup of patients with CKD.
Conclusions The safety of DES compared with BMS is observed in all patients regardless of renal function and is associated with reduced rates of MI and death in some subsets of patients with CKD. (J Am Coll Cardiol 2011; 58: 1859-69) (C) 2011 by the American College of Cardiology Foundation
C1 [Tsai, Thomas T.] Denver VA Med Ctr, Cardiol Sect 111B, Denver, CO 80220 USA.
[Tsai, Thomas T.; Messenger, John C.] Univ Colorado, Aurora, CO USA.
[Brennan, Matthew; Patel, Uptal D.; Dai, David; Anstrom, Kevin J.; Eisenstein, Eric L.; Dokholyan, Rachel S.; Peterson, Eric D.; Douglas, Pamela S.] Duke Univ Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Piana, Robert N.] Vanderbilt Univ Sch Med, Nashville, TN USA.
RP Tsai, TT (reprint author), Denver VA Med Ctr, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA.
EM Thomas.Tsai@va.gov
FU Agency for Healthcare Research and Quality, U.S. Department of Health
and Human Services as part of the Developing Evidence to Inform
Decisions about Effectiveness (DEcIDE) [HHSA29020050032I]; Medtronic
Cardiovascular; Eli Lilly Co.; Bristol-Myers Squibb/Sanofi; Merck;
Lilly; Johnson Johnson
FX This project was funded under contract no. HHSA29020050032I Task Order
No. 4 from the Agency for Healthcare Research and Quality, U.S.
Department of Health and Human Services as part of the Developing
Evidence to Inform Decisions about Effectiveness (DEcIDE) program. The
authors of this report are responsible for its content. Statements in
the report should not be construed as endorsement by the Agency for
Healthcare Research and Quality or the U.S. Department of Health and
Human Services. Dr. Eisenstein has received grant support from Medtronic
Cardiovascular and Eli Lilly & Co. Dr. Peterson has received research
support from Bristol-Myers Squibb/Sanofi, Merck, Lilly, and Johnson &
Johnson. All other authors have reported that they have no relationships
relevant to the contents of this paper to disclose.
NR 43
TC 42
Z9 43
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD OCT 25
PY 2011
VL 58
IS 18
BP 1859
EP 1869
DI 10.1016/j.jacc.2011.06.056
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 841UM
UT WOS:000296540200005
PM 22018296
ER
PT J
AU Deswal, A
AF Deswal, Anita
TI Obesity, Leptin, and Incident Heart Failure
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE heart failure; leptin; obesity
ID RAT VENTRICULAR MYOCYTES; ATHEROSCLEROSIS; RISK; MICE; HYPERTROPHY;
APOPTOSIS; DISEASE
C1 [Deswal, Anita] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Cardiol Sect, Houston, TX 77030 USA.
[Deswal, Anita] Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA.
RP Deswal, A (reprint author), Michael E DeBakey VA Med Ctr 111B, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM adeswal@bcm.edu
NR 19
TC 6
Z9 6
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD OCT 25
PY 2011
VL 58
IS 18
BP 1878
EP 1880
DI 10.1016/j.jacc.2011.07.030
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 841UM
UT WOS:000296540200007
PM 22018298
ER
PT J
AU Januzzi, JL
Rehman, SU
Mohammed, AA
Bhardwaj, A
Barajas, L
Barajas, J
Kim, HN
Baggish, AL
Weiner, RB
Chen-Tournoux, A
Marshall, JE
Moore, SA
Carlson, WD
Lewis, GD
Shin, J
Sullivan, D
Parks, K
Wang, TJ
Gregory, SA
Uthamalingam, S
Semigran, MJ
AF Januzzi, James L., Jr.
Rehman, Shafiq U.
Mohammed, Asim A.
Bhardwaj, Anju
Barajas, Linda
Barajas, Justine
Kim, Han-Na
Baggish, Aaron L.
Weiner, Rory B.
Chen-Tournoux, Annabel
Marshall, Jane E.
Moore, Stephanie A.
Carlson, William D.
Lewis, Gregory D.
Shin, Jordan
Sullivan, Dorothy
Parks, Kimberly
Wang, Thomas J.
Gregory, Shawn A.
Uthamalingam, Shanmugam
Semigran, Marc J.
TI Use of Amino-Terminal Pro-B-Type Natriuretic Peptide to Guide Outpatient
Therapy of Patients With Chronic Left Ventricular Systolic Dysfunction
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE heart failure; natriuretic peptides; outcomes
ID CHRONIC HEART-FAILURE; TRIAL; MANAGEMENT; BNP; MULTICENTER; PREDICTION;
CARE; CARVEDILOL; MORTALITY; SURVIVAL
AB Objectives The aim of this study was to evaluate whether chronic heart failure (HF) therapy guided by concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is superior to standard of care (SOC) management.
Background It is unclear whether standard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with standard management alone.
Methods In a prospective single-center trial, 151 subjects with HF due to left ventricular (LV) systolic dysfunction were randomized to receive either standard HF care plus a goal to reduce NT-proBNP concentrations <= 1,000 pg/ml or SOC management. The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations. Secondary endpoints included effects of NT-proBNP-guided care on patient quality of life as well as cardiac structure and function, assessed with echocardiography.
Results Through a mean follow-up period of 10 +/- 3 months, a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC (58 events vs. 100 events, p = 0.009; logistic odds for events 0.44, p = 0.02); Kaplan-Meier curves demonstrated significant differences in time to first event, favoring NT-proBNP-guided care (p = 0.03). No age interaction was found, with elderly patients bene-fitting similarly from NT-proBNP-guided care as younger subjects. Compared with SOC, NT-proBNP-guided patients had greater improvements in quality of life, demonstrated greater relative improvements in LV ejection fraction, and had more significant improvements in both LV end-systolic and -diastolic volume indexes.
Conclusions In patients with HF due to LV systolic dysfunction, NT-proBNP-guided therapy was superior to SOC, with reduced event rates, improved quality of life, and favorable effects on cardiac remodeling. (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting; NCT00351390) (J Am Coll Cardiol 2011;58:1881-9) (C) 2011 by the American College of Cardiology Foundation
C1 [Januzzi, James L., Jr.; Rehman, Shafiq U.; Mohammed, Asim A.; Bhardwaj, Anju; Barajas, Linda; Barajas, Justine; Kim, Han-Na; Baggish, Aaron L.; Weiner, Rory B.; Chen-Tournoux, Annabel; Marshall, Jane E.; Moore, Stephanie A.; Carlson, William D.; Lewis, Gregory D.; Shin, Jordan; Sullivan, Dorothy; Parks, Kimberly; Wang, Thomas J.; Gregory, Shawn A.; Uthamalingam, Shanmugam; Semigran, Marc J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA.
EM jjanuzzi@partners.org
FU Roche Diagnostics, Inc.; Balson Cardiac Scholar Fund; Siemens
Diagnostics; Critical Diagnostics; Dennis and Marilyn Barry Cardiology
Fellowship
FX This study was supported in part by Roche Diagnostics, Inc. Dr. Januzzi
is supported in part by the Balson Cardiac Scholar Fund; has received
research grants and consultancy fees from Roche Diagnostics, Inc.,
Siemens Diagnostics, and Critical Diagnostics; and has received speakers
fees from Roche Diagnostics, Inc. and Siemens Diagnostics. Drs. Rehman,
Mohammed, Bhardwaj, and Kim are supported by the Dennis and Marilyn
Barry Cardiology Fellowship. Dr. Shin has served as a consultant to
Acceleron Pharma. Dr. Wang has been a coinvestigator on studies that
received assay support from Siemens Diagnostics. All other authors have
reported that they have no relationships relevant to the contents of
this paper to disclose.
NR 32
TC 151
Z9 154
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD OCT 25
PY 2011
VL 58
IS 18
BP 1881
EP 1889
DI 10.1016/j.jacc.2011.03.072
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 841UM
UT WOS:000296540200008
PM 22018299
ER
PT J
AU Pau, VPT
Smith, FJ
Taylor, AB
Parfenova, LV
Samakai, E
Callaghan, MM
Abarca-Heidemann, K
Hart, PJ
Rothberg, BS
AF Pau, Victor P. T.
Smith, Frank J.
Taylor, Alexander B.
Parfenova, Liubov V.
Samakai, Elsie
Callaghan, Matthew M.
Abarca-Heidemann, Karin
Hart, P. John
Rothberg, Brad S.
TI Structure and function of multiple Ca2+-binding sites in a K+ channel
regulator of K+ conductance (RCK) domain
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE calcium; lipid bilayer; cooperativity
ID POTASSIUM CHANNEL; GATING RING; CRYSTAL-STRUCTURES; SLO FAMILY; MTHK;
MECHANISM; COMPLEX; BINDING; ACTIVATION; PROTEINS
AB Regulator of K+ conductance (RCK) domains control the activity of a variety of K+ transporters and channels, including the human large conductance Ca2+-activated K+ channel that is important for blood pressure regulation and control of neuronal firing, and MthK, a prokaryotic Ca2+-gated K+ channel that has yielded structural insight toward mechanisms of RCK domain-controlled channel gating. In MthK, a gating ring of eight RCK domains regulates channel activation by Ca2+. Here, using electrophysiology and X-ray crystallography, we show that each RCK domain contributes to three different regulatory Ca2+-binding sites, two of which are located at the interfaces between adjacent RCK domains. The additional Ca2+-binding sites, resulting in a stoichiometry of 24 Ca2+ ions per channel, is consistent with the steep relation between [Ca2+] and MthK channel activity. Comparison of Ca2+-bound and unliganded RCK domains suggests a physical mechanism for Ca2+-dependent conformational changes that underlie gating in this class of channels.
C1 [Pau, Victor P. T.; Smith, Frank J.; Samakai, Elsie; Callaghan, Matthew M.; Abarca-Heidemann, Karin; Rothberg, Brad S.] Temple Univ, Sch Med, Dept Biochem, Philadelphia, PA 19140 USA.
[Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78240 USA.
[Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78240 USA.
[Parfenova, Liubov V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78240 USA.
[Hart, P. John] S Texas Vet Hlth Care Syst, Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78240 USA.
RP Rothberg, BS (reprint author), Temple Univ, Sch Med, Dept Biochem, 3400 N Broad St, Philadelphia, PA 19140 USA.
EM rothberg@temple.edu
OI Rothberg, Brad/0000-0003-1982-2269
FU National Institutes of Health [GM068523]; Robert A. Welch Foundation
[AQ1399]; American Heart Association
FX We thank Daniel Yang and Andrew Thomson for helpful discussions, and the
X-ray Core Facility of University of Texas Health Science Center at San
Antonio for technical support. This research was supported by National
Institutes of Health Grant GM068523 (to B. S. R) and Robert A. Welch
Foundation Grant AQ1399 (to P.J.H.). V. P. P. has been supported by a
postdoctoral fellowship from the American Heart Association, Great
Rivers Affiliate.
NR 29
TC 13
Z9 15
U1 0
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 25
PY 2011
VL 108
IS 43
BP 17684
EP 17689
DI 10.1073/pnas.1107229108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 839OU
UT WOS:000296378100033
PM 21997217
ER
PT J
AU Wang, NJ
Sanborn, Z
Arnett, KL
Bayston, LJ
Liao, W
Proby, CM
Leigh, IM
Collisson, EA
Gordon, PB
Jakkula, L
Pennypacker, S
Zou, Y
Sharma, M
North, JP
Vemula, SS
Mauro, TM
Neuhaus, IM
LeBoit, PE
Hur, JS
Park, K
Huh, N
Kwok, PY
Arron, ST
Massion, PP
Bale, AE
Haussler, D
Cleaver, JE
Gray, JW
Spellman, PT
South, AP
Aster, JC
Blacklow, SC
Cho, RJ
AF Wang, Nicholas J.
Sanborn, Zachary
Arnett, Kelly L.
Bayston, Laura J.
Liao, Wilson
Proby, Charlotte M.
Leigh, Irene M.
Collisson, Eric A.
Gordon, Patricia B.
Jakkula, Lakshmi
Pennypacker, Sally
Zou, Yong
Sharma, Mimansa
North, Jeffrey P.
Vemula, Swapna S.
Mauro, Theodora M.
Neuhaus, Isaac M.
LeBoit, Philip E.
Hur, Joe S.
Park, Kyunghee
Huh, Nam
Kwok, Pui-Yan
Arron, Sarah T.
Massion, Pierre P.
Bale, Allen E.
Haussler, David
Cleaver, James E.
Gray, Joe W.
Spellman, Paul T.
South, Andrew P.
Aster, Jon C.
Blacklow, Stephen C.
Cho, Raymond J.
TI Loss-of-function mutations in Notch receptors in cutaneous and lung
squamous cell carcinoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cancer genetics; genomic; cellular signaling
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA;
GROWTH-FACTOR RECEPTOR; DROSOPHILA NOTCH; LIGAND-BINDING; C-MYC; SKIN;
GENE; HEAD; NECK
AB Squamous cell carcinomas (SCCs) are one of the most frequent forms of human malignancy, but, other than TP53 mutations, few causative somatic aberrations have been identified. We identified NOTCH1 or NOTCH2 mutations in similar to 75% of cutaneous SCCs and in a lesser fraction of lung SCCs, defining a spectrum for the most prevalent tumor suppressor specific to these epithelial malignancies. Notch receptors normally transduce signals in response to ligands on neighboring cells, regulating metazoan lineage selection and developmental patterning. Our findings therefore illustrate a central role for disruption of microenvironmental communication in cancer progression. NOTCH aberrations include frameshift and nonsense mutations leading to receptor truncations as well as point substitutions in key functional domains that abrogate signaling in cell-based assays. Oncogenic gain-of-function mutations in NOTCH1 commonly occur in human T-cell lymphoblastic leukemia/lymphoma and B-cell chronic lymphocytic leukemia. The bifunctional role of Notch in human cancer thus emphasizes the context dependency of signaling outcomes and suggests that targeted inhibition of the Notch pathway may induce squamous epithelial malignancies.
C1 [Liao, Wilson; Pennypacker, Sally; Mauro, Theodora M.; Neuhaus, Isaac M.; Kwok, Pui-Yan; Arron, Sarah T.; Cleaver, James E.; Cho, Raymond J.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Wang, Nicholas J.; Jakkula, Lakshmi] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
[Sanborn, Zachary; Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
[Arnett, Kelly L.; Bayston, Laura J.; Aster, Jon C.; Blacklow, Stephen C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Collisson, Eric A.] Univ Calif San Francisco, Dept Hematol & Oncol, San Francisco, CA 94143 USA.
[Sharma, Mimansa; North, Jeffrey P.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
[Proby, Charlotte M.; Leigh, Irene M.; South, Andrew P.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Div Canc Res, Dundee DD1 9SY, Scotland.
[Gordon, Patricia B.; Bale, Allen E.] Yale Univ, Dept Genet, New Haven, CT 06520 USA.
[Zou, Yong; Massion, Pierre P.] Vanderbilt Univ, Div Allergy Pulm & Crit Care Med, Nashville, TN 37232 USA.
[Vemula, Swapna S.; LeBoit, Philip E.] Univ Calif San Francisco, Serv Dermatopathol, San Francisco, CA 94115 USA.
[Hur, Joe S.] Samsung Elect Headquarters, Seoul 137857, South Korea.
[Park, Kyunghee; Huh, Nam] Samsung Adv Inst Technol, Emerging Technol Res Ctr, Kyonggi Do 446712, South Korea.
[Gray, Joe W.] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA.
[Spellman, Paul T.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA.
[Blacklow, Stephen C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Cleaver, JE (reprint author), Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
EM jcleaver@cc.ucsf.edu; chorj@derm.ucsf.edu
RI Arnett, Kelly/C-4816-2012; Kwok, Pui-Yan/F-7725-2014;
OI Kwok, Pui-Yan/0000-0002-5087-3059; Arnett, Kelly/0000-0001-5117-3647;
North, Jeffrey/0000-0003-3973-5314
FU Leukemia and Lymphoma Society; National Institutes of Health (NIH) [P01
CA119070, R01 CA092433]; European Research Council; Cancer Research-UK;
Department of Energy [DE-AC02-05CH11231]; NIH/National Cancer Institute
(NCI) [P50 CA 58207, U54 CA 112970]; National Human Genome Research
Institute [U24 CA 126551]; US Army Medical Research Acquisition Activity
[W81XWH-07-1-0663]; Stand Up To Cancer-American Association for Cancer
Research Dream Team [SU2C-AACR-DT0409]; University of California;
Dickson Emeritus Professorship; NIH/NCI [U24 CA1437991, KO8 CA137153];
Yale SPORE in Skin Cancer; National Cancer Institute [P50 CA121974]; NIH
[AR051930, R01AG028492]; Department of Veterans Affairs Medical Research
Service; NIH/National Institute of Arthritis and Musculoskeletal and
Skin Diseases [5KO8AR057763]; Samsung Advanced Institute of Technology;
Dermatology Foundation
FX We thank Andrew J. Cassidy, Karin J. Purdie, Zohreh AkhavanAghdam,
Catherine Chu, Sonia A. Mirza, Gad Getz, Kristian Cibulskis, and Rebecca
Terrell for technical expertise and assistance. J. C. A. and S. C. B.
were supported by Leukemia and Lymphoma Society grants and by National
Institutes of Health (NIH) Grants P01 CA119070 and R01 CA092433. I. M.
L. was supported by program grants from the European Research Council
and Cancer Research-UK. J. W. G. was supported by Department of Energy
Contract DE-AC02-05CH11231, NIH/National Cancer Institute (NCI) Grants
P50 CA 58207 and U54 CA 112970, National Human Genome Research Institute
Grant U24 CA 126551, US Army Medical Research Acquisition Activity Award
W81XWH-07-1-0663, and Stand Up To Cancer-American Association for Cancer
Research Dream Team Translational Cancer Research Grant
SU2C-AACR-DT0409. J. E. C. was supported by the University of California
Cancer Research Campaign and the Dickson Emeritus Professorship. P. T.
S. was supported by NIH/NCI Grant U24 CA1437991. A. E. B. and P. B. G.
were supported by the Yale SPORE in Skin Cancer funded by the National
Cancer Institute Grant P50 CA121974. T. M. M. was supported by NIH
Grants AR051930 and R01AG028492 and by the Department of Veterans
Affairs Medical Research Service. E. A. C. was supported by NIH/NCI
Grant KO8 CA137153. W. L. was supported by NIH/National Institute of
Arthritis and Musculoskeletal and Skin Diseases Grant 5KO8AR057763. R.
J. C. was supported by a Samsung Advanced Institute of Technology
unrestricted gift-grant and a Career Development Award from the
Dermatology Foundation.
NR 55
TC 164
Z9 168
U1 3
U2 26
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 25
PY 2011
VL 108
IS 43
BP 17761
EP 17766
DI 10.1073/pnas.1114669108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 839OU
UT WOS:000296378100046
PM 22006338
ER
PT J
AU Nagao, M
Feinstein, TN
Ezura, Y
Hayata, T
Notomi, T
Saita, Y
Hanyu, R
Hemmi, H
Izu, Y
Takeda, S
Wang, K
Rittling, S
Nakamoto, T
Kaneko, K
Kurosawa, H
Karsenty, G
Denhardt, DT
Vilardaga, JP
Noda, M
AF Nagao, Masashi
Feinstein, Timothy N.
Ezura, Yoichi
Hayata, Tadayoshi
Notomi, Takuya
Saita, Yoshitomo
Hanyu, Ryo
Hemmi, Hiroaki
Izu, Yayoi
Takeda, Shu
Wang, Kathryn
Rittling, Susan
Nakamoto, Tetsuya
Kaneko, Kazuo
Kurosawa, Hisashi
Karsenty, Gerard
Denhardt, David T.
Vilardaga, Jean-Pierre
Noda, Masaki
TI Sympathetic control of bone mass regulated by osteopontin
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE osteoporosis; G protein-coupled receptor; osteoblast
ID DENDRITIC CELLS; NERVOUS-SYSTEM; RECEPTOR; CAMP; OSTEOPOROSIS;
SUPPRESSION; STRESS; MICE
AB The sympathetic nervous system suppresses bone mass by mechanisms that remain incompletely elucidated. Using cell-based and murine genetics approaches, we show that this activity of the sympathetic nervous systemrequires osteopontin (OPN), a cytokine and one of the major members of the noncollagenous extracellular matrix proteins of bone. In this work, we found that the stimulation of the sympathetic tone by isoproterenol increased the level of OPN expression in the plasma and bone and that mice lacking OPN (OPN-KO) suppressed the isoproterenol-induced bone loss by preventing reduced osteoblastic and enhanced osteoclastic activities. In addition, we found that OPN is necessary for changes in the expression of genes related to bone resorption and bone formation that are induced by activation of the sympathetic tone. At the cellular level, we showed that intracellular OPN modulated the capacity of the beta 2-adrenergic receptor to generate cAMP with a corresponding modulation of cAMP-response element binding (CREB) phosphorylation and associated transcriptional events inside the cell. Our results indicate that OPN plays a critical role in sympathetic tone regulation of bone mass and that this OPN regulation is taking place through modulation of the beta 2-adrenergic receptor/cAMP signaling system.
C1 [Feinstein, Timothy N.; Vilardaga, Jean-Pierre] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Pittsburgh, PA 15261 USA.
[Nagao, Masashi; Ezura, Yoichi; Hayata, Tadayoshi; Notomi, Takuya; Hanyu, Ryo; Hemmi, Hiroaki; Izu, Yayoi; Nakamoto, Tetsuya; Noda, Masaki] Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Bunkyo Ku, Tokyo 1138510, Japan.
[Nagao, Masashi; Ezura, Yoichi; Hayata, Tadayoshi; Notomi, Takuya; Hanyu, Ryo; Hemmi, Hiroaki; Takeda, Shu; Nakamoto, Tetsuya; Noda, Masaki] Tokyo Med & Dent Univ, Global Ctr Excellence Program, Int Res Ctr Mol Sci Tooth & Bone Dis, Bunkyo Ku, Tokyo 1138510, Japan.
[Nagao, Masashi; Saita, Yoshitomo; Hanyu, Ryo; Kaneko, Kazuo; Kurosawa, Hisashi] Juntendo Univ, Sch Med, Dept Orthoped, Bunkyo Ku, Tokyo 1138421, Japan.
[Hemmi, Hiroaki; Noda, Masaki] Tokyo Med & Dent Univ, Med Res Inst, Med Top Track Program, Bunkyo Ku, Tokyo 1138510, Japan.
[Wang, Kathryn; Denhardt, David T.] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08701 USA.
[Rittling, Susan] Forsyth Inst, Boston, MA 02115 USA.
[Karsenty, Gerard] Columbia Univ Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA.
[Ezura, Yoichi; Noda, Masaki] Tokyo Med & Dent Univ, Adv Bone & Joint Sci Program, Bunkyo Ku, Tokyo 1138510, Japan.
[Ezura, Yoichi; Noda, Masaki] Tokyo Med & Dent Univ, Hard Tissue Genome Res Ctr, Bunkyo Ku, Tokyo 1138510, Japan.
RP Vilardaga, JP (reprint author), Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Pittsburgh, PA 15261 USA.
EM jpv@pitt.edu; noda.mph@mri.tmd.ac.jp
RI Ezura, Yoichi/L-9485-2016
FU Japanese Ministry of Education, International Research Center for
Molecular Science in Tooth and Bone Diseases [18109011, 18659438,
18123456, 20013014]; Japan Space Forum; National Institutes of Health
[R01DK087688]
FX This work was supported by Grants-in-Aid 18109011, 18659438, 18123456,
and 20013014 from the Japanese Ministry of Education (Global Center of
Excellence Program, International Research Center for Molecular Science
in Tooth and Bone Diseases), grants from the Japan Space Forum (to M.
Noda), and National Institutes of Health Award R01DK087688 (to J.-P.V.).
NR 22
TC 30
Z9 33
U1 2
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 25
PY 2011
VL 108
IS 43
BP 17767
EP 17772
DI 10.1073/pnas.1109402108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 839OU
UT WOS:000296378100047
PM 21990347
ER
PT J
AU Feige, E
Yokoyama, S
Levy, C
Khaled, M
Igras, V
Lin, RJ
Lee, S
Widlund, HR
Granter, SR
Kung, AL
Fisher, DE
AF Feige, Erez
Yokoyama, Satoru
Levy, Carmit
Khaled, Mehdi
Igras, Vivien
Lin, Richard J.
Lee, Stephen
Widlund, Hans R.
Granter, Scott R.
Kung, Andrew L.
Fisher, David E.
TI Hypoxia-induced transcriptional repression of the melanoma-associated
oncogene MITF
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cancer; pigmentation; signal transduction
ID RENAL-CELL CARCINOMAS; INTEGRATIVE GENOMIC ANALYSES; FACTOR DEC1 STRA13;
MALIGNANT-MELANOMA; GENE-EXPRESSION; PROLINE HYDROXYLATION; TFE3 GENE;
MICROPHTHALMIA LOCUS; PROGNOSTIC MARKER; LINEAGE SURVIVAL
AB Microphthalmia- associated transcription factor (MITF) regulates normal melanocyte development and is also a lineage-selective oncogene implicated in melanoma and clear-cell sarcoma (i.e., melanoma of soft parts). We have observed that MITF expression is potently reduced under hypoxic conditions in primary melanocytes and melanoma and clear cell sarcoma cells through hypoxia inducible factor 1 (HIF1)-mediated induction of the transcriptional repressor differentially expressed in chondrocytes protein 1 (DEC1) (BHLHE40), which subsequently binds and suppresses the promoter of M-MITF (melanocyte-restricted MITF isoform). Correspondingly, hypoxic conditions or HIF1 alpha stabilization achieved by using small-molecule prolyl-hydroxylase inhibitors reduced M-MITF expression, leading to melanoma cell growth arrest that was rescued by ectopic expression of M-MITF in vitro. Prolyl hydroxylase inhibition also potently suppressed melanoma growth in a mouse xenograft model. These studies illuminate a physiologic hypoxia response in pigment cells leading to M-MITF suppression, one that suggests a potential survival advantage mechanism for MITF amplification in metastatic melanoma and offers a small-molecule strategy for suppression of the MITF oncogene in vivo.
C1 [Feige, Erez; Yokoyama, Satoru; Levy, Carmit; Khaled, Mehdi; Igras, Vivien; Lin, Richard J.; Widlund, Hans R.; Kung, Andrew L.; Fisher, David E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Yokoyama, Satoru; Levy, Carmit; Khaled, Mehdi; Igras, Vivien; Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA.
[Lee, Stephen] Univ Ottawa, Fac Med, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada.
[Granter, Scott R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Fisher, DE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
EM dfisher3@partners.org
RI khaled, mehdi/C-4854-2012;
OI Lin, Richard/0000-0002-0834-7880; Kung, Andrew/0000-0002-9091-488X
FU Bonnie and Marty Tenenbaum Foundation; National Institutes of Health;
Melanoma Research Alliance; Adelson Medical Research Foundation
FX The authors thank Dr. William Kaelin for reagents and discussions; Dr.
Ruth Halaban for providing 501mel cells; Claudine Christoforides and
Abigail J. Bracha for help with early aspects of the studies; Renee
Wright for superb technical assistance; and all members of the D. E. F.
laboratory for useful discussions and comments. This work was supported
by the Bonnie and Marty Tenenbaum Foundation, a National Institutes of
Health grant, the Melanoma Research Alliance, and the Adelson Medical
Research Foundation. D.E.F. is Distinguished Clinical Scholar of the
Doris Duke Medical Foundation.
NR 59
TC 36
Z9 36
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 OCT 25
PY 2011
VL 108
IS 43
BP E924
EP E933
DI 10.1073/pnas.1106351108
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 839OU
UT WOS:000296378100010
PM 21949374
ER
PT J
AU Rutemark, C
Alicot, E
Bergman, A
Ma, MH
Getahun, A
Ellmerich, S
Carroll, MC
Heyman, B
AF Rutemark, Christian
Alicot, Elisabeth
Bergman, Anna
Ma, Minghe
Getahun, Andrew
Ellmerich, Stephan
Carroll, Michael C.
Heyman, Birgitta
TI Requirement for complement in antibody responses is not explained by the
classic pathway activator IgM
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE IgM mutation; natural IgM
ID HUMORAL IMMUNE-RESPONSE; FOLLICULAR DENDRITIC CELLS; A-DEFICIENT MICE;
MARGINAL ZONE; RECEPTORS 1; B-CELLS; MEDIATED ENHANCEMENT; TARGETED
DELETION; IMMUNOGLOBULIN-M; MEMBRANE IGM
AB Animals lacking complement factors C1q, C2, C3, or C4 have severely impaired Ab responses, suggesting a major role for the classic pathway. The classic pathway is primarily initiated by antigen-Ab complexes. Therefore, its role for primary Ab responses seems paradoxical because only low amounts of specific Abs are present in naive animals. A possible explanation could be that the classic pathway is initiated by IgM from naive mice, binding with sufficient avidity to the antigen. To test this hypothesis, a knock-in mouse strain, C mu 13, with a point mutation in the gene encoding the third constant domain of the mu-heavy chain was constructed. These mice produce IgM in which proline in position 436 is substituted with serine, a mutation previously shown to abrogate the ability of mouse IgM to activate complement. Unexpectedly, the Ab response to sheep erythrocytes and keyhole limpet hemocyanin in C mu 13 mice was similar to that in WT mice. Thus, although secreted IgM and the classic pathway activation are both required for the normal primary Ab response, this does not require that IgM activate C. This led us to test Ab responses in animals lacking one of three other endogenous activators of the classic pathway: specific intracellular adhesion molecule-grabbing nonintegrin R1, serum amyloid P component, and C-reactive protein. Ab responses were also normal in these animals.
C1 [Rutemark, Christian; Bergman, Anna; Heyman, Birgitta] Uppsala Univ, Dept Med Biochem & Microbiol, BMC, SE-75123 Uppsala, Sweden.
[Alicot, Elisabeth; Ma, Minghe; Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Alicot, Elisabeth; Ma, Minghe; Carroll, Michael C.] Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA.
[Alicot, Elisabeth; Ma, Minghe; Carroll, Michael C.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Getahun, Andrew] Univ Colorado, Sch Med, Dept Immunol, Denver, CO 80206 USA.
[Getahun, Andrew] Natl Jewish Hlth, Denver, CO 80206 USA.
[Ellmerich, Stephan] UCL, Ctr Amyloidosis & Acute Phase Prot, Div Med, London NW3 2PF, England.
RP Heyman, B (reprint author), Uppsala Univ, Dept Med Biochem & Microbiol, BMC, SE-75123 Uppsala, Sweden.
EM birgitta.heyman@imbim.uu.se
FU Uppsala University; Swedish Research Council; Ellen Foundation; Walter
Foundation; Lennart Hesselman Foundation; Hans von Kantzow Foundation;
King Gustaf V 80 Years Foundation; Ollie and Elof Ericsson Foundation;
Agnes and Mac Rudberg Foundation; National Institutes of Health [RO1
AI039246]
FX We thank Drs. Marina Botto, Bo Nilsson, Kristina Nilsson Ekdahl, Chae
Gyu Park, Mark Pepys, Marc Shulman, Steffen Thiel, Joshua Thurman, and
Raul Torres for helpful suggestions, comments, and generous gifts of
reagents and mice. This work was supported by Uppsala University; the
Swedish Research Council; the Ellen, Walter, and Lennart Hesselman
Foundation; the Hans von Kantzow Foundation; the King Gustaf V 80 Years
Foundation; the Ollie and Elof Ericsson Foundation; the Agnes and Mac
Rudberg Foundation (B.H.); and National Institutes of Health Grant RO1
AI039246 (to M.C.C.).
NR 65
TC 12
Z9 13
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 25
PY 2011
VL 108
IS 43
BP E934
EP E942
DI 10.1073/pnas.1109831108
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 839OU
UT WOS:000296378100011
PM 21987785
ER
PT J
AU Hochedlinger, K
AF Hochedlinger, Konrad
TI Embryonic Stem Cells: Testing the Germ-Cell Theory
SO CURRENT BIOLOGY
LA English
DT Editorial Material
ID MOUSE; ORIGIN; DERIVATION
C1 [Hochedlinger, Konrad] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
[Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA 02114 USA.
[Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Hochedlinger, K (reprint author), Harvard Univ, Howard Hughes Med Inst, 7 Divin Ave, Cambridge, MA 02138 USA.
EM khochedlinger@helix.mgh.harvard.edu
NR 16
TC 2
Z9 2
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD OCT 25
PY 2011
VL 21
IS 20
BP R850
EP R852
DI 10.1016/j.cub.2011.09.024
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 838NQ
UT WOS:000296299700010
PM 22032189
ER
PT J
AU Lee, J
Srinivasan, V
Radhakrishnan, H
Boas, DA
AF Lee, Jonghwan
Srinivasan, Vivek
Radhakrishnan, Harsha
Boas, David A.
TI Motion correction for phase-resolved dynamic optical coherence
tomography imaging of rodent cerebral cortex
SO OPTICS EXPRESS
LA English
DT Article
ID TRACKING; ARTIFACT; SYSTEM; PET
AB Cardiac and respiratory motions in animals are the primary source of image quality degradation in dynamic imaging studies, especially when using phase-resolved imaging modalities such as spectral-domain optical coherence tomography (SD-OCT), whose phase signal is very sensitive to movements of the sample. This study demonstrates a method with which to compensate for motion artifacts in dynamic SD-OCT imaging of the rodent cerebral cortex. We observed that respiratory and cardiac motions mainly caused, respectively, bulk image shifts (BISs) and global phase fluctuations (GPFs). A cross-correlation maximization-based shift correction algorithm was effective in suppressing BISs, while GPFs were significantly reduced by removing axial and lateral global phase variations. In addition, a non-origin-centered GPF correction algorithm was examined. Several combinations of these algorithms were tested to find an optimized approach that improved image stability from 0.5 to 0.8 in terms of the cross-correlation over 4 s of dynamic imaging, and reduced phase noise by two orders of magnitude in similar to 8% voxels. (C)2011 Optical Society of America
C1 [Lee, Jonghwan; Srinivasan, Vivek; Radhakrishnan, Harsha; Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Lee, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA.
EM jonghwan@nmr.mgh.harvard.edu
RI Radhakrishnan, Harsha/K-5557-2012
FU US National Institutes of Health [R01NS057476, P01NS055104, R01EB000790,
R01-EB001954, K99NS067050]; AFOSR [MFELFA9550-07-1-0101]
FX The authors acknowledge financial support from US National Institutes of
Health grants R01NS057476, P01NS055104, R01EB000790, R01-EB001954, and
K99NS067050, and the AFOSR (MFELFA9550-07-1-0101). The authors thank J.
Jiang at Thorlabs for helping with the SD-OCT system.
NR 19
TC 28
Z9 28
U1 1
U2 6
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1094-4087
J9 OPT EXPRESS
JI Opt. Express
PD OCT 24
PY 2011
VL 19
IS 22
BP 21258
EP 21270
DI 10.1364/OE.19.021258
PG 13
WC Optics
SC Optics
GA 842DC
UT WOS:000296568100017
PM 22108978
ER
PT J
AU Lim, PY
Keating, JA
Hoover, S
Striker, R
Bernard, KA
AF Lim, Pei-Yin
Keating, Julie A.
Hoover, Spencer
Striker, Rob
Bernard, Kristen A.
TI A Thiopurine Drug Inhibits West Nile Virus Production in Cell Culture,
but Not in Mice
SO PLOS ONE
LA English
DT Article
ID DEPENDENT RNA-POLYMERASES; HEPATITIS-C VIRUS; 6-METHYLMERCAPTOPURINE
RIBOSIDE; LIVER-TRANSPLANTATION; MYCOPHENOLIC-ACID; CHAIN-TERMINATORS;
CRYSTAL-STRUCTURE; VIRAL LOAD; CDNA-CLONE; RIBAVIRIN
AB Many viruses within the Flavivirus genus cause significant disease in humans; however, effective antivirals against these viruses are not currently available. We have previously shown that a thiopurine drug, 6-methylmercaptopurine riboside (6MMPr), inhibits replication of distantly related viruses within the Flaviviridae family in cell culture, including bovine viral diarrhea virus and hepatitis C virus replicon. Here we further examined the potential antiviral effect of 6MMPr on several diverse flaviviruses. In cell culture, 6MMPr inhibited virus production of yellow fever virus, dengue virus-2 (DENV-2) and West Nile virus (WNV) in a dose-dependent manner, and DENV-2 was significantly more sensitive to 6MMPr treatment than WNV. We then explored the use of 6MMPr as an antiviral against WNV in an immunocompetent mouse model. Once a day treatment of mice with 0.5 mg 6MMPr was just below the toxic dose in our mouse model, and this dose was used in subsequent studies. Mice were treated with 6MMPr immediately after subcutaneous inoculation with WNV for eight consecutive days. Treatment with 6MMPr exacerbated weight loss in WNV-inoculated mice and did not significantly affect mortality. We hypothesized that 6MMPr has low bioavailability in the central nervous system (CNS) and examined the effect of pre-treatment with 6MMPr on viral loads in the periphery and CNS. Pre-treatment with 6MMPr had no significant effect on viremia or viral titers in the periphery, but resulted in significantly higher viral loads in the brain, suggesting that the effect of 6MMPr is tissue-dependent. In conclusion, despite being a potent inhibitor of flaviviruses in cell culture, 6MMPr was not effective against West Nile disease in mice; however, further studies are warranted to reduce the toxicity and/or improve the bioavailability of this potential antiviral drug.
C1 [Lim, Pei-Yin; Bernard, Kristen A.] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA.
[Lim, Pei-Yin; Bernard, Kristen A.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
[Striker, Rob] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[Keating, Julie A.; Hoover, Spencer; Striker, Rob] Univ Wisconsin, Dept Med, Madison, WI USA.
RP Lim, PY (reprint author), Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA.
EM kbernard@vetmed.wisc.edu
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health (NIH) [1U01-AI061193, 2T32AI007414]; Northeast
Biodefence Center [U54-AI057158]
FX This work was partially supported by federal funds from the National
Institute of Allergy and Infectious Diseases, and the National
Institutes of Health (NIH) under 1U01-AI061193. The BSL-3 animal core,
which is funded in part by the Northeast Biodefence Center
(U54-AI057158), was used for the animal studies conducted at the
Wadsworth Center. JAK was supported by the NIH-funded Cellular and
Molecular Parasitology Training Program (2T32AI007414). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 34
TC 2
Z9 2
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 24
PY 2011
VL 6
IS 10
AR e26697
DI 10.1371/journal.pone.0026697
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 841MA
UT WOS:000296515200043
PM 22039536
ER
PT J
AU Sullivan, C
Chen, YY
Shan, Y
Hu, YG
Peng, C
Zhang, HJ
Kong, LH
Li, SG
AF Sullivan, Con
Chen, Yaoyu
Shan, Yi
Hu, Yiguo
Peng, Cong
Zhang, Haojian
Kong, Linghong
Li, Shaoguang
TI Functional Ramifications for the Loss of P-Selectin Expression on
Hematopoietic and Leukemic Stem Cells
SO PLOS ONE
LA English
DT Article
ID CHRONIC MYELOID-LEUKEMIA; MICE; INFLAMMATION
AB Hematopoiesis is a tightly regulated biological process that relies upon complicated interactions between blood cells and their microenvironment to preserve the homeostatic balance of long-term hematopoietic stem cells (LT-HSCs), short-term HSCs (ST-HSCs), multipotent progenitors (MPPs), and differentiated cells. Adhesion molecules like P-selectin (encoded by the Selp gene) are essential to hematopoiesis, and their dysregulation has been linked to leukemogenesis. Like HSCs, leukemic stem cells (LSCs) depend upon their microenvironments for survival and propagation. P-selectin plays a crucial role in Philadelphia chromosome -positive (Ph(+)) chronic myeloid leukemia (CML). In this paper, we show that cells deficient in P-selectin expression can repopulate the marrow more efficiently than wild type controls. This results from an increase in HSC self-renewal rather than alternative possibilities like increased homing velocity or cell cycle defects. We also show that P-selectin expression on LT-HSCs, but not ST-HSCs and MPPs, increases with aging. In the absence of P-selectin expression, mice at 6 months of age possess increased levels of short-term HSCs and multipotent progenitors. By 11 months of age, there is a shift towards increased levels of long-term HSCs. Recipients of BCR-ABL-transduced bone marrow cells from P-selectin-deficient donors develop a more aggressive CML, with increased percentages of LSCs and progenitors. Taken together, our data reveal that P-selectin expression on HSCs and LSCs has important functional ramifications for both hematopoiesis and leukemogenesis, which is most likely attributable to an intrinsic effect on stem cell self-renewal.
C1 [Sullivan, Con] Maine Inst Human Genet & Hlth, Bangor, ME USA.
[Chen, Yaoyu; Shan, Yi; Peng, Cong; Zhang, Haojian; Li, Shaoguang] Univ Massachusetts, Sch Med, Dept Med, Div Hematol Oncol, Worcester, MA USA.
[Sullivan, Con; Chen, Yaoyu; Hu, Yiguo; Peng, Cong; Zhang, Haojian; Kong, Linghong; Li, Shaoguang] Jackson Lab, Bar Harbor, ME 04609 USA.
[Hu, Yiguo] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Sullivan, C (reprint author), Maine Inst Human Genet & Hlth, Bangor, ME USA.
EM shaoguang.li@umassmed.edu
RI Peng, Cong/H-2286-2011; Zhang, Haojian/H-7897-2013; Shan, Yi/E-3862-2016
FU National Institutes of Health [CA122142, CA114199]
FX This work was supported by the National Institutes of Health
(CA122142,CA114199). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 15
TC 8
Z9 8
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 24
PY 2011
VL 6
IS 10
AR e26246
DI 10.1371/journal.pone.0026246
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 841MA
UT WOS:000296515200007
PM 22039451
ER
PT J
AU Grady, D
Berkowitz, SA
AF Grady, Deborah
Berkowitz, Seth A.
TI Why Is a Good Clinical Prediction Rule So Hard to Find?
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID IMPACT
C1 [Grady, Deborah; Berkowitz, Seth A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA.
[Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Grady, D (reprint author), Univ Calif San Francisco, Dept Med, 1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA.
EM Deborah.Grady@ucsf.edu
NR 10
TC 16
Z9 17
U1 0
U2 8
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 OCT 24
PY 2011
VL 171
IS 19
BP 1701
EP 1702
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 837JX
UT WOS:000296198200001
PM 22025427
ER
PT J
AU Deo, R
Vittinghoff, E
Lin, F
Tseng, ZH
Hulley, SB
Shlipak, MG
AF Deo, Rajat
Vittinghoff, Eric
Lin, Feng
Tseng, Zian H.
Hulley, Stephen B.
Shlipak, Michael G.
TI Risk Factor and Prediction Modeling for Sudden Cardiac Death in Women
With Coronary Artery Disease
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; ANTIARRHYTHMIC-DRUG THERAPY;
HEART-DISEASE; ESTROGEN/PROGESTIN REPLACEMENT; VENTRICULAR-ARRHYTHMIAS;
POSTMENOPAUSAL WOMEN; EJECTION FRACTION; UNEXPECTED DEATH;
RANDOMIZED-TRIAL; PREVENTION
AB Background: To our knowledge, the risk of sudden cardiac death (SCD) and the assessment of risk factors in prediction models have not been evaluated in women with coronary artery disease (CAD). We sought to evaluate the incidence of SCD as well as its risk factors and their predictive accuracy among a population of women with CAD.
Methods: The Heart and Estrogen/progestin Replacement Study evaluated the effects of hormone replacement therapy on cardiovascular events among 2763 postmenopausal women with CAD. Sudden cardiac death was defined as death resulting from a cardiac origin that occurred within 1 hour of symptom onset. The associations between candidate predictor variables and SCD were evaluated in a Cox proportional hazards model. The C-index was used to compare the predictive value of the clinical risk factors with left ventricular ejection fraction (LVEF) alone and in combination. The net reclassification improvement was also computed.
Results: Over a mean follow-up of 6.8 years, SCD comprised 136 of the 254 cardiac deaths. The annual SCD event rate was 0.79% (95% confidence interval, 0.67-0.94). The following variables were independently associated with SCD in the multivariate model: myocardial infarction, heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes. The incidences of SCD among women with 0 (n = 683), 1 (n = 1224), 2 (n = 610), and 3 plus (n = 246) risk factors at baseline were 0.3%, 0.5%, 1.2%, and 2.9% per year, respectively. The combination of clinical risk factors and LVEF (C-index, 0.681) were better predictors of SCD than LVEF alone (C-index, 0.600) and resulted in a net reclassification improvement of 0.20 (P < .001).
Conclusions: Sudden cardiac death comprised the majority of cardiac deaths among postmenopausal women with CAD. Independent predictors of SCD, including myocardial infarction, congestive heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes, improved SCD prediction when they were considered in addition to LVEF.
C1 [Deo, Rajat] Univ Penn, Sect Electrophysiol, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
[Vittinghoff, Eric; Lin, Feng; Hulley, Stephen B.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Tseng, Zian H.] Univ Calif San Francisco, Cardiac Electrophysiol Sect, Div Cardiol, Dept Med, San Francisco, CA 94143 USA.
[Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, Dept Med, San Francisco, CA USA.
RP Deo, R (reprint author), Univ Penn, Sect Electrophysiol, Div Cardiovasc Med, 3400 Spruce St,9 Founders Cardiol, Philadelphia, PA 19104 USA.
EM Rajat.Deo@uphs.upenn.edu
FU National Institutes of Health (NIH) [K23DK089118, R01 HL102090];
National Center for Research Resources, NIH [KL2 RR024132]; NIH Roadmap
for Medical Research; Kynett-FOCUS Junior Faculty Investigator Award for
Research in Women's Cardiovascular Health; Edna G. Kynett Memorial
Foundation at the University of Pennsylvania School of Medicine
FX Dr Deo was supported by grants K23DK089118 from the National Institutes
of Health (NIH) and KL2 RR024132 from the National Center for Research
Resources, a component of the NIH and NIH Roadmap for Medical Research.
Additional grant support was obtained from a Kynett-FOCUS Junior Faculty
Investigator Award for Research in Women's Cardiovascular Health funded
by the Edna G. Kynett Memorial Foundation at the University of
Pennsylvania School of Medicine. Dr Tseng is supported by grant R01
HL102090 from the NIH.
NR 40
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U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD OCT 24
PY 2011
VL 171
IS 19
BP 1703
EP 1709
DI 10.1001/archinternmed.2011.328
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 837JX
UT WOS:000296198200002
PM 21788534
ER
PT J
AU Paynter, NP
Mazer, NA
Pradhan, AD
Gaziano, JM
Ridker, PM
Cook, NR
AF Paynter, Nina P.
Mazer, Norman A.
Pradhan, Aruna D.
Gaziano, J. Michael
Ridker, Paul M.
Cook, Nancy R.
TI Cardiovascular Risk Prediction in Diabetic Men and Women Using
Hemoglobin A(1c) vs Diabetes as a High-Risk Equivalent
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID CORONARY-HEART-DISEASE; PRIMARY PREVENTION; VASCULAR-DISEASE; MELLITUS;
RECLASSIFICATION; METAANALYSIS; EVENTS; STATISTICS; FRAMINGHAM; ASPIRIN
AB Background: It is unclear whether models that include hemoglobin A(1c) (HbA(1c)) levels only for diabetic patients improve the ability to predict cardiovascular disease (CVD) risk compared with the currently recommended classification of diabetes as a cardiovascular risk equivalent.
Methods: A total of 24 674 women (including 685 diabetic participants at baseline) and 11 280 men (including 563 diabetic participants at baseline) were followed up prospectively for cardiovascular disease (CVD). One hundred twenty-five CVD events occurred in diabetic women (666 in nondiabetic women), and 170 events occurred in diabetic men (1382 in nondiabetic men). Models for CVD risk were generated separately for men and women using the traditional CVD risk factors with the addition of a term for HbA(1c) levels only for diabetic individuals. In diabetic participants, the resulting predicted risks were compared with classification of diabetes as a cardiovascular risk equivalent (10-year CVD risk of at least 20%).
Results: In women, the models including HbA(1c) levels in diabetic participants improved the C statistic by 0.177 (P < .001) over the risk equivalence model and showed improved reclassification (net reclassification improvement [NRI] of 26.7% [P = .001]). In men, the improvements were more modest but still statistically significant (C statistic change of 0.039 [P = .02]; NRI of 9.2% [P = .04]). Including HbA1c levels also improved prediction over a dichotomous term for diabetes in women (NRI of 11.8% [P = .03]) but not in men.
Conclusions: In both women and men with diabetes at baseline, we observed significant improvements in predictive ability of CVD risk using models incorporating HbA(1c) levels compared with classification of diabetes as a cardiovascular risk equivalent.
C1 [Paynter, Nina P.; Pradhan, Aruna D.; Gaziano, J. Michael; Ridker, Paul M.; Cook, Nancy R.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
[Mazer, Norman A.] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland.
[Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA.
RP Paynter, NP (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave, Boston, MA 02215 USA.
EM npaynter@partners.org
FU F. Hoffmann-La Roche, Ltd.; Leducq Foundation; Roche Diagnostics; Amgen,
Inc; AstraZeneca; Novartis; Merck; Abbott; sanofi-aventis;
Schering-Plough; Isis; Siemens; Vascular Biogenics; National Heart Lung
and Blood Institute [HL 043851, HL 080467, CA 047988, CA 97193, CA
34944, CA 40360, HL 26490, HL 34595]; National Cancer Institute,
Bethesda, Maryland; Donald W. Reynolds Foundation, Las Vegas, Nevada
FX Dr Paynter reports receiving investigator-initiated funding for this
project from F. Hoffmann-La Roche, Ltd. Dr Mazer reports employment by
and stock ownership in F. Hoffmann-La Roche, Ltd. Dr. Ridker reports
receiving investigator-initiated funding from the Leducq Foundation,
Roche Diagnostics, Amgen, Inc, AstraZeneca, Novartis, Merck, Abbott, and
sanofi-aventis; consulting fees from AstraZeneca, Novartis, Merck
Schering-Plough, sanofi-aventis, Isis, Siemens, and Vascular Biogenics;
and is listed as a coinventor on patents held by Brigham and Women's
Hospital that relate to the use of inflammatory biomarkers in CVD,
including the use of high-sensitivity C-reactive protein in the
evaluation of patients' risk of CVD. These patents have been licensed to
Siemens and AstraZeneca.; This work was carried out with support from F.
Hoffmann-La Roche Ltd; grants HL 043851, HL 080467, and CA 047988 for
the Women's Health Study and grants CA 97193, CA 34944, CA 40360, HL
26490, and HL 34595 for the Physician's Health Study II from the
National Heart Lung and Blood Institute and National Cancer Institute,
Bethesda, Maryland; and the Donald W. Reynolds Foundation, Las Vegas,
Nevada.
NR 27
TC 23
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U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD OCT 24
PY 2011
VL 171
IS 19
BP 1712
EP 1718
DI 10.1001/archinternmed.2011.351
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 837JX
UT WOS:000296198200004
PM 21788538
ER
PT J
AU Butt, AA
Justice, AC
Freiberg, MS
AF Butt, Adeel A.
Justice, Amy C.
Freiberg, Matthew S.
TI Risk of Heart Failure With Human Immunodeficiency Virus Is Greater Than
Hypertension? Reply
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
ID INFECTION; DISEASE
C1 [Butt, Adeel A.; Freiberg, Matthew S.] Univ Pittsburgh, Dept Med, Sch Med, Pittsburgh, PA 15213 USA.
[Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA.
[Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA.
RP Butt, AA (reprint author), Univ Pittsburgh, Dept Med, Sch Med, 3601 5th Ave,Ste 3A, Pittsburgh, PA 15213 USA.
EM butta@dom.pitt.edu
NR 4
TC 0
Z9 0
U1 0
U2 2
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 OCT 24
PY 2011
VL 171
IS 19
BP 1773
EP 1774
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 837JX
UT WOS:000296198200022
ER
PT J
AU Hilbert, A
Vogele, C
Tuschen-Caffier, B
Hartmann, AS
AF Hilbert, Anja
Voegele, Claus
Tuschen-Caffier, Brunna
Hartmann, Andrea S.
TI Psychophysiological responses to idiosyncratic stress in bulimia nervosa
and binge eating disorder
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE Stress; Psychophysiology; Heart rate variability; Bulimia nervosa; Binge
eating disorder
ID HEART-RATE-VARIABILITY; CARDIAC VAGAL TONE; MOMENTARY ASSESSMENT;
EMOTION REGULATION; BLOOD-PRESSURE; OBESE WOMEN; REACTIVITY; LEPTIN;
MOOD; PSYCHOPATHOLOGY
AB This study examined psychophysiological stress responses to idiosyncratically relevant stress in bulimia nervosa (BN) and binge eating disorder (BED), in relation to autonomic cardiac control and nutritional status. A total of 81 women with BN, BED and healthy controls (HC) took part in an in sensu exposure to idiosyncratic stress. Psychological and peripheral physiological parameters were measured, and tonic heart rate variability, nutritional status, and types of stress were determined. In response to stress exposure, both eating disordered groups showed a stronger reactivity of sadness, and the BED group showed a stronger reactivity of insecurity than the HC group. Desire to binge was increased in the context of interpersonal stress. Stress exposure led to increased cardiovascular activity and reduced electrodermal activity that did not differ by group. The BN-specific symptomatology moderated the association between autonomic cardiac control and psychophysiological stress responses. The results suggest common and specific psychophysiological processes in symptom maintenance through life stress in EN and BED. (C) 2011 Published by Elsevier Inc.
C1 [Hilbert, Anja] Univ Fribourg, Dept Psychol, CH-1700 Fribourg, Switzerland.
[Voegele, Claus] Univ Luxembourg, Res Unit INSIDE, L-7201 Walferdange, Luxembourg.
[Tuschen-Caffier, Brunna] Univ Freiburg, Inst Psychol, D-79085 Freiburg, Germany.
[Hartmann, Andrea S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA.
RP Hilbert, A (reprint author), Univ Fribourg, Dept Psychol, Rue P-A de Faucigny 2, CH-1700 Fribourg, Switzerland.
EM anja.hilbert@unifr.ch; Claus.Voegele@uni.lu;
tuschen@psychologie.uni-freiburg.de; ahartmann1@partners.org
FU German Research Foundation [TU 78/1-2]
FX Funding sources for this study include grant TU 78/1-2 funded by the
German Research Foundation (Dr. Tuschen-Caffier).
NR 60
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U1 2
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD OCT 24
PY 2011
VL 104
IS 5
BP 770
EP 777
DI 10.1016/j.physbeh.2011.07.013
PG 8
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA 837MP
UT WOS:000296208200017
PM 21839762
ER
PT J
AU Torterolo, P
Ramos, OV
Sampogna, S
Chase, MH
AF Torterolo, Pablo
Ramos, Oscar V.
Sampogna, Sharon
Chase, Michael H.
TI Hypocretinergic neurons are activated in conjunction with goal-oriented
survival-related motor behaviors
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE Orexin; Sleep; Motivation; Reward; Hypothalamus
ID MESENCEPHALIC LOCOMOTOR REGION; HYPOTHALAMIC OREXIN NEURONS;
SLEEP-WAKING CYCLE; C-FOS; SEXUAL-BEHAVIOR; LATERAL HYPOTHALAMUS; CANINE
NARCOLEPSY; SELF-STIMULATION; LOCUS-COERULEUS; KNOCKOUT MICE
AB Hypocretinergic neurons are located in the area of the lateral hypothalamus which is responsible for mediating goal-directed, survival-related behaviors. Consequently, we hypothesize that the hypocretinergic system functions to promote these behaviors including those patterns of somatomotor activation upon which they are based. Further, we hypothesize that the hypocretinergic system is not involved with repetitive motor activities unless they occur in conjunction with the goal-oriented behaviors that are governed by the lateral hypothalamus. In order to determine the veracity of these hypotheses, we examined Fos immunoreactivity (as a marker of neuronal activity) in hypocretinergic neurons in the cat during: a) Exploratory Motor Activity; b) Locomotion without Reward; c) Locomotion with Reward; and d) Wakefulness without Motor Activity. Significantly greater numbers of hypocretinergic neurons expressed c-fos when the animals were exploring an unknown environment during Exploratory Motor Activity compared with all other paradigms. In addition, a larger number of Hcrt + Fos + neurons were activated during Locomotion with Reward than during Wakefulness without Motor Activity. Finally, very few hypocretinergic neurons were activated during Locomotion without Reward and Wakefulness without Motor Activity, wherein there was an absence of goal-directed activities. We conclude that the hypocretinergic system does not promote wakefulness per se or motor activity per se but is responsible for mediating specific goal-oriented behaviors that take place during wakefulness. Accordingly, we suggest that the hypocretinergic system is responsible for controlling the somatomotor system and coordinating its activity with other systems in order to produce successful goal-oriented survival-related behaviors that are controlled by the lateral hypothalamus. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Ramos, Oscar V.; Sampogna, Sharon; Chase, Michael H.] WebSci Int, Los Angeles, CA 90024 USA.
[Torterolo, Pablo; Chase, Michael H.] Univ Republica, Fac Med, Dept Fisiol, Montevideo, Uruguay.
[Chase, Michael H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Chase, Michael H.] UCLA Sch Med, Dept Physiol, Los Angeles, CA USA.
[Chase, Michael H.] UCLA Sch Med, Brain Res Inst, Los Angeles, CA USA.
RP Chase, MH (reprint author), WebSci Int, 1251 Westwood Blvd, Los Angeles, CA 90024 USA.
EM mchase@websciences.org
FU USPHS [NS09999]; Brain Sciences Foundation
FX This work was supported by USPHS Grant NS09999 and the Brain Sciences
Foundation.
NR 74
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U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD OCT 24
PY 2011
VL 104
IS 5
BP 823
EP 830
DI 10.1016/j.physbeh.2011.07.032
PG 8
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA 837MP
UT WOS:000296208200024
PM 21839102
ER
PT J
AU Crowley, WF
AF Crowley, William F.
TI The developmental biology of the GnRH neurons
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Editorial Material
ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC
HYPOGONADISM; OF-FUNCTION MUTATIONS; KALLMANN-SYNDROME; GENE;
PROKINETICIN-2; DEFICIENCY; MOLECULES; ADHESION; PUBERTY
C1 Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr Excellence, Boston, MA 02114 USA.
RP Crowley, WF (reprint author), Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr Excellence, 55 Fruit St,Bartlett Hall Extens,5th Floor, Boston, MA 02114 USA.
FU NICHD NIH HHS [U54 HD028138, R01 HD015788]
NR 22
TC 8
Z9 8
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD OCT 22
PY 2011
VL 346
IS 1-2
SI SI
BP 1
EP 3
DI 10.1016/j.mce.2011.06.023
PG 3
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 846UQ
UT WOS:000296929100001
PM 21741438
ER
PT J
AU Balasubramanian, R
Crowley, WF
AF Balasubramanian, Ravikumar
Crowley, William F., Jr.
TI Isolated GnRH deficiency: A disease model serving as a unique prism into
the systems biology of the GnRH neuronal network
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE GnRH; GnRH deficiency; GnRH neuronal ontogeny; Puberty; Kallmann
syndrome; Hypogonadotropic hypogonadism
ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM;
GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; PULSATILE
LUTEINIZING-HORMONE; LINKED KALLMANN-SYNDROME; FERTILE EUNUCH SYNDROME;
MONKEY MACACA-MULATTA; HUMAN METASTIN-45-54; PROKINETICIN 2; MUTATIONS
C1 [Crowley, William F., Jr.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA.
RP Crowley, WF (reprint author), Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Bartlett Hall Extens,5th Floor,55 Fruit St, Boston, MA 02114 USA.
EM wcrowley@partners.org
FU NICHD NIH HHS [U54 HD028138-22, R01 HD015788-26, R01 HD015788, U54
HD028138]
NR 77
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U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD OCT 22
PY 2011
VL 346
IS 1-2
SI SI
BP 4
EP 12
DI 10.1016/j.mce.2011.07.012
PG 9
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 846UQ
UT WOS:000296929100002
PM 21782888
ER
PT J
AU Wahab, F
Quinton, R
Seminara, SB
AF Wahab, Fazal
Quinton, Richard
Seminara, Stephanie B.
TI The kisspeptin signaling pathway and its role in human isolated GnRH
deficiency
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE Kisspeptin; Hypogonadotropic hypogonadism; GnRH deficiency
ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM;
GONADOTROPIN-RELEASING-HORMONE; PROTEIN-COUPLED RECEPTOR; HAMSTERS
PHODOPUS-SUNGORUS; HYPOTHALAMIC KISS-1 SYSTEM; MESSENGER-RNA EXPRESSION;
KALLMANN-SYNDROME; SIBERIAN HAMSTERS; REPRODUCTIVE-SYSTEM; MUTATIONS
AB Amplification of the neurosecretory activity of the GnRH system is the defining neuroendocrine event for sexual maturation. The physiological mechanisms that drive GnRH secretion at puberty have been difficult to identify but the discovery in 2003 that the G protein coupled receptor KISS1R is a key regulator of pubertal development in mice and men has ushered in a new chapter in reproductive neuroendocrinology. KISS1R is activated by endogenous peptides derived from a precursor protein, kisspeptin. Despite kisspeptin's importance in driving the reproductive cascade, relatively few patients with GnRH deficient states and mutations in the kisspeptin pathway have been described. Yet, these cases, coupled with loss-of-function mouse models, provide unique and complementary information into the biological role of this signaling system in the control of GnRH secretion. This article will examine some of the subtleties in genotype-phenotype correlations in both mice and men carrying disabling mutations in the kisspeptin pathway. (C) 2011 Published by Elsevier Ireland Ltd.
C1 [Wahab, Fazal; Seminara, Stephanie B.] Massachusetts Gen Hosp, Harvard Ctr Reprod Sci, Boston, MA 02114 USA.
[Wahab, Fazal; Seminara, Stephanie B.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA.
[Quinton, Richard] Newcastle Univ, Inst Human Genet, Endocrinol Res Grp, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England.
RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Harvard Ctr Reprod Sci, Fruit St, Boston, MA 02114 USA.
EM sseminara@partners.org
RI Wahab, Fazal/G-2478-2012
FU Eunice Kennedy Shriver NICHD/NIH [U54 HD28138-17, R01 HD43341-09]
FX This research was supported by the Eunice Kennedy Shriver NICHD/NIH
through cooperative agreement [U54 HD28138-17] as part of the
Specialized Cooperative Centers Program in Reproduction and Infertility
Research and R01 HD43341-09.
NR 71
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U1 2
U2 12
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD OCT 22
PY 2011
VL 346
IS 1-2
SI SI
BP 29
EP 36
DI 10.1016/j.mce.2011.05.043
PG 8
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 846UQ
UT WOS:000296929100005
PM 21704672
ER
PT J
AU Balasubramanian, R
Plummer, L
Sidis, Y
Pitteloud, N
Martin, C
Zhou, QY
Crowley, WF
AF Balasubramanian, Ravikumar
Plummer, Lacey
Sidis, Yisrael
Pitteloud, Nelly
Martin, Cecilia
Zhou, Qun-Yong
Crowley, William F., Jr.
TI The puzzles of the prokineticin 2 pathway in human reproduction
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE Prokineticin 2; Prokineticin 2 receptor; GnRH deficiency; GnRH neuronal
ontogeny; Kallmann syndrome; Hypogonadotropic hypogonadism
ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; PROTEIN-COUPLED RECEPTORS;
KALLMANN-SYNDROME; HORMONE DEFICIENCY; PHARMACOLOGICAL CHARACTERIZATION;
SUPRACHIASMATIC NUCLEUS; BIALLELIC MUTATIONS; OLFACTORY-BULB;
SNAKE-VENOM; EG-VEGF
AB Prokineticin, 1 (PROK1) and prokineticin 2 (PROK2), are two closely related proteins that were identified as the mammalian homologs of their two amphibian homologs, mamba intestinal toxin (MIT-1) and Bv8. MIT-1 was initially identified as a non-toxic constituent in the venom of the black mamba snake (Dendroaspis polylepis) (Joubert and Strydom, 1980) while Bv8 was identified in the skin secretion of the toad, Bombina variegate (Mollay et al., 1999). All three homologs stimulate gastrointestinal motility thus accounting for their family name "prokineticins" (Schweitz et al., 1990, 1999). However, since its initial description, both PROK1 and PROK2 have been found to regulate a dazzling array of biological functions throughout the body. In particular, PROK1 acts as a potent angiogenic mitogen on endocrine vascular epithelium, thus earning its other name, Endocrine gland-vascular endothelial factor (EG-VEGF) (LeCouter et al., 2002). In contrast, the PROK2 signaling pathway is a critical regulator of olfactory bulb morphogenesis and sexual maturation in mammals and this function is the focus of this review. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Balasubramanian, Ravikumar; Plummer, Lacey; Sidis, Yisrael; Pitteloud, Nelly; Martin, Cecilia; Crowley, William F., Jr.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr Excellence, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA.
[Zhou, Qun-Yong] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92717 USA.
RP Crowley, WF (reprint author), Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr Excellence, Reprod Endocrine Unit, Dept Med, 55 Fruit St,Bartlett Hall Extens,5th Floor, Boston, MA 02114 USA.
EM wcrowley@partners.org
RI PITTELOUD, Nelly/K-2709-2014
FU National Institutes of Health [5R01HD015788, 2T32HD007396, 5U54HD028138]
FX This work was supported by National Institutes of Health Grants
5R01HD015788, 2T32HD007396 and 5U54HD028138, as part of the Specialized
Cooperative Centers Program in Reproduction and Infertility Research.
NR 47
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U1 0
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD OCT 22
PY 2011
VL 346
IS 1-2
SI SI
BP 44
EP 50
DI 10.1016/j.mce.2011.05.040
PG 7
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 846UQ
UT WOS:000296929100007
PM 21664414
ER
PT J
AU Chan, YM
AF Chan, Yee-Ming
TI A needle in a haystack: Mutations in GNRH1 as a rare cause of isolated
GnRH deficiency
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE Gonadotropin-releasing hormone (GnRH); Luteinizing-hormone releasing
hormone (LHRH, LRH); Human genetics; hypogonadal (hpg) mouse;
Hypogonadotropic hypogonadism
ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC
HYPOGONADISM; FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE;
PROLACTIN SECRETION; GENETIC-ANALYSIS; RECEPTOR GENES; HPG MOUSE;
PEPTIDE; PRECURSOR
AB GNRH1, the human gene that gives rise to GnRH, has long been an obvious candidate gene for idiopathic hypogonadotropic hypogonadism, particularly because the hpg mouse, a mouse model of isolated hypogonadotropic hypogonadism, carries a deletion that disrupts Gnrh1. In 2009, 25 years after the sequence of human GNRH1 was initially determined, two groups independently reported homozygous frameshift' mutations in GNRH I in patients with idiopathic hypogonadotropic hypogonadism. In two additional families, heterozygous GNRH1 mutations segregated with reproductive disorders. In the first family, the mutation occurred alone in five female subjects with idiopathic hypogonadotropic hypogonadism, whereas in the second it co-existed with a mutation in NR0B1/DAX1 in two female subjects with delayed puberty. While hemizygous mutations the X-linked NR0B1 are a well-known cause of hypogonadotropic hypogonadism and adrenal hypoplasia in male patients, heterozygous female carriers are generally asymptomatic. Thus, mutations in GNRH1 have been associated with both mild and severe forms of GnRH deficiency, and may work in combination with other gene mutations to produce GnRH-deficient phenotypes. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Chan, Yee-Ming] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA.
[Chan, Yee-Ming] Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, Boston, MA 02114 USA.
[Chan, Yee-Ming] Childrens Hosp Boston, Dept Med, Div Endocrinol, Boston, MA 02115 USA.
RP Chan, YM (reprint author), Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Reprod Endocrine Unit, Dept Med, 55 Fruit St,BHX 5, Boston, MA 02114 USA.
EM ymchan@partners.org
FU Specialized Cooperative Centers for Reproduction and Infertility
Research [U54 HD028138, R01 HD043341, R01 HD015788]; Charles A. King
Trust; Children's Hospital Boston
FX This work was supported by U54 HD028138 as part of the Specialized
Cooperative Centers for Reproduction and Infertility Research R01
HD043341 and R01 HD015788. Y.-M.C. is supported by a Charles A. King
Trust Postdoctoral Fellowship and a Faculty Development Award from
Children's Hospital Boston.
NR 47
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U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD OCT 22
PY 2011
VL 346
IS 1-2
SI SI
BP 51
EP 56
DI 10.1016/j.mce.2011.06.013
PG 6
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 846UQ
UT WOS:000296929100008
PM 21722705
ER
PT J
AU Au, MG
Crowley, WF
Buck, CL
AF Au, Margaret G.
Crowley, William F., Jr.
Buck, Cassandra L.
TI Genetic counseling for isolated GnRH deficiency
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE Genetic counseling; GnRH deficiency; Kallmann syndrome
ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC
HYPOGONADISM; OF-FUNCTION MUTATIONS; FACTOR RECEPTOR 1;
KALLMANN-SYNDROME; NEUROKININ B; PROKINETICIN-2; GPR54; PHENOTYPES;
DELETIONS
AB As our understanding of the complexities of the various etiologies and complex genetic architecture of GnRH deficiency grows, so too does the need to apply newly-developed genetic tools in a way that: (a) is meaningful to individuals and their families; (b) integrates all of the phenotypic features of this syndrome into a rationale; and (c) provides up-to-date diagnostic technologies in a cost-effective algorithm of genetic testing. Genetic counseling aims to accomplish these goals through ascertainment of detailed family histories, targeted comprehensive phenotypic evaluations, informed selection of genetic testing, interpretation of genetic test results, and the provision of highly specific risk assessments and psychological support to individuals diagnosed with this reproductive condition.
This chapter offers a guide to incorporating this rapidly evolving state of knowledge of the pedigree and phenotypes into the process of selecting and prioritizing genetic testing. In addition, the provision of risk assessment that accounts for nuanced genetic concepts such as variable expressivity, incomplete penetrance, and oligogenicity, all of which are emerging features of the genetics of this clinical syndrome, is considered. Beyond translating genetic information, genetic counseling should address the psychological impact of embarrassment, shame, anxiety, and guilt that are often seen among individuals with reproductive disorders. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Buck, Cassandra L.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA.
RP Buck, CL (reprint author), Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, 55 Fruit St,BHX-5, Boston, MA 02114 USA.
EM clbuck@partners.org
FU Eunice Kennedy Shriver NICHD/NIH [U54 HD28138, R01 HD15788]
FX This research was supported by the Eunice Kennedy Shriver NICHD/NIH
through cooperative agreement U54 HD28138 as part of the Specialized
Cooperative Centers Program in Reproduction and Infertility Research and
R01 HD15788.
NR 36
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U1 1
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD OCT 22
PY 2011
VL 346
IS 1-2
SI SI
BP 102
EP 109
DI 10.1016/j.mce.2011.05.041
PG 8
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 846UQ
UT WOS:000296929100014
PM 21664415
ER
PT J
AU Pinello, L
Lo Bosco, G
Hanlon, B
Yuan, GC
AF Pinello, Luca
Lo Bosco, Giosue
Hanlon, Bret
Yuan, Guo-Cheng
TI A motif-independent metric for DNA sequence specificity
SO BMC BIOINFORMATICS
LA English
DT Article
ID HISTONE MODIFICATIONS; NUCLEOSOME OCCUPANCY; GENOMIC SEQUENCES;
STEM-CELLS; IDENTIFICATION; SITES; DIFFERENTIATION; METHYLATION;
PREDICTION; ENHANCERS
AB Background: Genome-wide mapping of protein-DNA interactions has been widely used to investigate biological functions of the genome. An important question is to what extent such interactions are regulated at the DNA sequence level. However, current investigation is hampered by the lack of computational methods for systematic evaluating sequence specificity.
Results: We present a simple, unbiased quantitative measure for DNA sequence specificity called the Motif Independent Measure (MIM). By analyzing both simulated and real experimental data, we found that the MIM measure can be used to detect sequence specificity independent of presence of transcription factor (TF) binding motifs. We also found that the level of specificity associated with H3K4me1 target sequences is highly cell-type specific and highest in embryonic stem (ES) cells. We predicted H3K4me1 target sequences by using the N-score model and found that the prediction accuracy is indeed high in ES cells. The software to compute the MIM is freely available at: https://github.com/lucapinello/mim.
Conclusions: Our method provides a unified framework for quantifying DNA sequence specificity and serves as a guide for development of sequence-based prediction models.
C1 [Lo Bosco, Giosue] Dipartimento Matemat & Informat, I-90123 Palermo, Italy.
[Pinello, Luca; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Hanlon, Bret] Univ Wisconsin, Dept Stat, Madison, WI 53706 USA.
RP Lo Bosco, G (reprint author), Dipartimento Matemat & Informat, Via Archirafi 34, I-90123 Palermo, Italy.
EM giosue.lobosco@unipa.it; gcyuan@jimmy.harvard.edu
RI Lo Bosco, Giosue/C-7644-2011
OI Lo Bosco, Giosue/0000-0002-1602-0693
FU NIH [HG005085]; Harvard School of Public Health
FX We thank Zhen Shao for help with H3K4me1 data collection and initial
processing. GY's research was supported by the NIH grant HG005085 and a
Career Incubator Award from the Harvard School of Public Health.
NR 43
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U1 0
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD OCT 21
PY 2011
VL 12
AR 408
DI 10.1186/1471-2105-12-408
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 873JS
UT WOS:000298879700001
PM 22017798
ER
PT J
AU Abdel-Motal, UM
Sarkis, PTN
Han, T
Pudney, J
Anderson, DJ
Zhu, Q
Marasco, WA
AF Abdel-Motal, Ussama M.
Sarkis, Phuong T. N.
Han, Thomas
Pudney, Jeffery
Anderson, Deborah J.
Zhu, Quan
Marasco, Wayne A.
TI Anti-gp120 Minibody Gene Transfer to Female Genital Epithelial Cells
Protects against HIV-1 Virus Challenge In Vitro
SO PLOS ONE
LA English
DT Article
ID LEUKOCYTE PROTEASE INHIBITOR; IMMUNODEFICIENCY-VIRUS; ADENOASSOCIATED
VIRUS; MONOCLONAL-ANTIBODY; VAGINAL EPITHELIUM; LONG-TERM; EXPRESSION;
VECTOR; NEUTRALIZATION; TRANSDUCTION
AB Background: Although cervico-vaginal epithelial cells of the female lower genital tract provide the initial defense system against HIV-1 infection, the protection is sometimes incomplete. Thus, enhancing anti-HIV-1 humoral immunity at the mucosal cell surface by local expression of anti-HIV-1 broadly neutralizing antibodies (BnAb) that block HIV-1 entry would provide an important new intervention that could slow the spread of HIV/AIDS.
Methods and Findings: This study tested the hypothesis that adeno-associated virus (AAV)-BnAb gene transfer to cervico-vaginal epithelial cells will lead to protection against HIV-1. Accordingly, a recombinant AAV vector that encodes human b12 anti-HIV gp120 BnAb as a single-chain variable fragment Fc fusion (scFvFc), or "minibody'' was constructed. The secreted b12 minibody was shown to be biologically functional in binding to virus envelope protein, neutralizing HIV-1 and importantly, blocking transfer and infectivity of HIV-1(bal) in an organotypic human vaginal epithelial cell (VEC) model. Furthermore, cervico-vaginal epithelial stem cells were found to be efficiently transduced by the optimal AAV serotype mediated expression of GFP.
Conclusion: This study provides the foundation for a novel microbicide strategy to protect against sexual transmission of HIV-1 by AAV transfer of broadly neutralizing antibody genes to cervico-vaginal epithelial stem cells that could replenish b12 BnAb secreting cells through multiple menstrual cycles.
C1 [Abdel-Motal, Ussama M.; Sarkis, Phuong T. N.; Han, Thomas; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Pudney, Jeffery; Anderson, Deborah J.] Boston Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA 02118 USA.
RP Abdel-Motal, UM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA.
EM wayne_marasco@dfci.harvard.edu
OI Han, Thang/0000-0003-2570-0938
FU National Institutes of Health (NIH) [AI079767]
FX Funding: This work was supported by the National Institutes of Health
(NIH) grant AI079767 to Dr. Marasco. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 39
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U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 21
PY 2011
VL 6
IS 10
AR e26473
DI 10.1371/journal.pone.0026473
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 841LG
UT WOS:000296513200024
PM 22031835
ER
PT J
AU Arjomandi, M
Frelinger, J
Donde, A
Wong, H
Yellamilli, A
Raymond, W
AF Arjomandi, Mehrdad
Frelinger, Jessica
Donde, Aneesh
Wong, Hofer
Yellamilli, Amritha
Raymond, Wilfred
TI Secreted Osteopontin Is Highly Polymerized in Human Airways and
Fragmented in Asthmatic Airway Secretions
SO PLOS ONE
LA English
DT Article
ID RHEUMATOID-ARTHRITIS; POSTTRANSLATIONAL MODIFICATIONS; STRUCTURAL
REQUIREMENTS; INTEGRIN ALPHA-9-BETA-1; NEUTROPHIL INFILTRATION; TISSUE
TRANSGLUTAMINASE; BOVINE OSTEOPONTIN; DEFICIENT MICE; CROSS-LINKING;
MURINE MODEL
AB Background: Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family and a cytokine with diverse biologic roles. OPN undergoes extensive post-translational modifications, including polymerization and proteolytic fragmentation, which alters its biologic activity. Recent studies suggest that OPN may contribute to the pathogenesis of asthma.
Methodology: To determine whether secreted OPN (sOPN) is polymerized in human airways and whether it is qualitatively different in asthma, we used immunoblotting to examine sOPN in bronchoalveolar lavage (BAL) fluid samples from 12 healthy and 21 asthmatic subjects (and in sputum samples from 27 healthy and 21 asthmatic subjects). All asthmatic subjects had mild to moderate asthma and abstained from corticosteroids during the study. Furthermore, we examined the relationship between airway sOPN and cellular inflammation.
Principal Findings: We found that sOPN in BAL fluid and sputum exists in polymeric, monomeric, and cleaved forms, with most of it in polymeric form. Compared to healthy subjects, asthmatic subjects had proportionately less polymeric sOPN and more monomeric and cleaved sOPN. Polymeric sOPN in BAL fluid was associated with increased alveolar macrophage counts in airways in all subjects.
Conclusions: These results suggest that sOPN in human airways (1) undergoes extensive post-translational modification by polymerization and proteolytic fragmentation, (2) is more fragmented and less polymerized in subjects with mild to moderate asthma, and (3) may contribute to recruitment or survival of alveolar macrophages.
C1 [Arjomandi, Mehrdad; Frelinger, Jessica] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA.
[Arjomandi, Mehrdad; Frelinger, Jessica; Donde, Aneesh; Wong, Hofer; Yellamilli, Amritha] Univ Calif San Francisco, Dept Med, Human Exposure Lab, San Francisco, CA USA.
[Raymond, Wilfred] Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA.
[Arjomandi, Mehrdad; Frelinger, Jessica; Raymond, Wilfred] San Francisco VA Med Ctr, Pulm Res Grp, San Francisco, CA USA.
RP Arjomandi, M (reprint author), Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA.
EM mehrdad.arjomandi@ucsf.edu
FU National Institutes of Health (NIH) [K23 HL083099, NIH P01 HL024136];
NIH/NCRR/OD [KL2 RR024130]; Northern California Institute for Research
and Education; University of California San Francisco Cardiovascular
Research Institute
FX Funding: This work was supported by National Institutes of Health (NIH)
K23 HL083099, NIH P01 HL024136, NIH/NCRR/OD UCSF-CTSI Grant Number KL2
RR024130, Northern California Institute for Research and Education, and
University of California San Francisco Cardiovascular Research Institute
Faculty Development Funds. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 69
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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 OCT 21
PY 2011
VL 6
IS 10
AR e25678
DI 10.1371/journal.pone.0025678
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 841LG
UT WOS:000296513200005
PM 22031818
ER
PT J
AU Grassberger, C
Paganetti, H
AF Grassberger, C.
Paganetti, H.
TI Elevated LET components in clinical proton beams
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID RELATIVE BIOLOGICAL EFFECTIVENESS; MONTE-CARLO SIMULATIONS; LOW-ENERGY
PROTONS; V79 CELLS; THERAPY; RBE; INACTIVATION; PARTICLES; IONS;
DISTRIBUTIONS
AB This paper assesses the contribution of secondary particles to pencil and passively scattered proton beams, in particular when considering the dose-averaged linear energy transfer (LET(d)) in biological treatment planning. Proton Monte Carlo simulations are performed in water phantoms and for two patients, considering all primary and secondary particles, including recoils from inelastic nuclear interactions. Our results show that secondary protons exhibit LET(d) values up to a factor 10 higher than those of the primary protons at the same depth. Thus, secondary protons have a significant impact on the LET(d). Their contribution increases the LET(d) by similar to 50% along the central axis and even > 200% in the penumbra. Furthermore, the LET maximum after the peak changes from 12 to 15 keV mu m(-1) when adding secondary protons to the primary contribution. This is important when modeling LET(d) with analytical methods. The contribution of recoils (A > 3) is observed to be 1.2% in the entrance region considering a prostate case. The degree of biological damage inflicted by recoils remains hard to quantify, but is discussed on the basis of detailed energy spectra. The results highlight the role of secondary protons in LET-based radiobiological effectiveness calculations for proton therapy and when analyzing radiobiological experiments. Furthermore, the findings demonstrate the impact of inhomogeneities on the LET and the subtle changes between the LET distributions of passively scattered and actively scanned beams.
C1 [Grassberger, C.; Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Grassberger, C.; Paganetti, H.] Harvard Univ, Sch Med, Boston, MA USA.
[Grassberger, C.] Paul Scherrer Inst, Ctr Proton Radiotherapy, CH-5232 Villigen, Switzerland.
RP Grassberger, C (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
EM cgrassberger@partners.org
FU Federal Share of program income earned by Massachusetts General
Hospital, Proton Therapy Research and Treatment Center [C06 CA059267]
FX The authors thank Tony Lomax for many useful comments and suggestions,
as well as AlejandroCarabe-Fernandez and Jan Schumann for various lively
discussions around the topic. The project was supported by the Federal
Share of program income earned by Massachusetts General Hospital on C06
CA059267, Proton Therapy Research and Treatment Center.
NR 38
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U1 0
U2 8
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 OCT 21
PY 2011
VL 56
IS 20
BP 6677
EP 6691
DI 10.1088/0031-9155/56/20/011
PG 15
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 842MS
UT WOS:000296604200014
PM 21965268
ER
PT J
AU Hirschey, MD
Shimazu, T
Jing, E
Grueter, CA
Collins, AM
Aouizerat, B
Stancakova, A
Goetzman, E
Lam, MM
Schwer, B
Stevens, RD
Muehlbauer, MJ
Kakar, S
Bass, NM
Kuusisto, J
Laakso, M
Alt, FW
Newgard, CB
Farese, RV
Kahn, CR
Verdin, E
AF Hirschey, Matthew D.
Shimazu, Tadahiro
Jing, Enxuan
Grueter, Carrie A.
Collins, Amy M.
Aouizerat, Bradley
Stancakova, Alena
Goetzman, Eric
Lam, Maggie M.
Schwer, Bjoern
Stevens, Robert D.
Muehlbauer, Michael J.
Kakar, Sanjay
Bass, Nathan M.
Kuusisto, Johanna
Laakso, Markku
Alt, Frederick W.
Newgard, Christopher B.
Farese, Robert V., Jr.
Kahn, C. Ronald
Verdin, Eric
TI SIRT3 Deficiency and Mitochondrial Protein Hyperacetylation Accelerate
the Development of the Metabolic Syndrome
SO MOLECULAR CELL
LA English
DT Article
ID FATTY-ACID OXIDATION; DIET-INDUCED OBESITY; STEAROYL-COA DESATURASE-1;
HEPATIC INSULIN-RESISTANCE; HUMAN SKELETAL-MUSCLE; LYSINE ACETYLATION;
DEPENDENT DEACETYLASE; C57BL/6J MOUSE; BLOOD-LIPIDS; GENE REVEALS
AB Acetylation is increasingly recognized as an important metabolic regulatory posttranslational protein modification, yet the metabolic consequence of mitochondrial protein hyperacetylation is unknown. We find that high-fat diet (HFD) feeding induces hepatic mitochondrial protein hyperacetylation in mice and downregulation of the major mitochondrial protein deacetylase SIRT3. Mice lacking SIRT3 (SIRT3KO) placed on a HFD show accelerated obesity, insulin resistance, hyperlipidemia, and steatohepatitis compared to wild-type (WT) mice. The lipogenic enzyme stearoyl-CoA desaturase 1 is highly induced in SIRT3KO mice, and its deletion rescues both WT and SIRT3KO mice from HFD-induced hepatic steatosis and insulin resistance. We further identify a single nucleotide polymorphism in the human SIRT3 gene that is suggestive of a genetic association with the metabolic syndrome. This polymorphism encodes a point mutation in the SIRT3 protein, which reduces its overall enzymatic efficiency. Our findings show that loss of SIRT3 and dysregulation of mitochondrial protein acetylation contribute to the metabolic syndrome.
C1 [Hirschey, Matthew D.; Shimazu, Tadahiro; Collins, Amy M.; Schwer, Bjoern; Verdin, Eric] Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
[Jing, Enxuan; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Cellular & Mol Physiol, Boston, MA 02215 USA.
[Grueter, Carrie A.] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
[Aouizerat, Bradley] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA.
[Aouizerat, Bradley] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Lam, Maggie M.; Kakar, Sanjay] Univ Calif San Francisco, Dept Pathol, VA Med Ctr, San Francisco, CA 94143 USA.
[Lam, Maggie M.; Kakar, Sanjay] Univ Calif San Francisco, UCSF Liver Ctr, San Francisco, CA 94143 USA.
[Bass, Nathan M.; Farese, Robert V., Jr.; Verdin, Eric] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Farese, Robert V., Jr.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.
[Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Goetzman, Eric] Univ Pittsburgh, Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15201 USA.
[Stevens, Robert D.; Muehlbauer, Michael J.; Newgard, Christopher B.] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27704 USA.
[Stevens, Robert D.; Muehlbauer, Michael J.; Newgard, Christopher B.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27704 USA.
[Stevens, Robert D.; Muehlbauer, Michael J.; Newgard, Christopher B.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27704 USA.
[Alt, Frederick W.] Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Verdin, E (reprint author), Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
EM everdin@gladstone.ucsf.edu
OI Grueter, Carrie/0000-0002-1913-2527; Verdin, Eric/0000-0003-3703-3183;
Hirschey, Matthew/0000-0003-4541-5376
FU MMPC [DK59637]; National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) [U01DK061718, U01DK061728, U01DK061731, U01DK061732,
U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713];
National Institute of Child Health and Human Development (NICHD);
General Clinical Research Centers [UL1RR024989, M01RR000750, M01RR00188,
UL1RR02413101, M01RR000827, UL1RR02501401, M01RR000065, M01RR020359,
UL1RR025741]; Sandler Foundation; National Center for Research Resources
(NCRR); National Institutes of Health (NIH); NIH Roadmap for Medical
Research [KL2 RR024130]; Academy of Finland [124243]; Finnish Heart
Foundation; Finnish Diabetes Research Foundation, TEKES [1510/31/06];
Kuopio University Hospital [5232, 5263]; Elison Medical Foundation; UCSF
Liver Center though the NIDDK [P30 DK026743]; NIDDK [DK085610]; J. David
Gladstone Institutes
FX We thank C. Miller and J.D. Fish for histology preparation; C. Harris,
L. Swift, and the MMPC (DK59637) for plasma and tissue lipid analysis;
T. Tran for metabolic experiments; A. Wilson, G. Maki, and J. Carroll
for figure preparation; and G. Howard and S. Ordway for editorial
review. We thank the Nonalcoholic Steatohepatitis Clinical Research
Network (NASH CRN; a complete list of authors is located in the
Supplemental Information) for providing human patient samples. NASH CRN
is supported by the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) (grants U01DK061718, U01DK061728, U01DK061731,
U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, and
U01DK061713) and by the National Institute of Child Health and Human
Development (NICHD). Several NASH CRN clinical centers use support from
General Clinical Research Centers or Clinical and Translational Science
Awards in conduct of NASH CRN Studies (grants UL1RR024989, M01RR000750,
M01RR00188, UL1RR02413101, M01RR000827, UL1RR02501401, M01RR000065,
M01RR020359, and UL1RR025741). Funding for this work was supported in
part by a University of California, San Francisco (UCSF) Post-doctoral
Research Fellowship Award from the Sandler Foundation (M.D.H. and B.S.);
from the National Center for Research Resources (NCRR), a component of
the National Institutes of Health (NIH) and NIH Roadmap for Medical
Research (KL2 RR024130) (B.A.); by grants from the Academy of Finland
(contract 124243), The Finnish Heart Foundation, The Finnish Diabetes
Research Foundation, TEKES (contract 1510/31/06), and Kuopio University
Hospital (EVO grants 5232 and 5263), and a Senior Scholarship in Aging
from the Elison Medical Foundation (F.W.A. and E.V.); the UCSF Liver
Center though the NIDDK (P30 DK026743) (E.V.); an R24 grant from NIDDK
(DK085610) (C.B.N., C.R.K., and E.V.); and institutional support from
the J. David Gladstone Institutes (E.V.). F.W.A. is an Investigator of
the Howard Hughes Medical Institute.
NR 76
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U1 2
U2 30
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD OCT 21
PY 2011
VL 44
IS 2
BP 177
EP 190
DI 10.1016/j.molcel.2011.07.019
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 837OC
UT WOS:000296212100005
PM 21856199
ER
PT J
AU Pathania, S
Nguyen, J
Hill, SJ
Scully, R
Adelmant, GO
Marto, JA
Feunteun, J
Livingston, DM
AF Pathania, Shailja
Jenna Nguyen
Hill, Sarah J.
Scully, Ralph
Adelmant, Guillaume O.
Marto, Jarrod A.
Feunteun, Jean
Livingston, David M.
TI BRCA1 Is Required for Postreplication Repair after UV-Induced DNA Damage
SO MOLECULAR CELL
LA English
DT Article
ID STALLED REPLICATION FORKS; NUCLEOTIDE EXCISION-REPAIR; INDUCED NUCLEAR
FOCI; BREAST-CANCER; POLYMERASE-ETA; HUMAN-CELLS; HOMOLOGOUS
RECOMBINATION; XERODERMA-PIGMENTOSUM; GENOMIC INSTABILITY; S-PHASE
AB BRCA1 contributes to the response to UV irradiation. Utilizing its BRCT motifs, it is recruited during S/G2 to UV-damaged sites in a DNA replication-dependent but nucleotide excision repair (NER)-independent manner. More specifically, at UV-stalled replication forks, it promotes photoproduct excision, suppression of translesion synthesis, and the localization and activation of replication factor C complex (RFC) subunits. The last function, in turn, triggers post-UV checkpoint activation and postreplicative repair. These BRCA1 functions differ from those required for DSBR.
C1 [Pathania, Shailja; Livingston, David M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Scully, Ralph] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Adelmant, Guillaume O.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Pathania, Shailja; Jenna Nguyen; Hill, Sarah J.; Adelmant, Guillaume O.; Marto, Jarrod A.; Livingston, David M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Adelmant, Guillaume O.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA.
[Scully, Ralph] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Feunteun, Jean] Inst Gustave Roussy, UMR8200, Lab Stabilite Genet & Oncogenese, F-94805 Villejuif, France.
RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM david_livingston@dfci.harvard.edu
RI Scully, Ralph/F-5008-2013
FU National Cancer Institute; Dana-Farber/Harvard Cancer Center; Breast
Cancer Research Foundation; Susan B. Komen Foundation; Dana-Farber
Cancer Institute; National Institutes of Health, NHGRI [P50HG004233];
NINDS [P01NS047572]
FX We would like to thank Steve Elledge for helpful discussions and for
ATRIP antibody, Lucian Moldovan and Alan D'Andrea for help and advice in
setting up the supF assay, Alan Lehmann for the eGFP-PolH plasmid,
Veronique Smits for the Rad9-GFP-HA plasmid, Zhongsheng You for the
eGFP-CtIP plasmid, Richard Baer for CtIP antibody, Margaret Shipp for
the HA-tagged ubiquitin plasmid, and the RNAi Consortium at the Broad
Institute for shRNAs directed at BRCA1 mRNA. We also thank Daniel
Silver, Hua Wang, and multiple members of the Livingston laboratory for
invaluable discussions. This work was supported in part by grants to one
of us (D.M.L.) from the National Cancer Institute, by a SPORE grant in
breast cancer research to the Dana-Farber/Harvard Cancer Center, and by
grants from the Breast Cancer Research Foundation and the Susan B. Komen
Foundation for the Cure. Generous support for this work was also
provided by the Dana-Farber Cancer Institute and the National Institutes
of Health, NHGRI (P50HG004233), and NINDS (P01NS047572).
NR 68
TC 51
Z9 52
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD OCT 21
PY 2011
VL 44
IS 2
BP 235
EP 251
DI 10.1016/j.molcel.2011.09.002
PG 17
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 837OC
UT WOS:000296212100010
PM 21963239
ER
PT J
AU Egede, LE
Strom, JL
Fernandes, J
Knapp, RG
Rojugbokan, A
AF Egede, Leonard E.
Strom, Joni L.
Fernandes, Jyotika
Knapp, Rebecca G.
Rojugbokan, Adebola
TI Effectiveness of technology-assisted case management in low income
adults with Type 2 diabetes (TACM-DM): study protocol for a randomized
controlled trial
SO TRIALS
LA English
DT Article
ID NURSE CASE-MANAGEMENT; PSYCHOMETRIC PROPERTIES; GLYCEMIC CONTROL; CARE
MANAGEMENT; BLOOD-PRESSURE; SCALE; INTERVENTIONS; VETERANS; VALIDITY;
OUTCOMES
AB Background: An estimated 1 in 3 American adults will have diabetes by the year 2050. Nationally, South Carolina ranks 10(th) in cases of diagnosed diabetes compared to other states. In adults, type 2 diabetes (T2DM) accounts for approximately 90-95% of all diagnosed cases of diabetes. Clinically, provider and health system factors account for < 10% of the variance in major diabetes outcomes including hemoglobin A1c (HbA1c), lipid control, and resource use. Use of telemonitoring systems offer new opportunities to support patients with T2DM while waiting to be seen by their health care providers at actual office visits. A variety of interventions testing the efficacy of telemedicine interventions have been conducted, but the outcomes have yielded equivocal results, emphasizing the shortage of controlled, randomized trials in this area. This study provides a unique opportunity to address this gap in the literature by optimizing two strategies that have been shown to improve glycemic control, while simultaneously implementing clinical outcomes measures, using a sufficient sample size, and offering health care delivery to rural, underserved and low income communities with T2DM who are seen at Federally Qualified Health Centers (FQHCs) in coastal South Carolina.
Methods: We describe a four-year prospective, randomized clinical trial, which will test the effectiveness of technology-assisted case management in low income rural adults with T2DM. Two-hundred (200) male and female participants, 18 years of age or older and with an HbA1c >= 8%, will be randomized into one of two groups: (1) an intervention arm employing the innovative FORA system coupled with nurse case management or (2) a usual care group. Participants will be followed for 6-months to ascertain the effect of the interventions on glycemic control. Our primary hypothesis is that among indigent, rural adult patients with T2DM treated in FQHC's, participants randomized to the technology-assisted case management intervention will have significantly greater reduction in HbA1c at 6 months of follow-up compared to usual care.
Discussion: Results from this study will provide important insight into the effectiveness of technology-assisted case management intervention (TACM) for optimizing diabetes care in indigent, rural adult patients with T2DM treated in FQHC's.
C1 [Egede, Leonard E.; Knapp, Rebecca G.] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29401 USA.
[Egede, Leonard E.; Strom, Joni L.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC 29425 USA.
[Egede, Leonard E.; Strom, Joni L.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA.
[Fernandes, Jyotika] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA.
[Knapp, Rebecca G.] Med Univ S Carolina, Div Biostat & Epidemiol, Dept Med, Charleston, SC 29425 USA.
[Rojugbokan, Adebola] Franklin C Fetter Family Hlth Ctr Inc, Charleston, SC 29403 USA.
RP Egede, LE (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, 109 Bee St, Charleston, SC 29401 USA.
EM egedel@musc.edu
FU Department of Defense [W81XWH-10-2-0057]; Telemedicine & Advanced
Technology Research Center (TATRC), Fort Detrick, Maryland
[W81XWH-10-2-0057]
FX The study is funded by Grant # W81XWH-10-2-0057 from the Department of
Defense. This research and development project was conducted by the
Medical University of South Carolina and is made possible by a
cooperative agreement that was awarded and administered by the U.S. Army
Medical Research and Material Command (USAMRMC) and the Telemedicine &
Advanced Technology Research Center (TATRC), Fort Detrick, Maryland
21702, under Contract Number: W81XWH-10-2-0057.
NR 41
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Z9 6
U1 0
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD OCT 20
PY 2011
VL 12
AR 231
DI 10.1186/1745-6215-12-231
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 849OF
UT WOS:000297134200001
PM 22014122
ER
PT J
AU Sadik, CD
Kim, ND
Alekseeva, E
Luster, AD
AF Sadik, Christian D.
Kim, Nancy D.
Alekseeva, Elena
Luster, Andrew D.
TI IL-17RA Signaling Amplifies Antibody-Induced Arthritis
SO PLOS ONE
LA English
DT Article
ID COLLAGEN-INDUCED ARTHRITIS; AUTOANTIBODY-MEDIATED ARTHRITIS;
RHEUMATOID-ARTHRITIS; T-CELLS; CXC CHEMOKINE; MAST-CELLS; TH17 CELLS;
INTERLEUKIN-17; EXPRESSION; MICE
AB Objective: To investigate the role of IL-17RA signaling in the effector phase of inflammatory arthritis using the K/BxN serum-transfer model.
Methods: Wild-type and Il17ra(-/-) mice were injected with serum isolated from arthritic K/BxN mice and their clinical score was recorded daily. Mice were also harvested on days 12 and 21 and ankles were analyzed for cytokine and chemokine mRNA expression by qPCR on day 12 and for bone and cartilage erosions by histology on day 21, respectively. The induction of cytokine and chemokine expression levels by IL-17A in synovial-like fibroblasts was also analyzed using qPCR.
Results: Il17ra(-/-) mice were partially protected from clinical signs of arthritis and had markedly fewer cartilage and bone erosions. The expression of several pro-inflammatory mediators, including the chemokines KC/CXCL1, MIP-2/CXCL2, LIX/CXCL5 MIP-1c/CCL9, MCP-3/CCL7, MIP-3a/CCL20, the cytokines IL-1b, IL-6, RANKL and the matrix metalloproteinases MMP2, MMP3, and MMP13 were decreased in the ankles of Il17ra(-/-) mice compared to wild-type mice. Many of these proinflammatory genes attenuated in the ankles of Il17ra(-/-) mice were shown to be directly induced by IL-17A in synovial fibroblasts in vitro.
Conclusions: IL-17RA signaling plays a role as an amplifier of the effector phase of inflammatory arthritis. This effect is likely mediated by direct activation of synovial fibroblasts by IL-17RA to produce multiple inflammatory mediators, including chemokines active on neutrophils. Therefore, interrupting IL-17RA signaling maybe a promising pharmacological target for the treatment of inflammatory arthritis.
C1 [Sadik, Christian D.; Kim, Nancy D.; Alekseeva, Elena; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02115 USA.
RP Sadik, CD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02115 USA.
EM aluster@mgh.harvard.edu
RI Sadik, Christian/E-8404-2012
FU Deutsche Forschungsgemeinschaft [Sa1960/1-1]; National Institutes of
Health [R01-AI050892, K08-AR054094]
FX This work was supported by grants of the Deutsche Forschungsgemeinschaft
(Sa1960/1-1 to C. D. S.; www.dfg.de)) and of the National Institutes of
Health (R01-AI050892 to A. D. L. and K08-AR054094 to N.D.K.;
www.nih.gov). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 44
TC 18
Z9 18
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 OCT 20
PY 2011
VL 6
IS 10
AR e26342
DI 10.1371/journal.pone.0026342
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 841KI
UT WOS:000296510800036
PM 22028860
ER
PT J
AU Kumar, SK
Uno, H
Jacobus, SJ
Van Wier, SA
Ahmann, GJ
Henderson, KJ
Callander, NS
Haug, JL
Siegel, DS
Greipp, PR
Fonseca, R
Rajkumar, SV
AF Kumar, Shaji K.
Uno, Hajime
Jacobus, Susanna J.
Van Wier, Scott A.
Ahmann, Greg J.
Henderson, Kimberly J.
Callander, Natalie S.
Haug, Jessica L.
Siegel, David S.
Greipp, Philip R.
Fonseca, Rafael
Rajkumar, S. Vincent
TI Impact of gene expression profiling-based risk stratification in
patients with myeloma receiving initial therapy with lenalidomide and
dexamethasone
SO BLOOD
LA English
DT Article
ID DIAGNOSED MULTIPLE-MYELOMA; MOLECULAR CLASSIFICATION; INTERGROUPE
FRANCOPHONE; BORTEZOMIB; SURVIVAL; MODEL; DISEASE; TRIALS
AB Detection of specific chromosomal abnormalities by FISH and metaphase cytogenetics allows risk stratification in multiple myeloma; however, gene expression profiling (GEP) based signatures may enable more specific risk categorization. We examined the utility of 2 GEP-based risk stratification systems among patients undergoing initial therapy with lenalidomide in the context of a phase 3 trial. Among 45 patients studied at baseline, 7 (16%) and 10 (22%), respectively, were high-risk using the GEP70 and GEP15 signatures. The median overall survival for the GEP70 high-risk group was 19 months versus not reached for the rest (hazard ratio = 14.1). Although the medians were not reached, the GEP15 also predicted a poor outcome among the high-risk patients. The C-statistic for the GEP70, GEP15, and FISH based risk stratification systems was 0.74, 0.7, and 0.7, respectively. Here we demonstrate the prognostic value for GEP risk stratification in a group of patients primarily treated with novel agents. This trial was registered at www.clinicaltrials.gov as #NCT00098475. (Blood. 2011; 118(16):4359-4362)
C1 [Kumar, Shaji K.] Mayo Clin, Div Hematol, Rochester, MN 55905 USA.
[Uno, Hajime; Jacobus, Susanna J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Van Wier, Scott A.; Ahmann, Greg J.; Fonseca, Rafael] Mayo Clin Arizona, Scottsdale, AZ USA.
[Callander, Natalie S.] Univ Wisconsin, Madison, WI USA.
[Siegel, David S.] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
RP Kumar, SK (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA.
EM kumar.shaji@mayo.edu
RI Kumar, Shaji/A-9853-2008;
OI Kumar, Shaji/0000-0001-5392-9284; Fonseca, Rafael/0000-0002-5938-3769;
Rajkumar, S. Vincent/0000-0002-5862-1833
FU National Cancer Institute, National Institutes of Health; Department of
Health and Human Services [CA23318, CA66636, CA21115, CA13650, CA93842];
National Institutes of Health [CA90628]; Celgene
FX This work was coordinated by the Eastern Cooperative Oncology Group (Dr
Robert L. Comis, Chair) and supported by the National Cancer Institute,
National Institutes of Health, and the Department of Health and Human
Services (Public Health Service grants CA23318, CA66636, CA21115,
CA13650, and CA93842) and in part by the National Institutes of Health
(CA90628, S.K.K.).; S.K.K. is involved with sponsored research from
Celgene. The remaining authors declare no competing financial interests.
NR 25
TC 16
Z9 16
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 20
PY 2011
VL 118
IS 16
BP 4359
EP 4362
DI 10.1182/blood-2011-03-342089
PG 4
WC Hematology
SC Hematology
GA 838JY
UT WOS:000296286500015
PM 21860025
ER
PT J
AU Jacobsohn, DA
Arora, M
Klein, JP
Hassebroek, A
Flowers, ME
Cutler, CS
Urbano-Ispizua, A
Bolwell, BJ
Antin, JH
Boyiadzis, M
Cahn, JY
Cairo, MS
Herzig, RH
Isola, LM
Klumpp, TR
Lee, SJ
Petersdorf, EW
Santarone, S
Gale, RP
Schouten, HC
Spellman, SR
Weisdorf, DJ
Wingard, JR
Horowitz, MM
Pavletic, SZ
AF Jacobsohn, David A.
Arora, Mukta
Klein, John P.
Hassebroek, Anna
Flowers, Mary E.
Cutler, Corey S.
Urbano-Ispizua, Alvaro
Bolwell, Brian J.
Antin, Joseph H.
Boyiadzis, Michael
Cahn, Jean-Yves
Cairo, Mitchell S.
Herzig, Roger H.
Isola, Luis M.
Klumpp, Thomas R.
Lee, Stephanie J.
Petersdorf, Effie W.
Santarone, Stella
Gale, Robert P.
Schouten, Harry C.
Spellman, Stephen R.
Weisdorf, Daniel J.
Wingard, John R.
Horowitz, Mary M.
Pavletic, Steven Z.
TI Risk factors associated with increased nonrelapse mortality and with
poor overall survival in children with chronic graft-versus-host disease
SO BLOOD
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; UMBILICAL-CORD BLOOD; UNRELATED DONOR
TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; ACUTE-LEUKEMIA;
WEIGHT-LOSS; REGISTRY; THROMBOCYTOPENIA; RECIPIENTS; DIAGNOSIS
AB There is a paucity of information regarding the factors that affect nonrelapse mortality (NRM) and overall survival among children that develop chronic graft-versus-host disease (cGVHD). We performed multivariate analyses using data from the Center for International Blood and Marrow Transplant Research to identify risk factors for NRM and survival in 1117 pediatric subjects with leukemia or myelodysplastic syndrome, transplanted from related donors, unrelated donors (URD), or unrelated cord blood between 1995 and 2004. We identified 4 variables associated with higher NRM: HLA partially matched or mismatched URD, peripheral blood cell graft, Karnofsky/Lansky score < 80 at cGVHD diagnosis, and platelets < 100 x 10(9)/L at cGVHD diagnosis. Factors associated with significantly worse survival were: age > 10 years, transplantation from HLA partially matched or mismatched URD, advanced disease at transplantation, Karnofsky/Lansky < 80; and platelets < 100 x 10(9)/L. Cumulative incidence of discontinuation of systemic immune suppression at 1, 3, and 5 years after diagnosis of cGVHD were 22% (20%-25%), 34% (31%-37%), and 37% (34%-40%), respectively. This is the largest study elucidating variables affecting outcome after diagnosis of cGVHD in pediatric allograft recipients. These variables may be useful for risk stratification, development of future clinical trials, and family counseling in children with cGVHD. (Blood. 2011;118(16):4472-4479)
C1 [Jacobsohn, David A.] Childrens Natl Med Ctr, Div Blood & Marrow Transplantat, Ctr Canc & Blood Disorders, Washington, DC 20010 USA.
[Arora, Mukta; Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA.
[Klein, John P.; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Hassebroek, Anna; Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Flowers, Mary E.; Lee, Stephanie J.; Petersdorf, Effie W.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Cutler, Corey S.; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Urbano-Ispizua, Alvaro] Hosp Clin Barcelona, Barcelona, Spain.
[Bolwell, Brian J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Boyiadzis, Michael] Univ Pittsburgh, Ctr Canc, Pittsburgh, PA USA.
[Cahn, Jean-Yves] Ctr Hosp Univ Grenoble, Hosp A Michallon, Grenoble, France.
[Cairo, Mitchell S.] Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY USA.
[Herzig, Roger H.] Univ Louisville Hosp, James Brown Canc Ctr, Louisville, KY USA.
[Isola, Luis M.] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Klumpp, Thomas R.] Temple Univ, Bone Marrow Transplant Program, Philadelphia, PA 19122 USA.
[Santarone, Stella] Osped Civile, BMT Ctr Pescara, Pescara, Italy.
[Gale, Robert P.] Celgene Corp, Los Angeles, CA USA.
[Schouten, Harry C.] Acad Ziekenhuis Maastricht, Maastricht, Netherlands.
[Wingard, John R.] Shands HealthCare, Gainesville, FL USA.
[Wingard, John R.] Univ Florida, Gainesville, FL USA.
[Pavletic, Steven Z.] NCI, NIH, Bethesda, MD 20892 USA.
RP Jacobsohn, DA (reprint author), Childrens Natl Med Ctr, Div Blood & Marrow Transplantat, Ctr Canc & Blood Disorders, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM dajacobs@cnmc.org
RI Cahn, Jean-Yves/M-6493-2014
FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and
Blood Institute (NHLBI); National Institute of Allergy and Infectious
Diseases (NIAID), NHLBI [5U01HL069294]; Health Resources and Services
Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research
[N00014-06-1-0704, N00014-08-1-0058]; AABB; Allos Inc; Amgen Inc;
Medical College of Wisconsin; Astellas Pharma US Inc; 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; 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; Leukemia &
Lymphoma Society; Merck Company; 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; Wellpoint Inc
FX CIBMTR is supported by Public Health Service Grant/Cooperative Agreement
U24-CA76518 from the National Cancer Institute (NCI), the National
Heart, Lung and Blood Institute (NHLBI), and the National Institute of
Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement
5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with
Health Resources and Services Administration (HRSA/DHHS); grants
N00014-06-1-0704 and N00014-08-1-0058 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;
BloodCenter 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 &
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.
NR 36
TC 20
Z9 21
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 20
PY 2011
VL 118
IS 16
BP 4472
EP 4479
DI 10.1182/blood-2011-04-349068
PG 8
WC Hematology
SC Hematology
GA 838JY
UT WOS:000296286500030
PM 21878671
ER
PT J
AU Jacobs, PP
Sackstein, R
AF Jacobs, Pieter P.
Sackstein, Robert
TI CD44 and HCELL: Preventing hematogenous metastasis at step 1
SO FEBS LETTERS
LA English
DT Review
DE CD44; Hematopoietic cell E-/L-selectin ligand; Metastasis;
Glycosylation; Selectin
ID COLON-CARCINOMA CELLS; L-SELECTIN LIGAND; NECROSIS-FACTOR-ALPHA; MAJOR
E-SELECTIN; LEUKOCYTE ADHESION MOLECULE-1; PERIPHERAL-BLOOD MONOCYTES;
HUMAN COLORECTAL-CANCER; LYMPH-NODE METASTASIS; SIALYL-LEWIS-X;
P-SELECTIN
AB Despite great strides in our knowledge of the genetic and epigenetic changes underlying malignancy, we have limited information on the molecular basis of metastasis. Over 90% of cancer deaths are caused by spread of tumor cells from a primary site to distant organs and tissues, highlighting the pressing need to define the molecular effectors of cancer metastasis. Mounting evidence suggests that circulating tumor cells (CTCs) home to specific tissues by hijacking the normal leukocyte trafficking mechanisms. Cancer cells characteristically express CD44, and there is increasing evidence that hematopoietic cell E-/L-selectin ligand (HCELL), a sialofucosylated glycoform of CD44, serves as the major selectin ligand on cancer cells, allowing interaction of tumor cells with endothelium, leukocytes, and platelets. Here, we review the structural biology of CD44 and of HCELL, and present current data on the function of these molecules in mediating organ-specific homing/metastasis of CTCs. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
C1 [Jacobs, Pieter P.; Sackstein, Robert] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
[Sackstein, Robert] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Jacobs, Pieter P.; Sackstein, Robert] Harvard Univ, Sch Med, Harvard Skin Dis Res Ctr, Boston, MA USA.
[Sackstein, Robert] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Sackstein, R (reprint author), Harvard Inst Med, 77 Ave Louis Pasteur,6th Floor,Room 647, Boston, MA 02115 USA.
EM rsackstein@rics.bwh.harvard.edu
FU National Institutes of Health; National Heart Lung Blood Institute;
National Cancer Institute [PO1 HL107146, RO1 HL60528, RO1 HL73714, RO1
CA121335]
FX This work was supported by the National Institutes of Health, in
particular, the National Heart Lung Blood Institute and the National
Cancer Institute (PO1 HL107146, RO1 HL60528, RO1 HL73714, and RO1
CA121335). According to National Institutes of Health policies and
procedures, the Brigham and Women's Hospital has assigned intellectual
property rights regarding HCELL to the inventor (R.S.).
NR 176
TC 28
Z9 29
U1 2
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD OCT 20
PY 2011
VL 585
IS 20
BP 3148
EP 3158
DI 10.1016/j.febslet.2011.07.039
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 841LP
UT WOS:000296514100002
PM 21827751
ER
PT J
AU Talcott, JA
Yeap, BY
Clark, JA
Siegel, RD
Loggers, ET
Lu, C
Godley, PA
AF Talcott, James A.
Yeap, Beow Y.
Clark, Jack A.
Siegel, Robert D.
Loggers, Elizabeth Trice
Lu, Charles
Godley, Paul A.
TI Safety of Early Discharge for Low-Risk Patients With Febrile
Neutropenia: A Multicenter Randomized Controlled Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID EARLY HOSPITAL DISCHARGE; CANCER-PATIENTS; ANTIBIOTIC-THERAPY;
MULTINATIONAL-ASSOCIATION; OUTPATIENT MANAGEMENT; CLINICAL-PRACTICE;
ORAL ANTIBIOTICS; PREDICTION RULE; SUPPORTIVE-CARE; FEVER
AB Purpose
Febrile neutropenia commonly complicates cancer chemotherapy. Outpatient treatment may reduce costs and improve patient comfort but risk progression of undetected medical problems.
Patients and Methods
By using our validated algorithm, we identified medically stable inpatients admitted for febrile neutropenia (neutrophils <500/mu L) after chemotherapy and randomly assigned them to continued inpatient antibiotic therapy or early discharge to receive identical antibiotic treatment at home. Our primary outcome was the occurrence of any serious medical complication, defined as evidence of medical instability requiring urgent medical attention.
Results
We enrolled 117 patients with 121 febrile neutropenia episodes before study termination for poor accrual. We excluded five episodes as ineligible and three because of inadequate documentation of the study outcome. Treatment groups were clinically similar, but sociodemographic imbalances occurred because of block randomization. The median presenting absolute neutrophil count was 100/mu L. Hematopoietic growth factors were used in 38% of episodes. The median neutropenia duration was 4 days (range, 1 to 15 days). Five outpatients were readmitted to the hospital. Major medical complications occurred in five episodes (8%) in the hospital arm and four (9%) in the home arm (95% CI for the difference, -10% to 13%; P = .56). No study patient died. Patient-reported quality of life was similar on both arms.
Conclusion
We found no evidence of adverse medical consequences from home care, despite a protocol designed to detect evidence of clinical deterioration. These results should reassure clinicians who elect to treat rigorously characterized low-risk patients with febrile neutropenia in suitable outpatient settings with appropriate surveillance for unexpected clinical deterioration.
C1 [Talcott, James A.; Yeap, Beow Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Talcott, James A.] Harvard Univ, Sch Med, Boston, MA USA.
[Clark, Jack A.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Clark, Jack A.] VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Siegel, Robert D.] Helen & Harry Gray Canc Ctr, Hartford, CT USA.
[Loggers, Elizabeth Trice] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Loggers, Elizabeth Trice] Grp Hlth Res Inst, Seattle, WA USA.
[Lu, Charles] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Godley, Paul A.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
RP Talcott, JA (reprint author), Continuum Canc Ctr New York, 325 W 15th St, New York, NY 10011 USA.
EM jtalcott@chpnet.org
OI Clark, Jack/0000-0002-7424-1670
FU National Cancer Institute [R01 CA71125]
FX Supported by Grant No. R01 CA71125 from the National Cancer Institute.
NR 35
TC 18
Z9 18
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 20
PY 2011
VL 29
IS 30
BP 3977
EP 3983
DI 10.1200/JCO.2011.35.0884
PG 7
WC Oncology
SC Oncology
GA 841YS
UT WOS:000296551700012
PM 21931024
ER
PT J
AU Hendricks, AM
Loggers, ET
Talcott, JA
AF Hendricks, Ann M.
Loggers, Elizabeth Trice
Talcott, James A.
TI Costs of Home Versus Inpatient Treatment for Fever and Neutropenia:
Analysis of a Multicenter Randomized Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CANCER-PATIENTS; FEBRILE NEUTROPENIA; ECONOMIC-EVALUATION;
CLINICAL-TRIALS; PREDICTION RULE; OUTPATIENT; CARE; MANAGEMENT
AB Purpose
For patients with cancer who have febrile neutropenia, relative costs of home versus hospital treatment, including unreimbursed costs borne by patients and families, are poorly characterized. We estimated costs from a randomized trial of patients with low-risk febrile neutropenia for whom outpatient care was feasible, comparing inpatient treatment with discharge to home care after inpatient observation.
Methods
We collected direct medical and self-reported indirect costs for 57 inpatient and 35 outpatient treatment episodes of patients enrolled in a randomized trial from 1996 through 2000. Charges from hospital bills were converted to costs using Medicare cost-to-charge ratios. Patients kept daily logs of out-of-pocket payments and time spent by informal caregivers providing care. Dollar amounts were standardized to June 2008.
Results
Mean total charges for the hospital arm were 49% higher than for the home treatment arm ($16,341 v $10,977; P < .01). Mean estimated total costs for the hospital arm were 30% higher ($10,143 v $7,830; P < .01). Inspection of sparse available data suggests that payments made were similar by treatment arm. Inpatients and their caregivers spent more out of pocket than their outpatient counterparts (mean, $201 v $74; P < .01). Informal caregivers for both treatment arms reported similar time caring and lost from work.
Conclusion
Home intravenous antibiotic treatment was less costly than continued inpatient care for carefully selected patients with cancer having febrile neutropenia without significantly increased indirect costs or caregiver burden.
C1 [Hendricks, Ann M.] Boston Univ, VA Boston Healthcare Syst, Sch Publ Hlth, Boston, MA 02130 USA.
[Talcott, James A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Talcott, James A.] Harvard Univ, Sch Med, Boston, MA USA.
[Loggers, Elizabeth Trice] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Loggers, Elizabeth Trice] Grp Hlth Res Inst, Seattle, WA USA.
RP Hendricks, AM (reprint author), Boston Univ, VA Boston Healthcare Syst, Sch Publ Hlth, 150 S Huntington Ave, Boston, MA 02130 USA.
EM ann.hendricks@va.gov
FU National Cancer Institute [CA 71125]
FX Supported by National Cancer Institute Research Grant No. CA 71125.
NR 21
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Z9 25
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 20
PY 2011
VL 29
IS 30
BP 3984
EP 3989
DI 10.1200/JCO.2011.35.1247
PG 6
WC Oncology
SC Oncology
GA 841YS
UT WOS:000296551700013
PM 21931037
ER
PT J
AU Paugh, BS
Broniscer, A
Qu, CX
Miller, CP
Zhang, JY
Tatevossian, RG
Olson, JM
Geyer, JR
Chi, SN
da Silva, NS
Onar-Thomas, A
Baker, JN
Gajjar, A
Ellison, DW
Baker, SJ
AF Paugh, Barbara S.
Broniscer, Alberto
Qu, Chunxu
Miller, Claudia P.
Zhang, Junyuan
Tatevossian, Ruth G.
Olson, James M.
Geyer, J. Russell
Chi, Susan N.
da Silva, Nasjla Saba
Onar-Thomas, Arzu
Baker, Justin N.
Gajjar, Amar
Ellison, David W.
Baker, Suzanne J.
TI Genome-Wide Analyses Identify Recurrent Amplifications of Receptor
Tyrosine Kinases and Cell-Cycle Regulatory Genes in Diffuse Intrinsic
Pontine Glioma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID BRAIN-STEM GLIOMA; HIGH-GRADE GLIOMAS; PHASE-I TRIAL; PILOCYTIC
ASTROCYTOMAS; GLIOBLASTOMA-MULTIFORME; MALIGNANT GLIOMAS; FUSION GENE;
CHILDREN; CANCER; GROWTH
AB Purpose
Long-term survival for children with diffuse intrinsic pontine glioma (DIPG) is less than 10%, and new therapeutic targets are urgently required. We evaluated a large cohort of DIPGs to identify recurrent genomic abnormalities and gene expression signatures underlying DIPG.
Patients and Methods
Single-nucleotide polymorphism arrays were used to compare the frequencies of genomic copy number abnormalities in 43 DIPGs and eight low-grade brainstem gliomas with data from adult and pediatric (non-DIPG) glioblastomas, and expression profiles were evaluated using gene expression arrays for 27 DIPGs, six low-grade brainstem gliomas, and 66 nonbrainstem low-grade gliomas.
Results
Frequencies of specific large-scale and focal imbalances varied significantly between DIPGs and nonbrainstem pediatric glioblastomas. Focal amplifications of genes within the receptor tyrosine kinase-Ras-phosphoinositide 3-kinase signaling pathway were found in 47% of DIPGs, the most common of which involved PDGFRA and MET. Thirty percent of DIPGs contained focal amplifications of cell-cycle regulatory genes controlling retinoblastoma protein (RB) phosphorylation, and 21% had concurrent amplification of genes from both pathways. Some tumors showed heterogeneity in amplification patterns. DIPGs showed distinct gene expression signatures related to developmental processes compared with nonbrainstem pediatric high-grade gliomas, whereas expression signatures of low-grade brainstem and nonbrainstem gliomas were similar.
Conclusion
DIPGs comprise a molecularly related but distinct subgroup of pediatric gliomas. Genomic studies suggest that targeted inhibition of receptor tyrosine kinases and RB regulatory proteins may be useful therapies for DIPG.
C1 [Baker, Suzanne J.] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
[Broniscer, Alberto; Gajjar, Amar] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
[Olson, James M.; Geyer, J. Russell] Univ Washington, Seattle, WA 98195 USA.
[Chi, Susan N.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[da Silva, Nasjla Saba] Univ Fed Sao Paulo, Sao Paulo, Brazil.
RP Baker, SJ (reprint author), St Jude Childrens Hosp, Dept Dev Neurobiol, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM Suzanne.Baker@stjude.org
RI Tatevossian, Ruth/G-6377-2016;
OI Tatevossian, Ruth/0000-0002-1653-3026; Broniscer,
Alberto/0000-0001-9646-0463
FU National Institutes of Health [P01 CA096832]; National Brain Tumor
Society; Cure Starts Now Foundation; Smile for Sophie Forever
Foundation; Tyler's Treehouse Foundation; Musicians Against Childhood
Cancer; Noyes Brain Tumor Foundation; Pediatric Low Grade Astrocytoma
Foundation; American Lebanese Syrian Associated Charities
FX Supported by Grant No. P01 CA096832 from the National Institutes of
Health and by the Sydney Schlobohm Chair of Research from the National
Brain Tumor Society, Cure Starts Now Foundation, Smile for Sophie
Forever Foundation, Tyler's Treehouse Foundation, Musicians Against
Childhood Cancer, Noyes Brain Tumor Foundation, Pediatric Low Grade
Astrocytoma Foundation, and American Lebanese Syrian Associated
Charities.
NR 37
TC 104
Z9 105
U1 1
U2 6
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 20
PY 2011
VL 29
IS 30
BP 3999
EP 4006
DI 10.1200/JCO.2011.35.5677
PG 8
WC Oncology
SC Oncology
GA 841YS
UT WOS:000296551700015
PM 21931021
ER
PT J
AU Liu, YY
Slotine, JJ
Barabasi, AL
AF Liu, Yang-Yu
Slotine, Jean-Jacques
Barabasi, Albert-Laszlo
TI Few inputs can reprogram biological networks Reply
SO NATURE
LA English
DT Letter
C1 [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
[Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys Comp Sci & Biol, Boston, MA 02115 USA.
[Liu, Yang-Yu; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
[Slotine, Jean-Jacques] MIT, Nonlinear Syst Lab, Cambridge, MA 02139 USA.
[Slotine, Jean-Jacques] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
[Slotine, Jean-Jacques] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Liu, YY (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
EM alb@neu.edu
RI Liu, Yang-Yu/G-8885-2011
OI Liu, Yang-Yu/0000-0003-2728-4907
NR 8
TC 8
Z9 8
U1 1
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 20
PY 2011
VL 478
IS 7369
BP E4
EP E5
DI 10.1038/nature10544
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100002
ER
PT J
AU Blanc, FX
Sok, T
Laureillard, D
Borand, L
Rekacewicz, C
Nerrienet, E
Madec, Y
Marcy, O
Chan, S
Prak, N
Kim, C
Lak, KK
Hak, C
Dim, B
Sin, CI
Sun, S
Guillard, B
Sar, B
Vong, S
Fernandez, M
Fox, L
Delfraissy, JF
Goldfeld, AE
AF Blanc, Francois-Xavier
Sok, Thim
Laureillard, Didier
Borand, Laurence
Rekacewicz, Claire
Nerrienet, Eric
Madec, Yoann
Marcy, Olivier
Chan, Sarin
Prak, Narom
Kim, Chindamony
Lak, Khemarin Kim
Hak, Chanroeurn
Dim, Bunnet
Sin, Chhun Im
Sun, Sath
Guillard, Bertrand
Sar, Borann
Vong, Sirenda
Fernandez, Marcelo
Fox, Lawrence
Delfraissy, Jean-Francois
Goldfeld, Anne E.
CA CAMELIA ANRS 1295-CIPRA KH001
TI Earlier versus Later Start of Antiretroviral Therapy in HIV-Infected
Adults with Tuberculosis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID SUB-SAHARAN AFRICA; MORTALITY; CAMBODIA; OUTCOMES; PROGRAM; PREVALENCE;
DIAGNOSIS; SURVIVAL; THAILAND; IMPACT
AB Background Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy.
Methods We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival.
Results A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log(10) copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P = 0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients.
Conclusions Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health; CAMELIA ClinicalTrials.gov number, NCT01300481.)
C1 [Blanc, Francois-Xavier; Delfraissy, Jean-Francois] Hop Bicetre, AP HP, Dept Internal Med, Pneumol Unit, Le Kremlin Bicetre, France.
[Delfraissy, Jean-Francois] Univ Paris 11, INSERM, U1012, Le Kremlin Bicetre, France.
[Sok, Thim; Laureillard, Didier; Marcy, Olivier; Chan, Sarin; Lak, Khemarin Kim; Dim, Bunnet; Sun, Sath; Fernandez, Marcelo; Goldfeld, Anne E.] Khmer Soviet Friendship Hosp, Cambodian Hlth Comm, Phnom Penh, Cambodia.
[Borand, Laurence; Nerrienet, Eric; Guillard, Bertrand; Sar, Borann; Vong, Sirenda] Khmer Soviet Friendship Hosp, Inst Pasteur Cambodia, Phnom Penh, Cambodia.
[Prak, Narom] Khmer Soviet Friendship Hosp, Dept Infect Dis, Phnom Penh, Cambodia.
[Sin, Chhun Im] Khmer Soviet Friendship Hosp, Dept Pneumol, Phnom Penh, Cambodia.
[Kim, Chindamony; Dim, Bunnet] Med Sans Frontieres, Phnom Penh, Cambodia.
[Hak, Chanroeurn] Calmette Hosp, Phnom Penh, Cambodia.
[Kim, Chindamony] Donkeo Prov Hosp, Takeo, Cambodia.
[Lak, Khemarin Kim; Sun, Sath] Svay Rieng Prov Hosp, Svay Rieng, Cambodia.
[Dim, Bunnet] Siem Reap Prov Hosp, Siem Reap, Cambodia.
[Laureillard, Didier] Georges Pompidou European Hosp, AP HP, Dept Clin Immunol, Paris, France.
[Rekacewicz, Claire; Delfraissy, Jean-Francois] Agence Natl Rech Sida & Hepatites Virales, Paris, France.
[Madec, Yoann] Inst Pasteur, Unite Epidemiol Malad Emergentes, Paris, France.
[Fox, Lawrence] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Goldfeld, Anne E.] Harvard Univ, Sch Med, Childrens Hosp, Immune Dis Inst, Boston, MA USA.
[Goldfeld, Anne E.] Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA.
RP Blanc, FX (reprint author), CHU Bicetre, Unite Fonct Pneumol, 78 Rue Gen Leclerc, F-94275 Le Kremlin Bicetre, France.
EM xavier.blanc@bct.aphp.fr; goldfeld@idi.harvard.edu
RI Blanc, Francois-Xavier/D-7425-2015
FU French National Agency for Research on AIDS and Viral Hepatitis [ANRS
1295]; National Institutes of Health; National Institutes of Health,
National Institute of Allergy and Infectious Diseases, Division of AIDS
[CIPRA KH001/DAID-ES ID 10425]; Annenberg Foundation; Aeras Global TB
Vaccine Foundation; scientific team of the ANRS; logistic team of the
ANRS; Organisation Franco-Cambodgienne de Pneumologie
FX Funded by the French National Agency for Research on AIDS and Viral
Hepatitis and the National Institutes of Health; CAMELIA
ClinicalTrials.gov number, NCT01300481.; Supported by the French
National Agency for Research on AIDS and Viral Hepatitis (ANRS 1295) and
the National Institutes of Health, National Institute of Allergy and
Infectious Diseases, Division of AIDS (CIPRA KH001/DAID-ES ID 10425).;
Dr. Delfraissy reports serving on the international board for HIV
treatment of GlaxoSmithKline, Merck Sharp & Dohme-Chibret, Gilead, and
Bristol-Myers Squibb; and Dr. Goldfeld, receiving funds from the
Annenberg Foundation to her laboratory and to the Cambodian Health
Committee to conduct studies and serving as a consultant for the Aeras
Global TB Vaccine Foundation, which provides funds to the Cambodian
Health Committee to conduct studies. No other potential conflict of
interest relevant to this article was reported.; We thank the patients
for their participation in the trial; Franoise Barre-Sinoussi for her
help with initiating the CIPRA project and the CAMELIA trial and for her
support throughout the trial; H. E. Eng Huot for his early and
continuing support; Philippe Glaziou for providing the initial design of
the study; Charles Mayaud for his clinical mentorship; Jean-Louis
Sarthou for ensuring high-quality laboratory and basic scientific
support during the trial; H. E. Mean Chhivun and H. E. Mao Tan Eang for
the support of the Cambodian National AIDS and Tuberculosis Programs,
respectively; Takmao, Kossamak, and Kampong Trach Hospitals for
referring patients to the study sites; Bart Janssens, Petros Isaakidis,
and Tony Reid for the support from Medecins sans Frontieres Belgium to
two of our study sites (Donkeo and Siem Reap Provincial Hospitals); the
data and safety monitoring board, chaired by John Modlin, and the
scientific advisory board, chaired by Charles Mayaud, for their
significant contributions to the study; the scientific and logistic
teams of the ANRS (Brigitte Bazin, Severine Blesson, Alpha Diallo, Annie
Metro, Saphonn Vonthanak, Isabelle Fournier-Nicolle, and Michel
Kazatchkine) and the National Institutes of Health (Jane E. Bupp, Ray Y.
Chen, Margaret Matula, Rod Hoff, Sandra Nusinoff Lehrman, Karen Near,
Barbara Laughon, Mike Ussery, Trinh Ly, Mary Fanning, and Ana Martinez)
for their support and intellectual contributions; and Pierre L'Her,
Etienne Leroy-Terquem, the Organisation Franco-Cambodgienne de
Pneumologie, Pean Polidy, Sylvia Taylor, Josephine Braun, Vincent
Guillemet, Adrienne Shapiro, Catherine Quillet, Jean-Paul Dousset,
Anne-Marie Taburet, Wayne Wilson, and Vincent Deubel for their support.
NR 33
TC 297
Z9 304
U1 2
U2 19
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 20
PY 2011
VL 365
IS 16
BP 1471
EP 1481
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 835BW
UT WOS:000296009500001
PM 22010913
ER
PT J
AU Shah, U
Shenoy-Bhangle, AS
AF Shah, Uzma
Shenoy-Bhangle, Anuradha S.
TI Case 32-2011: A 19-Year-Old Man with Recurrent Pancreatitis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID IDIOPATHIC CHRONIC-PANCREATITIS; HEREDITARY PANCREATITIS; CHILDREN;
CHOLANGIOPANCREATOGRAPHY; GALLSTONES; INHIBITOR; RISK; GENE
C1 [Shah, Uzma] Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Boston, MA 02114 USA.
[Shah, Uzma] Massachusetts Gen Hosp, Dept Hepatol, Boston, MA 02114 USA.
[Shah, Uzma] Massachusetts Gen Hosp, Dept Nutr, Boston, MA 02114 USA.
[Shenoy-Bhangle, Anuradha S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Shah, Uzma] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Shenoy-Bhangle, Anuradha S.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP Shah, U (reprint author), Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Boston, MA 02114 USA.
NR 24
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 OCT 20
PY 2011
VL 365
IS 16
BP 1528
EP 1536
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 835BW
UT WOS:000296009500009
PM 22010920
ER
PT J
AU Rosenbluh, J
Nijhawan, D
Chen, Z
Wong, KK
Masutomi, K
Hahn, WC
AF Rosenbluh, Joseph
Nijhawan, Deepak
Chen, Zhao
Wong, Kwok-Kin
Masutomi, Kenkichi
Hahn, William C.
TI RMRP Is a Non-Coding RNA Essential for Early Murine Development
SO PLOS ONE
LA English
DT Article
ID CARTILAGE-HAIR HYPOPLASIA; MUTATIONS
AB RMRP is a non-coding RNA that is ubiquitously expressed in both humans and mice. RMRP mutations that lead to decreased RMRP levels are found in the pleiotropic syndrome Cartilage Hair Hypoplasia. To assess the effects of deleting RMRP, we engineered a targeting vector that contains loxP sequences flanking RMRP and created hemizygous mice harboring this engineered allele (RMRP conditional). We found that insertion of this cassette suppressed RMRP expression, and we failed to obtain viable mice homozygous for the RMRP conditional allele. Furthermore, we were unable to obtain viable homozygous RMRP null mice, indicating that RMRP is essential for early embryonic development.
C1 [Rosenbluh, Joseph; Nijhawan, Deepak; Chen, Zhao; Wong, Kwok-Kin; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Rosenbluh, Joseph; Nijhawan, Deepak; Chen, Zhao; Wong, Kwok-Kin; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Rosenbluh, Joseph; Nijhawan, Deepak; Chen, Zhao; Wong, Kwok-Kin; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA USA.
[Rosenbluh, Joseph; Nijhawan, Deepak; Hahn, William C.] Broad Inst Harvard & Massachusetts Inst Technol M, Cambridge, MA USA.
[Masutomi, Kenkichi] Natl Canc Ctr, Res Inst, Div Canc Stem Cell, Tokyo 104, Japan.
RP Rosenbluh, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM kmasutom@ncc.go.jp; William_Hahn@dfci.harvard.edu
OI wong, kwok kin/0000-0001-6323-235X
FU US National Institutes of Health [F32GM090437-01, R01 AG23145]
FX This research was supported by a US National Institutes of Health
postdoctoral fellowship to J.R. F32GM090437-01, and R01 AG23145 (WCH).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 7
TC 12
Z9 13
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 OCT 19
PY 2011
VL 6
IS 10
AR e26270
DI 10.1371/journal.pone.0026270
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 841JB
UT WOS:000296507500047
PM 22039455
ER
PT J
AU Garrigues, GE
Wray, WH
Lindenhovius, ALC
Ring, DC
Ruch, DS
AF Garrigues, Grant E.
Wray, Walter H., III
Lindenhovius, Anneluuk L. C.
Ring, David C.
Ruch, David S.
TI Fixation of the Coronoid Process in Elbow Fracture-Dislocations
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID MEDIAL COLLATERAL LIGAMENT; TERRIBLE TRIAD INJURY; RADIAL HEAD;
INSTABILITY; REPAIR
AB Background: Terrible triad injuries consist of a posterior dislocation of the elbow, a coronoid fracture, and a radial head fracture. The coronoid plays a pivotal role as an anterior buttress, yet the optimal management of the coronoid fracture remains unknown. We hypothesize that suture lasso fixation of the coronoid fracture leads to fewer complications and improved outcomes compared with screw or suture anchor fixation techniques.
Methods:. A retrospective chart review performed at three tertiary care centers identified forty consecutive patients treated for terrible triad injuries of the elbow with a minimum follow-up of eighteen months (mean, twenty-four months; range, eighteen to fifty-three months). All patients were managed with a standard approach consisting of: (1) repair or replacement of the radial head; (2) repair of the lateral ulnar collateral ligament (LUCL) of the elbow; and (3) repair of the coronoid fracture with one of two techniques: Group I (n = 28) consisted of the "lasso" technique and Group II (n = 12) consisted of open reduction and internal fixation (ORIF) with screws or suture anchors.
Results: For the study population, the mean postoperative arc of elbow motion was 115 degrees (range, 75 degrees to 140 degrees), the average Disabilities of the Arm, Shoulder and Hand (DASH) score was 16 (range, 0 to 43), and the average Broberg-Morrey score was 90 (range, 64 to 100). For repair of the coronoid fracture, the suture lasso technique was more stable than the other techniques intraoperatively, both before (p < 0.05) and after (p < 0.05) LUCL repair, and at the final follow-up (p < 0.05). ORIF was associated with a higher prevalence of implant failure (p < 0.05), and suture anchors were associated with a higher prevalence of malunion and nonunion (p < 0.05).
Conclusions: For terrible triad injuries, greater stability with fewer complications was achieved With use of the suture lasso technique for coronoid fracture fixation.
C1 [Garrigues, Grant E.] Duke Univ, Dept Orthopaed Surg, Med Ctr, Durham, NC 27710 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Garrigues, GE (reprint author), Duke Univ, Dept Orthopaed Surg, Med Ctr, Box 3466, Durham, NC 27710 USA.
EM d.ruch@duke.edu
NR 26
TC 34
Z9 45
U1 0
U2 8
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD OCT 19
PY 2011
VL 93A
IS 20
BP 1873
EP 1881
DI 10.2106/JBJS.I.01673
PG 9
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 836AE
UT WOS:000296077600003
PM 22012524
ER
PT J
AU Lu, J
Liu, HS
Zhang, M
Wang, DH
Cao, YX
Ma, QF
Rong, DD
Wang, XY
Buckner, RL
Li, KC
AF Lu, Jie
Liu, Hesheng
Zhang, Miao
Wang, Danhong
Cao, Yanxiang
Ma, Qingfeng
Rong, Dongdong
Wang, Xiaoyi
Buckner, Randy L.
Li, Kuncheng
TI Focal Pontine Lesions Provide Evidence That Intrinsic Functional
Connectivity Reflects Polysynaptic Anatomical Pathways
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SPONTANEOUS FLUCTUATIONS; STRUCTURAL CONNECTIVITY; HUMAN BRAIN; STROKE;
ORGANIZATION; CORTEX; MONKEY; ARCHITECTURE; PROJECTIONS; DISORDERS
AB Intrinsic functional connectivity detected by functional MRI (fMRI) provides a useful but indirect approach to study the organization of human brain systems. An unresolved question is whether functional connectivity measured by resting-state fMRI reflects anatomical connections. In this study, we used the well-characterized anatomy of cerebrocerebellar circuits to directly test whether intrinsic functional connectivity is associated with an anatomic pathway. Eleven first-episode stroke patients were scanned five times during a period of 6 months, and 11 healthy control subjects were scanned three times within 1 month. In patients with right pontine strokes, the functional connectivity between the right motor cortex and the left cerebellum was selectively reduced. This connectivity pattern was reversed in patients with left pontine strokes. Although factors beyond anatomical connectivity contribute to fMRI measures of functional correlation, these results provide direct evidence that functional connectivity depends on intact connections within a specific polysynaptic pathway.
C1 [Lu, Jie; Zhang, Miao; Cao, Yanxiang; Rong, Dongdong; Wang, Xiaoyi; Li, Kuncheng] Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing 100053, Peoples R China.
[Ma, Qingfeng] Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China.
[Liu, Hesheng; Wang, Danhong; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA.
[Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA.
[Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Buckner, Randy L.] Howard Hughes Med Inst, Cambridge, MA 02138 USA.
RP Li, KC (reprint author), Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing 100053, Peoples R China.
EM randy_buckner@harvard.edu; likuncheng1955@yahoo.com.cn
RI wang, danhong/C-8353-2014; wang, danhong/M-2699-2014;
OI Liu, Hesheng/0000-0002-7233-1509
FU NINDS [K25NS069805]; NIA [AG021910]; NCRR [P41RR14074]; Howard Hughes
Medical Institute
FX This work was supported by NINDS Grant K25NS069805, NIA Grant AG021910,
NCRR Grant P41RR14074, and the Howard Hughes Medical Institute. We thank
Fenna Krienen, Avram Holmes, and Jorge Sepulcre for assistance with data
analysis, Judith Schaechter for discussion of behavioral assessment,
Jeremy Schmahmann for discussion of anatomy, and Haderer & Muller
Biomedical Art for illustration.
NR 35
TC 42
Z9 42
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 OCT 19
PY 2011
VL 31
IS 42
BP 15065
EP 15071
DI 10.1523/JNEUROSCI.2364-11.2011
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 838FY
UT WOS:000296274000026
PM 22016540
ER
PT J
AU Kahn, I
Desai, M
Knoblich, U
Bernstein, J
Henninger, M
Graybiel, AM
Boyden, ES
Buckner, RL
Moore, CI
AF Kahn, Itamar
Desai, Mitul
Knoblich, Ulf
Bernstein, Jacob
Henninger, Michael
Graybiel, Ann M.
Boyden, Edward S.
Buckner, Randy L.
Moore, Christopher I.
TI Characterization of the Functional MRI Response Temporal Linearity via
Optical Control of Neocortical Pyramidal Neurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID TRANSGENIC MICE; HUMAN BRAIN; TELL US; FMRI; CHANNELRHODOPSIN-2;
ACTIVATION; CORTEX; DRIVEN
AB The blood oxygenation level-dependent (BOLD) signal serves as the basis for human functional MRI(fMRI). Knowledge of the properties of the BOLD signal, such as how linear its response is to sensory stimuli, is essential for the design and interpretation of fMRI experiments. Here, we combined the cell-type and site-specific causal control provided by optogenetics and fMRI (opto-fMRI) in mice to test the linearity of BOLD signals driven by locally induced excitatory activity. We employed high-resolution mouse fMRI at 9.4 tesla to measure the BOLD response, and extracellular electrophysiological recordings to measure the effects of stimulation on single unit, multiunit, and local field potential activity. Optically driven stimulation of layer V neocortical pyramidal neurons resulted in a positive local BOLD response at the stimulated site. Consistent with a linear transform model, this locally driven BOLD response summated in response to closely spaced trains of stimulation. These properties were equivalent to responses generated through the multisynaptic method of driving neocortical activity by tactile sensory stimulation, and paralleled changes in electrophysiological measures. These results illustrate the potential of the opto-fMRI method and reinforce the critical assumption of human functional neuroimaging that-to first approximation-the BOLD response tracks local neural activity levels.
C1 [Kahn, Itamar; Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
[Kahn, Itamar; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Kahn, Itamar; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Desai, Mitul; Knoblich, Ulf; Bernstein, Jacob; Henninger, Michael; Graybiel, Ann M.; Boyden, Edward S.; Moore, Christopher I.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Bernstein, Jacob; Henninger, Michael; Boyden, Edward S.] MIT, MIT Media Lab, Synthet Neurobiol Grp, Cambridge, MA 02139 USA.
[Bernstein, Jacob; Henninger, Michael; Boyden, Edward S.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat & Radiol, Boston, MA 02114 USA.
RP Boyden, ES (reprint author), MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM kahn@technion.ac.il; esb@media.mit.edu; randy_buckner@harvard.edu;
cim@mit.edu
RI Knoblich, Ulf/A-1762-2010
OI Knoblich, Ulf/0000-0002-0756-5587
FU National Science Foundation; National Institutes of Health; Howard
Hughes Medical Institute; McGovern Institute for Brain Research
FX This work was supported by the National Science Foundation, National
Institutes of Health, the Howard Hughes Medical Institute, and the
McGovern Institute for Brain Research. We thank Jessica Cardin, Robert
Haslinger, Dominique Pritchett, Jason Ritt, and Jackie Schiller for
helpful discussions, Jessica Cardin for technical assistance with
histology, and Harvard Center for Brain Science Optical Imaging Core and
Steve Turney for assistance with fluorescence imaging.
NR 26
TC 54
Z9 55
U1 2
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 19
PY 2011
VL 31
IS 42
BP 15086
EP 15091
DI 10.1523/JNEUROSCI.0007-11.2011
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 838FY
UT WOS:000296274000028
PM 22016542
ER
PT J
AU Behrens, CR
Hooker, JM
Obermeyer, AC
Romanini, DW
Katz, EM
Francis, MB
AF Behrens, Christopher R.
Hooker, Jacob M.
Obermeyer, Allie C.
Romanini, Dante W.
Katz, Elan M.
Francis, Matthew B.
TI Rapid Chemoselective Bioconjugation through Oxidative Coupling of
Anilines and Aminophenols
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID VIRUS-LIKE PARTICLES; GENETIC-CODE; AMINO-ACIDS; SURFACE; PEPTIDES;
PROTEINS; BACTERIOPHAGE-MS2; SELECTIVITY; CHEMISTRY; MOLECULE
AB A highly efficient protein bioconjugation method is described involving addition of anilines to o-aminophenols in the presence of sodium periodate. The reaction takes place in aqueous buffer at pH 6.5 and can reach high conversion in 2-5 min. The major product was characterized using X-ray crystallography, which revealed that an unprecedented oxidative ring contraction occurs after the coupling step. The compatibility of the reaction with protein substrates has been demonstrated through attachment of small molecules, polymer chains, and peptides to p-aminophenylalanine residues introduced into viral capsids through amber stop codon suppression. Coupling of anilines to o-aminophenol groups derived from tyrosine residues is also described. The compatibility of this method with thiol modification chemistry is shown through attachment of a near-IR fluorescent chromophore to cysteine residues inside the viral capsid shells, followed by attachment of integrin-targeting RGD peptides to anilines on the exterior surface.
C1 [Behrens, Christopher R.; Obermeyer, Allie C.; Romanini, Dante W.; Katz, Elan M.; Francis, Matthew B.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Hooker, Jacob M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02129 USA.
[Francis, Matthew B.] Lawrence Berkeley Natl Labs, Div Mat Sci, Berkeley, CA 94720 USA.
RP Francis, MB (reprint author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
EM mbfrancis@berkeley.edu
OI Hooker, Jacob/0000-0002-9394-7708
FU DOD [BC061995]; NSF; UC Berkeley [1 T32 GMO66698]; DOE California
Alliance for Radiotracer Education [DESC0002061]
FX These studies were supported by the DOD Breast Cancer Research Program
(BC061995). C.R.B. was supported by DOE California Alliance for
Radiotracer Education grant DESC0002061, and A.C.O. was supported by an
NSF graduate research fellowship. The UC Berkeley Chemical Biology
Graduate Program (Training Grant 1 T32 GMO66698) is also acknowledged
for their support of C.RB., D.W.R, and A.C.O.
NR 35
TC 31
Z9 31
U1 2
U2 51
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD OCT 19
PY 2011
VL 133
IS 41
BP 16398
EP 16401
DI 10.1021/ja2033298
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 834XJ
UT WOS:000295997500021
PM 21919497
ER
PT J
AU Kansagara, D
Englander, H
Salanitro, A
Kagen, D
Theobald, C
Freeman, M
Kripalani, S
AF Kansagara, Devan
Englander, Honora
Salanitro, Amanda
Kagen, David
Theobald, Cecelia
Freeman, Michele
Kripalani, Sunil
TI Risk Prediction Models for Hospital Readmission A Systematic Review
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID QUALITY-OF-CARE; GENERAL MEDICINE PATIENTS; HEART-FAILURE;
STATISTICAL-MODELS; PATIENT PREDICTORS; 30-DAY READMISSION; FOLLOW-UP;
TRANSITIONS; PERFORMANCE; VALIDATION
AB Context Predicting hospital readmission risk is of great interest to identify which patients would benefit most from care transition interventions, as well as to risk-adjust readmission rates for the purposes of hospital comparison.
Objective To summarize validated readmission risk prediction models, describe their performance, and assess suitability for clinical or administrative use.
Data Sources and Study Selection The databases of MEDLINE, CINAHL, and the Cochrane Library were searched from inception through March 2011, the EMBASE database was searched through August 2011, and hand searches were performed of the retrieved reference lists. Dual review was conducted to identify studies published in the English language of prediction models tested with medical patients in both derivation and validation cohorts.
Data Extraction Data were extracted on the population, setting, sample size, follow-up interval, readmission rate, model discrimination and calibration, type of data used, and timing of data collection.
Data Synthesis Of 7843 citations reviewed, 30 studies of 26 unique models met the inclusion criteria. The most common outcome used was 30-day readmission; only 1 model specifically addressed preventable readmissions. Fourteen models that relied on retrospective administrative data could be potentially used to risk-adjust readmission rates for hospital comparison; of these, 9 were tested in large US populations and had poor discriminative ability (c statistic range: 0.55-0.65). Seven models could potentially be used to identify high-risk patients for intervention early during a hospitalization (c statistic range: 0.56-0.72), and 5 could be used at hospital discharge (c statistic range: 0.68-0.83). Six studies compared different models in the same population and 2 of these found that functional and social variables improved model discrimination. Although most models incorporated variables for medical comorbidity and use of prior medical services, few examined variables associated with overall health and function, illness severity, or social determinants of health.
Conclusions Most current readmission risk prediction models that were designed for either comparative or clinical purposes perform poorly. Although in certain settings such models may prove useful, efforts to improve their performance are needed as use becomes more widespread. JAMA. 2011;306(15):1688-1698
C1 [Kansagara, Devan; Freeman, Michele] Portland VA Med Ctr, VA Evidence Based Synth Program, Portland, OR 97239 USA.
[Kansagara, Devan; Kagen, David] Portland VA Med Ctr, Dept Gen Internal Med, Portland, OR 97239 USA.
[Kansagara, Devan; Englander, Honora; Kagen, David] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA.
[Salanitro, Amanda] VA Tennessee Valley Healthcare Syst, Ctr Geriatr Res Educ & Clin, Nashville, TN USA.
[Salanitro, Amanda; Theobald, Cecelia; Kripalani, Sunil] Vanderbilt Univ, Dept Med, Div Gen Internal Med & Publ Hlth, Sect Hosp Med, Nashville, TN USA.
RP Kansagara, D (reprint author), Portland VA Med Ctr, VA Evidence Based Synth Program, Mailcode RD71,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM kansagar@ohsu.edu
FU Department of Veterans Affairs; Veterans Health Administration, Office
of Research and Development, Health Services Research and Development;
National Center for Research Resources, National Institutes of Health [1
UL1 RR024976]
FX This report is based on research conducted by the Evidence-Based
Synthesis Program Center located at the Portland VA Medical Center, and
funded by the Department of Veterans Affairs and the Veterans Health
Administration, Office of Research and Development, Health Services
Research and Development. The research also was funded in part by
Vanderbilt CTSA grant 1 UL1 RR024976 from the National Center for
Research Resources, National Institutes of Health.
NR 62
TC 453
Z9 454
U1 9
U2 89
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 19
PY 2011
VL 306
IS 15
BP 1688
EP 1698
DI 10.1001/jama.2011.1515
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 834MA
UT WOS:000295963200028
PM 22009101
ER
PT J
AU Gheorghiade, M
Braunwald, E
AF Gheorghiade, Mihai
Braunwald, Eugene
TI Hospitalizations for Heart Failure in the United States-A Sign of Hope
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID VASOPRESSIN ANTAGONISM; PERFORMANCE-MEASURES; EJECTION FRACTION;
OUTCOMES; ASSOCIATION; MORBIDITY; TOLVAPTAN; MORTALITY; EFFICACY;
DIGOXIN
C1 [Gheorghiade, Mihai] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
[Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp,Dept Med,Med Sch, Boston, MA 02115 USA.
RP Gheorghiade, M (reprint author), Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Dept Med, 645 N Michigan Ave,Ste 1006, Chicago, IL 60611 USA.
EM m-gheorghiade@northwestern.edu
NR 20
TC 19
Z9 21
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 19
PY 2011
VL 306
IS 15
BP 1705
EP 1706
DI 10.1001/jama.2011.1510
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 834MA
UT WOS:000295963200032
PM 22009103
ER
PT J
AU Turkbey, EB
Backlund, JYC
Genuth, S
Jain, A
Miao, CL
Cleary, PA
Lachin, JM
Nathan, DM
van der Geest, RJ
Soliman, EZ
Liu, CY
Lima, JAC
Bluemke, DA
AF Turkbey, Evrim B.
Backlund, Jye-Yu C.
Genuth, Saul
Jain, Aditya
Miao, Cuilian
Cleary, Patricia A.
Lachin, John M.
Nathan, David M.
van der Geest, Rob J.
Soliman, Elsayed Z.
Liu, Chia-Ying
Lima, Joao A. C.
Bluemke, David A.
CA DCCT EDIC Res Grp
TI Myocardial Structure, Function, and Scar in Patients With Type 1
Diabetes Mellitus
SO CIRCULATION
LA English
DT Article
DE cardiovascular diseases; diabetes mellitus, type 1; magnetic resonance
imaging; risk factors
ID LEFT-VENTRICULAR MASS; CARDIAC MAGNETIC-RESONANCE;
CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; RISK-FACTORS;
COMPLICATIONS TRIAL/EPIDEMIOLOGY; ARTERY-DISEASE; BODY-SIZE; FOLLOW-UP;
INFARCTION
AB Background-We report relationships between cardiovascular disease risk factors and myocardial structure, function, and scar in patients with type 1 diabetes mellitus in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.
Methods and Results-Cardiac magnetic resonance was obtained in 1017 patients with type 1 diabetes mellitus. Gadolinium cardiac magnetic resonance was also obtained in 741 patients. The mean age was 49 +/- 7 years; 52% were men; and mean duration of diabetes mellitus was 28 +/- 5 years. Associations of cardiovascular disease risk factors with cardiac magnetic resonance parameters were examined with linear and logistic regression models. History of macroalbuminuria was positively associated with left ventricular mass (by 14.8 g), leading to a significantly higher ratio of left ventricular mass to end-diastolic volume (by 8%). Mean hemoglobin A(1c) levels over the preceding 22 years were inversely associated with end-diastolic volume (-3.0 mL per unit mean hemoglobin A(1c) percent) and stroke volume (-2.3 mL per unit mean hemoglobin A(1c) percent) and positively related to the ratio of elevated left ventricular mass to end-diastolic volume (0.02 g/mL per unit). The overall prevalence of myocardial scar was 4.3% by cardiac magnetic resonance and 1.4% by clinical adjudication of myocardial infarction. Both mean hemoglobin A(1c) (odds ratio, 1.5 [95% confidence interval, 1.0-2.2] per unit) and macroalbuminuria (odds ratio, 3.5 [95% confidence interval, 1.2-9.9]) were significantly associated with myocardial scar and traditional cardiovascular disease risk factors.
Conclusions-In addition to traditional cardiovascular disease risk factors, elevated mean hemoglobin A(1c) and macroalbuminuria were significantly associated with alterations in left ventricular structure and function. The prevalence of myocardial scar was 4.3% in this subcohort of DCCT/EDIC participants with relatively preserved renal function.
C1 [Turkbey, Evrim B.; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Backlund, Jye-Yu C.; Cleary, Patricia A.; Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[Genuth, Saul] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
[Lima, Joao A. C.] Johns Hopkins Univ, Dept Radiol, Div Cardiol, Baltimore, MD USA.
[Lima, Joao A. C.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA.
[Miao, Cuilian] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA.
[Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA USA.
[van der Geest, Rob J.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
RP Bluemke, DA (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 1C355, Bethesda, MD 20892 USA.
EM bluemked@nih.gov
RI van der Geest, Rob/J-8193-2015;
OI van der Geest, Rob/0000-0002-9084-5597; Lachin,
John/0000-0001-9838-2841; Bluemke, David/0000-0002-8323-8086
FU Division of Diabetes, Endocrinology and Metabolic Diseases of the
National Institute of Diabetes and Digestive and Kidney Diseases;
National Eye Institute; National Institute of Neurological Disorders and
Stroke; General Clinical Research Centers Program; National Center for
Research Resources; Genentech; National Institute of Diabetes and
Digestive and Kidney Diseases; NIH
FX The DCCT/EDIC project is supported by contracts with the Division of
Diabetes, Endocrinology and Metabolic Diseases of the National Institute
of Diabetes and Digestive and Kidney Diseases; National Eye Institute;
National Institute of Neurological Disorders and Stroke; the General
Clinical Research Centers Program; and the Clinical and Translation
Science Centers Program, National Center for Research Resources, as well
as by Genentech through a Cooperative Research and Development Agreement
with the National Institute of Diabetes and Digestive and Kidney
Diseases. Drs Bluemke and Turkbey are supported by the NIH Intramural
research program.
NR 42
TC 30
Z9 33
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD OCT 18
PY 2011
VL 124
IS 16
BP 1737
EP U112
DI 10.1161/CIRCULATIONAHA.111.022327
PG 17
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 842BW
UT WOS:000296562900018
PM 21947298
ER
PT J
AU Odajima, J
Wills, ZP
Ndassa, YM
Terunuma, M
Kretschmannova, K
Deeb, TZ
Geng, Y
Gawrzak, S
Quadros, IM
Newman, J
Das, M
Jecrois, ME
Yu, QY
Li, N
Bienvenu, F
Moss, SJ
Greenberg, ME
Marto, JA
Sicinski, P
AF Odajima, Junko
Wills, Zachary P.
Ndassa, Yasmine M.
Terunuma, Miho
Kretschmannova, Karla
Deeb, Tarek Z.
Geng, Yan
Gawrzak, Sylwia
Quadros, Isabel M.
Newman, Jennifer
Das, Manjusri
Jecrois, Marie E.
Yu, Qunyan
Li, Na
Bienvenu, Frederic
Moss, Stephen J.
Greenberg, Michael E.
Marto, Jarrod A.
Sicinski, Piotr
TI Cyclin E Constrains Cdk5 Activity to Regulate Synaptic Plasticity and
Memory Formation
SO DEVELOPMENTAL CELL
LA English
DT Article
ID DEPENDENT KINASE-5; NERVOUS-SYSTEM; PROTEIN-KINASE; NMDA RECEPTORS;
CELL-CYCLE; G1 CYCLIN; NEURONS; MICE; FAMILY; MOUSE
AB Cyclin E is a component of the core cell cycle machinery, and it drives cell proliferation by regulating entry and progression of cells through the DNA synthesis phase. Cyclin E expression is normally restricted to proliferating cells. However, high levels of cyclin E are expressed in the adult brain. The function of cyclin E in quiescent, postmitotic nervous system remains unknown. Here we use a combination of in vivo quantitative proteomics and analyses of cyclin E knockout mice to demonstrate that in terminally differentiated neurons cyclin E forms complexes with Cdk5 and controls synapse function by restraining Cdk5 activity. Ablation of cyclin E led to a decreased number of synapses, reduced number and volume of dendritic spines, and resulted in impaired synaptic plasticity and memory formation in cyclin E-deficient animals. These results reveal a cell cycle-independent role for a core cell cycle protein, cyclin E, in synapse function and memory.
C1 [Odajima, Junko; Ndassa, Yasmine M.; Geng, Yan; Gawrzak, Sylwia; Das, Manjusri; Jecrois, Marie E.; Yu, Qunyan; Li, Na; Bienvenu, Frederic; Marto, Jarrod A.; Sicinski, Piotr] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA.
[Odajima, Junko; Geng, Yan; Gawrzak, Sylwia; Jecrois, Marie E.; Li, Na; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Wills, Zachary P.; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Ndassa, Yasmine M.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Ndassa, Yasmine M.; Marto, Jarrod A.] Harvard Univ, Sch Med, Biophys Program, Boston, MA 02115 USA.
[Terunuma, Miho; Kretschmannova, Karla; Deeb, Tarek Z.; Quadros, Isabel M.; Newman, Jennifer; Moss, Stephen J.] Tufts Univ, Sch Med, Dept Neurosci, Neurosci Res Ctr, Boston, MA 02111 USA.
[Moss, Stephen J.] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England.
RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
EM jarrod_marto@dfci.harvard.edu; peter_sicinski@dfci.harvard.edu
OI Quadros, Isabel/0000-0002-5200-2214
FU NIH [R01 CA108950]
FX We thank Drs. R. Bronson, J-S Guan, M. Morabito, G. Corfas, Q. Ma, L-H.
Tsai, H. Gardner, M. Ericsson, J. Wang, L. Richey, Y. Haydon, and J.C.
Dodart for help and advice, Dr. L. Le Cam for cyclin E1flox
construct, Y. Kim and P. Greengard for anti-phospho-S310 and -S441 and
anti-total Wave1 antibodies, R. Betarbet for anti-phospho-Ser897 NR1
antibody, T. Ryan and P. De Camilli for Synapsin I cDNA. This work was
supported by NIH grant R01 CA108950 (to P.S.).
NR 49
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U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD OCT 18
PY 2011
VL 21
IS 4
BP 655
EP 668
DI 10.1016/j.devcel.2011.08.009
PG 14
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 839LA
UT WOS:000296366000010
PM 21944720
ER
PT J
AU Kerlikowske, K
Hubbard, RA
Miglioretti, DL
Geller, BM
Yankaskas, BC
Lehman, CD
Taplin, SH
Sickles, EA
AF Kerlikowske, Karla
Hubbard, Rebecca A.
Miglioretti, Diana L.
Geller, Berta M.
Yankaskas, Bonnie C.
Lehman, Constance D.
Taplin, Stephen H.
Sickles, Edward A.
CA Breast Canc Surveillance Consortiu
TI Comparative Effectiveness of Digital Versus Film-Screen Mammography in
Community Practice in the United States A Cohort Study
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID CANCER SURVEILLANCE CONSORTIUM; CARCINOMA IN-SITU; BREAST-CANCER;
THERAPY USE; POPULATION; ACCURACY; DENSITY; PROGRAM; PERFORMANCE; WOMEN
AB Background: Few studies have examined the comparative effectiveness of digital versus film-screen mammography in U. S. community practice.
Objective: To determine whether the interpretive performance of digital and film-screen mammography differs.
Design: Prospective cohort study.
Setting: Mammography facilities in the Breast Cancer Surveillance Consortium.
Participants: 329 261 women aged 40 to 79 years underwent 869 286 mammograms (231 034 digital; 638 252 film-screen).
Measurements: Invasive cancer or ductal carcinoma in situ diagnosed within 12 months of a digital or film-screen examination and calculation of mammography sensitivity, specificity, cancer detection rates, and tumor outcomes.
Results: Overall, cancer detection rates and tumor characteristics were similar for digital and film-screen mammography, but the sensitivity and specificity of each modality varied by age, tumor characteristics, breast density, and menopausal status. Compared with film-screen mammography, the sensitivity of digital mammography was significantly higher for women aged 60 to 69 years (89.9% vs. 83.0%; P = 0.014) and those with estrogen receptor-negative cancer (78.5% vs. 65.8%; P = 0.016); borderline significantly higher for women aged 40 to 49 years (82.4% vs. 75.6%; P = 0.071), those with extremely dense breasts (83.6% vs. 68.1%; P = 0.051), and pre- or perimenopausal women (87.1% vs. 81.7%; P = 0.057); and borderline significantly lower for women aged 50 to 59 years (80.5% vs. 85.1%; P = 0.097). The specificity of digital and film-screen mammography was similar by decade of age, except for women aged 40 to 49 years (88.0% vs. 89.7%; P < 0.001).
Limitation: Statistical power for subgroup analyses was limited.
Conclusion: Overall, cancer detection with digital or film-screen mammography is similar in U. S. women aged 50 to 79 years undergoing screening mammography. Women aged 40 to 49 years are more likely to have extremely dense breasts and estrogen receptor-negative tumors; if they are offered mammography screening, they may choose to undergo digital mammography to optimize cancer detection.
C1 [Kerlikowske, Karla] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Univ Washington, Sch Publ Hlth & Community Med, Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98195 USA.
Univ Washington, Sch Med, Seattle, WA USA.
Univ Vermont, Coll Med, Burlington, VT USA.
Univ N Carolina, Chapel Hill, NC USA.
NCI, Appl Res Program, Rockville, MD USA.
RP Kerlikowske, K (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA.
EM Karla.Kerlikowske@ucsf.edu
OI Hubbard, Rebecca/0000-0003-0879-0994
FU National Cancer Institute [U01CA63740, U01CA86076, U01CA86082,
U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040, R03CA150007,
RC2CA148577]
FX By the National Cancer Institute-funded BCSC cooperative agreement
(grants U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013,
U01CA69976, U01CA63731, and U01CA70040) and National Cancer Institute
grants R03CA150007 and RC2CA148577. The collection of cancer data used
in this study was supported in part by several state public health
departments and cancer registries throughout the United States; for a
full description of these sources, see
http://breastscreening.cancer.gov/work/acknowledgement.html.
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U2 14
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD OCT 18
PY 2011
VL 155
IS 8
BP 493
EP U64
DI 10.7326/0003-4819-155-8-201110180-00005
PG 18
WC Medicine, General & Internal
SC General & Internal Medicine
GA 835WB
UT WOS:000296066300014
PM 22007043
ER
PT J
AU Cai, CM
He, HSHS
Chen, S
Coleman, I
Wang, HY
Fang, Z
Chen, SY
Nelson, PS
Liu, XS
Brown, M
Balk, SP
AF Cai, Changmeng
He, Housheng Hansen
Chen, Sen
Coleman, Ilsa
Wang, Hongyun
Fang, Zi
Chen, Shaoyong
Nelson, Peter S.
Liu, X. Shirley
Brown, Myles
Balk, Steven P.
TI Androgen Receptor Gene Expression in Prostate Cancer Is Directly
Suppressed by the Androgen Receptor Through Recruitment of
Lysine-Specific Demethylase 1
SO CANCER CELL
LA English
DT Article
ID MESSENGER-RNA; TRANSCRIPTIONAL REGULATION; LSD1; PHOSPHORYLATION;
PROGRESSION; ACTIVATION; MECHANISMS; CASTRATION; THERAPY; PROTEIN
AB Androgen receptor (AR) is reactivated in castration-resistant prostate cancer (CRPC) through mechanisms including marked increases in AR gene expression. We identify an enhancer in the AR second intron contributing to increased AR expression at low androgen levels in CRPC. Moreover, at increased androgen levels, the AR binds this site and represses AR gene expression through recruitment of lysine-specific demethylase 1 (LSD1) and H3K4me1,2 demethylation. AR similarly represses expression of multiple genes mediating androgen synthesis, DNA synthesis, and proliferation while stimulating genes mediating lipid and protein biosynthesis. Androgen levels in CRPC appear adequate to stimulate AR activity on enhancer elements, but not suppressor elements, resulting in increased expression of AR and AR repressed genes that contribute to cellular proliferation.
C1 [Cai, Changmeng; Chen, Sen; Wang, Hongyun; Fang, Zi; Chen, Shaoyong; Balk, Steven P.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA.
[Cai, Changmeng; Chen, Sen; Wang, Hongyun; Fang, Zi; Chen, Shaoyong; Balk, Steven P.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[He, Housheng Hansen; Brown, Myles] Dana Farber Canc Inst, Div Mol & Cellular Oncol, Boston, MA 02115 USA.
[He, Housheng Hansen; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[He, Housheng Hansen; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[He, Housheng Hansen; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Coleman, Ilsa; Nelson, Peter S.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
RP Balk, SP (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA.
EM sbalk@bidmc.harvard.edu
RI He, Housheng/G-9614-2011;
OI Brown, Myles/0000-0002-8213-1658; Cai, Changmeng/0000-0002-8701-2586
FU National Institutes of Health [R01 CA111803, P50 CA090381, R00 CA135592,
P50 CA097186, RO1 CA146849]; Department of Defense [PC060807, PC093509];
Prostate Cancer Foundation
FX We thank J. He for analyzing three AR binding sites among species; and
E. A. Mostaghel, B. Marck, and A. M. Matsumoto for measuring
intratumoral level of steroids. This work was supported by the National
Institutes of Health (grant R01 CA111803 to S.P.B., Prostate SPORE P50
CA090381 to S.P.B. and M.B., a Career Development Award from the
Prostate SPORE to C.C., grant R00 CA135592 to S.C., and grants Prostate
SPORE P50 CA097186 and RO1 CA146849 to P.S.N.), Department of Defense
Prostate Cancer Research Program (grant PC060807 to S.P.B., postdoctoral
fellowships to C.C. and H.W., and grant PC093509 to P.S.N.), and a
Challenge Grant from the Prostate Cancer Foundation.
NR 38
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U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD OCT 18
PY 2011
VL 20
IS 4
BP 457
EP 471
DI 10.1016/j.ccr.2011.09.001
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 836OP
UT WOS:000296121300008
PM 22014572
ER
PT J
AU Ando, T
Xuan, WJ
Xu, T
Dai, TH
Sharma, SK
Kharkwal, GB
Huang, YY
Wu, QH
Whalen, MJ
Sato, S
Obara, M
Hamblin, MR
AF Ando, Takahiro
Xuan, Weijun
Xu, Tao
Dai, Tianhong
Sharma, Sulbha K.
Kharkwal, Gitika B.
Huang, Ying-Ying
Wu, Qiuhe
Whalen, Michael J.
Sato, Shunichi
Obara, Minoru
Hamblin, Michael R.
TI Comparison of Therapeutic Effects between Pulsed and Continuous Wave
810-nm Wavelength Laser Irradiation for Traumatic Brain Injury in Mice
SO PLOS ONE
LA English
DT Article
ID CONTROLLED CORTICAL IMPACT; HELIUM-NEON LASER; TERM NEUROLOGICAL
DEFICITS; LEVEL LIGHT THERAPY; CLOSED-HEAD INJURY; SPINAL-CORD-INJURY;
PROMOTES REGENERATION; FUNCTIONAL RECOVERY; MEMORY PERFORMANCE;
ISCHEMIC-STROKE
AB Background and Objective: Transcranial low-level laser therapy (LLLT) using near-infrared light can efficiently penetrate through the scalp and skull and could allow non-invasive treatment for traumatic brain injury (TBI). In the present study, we compared the therapeutic effect using 810-nm wavelength laser light in continuous and pulsed wave modes in a mouse model of TBI.
Study Design/Materials and Methods: TBI was induced by a controlled cortical-impact device and 4-hours post-TBI 1-group received a sham treatment and 3-groups received a single exposure to transcranial LLLT, either continuous wave or pulsed at 10-Hz or 100-Hz with a 50% duty cycle. An 810-nm Ga-Al-As diode laser delivered a spot with diameter of 1-cm onto the injured head with a power density of 50-mW/cm(2) for 12-minutes giving a fluence of 36-J/cm(2). Neurological severity score (NSS) and body weight were measured up to 4 weeks. Mice were sacrificed at 2, 15 and 28 days post-TBI and the lesion size was histologically analyzed. The quantity of ATP production in the brain tissue was determined immediately after laser irradiation. We examined the role of LLLT on the psychological state of the mice at 1 day and 4 weeks after TBI using tail suspension test and forced swim test.
Results: The 810-nm laser pulsed at 10-Hz was the most effective judged by improvement in NSS and body weight although the other laser regimens were also effective. The brain lesion volume of mice treated with 10-Hz pulsed-laser irradiation was significantly lower than control group at 15-days and 4-weeks post-TBI. Moreover, we found an antidepressant effect of LLLT at 4-weeks as shown by forced swim and tail suspension tests.
Conclusion: The therapeutic effect of LLLT for TBI with an 810-nm laser was more effective at 10-Hz pulse frequency than at CW and 100-Hz. This finding may provide a new insight into biological mechanisms of LLLT.
C1 [Ando, Takahiro; Xuan, Weijun; Xu, Tao; Dai, Tianhong; Sharma, Sulbha K.; Kharkwal, Gitika B.; Huang, Ying-Ying; Wu, Qiuhe; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Ando, Takahiro; Obara, Minoru] Keio Univ, Dept Elect & Elect Engn, Yokohama, Kanagawa 223, Japan.
[Xuan, Weijun; Xu, Tao; Dai, Tianhong; Kharkwal, Gitika B.; Huang, Ying-Ying; Wu, Qiuhe; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Xuan, Weijun] Tradit Chinese Med Univ Guangxi, Dept Otolaryngol, Nanning, Peoples R China.
[Xu, Tao] Shanghai Jiao Tong Univ, Lab Anesthesiol, Shanghai 200030, Peoples R China.
[Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China.
[Wu, Qiuhe] Shandong Univ, Jinan Cent Hosp, Dept Burns & Plast Surg, Jinan 250100, Peoples R China.
[Whalen, Michael J.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Sato, Shunichi] Natl Def Med Coll, Res Inst, Div Biomed Informat Sci, Tokorozawa, Saitama 359, Japan.
[Hamblin, Michael R.] Harvard Univ, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02138 USA.
RP Ando, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
EM hamblin@helix.mgh.harvard.edu
RI Huang, Ying-ying/G-3153-2011;
OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin,
Michael/0000-0001-6431-4605
FU National Institutes of Health (NIH) [R01AI050875]; Center for
Integration of Medicine and Innovative Technology [DAMD17-02-2-0006];
Congressionally Directed Medical Research Program in Traumatic Brain
Injury [W81XWH-09-1-0514]; Air Force Office of Scientific Research
[FA9950-04-1-0079]; Ministry of Education, Culture, Sport, Science and
Technology, Japan; Japan Society for the Promotion of Science (JSPS)
FX This research was supported by National Institutes of Health (NIH) grant
R01AI050875 (to Dr. Hamblin), Center for Integration of Medicine and
Innovative Technology (DAMD17-02-2-0006), Congressionally Directed
Medical Research Program in Traumatic Brain Injury (W81XWH-09-1-0514)
and Air Force Office of Scientific Research Military Photomedicine
Program (FA9950-04-1-0079). Dr. Ando was supported in part by a
Grant-in-Aid for the Global Center of Excellence for High-Level Global
Cooperation for Leading-Edge Platform on Access Spaces from the Ministry
of Education, Culture, Sport, Science and Technology, Japan, and a
Grant-in-Aid for Research Fellows of the Japan Society for the Promotion
of Science (JSPS). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 67
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U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 18
PY 2011
VL 6
IS 10
AR e26212
DI 10.1371/journal.pone.0026212
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837ID
UT WOS:000296186900034
PM 22028832
ER
PT J
AU Becerra, L
Pendse, G
Chang, PC
Bishop, J
Borsook, D
AF Becerra, Lino
Pendse, Gautam
Chang, Pei-Ching
Bishop, James
Borsook, David
TI Robust Reproducible Resting State Networks in the Awake Rodent Brain
SO PLOS ONE
LA English
DT Article
ID INDEPENDENT COMPONENT ANALYSIS; BOLD SIGNAL FLUCTUATIONS; ANESTHETIZED
RAT-BRAIN; FUNCTIONAL CONNECTIVITY; SPATIOTEMPORAL DYNAMICS; INSULAR
CORTEX; BASAL GANGLIA; DEFAULT MODE; FREQUENCY; ORGANIZATION
AB Resting state networks (RSNs) have been studied extensively with functional MRI in humans in health and disease to reflect brain function in the un-stimulated state as well as reveal how the brain is altered with disease. Rodent models of disease have been used comprehensively to understand the biology of the disease as well as in the development of new therapies. RSN reported studies in rodents, however, are few, and most studies are performed with anesthetized rodents that might alter networks and differ from their non-anesthetized state. Acquiring RSN data in the awake rodent avoids the issues of anesthesia effects on brain function. Using high field fMRI we determined RSNs in awake rats using an independent component analysis (ICA) approach, however, ICA analysis can produce a large number of components, some with biological relevance (networks). We further have applied a novel method to determine networks that are robust and reproducible among all the components found with ICA. This analysis indicates that 7 networks are robust and reproducible in the rat and their putative role is discussed.
C1 [Becerra, Lino; Pendse, Gautam; Chang, Pei-Ching; Bishop, James; Borsook, David] Massachusetts Gen Hosp, Pain & Analgesia Imaging Neurosci Grp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
RP Becerra, L (reprint author), Massachusetts Gen Hosp, Pain & Analgesia Imaging Neurosci Grp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
EM becerra@nmr.mgh.harvard.edu
FU National Institute of Drug Abuse [K24NS064050-DB]; Herlands Fund for
Pain Research; National Center For Research Resources [S10RR031599,
1S10RR023401, 1S10RR019307, 1S10RR023043]
FX The work was supported by National Institute of Drug Abuse (grant number
K24NS064050-DB) and The Herlands Fund for Pain Research (DB, LB). The
project described was supported by Award Numbers S10RR031599,
1S10RR023401, 1S10RR019307, and 1S10RR023043 from the National Center
For Research Resources. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Center For Research Resources or the National Institutes of
Health. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 18
PY 2011
VL 6
IS 10
AR e25701
DI 10.1371/journal.pone.0025701
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837ID
UT WOS:000296186900016
PM 22028788
ER
PT J
AU Tan, KY
Eminli, S
Hettmer, S
Hochedlinger, K
Wagers, AJ
AF Tan, Kah Yong
Eminli, Sarah
Hettmer, Simone
Hochedlinger, Konrad
Wagers, Amy J.
TI Efficient Generation of iPS Cells from Skeletal Muscle Stem Cells
SO PLOS ONE
LA English
DT Article
ID BETA-CELLS; DIFFERENTIATION; PROGENITORS; SYSTEM; MOUSE; FAT
AB Reprogramming of somatic cells into inducible pluripotent stem cells generally occurs at low efficiency, although what limits reprogramming of particular cell types is poorly understood. Recent data suggest that the differentiation status of the cell targeted for reprogramming may influence its susceptibility to reprogramming as well as the differentiation potential of the induced pluripotent stem (iPS) cells that are derived from it. To assess directly the influence of lineage commitment on iPS cell derivation and differentiation, we evaluated reprogramming in adult stem cell and mature cell populations residing in skeletal muscle. Our data using clonal assays and a second-generation inducible reprogramming system indicate that stem cells found in mouse muscle, including resident satellite cells and mesenchymal progenitors, reprogram with significantly greater efficiency than their more differentiated daughters (myoblasts and fibroblasts). However, in contrast to previous reports, we find no evidence of biased differentiation potential among iPS cells derived from myogenically committed cells. These data support the notion that adult stem cells reprogram more efficiently than terminally differentiated cells, and argue against the suggestion that "epigenetic memory" significantly influences the differentiation potential of iPS cells derived from distinct somatic cell lineages in skeletal muscle.
C1 [Tan, Kah Yong; Hettmer, Simone; Wagers, Amy J.] Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA.
[Tan, Kah Yong; Eminli, Sarah; Hettmer, Simone; Hochedlinger, Konrad; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Tan, Kah Yong; Eminli, Sarah; Hettmer, Simone; Hochedlinger, Konrad; Wagers, Amy J.] Harvard Stem Cell Inst, Cambridge, MA USA.
[Tan, Kah Yong] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Eminli, Sarah; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Eminli, Sarah; Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA USA.
[Eminli, Sarah] Free Univ Berlin, Dept Biol Chem & Pharm, D-1000 Berlin, Germany.
[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.
[Hochedlinger, Konrad; Wagers, Amy J.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Tan, KY (reprint author), Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA.
EM amy.wagers@joslin.harvard.edu
OI Tan, Kah Yong/0000-0002-6825-2752
FU Beckman Foundation; Joslin Diabetes Center; NIH [1DP2OD003266-01];
Harvard Stem Cell Institute [DP-0003-07-03, CF-0003-08-00]; Hope Street
Kids; Alex's Lemonade Stand Foundation; Bear Necessities; NIDDK
[P30DK036836]
FX The authors gratefully acknowledge support for this project from the
Beckman Foundation (http://www.beckman-foundation.com), and Joslin
Diabetes Center (www.joslinresearch.org) (to AW, no Award Number), NIH
Innovator Award (to KH, Award Number 1DP2OD003266-01), the Harvard Stem
Cell Institute (www.hsci.harvard.edu, to AW and KH, Award number
DP-0003-07-03), and by Hope Street Kids (www.hopestreetkids.org), P. A.
L. S. Bermuda/St. Baldrick's (www.stbaldricks.org), Alex's Lemonade
Stand Foundation (www.alexlemonade.org) and Bear Necessities
(www.bearnecessities.org) (to SH). Flow cytometry facilities were
supported in by grants from the Harvard Stem Cell Institute (Award
Number CF-0003-08-00) and NIDDK (Award Number P30DK036836). KY is a
fellow of the Agency of Science, Technology and Research, Singapore
(www.a-star.edu.sg). The content of this manuscript is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIH or other funding agencies that supported this
work. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 22
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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 OCT 18
PY 2011
VL 6
IS 10
AR e26406
DI 10.1371/journal.pone.0026406
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837ID
UT WOS:000296186900059
PM 22028872
ER
PT J
AU Motivala, AA
Cannon, CP
Srinivas, VS
Dai, D
Hernandez, AF
Peterson, ED
Bhatt, DL
Fonarow, GC
AF Motivala, Apurva A.
Cannon, Christopher P.
Srinivas, Vankeepuram S.
Dai, David
Hernandez, Adrian F.
Peterson, Eric D.
Bhatt, Deepak L.
Fonarow, Gregg C.
TI Changes in Myocardial Infarction Guideline Adherence as a Function of
Patient Risk An End to Paradoxical Care?
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE guideline adherence; interventional; management; myocardial infarction;
paradox; risk; trends
ID ACUTE CORONARY SYNDROMES; AMERICAN-COLLEGE; PROGRAM; DISEASE;
PREVENTION; MORTALITY; TIME
AB Objectives The goals of this analysis were to determine: 1) whether guideline-based care during hospitalization for a myocardial infarction (MI) varied as a function of patients' baseline risk; and 2) whether temporal improvements in guideline adherence occurred in all risk groups.
Background Guideline-based care of patients with MI improves outcomes, especially among those at higher risk. Previous studies suggest that this group is paradoxically less likely to receive guideline-based care (risk-treatment mismatch).
Methods A total of 112,848 patients with MI were enrolled at 279 hospitals participating in Get With The Guidelines-Coronary Artery Disease (GWTG-CAD) between August 2000 and December 2008. We developed and validated an in-hospital mortality model (C-statistic: 0.75) to stratify patients into risk tertiles: low (0% to 3%), intermediate (3% to 6.5%), and high (>6.5%). Use of guideline-based care and temporal trends were examined.
Results High-risk patients were significantly less likely to receive aspirin, beta-blockers, angiotensin-converting inhibitors/angiotensin receptor blockers, statins, diabetic treatment, smoking cessation advice, or cardiac rehabilitation referral at discharge compared with those at lower risk (all p < 0.0001). However, use of guideline-recommended therapies increased significantly in all risk groups per year (low-risk odds ratio: 1.33 [95% confidence interval (CI): 1.22 to 1.45]; intermediate-risk odds ratio: 1.30 [95% CI: 1.21 to 1.38]; and high-risk odds ratio: 1.30 [95% confidence interval: 1.23 to 1.37]). Also, there was a narrowing in the guideline adherence gap between low- and high-risk patients over time (p = 0.0002).
Conclusions Although adherence to guideline-based care remains paradoxically lower in those MI patients at higher risk of mortality and most likely to benefit from treatment, care is improving for eligible patients within all risk categories, and the gaps between low- and high-risk groups seem to be narrowing. (J Am Coll Cardiol 2011;58:1760-5) (C) 2011 by the American College of Cardiology Foundation
C1 [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA 90095 USA.
[Motivala, Apurva A.; Srinivas, Vankeepuram S.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Cannon, Christopher P.; Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Dai, David; Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Med Ctr, Durham, NC USA.
[Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA.
RP Fonarow, GC (reprint author), Univ Calif Los Angeles, Div Cardiol, Room 247,200 Med Plaza, Los Angeles, CA 90095 USA.
EM gfonarow@mednet.ucla.edu
RI Hernandez, Adrian F./A-7818-2016
OI Hernandez, Adrian F./0000-0003-3387-9616
FU American Heart Association; Pfizer Inc.; Merck/Schering-Plough;
Accumetrics; AstraZeneca; GlaxoSmithKline; Intekrin Therapeutics; Merck;
Takeda; Bristol-Myers Squibb/Sanofi Pharmaceuticals; Novartis;
Proventys; Amylin; Johnson Johnson; Bristol-Myers Squibb/Sanofi; Lilly;
Bristol-Myers Squibb; Eisai; Sanofi-Aventis; The Medicines Company;
Pfizer
FX The Get With The Guidelines Program is funded by the American Heart
Association. The program is also supported in part by unrestricted
educational grants to the American Heart Association by Pfizer Inc. and
the Merck/Schering-Plough Partnership, who did not participate in the
design, analysis, manuscript preparation, or approval. Dr. Cannon has
received research grants/support from Accumetrics, AstraZeneca,
GlaxoSmithKline, Intekrin Therapeutics, Merck, and Takeda; has served on
the advisory board (with funds donated to charity) of the Bristol-Myers
Squibb/Sanofi Pharmaceuticals Partnership and Novartis; and has acted as
a clinical advisor-equity in Automedics Medical Systems. Dr. Hernandez
has received research grants/support from Proventys, Amylin, Merck,
Johnson & Johnson, and AstraZeneca. Dr. Peterson has received research
grants/support from Bristol-Myers Squibb/Sanofi, Lilly, Johnson &
Johnson, and Merck/Schering-Plough. Dr. Bhatt has received research
grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Sanofi-Aventis,
and The Medicines Company. Dr. Fonarow has received research
grants/support from Bristol-Myers Squibb/Sanofi, Merck/Schering-Plough,
Pfizer, and AstraZeneca. All other authors have reported that they have
no relationships relevant to the contents of this paper to disclose.
NR 14
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD OCT 18
PY 2011
VL 58
IS 17
BP 1760
EP 1765
DI 10.1016/j.jacc.2011.06.050
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 833KL
UT WOS:000295883900006
PM 21996387
ER
PT J
AU Noseworthy, PA
Tikkanen, JT
Porthan, K
Salomaa, V
Newton-Cheh, C
Huikuri, HV
AF Noseworthy, Peter A.
Tikkanen, Jani T.
Porthan, Kimmo
Salomaa, Veikko
Newton-Cheh, Christopher
Huikuri, Heikki V.
TI The Early Repolarization Pattern: What's in the Name? Reply
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Letter
C1 [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM cnewtoncheh@chgr.mgh.harvard.edu
NR 3
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD OCT 18
PY 2011
VL 58
IS 17
BP 1830
EP 1831
DI 10.1016/j.jacc.2011.07.027
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 833KL
UT WOS:000295883900021
ER
PT J
AU Limmer, S
Haller, S
Drenkard, E
Lee, J
Yu, S
Kocks, C
Ausubel, FM
Ferrandon, D
AF Limmer, Stefanie
Haller, Samantha
Drenkard, Eliana
Lee, Janice
Yu, Shen
Kocks, Christine
Ausubel, Frederick M.
Ferrandon, Dominique
TI Pseudomonas aeruginosa RhlR is required to neutralize the cellular
immune response in a Drosophila melanogaster oral infection model
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE innate immunity; host-pathogen interactions; systemic immunity;
intestinal immunity; phagocytosis
ID III SECRETION SYSTEM; BACTERIAL-INFECTION; VIRULENCE FACTORS;
GENE-EXPRESSION; HOST; REVEALS; PATHOGENESIS; RESISTANCE; MUTANTS;
ANIMALS
AB An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host-pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated.
C1 [Drenkard, Eliana; Lee, Janice; Yu, Shen; Kocks, Christine; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Limmer, Stefanie; Haller, Samantha; Ferrandon, Dominique] Univ Strasbourg, Inst Biol Mol & Cellulaire, CNRS, Equipe Fdn Rech Med,Unite Propre Rech 9022, F-67084 Strasbourg, France.
[Lee, Janice; Kocks, Christine] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Drenkard, Eliana; Yu, Shen; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM ausubel@molbio.mgh.harvard.edu; d.ferrandon@ibmc.u-strasbg.fr
OI FERRANDON, Dominique/0000-0001-7680-7773; Schirmeier,
Stefanie/0000-0001-8431-9593
FU Centre National de la Recherche Scientifique; National Institutes of
Health [P01 AI044220, R01 AI085581]; Fondation Recherche Medicale
(Equipe Fondation pour la Recherche Medicale); French Ministry of
Research
FX We thank M. C. Lafarge and J. Bourdeaux for expert technical help. We
are grateful to Dr. C. Makino and Dr. H. Fukuyama for a reporter fly
line; to Dr. R. Feinbaum, Dr. D. K. Newman, Dr. R. Kolter, and Dr. E.
Deziel for bacterial strains; and to Dr. S. Lory for plasmids. This work
was funded by Centre National de la Recherche Scientifique; National
Institutes of Health Grant P01 AI044220 (to F.M.A., C.K., and D.F.) and
Grant R01 AI085581 (to F.M.A.); Fondation Recherche Medicale (Equipe
Fondation pour la Recherche Medicale) (D.F.); and the French Ministry of
Research (S.L. and S.H.).
NR 40
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 18
PY 2011
VL 108
IS 42
BP 17378
EP 17383
DI 10.1073/pnas.1114907108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834PP
UT WOS:000295975300035
PM 21987808
ER
PT J
AU Agam, Y
Hamalainen, MS
Lee, AKC
Dyckman, KA
Friedman, JS
Isom, M
Makris, N
Manoach, DS
AF Agam, Yigal
Haemaelaeinen, Matti S.
Lee, Adrian K. C.
Dyckman, Kara A.
Friedman, Jesse S.
Isom, Marlisa
Makris, Nikos
Manoach, Dara S.
TI Multimodal neuroimaging dissociates hemodynamic and electrophysiological
correlates of error processing
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE multimodal imaging; error processing; response monitoring; action
monitoring; medial frontal cortex
ID ANTERIOR CINGULATE CORTEX; MEDIAL FRONTAL-CORTEX; HUMAN CEREBRAL-CORTEX;
EVENT-RELATED FMRI; RESPONSE-INHIBITION; EXECUTIVE FUNCTIONS;
ANTISACCADE TASK; BRAIN; PERFORMANCE; REWARD
AB Recognizing errors and adjusting responses are fundamental to adaptive behavior. The error-related negativity (ERN) and error-related functional MRI (fMRI) activation of the dorsal anterior cingulate cortex (dACC) index these processes and are thought to reflect the same neural mechanism. In the present study, we evaluated this hypothesis. Although errors elicited robust dACC activation using fMRI, combined electroencephalography and magnetoencephalography data localized the ERN to the posterior cingulate cortex (PCC). ERN amplitude correlated with fMRI activation in both the PCC and dACC, and these two regions showed coordinated activity based on functional connectivity MRI. Finally, increased microstructural integrity of the posterior cingulum bundle, as measured by diffusion tensor imaging, predicted faster error correction. These findings suggest that the PCC generates the ERN and communicates with the dACC to subserve error processing. They challenge current models that view fMRI activation of the dACC as the hemodynamic reflection of the ERN.
C1 [Agam, Yigal; Dyckman, Kara A.; Friedman, Jesse S.; Isom, Marlisa; Makris, Nikos; Manoach, Dara S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02215 USA.
[Haemaelaeinen, Matti S.; Lee, Adrian K. C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02215 USA.
[Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02215 USA.
[Agam, Yigal; Haemaelaeinen, Matti S.; Lee, Adrian K. C.; Dyckman, Kara A.; Friedman, Jesse S.; Isom, Marlisa; Makris, Nikos; Manoach, Dara S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Manoach, DS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02215 USA.
EM dara@nmr.mgh.harvard.edu
RI Hamalainen, Matti/C-8507-2013;
OI Lee, Adrian KC/0000-0002-7611-0500
FU National Institute for Mental Health [F32 MH088081, F32 MH082514,
1R21MH084041-01A1, R01 MH67720]; National Institute on Drug Abuse
[1R01DA027804-01]; Massachusetts General Hospital; National Center for
Research Resources [P41 RR014075-11]; National Institute of Biomedical
Imaging and Bioengineering [5R01EB009048]; American Recovery and
Reinvestment Act (ARRA) - National Center for Complementary and
Alternative Medicine (NCCAM)
FX We thank Randy Buckner, Hesheng Liu, and Mark Vangel for consultation.
Support for this study was provided by National Institute for Mental
Health Grants F32 MH088081 (to Y.A.), F32 MH082514 (to K.A.D.),
1R21MH084041-01A1 (to N.M.) and R01 MH67720 (to D.S.M.); National
Institute on Drug Abuse Grant 1R01DA027804-01 (to N.M.); the
Massachusetts General Hospital Fund for Medical Discovery (to Y.A.);
National Center for Research Resources Grant P41 RR014075-11 (to
M.S.H.); National Institute of Biomedical Imaging and Bioengineering
Grant 5R01EB009048 (to M.S.H.); and the American Recovery and
Reinvestment Act (ARRA) - National Center for Complementary and
Alternative Medicine (NCCAM) (to N.M.).
NR 54
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 18
PY 2011
VL 108
IS 42
BP 17556
EP 17561
DI 10.1073/pnas.1103475108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834PP
UT WOS:000295975300065
PM 21969565
ER
PT J
AU Falskov, B
Hermann, TS
Raunso, J
Christiansen, B
Rask-Madsen, C
Major-Pedersen, A
Kober, L
Torp-Pedersen, C
Dominguez, H
AF Falskov, Britt
Hermann, Thomas Steffen
Raunso, Jakob
Christiansen, Buris
Rask-Madsen, Christian
Major-Pedersen, Atheline
Kober, Lars
Torp-Pedersen, Christian
Dominguez, Helena
TI Endothelial function is unaffected by changing between carvedilol and
metoprolol in patients with heart failure-a randomized study
SO CARDIOVASCULAR DIABETOLOGY
LA English
DT Article
DE Heart failure; Endothelial function; Beta blocker
ID CORONARY-ARTERY-DISEASE; EUROPEAN TRIAL COMET; INSULIN-RESISTANCE;
DILATED CARDIOMYOPATHY; VASODILATION; DYSFUNCTION
AB Background: Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF.
Methods: Twenty-seven patients with mild HF, all initially treated with carvedilol, were randomized to a two-month treatment with carvedilol, metoprolol tartrate or metoprolol succinate. Venous occlusion plethysmography, 24-hour blood pressure and heart rate measurements were done before and after a two-month treatment period.
Results: Endothelium-dependent vasodilatation was not affected by changing from carvedilol to either metoprolol tartrate or metoprolol succinate. The relative forearm blood flow at the highest dose of serotonin was 2.42 +/- 0.33 in the carvedilol group at baseline and 2.14 +/- 0.24 after two months continuation of carvedilol (P = 0.34); 2.57 +/- 0.33 before metoprolol tartrate treatment and 2.42 +/- 0.55 after treatment (p = 0.74) and in the metoprolol succinate group 1.82 +/- 0.29 and 2.10 +/- 0.37 before and after treatment, respectively (p = 0.27). Diurnal blood pressures as well as heart rate were also unchanged by changing from carvedilol to metoprolol tartrate or metoprolol succinate.
Conclusion: Endothelial function remained unchanged when switching the beta blocker treatment from carvedilol to either metoprolol tartrate or metoprolol succinate in this study, where blood pressure and heart rate also remained unchanged in patients with mild HF.
C1 [Falskov, Britt; Hermann, Thomas Steffen; Raunso, Jakob; Christiansen, Buris; Major-Pedersen, Atheline; Torp-Pedersen, Christian] Gentofte Univ Hosp, Dept Cardiol, Hellerup, Denmark.
[Dominguez, Helena] Herlev Hosp, Dept Cardiol, DK-2730 Herlev, Denmark.
[Rask-Madsen, Christian] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Kober, Lars] Rigshosp, Dept Cardiol, Ctr Heart, DK-2100 Copenhagen, Denmark.
RP Falskov, B (reprint author), Gentofte Univ Hosp, Dept Cardiol, Hellerup, Denmark.
EM bk@heart.dk
OI DOMINGUEZ, HELENA/0000-0002-7089-2636
FU Danish Heart Foundation; Bispebjerg Hospital Research Foundation
FX Grant has been provided for Britt Falskov from The Danish Heart
Foundation and Bispebjerg Hospital Research Foundation.
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U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2840
J9 CARDIOVASC DIABETOL
JI Cardiovasc. Diabetol.
PD OCT 15
PY 2011
VL 10
AR 91
DI 10.1186/1475-2840-10-91
PG 10
WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism
SC Cardiovascular System & Cardiology; Endocrinology & Metabolism
GA 845OT
UT WOS:000296833100001
PM 21999413
ER
PT J
AU Chen, BB
Glasser, JR
Coon, TA
Mallampalli, RK
AF Chen, Bill B.
Glasser, Jennifer R.
Coon, Tiffany A.
Mallampalli, Rama K.
TI FBXL2 is a ubiquitin E3 ligase subunit that triggers mitotic arrest
SO CELL CYCLE
LA English
DT Article
DE F-box protein; centrosome; mitosis; cyclin D3; Aurora A
ID CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; PROTEIN-KINASE; F-BOX;
CHROMOSOMAL STABILITY; REGULATORY ENZYME; CYCLIN D3; DEGRADATION;
EXPRESSION; IDENTIFICATION; CYTOKINESIS
AB Mitotic progression is regulated by ubiquitin E3 ligase complexes to carefully orchestrate eukaryotic cell division. Here, we show that a relatively new E3 ligase component belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family, SCF(FBXL2), impairs cell proliferation by mediating cyclin D3 polyubiquitination and degradation. Both cyclin D3 and FBXL2 colocalize within the centrosome. FBXL2 overexpression led to G(2)/M-phase arrest in transformed epithelia, resulting in the appearance of supernumerary centrosomes, tetraploidy and nuclei where condensed chromosomes are arranged on circular monopolar spindles typical of mitotic arrest. RNAi-mediated knockdown of cyclin D3 recapitulated effects of SCF(FBXL2) expression. SCF(FBXL2) impaired the ability of cyclin D3 to associate with centrosomal assembly proteins [ Aurora A, polo-like kinase 4 (Plk4), CDK11]. Thus, these results suggest a role for SCF(FBXL2) in regulating the fidelity of cellular division.
C1 [Chen, Bill B.; Glasser, Jennifer R.; Coon, Tiffany A.; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA.
[Chen, Bill B.; Glasser, Jennifer R.; Coon, Tiffany A.; Mallampalli, Rama K.] Univ Pittsburgh, Acute Lung Injury Ctr Excellence, Pittsburgh, PA USA.
[Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA USA.
[Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA.
RP Chen, BB (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA.
EM chenb@upmc.edu
FU US Department of Veterans Affairs, Veterans Health Administration,
Office of Research and Development, Biomedical Laboratory Research and
Development; US Department of Veterans Affairs; National Institutes of
Health [HL096376, HL097376, HL098174]
FX We thank A. F. Stewart for critical review of the manuscript and helpful
suggestions. This material is based upon work supported, in part, by the
US Department of Veterans Affairs, Veterans Health Administration,
Office of Research and Development, Biomedical Laboratory Research and
Development. This work was supported by a Merit Review Award from the US
Department of Veterans Affairs and National Institutes of Health R01
grants HL096376, HL097376 and HL098174 (to R. K. M.). The contents
presented do not represent the views of the Department of Veterans
Affairs or the United States Government.
NR 36
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U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD OCT 15
PY 2011
VL 10
IS 20
BP 3487
EP 3494
DI 10.4161/cc.10.20.17742
PG 8
WC Cell Biology
SC Cell Biology
GA 842DR
UT WOS:000296570700026
PM 22024926
ER
PT J
AU Rosenthal, DT
Iyer, H
Escudero, S
Bao, LW
Wu, ZF
Ventura, AC
Kleer, CG
Arruda, EM
Garikipati, K
Merajver, SD
AF Rosenthal, Devin T.
Iyer, Harish
Escudero, Silvia
Bao, Liwei
Wu, Zhifen
Ventura, Alejandra C.
Kleer, Celina G.
Arruda, Ellen M.
Garikipati, Krishna
Merajver, Sofia D.
TI p38 gamma Promotes Breast Cancer Cell Motility and Metastasis through
Regulation of RhoC GTPase, Cytoskeletal Architecture, and a Novel
Leading Edge Behavior
SO CANCER RESEARCH
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; P38 MAPK; RAS TRANSFORMATION;
ESTROGEN-RECEPTOR; SKELETAL-MUSCLE; IN-SITU; INVASION; PATHWAY;
EXPRESSION; DEGRADATION
AB Understanding the molecular alterations that confer cancer cells with motile, metastatic properties is needed to improve patient survival. Here, we report that p38 gamma motogen-activated protein kinase regulates breast cancer cell motility and metastasis, in part, by controlling expression of the metastasis-associated small GTPase RhoC. This p38 gamma-RhoC regulatory connection was mediated by a novel mechanism of modulating RhoC ubiquitination. This relationship persisted across multiple cell lines and in clinical breast cancer specimens. Using a computational mechanical model based on the finite element method, we showed that p38 gamma-mediated cytoskeletal changes are sufficient to control cell motility. This model predicted novel dynamics of leading edge actin protrusions, which were experimentally verified and established to be closely related to cell shape and cytoskeletal morphology. Clinical relevance was supported by evidence that elevated expression of p38 gamma is associated with lower overall survival of patients with breast cancer. Taken together, our results offer a detailed characterization of how p38 gamma contributes to breast cancer progression. Herein we present a new mechanics-based analysis of cell motility, and report on the discovery of a leading edge behavior in motile cells to accommodate modified cytoskeletal architecture. In summary, these findings not only identify a novel mechanism for regulating RhoC expression but also advance p38 gamma as a candidate therapeutic target. Cancer Res; 71(20); 6338-49. (C) 2011 AACR.
C1 [Kleer, Celina G.; Merajver, Sofia D.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Rosenthal, Devin T.; Bao, Liwei; Wu, Zhifen; Merajver, Sofia D.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Iyer, Harish; Arruda, Ellen M.; Garikipati, Krishna] Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA.
[Kleer, Celina G.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Rosenthal, Devin T.; Kleer, Celina G.; Merajver, Sofia D.] Univ Michigan, Cellular & Mol Biol Program, Ann Arbor, MI 48109 USA.
[Escudero, Silvia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Escudero, Silvia] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA.
[Ventura, Alejandra C.] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Lab Fisiol & Biol Mol, Dept Fisiol Biol Mol & Celular,IFIBYNE CONICET, Buenos Aires, DF, Argentina.
RP Merajver, SD (reprint author), Univ Michigan, Ctr Comprehens Canc, 1500 E Med Ctr Dr,Room 7217, Ann Arbor, MI 48109 USA.
EM smerajve@umich.edu
FU Department of Defense [BC083262]; NIH [T32-GM07315]; Burroughs Wellcome
Fund; Breast Cancer Research Foundation; Department of Energy
FX This work was supported by the Department of Defense Breast Cancer
Research Program through a Predoctoral Traineeship award (BC083262; to
D. T. Rosenthal) and a Multidisciplinary Postdoctoral award (A. C.
Ventura), an NIH Cellular and Molecular Biology Training grant
(T32-GM07315; D. T. Rosenthal), the Burroughs Wellcome Fund (S. D.
Merajver), the Breast Cancer Research Foundation (S. D. Merajver), and a
Department of Energy PECASE award (K. Garikipati). A. C. Ventura is a
member of the Carrera del Investigador Cientifico (CONICET).
NR 48
TC 28
Z9 30
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD OCT 15
PY 2011
VL 71
IS 20
BP 6338
EP 6349
DI 10.1158/0008-5472.CAN-11-1291
PG 12
WC Oncology
SC Oncology
GA 836WT
UT WOS:000296148900006
PM 21862636
ER
PT J
AU Fulciniti, M
Amin, S
Nanjappa, P
Rodig, S
Prabhala, R
Li, C
Minvielle, S
Tai, YT
Tassone, P
Avet-Loiseau, H
Hideshima, T
Anderson, KC
Munshi, NC
AF Fulciniti, Mariateresa
Amin, Samir
Nanjappa, Puru
Rodig, Scott
Prabhala, Rao
Li, Cheng
Minvielle, Stephane
Tai, Yu-tzu
Tassone, Pierfrancesco
Avet-Loiseau, Herve
Hideshima, Teru
Anderson, Kenneth C.
Munshi, Nikhil C.
TI Significant Biological Role of Sp1 Transactivation in Multiple Myeloma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; PANCREATIC-CANCER CELLS; METHYLATED
NORDIHYDROGUAIARETIC ACIDS; TRANSCRIPTION FACTOR SP1; HUMAN
GASTRIC-CANCER; GENE-TRANSCRIPTION; SURVIVIN GENE; ANTIVIRAL ACTIVITIES;
ANTICANCER ACTIVITY; TOLFENAMIC ACID
AB Purpose: The transcription factor specificity protein 1 (Sp1) controls number of cellular processes by regulating the expression of critical cell cycle, differentiation, and apoptosis-related genes containing proximal GC/GT-rich promoter elements. We here provide experimental and clinical evidence that Sp1 plays an important regulatory role in multiple myeloma (MM) cell growth and survival.
Experimental Design: We have investigated the functional Sp1 activity in MM cells using a plasmid with Firefly luciferase reporter gene driven by Sp1-responsive promoter. We have also used both siRNA- and short hairpin RNA-mediated Sp1 knockdown to investigate the growth and survival effects of Sp1 on MM cells and further investigated the anti-MM activity of terameprocol (TMP), a small molecule that specifically competes with Sp1-DNA binding in vitro and in vivo.
Results: We have confirmed high Sp1 activity in MM cells that is further induced by adhesion to bone marrow stromal cells (BMSC). Sp1 knockdown decreases MM cell proliferation and induces apoptosis. Sp1-DNA binding inhibition by TMP inhibits MM cell growth both in vitro and in vivo, inducing caspase-9-dependent apoptosis and overcoming the protective effects of BMSCs.
Conclusions: Our results show Sp1 as an important transcription factor in myeloma that can be therapeutically targeted for clinical application by TMP. Clin Cancer Res; 17(20); 6500-9. (C) 2011 AACR.
C1 [Fulciniti, Mariateresa; Amin, Samir; Nanjappa, Puru; Rodig, Scott; Li, Cheng; Tai, Yu-tzu; Hideshima, Teru; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
[Fulciniti, Mariateresa; Prabhala, Rao; Munshi, Nikhil C.] Harvard Univ, VA Boston Healthcare Syst, Sch Med, Boston, MA 02115 USA.
[Minvielle, Stephane; Avet-Loiseau, Herve] Ctr Hosp Univ Nantes, IRCNA, Hematol Lab, Nantes, France.
[Tassone, Pierfrancesco] Magna Graecia Univ Catanzaro, Catanzaro, Italy.
RP Munshi, NC (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Jerome Lipper Multiple Myeloma Ctr, 450 Brookline Ave, Boston, MA 02115 USA.
EM Nikhil_Munshi@dfci.harvard.edu
RI Minvielle, Stephane/K-8251-2015;
OI Amin, Samir/0000-0002-3207-9505
FU DF/HCC myeloma SPORE Career Development Award; Manton Foundation; Dept.
of Veterans Affairs; NIH [RO1-124929, PO1-155258, P50-100007, PO1-78378]
FX This work was supported in part by DF/HCC myeloma SPORE Career
Development Award to M. Fulciniti, Manton Foundation to N.C. Munshi,
grants from the Dept. of Veterans Affairs Merit Review Awards, and
grants from the NIH (RO1-124929 and PO1-155258 to N.C. Munshi and
P50-100007 and PO1-78378 to N.C. Munshi and K.C. Anderson).
NR 50
TC 23
Z9 23
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD OCT 15
PY 2011
VL 17
IS 20
BP 6500
EP 6509
DI 10.1158/1078-0432.CCR-11-1036
PG 10
WC Oncology
SC Oncology
GA 839IR
UT WOS:000296359400016
PM 21856768
ER
PT J
AU Grau, DJ
Chapman, BA
Garlick, JD
Borowsky, M
Francis, NJ
Kingston, RE
AF Grau, Daniel J.
Chapman, Brad A.
Garlick, Joe D.
Borowsky, Mark
Francis, Nicole J.
Kingston, Robert E.
TI Compaction of chromatin by diverse Polycomb group proteins requires
localized regions of high charge
SO GENES & DEVELOPMENT
LA English
DT Article
DE Polycomb; chromatin; transcriptional repression; intrinsic disorder
ID HISTONE METHYLTRANSFERASE ACTIVITY; EMBRYONIC STEM-CELLS; POSTERIOR SEX
COMBS; IN-VITRO; TRANSCRIPTIONAL ACTIVATION; DEVELOPMENTAL REGULATORS;
DROSOPHILA-MELANOGASTER; GROUP-COMPLEXES; GENE; BINDING
AB Polycomb group (PcG) proteins are required for the epigenetic maintenance of developmental genes in a silent state. Proteins in the Polycomb-repressive complex 1 (PRC1) class of the PcG are conserved from flies to humans and inhibit transcription. One hypothesis for PRC1 mechanism is that it compacts chromatin, based in part on electron microscopy experiments demonstrating that Drosophila PRC1 compacts nucleosomal arrays. We show that this function is conserved between Drosophila and mouse PRC1 complexes and requires a region with an overrepresentation of basic amino acids. While the active region is found in the Posterior Sex Combs (PSC) subunit in Drosophila, it is unexpectedly found in a different PRC1 subunit, a Polycomb homolog called M33, in mice. We provide experimental support for the general importance of a charged region by predicting the compacting capability of PcG proteins from species other than Drosophila and mice and by testing several of these proteins using solution assays and microscopy. We infer that the ability of PcG proteins to compact chromatin in vitro can be predicted by the presence of domains of high positive charge and that PRC1 components from a variety of species conserve this highly charged region. This supports the hypothesis that compaction is a key aspect of PcG function.
C1 [Grau, Daniel J.; Chapman, Brad A.; Garlick, Joe D.; Borowsky, Mark; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Grau, Daniel J.; Chapman, Brad A.; Garlick, Joe D.; Borowsky, Mark; Kingston, Robert E.] Harvard Univ, Harvard Med Sch, Dept Genet, Cambridge, MA 02138 USA.
[Francis, Nicole J.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM kingston@molbio.mgh.harvard.edu
OI Chapman, Brad/0000-0002-3026-1856
FU NIH [GM043901, GM078456-01]
FX We thank Sarah K. Bowman, Jose M. Antao, Karim Bouazoune, and Leslie Beh
for critically reading the manuscript and thoughtful discussions, and
Anders Naar and C. Ting Wu for critical discussions and experimental
suggestions. This work was supported by grants from the NIH (GM043901 to
R. E. K., and GM078456-01 to N.J.F.).
NR 65
TC 56
Z9 57
U1 0
U2 2
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD OCT 15
PY 2011
VL 25
IS 20
BP 2210
EP 2221
DI 10.1101/gad.17288211
PG 12
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 841EU
UT WOS:000296496100009
PM 22012622
ER
PT J
AU Kwok, AC
Semel, ME
Lipsitz, SR
Bader, AM
Barnato, AE
Gawande, AA
Jha, AK
AF Kwok, Alvin C.
Semel, Marcus E.
Lipsitz, Stuart R.
Bader, Angela M.
Barnato, Amber E.
Gawande, Atul A.
Jha, Ashish K.
TI The intensity and variation of surgical care at the end of life: a
retrospective cohort study
SO LANCET
LA English
DT Article
ID MEDICARE EXPENDITURES; UNITED-STATES; CANCER; TRENDS; ICD-9-CM;
OUTCOMES; QUALITY; AGE
AB Background Although the extent of hospital and intensive-care use at the end of life is well known, patterns of surgical care during this period are poorly understood. We examined national patterns of surgical care in the USA among elderly fee-for-service Medicare beneficiaries in their last year of life.
Methods We did a retrospective cohort study of elderly beneficiaries of fee-for-service Medicare in the USA, aged 65 years or older, who died in 2008. We identified claims for inpatient surgical procedures in the year before death and examined the relation between receipt of an inpatient procedure and both age and geographical region. We calculated an end-of-life surgical intensity (EOLSI) score for each hospital referral region defined as proportion of decedents who underwent a surgical procedure during the year before their death, adjusted for age, sex, race, and income. We compared patient characteristics with Rao-Scott chi(2) tests, resource use with generalised estimating equations, regional differences with generalised estimating equations Wald tests, and end-of-life surgical intensity scores with Spearman's partial-rank-order correlation coefficients.
Findings Of 1 802 029 elderly beneficiaries of fee-for-service Medicare who died in 2008, 31.9% (95% CI 31.9-32.0; 575596 of 1802 029) underwent an inpatient surgical procedure during the year before death, 18.3% (18.2-18.4; 329 771 of 1802 029) underwent a procedure in their last month of life, and 8.0% (8.0-8.1; 144 162 of 1 802 029) underwent a procedure during their last week of life. Between the ages of 80 and 90 years, the percentage of decedents undergoing a surgical procedure in the last year of life decreased by 33% (35.3% [95% CI 34.7-35.9; 8858 of 25 094] to 23.6% [22.9-24.3; 3340 of 14 152]). EOLSI score in the highest intensity region (Munster, IN) was 34.4(95% Cl 33.7-35.1) and in the lowest intensity region (Honolulu, HI) was 11.5 (11.3-11.7). Regions with a high number of hospital beds per head had high end-of-life surgical intensity (r=0.37, 95% CI 0.27-0.46; p<0.0001), as did regions with high total Medicare spending (r=0.50, 0.41-0.58; p<0.0001).
Interpretation Many elderly people in the USA undergo surgery in the year before their death. The rate at which they undergo surgery varies substantially with age and region and might suggest discretion in health-care providers' decisions to intervene surgically at the end of life.
C1 [Kwok, Alvin C.; Bader, Angela M.; Gawande, Atul A.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Kwok, Alvin C.; Semel, Marcus E.; Lipsitz, Stuart R.; Bader, Angela M.; Gawande, Atul A.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA.
[Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA.
[Barnato, Amber E.] Univ Pittsburgh, Med Ctr, Div Gen Med, Pittsburgh, PA USA.
RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA.
EM ajha@hsph.harvard.edu
OI Gawande, Atul/0000-0002-1824-9176
NR 29
TC 103
Z9 104
U1 3
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 OCT 15
PY 2011
VL 378
IS 9800
BP 1408
EP 1413
DI 10.1016/S0140-6736(11)61268-3
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 838EM
UT WOS:000296269600027
PM 21982520
ER
PT J
AU Delmonico, FL
Dominguez-Gil, B
Matesanz, R
Noel, L
AF Delmonico, Francis L.
Dominguez-Gil, Beatriz
Matesanz, Rafael
Noel, Luc
TI Organ Transplantation 1 A call for government accountability to achieve
national self-sufficiency in organ donation and transplantation
SO LANCET
LA English
DT Article
ID MEDICAL GUIDELINES; EUROPEAN COUNTRIES; DEATH; DONOR; CARE; TRAFFICKING;
TOURISM; FORUM
AB Roughly 100 000 patients worldwide undergo organ transplantation annually, but many other patients remain on waiting lists. Transplantation rates vary substantially across countries. Affluent patients in nations with long waiting lists do not always wait for donations from within their own countries. Commercially driven transplantation, however, does not always ensure proper medical care of recipients or donors, and might lengthen waiting times for resident patients or increase the illegal and unethical purchase of organs from living donors. Governments should systematically address the needs of their countries according to a legal framework. Medical strategies to prevent end-stage organ failure must also be implemented. In view of the Madrid Resolution, the Declaration of Istanbul, and the 63rd World Health Assembly Resolution, a new paradigm of national self-sufficiency is needed. Each country or region should strive to provide a sufficient number of organs from within its own population, guided by WHO ethics principles.
C1 [Delmonico, Francis L.] New England Organ Bank Inc, Waltham, MA 02451 USA.
[Delmonico, Francis L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Cambridge, MA 02138 USA.
[Dominguez-Gil, Beatriz; Matesanz, Rafael] Org Nacl Trasplantes, Madrid, Spain.
[Noel, Luc] WHO, CH-1211 Geneva, Switzerland.
RP Delmonico, FL (reprint author), New England Organ Bank Inc, 60 1st Ave, Waltham, MA 02451 USA.
EM francis_delmonico@neob.org
NR 20
TC 52
Z9 57
U1 0
U2 6
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 OCT 15
PY 2011
VL 378
IS 9800
BP 1414
EP 1418
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 838EM
UT WOS:000296269600028
PM 22000137
ER
PT J
AU Coldren, CD
Miller, YE
AF Coldren, Christopher D.
Miller, York E.
TI Progressive Endobronchial Premalignancy: Marked by Original CIN
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID LUNG-CANCER; PRENEOPLASTIC LESIONS; CHROMOSOMAL ANEUSOMY; FLUORESCENCE;
EPITHELIUM
C1 [Coldren, Christopher D.; Miller, York E.] Univ Colorado, Sch Med, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA.
[Miller, York E.] Eastern Colorado Hlth Care Syst, Denver Vet Affairs Med Ctr, Denver, CO USA.
RP Coldren, CD (reprint author), Univ Colorado, Sch Med, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA.
FU NCI NIH HHS [CA 58187, P50 CA058187]
NR 15
TC 1
Z9 1
U1 0
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD OCT 15
PY 2011
VL 184
IS 8
BP 869
EP 870
DI 10.1164/rccm.201108-1476ED
PG 3
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 835PG
UT WOS:000296047700005
PM 22003147
ER
PT J
AU Rosales, KR
Singh, G
Wu, K
Chen, J
Janes, MR
Lilly, MB
Peralta, ER
Siskind, LJ
Bennett, MJ
Fruman, DA
Edinger, AL
AF Rosales, Kimberly Romero
Singh, Gurpreet
Wu, Kevin
Chen, Jie
Janes, Matthew R.
Lilly, Michael B.
Peralta, Eigen R.
Siskind, Leah J.
Bennett, Michael J.
Fruman, David A.
Edinger, Aimee L.
TI Sphingolipid-based drugs selectively kill cancer cells by
down-regulating nutrient transporter proteins
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE AAL-149; autophagy; bioenergetics; FTY720; leukaemia; nutrient
limitation
ID SPHINGOSINE 1-PHOSPHATE; AEROBIC GLYCOLYSIS; ENDOTHELIAL-CELLS;
CELLULAR-ENERGY; PROSTATE-CANCER; HEART-RATE; FTY720; APOPTOSIS; KINASE;
GROWTH
AB Cancer cells are hypersensitive to nutrient limitation because oncogenes constitutively drive glycolytic and TCA (tricarboxylic acid) cycle intermediates into biosynthetic pathways. As the anaplerotic reactions that replace these intermediates are fueled by imported nutrients, the cancer cell's ability to generate ATP becomes compromised under nutrient-limiting conditions. In addition, most cancer cells have defects in autophagy, the catabolic process that provides nutrients from internal sources when external nutrients are unavailable. Normal cells, in contrast, can adapt to the nutrient stress that kills cancer cells by becoming quiescent and catabolic. In the present study we show that FFY720, a water-soluble sphingolipid drug that is effective in many animal cancer models, selectively starves cancer cells to death by down-regulating nutrient transporter proteins. Consistent with a bioenergetic mechanism of action, FTY720 induced homoeostatic autophagy. Cells were protected from FTY720 by cell-permeant nutrients or by reducing nutrient demand, but blocking apoptosis was ineffective. Importantly, AAL-149, a FTY720 analogue that lacks FTY720's dose-limiting toxicity, also triggered transporter loss and killed patient-derived leukaemias while sparing cells isolated from normal donors. As they target the metabolic profile of cancer cells rather than specific oncogenic mutations, FTY720 analogues such as AAL-149 should be effective against many different tumour types, particularly in combination with drugs that inhibit autophagy.
C1 [Rosales, Kimberly Romero; Singh, Gurpreet; Wu, Kevin; Peralta, Eigen R.; Edinger, Aimee L.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA.
[Chen, Jie; Bennett, Michael J.] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Janes, Matthew R.; Fruman, David A.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
[Janes, Matthew R.; Fruman, David A.] Univ Calif Irvine, Inst Immunol, Irvine, CA 92697 USA.
[Lilly, Michael B.] Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92697 USA.
[Siskind, Leah J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA.
[Siskind, Leah J.] Med Univ S Carolina, Dept Med, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA.
RP Edinger, AL (reprint author), Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA.
EM aedinger@uci.edu
FU National Institutes for Health [F31 CA126494, P20 RR17677, K08 CA100526,
R01 GM089919]; Gabrielle's Angel Foundation; University of California;
Cancer Research Coordinating Committee (UC CRCC); University of
California, Irvine; Council on Research Computing and Libraries (UCI
CORCL); VA [CDA-2]; VA REAP; ACS [IRG 97-219-11]
FX This work was supported by the National Institutes for Health [grant
numbers F31 CA126494 (to K.R.R.), P20 RR17677, K08 CA100526 and R01
GM089919], the Gabrielle's Angel Foundation, the University of
California, Cancer Research Coordinating Committee (UC CRCC), a Single
Investigator Innovation Grant from the University of California, Irvine,
Council on Research Computing and Libraries (UCI CORCL) to A.L.E., VA
CDA-2, VA REAP and ACS [grant number IRG 97-219-11 (to L.J.S.)].
NR 66
TC 17
Z9 18
U1 0
U2 13
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0264-6021
J9 BIOCHEM J
JI Biochem. J.
PD OCT 15
PY 2011
VL 439
BP 299
EP 311
DI 10.1042/BJ20110853
PN 2
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 836PO
UT WOS:000296123800012
ER
PT J
AU Brody, AL
Cook, IA
AF Brody, Arthur L.
Cook, Ian A.
TI Manipulation of Cigarette Craving with Transcranial Magnetic Stimulation
SO BIOLOGICAL PSYCHIATRY
LA English
DT Editorial Material
ID BRAIN
C1 [Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Greater Los Angeles Vet Affairs Smoking Cessat Pr, Los Angeles, CA 90095 USA.
[Brody, Arthur L.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Psychiat, Los Angeles, CA USA.
RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Greater Los Angeles Vet Affairs Smoking Cessat Pr, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA.
EM abrody@ucla.edu
FU NIDA NIH HHS [R01 DA020872, R01 DA20872]
NR 10
TC 4
Z9 4
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD OCT 15
PY 2011
VL 70
IS 8
BP 702
EP 703
DI 10.1016/j.biopsych.2011.08.001
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 835HG
UT WOS:000296026600003
PM 21967985
ER
PT J
AU Touma, M
Keskin, DB
Shiroki, F
Saito, I
Koyasu, S
Reinherz, EL
Clayton, LK
AF Touma, Maki
Keskin, Derin B.
Shiroki, Fumiko
Saito, Ibuki
Koyasu, Shigeo
Reinherz, Ellis L.
Clayton, Linda K.
TI Impaired B Cell Development and Function in the Absence of I kappa BNS
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CLASS-SWITCH RECOMBINATION; C-H TRANSCRIPTION; FOLLICULAR DENDRITIC
CELLS; INDUCED IL-6 PRODUCTION; MARGINAL-ZONE; GERMINAL-CENTER;
SELECTIVE DEFECTS; IMMUNE-RESPONSES; PLASMA-CELL; PROTEIN
AB I kappa BNS has been identified as a member of the I kappa B family of NF-kappa B inhibitors, which undergoes induction upon TCR signaling. Mice carrying a targeted gene disruption of I kappa BNS demonstrate dysregulation of cytokines in T cells, macrophages, and dendritic cells. I kappa BNS mediates both positive and negative gene regulation, depending on individual cell type and/or cytokine. In this study, we demonstrate an additional role for I kappa BNS in the B cell lineage. B cells from I kappa BNS knockout ( KO) mice were impaired in proliferative responses to LPS and anti-CD40. IgM and IgG3 Igs were drastically reduced in the serum of I kappa BNS KO mice, although I kappa BNS KO B cells exhibited a higher level of surface IgM than that found in wild-type mice. Switching to IgG3 was significantly reduced in I kappa BNS KO B cells. The in vitro induction of plasma cell development demonstrated that progression to Ab-secreting cells was impaired in I kappa BNS KO B cells. In agreement with this finding, the number of Ab-secreting cells in the spleens of I kappa BNS KO mice was reduced and production of Ag-specific Igs was lower in I kappa BNS KO mice after influenza infection as compared with wild-type mice. Additionally, I kappa BNS KO mice lacked B1 B cells and exhibited a reduction in marginal zone B cells. Thus, I kappa BNS significantly impacts the development and functions of B cells and plasma cells. The Journal of Immunology, 2011, 187: 3942-3952.
C1 [Clayton, Linda K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02215 USA.
[Touma, Maki; Keskin, Derin B.; Reinherz, Ellis L.; Clayton, Linda K.] Dana Farber Canc Inst, Immunobiol Lab, Dept Med Oncol, Boston, MA 02115 USA.
[Shiroki, Fumiko; Koyasu, Shigeo] Keio Univ, Sch Med, Dept Microbiol & Immunol, Shinjuku Ku, Tokyo 1608582, Japan.
[Saito, Ibuki] Niigata Univ, Dept Life Sci, Grad Sch Sci & Technol, Nishi Ku, Niigata 9502181, Japan.
RP Clayton, LK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, 450 Brookline Ave, Boston, MA 02215 USA.
EM linda_clayton@dfci.harvard.edu
RI Koyasu, Shigeo/J-5583-2015
OI Koyasu, Shigeo/0000-0001-9585-3038
FU National Institutes of Health [AI19807, AI51779]; KAKENHI [22790457];
Uehara Memorial Foundation; Hayashi Memorial Foundation for Female
Natural Scientists; Ministry of Education, Culture, Sports, Science, and
Technology of Japan
FX This work was supported by National Institutes of Health Grants AI19807
(to E.L.R.) and AI51779 (to L.K.C.) and by KAKENHI Grant 22790457, the
Uehara Memorial Foundation, and the Hayashi Memorial Foundation for
Female Natural Scientists (to M.T.). F.S. is a postdoctoral fellow of
the Global Center of Excellence Program supported by the Ministry of
Education, Culture, Sports, Science, and Technology of Japan.
NR 76
TC 14
Z9 14
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 15
PY 2011
VL 187
IS 8
BP 3942
EP 3952
DI 10.4049/jimmunol.1002109
PG 11
WC Immunology
SC Immunology
GA 829YN
UT WOS:000295623100006
PM 21900180
ER
PT J
AU Norgaard, M
Nielsen, RB
Jacobsen, JB
Gradus, JL
Stenager, E
Koch-Henriksen, N
Lash, TL
Sorensen, HT
AF Norgaard, Mette
Nielsen, Rikke Beck
Jacobsen, Jacob Bonde
Gradus, Jaimie L.
Stenager, Egon
Koch-Henriksen, Nils
Lash, Timothy L.
Sorensen, Henrik Toft
TI Use of Penicillin and Other Antibiotics and Risk of Multiple Sclerosis:
A Population-based Case-Control Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE anti-bacterial agents; case-control studies; multiple sclerosis;
penicillins; risk
ID DIAGNOSTIC-CRITERIA; EPIDEMIOLOGY; HISTORY; COHORT
AB A 2006 study from the United Kingdom found that penicillin use may decrease the risk of multiple sclerosis (MS). To confirm this finding, the authors conducted a nationwide case-control study in Denmark, using the Danish Multiple Sclerosis Registry to identify 3,259 patients with MS onset from 1996 to 2008, and selected 10 population controls per case (n = 32,590), matched on sex and age. Through the National Prescription Database, prescriptions for antibiotics redeemed from 1995 to 2008 and before the date of first MS symptom/index date were identified. Conditional logistic regression analysis was used to compute odds ratios associating antibiotic use with MS occurrence. In total, 1,922 patients (59%) redeemed penicillin prescriptions before the index date and 2,292 (70%) redeemed any type of antibiotic prescription. Penicillin use was associated with an increased risk of MS (odds ratio = 1.21, 95% confidence interval: 1.10, 1.27). Use of any type of antibiotic was similarly associated with an increased risk of MS (odds ratio = 1.41, 95% confidence interval: 1.29, 1.53). The odds ratios for different types of antibiotics ranged between 1.08 and 1.83. Thus, this study found that penicillin use and use of other antibiotics were similarly associated with increased risk of MS, suggesting that the underlying infections may be causally associated with MS.
C1 [Norgaard, Mette; Nielsen, Rikke Beck; Jacobsen, Jacob Bonde; Lash, Timothy L.; Sorensen, Henrik Toft] Aarhus Univ Hosp, Dept Clin Epidemiol, Inst Clin, DK-9000 Aalborg, Denmark.
[Gradus, Jaimie L.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Gradus, Jaimie L.; Lash, Timothy L.; Sorensen, Henrik Toft] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Stenager, Egon; Koch-Henriksen, Nils] Copenhagen Univ Hosp, Danish Multiple Sclerosis Registry, Rigshosp, Copenhagen, Denmark.
[Stenager, Egon] Univ So Denmark, Inst Reg Hlth Res Serv, Odense, Denmark.
MS Clin So Jutland, Dept Neurol, Sonderborg, Denmark.
[Koch-Henriksen, Nils] Aarhus Univ Hosp, Dept Neurol, DK-9000 Aalborg, Denmark.
RP Norgaard, M (reprint author), Aarhus Univ Hosp, Dept Clin Epidemiol, Inst Clin Med, Sdr Skovvej 15, DK-9000 Aalborg, Denmark.
EM m.noergaard@rn.dk
OI Gradus, Jaimie/0000-0003-1459-5327
FU Clinical Epidemiology Research Foundation, Aarhus University Hospital,
Aarhus, Denmark
FX This work was supported by the Clinical Epidemiology Research
Foundation, Aarhus University Hospital, Aarhus, Denmark.
NR 17
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U1 2
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD OCT 15
PY 2011
VL 174
IS 8
BP 945
EP 948
DI 10.1093/aje/kwr201
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 830TI
UT WOS:000295679700009
PM 21920946
ER
PT J
AU Ito, H
Pacold, IV
Durazo-Arvizu, R
Liu, K
Shilipak, MG
Goff, DC
Tracy, RP
Kramer, H
AF Ito, Hiroki
Pacold, Ivan V.
Durazo-Arvizu, Ramon
Liu, Kiang
Shilipak, Michael G.
Goff, David C., Jr.
Tracy, Russell P.
Kramer, Holly
CA Multiethnic Study Atherosclerosis
TI The Effect of Including Cystatin C or Creatinine in a Cardiovascular
Risk Model for Asymptomatic Individuals
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cardiovascular diseases; creatinine; cystatin C; risk model
ID CHRONIC KIDNEY-DISEASE; CORONARY-HEART-DISEASE; REACTIVE PROTEIN;
MORTALITY; ASSOCIATION; PREDICTION; OLDER; ATHEROSCLEROSIS;
STRATIFICATION; CLASSIFICATION
AB The authors studied the incremental value of adding serum cystatin C or creatinine to the Framingham risk score variables (FRSVs) for the prediction of incident cardiovascular disease (CVD) among 6,653 adults without clinical CVD utilizing the Multi-Ethnic Study of Atherosclerosis (2000-2008). CVD events included coronary heart disease, heart failure, stroke, and peripheral arterial disease. Variables were transformed to yield optimal prediction of 6-year CVD events in sex-stratified models with FRSVs alone, FRSVs + cystatin C, and FRSVs + creatinine. Risk prediction in the 3 models was assessed by using the C statistic, and net reclassification improvement was calculated. The mean ages were 61.9 and 64.6 years for individuals with and without diabetes, respectively. After 6 years of follow-up, 447 (7.2%) CVD events occurred. In the total cohort, no significant change in the C statistic was noted with FRSVs + cystatin C and FRSVs + creatinine compared with FRSVs alone, and net reclassification improvement for CVD risk was extremely small and not significant with the addition of cystatin C or creatinine to FRSVs. Similar findings were noted after stratifying by baseline presence of diabetes. In conclusion, the addition of cystatin C or serum creatinine to FRSVs does not improve CVD risk prediction among adults without clinical CVD.
C1 [Ito, Hiroki; Pacold, Ivan V.] Loyola Univ, Med Ctr, Div Cardiol, Dept Med, Maywood, IL 60153 USA.
[Durazo-Arvizu, Ramon; Kramer, Holly] Loyola Univ, Med Ctr, Dept Prevent Med, Maywood, IL 60153 USA.
[Liu, Kiang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Shilipak, Michael G.] San Francisco VA Med Ctr, Dept Epidemiol & Biostat, San Francisco, CA USA.
[Goff, David C., Jr.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol & Lab Med, Burlington, VT USA.
RP Ito, H (reprint author), Loyola Univ, Med Ctr, Div Cardiol, Dept Med, 2160 S 1st Ave, Maywood, IL 60153 USA.
EM itohiroki@gmail.com
OI Kramer, Holly/0000-0002-6374-837X
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland
[N01-HC-95159, N01-HC-95165, N01-HC-95167]
FX This research was supported by contracts N01-HC-95159 through
N01-HC-95165 and N01-HC-95167 from the National Heart, Lung, and Blood
Institute, Bethesda, Maryland.
NR 29
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U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD OCT 15
PY 2011
VL 174
IS 8
BP 949
EP 957
DI 10.1093/aje/kwr185
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 830TI
UT WOS:000295679700010
PM 21880578
ER
PT J
AU O'Brien, LL
Grimaldi, M
Kostun, Z
Wingert, RA
Selleck, R
Davidson, AJ
AF O'Brien, Lori L.
Grimaldi, Michael
Kostun, Zachary
Wingert, Rebecca A.
Selleck, Rori
Davidson, Alan J.
TI Wt1a, Foxc1a, and the Notch mediator Rbpj physically interact and
regulate the formation of podocytes in zebrafish
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Zebrafish; Kidney; Glomerulus; Embryo; Podocyte; Wilms' tumor
suppressor-1; Notch; Foxc1a
ID WILMS-TUMOR SUPPRESSOR; HELIX TRANSCRIPTION FACTORS; DEVELOPING MOUSE
KIDNEY; CELL FATE; EXPRESSION ANALYSIS; PRONEPHRIC DUCT; SLIT DIAPHRAGM;
GENE; NEPHRON; PROTEIN
AB Podocytes help form the glomerular blood filtration barrier in the kidney and their injury or loss leads to renal disease. The Wilms' tumor suppressor-1 (Wt1) and the FoxC1/2 transcription factors, as well as Notch signaling, have been implicated as important regulators of podocyte fate. It is not known whether these factors work in parallel or sequentially on different gene targets, or as higher-order transcriptional complexes on common genes. Here, we use the zebrafish to demonstrate that embryos treated with morpholinos against wt1a, foxc1a, or the Notch transcriptional mediator rbpj develop fewer podocytes, as determined by wt1b, hey 1 and nephrin expression, while embryos deficient in any two of these factors completely lack podocytes. From GST-pull-downs and co-immunoprecipitation experiments we show that Wt1a, Foxc1a, and Rbpj can physically interact with each other, whereas only Rbpj binds to the Notch intracellular domain (NICD). In transactivation assays, combinations of Wt1. FoxC1/2, and NICD synergistically induce the Hey1 promoter, and have additive or repressive effects on the Podocalyxin promoter, depending on dosage. Taken together, these data suggest that Wt1, FoxC1/2, and Notch signaling converge on common target genes where they physically interact to regulate a podocyte-specific gene program. These findings further our understanding of the transcriptional circuitry responsible for podocyte formation and differentiation during kidney development. (C) 2011 Elsevier Inc. All rights reserved.
C1 Harvard Univ, Ctr Regenerat Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, Boston, MA 02114 USA.
Harvard Stem Cell Inst, Boston, MA 02114 USA.
RP Davidson, AJ (reprint author), Univ Auckland, Dept Mol Med & Pathol, Auckland 1, New Zealand.
EM a.davidson@auckland.ac.nz
FU NIDDK NIH HHS [R01 DK077186, R01 DK077186-03]
NR 86
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U1 0
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD OCT 15
PY 2011
VL 358
IS 2
BP 318
EP 330
DI 10.1016/j.ydbio.2011.08.005
PG 13
WC Developmental Biology
SC Developmental Biology
GA 829SF
UT WOS:000295603900005
PM 21871448
ER
PT J
AU Maxwell, MM
Tomkinson, EM
Nobles, J
Wizeman, JW
Amore, AM
Quinti, L
Chopra, V
Hersch, SM
Kazantsev, AG
AF Maxwell, Michele M.
Tomkinson, Elizabeth M.
Nobles, Johnathan
Wizeman, John W.
Amore, Allison M.
Quinti, Luisa
Chopra, Vanita
Hersch, Steven M.
Kazantsev, Aleksey G.
TI The Sirtuin 2 microtubule deacetylase is an abundant neuronal protein
that accumulates in the aging CNS
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID FAMILIAL DYSAUTONOMIA; HUNTINGTONS-DISEASE; TUBULIN ACETYLATION; SIR2
FAMILY; IN-VIVO; TRANSPORT; LONGEVITY; HDAC6; HISTONE-DEACETYLASE-6;
NEUROPROTECTION
AB Sirtuin 2 (SIRT2) is one of seven known mammalian protein deacetylases homologous to the yeast master lifespan regulator Sir2. In recent years, the sirtuin protein deacetylases have emerged as candidate therapeutic targets for many human diseases, including metabolic and age-dependent neurological disorders. In non-neuronal cells, SIRT2 has been shown to function as a tubulin deacetylase and a key regulator of cell division and differentiation. However, the distribution and function of the SIRT2 microtubule (MT) deacetylase in differentiated, postmitotic neurons remain largely unknown. Here, we show abundant and preferential expression of specific isoforms of SIRT2 in the mammalian central nervous system and find that a previously uncharacterized form, SIRT2.3, exhibits age-dependent accumulation in the mouse brain and spinal cord. Further, our studies reveal that focal areas of endogenous SIRT2 expression correlate with reduced a-tubulin acetylation in primary mouse cortical neurons and suggest that the brain-enriched species of SIRT2 may function as the predominant MT deacetylases in mature neurons. Recent reports have demonstrated an association between impaired tubulin acetyltransferase activity and neurodegenerative disease; viewed in this light, our results showing age-dependent accumulation of the SIRT2 neuronal MT deacetylase in wild-type mice suggest a functional link between tubulin acetylation patterns and the aging brain.
C1 [Maxwell, Michele M.; Tomkinson, Elizabeth M.; Nobles, Johnathan; Wizeman, John W.; Amore, Allison M.; Quinti, Luisa; Chopra, Vanita; Hersch, Steven M.; Kazantsev, Aleksey G.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02115 USA.
[Maxwell, Michele M.; Quinti, Luisa; Chopra, Vanita; Hersch, Steven M.; Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Boston, MA USA.
RP Maxwell, MM (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA.
EM mmmaxwell@partners.org
FU MassGeneral Institute for Neurodegenerative Disease; National Institutes
of Health [R21-NS062189, P01-NS058793]; ALS Therapy Alliance; R.J.G.
Foundation; Milton Carmen Foundation; HDSA New England Center of
Excellence; HDSA Coalition for the Cure
FX This work was supported by the MassGeneral Institute for
Neurodegenerative Disease and by grants from the National Institutes of
Health (R21-NS062189 to M.M.M.; P01-NS058793 to S.M.H.); the ALS Therapy
Alliance (to M.M.M.); the R.J.G. Foundation (to A.G.K.); the Milton
Carmen Foundation (to A.G.K.); the HDSA New England Center of Excellence
(to S.M.H.); and the HDSA Coalition for the Cure (to S.M.H.).
NR 47
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U1 2
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 15
PY 2011
VL 20
IS 20
BP 3986
EP 3996
DI 10.1093/hmg/ddr326
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 824AN
UT WOS:000295171200009
PM 21791548
ER
PT J
AU Tin, A
Woodward, OM
Kao, WHL
Liu, CT
Lu, XN
Nalls, MA
Shriner, D
Semmo, M
Akylbekova, EL
Wyatt, SB
Hwang, SJ
Yang, Q
Zonderman, AB
Adeyemo, AA
Palmer, C
Meng, Y
Reilly, M
Shlipak, MG
Siscovick, D
Evans, MK
Rotimi, CN
Flessner, MF
Kottgen, M
Cupples, LA
Fox, CS
Kottgen, A
AF Tin, Adrienne
Woodward, Owen M.
Kao, Wen Hong Linda
Liu, Ching-Ti
Lu, Xiaoning
Nalls, Michael A.
Shriner, Daniel
Semmo, Mariam
Akylbekova, Ermeg L.
Wyatt, Sharon B.
Hwang, Shih-Jen
Yang, Qiong
Zonderman, Alan B.
Adeyemo, Adebowale A.
Palmer, Cameron
Meng, Yan
Reilly, Muredach
Shlipak, Michael G.
Siscovick, David
Evans, Michele K.
Rotimi, Charles N.
Flessner, Michael F.
Koettgen, Michael
Cupples, L. Adrienne
Fox, Caroline S.
Koettgen, Anna
CA CARe & CHARGE Consortia
TI Genome-wide association study for serum urate concentrations and gout
among African Americans identifies genomic risk loci and a novel URAT1
loss-of-function allele
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID URIC-ACID; CARDIOVASCULAR-DISEASE; GENETIC-LOCI; POPULATION; DESIGN;
TRANSPORTER; FRAMINGHAM; GLUCOSE; SLC2A9; HEART
AB Serum urate concentrations are highly heritable and elevated serum urate is a key risk factor for gout. Genome-wide association studies (GWAS) of serum urate in African American (AA) populations are lacking. We conducted a meta-analysis of GWAS of serum urate levels and gout among 5820 AA and a large candidate gene study among 6890 AA and 21 708 participants of European ancestry (EA) within the Candidate Gene Association Resource Consortium. Findings were tested for replication among 1996 independent AA individuals, and evaluated for their association among 28 283 EA participants of the CHARGE Consortium. Functional studies were conducted using (14)C-urate transport assays in mammalian Chinese hamster ovary cells. In the discovery GWAS of serum urate, three loci achieved genome-wide significance (P < 5.0 x 10(-8)): a novel locus near SGK1/SLC2A12 on chromosome 6 (rs9321453, P = 1.0 x 10(-9)), and two loci previously identified in EA participants, SLC2A9 (P = 3.8 x 10(-32)) and SLC22A12 (P = 2.1 x 10(-10)). A novel rare non-synonymous variant of large effect size in SLC22A12, rs12800450 (minor allele frequency 0.01, G65W), was identified and replicated (beta -1.19 mg/dl, P = 2.7 x 10(-16)). (14)C-urate transport assays showed reduced urate transport for the G65W URAT1 mutant. Finally, in analyses of 11 loci previously associated with serum urate in EA individuals, 10 of 11 lead single-nucleotide polymorphisms showed direction-consistent association with urate among AA. In summary, we identified and replicated one novel locus in association with serum urate levels and experimentally characterize the novel G65W variant in URAT1 as a functional allele. Our data support the importance of multi-ethnic GWAS in the identification of novel risk loci as well as functional variants.
C1 [Koettgen, Anna] Freiburg Univ Hosp, Dept Med 4, Div Renal, D-79110 Freiburg, Germany.
[Tin, Adrienne; Kao, Wen Hong Linda; Koettgen, Anna] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Woodward, Owen M.] Johns Hopkins Univ, Dept Physiol, Sch Med, Baltimore, MD 21205 USA.
[Liu, Ching-Ti; Lu, Xiaoning; Cupples, L. Adrienne] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02118 USA.
[Shriner, Daniel; Adeyemo, Adebowale A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Shriner, Daniel; Koettgen, Michael] Natl Human Genome Res Inst, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
[Akylbekova, Ermeg L.] Jackson State Univ, Jackson, MS 39213 USA.
[Wyatt, Sharon B.] Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA.
[Wyatt, Sharon B.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Hwang, Shih-Jen; Cupples, L. Adrienne; Fox, Caroline S.] NHLBI Framingham Heart Study, Framingham, MA 01702 USA.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Zonderman, Alan B.] NIA, Lab Personal & Cognit, Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Reilly, Muredach] Univ Penn, Med Ctr, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Reilly, Muredach] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94143 USA.
[Shlipak, Michael G.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA.
[Siscovick, David] Univ Washington, Dept Med, Seattle, WA 98101 USA.
[Evans, Michele K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Palmer, Cameron] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Palmer, Cameron] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Palmer, Cameron] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Palmer, Cameron] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Palmer, Cameron; Meng, Yan] Broad Inst Harvard & MIT, Metab Dis Initiat, Cambridge, MA USA.
[Flessner, Michael F.] NIDDK, KUH, NIH, Bethesda, MD 20892 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Kottgen, A (reprint author), Freiburg Univ Hosp, Dept Med 4, Div Renal, Berliner Allee 29, D-79110 Freiburg, Germany.
EM akottgen@jhsph.edu
RI Kottgen, Anna/D-2920-2012; Yang, Qiong/G-5438-2014;
OI Cupples, L. Adrienne/0000-0003-0273-7965; Adeyemo,
Adebowale/0000-0002-3105-3231; Zonderman, Alan B/0000-0002-6523-4778
FU National Heart, Lung and Blood Institute; NIH, National Institute on
Aging; National Center on Minority Health and Health Disparities
[Z01-AG000513, 2009-149]; National Institutes of Health
[S06GM008016-320107, S06GM008016-380111, 2M01RR010284]; Center for
Research on Genomics and Global Health; National Human Genome Research
Institute; National Institute of Diabetes and Digestive and Kidney
Diseases; Center for Information Technology; Office of the Director at
the National Institutes of Health [Z01HG200362]; NIDDK [DK032753-25A1];
German Research Foundation
FX The authors wish to acknowledge the support of the National Heart, Lung
and Blood Institute and the contributions of the research institutions,
study investigators, field staff and study participants in creating this
resource for biomedical research. We would like to thank Dr Yohannes
Hagos who kindly provided the URAT1 plasmid, Dr H. Endou for the
permission to use it, as well as Dr William B. Guggino for contributing
experimental resources.; Healthy Aging in Neighborhoods of Diversity
across the Life Span Study (HANDLS): this research was supported by the
Intramural Research Program of the NIH, National Institute on Aging and
the National Center on Minority Health and Health Disparities
(intramural project # Z01-AG000513 and human subjects protocol #
2009-149). Data analyses for the HANDLS study utilized the
high-performance computational capabilities of the Biowulf Linux cluster
at the National Institutes of Health, Bethesda, Md.
(http://biowulf.nih.gov).; Howard University Family Study (HUFS): The
Howard University Family Study was supported by National Institutes of
Health grants S06GM008016-320107 and S06GM008016-380111. Enrollment was
carried out at the Howard University General Clinical Research Center,
supported by National Institutes of Health grant 2M01RR010284. This
research was supported in part by the Intramural Research Program of the
Center for Research on Genomics and Global Health. The Center for
Research on Genomics and Global Health is supported by the National
Human Genome Research Institute, the National Institute of Diabetes and
Digestive and Kidney Diseases, the Center for Information Technology and
the Office of the Director at the National Institutes of Health
(Z01HG200362). Genotyping support was provided by the Coriell Institute
for Medical Research. We thank the participants of the Howard University
Family Study. The contents of this publication are solely the
responsibility of the authors and do not necessarily represent the
official view of the National Institutes of Health.; Individual support:
O.M.W. was supported by NIDDK: DK032753-25A1, A.K. was supported by the
Emmy Noether Programme of the German Research Foundation.
NR 53
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U1 0
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 15
PY 2011
VL 20
IS 20
BP 4056
EP 4068
DI 10.1093/hmg/ddr307
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 824AN
UT WOS:000295171200015
PM 21768215
ER
PT J
AU Cohen, DM
Mittalhenkle, A
Scott, DL
Young, CJ
Norman, DJ
AF Cohen, David M.
Mittalhenkle, Anuja
Scott, David L.
Young, Carlton J.
Norman, Douglas J.
TI African American Living-Kidney Donors Should Be Screened for APOL1 Risk
Alleles
SO TRANSPLANTATION
LA English
DT Article
DE Genetics; Allele; Kidney
ID STAGE RENAL-DISEASE; MYH9; TRANSPLANTATION; OUTCOMES; GENE
AB The adjusted rate of end-stage kidney disease (ESKD) among African Americans is markedly increased relative to European Americans. African Americans are overrepresented on the kidney transplantation waiting list and experience longer wait times. In aggregate, these pressures drive recommendations for living donor transplantation. Genovese et al. recently implicated the APOL1 gene in ESKD risk among African Americans (Genovese et al. Science 2010; 329: 841). The presence of two APOL1 risk alleles doubles the relative risk for ESKD; moreover, the alleles are prevalent among African Americans. We propose a strategy for screening for the presence of APOL1 risk alleles among African American living kidney donors and for living-related donors for African American recipients.
C1 [Cohen, David M.] Portland VA Med Ctr, Nephrol Sect, Portland, OR 97239 USA.
[Cohen, David M.; Mittalhenkle, Anuja; Norman, Douglas J.] Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97201 USA.
[Scott, David L.] Oregon Hlth & Sci Univ, Dept Surg, Div Liver & Pancreas Transplantat, Portland, OR 97201 USA.
[Young, Carlton J.] Univ Alabama, Sch Med, Dept Surg, Div Transplantat, Birmingham, AL 35294 USA.
RP Cohen, DM (reprint author), Portland VA Med Ctr, Nephrol Sect, Mailcode R&D 10,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM cohend@ohsu.edu
FU Department of Veterans Affairs; National Institute of Diabetes and
Digestive and Kidney Diseases of the National Institutes of Health
FX This work was supported by the Department of Veterans Affairs (D. M. C.,
A. M., and D. L. S.) and the National Institute of Diabetes and
Digestive and Kidney Diseases of the National Institutes of Health
(D.M.C.).
NR 17
TC 24
Z9 24
U1 1
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 OCT 15
PY 2011
VL 92
IS 7
BP 722
EP 725
DI 10.1097/TP.0b013e31822eec39
PG 4
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 825YY
UT WOS:000295319500006
PM 21878839
ER
PT J
AU Stenzel, D
Lundkvist, A
Sauvaget, D
Busse, M
Graupera, M
van der Flier, A
Wijelath, ES
Murray, J
Sobel, M
Costell, M
Takahashi, S
Fassler, R
Yamaguchi, Y
Gutmann, DH
Hynes, RO
Gerhardt, H
AF Stenzel, Denise
Lundkvist, Andrea
Sauvaget, Dominique
Busse, Marta
Graupera, Mariona
van der Flier, Arjan
Wijelath, Errol S.
Murray, Jacqueline
Sobel, Michael
Costell, Mercedes
Takahashi, Seiichiro
Faessler, Reinhard
Yamaguchi, Yu
Gutmann, David H.
Hynes, Richard O.
Gerhardt, Holger
TI Integrin-dependent and -independent functions of astrocytic fibronectin
in retinal angiogenesis
SO DEVELOPMENT
LA English
DT Article
DE Angiogenesis; Tip cells; Extracellular matrix; Cell migration;
Endothelial guidance
ID ENDOTHELIAL-CELL MIGRATION; HEPARAN-SULFATE; EXTRACELLULAR-MATRIX;
VASCULAR DEVELOPMENT; BIOLOGICAL-ACTIVITY; PRECURSOR CELLS; IN-VIVO;
VEGF; EXPRESSION; GRADIENTS
AB Fibronectin (FN) is a major component of the extracellular matrix and functions in cell adhesion, cell spreading and cell migration. In the retina, FN is transiently expressed and assembled on astrocytes (ACs), which guide sprouting tip cells and deposit a provisional matrix for sprouting angiogenesis. The precise function of FN in retinal angiogenesis is largely unknown. Using genetic tools, we show that astrocytes are the major source of cellular FN during angiogenesis in the mouse retina. Deletion of astrocytic FN reduces radial endothelial migration during vascular plexus formation in a gene dose-dependent manner. This effect correlates with reduced VEGF receptor 2 and PI3K/AKT signalling, and can be mimicked by selectively inhibiting VEGF-A binding to FN through intraocular injection of blocking peptides. By contrast, AC-specific replacement of the integrin-binding RGD sequence with FN-RGE or endothelial deletion of itga5 shows little effect on migration and PI3K/AKT signalling, but impairs filopodial alignment along AC processes, suggesting that FN-integrin alpha 5 beta 1 interaction is involved in filopodial adhesion to the astrocytic matrix. AC FN shares its VEGF-binding function and cell-surface distribution with heparan-sulfate (HS), and genetic deletion of both FN and HS together greatly enhances the migration defect, indicating a synergistic function of FN and HS in VEGF binding. We propose that in vivo the VEGF-binding properties of FN and HS promote directional tip cell migration, whereas FN integrin-binding functions to support filopodia adhesion to the astrocytic migration template.
C1 [Stenzel, Denise; Lundkvist, Andrea; Sauvaget, Dominique; Busse, Marta; Gerhardt, Holger] London Res Inst Canc Res UK, Vasc Biol Lab, London WC2A 3PX, England.
[Graupera, Mariona] Hosp Duran i Reynals 3 Planta, Oncol Mol Lab, Grp Angiogenesi, Inst Invest Biomed Bellvitge IDIBELL, Barcelona 08907, Spain.
[van der Flier, Arjan; Hynes, Richard O.] MIT, Howard Hughes Med Inst, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Wijelath, Errol S.; Murray, Jacqueline; Sobel, Michael] Vet Affairs Puget Sound Hlth Care Syst, Div Vasc Surg, Dept Surg, Seattle, WA 98195 USA.
[Wijelath, Errol S.; Murray, Jacqueline; Sobel, Michael] Univ Washington, Sch Med, Seattle, WA 98195 USA.
[Costell, Mercedes] Univ Valencia, Dept Bioquim & Biol Mol, E-46100 Burjassot, Spain.
[Takahashi, Seiichiro; Faessler, Reinhard] Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany.
[Yamaguchi, Yu] Sanford Childrens Hlth Res Ctr, Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
[Gutmann, David H.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Gerhardt, Holger] VIB, Vesalius Res Ctr, Vasc Patterning Lab, B-3000 Louvain, Belgium.
RP Gerhardt, H (reprint author), London Res Inst Canc Res UK, Vasc Biol Lab, London WC2A 3PX, England.
EM holger.gerhardt@cancer.org.uk
RI Gerhardt, Holger/G-4610-2011;
OI Graupera, Mariona/0000-0003-4608-4185; Gerhardt,
Holger/0000-0001-9228-7472; Gerhardt, Holger/0000-0002-3030-0384
FU Cancer Research UK; EMBO; Lister Institute of Preventive Medicine;
Leducq Transatlantic Network ARTEMIS; DFG; Max-Planck Society; National
Institutes of Health [RO1 HL079182, PO1-HL66105]; NIGMS Cell Migration
Consortium [GC11451.126452]
FX This work was funded by Cancer Research UK, EMBO Young Investigator
Program, The Lister Institute of Preventive Medicine, the Leducq
Transatlantic Network ARTEMIS (H. G.), DFG and Max-Planck Society. This
work was further supported by grants from the National Institutes of
Health (RO1 HL079182 to M. S. and E. S. W., PO1-HL66105 and the NIGMS
Cell Migration Consortium, GC11451.126452; A. F. Horwitz is the P. I.)
and by the Howard Hughes Medical Institute of which R.O.H. is an
Investigator. Deposited in PMC for release after 6 months.
NR 47
TC 53
Z9 54
U1 0
U2 9
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD OCT 15
PY 2011
VL 138
IS 20
BP 4451
EP 4463
DI 10.1242/dev.071381
PG 13
WC Developmental Biology
SC Developmental Biology
GA 822YD
UT WOS:000295085600013
PM 21880786
ER
PT J
AU Zhu, C
Smith, T
McNulty, J
Rayla, AL
Lakshmanan, A
Siekmann, AF
Buffardi, M
Meng, XD
Shin, J
Padmanabhan, A
Cifuentes, D
Giraldez, AJ
Look, AT
Epstein, JA
Lawson, ND
Wolfe, SA
AF Zhu, Cong
Smith, Tom
McNulty, Joseph
Rayla, Amy L.
Lakshmanan, Abirami
Siekmann, Arndt F.
Buffardi, Matthew
Meng, Xiangdong
Shin, Jimann
Padmanabhan, Arun
Cifuentes, Daniel
Giraldez, Antonio J.
Look, A. Thomas
Epstein, Jonathan A.
Lawson, Nathan D.
Wolfe, Scot A.
TI Evaluation and application of modularly assembled zinc-finger nucleases
in zebrafish
SO DEVELOPMENT
LA English
DT Article
DE gata2; Vascular development; Zebrafish; Zinc-finger nuclease
ID ARTIFICIAL TRANSCRIPTION FACTORS; DNA-BINDING PROTEINS; GENE-EXPRESSION;
KNOCKOUT RATS; CONSTRUCTION; RECOGNITION; SEQUENCES; SPECIFICITY;
DESIGN; DROSOPHILA
AB Zinc-finger nucleases (ZFNs) allow targeted gene inactivation in a wide range of model organisms. However, construction of target-specific ZFNs is technically challenging. Here, we evaluate a straightforward modular assembly-based approach for ZFN construction and gene inactivation in zebrafish. From an archive of 27 different zinc-finger modules, we assembled more than 70 different zinc-finger cassettes and evaluated their specificity using a bacterial one-hybrid assay. In parallel, we constructed ZFNs from these cassettes and tested their ability to induce lesions in zebrafish embryos. We found that the majority of zinc-finger proteins assembled from these modules have favorable specificities and nearly one-third of modular ZFNs generated lesions at their targets in the zebrafish genome. To facilitate the application of ZFNs within the zebrafish community we constructed a public database of sites in the zebrafish genome that can be targeted using this archive. Importantly, we generated new germline mutations in eight different genes, confirming that this is a viable platform for heritable gene inactivation in vertebrates. Characterization of one of these mutants, gata2a, revealed an unexpected role for this transcription factor in vascular development. This work provides a resource to allow targeted germline gene inactivation in zebrafish and highlights the benefit of a definitive reverse genetic strategy to reveal gene function.
C1 [Zhu, Cong; Smith, Tom; McNulty, Joseph; Rayla, Amy L.; Lakshmanan, Abirami; Siekmann, Arndt F.; Buffardi, Matthew; Meng, Xiangdong; Lawson, Nathan D.; Wolfe, Scot A.] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
[Shin, Jimann; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Padmanabhan, Arun; Epstein, Jonathan A.] Univ Penn, Perelman Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
[Cifuentes, Daniel; Giraldez, Antonio J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Wolfe, Scot A.] Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA.
RP Lawson, ND (reprint author), Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
EM nathan.lawson@umassmed.edu; scot.wolfe@umassmed.edu
OI Cifuentes Buira, Daniel/0000-0001-5442-4843
FU NIH National Heart, Lung, and Blood Institute [R01 HL093766, R01
HL079266]; Department of Defense (DOD) [NF050175]; National Institute of
General Medical Sciences [R01 GM081602]
FX This work was funded by grants from the NIH National Heart, Lung, and
Blood Institute to S. A. W. and N.D.L. (R01 HL093766) and to N.D.L. (R01
HL079266) and from the Department of Defense to A. T. L. and J.A.E.
(DOD, NF050175), and from the National Institute of General Medical
Sciences to A.J.G. (R01 GM081602). Deposited in PMC for release after 12
months.
NR 63
TC 47
Z9 47
U1 0
U2 5
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD OCT 15
PY 2011
VL 138
IS 20
BP 4555
EP 4564
DI 10.1242/dev.066779
PG 10
WC Developmental Biology
SC Developmental Biology
GA 822YD
UT WOS:000295085600022
PM 21937602
ER
PT J
AU Martins, PN
AF Martins, Paulo N.
TI Follicular dendritic cell sarcoma of the liver: unusual presentation of
a rare tumor and literature review (vol 10, pg 443, 2011)
SO HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL
LA English
DT Correction
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Transplantat,Dept Surg, Boston, MA 02114 USA.
RP Martins, PN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Transplantat,Dept Surg, 55 Fruit St, Boston, MA 02114 USA.
EM pnmartins@partners.org
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ZHEJIANG UNIV SCH MEDICINE
PI HANGZHOU
PA FIRST AFFILIATED HOSPITAL, 79 QINGCHUN ROAD, HANGZHOU, 310003, PEOPLES R
CHINA
SN 1499-3872
J9 HEPATOB PANCREAT DIS
JI Hepatob. Pancreatic. Dis. Int.
PD OCT 15
PY 2011
VL 10
IS 5
BP 556
EP 556
DI 10.1016/S1499-3872(11)60094-5
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 823TH
UT WOS:000295148900016
ER
PT J
AU Burdo, TH
Lo, J
Abbara, S
Wei, J
DeLelys, ME
Preffer, F
Rosenberg, ES
Williams, KC
Grinspoon, S
AF Burdo, Tricia H.
Lo, Janet
Abbara, Suhny
Wei, Jeffrey
DeLelys, Michelle E.
Preffer, Fred
Rosenberg, Eric S.
Williams, Kenneth C.
Grinspoon, Steven
TI Soluble CD163, a Novel Marker of Activated Macrophages, Is Elevated and
Associated With Noncalcified Coronary Plaque in HIV-Infected Patients
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID SCAVENGER RECEPTOR CD163; IMMUNE ACTIVATION; ANTIRETROVIRAL THERAPY;
COMPUTED-TOMOGRAPHY; FLOW-CYTOMETRY; RISK-FACTOR; DISEASE;
ATHEROSCLEROSIS; HEMOGLOBIN; CYTOMEGALOVIRUS
AB Background. Pro-inflammatory monocytes/macrophages may contribute to increased atherosclerosis in human immunodeficiency virus (HIV)-infected patients. We investigated to our knowledge, for the first time-sCD163 and other markers of monocyte activation in relationship to atherosclerotic plaque in HIV-infected patients.
Methods. One hundred two HIV-infected and 41 HIV-seronegative men with equivalent cardiovascular risk factors and without history of coronary artery disease were prospectively recruited and underwent computed tomography coronary angiography.
Results. sCD163 levels and presence of plaque were significantly higher among antiretroviral-treated subjects with undetectable HIV RNA levels, compared with seronegative controls (1172 +/- 646 vs. 883 +/- 561 ng/mL [P = .02] for sCD163 and 61% vs. 39% [P = .03] for presence of plaque). After adjusting for age, race, lipids, blood pressure, glucose, smoking, sCD14, and HIV infection, sCD163 remained independently associated with noncalcified plaque (P = .008). Among HIV-infected patients, sCD163 was associated with coronary segments with noncalcified plaque (r = 0.21; P = .04), but not with calcium score. In contrast, markers of generalized inflammation, including C-reactive protein level, and D-dimer were not associated with sCD163 or plaque among HIV-infected patients.
Conclusions. sCD163, a monocyte/macrophage activation marker, is increased in association with noncalcified coronary plaque in men with chronic HIV infection and low or undetectable viremia. These data suggest a potentially important role of chronic monocyte/macrophage activation in the development of noncalcified vulnerable plaque.
Clinical Trial Registration. NCT00455793.
C1 [Burdo, Tricia H.; Williams, Kenneth C.] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA.
[Lo, Janet; Wei, Jeffrey; Grinspoon, Steven] Mass Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA.
[Abbara, Suhny] Dept Radiol, Boston, MA USA.
[DeLelys, Michelle E.; Preffer, Fred] Dept Pathol, Boston, MA USA.
[Rosenberg, Eric S.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Grinspoon, S (reprint author), Mass Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA.
EM sgrinspoon@partners.org
FU Bristol Myers Squibb; National Institutes of Health [K23 HL092792,
NS37654, NS40237, K24 DK064545, R01 HL 095123, R01 AI071915, M01
RR01066-25S1]; Mary Fisher Clinical AIDS Research and Education Fund
FX This work was supported by Bristol Myers Squibb; National Institutes of
Health (K23 HL092792 to J. L., NS37654 and NS40237 to K. C. W., K24
DK064545 and R01 HL 095123 to S. G., R01 AI071915 to E. S. R., and M01
RR01066-25S1); and the Mary Fisher Clinical AIDS Research and Education
Fund. Funding sources had no role in the design of the study, data
analysis, or the writing of the manuscript.
NR 34
TC 171
Z9 172
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD OCT 15
PY 2011
VL 204
IS 8
BP 1227
EP 1236
DI 10.1093/infdis/jir520
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 821JB
UT WOS:000294970100012
PM 21917896
ER
PT J
AU Tay, Y
Kats, L
Salmena, L
Weiss, D
Tan, SM
Ala, U
Karreth, F
Poliseno, L
Provero, P
Di Cunto, F
Lieberman, J
Rigoutsos, I
Pandolfi, PP
AF Tay, Yvonne
Kats, Lev
Salmena, Leonardo
Weiss, Dror
Tan, Shen Mynn
Ala, Ugo
Karreth, Florian
Poliseno, Laura
Provero, Paolo
Di Cunto, Ferdinando
Lieberman, Judy
Rigoutsos, Isidore
Pandolfi, Pier Paolo
TI Coding-Independent Regulation of the Tumor Suppressor PTEN by Competing
Endogenous mRNAs
SO CELL
LA English
DT Article
ID MICRORNA; EXPRESSION; IDENTIFICATION; REGIONS; GENE; MIR-17-92; TARGETS;
PROTEIN; CLUSTER
AB Here, we demonstrate that protein-coding RNA transcripts can crosstalk by competing for common microRNAs, with microRNA response elements as the foundation of this interaction. We have termed such RNA transcripts as competing endogenous RNAs (ceRNAs). We tested this hypothesis in the context of PTEN, a key tumor suppressor whose abundance determines critical outcomes in tumorigenesis. By a combined computational and experimental approach, we identified and validated endogenous protein-coding transcripts that regulate PTEN, antagonize PI3K/AKT signaling, and possess growth-and tumor-suppressive properties. Notably, we also show that these genes display concordant expression patterns with PTEN and copy number loss in cancers. Our study presents a road map for the prediction and validation of ceRNA activity and networks and thus imparts a trans-regulatory function to protein-coding mRNAs.
C1 [Tay, Yvonne; Kats, Lev; Salmena, Leonardo; Weiss, Dror; Ala, Ugo; Karreth, Florian; Poliseno, Laura; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Canc Genet Program,Beth Israel Deaconess Med Ctr, Div Genet,Beth Israel Deaconess Canc Ctr,Dept Med, Boston, MA 02115 USA.
[Tan, Shen Mynn; Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Tan, Shen Mynn; Lieberman, Judy] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, Boston, MA 02115 USA.
[Tan, Shen Mynn; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Ala, Ugo; Provero, Paolo; Di Cunto, Ferdinando] Univ Turin, Mol Biotechnol Ctr, Turin, Italy.
[Ala, Ugo; Provero, Paolo; Di Cunto, Ferdinando] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy.
[Rigoutsos, Isidore] Thomas Jefferson Univ, Computat Med Ctr, Jefferson Med Coll, Philadelphia, PA 19107 USA.
RP Pandolfi, PP (reprint author), Harvard Univ, Sch Med, Canc Genet Program,Beth Israel Deaconess Med Ctr, Div Genet,Beth Israel Deaconess Canc Ctr,Dept Med, Boston, MA 02115 USA.
EM ppandolf@bidmc.harvard.edu
RI Lieberman, Judy/A-2717-2015; Poliseno, Laura/B-5711-2012; Ala,
Ugo/K-2029-2016;
OI Poliseno, Laura/0000-0001-6557-955X; Ala, Ugo/0000-0001-5408-6397;
Rigoutsos, Isidore/0000-0003-1529-8631; di cunto,
ferdinando/0000-0001-9367-6357
FU Harvard Catalyst; The Harvard Clinical and Translational Science Center
(NIH) [UL1 RR 025758]; Human Frontier Science Program; Canadian
Institutes of Health Research; Fondazione per la Ricerca Biomedica ONLUS
of Torino; Department of Defense (DOD); Italian Association for Cancer
Research (AIRC) [IG-9408]; Jefferson Medical College of Thomas Jefferson
University; NIH [R01 CA-82328-09]
FX We thank Pandolfi laboratory members for critical discussions. Real-time
PCR analysis was conducted through the Harvard Catalyst Laboratory for
Innovative Translational Technologies with support from Harvard Catalyst
vertical bar 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. We thank B.
Vogelstein for DICEREx5 cells, M. Gorospe for the pMS2
plasmids, and I. Legnini for experimental support. Y.T. was supported by
a Special Fellow Award from The Leukemia & Lymphoma Society. L. K. was
supported by an NHMRC Overseas Postdoctoral Fellowship. L. S. was
supported by fellowships from the Human Frontier Science Program and the
Canadian Institutes of Health Research. U. A. was supported by a
fellowship from the Fondazione per la Ricerca Biomedica ONLUS of Torino.
S. M. T. was supported by a Department of Defense (DOD) Breast Cancer
Research Program (BCRP) postdoctoral fellowship award. P. P. and U. A.
gratefully acknowledge support from the Italian Association for Cancer
Research (AIRC) under grant IG-9408. I. R. was supported by funding from
the Jefferson Medical College of Thomas Jefferson University. This work
was supported, in part, by NIH grant R01 CA-82328-09 to P.P.
NR 38
TC 359
Z9 399
U1 13
U2 76
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 14
PY 2011
VL 147
IS 2
BP 344
EP 357
DI 10.1016/j.cell.2011.09.029
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 837KD
UT WOS:000296199300013
PM 22000013
ER
PT J
AU Karreth, FA
Tay, Y
Perna, D
Ala, U
Tan, SM
Rust, AG
DeNicola, G
Webster, KA
Weiss, D
Perez-Mancera, PA
Krauthammer, M
Halaban, R
Provero, P
Adams, DJ
Tuveson, DA
Pandolfi, PP
AF Karreth, Florian A.
Tay, Yvonne
Perna, Daniele
Ala, Ugo
Tan, Shen Mynn
Rust, Alistair G.
DeNicola, Gina
Webster, Kaitlyn A.
Weiss, Dror
Perez-Mancera, Pedro A.
Krauthammer, Michael
Halaban, Ruth
Provero, Paolo
Adams, David J.
Tuveson, David A.
Pandolfi, Pier Paolo
TI In Vivo Identification of Tumor-Suppressive PTEN ceRNAs in an Oncogenic
BRAF-Induced Mouse Model of Melanoma
SO CELL
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; MIR-200 FAMILY;
CLINICAL-IMPLICATIONS; MICRORNA TARGETS; REPRESSORS ZEB1;
MESSENGER-RNAS; CANCER; GENE; MUTATIONS; MICE
AB We recently proposed that competitive endogenous RNAs (ceRNAs) sequester microRNAs to regulate mRNA transcripts containing common microRNA recognition elements (MREs). However, the functional role of ceRNAs in cancer remains unknown. Loss of PTEN, a tumor suppressor regulated by ceRNA activity, frequently occurs in melanoma. Here, we report the discovery of significant enrichment of putative PTEN ceRNAs among genes whose loss accelerates tumorigenesis following Sleeping Beauty insertional mutagenesis in a mouse model of melanoma. We validated several putative PTEN ceRNAs and further characterized one, the ZEB2 transcript. We show that ZEB2 modulates PTEN protein levels in a microRNA-dependent, protein coding-independent manner. Attenuation of ZEB2 expression activates the PI3K/AKT pathway, enhances cell transformation, and commonly occurs in human melanomas and other cancers expressing low PTEN levels. Our study genetically identifies multiple putative microRNA decoys for PTEN, validates ZEB2 mRNA as a bona fide PTEN ceRNA, and demonstrates that abrogated ZEB2 expression cooperates with BRAF(V600E) to promote melanomagenesis.
C1 [Karreth, Florian A.; Tay, Yvonne; Ala, Ugo; Webster, Kaitlyn A.; Weiss, Dror; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Canc Ctr, Beth Israel Deaconess Med Ctr, Canc Genet Program,Div Genet,Dept Med & Pathol,Me, Boston, MA 02215 USA.
[DeNicola, Gina] Harvard Univ, Beth Israel Deaconess Canc Ctr, Beth Israel Deaconess Med Ctr, Div Signal Transduct,Dept Med & Pathol,Med Sch, Boston, MA 02215 USA.
[Perna, Daniele; Perez-Mancera, Pedro A.; Tuveson, David A.] CRUK, Li Ka Shing Ctr, Cambridge Res Inst, Cambridge CB2 0RE, England.
[Ala, Ugo; Provero, Paolo] Univ Turin, Mol Biotechnol Ctr, Turin, Italy.
[Ala, Ugo; Provero, Paolo] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy.
[Tan, Shen Mynn] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02215 USA.
[Tan, Shen Mynn] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, Boston, MA 02215 USA.
[Tan, Shen Mynn] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA.
[Rust, Alistair G.; Adams, David J.] Wellcome Trust Sanger Inst, Hinxton CB10 1HH, England.
[Krauthammer, Michael] Yale Univ, Dept Pathol, New Haven, CT 06520 USA.
[Halaban, Ruth] Yale Univ, Dept Dermatol, New Haven, CT 06520 USA.
RP Pandolfi, PP (reprint author), Harvard Univ, Beth Israel Deaconess Canc Ctr, Beth Israel Deaconess Med Ctr, Canc Genet Program,Div Genet,Dept Med & Pathol,Me, Boston, MA 02215 USA.
EM ppandolf@bidmc.harvard.edu
RI Ala, Ugo/K-2029-2016;
OI Ala, Ugo/0000-0001-5408-6397; Rust, Alistair/0000-0001-7287-192X
FU Harvard Catalyst; The Harvard Clinical and Translational Science Center
(NIH) [UL1 RR 025758]; Harvard University and its affiliated academic
health care centers; University of Cambridge,; Cancer Research UK; The
Li Ka Shing Foundation; Hutchison Whampoa Limited; NIHR Cambridge
Biomedical Research Centre; The Wellcome Trust; The Leukemia & Lymphoma
Society; Italian Association for Cancer Research (AIRC); Fundacion
Ibercaja; Fondazione per la Ricerca Biomedica ONLUS of Torino;
Department of Defense; AIRC [IG-9408]; Yale SPORE in Skin Cancer;
National Cancer Institute [1 P50 CA121974]; NIH [R01 CA-82328-09]
FX We thank Pandolfi and Tuveson laboratory members for critical
discussions. qRT-PCR analysis was conducted with support from Harvard
Catalyst vertical bar 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. We
thank B. Vogelstein for DICER-/- cells and M. Bosenberg for
TyrCreERt2 mice. We thank F. Connor and other members of the Tuveson lab
for assistance and the animal care staff and histology core at CRI. Mice
were maintained in compliance with the UK home office regulations. This
research was supported by the University of Cambridge, Cancer Research
UK, The Li Ka Shing Foundation, Hutchison Whampoa Limited, the NIHR
Cambridge Biomedical Research Centre, and The Wellcome Trust. Y.T. was
supported by a Special Fellow Award from The Leukemia & Lymphoma
Society. D. P. received an International Fellowship in Cancer Research
from the Italian Association for Cancer Research (AIRC). P.A.P.-M. was
supported by the Fundacion Ibercaja. U. A. received a fellowship from
the Fondazione per la Ricerca Biomedica ONLUS of Torino. S. M. T. was
supported by a Department of Defense Breast Cancer Research Program
fellowship. P. P. and U. A. received support from AIRC under grant
IG-9408. This work was supported by the Yale SPORE in Skin Cancer funded
by the National Cancer Institute grant number 1 P50 CA121974 to R. H.
and by NIH grant R01 CA-82328-09 to P.P.P.
NR 36
TC 274
Z9 301
U1 6
U2 53
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 14
PY 2011
VL 147
IS 2
BP 382
EP 395
DI 10.1016/j.cell.2011.09.032
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 837KD
UT WOS:000296199300016
PM 22000016
ER
PT J
AU Emanuele, MJ
Elia, AEH
Xu, QK
Thoma, CR
Izhar, L
Leng, YM
Guo, AL
Chen, YN
Rush, J
Hsu, PWC
Yen, HCS
Elledge, SJ
AF Emanuele, Michael J.
Elia, Andrew E. H.
Xu, Qikai
Thoma, Claudio R.
Izhar, Lior
Leng, Yumei
Guo, Ailan
Chen, Yi-Ning
Rush, John
Hsu, Paul Wei-Che
Yen, Hsueh-Chi Sherry
Elledge, Stephen J.
TI Global Identification of Modular Cullin-RING Ligase Substrates
SO CELL
LA English
DT Article
ID CUL3-BASED E3 LIGASE; UBIQUITIN-LIGASE; PROTEIN NETWORKS; F-BOX; SCF;
COMPLEX; NEDD8; DEGRADATION; CONJUGATION; INHIBITOR
AB Cullin-RING ligases (CRLs) represent the largest E3 ubiquitin ligase family in eukaryotes, and the identification of their substrates is critical to understanding regulation of the proteome. Using genetic and pharmacologic Cullin inactivation coupled with genetic (GPS) and proteomic (QUAINT) assays, we have identified hundreds of proteins whose stabilities or ubiquitylation status are regulated by CRLs. Together, these approaches yielded many known CRL substrates as well as a multitude of previously unknown putative substrates. We demonstrate that one substrate, NUSAP1, is an SCFCyclin F substrate during S and G2 phases of the cell cycle and is also degraded in response to DNA damage. This collection of regulated substrates is highly enriched for nodes in protein interaction networks, representing critical connections between regulatory pathways. This demonstrates the broad role of CRL ubiquitylation in all aspects of cellular biology and provides a set of proteins likely to be key indicators of cellular physiology.
C1 [Emanuele, Michael J.; Elia, Andrew E. H.; Xu, Qikai; Thoma, Claudio R.; Izhar, Lior; Leng, Yumei; Yen, Hsueh-Chi Sherry; Elledge, Stephen J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
[Emanuele, Michael J.; Elia, Andrew E. H.; Xu, Qikai; Thoma, Claudio R.; Izhar, Lior; Leng, Yumei; Yen, Hsueh-Chi Sherry; Elledge, Stephen J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Elia, Andrew E. H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Guo, Ailan; Rush, John] Cell Signaling Technol, Danvers, MA 01923 USA.
[Chen, Yi-Ning; Hsu, Paul Wei-Che; Yen, Hsueh-Chi Sherry] Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan.
[Emanuele, Michael J.; Elia, Andrew E. H.; Xu, Qikai; Thoma, Claudio R.; Izhar, Lior; Leng, Yumei; Yen, Hsueh-Chi Sherry; Elledge, Stephen J.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Yen, HCS (reprint author), Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA.
EM hyen@imb.sinica.edu.tw; selledge@genetics.med.harvard.edu
FU The Jane Coffin Childs Foundation; The American Society for Radiation
Oncology; EMBO and HFSP fellowship; American Cancer Society; NSC
[NSC100-2628-B-001-014-MY3]; NIH
FX We thank the members of the Elledge lab for helpful discussions. We
thank W. Harper for the Cul3 and Cul4 dominant-negative clones and F box
siRNA; S. Gygi for access to and assistance with MS/MS analysis
software; the IMB Bioinformatics Services Core of Academia Sinica for
technical support; and Michele Pagano for cyclin F plasmids. We thank
Marc Vidal and David Hill for the ORFeome library. M.J.E. is the Philip
O'Bryan Montgomery Jr., MD fellow of the Damon Runyon Cancer Research
Foundation (DRG-1996-08). A.E.H.E. is supported by fellowships from The
Jane Coffin Childs Foundation and The American Society for Radiation
Oncology. C.R.T. is funded by an EMBO and HFSP fellowship. Q.X. is
supported by a fellowship from the American Cancer Society. H.-C.S.Y.
was supported by an NSC grant (NSC100-2628-B-001-014-MY3). This work was
supported by an NIH grant to S.J.E. S.J.E. is an Investigator with the
Howard Hughes Medical Institute.
NR 49
TC 170
Z9 174
U1 2
U2 25
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 14
PY 2011
VL 147
IS 2
BP 459
EP 474
DI 10.1016/j.cell.2011.09.019
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 837KD
UT WOS:000296199300022
PM 21963094
ER
PT J
AU Thorsen, K
Schepeler, T
Oster, B
Rasmussen, MH
Vang, S
Wang, K
Hansen, KQ
Lamy, P
Pedersen, JS
Eller, A
Mansilla, F
Laurila, K
Wiuf, C
Laurberg, S
Dyrskjot, L
Orntoft, TF
Andersen, CL
AF Thorsen, Kasper
Schepeler, Troels
Oster, Bodil
Rasmussen, Mads H.
Vang, Soren
Wang, Kai
Hansen, Kristian Q.
Lamy, Philippe
Pedersen, Jakob Skou
Eller, Asger
Mansilla, Francisco
Laurila, Kirsti
Wiuf, Carsten
Laurberg, Soren
Dyrskjot, Lars
Orntoft, Torben F.
Andersen, Claus L.
TI Tumor-specific usage of alternative transcription start sites in
colorectal cancer identified by genome-wide exon array analysis
SO BMC GENOMICS
LA English
DT Article
ID HUMAN GENES; MESSENGER-RNA; PREDICTION; CELLS; EXPRESSION; PROMOTERS;
SEQUENCE; DATABASE; COLON; CONSERVATION
AB Background: Approximately half of all human genes use alternative transcription start sites (TSSs) to control mRNA levels and broaden the transcriptional output in healthy tissues. Aberrant expression patterns promoting carcinogenesis, however, may arise from alternative promoter usage.
Results: By profiling 108 colorectal samples using exon arrays, we identified nine genes (TCF12, OSBPL1A, TRAK1, ANK3, CHEK1, UGP2, LMO7, ACSL5, and SCIN) showing tumor-specific alternative TSS usage in both adenoma and cancer samples relative to normal mucosa. Analysis of independent exon array data sets corroborated these findings. Additionally, we confirmed the observed patterns for selected mRNAs using quantitative real-time reverse-transcription PCR. Interestingly, for some of the genes, the tumor-specific TSS usage was not restricted to colorectal cancer. A comprehensive survey of the nine genes in lung, bladder, liver, prostate, gastric, and brain cancer revealed significantly altered mRNA isoform ratios for CHEK1, OSBPL1A, and TCF12 in a subset of these cancer types. To identify the mechanism responsible for the shift in alternative TSS usage, we antagonized the Wnt-signaling pathway in DLD1 and Ls174T colorectal cancer cell lines, which remarkably led to a shift in the preferred TSS for both OSBPL1A and TRAK1. This indicated a regulatory role of the Wnt pathway in selecting TSS, possibly also involving TP53 and SOX9, as their transcription binding sites were enriched in the promoters of the tumor preferred isoforms together with their mRNA levels being increased in tumor samples. Finally, to evaluate the prognostic impact of the altered TSS usage, immunohistochemistry was used to show deregulation of the total protein levels of both TCF12 and OSBPL1A, corresponding to the mRNA levels observed. Furthermore, the level of nuclear TCF12 had a significant correlation to progression free survival in a cohort of 248 stage II colorectal cancer samples.
Conclusions: Alternative TSS usage in colorectal adenoma and cancer samples has been shown for nine genes, and OSBPL1A and TRAK1 were found to be regulated in vitro by Wnt signaling. TCF12 protein expression was upregulated in cancer samples and correlated with progression free survival.
C1 [Thorsen, Kasper; Schepeler, Troels; Oster, Bodil; Rasmussen, Mads H.; Vang, Soren; Hansen, Kristian Q.; Lamy, Philippe; Pedersen, Jakob Skou; Eller, Asger; Mansilla, Francisco; Dyrskjot, Lars; Orntoft, Torben F.; Andersen, Claus L.] Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus N, Denmark.
[Wang, Kai] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Wang, Kai] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Lamy, Philippe; Wiuf, Carsten] Aarhus Univ, Bioinformat Res Ctr BiRC, DK-8000 Aarhus C, Denmark.
[Laurila, Kirsti] Tampere Univ Technol, Dept Signal Proc, FIN-33101 Tampere, Finland.
[Laurberg, Soren] Aarhus Univ Hosp, Dept Surg P, THG, DK-8000 Aarhus C, Denmark.
RP Andersen, CL (reprint author), Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus N, Denmark.
EM cla@ki.au.dk
RI Dyrskjot, Lars/H-4922-2012; Andersen, Claus/C-1477-2017; Pedersen,
Jakob/G-3382-2012; Wiuf, Carsten/H-6320-2011; Andersen, Claus
Lindbjerg/A-9217-2012
OI Andersen, Claus/0000-0002-7406-2103; Pedersen,
Jakob/0000-0002-7236-4001; Wiuf, Carsten/0000-0002-1302-4445; Andersen,
Claus Lindbjerg/0000-0002-7406-2103
FU John and Birthe Meyer Foundation; EU [201630]; Danish Council for
Independent Research Medical Sciences; Danish Council for Strategic
Research; Lundbeck Foundation; Danish Ministry of the Interior and
Health
FX The excellent technical assistance of Hanne Steen, Pamela Celis,
Inge-Lis Thorsen Lisbet Kjeldsen, and Gitte Hoj is gratefully
appreciated. We thank Dr. Hans Clevers (The Hubrecht Laboratory, The
Netherlands) for the inducible Ls174T-derived and DLD1-derived cell
lines. Previously described dnTCF4 gene expression profiles were kindly
provided by Laurens G. van der Flier (The Hubrecht Laboratory, The
Netherlands). This work was supported by The John and Birthe Meyer
Foundation, the EU project GENICA Grant number 201630, The Danish
Council for Independent Research Medical Sciences, The Danish Council
for Strategic Research, The Lundbeck Foundation, and The Danish Ministry
of the Interior and Health.
NR 51
TC 23
Z9 24
U1 2
U2 16
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 OCT 14
PY 2011
VL 12
AR 505
DI 10.1186/1471-2164-12-505
PG 14
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 842TC
UT WOS:000296622200001
PM 21999571
ER
PT J
AU Liu, XH
Yao, S
Qiao, RF
Levine, AC
Kirschenbaum, A
Pan, JP
Wu, Y
Qin, WP
Bauman, WA
Cardozo, CP
AF Liu, Xin-Hua
Yao, Shen
Qiao, Rui-Fang
Levine, Alice C.
Kirschenbaum, Alexander
Pan, Jiangping
Wu, Yong
Qin, Weiping
Bauman, William A.
Cardozo, Christopher P.
TI Nandrolone reduces activation of Notch signaling in denervated muscle
associated with increased Numb expression
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Anabolic steroids; Muscle atrophy; Notch; Numb; Androgens; Nandrolone
ID SKELETAL-MUSCLE; SATELLITE CELLS; TESTOSTERONE SUPPLEMENTATION;
POSTNATAL MYOGENESIS; FIBER HYPERTROPHY; MEN; DIFFERENTIATION; KINASE;
MOUSE; MODEL
AB Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy. (C) 2011 Published by Elsevier Inc.
C1 [Liu, Xin-Hua; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.] James J Peter VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA.
[Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA.
[Kirschenbaum, Alexander] Mt Sinai Sch Med, Dept Urol, New York, NY 10029 USA.
RP Cardozo, CP (reprint author), James J Peter VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM chris.cardozo@mssm.edu
FU Veterans Health Administration, Rehabilitation Research and Development
Service [B4162C, B4616R, B3347 K]
FX This work was supported by the Veterans Health Administration,
Rehabilitation Research and Development Service (Grants B4162C, B4616R
and B3347 K).
NR 26
TC 6
Z9 8
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD OCT 14
PY 2011
VL 414
IS 1
BP 165
EP 169
DI 10.1016/j.bbrc.2011.09.048
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 837PH
UT WOS:000296215200030
PM 21945932
ER
PT J
AU Mar, JC
Matigian, NA
Quackenbush, J
Wells, CA
AF Mar, Jessica C.
Matigian, Nicholas A.
Quackenbush, John
Wells, Christine A.
TI attract: A Method for Identifying Core Pathways That Define Cellular
Phenotypes
SO PLOS ONE
LA English
DT Article
ID GENE SET ENRICHMENT; COEXPRESSION NETWORK ANALYSIS; EXPRESSION PROFILES
AB attract is a knowledge-driven analytical approach for identifying and annotating the gene-sets that best discriminate between cell phenotypes. attract finds distinguishing patterns within pathways, decomposes pathways into meta-genes representative of these patterns, and then generates synexpression groups of highly correlated genes from the entire transcriptome dataset. attract can be applied to a wide range of biological systems and is freely available as a Bioconductor package and has been incorporated into the MeV software system.
C1 [Mar, Jessica C.; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Mar, Jessica C.; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Matigian, Nicholas A.; Quackenbush, John; Wells, Christine A.] Griffith Univ, Natl Ctr Adult Stem Cell Res, Eskitis Inst Cell & Mol Therapies, Brisbane, Qld 4111, Australia.
[Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Wells, Christine A.] Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld, Australia.
RP Mar, JC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
EM jess@jimmy.harvard.edu; johnq@jimmy.harvard.edu; c.wells@uq.edu.au
RI Matigian, Nicholas/A-4935-2009; Wells, Christine/A-5071-2010
OI Matigian, Nicholas/0000-0001-7735-9415; Wells,
Christine/0000-0003-3133-3628
FU US National Human Genome Research Institute [P50-HG004233]; Griffith
University; Harvard Club of Australia Foundation; US National Library of
Medicine [R01-LM010129]; Australian Research Council [LX0882502];
Australian Stem Cell Centre; National Health and Medical Research
Council Australia [481945]
FX JQ and JCM are supported by a grant from the US National Human Genome
Research Institute (P50-HG004233). JQ is also supported, in part, by a
Jackson Memorial Visiting Fellowship from Griffith University
(www.griffith.edu.au) and a Harvard Club of Australia Foundation
Fellowship (http://hcag.org.au/), and from the US National Library of
Medicine (R01-LM010129). CAW is supported by the Australian Research
Council (www.arc.gov.au) International linkage scheme (LX0882502), The
Australian Stem Cell Centre and the National Health and Medical Research
Council Australia (www.nhmrc.gov.au) CDA fellowship (481945). The
funders had no role in study design, data collection and analysis,
decision to publish or the preparation of the manuscript.
NR 16
TC 19
Z9 19
U1 0
U2 2
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 OCT 14
PY 2011
VL 6
IS 10
AR e25445
DI 10.1371/journal.pone.0025445
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834RQ
UT WOS:000295981600008
PM 22022396
ER
PT J
AU McCarthy, PL
Owzar, K
Anderson, K
AF McCarthy, Philip L.
Owzar, Kouros
Anderson, Kenneth
TI "Sowing dragon's teeth?" Myeloma and AML
SO BLOOD
LA English
DT Editorial Material
ID MYELOMONOCYTIC LEUKEMIA; MULTIPLE-MYELOMA; BALB/C MICE
C1 [McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
Duke Univ, Med Ctr, Durham, NC 27706 USA.
Dana Farber Canc Inst, Boston, MA USA.
RP McCarthy, PL (reprint author), Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
NR 12
TC 1
Z9 1
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 13
PY 2011
VL 118
IS 15
BP 4008
EP 4009
DI 10.1182/blood-2011-08-372243
PG 4
WC Hematology
SC Hematology
GA 838IT
UT WOS:000296282200003
PM 21998330
ER
PT J
AU Gutierrez, A
Kentsis, A
Sanda, T
Holmfeldt, L
Chen, SC
Zhang, JH
Protopopov, A
Chin, L
Dahlberg, SE
Neuberg, DS
Silverman, LB
Winter, SS
Hunger, SP
Sallan, SE
Zha, S
Alt, FW
Downing, JR
Mullighan, CG
Look, AT
AF Gutierrez, Alejandro
Kentsis, Alex
Sanda, Takaomi
Holmfeldt, Linda
Chen, Shann-Ching
Zhang, Jianhua
Protopopov, Alexei
Chin, Lynda
Dahlberg, Suzanne E.
Neuberg, Donna S.
Silverman, Lewis B.
Winter, Stuart S.
Hunger, Stephen P.
Sallan, Stephen E.
Zha, Shan
Alt, Frederick W.
Downing, James R.
Mullighan, Charles G.
Look, A. Thomas
TI The BCL11B tumor suppressor is mutated across the major molecular
subtypes of T-cell acute lymphoblastic leukemia
SO BLOOD
LA English
DT Article
ID T(5/14)(Q35,Q32); PROTEIN; MODEL; GENE; HAPLOINSUFFICIENCY; ACTIVATION;
CHECKPOINT; EXPRESSION; DELETION; LINEAGE
AB The BCL11B transcription factor is required for normal T-cell development, and has recently been implicated in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) induced by TLX overexpression or Atm deficiency. To comprehensively assess the contribution of BCL11B inactivation to human T-ALL, we performed DNA copy number and sequencing analyses of T-ALL diagnostic specimens, revealing monoallelic BCL11B deletions or missense mutations in 9% (n = 10 of 117) of cases. Structural homology modeling revealed that several of the BCL11B mutations disrupted the structure of zinc finger domains required for this transcription factor to bind DNA. BCL11B haploinsufficiency occurred across each of the major molecular subtypes of T-ALL, including early T-cell precursor, HOXA-positive, LEF1-inactivated, and TAL1-positive subtypes, which have differentiation arrest at diverse stages of thymocyte development. Our findings provide compelling evidence that BCL11B is a haploinsufficient tumor suppressor that collaborates with all major T-ALL oncogenic lesions in human thymocyte transformation. (Blood. 2011; 118(15):4169-4173)
C1 [Gutierrez, Alejandro; Kentsis, Alex; Sanda, Takaomi; Silverman, Lewis B.; Sallan, Stephen E.; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Gutierrez, Alejandro; Kentsis, Alex; Silverman, Lewis B.; Sallan, Stephen E.; Look, A. Thomas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Holmfeldt, Linda; Chen, Shann-Ching; Downing, James R.; Mullighan, Charles G.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Zhang, Jianhua; Protopopov, Alexei; Chin, Lynda] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Dahlberg, Suzanne E.; Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Winter, Stuart S.] Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Hunger, Stephen P.] Univ Colorado, Sch Med, Sect Pediat Hematol Oncol, Aurora, CO USA.
[Hunger, Stephen P.] Childrens Hosp, Aurora, CO USA.
[Zha, Shan] Columbia Univ, Dept Pathol, Inst Canc Genet, Med Ctr, New York, NY USA.
[Zha, Shan] Columbia Univ, Dept Pediat, Inst Canc Genet, Med Ctr, New York, NY 10027 USA.
[Alt, Frederick W.] Harvard Univ, Sch Med, Boston, MA USA.
[Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA.
RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer 630,44 Binney St, Boston, MA 02215 USA.
EM thomas_look@dfci.harvard.edu
OI Kentsis, Alex/0000-0002-8063-9191; Gutierrez,
Alejandro/0000-0002-0249-9007; Mullighan, Charles/0000-0002-1871-1850;
Holmfeldt, Linda/0000-0003-4140-3423
FU National Institute of Health [2P01CA109901, 5P01CA68484, 1RO1CA158073,
CA98543, CA114766, CA98413, CA30969, CA29139, 1K08CA133103]; COG 9900
cell biology study; St Jude Children's Research Hospital-Washington
University
FX This work was funded by National Institute of Health grants 2P01CA109901
(A. T. L. and F. W. A.), 5P01CA68484 (S. E. S. and A. T. L.), and
1RO1CA158073 (S.Z.). COG cell banking and sample distribution were
supported by the COG 9900 cell biology study and grants CA98543,
CA114766, CA98413, CA30969, and CA29139 from the National Institutes of
Health. Sequence and analysis of St Jude, AEIOP, and COG samples was
supported by the St Jude Children's Research Hospital-Washington
University Pediatric Cancer Genome Project. A. G. is supported by
National Institutes of Health grant 1K08CA133103 and is a scholar of the
American Society of Hematology-Amos Medical Faculty Development program.
L. H. is supported by the Swedish Research Council. S. S. W. is the T.
John Gribble Chair of Pediatric Hematology/Oncology at the University of
New Mexico. S. P. H. is the Ergen Family Chair in Pediatric Cancer at
The Children's Hospital, Aurora, CO. S.Z. is supported by the Leukemia &
Lymphoma Society, the St Baldrick Foundation, and the Johns M. Driscoll
Jr Children's Fund. C. G. M. is a Pew Scholar in the Biomedical
Sciences. The array CGH analyses were performed and supported in part by
the Belfer Institute for Applied Cancer Science.
NR 25
TC 59
Z9 59
U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 13
PY 2011
VL 118
IS 15
BP 4169
EP 4173
DI 10.1182/blood-2010-11-318873
PG 5
WC Hematology
SC Hematology
GA 838IT
UT WOS:000296282200025
PM 21878675
ER
PT J
AU Steinbicker, AU
Bartnikas, TB
Lohmeyer, LK
Leyton, P
Mayeur, C
Kao, SM
Pappas, AE
Peterson, RT
Bloch, DB
Yu, PB
Fleming, MD
Bloch, KD
AF Steinbicker, Andrea U.
Bartnikas, Thomas B.
Lohmeyer, Lisa K.
Leyton, Patricio
Mayeur, Claire
Kao, Sonya M.
Pappas, Alexandra E.
Peterson, Randall T.
Bloch, Donald B.
Yu, Paul B.
Fleming, Mark D.
Bloch, Kenneth D.
TI Perturbation of hepcidin expression by BMP type I receptor deletion
induces iron overload in mice
SO BLOOD
LA English
DT Article
ID MOUSE EMBRYOGENESIS; KNOCKOUT MICE; HEREDITARY HEMOCHROMATOSIS; JUVENILE
HEMOCHROMATOSIS; GENE-EXPRESSION; RAT-LIVER; METABOLISM; GASTRULATION;
FERROPORTIN; ALK2
AB Bone morphogenetic protein (BMP) signaling induces hepatic expression of the peptide hormone hepcidin. Hepcidin reduces serum iron levels by promoting degradation of the iron exporter ferroportin. A relative deficiency of hepcidin underlies the pathophysiology of many of the genetically distinct iron overload disorders, collectively termed hereditary hemochromatosis. Conversely, chronic inflammatory conditions and neoplastic diseases can induce high hepcidin levels, leading to impaired mobilization of iron stores and the anemia of chronic disease. Two BMP type I receptors, Alk2 (Acvr1) and Alk3 (Bmpr1a), are expressed in murine hepatocytes. We report that liver-specific deletion of either Alk2 or Alk3 causes iron overload in mice. The iron overload phenotype was more marked in Alk3- than in Alk2-deficient mice, and Alk3 deficiency was associated with a nearly complete ablation of basal BMP signaling and hepcidin expression. Both Alk2 and Alk3 were required for induction of hepcidin gene expression by BMP2 in cultured hepatocytes or by iron challenge in vivo. These observations demonstrate that one type I BMP receptor, Alk3, is critically responsible for basal hepcidin expression, whereas 2 type I BMP receptors, Alk2 and Alk3, are required for regulation of hepcidin gene expression in response to iron and BMP signaling. (Blood. 2011;118(15):4224-4230)
C1 [Steinbicker, Andrea U.; Lohmeyer, Lisa K.; Leyton, Patricio; Mayeur, Claire; Kao, Sonya M.; Pappas, Alexandra E.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Steinbicker, Andrea U.; Bartnikas, Thomas B.; Lohmeyer, Lisa K.; Leyton, Patricio; Mayeur, Claire; Kao, Sonya M.; Pappas, Alexandra E.; Bloch, Donald B.; Fleming, Mark D.; Bloch, Kenneth D.] Harvard Univ, Sch Med, Boston, MA USA.
[Steinbicker, Andrea U.] Univ Munster, Dept Anesthesiol & Intens Care Med, D-48149 Munster, Germany.
[Bartnikas, Thomas B.; Fleming, Mark D.; Bloch, Kenneth D.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Peterson, Randall T.; Yu, Paul B.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Bloch, Donald B.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
RP Steinbicker, AU (reprint author), Univ Munster, Dept Anesthesia & Intens Care Med, Univ Hosp Muenster, Albert Schweitzer Campus 1, D-48149 Munster, Germany.
EM andrea.steinbicker@gmail.com
OI Yu, Paul/0000-0003-2145-4944
FU Deutsche Forschungsgemeinschaft (DFG) [SW 119/3-1]; National Institute
of Diabetes and Digestive and Kidney Diseases [K99DK084122,
R01DK082971]; Fondation LeDucq
FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG SW
119/3-1, A.U.S.), the National Institute of Diabetes and Digestive and
Kidney Diseases (K99DK084122 to T.B.B., R01DK082971 to M.D.F., and
R01DK082971 to R.T.P. and K.D.B.), and the Fondation LeDucq (P.B.Y. and
K.D.B).
NR 45
TC 63
Z9 64
U1 0
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 13
PY 2011
VL 118
IS 15
BP 4224
EP 4230
DI 10.1182/blood-2011-03-339952
PG 7
WC Hematology
SC Hematology
GA 838IT
UT WOS:000296282200032
PM 21841161
ER
PT J
AU Arai, S
Jagasia, M
Storer, B
Chai, XY
Pidala, J
Cutler, C
Arora, M
Weisdorf, DJ
Flowers, MED
Martin, PJ
Palmer, J
Jacobsohn, D
Pavletic, SZ
Vogelsang, GB
Lee, SJ
AF Arai, Sally
Jagasia, Madan
Storer, Barry
Chai, Xiaoyu
Pidala, Joseph
Cutler, Corey
Arora, Mukta
Weisdorf, Daniel J.
Flowers, Mary E. D.
Martin, Paul J.
Palmer, Jeanne
Jacobsohn, David
Pavletic, Steven Z.
Vogelsang, Georgia B.
Lee, Stephanie J.
TI Global and organ-specific chronic graft-versus-host disease severity
according to the 2005 NIH Consensus Criteria
SO BLOOD
LA English
DT Article
ID WORKING GROUP-REPORT; BONE-MARROW TRANSPLANTATION; STEM-CELL
TRANSPLANTATION; DEVELOPMENT PROJECT; CLINICAL-TRIALS; CHRONIC GVHD;
CLASSIFICATION; DURATION
AB In 2005, the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD proposed a new scoring system for individual organs and an algorithm for calculating global severity (mild, moderate, severe). The Chronic GVHD Consortium was established to test these new criteria. This report includes the first 298 adult patients enrolled at 5 centers of the Consortium. Patients were assessed every 3-6 months using standardized forms recommended by the Consensus Conference. At the time of study enrollment, global chronic GVHD severity was mild in 10% (n = 32), moderate in 59% (n = 175), and severe in 31% (n = 91). Skin, lung, or eye scores determined the global severity score in the majority of cases, with the other 5 organs determining 16% of the global severity scores. Conventional risk factors predictive for onset of chronic GVHD and nonrelapse mortality in people with chronic GVHD were not associated with NIH global severity scores. Global severity scores at enrollment were associated with nonrelapse mortality (P < .0001) and survival (P < .0001); 2-year overall survival was 62% (severe), 86% (moderate), and 97% (mild). Patients with mild chronic GVHD have a good prognosis, while patients with severe chronic GVHD have a poor prognosis. This study was registered at www.clinicaltrials.gov as no. NCT00637689. (Blood. 2011;118(15):4242-4249)
C1 [Storer, Barry; Chai, Xiaoyu; Flowers, Mary E. D.; Martin, Paul J.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Arai, Sally] Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA.
[Jagasia, Madan] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
[Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Arora, Mukta; Weisdorf, Daniel J.] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA.
[Palmer, Jeanne] Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA.
[Jacobsohn, David] Childrens Natl Med Ctr, Div Blood & Marrow Transplantat, Washington, DC 20010 USA.
[Pavletic, Steven Z.] NCI, NIH, Bethesda, MD 20892 USA.
[Vogelsang, Georgia B.] Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21287 USA.
RP Lee, SJ (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-290, Seattle, WA 98109 USA.
EM sjlee@fhcrc.org
FU National Institutes of Health/National Cancer Institute [CA 118953]
FX This work was supported by National Institutes of Health/National Cancer
Institute grant CA 118953.
NR 22
TC 83
Z9 86
U1 1
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 13
PY 2011
VL 118
IS 15
BP 4242
EP 4249
DI 10.1182/blood-2011-03-344390
PG 8
WC Hematology
SC Hematology
GA 838IT
UT WOS:000296282200035
PM 21791424
ER
PT J
AU Trinh, NHT
Bedoya, CA
Chang, TE
Flaherty, K
Fava, M
Yeung, A
AF Trinh, Nhi-Ha T.
Bedoya, C. A.
Chang, Trina E.
Flaherty, Katherine
Fava, Maurizio
Yeung, Albert
TI A study of a culturally focused psychiatric consultation service for
Asian American and Latino American primary care patients with depression
SO BMC PSYCHIATRY
LA English
DT Article
ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; DSM-IV; CHINESE-AMERICANS;
ETHNIC-MINORITIES; MAJOR DEPRESSION; VALIDATION; INTERVENTIONS;
DISPARITIES; MANAGEMENT; DISORDERS
AB Background: Ethnic minorities with depression are more likely to seek mental health care through primary care providers (PCPs) than mental health specialists. However, both provider and patient-specific challenges exist. PCP-specific challenges include unfamiliarity with depressive symptom profiles in diverse patient populations, limited time to address mental health, and limited referral options for mental health care. Patient specific challenges include stigma around mental health issues and reluctance to seek mental health treatment. To address these issues, we implemented a multi-component intervention for Asian American and Latino American primary care patients with depression at Massachusetts General Hospital (MGH).
Methods/Design: We propose a randomized controlled trial to evaluate a culturally appropriate intervention to improve the diagnosis and treatment of depression in our target population. Our goals are to facilitate a) primary care providers' ability to provide appropriate, culturally informed care of depression, and b) patients' knowledge of and resources for receiving treatment for depression. Our two-year long intervention targets Asian American and Latino American adult (18 years of age or older) primary care patients at MGH screening positive for symptoms of depression. All eligible patients in the intervention arm of the study who screen positive will be offered a culturally focused psychiatric (CFP) consultation. Patients will meet with a study clinician and receive toolkits that include psychoeducational booklets, worksheets and community resources. Within two weeks of the initial consultation, patients will attend a follow-up visit with the CFP clinicians. Primary outcomes will determine the feasibility and cost associated with implementation of the service, and evaluate patient and provider satisfaction with the CFP service. Exploratory aims will describe the study population at screening, recruitment, and enrollment and identify which variables influenced patient participation in the program.
Discussion: The study involves an innovative yet practical intervention that builds on existing resources and strives to improve quality of care for depression for minorities. Additionally, it complements the current movement in psychiatry to enhance the treatment of depression in primary care settings. If found beneficial, the intervention will serve as a model for care of Asian American and Latino American patients.
C1 [Trinh, Nhi-Ha T.; Chang, Trina E.; Fava, Maurizio; Yeung, Albert] Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA.
[Bedoya, C. A.] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA.
[Flaherty, Katherine] ABT Associates Inc, Cambridge, MA 02138 USA.
RP Trinh, NHT (reprint author), Massachusetts Gen Hosp, Depress & Clin Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA.
EM ntrinh@partners.org
FU Robert Wood Johnson Foundation (RWJF) [66709]; MGH Development Office
FX This research project is funded by a grant from the Robert Wood Johnson
Foundation's program, "Finding Answers: Disparities Research for Change"
(RWJF grant number 66709) to Dr. Trinh, with additional support from the
MGH Department of Psychiatry. The authors would like to thank the
professional and support staff at the participating sites for their
commitment and participation in the study: MGH Charlestown Healthcare
Center, MGH Chelsea Healthcare Center, MGH Revere Healthcare Center and
MGH Internal Medicine Associates. The authors would also like to thank
Drs. Joseph Betancourt and Alexander Green from the MGH Disparities
Solutions Center for their contributions to the conception and design of
the study, Jennifer Riconda and the MGH Development Office for their
support of the grant, Dr. Jerrold Rosenbaum the chief of the MGH
Department of Psychiatry for his support of the study, and Charlotte
Brill, Katherine Hails, Soo Jeong Yoon, Jenny Man for their technical
assistance in the study.
NR 35
TC 8
Z9 8
U1 8
U2 15
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 OCT 13
PY 2011
VL 11
AR 166
DI 10.1186/1471-244X-11-166
PG 10
WC Psychiatry
SC Psychiatry
GA 843CZ
UT WOS:000296651200001
PM 21995514
ER
PT J
AU Kovac, A
Erickson, MA
Banks, WA
AF Kovac, Andrej
Erickson, Michelle A.
Banks, William A.
TI Brain microvascular pericytes are immunoactive in culture: cytokine,
chemokine, nitric oxide, and LRP-1 expression in response to
lipopolysaccharide
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE mouse brain pericytes; LPS; neurovascular unit; cytokines; chemokines;
LRP-1; Alzheimers disease; nitric oxide
ID RECEPTOR-RELATED PROTEIN-1; IL-12 P40 HOMODIMER; BLOOD-BRAIN;
ALZHEIMERS-DISEASE; ENDOTHELIAL-CELLS; MICROGLIAL CELLS; CNS; BARRIER;
MACROPHAGES; SURVIVAL
AB Background: Brain microvascular pericytes are important constituents of the neurovascular unit. These cells are physically the closest cells to the microvascular endothelial cells in brain capillaries. They significantly contribute to the induction and maintenance of the barrier functions of the blood-brain barrier. However, very little is known about their immune activities or their roles in neuroinflammation. Here, we focused on the immunological profile of brain pericytes in culture in the quiescent and immune-challenged state by studying their production of immune mediators such as nitric oxide (NO), cytokines, and chemokines. We also examined the effects of immune challenge on pericyte expression of low density lipoprotein receptor-related protein-1 (LRP-1), a protein involved in the processing of amyloid precursor protein and the brain-to-blood efflux of amyloid-beta peptide.
Methods: Supernatants were collected from primary cultures of mouse brain pericytes. Release of nitric oxide (NO) was measured by the Griess reaction and the level of S-nitrosylation of pericyte proteins measured with a modified "biotin-switch" method. Specific mitogen-activated protein kinase (MAPK) pathway inhibitors were used to determine involvement of these pathways on NO production. Cytokines and chemokines were analyzed by multianalyte technology. The expression of both subunits of LRP-1 was analyzed by western blot.
Results: Lipopolysaccharide (LPS) induced release of NO by pericytes in a dose-dependent manner that was mediated through MAPK pathways. Nitrative stress resulted in S-nitrosylation of cellular proteins. Eighteen of twenty-three cytokines measured were released constitutively by pericytes or with stimulation by LPS, including interleukin (IL)-12, IL-13, IL-9, IL-10, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, eotaxin, chemokine (C-C motif) ligand (CCL)-3, and CCL-4. Pericyte expressions of both subunits of LRP-1 were upregulated by LPS.
Conclusions: Our results show that cultured mouse brain microvascular pericytes secrete cytokines, chemokines, and nitric oxide and respond to the innate immune system stimulator LPS. These immune properties of pericytes are likely important in their communication within the neurovascular unit and provide a mechanism by which they participate in neuroinflammatory processes in brain infections and neurodegenerative diseases.
C1 [Erickson, Michelle A.; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA.
[Kovac, Andrej; Banks, William A.] Univ Washington, Div Gerontol & Geriatr Med, Dept Internal Med, Seattle, WA 98195 USA.
[Erickson, Michelle A.; Banks, William A.] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA.
[Kovac, Andrej] Slovak Acad Sci, Inst Neuroimmunol, Bratislava, Slovakia.
RP Banks, WA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA.
EM wabanks1@uw.edu
FU VA Merit Review [RO1 AG029839, R01 DK083485]
FX Supported by VA Merit Review, RO1 AG029839, and R01 DK083485.
NR 47
TC 56
Z9 56
U1 0
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD OCT 13
PY 2011
VL 8
AR 139
DI 10.1186/1742-2094-8-139
PG 9
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 841SF
UT WOS:000296532700001
PM 21995440
ER
PT J
AU Ashktorab, H
Nguza, B
Fatemi, M
Nouraie, M
Smoot, DT
Schaffer, AA
Kupfer, SS
Camargo, CA
Brim, H
AF Ashktorab, Hassan
Nguza, Bijou
Fatemi, Mehrnaz
Nouraie, Mehdi
Smoot, Duane T.
Schaeffer, Alejandro A.
Kupfer, Sonia S.
Camargo, Carlos A., Jr.
Brim, Hassan
TI Case-Control Study of Vitamin D, dickkopf homolog 1 (DKK1) Gene
Methylation, VDR Gene Polymorphism and the Risk of Colon Adenoma in
African Americans
SO PLOS ONE
LA English
DT Article
ID D-RECEPTOR GENE; BREAST-CANCER RISK; COLORECTAL-CANCER; RECTAL-CANCER;
CIRCULATING 25-HYDROXYVITAMIN-D; D DEFICIENCY; PREVENTION; POPULATION;
ASSOCIATIONS; METAANALYSIS
AB Background: There are sparse data on genetic, epigenetic and vitamin D exposure in African Americans (AA) with colon polyp. Consequently, we evaluated serum 25(OH) D levels, vitamin D receptor (VDR) polymorphisms and the methylation status of the tumor suppressor gene dickkopf homolog 1 (DKK1) as risk factors for colon polyp in this population.
Methods: The case-control study consisted of 93 patients with colon polyp (cases) and 187 healthy individuals (controls) at Howard University Hospital. Serum levels of 25(OH)D (including D3, D2, and total) were measured by liquid chromatography-mass spectrometry. DNA analysis focused on 49 single nucleotide polymorphisms (SNPs) in the VDR gene. Promoter methylation analysis of DKK1 was also performed. The resulting data were processed in unadjusted and multivariable logistic regression analyses.
Results: Cases and controls differed in vitamin D status (D-3 < 50 nmol/L: Median of 35.5 in cases vs. 36.8 in controls nmol/L; P = 0.05). Low levels of 25(OH)D-3 (< 50 nmol/L) were observed in 86% of cases and 68% of controls and it was associated with higher risks of colon polyp (odds ratio of 2.7, 95% confidence interval 1.3-3.4). The SNP analysis showed no association between 46 VDR polymorphisms and colon polyp. The promoter of the DKK1 gene was unmethylated in 96% of the samples.
Conclusion: We found an inverse association between serum 25(OH)D-3 and colon polyp in AAs. VDR SNPs and DKK1 methylation were not associated with colon polyp. Vitamin D levels may in part explain the higher incidence of polyp in AAs.
C1 [Ashktorab, Hassan; Nguza, Bijou; Fatemi, Mehrnaz; Smoot, Duane T.] Howard Univ, Coll Med, Dept Med, Washington, DC 20059 USA.
[Ashktorab, Hassan; Nguza, Bijou; Fatemi, Mehrnaz; Smoot, Duane T.] Howard Univ, Ctr Canc, Coll Med, Washington, DC 20059 USA.
[Nouraie, Mehdi] Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC USA.
[Brim, Hassan] Howard Univ, Coll Med, Dept Pathol, Washington, DC USA.
[Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Kupfer, Sonia S.] Univ Chicago, Dept Med, Gastroenterol Sect, Chicago, IL 60637 USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
RP Ashktorab, H (reprint author), Howard Univ, Coll Med, Dept Med, Washington, DC 20059 USA.
EM hashktorab@howard.edu
RI Schaffer, Alejandro/F-2902-2012
FU National Institutes of Health [CA102681]; Massachusetts General Hospital
Center for D-receptor Activation Research; NIH, NLM
FX This work was supported in part by a PHS grant from the National
Institutes of Health CA102681, (H.A) and by the Massachusetts General
Hospital Center for D-receptor Activation Research (C.A.C). The Cancer
Research Foundation (S.S.K.) and the Digestive Disease Research Core
Center (P30 DK42086). This work was also supported by the Intramural
Research Program of the NIH, NLM (A.A.S.). No additional external
funding received for this study. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 45
TC 9
Z9 9
U1 0
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 OCT 13
PY 2011
VL 6
IS 10
AR e25314
DI 10.1371/journal.pone.0025314
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834QT
UT WOS:000295978600012
PM 22022386
ER
PT J
AU Aster, JC
Bodnar, N
Xu, LW
Karnell, F
Milholland, JM
Maillard, I
Histen, G
Nam, Y
Blacklow, SC
Pear, WS
AF Aster, Jon C.
Bodnar, Nick
Xu, Lanwei
Karnell, Fredrick
Milholland, John M.
Maillard, Ivan
Histen, Gavin
Nam, Yunsun
Blacklow, Stephen C.
Pear, Warren S.
TI Notch Ankyrin Repeat Domain Variation Influences Leukemogenesis and Myc
Transactivation
SO PLOS ONE
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; PROTEIN SECONDARY STRUCTURE; T-CELL
LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; C-MYC; CIRCULAR-DICHROISM;
INTRACELLULAR DOMAINS; TRANSCRIPTIONAL ACTIVATION; NEGATIVE
AUTOREGULATION; CRYSTAL-STRUCTURE
AB Background: The functional interchangeability of mammalian Notch receptors (Notch1-4) in normal and pathophysiologic contexts such as cancer is unsettled. We used complementary in vivo, cell-based and structural analyses to compare the abilities of activated Notch1-4 to support T cell development, induce T cell acute lymphoblastic leukemia/lymphoma (T-ALL), and maintain T-ALL cell growth and survival.
Principal Findings: We find that the activated intracellular domains of Notch1-4 (ICN1-4) all support T cell development in mice and thymic organ culture. However, unlike ICN1-3, ICN4 fails to induce T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and is unable to rescue the growth of Notch1-dependent T-ALL cell lines. The ICN4 phenotype is mimicked by weak gain-of-function forms of Notch1, suggesting that it stems from a failure to transactivate one or more critical target genes above a necessary threshold. Experiments with chimeric receptors demonstrate that the Notch ankyrin repeat domains differ in their leukemogenic potential, and that this difference correlates with activation of Myc, a direct Notch target that has an important role in Notch-associated T-ALL.
Conclusions/Significance: We conclude that the leukemogenic potentials of Notch receptors vary, and that this functional difference stems in part from divergence among the highly conserved ankyrin repeats, which influence the transactivation of specific target genes involved in leukemogenesis.
C1 [Aster, Jon C.; Histen, Gavin; Blacklow, Stephen C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Xu, Lanwei; Karnell, Fredrick; Milholland, John M.; Maillard, Ivan; Pear, Warren S.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Abramson Family Canc Res Inst,Inst Med & Engn, Philadelphia, PA 19104 USA.
[Bodnar, Nick; Blacklow, Stephen C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Bodnar, Nick; Nam, Yunsun; Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Aster, JC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM jaster@rics.bwh.harvard.edu; wpear@mail.med.upenn.edu
FU National Institutes of Health [T32 CA09140]; Leukemia and Lymphoma
Society
FX This work was supported by grants from the National Institutes of Health
(WSP, JCA, and SCB) and the Leukemia and Lymphoma Society SCOR Program
(WSP, JCA, and SCB). JMM was supported by NIH training grant T32
CA09140. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 57
TC 3
Z9 3
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 OCT 13
PY 2011
VL 6
IS 10
AR e25645
DI 10.1371/journal.pone.0025645
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834QT
UT WOS:000295978600025
PM 22022427
ER
PT J
AU Singh, T
Katiyar, SK
AF Singh, Tripti
Katiyar, Santosh K.
TI Green Tea Catechins Reduce Invasive Potential of Human Melanoma Cells by
Targeting COX-2, PGE(2) Receptors and Epithelial-to-Mesenchymal
Transition
SO PLOS ONE
LA English
DT Article
ID NF-KAPPA-B; GRAPE SEED PROANTHOCYANIDINS; LUNG-CANCER; INFLAMMATORY
RESPONSES; GUANYLATE-CYCLASE; PROSTAGLANDIN E-2; CARCINOMA-CELLS;
NITRIC-OXIDE; SKIN-CANCER; DNA-REPAIR
AB Melanoma is the most serious type of skin disease and a leading cause of death from skin disease due to its highly metastatic ability. To develop more effective chemopreventive agents for the prevention of melanoma, we have determined the effect of green tea catechins on the invasive potential of human melanoma cells and the molecular mechanisms underlying these effects using A375 (BRAF-mutated) and Hs294t (Non-BRAF-mutated) melanoma cell lines as an in vitro model. Employing cell invasion assays, we found that the inhibitory effects of green tea catechins on the cell migration were in the order of (-)-epigallocatechin-3-gallate (EGCG)>(-)-epigallocatechin >(-)-epicatechin-3-gallate >(-)-gallocatechin >(-)-epicatechin. Treatment of A375 and Hs294t cells with EGCG resulted in a dose-dependent inhibition of cell migration or invasion of these cells, which was associated with a reduction in the levels of cyclooxygenase (COX)-2, prostaglandin (PG) E-2 and PGE(2) receptors (EP2 and EP4). Treatment of cells with celecoxib, a COX-2 inhibitor, also inhibited melanoma cell migration. EGCG inhibits 12-O-tetradecanoylphorbol-13-acetate-, an inducer of COX-2, and PGE(2)-induced cell migration of cells. EGCG decreased EP2 agonist (butaprost)- and EP4 agonist (Cay10580)-induced cell migration ability. Moreover, EGCG inhibited the activation of NF-kappa B/p65, an upstream regulator of COX-2, in A375 melanoma cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NF-kappa B, also inhibited cell migration. Inhibition of melanoma cell migration by EGCG was associated with transition of mesenchymal stage to epithelial stage, which resulted in an increase in the levels of epithelial biomarkers (E-cadherin, cytokeratin and desmoglein 2) and a reduction in the levels of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin) in A375 melanoma cells. Together, these results indicate that EGCG, a major green tea catechin, has the ability to inhibit melanoma cell invasion/migration, an essential step of metastasis, by targeting the endogenous expression of COX-2, PGE2 receptors and epithelial-to-mesenchymal transition.
C1 [Singh, Tripti; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA.
[Katiyar, Santosh K.] Univ Alabama, Nutr Obes Res Ctr, Birmingham, AL USA.
[Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
[Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
RP Singh, T (reprint author), Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA.
EM skatiyar@uab.edu
FU National Center for Complementary and Alternative Medicine, NCCAM/NIH
[5RO1 AT002536]; Veterans Administration
FX This work was supported by funds from the 5RO1 AT002536 by National
Center for Complementary and Alternative Medicine, NCCAM/NIH (SKK)
(http//www.cancer.gov), and Veterans Administration Merit Review Award
(SKK). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 37
TC 39
Z9 43
U1 0
U2 22
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 13
PY 2011
VL 6
IS 10
AR e25224
DI 10.1371/journal.pone.0025224
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834QT
UT WOS:000295978600011
PM 22022384
ER
PT J
AU Papaemmanuil, E
Cazzola, M
Boultwood, J
Malcovati, L
Vyas, P
Bowen, D
Pellagatti, A
Wainscoat, JS
Hellstrom-Lindberg, E
Gambacorti-Passerini, C
Godfrey, AL
Rapado, I
Cvejic, A
Rance, R
McGee, C
Ellis, P
Mudie, LJ
Stephens, PJ
McLaren, S
Massie, CE
Tarpey, PS
Varela, I
Nik-Zainal, S
Davies, HR
Shlien, A
Jones, D
Raine, K
Hinton, J
Butler, AP
Teague, JW
Baxter, EJ
Score, J
Galli, A
Della Porta, MG
Travaglino, E
Groves, M
Tauro, S
Munshi, NC
Anderson, KC
El-Naggar, A
Fischer, A
Mustonen, V
Warren, AJ
Cross, NCP
Green, AR
Futreal, PA
Stratton, MR
Campbell, PJ
AF Papaemmanuil, E.
Cazzola, M.
Boultwood, J.
Malcovati, L.
Vyas, P.
Bowen, D.
Pellagatti, A.
Wainscoat, J. S.
Hellstrom-Lindberg, E.
Gambacorti-Passerini, C.
Godfrey, A. L.
Rapado, I.
Cvejic, A.
Rance, R.
McGee, C.
Ellis, P.
Mudie, L. J.
Stephens, P. J.
McLaren, S.
Massie, C. E.
Tarpey, P. S.
Varela, I.
Nik-Zainal, S.
Davies, H. R.
Shlien, A.
Jones, D.
Raine, K.
Hinton, J.
Butler, A. P.
Teague, J. W.
Baxter, E. J.
Score, J.
Galli, A.
Della Porta, M. G.
Travaglino, E.
Groves, M.
Tauro, S.
Munshi, N. C.
Anderson, K. C.
El-Naggar, A.
Fischer, A.
Mustonen, V.
Warren, A. J.
Cross, N. C. P.
Green, A. R.
Futreal, P. A.
Stratton, M. R.
Campbell, P. J.
CA Int Canc Genome Consortium
TI Somatic SF3B1 Mutation in Myelodysplasia with Ring Sideroblasts
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; DNMT3A MUTATIONS; EXPRESSION PROFILES; FREQUENT
MUTATION; GENE ASXL1; CANCER; GENOME; NEOPLASMS; CELLS; CLASSIFICATION
AB BACKGROUND
Myelodysplastic syndromes are a diverse and common group of chronic hematologic cancers. The identification of new genetic lesions could facilitate new diagnostic and therapeutic strategies.
METHODS
We used massively parallel sequencing technology to identify somatically acquired point mutations across all protein-coding exons in the genome in 9 patients with low-grade myelodysplasia. Targeted resequencing of the gene encoding RNA splicing factor 3B, subunit 1 (SF3B1), was also performed in a cohort of 2087 patients with myeloid or other cancers.
RESULTS
We identified 64 point mutations in the 9 patients. Recurrent somatically acquired mutations were identified in SF3B1. Follow-up revealed SF3B1 mutations in 72 of 354 patients (20%) with myelodysplastic syndromes, with particularly high frequency among patients whose disease was characterized by ring sideroblasts (53 of 82 [65%]). The gene was also mutated in 1 to 5% of patients with a variety of other tumor types. The observed mutations were less deleterious than was expected on the basis of chance, suggesting that the mutated protein retains structural integrity with altered function. SF3B1 mutations were associated with down-regulation of key gene networks, including core mitochondrial pathways. Clinically, patients with SF3B1 mutations had fewer cytopenias and longer event-free survival than patients without SF3B1 mutations.
CONCLUSIONS
Mutations in SF3B1 implicate abnormalities of messenger RNA splicing in the pathogenesis of myelodysplastic syndromes. (Funded by the Wellcome Trust and others.)
C1 [Papaemmanuil, E.; Rapado, I.; Cvejic, A.; Rance, R.; McGee, C.; Ellis, P.; Mudie, L. J.; Stephens, P. J.; McLaren, S.; Tarpey, P. S.; Varela, I.; Nik-Zainal, S.; Davies, H. R.; Shlien, A.; Jones, D.; Raine, K.; Hinton, J.; Butler, A. P.; Teague, J. W.; Fischer, A.; Mustonen, V.; Futreal, P. A.; Stratton, M. R.; Campbell, P. J.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England.
[Boultwood, J.; Pellagatti, A.] Univ Oxford, Nuffield Dept Clin Lab Sci, Oxford, England.
[Vyas, P.] Univ Oxford, Weatherall Inst Mol Med, Oxford, England.
[Bowen, D.] St James Hosp, St James Inst Oncol, Leeds LS9 7TF, W Yorkshire, England.
[Godfrey, A. L.; Cvejic, A.; Massie, C. E.; Baxter, E. J.; Warren, A. J.; Green, A. R.; Campbell, P. J.] Univ Cambridge, Dept Haematol, Cambridge, England.
[Warren, A. J.] Univ Cambridge, MRC, Mol Biol Lab, Cambridge, England.
[Warren, A. J.; Green, A. R.; Campbell, P. J.] Addenbrookes Hosp, Dept Haematol, Cambridge CB2 2QQ, England.
[Score, J.; Cross, N. C. P.] Univ Southampton, Sch Med, Southampton, Hants, England.
[Groves, M.; Tauro, S.] Univ Dundee, Div Med Sci, Dundee, Scotland.
[Cazzola, M.; Malcovati, L.; Galli, A.; Della Porta, M. G.; Travaglino, E.] Univ Pavia, Policlin San Matteo, Fdn Ist Ricovero & Cura Carattere Sci, I-27100 Pavia, Italy.
[Hellstrom-Lindberg, E.] Karolinska Inst, Dept Hematol, Stockholm, Sweden.
[Gambacorti-Passerini, C.] S Gerardo Hosp, Dept Hematol, Monza, Italy.
[Gambacorti-Passerini, C.] Univ Milano Bicocca, Milan, Italy.
[Munshi, N. C.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Munshi, N. C.] VA Boston Healthcare Syst, Boston, MA USA.
[El-Naggar, A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Fischer, A.] Univ Cologne, Inst Theoret Phys, D-5000 Cologne, Germany.
RP Campbell, PJ (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England.
EM pc8@sanger.ac.uk
RI Cross, Nicholas/B-4817-2009; Varela, Ignacio/G-1699-2016;
OI Cross, Nicholas/0000-0001-5481-2555; Varela,
Ignacio/0000-0002-0969-506X; GAMBACORTI PASSERINI,
CARLO/0000-0001-6058-515X
FU Wellcome Trust [077012/Z/05/Z, WT088340MA]; Kay Kendall Leukaemia Fund;
Leukemia Lymphoma Research; Adenoid Cystic Carcinoma Research
Foundation; Medical Research Council (MRC); Oxford National Institutes
for Health Research Biomedical Research Centre; International Human
Frontier Science Program Organization; Department of Veterans Affairs;
National Institutes of Health [R01-124929, P01-155249, P50-100007,
P01-78378]; Association for International Cancer Research; Leukemia
Lymphoma Society; Associazione Italiana per la Ricerca sul Cancro;
Fondazione Cariplo
FX Supported by grants from the Wellcome Trust (077012/Z/05/Z, for the
overall study, as well as WT088340MA, to Dr. Campbell), the Kay Kendall
Leukaemia Fund, Leukemia Lymphoma Research (for the overall study and to
Drs. Boultwood, Green, Vyas, and Wainscoat), the Adenoid Cystic
Carcinoma Research Foundation, the Medical Research Council (MRC) (to
Dr. Warren), the Oxford National Institutes for Health Research
Biomedical Research Centre (to Drs. Boultwood, Vyas, and Wainscoat), the
Swedish Cancer Society (to Dr. Hellstrom-Lindburg), the International
Human Frontier Science Program Organization (to Dr. Varela), the
Department of Veterans Affairs and the National Institutes of Health
(R01-124929, P01-155249, P50-100007, and P01-78378, to Drs. Munshi and
Anderson), the Association for International Cancer Research and the
Leukemia Lymphoma Society (to Drs. Warren and Green), Associazione
Italiana per la Ricerca sul Cancro (to the University of Pavia, the
University of Milan Bicocca, and Dr. Cazzola), and Fondazione Cariplo
(to the University of Pavia and the University of Milan Bicocca).
NR 40
TC 428
Z9 441
U1 2
U2 33
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 13
PY 2011
VL 365
IS 15
BP 1384
EP 1395
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 832DQ
UT WOS:000295782500006
PM 21995386
ER
PT J
AU Diller, L
AF Diller, Lisa
TI Adult Primary Care after Childhood Acute Lymphoblastic Leukemia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID LONG-TERM SURVIVORS; CENTRAL-NERVOUS-SYSTEM; BONE-MINERAL DENSITY;
CANCER SURVIVOR; GROWTH-HORMONE; 2ND NEOPLASMS; FOLLOW-UP; SECONDARY
NEOPLASMS; 5-YEAR SURVIVORS; PEDIATRIC CANCER
AB A 26-year-old woman presents to an internist to establish primary care. Her medical history includes a diagnosis of acute lymphoblastic leukemia (ALL) at 3 years of age. She does not know what therapies she received, but her parents told her that she was treated for 2 years and that her leukemia never recurred. She is a high-school graduate and works as a receptionist. What are the issues to consider in the care of this long-term survivor of childhood leukemia?
C1 [Diller, Lisa] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Dept Med,Childrens Hosp, Boston, MA 02215 USA.
[Diller, Lisa] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA.
RP Diller, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Dept Med,Childrens Hosp, 450 Brookline Ave, Boston, MA 02215 USA.
EM lisa_diller@dfci.harvard.edu
FU Hyundai
FX Dr. Diller reports receiving fees for serving on the medical advisory
committee for the Hope on Wheels Foundation, which is sponsored by
Hyundai. No other potential conflict of interest relevant to this
article was reported.
NR 52
TC 21
Z9 22
U1 0
U2 4
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 13
PY 2011
VL 365
IS 15
BP 1417
EP 1424
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 832DQ
UT WOS:000295782500009
PM 21995389
ER
PT J
AU Lanuti, M
Sequist, LV
Sharma, A
Mino-Kenudson, M
AF Lanuti, Michael
Sequist, Lecia V.
Sharma, Amita
Mino-Kenudson, Mari
TI Case 31-2011: A 55-Year-Old Man with Oligometastatic Lung Cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID FACTOR-RECEPTOR MUTATIONS; SYNCHRONOUS BRAIN METASTASES;
CHEMOTHERAPY-NAIVE PATIENTS; CLINICAL-PRACTICE GUIDELINE;
SURGICAL-TREATMENT; CEREBRAL METASTASIS; EGFR MUTATIONS; GENE-MUTATIONS;
PHASE-II; GEFITINIB
C1 [Lanuti, Michael] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA.
[Sharma, Amita] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Lanuti, Michael] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Sequist, Lecia V.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Sharma, Amita] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Lanuti, M (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA.
FU Department of Continuing Education, Harvard Medical School, Boston;
Boston Scientific; GlaxoSmithKline; Telik
FX This case was discussed at the postgraduate course General Thoracic
Surgery, directed by Douglas J. Mathisen, M.D., and Cameron Wright,
M.D., of the Division of Thoracic Surgery, Massachusetts General
Hospital, sponsored by the Department of Continuing Education, Harvard
Medical School, Boston, and moderated by Eugene Mark, M.D.; Dr. Lanuti
reports receiving consulting fees from Boston Scientific, and Dr.
Sequist receiving consulting fees from GlaxoSmithKline, Telik, and
Clovis Oncology and performing gratis consulting for Daiichi Sankyo and
Merrimack Pharmaceuticals. No other potential conflict of interest
relevant to this article was reported.
NR 35
TC 3
Z9 3
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 13
PY 2011
VL 365
IS 15
BP 1426
EP 1435
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 832DQ
UT WOS:000295782500012
PM 21995391
ER
PT J
AU Singh, JA
Sperling, JW
Cofield, RH
AF Singh, Jasvinder A.
Sperling, John W.
Cofield, Robert H.
TI Ninety day mortality and its predictors after primary shoulder
arthroplasty: an analysis of 4,019 patients from 1976-2008
SO BMC MUSCULOSKELETAL DISORDERS
LA English
DT Article
DE mortality; shoulder arthroplasty; humeral head replacement; shoulder
hemiarthroplasty
ID BODY-MASS INDEX; TOTAL HIP-ARTHROPLASTY; 30-DAY MORTALITY; OBESITY
PARADOX; OUTCOMES; REGISTRY; SURGERY; EVENTS; RISK
AB Background: Examine 90-day postoperative mortality and its predictors following shoulder arthroplasty
Methods: We identified vital status of all adults who underwent primary shoulder arthroplasty (Total shoulder arthroplasty (TSA) or humeral head replacement (HHR)) at the Mayo Clinic from 1976-2008, using the prospectively collected information from Total Joint Registry. We used univariate logistic regression models to assess the association of gender, age, body mass index, American Society of Anesthesiologist (ASA) class, Deyo-Charlson comorbidity index, an underlying diagnosis and implant fixation with odds of 90-day mortality after TSA or HHR. Multivariable models additionally adjusted for the type of surgery (TSA versus HHR). Adjusted Odds ratio (OR) with 95% confidence interval (CI) were calculated.
Results: Twenty-eight of the 3, 480 patient operated died within 90-days of shoulder arthroplasty (0.8%). In multivariable-adjusted analyses, the following factors were associated with significantly higher odds of 90-day mortality: higher Deyo-Charlson index (OR, 1.54; 95% CI: 1.39, 1.70; p < 0.001); a diagnosis of tumor (OR, 16.2; 95% CI: 7.1, 36.7); and ASA class III (OR, 3.57; 95% CI: 1.29, 9.91; p = 0.01) or class IV (OR, 13.4; 95% CI: 2.44, 73.86; p = 0.003). BMI >= 30 was associated with lower risk of 90-day mortality (OR, 0.25; 95% CI: 0.08, 0.78). In univariate analyses, patients undergoing TSA had significantly lower 90-day mortality of 0.4% (8/2, 580) compared to 1% in HHR (20/1, 411) (odds ratio, 0.22 (95% CI: 0.10, 0.50); p = 0.0003).
Conclusions: 90-day mortality following shoulder arthroplasty was low. An underlying diagnosis of tumor, higher comorbidity and higher ASA class were risk factors for higher 90-day mortality, while higher BMI was protective. Pre-operative comorbidity management may impact 90-day mortality following shoulder arthroplasty. A higher unadjusted mortality in patients undergoing TSA versus HHR may indicate the underlying differences in patients undergoing these procedures.
C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA.
[Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA.
[Singh, Jasvinder A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Singh, Jasvinder A.] Univ Alabama, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA.
[Singh, Jasvinder A.; Sperling, John W.; Cofield, Robert H.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA.
RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA.
EM Jasvinder.md@gmail.com
OI singh, jasvinder/0000-0003-3485-0006
FU National Institute of Health (NIH) (Mayo Clinic Center for Clinical and
Translational Research) [1 KL2 RR024151-01]
FX This material is the result of work supported with National Institute of
Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01
(Mayo Clinic Center for Clinical and Translational Research) and the
resources and the use of facilities at the Birmingham VA Medical Center,
Alabama, USA. We thank Scott Harmsen, MS and Cathy Schleck, BS for
performing statistical analyses and Youlonda Lochler for providing the
study cohort.
NR 21
TC 23
Z9 23
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2474
J9 BMC MUSCULOSKEL DIS
JI BMC Musculoskelet. Disord.
PD OCT 12
PY 2011
VL 12
AR 231
DI 10.1186/1471-2474-12-231
PG 7
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 839OE
UT WOS:000296376400002
PM 21992475
ER
PT J
AU Ebrahimi-Fakhari, D
Cantuti-Castelvetri, I
Fan, ZY
Rockenstein, E
Masliah, E
Hyman, BT
McLean, PJ
Unni, VK
AF Ebrahimi-Fakhari, Darius
Cantuti-Castelvetri, Ippolita
Fan, Zhanyun
Rockenstein, Edward
Masliah, Eliezer
Hyman, Bradley T.
McLean, Pamela J.
Unni, Vivek K.
TI Distinct Roles In Vivo for the Ubiquitin-Proteasome System and the
Autophagy-Lysosomal Pathway in the Degradation of alpha-Synuclein
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CHAPERONE-MEDIATED AUTOPHAGY; FAMILIAL PARKINSONS-DISEASE;
INCLUSION-BODY FORMATION; PROTEIN-DEGRADATION; CELL-DEATH;
NEURODEGENERATIVE DISEASE; 26S PROTEASOMES; TRANSGENIC MICE; NEURONAL
CELLS; GENE-TRANSFER
AB Increased intracellular levels of alpha-synuclein are implicated in Parkinson's disease and related disorders and may be caused by alterations in the ubiquitin-proteasome system (UPS) or the autophagy-lysosomal pathway (ALP). A critical question remains how alpha-synuclein is degraded by neurons in vivo. To address this, our study uses alpha-synuclein transgenic mice, expressing human alpha-synuclein or alpha-synuclein-eGFP under the (h) PDGF-beta promoter, in combination with in vivo pharmacologic and multiphoton imaging strategies to systematically test degradation pathways in the living mouse brain. We demonstrate that the UPS is the main degradation pathway for alpha-synuclein under normal conditions in vivo while with increased alpha-synuclein burden the ALP is recruited. Moreover, we report alterations of the UPS in alpha-synuclein transgenic mice and age dependence to the role of the UPS in alpha-synuclein degradation. In addition, we provide evidence that the UPS and ALP might be functionally connected such that impairment of one can upregulate the other. These results provide a novel link between the UPS, the ALP, and alpha-synuclein pathology and may have important implications for future therapeutics targeting degradation pathways.
C1 [Ebrahimi-Fakhari, Darius; Cantuti-Castelvetri, Ippolita; Fan, Zhanyun; Hyman, Bradley T.; McLean, Pamela J.; Unni, Vivek K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Dept Neurol, Boston, MA 02129 USA.
[Ebrahimi-Fakhari, Darius] Univ Heidelberg, Inst Anat & Cell Biol, D-69120 Heidelberg, Germany.
[Rockenstein, Edward; Masliah, Eliezer] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
RP McLean, PJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02219 USA.
EM pmclean@partners.org; unni@ohsu.edu
OI Ebrahimi-Fakhari, Darius/0000-0002-0026-4714
FU National Institutes of Health [NS038372, NS063963, T32 AG000222, T32
NS048005, K08 NS069625, AG18840, AG022074, AG10435]; Michael J. Fox
Foundation; German National Academic Foundation; Hamburg Foundation for
International Research and Studies; Parkinson's Disease Foundation;
Vector Production Core (National Institutes of Health) at Massachusetts
General Hospital [P30NS045776]
FX This work was supported by National Institutes of Health Grants NS038372
(B. T. H.), NS063963 (P.J.M.), T32 AG000222, T32 NS048005, K08 NS069625
(V. K. U.), and AG18840, AG022074, AG10435 (E. R., E. M.); The Michael
J. Fox Foundation (I. C.-C.); the German National Academic Foundation
(D.E.-F.); the Hamburg Foundation for International Research and Studies
(D.E.-F.); and the Parkinson's Disease Foundation (D.E.-F.). We thank
Dr. Bakhos A. Tannous and the Vector Production Core (National
Institutes of Health Grant P30NS045776) at Massachusetts General
Hospital.
NR 83
TC 128
Z9 133
U1 2
U2 24
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 12
PY 2011
VL 31
IS 41
BP 14508
EP 14520
DI 10.1523/JNEUROSCI.1560-11.2011
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 835FB
UT WOS:000296019600008
PM 21994367
ER
PT J
AU Sheridan, SD
Theriault, KM
Reis, SA
Zhou, F
Madison, JM
Daheron, L
Loring, JF
Haggarty, SJ
AF Sheridan, Steven D.
Theriault, Kraig M.
Reis, Surya A.
Zhou, Fen
Madison, Jon M.
Daheron, Laurence
Loring, Jeanne F.
Haggarty, Stephen J.
TI Epigenetic Characterization of the FMR1 Gene and Aberrant
Neurodevelopment in Human Induced Pluripotent Stem Cell Models of
Fragile X Syndrome
SO PLOS ONE
LA English
DT Article
ID MENTAL-RETARDATION GENE-1; REPEAT EXPANSION; MESSENGER-RNA;
DIFFERENTIATION; METHYLATION; INSTABILITY; DISEASE; PROTEIN;
PYROSEQUENCING(TM); INVOLVEMENT
AB Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. In addition to cognitive deficits, FXS patients exhibit hyperactivity, attention deficits, social difficulties, anxiety, and other autistic-like behaviors. FXS is caused by an expanded CGG trinucleotide repeat in the 59 untranslated region of the Fragile X Mental Retardation (FMR1) gene leading to epigenetic silencing and loss of expression of the Fragile X Mental Retardation protein (FMRP). Despite the known relationship between FMR1 CGG repeat expansion and FMR1 silencing, the epigenetic modifications observed at the FMR1 locus, and the consequences of the loss of FMRP on human neurodevelopment and neuronal function remain poorly understood. To address these limitations, we report on the generation of induced pluripotent stem cell (iPSC) lines from multiple patients with FXS and the characterization of their differentiation into post-mitotic neurons and glia. We show that clones from reprogrammed FXS patient fibroblast lines exhibit variation with respect to the predominant CGG-repeat length in the FMR1 gene. In two cases, iPSC clones contained predominant CGG-repeat lengths shorter than measured in corresponding input population of fibroblasts. In another instance, reprogramming a mosaic patient having both normal and pre-mutation length CGG repeats resulted in genetically matched iPSC clonal lines differing in FMR1 promoter CpG methylation and FMRP expression. Using this panel of patient-specific, FXS iPSC models, we demonstrate aberrant neuronal differentiation from FXS iPSCs that is directly correlated with epigenetic modification of the FMR1 gene and a loss of FMRP expression. Overall, these findings provide evidence for a key role for FMRP early in human neurodevelopment prior to synaptogenesis and have implications for modeling of FXS using iPSC technology. By revealing disease-associated cellular phenotypes in human neurons, these iPSC models will aid in the discovery of novel therapeutics for FXS and other autism-spectrum disorders sharing common pathophysiology.
C1 [Sheridan, Steven D.; Theriault, Kraig M.; Reis, Surya A.; Zhou, Fen; Madison, Jon M.; Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02115 USA.
[Sheridan, Steven D.; Reis, Surya A.; Zhou, Fen; Madison, Jon M.; Haggarty, Stephen J.] Broad Inst Harvard & Massachusetts Inst Technol, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Daheron, Laurence] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Daheron, Laurence] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Loring, Jeanne F.] Scripps Res Inst, Dept Physiol Chem, Ctr Regenerat Med, La Jolla, CA 92037 USA.
RP Sheridan, SD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02115 USA.
EM haggarty@chgr.mgh.harvard.edu
FU FRAXA Research Foundation; Harvard Stem Cell Institute; Stanley Medical
Research Institute; National Institute Of Mental Health [R33MH087896]
FX This work was supported in part by the FRAXA Research Foundation, a seed
grant from the Harvard Stem Cell Institute, the Stanley Medical Research
Institute, and a grant (#R33MH087896) from the National Institute Of
Mental Health. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National
Institute Of Mental Health or the 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 44
TC 120
Z9 125
U1 1
U2 18
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 12
PY 2011
VL 6
IS 10
AR e26203
DI 10.1371/journal.pone.0026203
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834PW
UT WOS:000295976000085
PM 22022567
ER
PT J
AU Wakabayashi-Ito, N
Doherty, OM
Moriyama, H
Breakefield, XO
Gusella, JF
O'Donnell, JM
Ito, N
AF Wakabayashi-Ito, Noriko
Doherty, Olugbenga M.
Moriyama, Hideaki
Breakefield, Xandra O.
Gusella, James F.
O'Donnell, Janis M.
Ito, Naoto
TI dtorsin, the Drosophila Ortholog of the Early-Onset Dystonia TOR1A
(DYT1), Plays a Novel Role in Dopamine Metabolism
SO PLOS ONE
LA English
DT Article
ID TORSION DYSTONIA; TYROSINE-HYDROXYLASE; PHENOTYPIC ANALYSIS; PROTEIN
TORSINA; PUNCH LOCUS; MOUSE MODEL; FRUIT-FLY; MELANOGASTER; GENE;
LOCOMOTION
AB Dystonia represents the third most common movement disorder in humans. At least 15 genetic loci (DYT1-15) have been identified and some of these genes have been cloned. TOR1A (formally DYT1), the gene responsible for the most common primary hereditary dystonia, encodes torsinA, an AAA ATPase family protein. However, the function of torsinA has yet to be fully understood. Here, we have generated and characterized a complete loss-of-function mutant for dtorsin, the only Drosophila ortholog of TOR1A. Null mutation of the X-linked dtorsin was semi-lethal with most male flies dying by the pre-pupal stage and the few surviving adults being sterile and slow moving, with reduced cuticle pigmentation and thin, short bristles. Third instar male larvae exhibited locomotion defects that were rescued by feeding dopamine. Moreover, biochemical analysis revealed that the brains of third instar larvae and adults heterozygous for the loss-of-function dtorsin mutation had significantly reduced dopamine levels. The dtorsin mutant showed a very strong genetic interaction with Pu (Punch: GTP cyclohydrolase), the ortholog of the human gene underlying DYT14 dystonia. Biochemical analyses revealed a severe reduction of GTP cyclohydrolase protein and activity, suggesting that dtorsin plays a novel role in dopamine metabolism as a positive-regulator of GTP cyclohydrolase protein. This dtorsin mutant line will be valuable for understanding this relationship and potentially other novel torsin functions that could play a role in human dystonia.
C1 [Wakabayashi-Ito, Noriko; Gusella, James F.; Ito, Naoto] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Doherty, Olugbenga M.; O'Donnell, Janis M.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL USA.
[Moriyama, Hideaki] Univ Nebraska, Sch Biol Sci, Lincoln, NE USA.
[Wakabayashi-Ito, Noriko; Breakefield, Xandra O.; Ito, Naoto] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Radiol, Boston, MA USA.
[Wakabayashi-Ito, Noriko; Breakefield, Xandra O.; Ito, Naoto] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
RP Wakabayashi-Ito, N (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM iton@chgr.mgh.harvard.edu
FU NIH/NIDS [NS037409]; Nebraska Tobacco Settlement Biomedical Research
Development Funds; Dystonia Medical Research Foundation; University of
Alabama
FX NIH/NIDS Grant NS037409 (JFG) (http://www.ninds.nih.gov/), Nebraska
Tobacco Settlement Biomedical Research Development Funds (HM), Dystonia
Medical Research Foundation (NI and JFG)
(http://www.dystonia-foundation.org/) and The University of Alabama (JMO
and OMD)(http://www.ua.edu/). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 57
TC 15
Z9 15
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 OCT 12
PY 2011
VL 6
IS 10
AR e26183
DI 10.1371/journal.pone.0026183
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834PW
UT WOS:000295976000082
PM 22022556
ER
PT J
AU Walcott, BP
Coumans, JV
Mian, MK
Nahed, BV
Kahle, KT
AF Walcott, Brian P.
Coumans, Jean-Valery
Mian, Matthew K.
Nahed, Brian V.
Kahle, Kristopher T.
TI Interfacility Helicopter Ambulance Transport of Neurosurgical Patients:
Observations, Utilization, and Outcomes from a Quaternary Level Care
Hospital
SO PLOS ONE
LA English
DT Article
ID HEAD-INJURED PATIENTS; INTRACEREBRAL HEMORRHAGE; EXTRADURAL HEMATOMA;
TRAUMA CENTERS; SERVICES; STROKE; IMPACT; MORTALITY; TRANSFERS; IMPROVE
AB Background: The clinical benefit of helicopter transport over ground transportation for interfacility transport is unproven. We sought to determine actual practice patterns, utilization, and outcomes of patients undergoing interfacility transport for neurosurgical conditions.
Methodology/Principal Findings: We retrospectively examined all interfacility helicopter transfers to a single trauma center during 2008. We restricted our analysis to those transfers leading either to admission to the neurosurgical service or to formal consultation upon arrival. Major exclusion criteria included transport from the scene, death during transport, and transport to any area of the hospital other than the emergency department. The primary outcome was time interval to invasive intervention. Secondary outcomes were estimated ground transportation times from the referring hospital, admitting disposition, and discharge disposition. Of 526 candidate interfacility helicopter transfers to our emergency department in 2008, we identified 167 meeting study criteria. Seventy-five (45%) of these patients underwent neurosurgical intervention. The median time to neurosurgical intervention ranged from 1.0 to 117.8 hours, varying depending on the diagnosis. For 101 (60%) of the patients, estimated driving time from the referring institution was less than one hour. Four patients (2%) expired in the emergency department, and 34 patients (20%) were admitted to a non-ICU setting. Six patients were discharged home within 24 hours. For those admitted, in-hospital mortality was 28%.
Conclusions/Significance: Many patients undergoing interfacility transfer for neurosurgical evaluation are inappropriately triaged to helicopter transport, as evidenced by actual times to intervention at the accepting institution and estimated ground transportation times from the referring institution. In a time when there is growing interest in health care cost containment, practitioners must exercise discretion in the selection of patients for air ambulance transport-particularly when it may not bear influence on clinical outcome. Neurosurgical evaluation via telemedicine may be one strategy for improving air transport triage.
C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
EM walcott.brian@mgh.harvard.edu
FU Harvard Catalyst | The Harvard Clinical and Translational Science Center
(National Institutes of Health [UL1 RR 025758]; Harvard University;
Massachusetts General Hospital, Department of Neurosurgery
FX 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. Additional
research support was provided using departmental research funds from the
Massachusetts General Hospital, Department of Neurosurgery. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 31
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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 OCT 12
PY 2011
VL 6
IS 10
AR e26216
DI 10.1371/journal.pone.0026216
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834PW
UT WOS:000295976000089
PM 22022572
ER
PT J
AU Walensky, RP
Morris, BL
Reichmann, WM
Paltiel, AD
Arbelaez, C
Donnell-Fink, L
Katz, JN
Losina, E
AF Walensky, Rochelle P.
Morris, Bethany L.
Reichmann, William M.
Paltiel, A. David
Arbelaez, Christian
Donnell-Fink, Laurel
Katz, Jeffrey N.
Losina, Elena
TI Resource Utilization and Cost-Effectiveness of Counselor-vs.
Provider-Based Rapid Point-of-Care HIV Screening in the Emergency
Department
SO PLOS ONE
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED
CONTROLLED-TRIAL; UNITED-STATES; OPPORTUNISTIC INFECTIONS; PREVENTION;
LOPINAVIR/RITONAVIR; RECOMMENDATIONS; EMTRICITABINE; ADOLESCENTS
AB Background: Routine HIV screening in emergency department (ED) settings may require dedicated personnel. We evaluated the outcomes, costs and cost-effectiveness of HIV screening when offered by either a member of the ED staff or by an HIV counselor.
Methods: We employed a mathematical model to extend data obtained from a randomized clinical trial of provider-vs. counselor-based HIV screening in the ED. We compared the downstream survival, costs, and cost-effectiveness of three HIV screening modalities: 1) no screening program; 2) an ED provider-based program; and 3) an HIV counselor-based program. Trial arm-specific data were used for test offer and acceptance rates (provider offer 36%, acceptance 75%; counselor offer 80%, acceptance 71%). Undiagnosed HIV prevalence (0.4%) and linkage to care rates (80%) were assumed to be equal between the screening modalities. Personnel costs were derived from trial-based resource utilization data. We examined the generalizability of results by conducting sensitivity analyses on offer and acceptance rates, undetected HIV prevalence, and costs.
Results: Estimated HIV screening costs in the provider and counselor arms averaged $8.10 and $31.00 per result received. The Provider strategy (compared to no screening) had an incremental cost-effectiveness ratio of $58,700/quality-adjusted life year (QALY) and the Counselor strategy (compared to the Provider strategy) had an incremental cost-effectiveness ratio of $64,500/QALY. Results were sensitive to the relative offer and acceptance rates by strategy and the capacity of providers to target-screen, but were robust to changes in undiagnosed HIV prevalence and programmatic costs.
Conclusions: The cost-effectiveness of provider-based HIV screening in an emergency department setting compares favorably to other US screening programs. Despite its additional cost, counselor-based screening delivers just as much return on investment as provider based-screening. Investment in dedicated HIV screening personnel is justified in situations where ED staff resources may be insufficient to provide comprehensive, sustainable screening services.
C1 [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA.
[Walensky, Rochelle P.; Morris, Bethany L.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA.
[Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA.
[Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Reichmann, William M.; Donnell-Fink, Laurel; Katz, Jeffrey N.; Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA.
[Arbelaez, Christian] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Walensky, Rochelle P.; Losina, Elena] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA.
[Paltiel, A. David] Yale Univ, Sch Med, New Haven, CT USA.
[Reichmann, William M.; Losina, Elena] Boston Univ Sch Publ Hlth, Dept Biostat, Boston, MA USA.
RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA.
EM rwalensky@partners.org
OI Walensky, Rochelle P./0000-0002-8795-379X
FU National Institute of Mental Health [R01 MH073445, R01 MH65869]; Doris
Duke Charitable Foundation
FX This work was funded by the National Institute of Mental Health (R01
MH073445, R01 MH65869), and the Doris Duke Charitable Foundation,
Clinical Scientist Development Award to RPW. 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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U1 0
U2 3
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 OCT 12
PY 2011
VL 6
IS 10
AR e25575
DI 10.1371/journal.pone.0025575
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834PW
UT WOS:000295976000022
PM 22022415
ER
PT J
AU Ferraro, F
Lymperi, S
Mendez-Ferrer, S
Saez, B
Spencer, JA
Yeap, BY
Masselli, E
Graiani, G
Prezioso, L
Rizzini, EL
Mangoni, M
Rizzoli, V
Sykes, SM
Lin, CP
Frenette, PS
Quaini, F
Scadden, DT
AF Ferraro, Francesca
Lymperi, Stefania
Mendez-Ferrer, Simon
Saez, Borja
Spencer, Joel A.
Yeap, Beow Y.
Masselli, Elena
Graiani, Gallia
Prezioso, Lucia
Rizzini, Elisa Lodi
Mangoni, Marcellina
Rizzoli, Vittorio
Sykes, Stephen M.
Lin, Charles P.
Frenette, Paul S.
Quaini, Federico
Scadden, David T.
TI Diabetes Impairs Hematopoietic Stem Cell Mobilization by Altering Niche
Function
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID ENDOTHELIAL PROGENITOR CELLS; COLONY-STIMULATING FACTOR; MARROW STROMAL
CELLS; BONE-MARROW; CXCR4 ANTAGONIST; G-CSF; TRANSPLANTATION; AMD3100;
EXPRESSION; MELLITUS
AB Success with transplantation of autologous hematopoietic stem and progenitor cells (HSPCs) in patients depends on adequate collection of these cells after mobilization from the bone marrow niche by the cytokine granulocyte colony-stimulating factor (G-CSF). However, some patients fail to achieve sufficient HSPC mobilization. Retrospective analysis of bone marrow transplant patient records revealed that diabetes correlated with poor mobilization of CD34(+) HSPCs. In mouse models of type 1 and type 2 diabetes (streptozotocin-induced and db/db mice, respectively), we found impaired egress of murine HSPCs from the bone marrow after G-CSF treatment. Furthermore, HSPCs were aberrantly localized in the marrow niche of the diabetic mice, and abnormalities in the number and function of sympathetic nerve termini were associated with this mislocalization. Aberrant responses to beta-adrenergic stimulation of the bone marrow included an inability of marrow mesenchymal stem cells expressing the marker nestin to down-modulate the chemokine CXCL12 in response to G-CSF treatment (mesenchymal stem cells are reported to be critical for HSPC mobilization). The HSPC mobilization defect was rescued by direct pharmacological inhibition of the interaction of CXCL12 with its receptor CXCR4 using the drug AMD3100. These data suggest that there are diabetes-induced changes in bone marrow physiology and microanatomy and point to a potential intervention to overcome poor HSPC mobilization in diabetic patients.
C1 [Ferraro, Francesca; Lymperi, Stefania; Saez, Borja; Sykes, Stephen M.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Ferraro, Francesca; Lymperi, Stefania; Saez, Borja; Sykes, Stephen M.; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Mendez-Ferrer, Simon] Ctr Nacl Invest Cardiovasc, Cardiovasc Dev Biol Dept, Madrid 28029, Spain.
[Spencer, Joel A.; Lin, Charles P.] Massachusetts Gen Hosp, Adv Microscopy Program, Ctr Syst Biol, Boston, MA 02114 USA.
[Spencer, Joel A.; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Spencer, Joel A.] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA.
[Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Masselli, Elena; Rizzini, Elisa Lodi; Mangoni, Marcellina; Rizzoli, Vittorio] Univ Parma, Dept Hematol & Bone Marrow Transplantat, I-43126 Parma, Italy.
[Graiani, Gallia; Prezioso, Lucia; Quaini, Federico] Univ Parma, Dept Internal Med & Biomed Sci, I-43126 Parma, Italy.
[Frenette, Paul S.] Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, Bronx, NY 10461 USA.
[Ferraro, Francesca; Lymperi, Stefania; Saez, Borja; Sykes, Stephen M.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
RP Quaini, F (reprint author), Univ Parma, Dept Internal Med & Biomed Sci, I-43126 Parma, Italy.
EM federico.quaini@unipr.it; dscadden@mgh.harvard.edu
RI Frenette, Paul/J-8272-2012; Spencer, Joel/A-4590-2013; Masselli,
Elena/J-9238-2016;
OI Masselli, Elena/0000-0002-4765-0428; Mendez-Ferrer,
Simon/0000-0002-9805-9988
FU Collegio Ghislieri, Associazione Italiana Leucemie, Associazione
Cristina Bassi; National Heart, Lung, and Blood Institute (NHLBI)
[U01HL100402]; American Society of Hematology (ASH); Chamber of Industry
and Commerce of the Government of Spain; NHLBI [5T32HL007623-24]; NIH
[R01HL097819, R01DK056638]; Italian Ministry of Health THEAPPL; NIH
NHLBI [HL097794, HL097748, HL100402, DK050234]; Ellison Foundation;
Harvard Stem Cell Institute; [FP7-BIOSCENT]; [NMP-214539 2007]; [PRIN
AL2YNC 2007]
FX F. F. was supported by fellowships from Collegio Ghislieri, Associazione
Italiana Leucemie, Associazione Cristina Bassi, and National Heart,
Lung, and Blood Institute (NHLBI) U01HL100402. S.M.-F. is thankful to
American Society of Hematology (ASH) for the supporting scholarship. B.
S. was supported by the Chamber of Industry and Commerce of the
Government of Spain. S. M. S. was supported by NHLBI 5T32HL007623-24. P.
S. F. was funded by NIH grants R01HL097819 and R01DK056638. F. Q. was
supported by the following grants: FP7-BIOSCENT, NMP-214539 2007, PRIN
AL2YNC 2007, and Italian Ministry of Health THEAPPL 2008. D. T. S. is
supported by the NIH NHLBI HL097794, HL097748, HL100402 and DK050234,
the Ellison Foundation, and the Harvard Stem Cell Institute.
NR 51
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Z9 63
U1 0
U2 8
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 OCT 12
PY 2011
VL 3
IS 104
AR 104ra101
DI 10.1126/scitranslmed.3002191
PG 13
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 836WV
UT WOS:000296149300004
PM 21998408
ER
PT J
AU Ochoa, CD
Garg, HG
Hales, CA
Quinn, DA
AF Ochoa, Christiaan D.
Garg, Hari G.
Hales, Charles A.
Quinn, Deborah A.
TI Low molecular weight hyaluronan, via AP-1 and NF-kappa B signalling,
induces IL-8 in transformed bronchial epithelial cells
SO SWISS MEDICAL WEEKLY
LA English
DT Article
DE low molecular weight hyaluronan; IL-8; AP-1; NF-kappa B; mechanical
strain; high tidal volume mechanical ventilation; bronchial epithelium
ID HYPOXIC PULMONARY-HYPERTENSION; INDUCED LUNG INJURY; MOUSE MACROPHAGES;
EXPRESSION; SYNTHASE; KB; INFLAMMATION; VENTILATION; INHIBITION;
PRESSURE
AB ANOVA: Analysis of Variance; AP-1: Activator Protein-1; BEGM: Bronchial Epithelial Cell Growth System; DNA: deoxyribonucleic acid; ELISA: Enzyme-linked Immunosorbent Assay; GAG: Glucosaminoglycans; HA: Hyaluronan; HAdase: Hyaluronydase; HAS: Hyaluronan Synthase; HMW-HA: High Molecular Weight Hyaluronan; IFN: Interferon; IL-8: Interleukin-8; JNK: c-Jun NH(2)-terminal Kinase; ERK 1/2: Extracellular Signal-regulated Kinase 1/2; JAK/STAT pathway: Janus Kinase/Signal Transducers and Activator of Transcription pathway; LDH: Lactate dehydrogenase; LMW-HA: Low Molecular Weight Hyaluronan; NF-kappa B: Nuclear Factor kappa-light-chain-enhancer of activated B cells; MAPK: Mitogen-activated Protein Kinase; TLR: Toll-like Receptors; TNF: Tumour Necrosis Factor; VALI: Ventilator-associated Lung Injury.
C1 Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Ochoa, CD (reprint author), Univ S Alabama, Ctr Lung Biol, Dept Pharmacol, 307 N Univ Blvd,MSB 3362, Usa Mobile, AL 36688 USA.
EM cdo701@jaguar1.usouthal.edu
FU Susannah Wood Fund; AHA [EIA 0440146N, 0526046H, HL007874, HL39150]
FX This work was partially supported by grants from the Susannah Wood Fund
and AHA EIA 0440146N (D.A.Q), AHA 0526046H (C.D.O), and HL007874, and
HL39150 (C.A.H). D.A.Q. is now employed by Novartis Pharmaceuticals.
Novartis did not support this work and was not involved in the planning
or execution of this work.
NR 37
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Z9 2
U1 0
U2 2
PU E M H SWISS MEDICAL PUBLISHERS LTD
PI MUTTENZ
PA FARNSBURGERSTR 8, CH-4132 MUTTENZ, SWITZERLAND
SN 1424-7860
J9 SWISS MED WKLY
JI Swiss Med. Wkly.
PD OCT 12
PY 2011
VL 141
AR w13255
DI 10.4414/smw.2011.13255
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 834CS
UT WOS:000295936800001
PM 21989944
ER
PT J
AU Rice, TW
Wheeler, AP
Thompson, BT
DeBoisblanc, BP
Steingrub, J
Rock, P
AF Rice, Todd W.
Wheeler, Arthur P.
Thompson, B. Taylor
DeBoisblanc, Bennett P.
Steingrub, Jay
Rock, Peter
CA NHLBI ARDS Clinical Trials Network
TI Enteral Omega-3 Fatty Acid, gamma-Linolenic Acid, and Antioxidant
Supplementation in Acute Lung Injury
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID RESPIRATORY-DISTRESS-SYNDROME; MECHANICALLY VENTILATED PATIENTS;
CRITICALLY-ILL PATIENTS; EICOSAPENTAENOIC ACID; FATTY-ACIDS; FISH-OIL;
CLINICAL-TRIAL; PLASMA; INFLAMMATION; NUTRITION
AB Context The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with gamma-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury.
Objective To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28.
Design, Setting, and Participants The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up.
Interventions Twice-daily enteral supplementation of n-3 fatty acids, gamma-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement.
Main Outcome Measure Ventilator-free days to study day 28.
Results The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P=.02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P=.04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P=.02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P=.054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P=.11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P=.001).
Conclusions Twice-daily enteral supplementation of n-3 fatty acids, gamma-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful.
C1 [Rice, Todd W.] Vanderbilt Univ, Div Allergy Pulm & Crit Care Med, Vanderbilt Med Ctr, Sch Med, Nashville, TN 37232 USA.
[Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[DeBoisblanc, Bennett P.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA.
[Steingrub, Jay] Baystate Med Ctr, Springfield, MA USA.
[Rock, Peter] Univ Maryland, Dept Anesthesiol, Sch Med, Baltimore, MD 21201 USA.
RP Rice, TW (reprint author), Vanderbilt Univ, Div Allergy Pulm & Crit Care Med, Vanderbilt Med Ctr, Sch Med, T-1218 MCN, Nashville, TN 37232 USA.
EM todd.rice@vanderbilt.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268200536165C,
HHSN268200536176C, HHSN268200536179C]
FX This study was supported by National Heart, Lung, and Blood Institute
(NHLBI) contracts HHSN268200536165C, HHSN268200536176C, and
HHSN268200536179C. Abbott Nutrition, Columbus, Ohio, provided the
omega-3 fatty acid, gamma-linolenic acid, antioxidant, and control
supplements used in the study.
NR 31
TC 171
Z9 180
U1 1
U2 30
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 12
PY 2011
VL 306
IS 14
BP 1574
EP 1581
DI 10.1001/jama.2011.1435
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 831FS
UT WOS:000295714700023
PM 21976613
ER
PT J
AU Lau, FH
Deo, RC
Mowrer, G
Caplin, J
Ahfeldt, T
Kaplan, A
Ptaszek, L
Walker, JD
Rosengard, BR
Cowan, CA
AF Lau, Frank H.
Deo, Rahul C.
Mowrer, Gregory
Caplin, Joshua
Ahfeldt, Tim
Kaplan, Adam
Ptaszek, Leon
Walker, Jennifer D.
Rosengard, Bruce R.
Cowan, Chad A.
TI Pattern Specification and Immune Response Transcriptional Signatures of
Pericardial and Subcutaneous Adipose Tissue
SO PLOS ONE
LA English
DT Article
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CORONARY-ARTERY-DISEASE;
SMOOTH-MUSCLE-CELLS; CARDIOVASCULAR-DISEASE; RISK-FACTORS;
ATHEROSCLEROTIC LESIONS; OBESE SUBJECTS; HEART-DISEASE; BODY-FAT;
EXPRESSION
AB Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Recent studies suggest that pericardial adipose tissue (PCAT) secretes inflammatory factors that contribute to the development of CVD. To better characterize the role of PCAT in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between PCAT and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals. As it was unknown whether PCAT-secreted factors are produced by adipocytes or cells in the supporting stromal fraction, we also sought to identify differentially expressed genes in isolated pericardial adipocytes vs. isolated subcutaneous adipocytes. Using microarray analysis, we found that: 1) pericardial adipose tissue and isolated pericardial adipocytes both overexpress atherosclerosis-promoting chemokines and 2) pericardial and subcutaneous fat depots, as well as isolated pericardial adipocytes and subcutaneous adipocytes, express specific patterns of homeobox genes. In contrast, a core set of lipid processing genes showed no significant overlap with differentially expressed transcripts. These depot-specific homeobox signatures and transcriptional profiles strongly suggest different functional roles for the pericardial and subcutaneous adipose depots. Further characterization of these inter-depot differences should be a research priority.
C1 [Lau, Frank H.; Deo, Rahul C.; Mowrer, Gregory; Ahfeldt, Tim; Kaplan, Adam; Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Lau, Frank H.; Deo, Rahul C.; Mowrer, Gregory; Ahfeldt, Tim; Kaplan, Adam; Cowan, Chad A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Ahfeldt, Tim; Cowan, Chad A.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Caplin, Joshua; Ptaszek, Leon] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA.
[Walker, Jennifer D.; Rosengard, Bruce R.] Massachusetts Gen Hosp, Div Cardiac Surg, Dept Surg, Boston, MA 02114 USA.
RP Lau, FH (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
EM ccowan@fas.harvard.edu
RI Ahfeldt, Tim/E-2935-2017
FU GlaxoSmithKline; Stowers Institute for Medical Research
FX This work was supported by a grant from GlaxoSmithKline
(http://www.gsk.com/) and by the Stowers Institute for Medical Research
(http://www.stowers-institute.org/). The funders had no role in the
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 54
TC 3
Z9 3
U1 1
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 OCT 11
PY 2011
VL 6
IS 10
AR e26092
DI 10.1371/journal.pone.0026092
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834OZ
UT WOS:000295973200034
PM 22022522
ER
PT J
AU Sturla, LM
Zinn, PO
Ng, K
Nitta, M
Kozono, D
Chen, CC
Kasper, EM
AF Sturla, L-M
Zinn, P. O.
Ng, K.
Nitta, M.
Kozono, D.
Chen, C. C.
Kasper, E. M.
TI Src homology domain-containing phosphatase 2 suppresses cellular
senescence in glioblastoma
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE glioblastoma; phosphatases; SHP2; senescence
ID PROTEIN-TYROSINE-PHOSPHATASE; INTEGRATED GENOMIC ANALYSIS; GROWTH-FACTOR
RECEPTOR; TELOMERASE ACTIVITY; NOONAN-SYNDROME; EGFR; MULTIFORME;
RADIATION; TUMORS; SHP-2
AB BACKGROUND: Epidermal growth factor receptor (EGFR) signalling is frequently altered during glioblastoma de novo pathogenesis. An important downstream modulator of this signal cascade is SHP2 (Src homology domain-containing phosphatase 2).
METHODS: We examined the The Cancer Genome Atlas (TCGA) database for SHP2 mutations. We also examined the expression of a further 191 phosphatases in the TCGA database and used principal component and comparative marker analysis available from the Broad Institute to recapitulate the TCGA-defined subgroups and identify the specific phosphatases defining each subgroup. We identified five siRNAs from two independent commercial sources that were reported by the vendor to be pre-optimised in their specificity of SHP2 silencing. The specificity and physiological effects of these siRNAs were tested using an in vitro glioma model.
RESULTS: TCGA data demonstrate SHP2 to be mutated in 2% of the glioblastoma multiforme's studied. Both mutations identified in this study are likely to be activating mutations. We found that the four subgroups of GBM as defined by TCGA differ significantly with regard to the expression level of specific phosphatases as revealed by comparative marker analysis. Surprisingly, the four subgroups can be defined solely on the basis of phosphatase expression level by principal component analysis. This result suggests that critical phosphatases are responsible for the modulation of specific molecular pathways within each subgroup. Src homology domain-containing phosphatase 2 constitutes one of the 12 phosphatases that define the classical subgroup. We confirmed the biological significance by siRNA knockdown of SHP2. All five siRNAs tested reduced SHP2 expression by 70-100% and reduced glioblastoma cell line growth by up to 80%. Profiling the established molecular targets of SHP2 (ERK1/2 and STAT3) confirmed specificity of these siRNAs. The loss of cell viability induced by SHP2 silencing could not be explained by a significant increase in apoptosis alone as demonstrated by terminal deoxyribonucleotidyl transferase-mediated nick-end labelling and propidium iodide staining. Src homology domain-containing phosphatase 2 silencing, however, did induce an increase in beta-galactosidase staining. Propidium iodide staining also showed that SHP2 silencing increases the population of glioblastoma cells in the G1 phase of the cell cycle and reduces the population of such cells in the G2/M- and S-phase.
CONCLUSION: Src homology domain-containing phosphatase 2 promotes the growth of glioblastoma cells by suppression of cellular senescence, a phenomenon not described previously. Selective inhibitors of SHP2 are commercially available and may be considered as a strategy for glioblastoma therapy. British Journal of Cancer (2011) 105, 1235-1243. doi:10.1038/bjc.2011.345 www.bjcancer.com Published online 20 September 2011 (C) 2011 Cancer Research UK
C1 [Sturla, L-M; Zinn, P. O.; Chen, C. C.; Kasper, E. M.] Beth Israel Deaconess Med Ctr, Dept Neurosurg, Boston, MA 02215 USA.
[Sturla, L-M; Zinn, P. O.; Ng, K.; Nitta, M.; Kozono, D.; Chen, C. C.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Nitta, M.] Tokyo Womens Med Univ, Dept Neurosurg, Tokyo, Japan.
RP Sturla, LM (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurosurg, Boston, MA 02215 USA.
EM lisa.sturla@excaliburbioconsulting.com
NR 34
TC 9
Z9 11
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD OCT 11
PY 2011
VL 105
IS 8
BP 1235
EP 1243
DI 10.1038/bjc.2011.345
PG 9
WC Oncology
SC Oncology
GA 836VR
UT WOS:000296144900021
PM 21934682
ER
PT J
AU Minamishima, S
Kida, K
Tokuda, K
Wang, HF
Sips, PY
Kosugi, S
Mandeville, JB
Buys, ES
Brouckaert, P
Liu, PK
Liu, CH
Bloch, KD
Ichinose, F
AF Minamishima, Shizuka
Kida, Kotaro
Tokuda, Kentaro
Wang, Huifang
Sips, Patrick Y.
Kosugi, Shizuko
Mandeville, Joseph B.
Buys, Emmanuel S.
Brouckaert, Peter
Liu, Philip K.
Liu, Christina H.
Bloch, Kenneth D.
Ichinose, Fumito
TI Inhaled Nitric Oxide Improves Outcomes After Successful Cardiopulmonary
Resuscitation in Mice
SO CIRCULATION
LA English
DT Article
DE cardiopulmonary resuscitation; heart arrest; magnetic resonance imaging;
nitric oxide synthase; physiology
ID EMERGENCY CARDIOVASCULAR CARE; ISCHEMIA-REPERFUSION INJURY;
AMERICAN-HEART-ASSOCIATION; DECREASES INFARCTION SIZE; CARDIAC-ARREST;
MYOCARDIAL-ISCHEMIA; SYNTHASE; MODEL; NEURODEGENERATION; DYSFUNCTION
AB Background-Sudden cardiac arrest (CA) is a leading cause of death worldwide. Breathing nitric oxide (NO) reduces ischemia/reperfusion injury in animal models and in patients. The objective of this study was to learn whether inhaled NO improves outcomes after CA and cardiopulmonary resuscitation (CPR).
Methods and Results-Adult male mice were subjected to potassium-induced CA for 7.5 minutes whereupon CPR was performed with chest compression and mechanical ventilation. One hour after CPR, mice were extubated and breathed air alone or air supplemented with 40 ppm NO for 23 hours. Mice that were subjected to CA/CPR and breathed air exhibited a poor 10-day survival rate (4 of 13), depressed neurological and left ventricular function, and increased caspase-3 activation and inflammatory cytokine induction in the brain. Magnetic resonance imaging revealed brain regions with marked water diffusion abnormality 24 hours after CA/CPR in mice that breathed air. Breathing air supplemented with NO for 23 hours starting 1 hour after CPR attenuated neurological and left ventricular dysfunction 4 days after CA/CPR and markedly improved 10-day survival rate (11 of 13; P=0.003 versus mice breathing air). The protective effects of inhaled NO on the outcome after CA/CPR were associated with reduced water diffusion abnormality, caspase-3 activation, and cytokine induction in the brain and increased serum nitrate/nitrite levels. Deficiency of the alpha 1 subunit of soluble guanylate cyclase, a primary target of NO, abrogated the ability of inhaled NO to improve outcomes after CA/CPR.
Conclusions-These results suggest that NO inhalation after CA and successful CPR improves outcome via soluble guanylate cyclase-dependent mechanisms. (Circulation. 2011;124:1645-1653.)
C1 [Minamishima, Shizuka; Kida, Kotaro; Tokuda, Kentaro; Sips, Patrick Y.; Kosugi, Shizuko; Buys, Emmanuel S.; Bloch, Kenneth D.; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Charlestown, MA 02129 USA.
[Wang, Huifang; Mandeville, Joseph B.; Liu, Philip K.; Liu, Christina H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA.
[Brouckaert, Peter] VIB, Dept Mol Biomed Res, Ghent, Belgium.
[Brouckaert, Peter] Univ Ghent, Dept Med Mol Biol, B-9000 Ghent, Belgium.
RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, 149 13th St,4315, Charlestown, MA 02129 USA.
EM fichinose@partners.org
OI Sips, Patrick/0000-0001-9241-5980; Liu, Christina/0000-0002-5723-177X
FU Jikei University School of Medicine; American Heart Association
[09POST2220133, 10SDG2610313, GIA0855887D]; Philips [09POST2220133];
National Institutes of Health [DA26108, GM79360, HL101930]; MGH; IKARIA
Inc
FX This work was supported by funding from the Jikei University School of
Medicine (Dr Kida); Resuscitation Fellowship Award 09POST2220133 from
the American Heart Association and Philips (Dr Sips); AHA scientist
development grant 10SDG2610313 (Dr Buys); AHA grant-in-aid GIA0855887D
(Dr Liu); National Institutes of Health R01 grants DA26108 (Dr Liu),
GM79360 (Dr Ichinose), and HL101930 (Dr Ichinose); and a sponsored
research agreement between MGH and IKARIA Inc (Dr Bloch).
NR 33
TC 34
Z9 39
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 11
PY 2011
VL 124
IS 15
BP 1645
EP U135
DI 10.1161/CIRCULATIONAHA.111.025395
PG 17
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 835PW
UT WOS:000296049300014
PM 21931083
ER
PT J
AU Lauer, A
Cianchetti, FA
Van Cott, EM
Schlunk, F
Schulz, E
Pfeilschifter, W
Steinmetz, H
Schaffer, CB
Lo, EH
Foerch, C
AF Lauer, Arne
Cianchetti, Flor A.
Van Cott, Elizabeth M.
Schlunk, Frieder
Schulz, Elena
Pfeilschifter, Waltraud
Steinmetz, Helmuth
Schaffer, Chris B.
Lo, Eng H.
Foerch, Christian
TI Anticoagulation With the Oral Direct Thrombin Inhibitor Dabigatran Does
Not Enlarge Hematoma Volume in Experimental Intracerebral Hemorrhage
SO CIRCULATION
LA English
DT Article
DE anticoagulants; cerebral hemorrhage; intracerebral hemorrhage; warfarin;
dabigatran; stroke
ID DEEP-VEIN THROMBOSIS; TOTAL HIP-REPLACEMENT; VENOUS THROMBOEMBOLISM;
FIBRIN POLYMERIZATION; BLEEDING-TIME; IN-VITRO; FACTOR-X; WARFARIN;
COAGULATION; ETEXILATE
AB Background-The direct thrombin inhibitor dabigatran etexilate (DE) may constitute a future replacement of vitamin K antagonists for long-term anticoagulation. Whereas warfarin pretreatment is associated with greater hematoma expansion after intracerebral hemorrhage (ICH), it remains unclear what effect direct thrombin inhibitors would have. Using different experimental models of ICH, this study compared hematoma volume among DE-treated mice, warfarin-treated mice, and controls.
Methods and Results-CD-1 mice were fed with DE or warfarin. Sham-treated mice served as controls. At the time point of ICH induction, DE mice revealed an increased activated partial thromboplastin time compared with controls (mean +/- SD 46.1 +/- 5.0 versus 18.0 +/- 1.5 seconds; P=0.022), whereas warfarin pretreatment resulted in a prothrombin time prolongation (51.4 +/- 17.9 versus 10.4 +/- 0.3 seconds; P=0.001). Twenty-four hours after collagenase-induced ICH formation, hematoma volume was 3.8 +/- 2.9 mu L in controls, 4.8 +/- 2.7 mu L in DE mice, and 14.5 +/- 11.8 mu L in warfarin mice (n=16; Welch ANOVA between-group differences P=0.007; posthoc analysis with the Dunnett method: DE versus controls, P=0.899; warfarin versus controls, P<0.001; DE versus warfarin, P=0.001). In addition, a model of laser-induced cerebral microhemorrhage was applied, and the distances that red blood cells and blood plasma were pushed into the brain were quantified. Warfarin mice showed enlarged red blood cell and blood plasma diameters compared to controls, but no difference was found between DE mice and controls.
Conclusions-In contrast with warfarin, pretreatment with DE did not increase hematoma volume in 2 different experimental models of ICH. In terms of safety, this observation may represent a potential advantage of anticoagulation with DE over warfarin. (Circulation. 2011;124:1654-1662.)
C1 [Lauer, Arne; Schlunk, Frieder; Schulz, Elena; Pfeilschifter, Waltraud; Steinmetz, Helmuth; Foerch, Christian] Goethe Univ Frankfurt, Dept Neurol, D-60528 Frankfurt, Germany.
[Schlunk, Frieder; Schulz, Elena; Lo, Eng H.; Foerch, Christian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Boston, MA USA.
[Van Cott, Elizabeth M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA.
[Cianchetti, Flor A.; Schaffer, Chris B.] Cornell Univ, Dept Biomed Engn, Ithaca, NY USA.
RP Foerch, C (reprint author), Goethe Univ Frankfurt, Dept Neurol, Schleusenweg 2-16, D-60528 Frankfurt, Germany.
EM foerch@em.uni-frankfurt.de
RI Pfeilschifter, Waltraud/K-6134-2012; Schaffer, Chris/A-7409-2008
OI Pfeilschifter, Waltraud/0000-0001-6935-8842; Schaffer,
Chris/0000-0002-7800-9596
FU National Institutes of Health [EB002019, R37-NS37074, R01-NS56458,
P01-NS55104]
FX This work was partially supported by grants from the National Institutes
of Health (EB002019 to Dr Schaffer and R37-NS37074, R01-NS56458, and
P01-NS55104 to Dr Lo). The authors did not receive industrial funding
for performing this study.
NR 42
TC 44
Z9 45
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 11
PY 2011
VL 124
IS 15
BP 1654
EP 1662
DI 10.1161/CIRCULATIONAHA.111.035972
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 835PW
UT WOS:000296049300015
PM 21911784
ER
PT J
AU Losina, E
Freedberg, KA
AF Losina, Elena
Freedberg, Kenneth A.
TI Life expectancy in HIV
SO BRITISH MEDICAL JOURNAL
LA English
DT Editorial Material
ID AIDS; COHORT
C1 [Losina, Elena] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Freedberg, Kenneth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Losina, E (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM elosina@partners.org
NR 12
TC 5
Z9 5
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD OCT 11
PY 2011
VL 343
AR d6015
DI 10.1136/bmj.d6015
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 835EJ
UT WOS:000296017500003
PM 21990259
ER
PT J
AU Ehrlich, ME
Gandy, S
AF Ehrlich, Michelle E.
Gandy, Sam
TI Chromatin plasticity and the pathogenesis of Huntington disease
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID PROTEIN-1; ROLES
C1 [Gandy, Sam] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, Dept Neurol, New York, NY 10029 USA.
Mt Sinai Sch Med, Alzheimers Dis Res Ctr, Dept Pediat, New York, NY 10029 USA.
Mt Sinai Sch Med, Alzheimers Dis Res Ctr, Dept Psychiat, New York, NY 10029 USA.
James J Peters VA Med Ctr, New York, NY 10029 USA.
RP Gandy, S (reprint author), Mt Sinai Sch Med, Alzheimers Dis Res Ctr, Dept Neurol, New York, NY 10029 USA.
EM samuel.gandy@mssm.edu
FU NINDS NIH HHS [R01 NS059936]
NR 16
TC 2
Z9 2
U1 1
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 11
PY 2011
VL 108
IS 41
BP 16867
EP 16868
DI 10.1073/pnas.1113321108
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834PD
UT WOS:000295973800006
PM 21969556
ER
PT J
AU Hu, Y
Chopra, V
Chopra, R
Locascio, JJ
Liao, ZX
Ding, HL
Zheng, B
Matson, WR
Ferrante, RJ
Rosas, HD
Hersch, SM
Scherzer, CR
AF Hu, Yi
Chopra, Vanita
Chopra, Raman
Locascio, Joseph J.
Liao, Zhixiang
Ding, Hongliu
Zheng, Bin
Matson, Wayne R.
Ferrante, Robert J.
Rosas, H. Diana
Hersch, Steven M.
Scherzer, Clemens R.
TI Transcriptional modulator H2A histone family, member Y (H2AFY) marks
Huntington disease activity in man and mouse
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE macroH2A; transcriptional profiling; gene expression; sodium
phenylbutyrate
ID GENE-EXPRESSION; PARKINSONS-DISEASE; VARIANT MACROH2A; HUMAN BLOOD;
PHENYLBUTYRATE; MODEL; BIOMARKERS; BINDING; BRAIN; MICE
AB Huntington disease (HD) is a progressive neurodegenerative disease that affects 30,000 individuals in North America. Treatments that slow its relentless course are not yet available, and biomarkers that can reliably measure disease activity and therapeutic response are urgently needed to facilitate their development. Here, we interrogated 119 human blood samples for transcripts associated with HD. We found that the dynamic regulator of chromatin plasticity H2A histone family, member Y (H2AFY) is specifically overexpressed in the blood and frontal cortex of patients with HD compared with controls. This association precedes the onset of clinical symptoms, was confirmed in two mouse models, and was independently replicated in cross-sectional and longitudinal clinical studies comprising 142 participants. A histone deacetylase inhibitor that suppresses neurodegeneration in animal models reduces H2AFY levels in a randomized phase II clinical trial. This study identifies the chromatin regulator H2AFY as a potential biomarker associated with disease activity and pharmacodynamic response that may become useful for enabling disease-modifying therapeutics for HD.
C1 [Chopra, Vanita; Chopra, Raman; Hersch, Steven M.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Lab Neurodegenerat & Neurotherapeut, Charlestown, MA 02129 USA.
[Hu, Yi; Locascio, Joseph J.; Liao, Zhixiang; Ding, Hongliu; Zheng, Bin; Scherzer, Clemens R.] Harvard Univ, Sch Med, Ctr Neurol Dis, Lab Neurogen, Cambridge, MA 02139 USA.
Brigham & Womens Hosp, Cambridge, MA 02139 USA.
[Rosas, H. Diana] Massachusetts Gen Hosp, Ctr Neuroimaging Aging & Neurodegenerat Dis, Charlestown, MA 02129 USA.
[Rosas, H. Diana] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Locascio, Joseph J.; Rosas, H. Diana; Scherzer, Clemens R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Matson, Wayne R.] New England Vet Adm, Geriatr Res Educ Clin Ctr, Bedford, MA 01730 USA.
[Ferrante, Robert J.] Vet Adm Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA.
[Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15213 USA.
[Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA.
[Ferrante, Robert J.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15213 USA.
[Scherzer, Clemens R.] Harvard NeuroDiscovery Ctr Biomarker Program, Cambridge, MA 02139 USA.
RP Hersch, SM (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Lab Neurodegenerat & Neurotherapeut, Charlestown, MA 02129 USA.
EM hersch@helix.mgh.harvard.edu; cscherzer@rics.bwh.harvard.edu
FU Michael J. Fox Foundation; National Institutes of Health [P01NS058793,
R01NS064155, R21NS060227, P01NS045242, R01NS042861]; Maximillian E. &
Marion O. Hoffman Foundation; RJG Foundation; Huntington's Disease
Society of America (HDSA) Coalition for the Cure; HDSA New England
Center for Excellence for Huntington Disease
FX Conflict of interest statement: C. R. S. has served as a consultant to
Link Medicine Corporation and was a scientific collaborator of DiaGenic
in a study funded by the Michael J. Fox Foundation. He is listed as
coinventor on US patent/applications held by the Brigham and Women's
Hospital relating to diagnostics in neurodegenerative diseases. S. M. H.
is a scientific collaborator with the Novartis Institutes for Biomedical
Research. He is listed as coinventor on US patent/applications held by
the Massachusetts General Hospital relating to therapeutics and
diagnostics in neurodegenerative diseases.; We thank Drs. Marian
DiFiglia and Antonio Valencia for 140-CAG knock-in mouse brain tissues.
This study was funded by National Institutes of Health Grants
P01NS058793 (to C. R. S., S. M. H., H. D. R., and R.J.F.), R01NS064155
(to C. R. S.), R21NS060227 (to C. R. S.), P01NS045242 (to S. M. H. and
H. D. R.), and R01NS042861 (to H. D. R.); the Maximillian E. & Marion O.
Hoffman Foundation (to C. R. S.); the RJG Foundation (to C. R. S.); the
Huntington's Disease Society of America (HDSA) Coalition for the Cure
(to S. M. H. and V. C.); and the HDSA New England Center for Excellence
for Huntington Disease (to S. M. H. and H.D.R.).
NR 44
TC 40
Z9 41
U1 0
U2 10
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 11
PY 2011
VL 108
IS 41
BP 17141
EP 17146
DI 10.1073/pnas.1104409108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834PD
UT WOS:000295973800054
PM 21969577
ER
PT J
AU Lee, PT
Kruse, GR
Chan, BT
Massaquoi, MBF
Panjabi, RR
Dahn, BT
Gwenigale, WT
AF Lee, Patrick T.
Kruse, Gina R.
Chan, Brian T.
Massaquoi, Moses B. F.
Panjabi, Rajesh R.
Dahn, Bernice T.
Gwenigale, Walter T.
TI An analysis of Liberia's 2007 national health policy: lessons for health
systems strengthening and chronic disease care in poor, post-conflict
countries
SO GLOBALIZATION AND HEALTH
LA English
DT Article
ID SUB-SAHARAN AFRICA; MIDDLE-INCOME COUNTRIES; MENTAL-HEALTH;
ANTIRETROVIRAL TREATMENT; HUMAN-RESOURCES; HEART-DISEASE; HIV TREATMENT;
MEDICAL HOME; BURDEN; HYPERTENSION
AB Background: Globally, chronic diseases are responsible for an enormous burden of deaths, disability, and economic loss, yet little is known about the optimal health sector response to chronic diseases in poor, post-conflict countries. Liberia's experience in strengthening health systems and health financing overall, and addressing HIV/AIDS and mental health in particular, provides a relevant case study for international stakeholders and policymakers in other poor, post-conflict countries seeking to understand and prioritize the global response to chronic diseases.
Methods: We conducted a historical review of Liberia's post-conflict policies and their impact on general economic and health indicators, as well as on health systems strengthening and chronic disease care and treatment. Key sources included primary documents from Liberia's Ministry of Health and Social Welfare, published and gray literature, and personal communications from key stakeholders engaged in Liberia's Health Sector Reform. In this case study, we examine the early reconstruction of Liberia's health care system from the end of conflict in 2003 to the present time, highlight challenges and lessons learned from this initial experience, and describe future directions for health systems strengthening and chronic disease care and treatment in Liberia.
Results: Six key lessons emerge from this analysis: (i) the 2007 National Health Policy's 'one size fits all' approach met aggregate planning targets but resulted in significant gaps and inefficiencies throughout the system; (ii) the innovative Health Sector Pool Fund proved to be an effective financing mechanism to recruit and align health actors with the 2007 National Health Policy; (iii) a substantial rural health delivery gap remains, but it could be bridged with a robust cadre of community health workers integrated into the primary health care system; (iv) effective strategies for HIV/AIDS care in other settings should be validated in Liberia and adapted for use in other chronic diseases; (v) mental health disorders are extremely prevalent in Liberia and should remain a top chronic disease priority; and (vi) better information systems and data management are needed at all levels of the health system.
Conclusions: The way forward for chronic diseases in Liberia will require an increased emphasis on quality over quantity, better data management to inform rational health sector planning, corrective mechanisms to more efficiently align health infrastructure and personnel with existing needs, and innovative methods to improve long-term retention in care and bridge the rural health delivery gap.
C1 [Lee, Patrick T.; Kruse, Gina R.; Chan, Brian T.; Panjabi, Rajesh R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lee, Patrick T.; Kruse, Gina R.; Chan, Brian T.; Panjabi, Rajesh R.] Harvard Univ, Sch Med, Boston, MA USA.
[Lee, Patrick T.; Kruse, Gina R.; Chan, Brian T.; Panjabi, Rajesh R.] Tiyatien Hlth, Zwedru, Grand Gedeh Cou, Liberia.
[Massaquoi, Moses B. F.] Clinton Hlth Access Initiat, Boston, MA USA.
[Massaquoi, Moses B. F.; Dahn, Bernice T.; Gwenigale, Walter T.] Minist Hlth & Social Welf, Capital Bypass, Monrovia, Liberia.
RP Lee, PT (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM ptlee@partners.org
NR 83
TC 6
Z9 6
U1 1
U2 23
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1744-8603
J9 GLOBALIZATION HEALTH
JI Global. Health
PD OCT 10
PY 2011
VL 7
AR 37
DI 10.1186/1744-8603-7-37
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 872MT
UT WOS:000298814500001
PM 21985150
ER
PT J
AU Tyekucheva, S
Yolken, RH
McCombie, WR
Parla, J
Kramer, M
Wheelan, SJ
Sabunciyan, S
AF Tyekucheva, Svitlana
Yolken, Robert H.
McCombie, W. Richard
Parla, Jennifer
Kramer, Melissa
Wheelan, Sarah J.
Sabunciyan, Sarven
TI Establishing the baseline level of repetitive element expression in the
human cortex
SO BMC GENOMICS
LA English
DT Article
ID ENDOGENOUS RETROVIRAL PROMOTER; HUMAN GENOME; GENE; RETROTRANSPOSON;
TRANSCRIPTOME; SEQUENCES; SCHIZOPHRENIA; METHYLATION; EVOLUTION; DISEASE
AB Background: Although nearly half of the human genome is comprised of repetitive sequences, the expression profile of these elements remains largely uncharacterized. Recently developed high throughput sequencing technologies provide us with a powerful new set of tools to study repeat elements. Hence, we performed whole transcriptome sequencing to investigate the expression of repetitive elements in human frontal cortex using postmortem tissue obtained from the Stanley Medical Research Institute.
Results: We found a significant amount of reads from the human frontal cortex originate from repeat elements. We also noticed that Alu elements were expressed at levels higher than expected by random or background transcription. In contrast, L1 elements were expressed at lower than expected amounts.
Conclusions: Repetitive elements are expressed abundantly in the human brain. This expression pattern appears to be element specific and can not be explained by random or background transcription. These results demonstrate that our knowledge about repetitive elements is far from complete. Further characterization is required to determine the mechanism, the control, and the effects of repeat element expression.
C1 [Wheelan, Sarah J.] Johns Hopkins Univ, Sch Med, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
[Tyekucheva, Svitlana] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Tyekucheva, Svitlana] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Yolken, Robert H.; Sabunciyan, Sarven] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA.
[McCombie, W. Richard; Parla, Jennifer; Kramer, Melissa] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, Cold Spring Harbor, NY 11724 USA.
[Wheelan, Sarah J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
[Wheelan, Sarah J.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
RP Wheelan, SJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, 550 N Broadway, Baltimore, MD 21205 USA.
EM swheelan@jhmi.edu; ssabunc1@jhmi.edu
OI McCombie, W. Richard/0000-0003-1899-0682
FU Stanley Medical Research Institute
FX The authors would like to thank the Stanley Medical Research Institute
and Dr. Fuller Torrey and Maree Webster for kindly providing the
postmortem cortical tissue used in this study. The authors are grateful
to The Stanley Medical Research Institute for funding this research at
Johns Hopkins Stanley Division of Developmental Neurovirology and
through the Stanley Institute for Cognitive Genomics at CSHL.
NR 33
TC 7
Z9 8
U1 0
U2 1
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 OCT 10
PY 2011
VL 12
AR 495
DI 10.1186/1471-2164-12-495
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 842SV
UT WOS:000296621400001
PM 21985647
ER
PT J
AU Pritchard, KI
Shepherd, LE
Chapman, JAW
Norris, BD
Cantin, J
Goss, PE
Dent, SF
Walde, D
Vandenberg, TA
Findlay, B
O'Reilly, SE
Wilson, CF
Han, L
Piura, E
Whelan, TJ
Pollak, MN
AF Pritchard, Kathleen I.
Shepherd, Lois E.
Chapman, Judith-Anne W.
Norris, Brian D.
Cantin, Jacques
Goss, Paul E.
Dent, Susan F.
Walde, David
Vandenberg, Ted A.
Findlay, Brian
O'Reilly, Susan E.
Wilson, Carolyn F.
Han, Lei
Piura, Ettie
Whelan, Timothy J.
Pollak, Michael N.
TI Randomized Trial of Tamoxifen Versus Combined Tamoxifen and Octreotide
LAR Therapy in the Adjuvant Treatment of Early-Stage Breast Cancer in
Postmenopausal Women: NCIC CTG MA.14
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SOMATOSTATIN ANALOGS; GROWTH-FACTOR; INSULIN; METFORMIN
AB Purpose Somatostatin analogs act directly on breast cancer cells and indirectly on insulin and insulin-like growth factor 1 (IGF-1) levels. This trial was undertaken to assess whether octreotide would lower insulin and IGF-1 levels and reduce risk of breast cancer recurrence.
Patients and Methods The NCIC CTG MA. 14 (NCIC Clinical Trials Group MA. 14) trial randomly assigned postmenopausal women to 5 years of tamoxifen 20 mg daily (TAM) or TAM plus 2 years of octreotide 90 mg depot intramuscular injections monthly (TAM-OCT) as adjuvant therapy. The primary end point was event-free survival (EFS). Secondary end points were relapse-free survival (RFS), overall survival (OS), toxicity, and effects of treatment on IGF physiology.
Results Among 667 women with a median follow-up of 7.9 years, 220 events occurred-108 with TAM-OCT and 112 with TAM. Adjusted hazard ratios (HRs; TAM-OCT to TAM) were 0.93 for EFS (95% CI, 0.71 to 1.22; P = .62), 0.84 for RFS (95% CI, 0.59 to 1.18; P = .31), and 0.97 for OS (95% CI, 0.69 to 1.37; P = .86). Among patients with normal baseline gallbladder imaging, cholecystectomy was required in 23.0% of those receiving TAM-OCT but in only 1.4% of those receiving TAM (P < .001). At 4 months, TAM-OCT had significantly (P < .001) lowered IGF-1, IGF binding protein 3, and C-peptide levels. Older age (P = .02), tumor size (P = .001), nodal status (P = .01), high C-peptide levels (P < .001), and higher body mass index (BMI) in models excluding C-peptide (P < .001) were associated with poorer EFS in multivariate analysis.
Conclusion Octreotide-related changes in circulating IGF-1 and C-peptide levels were statistically significant. Octreotide did not add significant clinical benefit. High C-peptide levels (surrogate for insulin secretion rate) and high BMI were associated with poor outcome.
C1 [Pritchard, Kathleen I.] Sunnybrook Odette Canc Ctr, Toronto, ON M4N 3M5, Canada.
[Pritchard, Kathleen I.] Univ Toronto, Toronto, ON M4N 3M5, Canada.
[Shepherd, Lois E.; Chapman, Judith-Anne W.; Wilson, Carolyn F.; Han, Lei] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada.
[Dent, Susan F.] Ottawa Hosp Canc Ctr, Ottawa, ON, Canada.
[Walde, David] Sault Area Hosp, Algoma Dist Canc Program, Sault Ste Marie, ON, Canada.
[Vandenberg, Ted A.] London Reg Canc Program, London, ON, Canada.
[Findlay, Brian] Niagara Hlth Syst, St Catharines, ON, Canada.
[Whelan, Timothy J.] McMaster Univ, Hamilton, ON, Canada.
[Norris, Brian D.] British Columbia Canc Agcy, Surrey, BC, Canada.
[O'Reilly, Susan E.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Cantin, Jacques] Univ Montreal, Ctr Hosp, Hotel Dieu, Montreal, PQ H3C 3J7, Canada.
[Piura, Ettie; Pollak, Michael N.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada.
[Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Pritchard, KI (reprint author), Sunnybrook Odette Canc Ctr, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada.
EM kathy.pritchard@sunnybrook.ca
RI Pollak, Michael/G-9094-2011; Whelan, Timothy/D-3185-2017; Pritchard,
Kathleen/I-2184-2014
OI Pollak, Michael/0000-0003-3047-0604; Pritchard,
Kathleen/0000-0003-0758-9666
FU Canadian Cancer Society Research Institute [16512]; Novartis
Pharmaceuticals Canada; Israel Cancer Research Fund; Ted A. Vandenberg;
GlaxoSmithKline Expert Testimony: Kathleen I. Pritchard; Novartis;
AstraZeneca
FX Supported by Grant No. 16512 from Canadian Cancer Society Research
Institute (M.N.P); a grant from Novartis Pharmaceuticals Canada
(M.N.P.); and a fellowship from the Israel Cancer Research Fund (E.P.).;
Employment or Leadership Position: None Consultant or Advisory Role:
Kathleen I. Pritchard, Roche (C), Novartis (C), AstraZeneca (C), Abraxis
BioScience (C), Boehringer Ingelheim (C); Ted A. Vandenberg, Novartis
(C), Abraxis BioScience (C), GlaxoSmithKline (C) Stock Ownership: None
Honoraria: Kathleen I. Pritchard, Roche, Novartis, Abraxis BioScience,
AstraZeneca, Boehringer Ingelheim; Paul E. Goss, Novartis; Ted A.
Vandenberg, GlaxoSmithKline, Roche; Brian Findlay, Novartis Research
Funding: Ted A. Vandenberg, GlaxoSmithKline Expert Testimony: Kathleen
I. Pritchard, Novartis (U), AstraZeneca (U) Other Remuneration: None
NR 29
TC 56
Z9 57
U1 0
U2 4
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 10
PY 2011
VL 29
IS 29
BP 3869
EP 3876
DI 10.1200/JCO.2010.33.7006
PG 8
WC Oncology
SC Oncology
GA 833LE
UT WOS:000295886200010
PM 21911723
ER
PT J
AU Arvold, ND
Taghian, AG
Niemierko, A
Raad, RFA
Sreedhara, M
Nguyen, PL
Bellon, JR
Wong, JS
Smith, BL
Harris, JR
AF Arvold, Nils D.
Taghian, Alphonse G.
Niemierko, Andrzej
Raad, Rita F. Abi
Sreedhara, Meera
Nguyen, Paul L.
Bellon, Jennifer R.
Wong, Julia S.
Smith, Barbara L.
Harris, Jay R.
TI Age, Breast Cancer Subtype Approximation, and Local Recurrence After
Breast-Conserving Therapy
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID COMPARING TOTAL MASTECTOMY; SURGICAL ADJUVANT BREAST; 20-YEAR FOLLOW-UP;
TUMOR RECURRENCE; STAGE-I; YOUNG-WOMEN; CONSERVATION THERAPY;
RADIATION-THERAPY; RANDOMIZED-TRIAL; CLINICAL IMPLICATIONS
AB Purpose Prior results of breast-conserving therapy (BCT) have shown substantial rates of local recurrence (LR) in young patients with breast cancer (BC).
Patients and Methods We studied 1,434 consecutive patients with invasive BC who received BCT from December 1997 to July 2006. Ninety-one percent received adjuvant systemic therapy; no patients received trastuzumab. Five BC subtypes were approximated: estrogen receptor (ER) or progesterone receptor (PR) positive, HER2 negative, and grades 1 to 2 (ie, luminal A); ER positive or PR positive, HER2 negative, and grade 3 (ie, luminal B); ER or PR positive, and HER2 positive (ie, luminal HER2); ER negative, PR negative, and HER2 positive (ie, HER2); and ER negative, PR negative, and HER2 negative (ie, triple negative). Actuarial rates of LR were calculated by using the Kaplan-Meier method.
Results Median follow-up was 85 months. Overall 5-year cumulative incidence of LR was 2.1% (95% CI, 1.4% to 3.0%). The 5-year cumulative incidence of LR was 5.0% (95% CI, 3.0% to 8.3%) for age quartile 23 to 46 years; 2.2% (95% CI, 1.0% to 4.6%) for ages 47 to 54 years; 0.9% (95% CI, 0.3% to 2.6%) for ages 55 to 63 years; and 0.6% (95% CI, 0.1% to 2.2%) for ages 64 to 88 years. The 5-year cumulative incidence of LR was 0.8% (95% CI, 0.4% to 1.8%) for luminal A; 2.3% (95% CI, 0.8% to 5.9%) for luminal B; 1.1% (95% CI, 0.2% 7.4%) for luminal HER2; 10.8% (95% CI, 4.6% to 24.4%) for HER2; and 6.7% (95% CI, 3.6% to 12.2%) for triple negative. On multivariable analysis, increasing age was associated with decreased risk of LR (adjusted hazard ratio, 0.97; 95% CI, 0.94 to 0.99; P = .009).
Conclusion In the era of systemic therapy and BC subtyping, age remains an independent prognostic factor after BCT. However, the risk of LR for young women appears acceptably low.
C1 [Arvold, Nils D.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA.
[Taghian, Alphonse G.; Niemierko, Andrzej; Raad, Rita F. Abi; Smith, Barbara L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Harris, Jay R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA.
[Sreedhara, Meera; Nguyen, Paul L.; Bellon, Jennifer R.; Wong, Julia S.; Harris, Jay R.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Harris, JR (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Dana 1622,450 Brookline Ave, Boston, MA 02215 USA.
EM jharris@lroc.harvard.edu
FU National Cancer Institute [R01CA139118, P50CA089393]; Jane Mailloux
Research Fund; Blanche Montesi Fund; Tim Levy Fund for breast cancer
research
FX Supported in part by award No. R01CA139118 (A.G.T.) and award No.
P50CA089393 (A.G.T.) from the National Cancer Institute; also supported
in part by the Jane Mailloux Research Fund, the Blanche Montesi Fund,
and the Tim Levy Fund for breast cancer research.
NR 63
TC 151
Z9 159
U1 1
U2 11
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 10
PY 2011
VL 29
IS 29
BP 3885
EP 3891
DI 10.1200/JCO.2011.36.1105
PG 7
WC Oncology
SC Oncology
GA 833LE
UT WOS:000295886200012
PM 21900114
ER
PT J
AU Griggs, JJ
Somerfield, MR
Anderson, H
Henry, NL
Hudis, CA
Khatcheressian, JL
Partridge, AH
Prestrud, AA
Davidson, NE
AF Griggs, Jennifer J.
Somerfield, Mark R.
Anderson, Holly
Henry, N. Lynn
Hudis, Clifford A.
Khatcheressian, James L.
Partridge, Ann H.
Prestrud, Ann Alexis
Davidson, Nancy E.
TI American Society of Clinical Oncology Endorsement of the Cancer Care
Ontario Practice Guideline on Adjuvant Ovarian Ablation in the Treatment
of Premenopausal Women With Early-Stage Invasive Breast Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ESTRADIOL; PLASMA
AB Purpose The American Society of Clinical Oncology (ASCO) has policies and procedures for endorsing practice guidelines that have been developed by other professional organizations.
Methods The Cancer Care Ontario (CCO) Guideline on Adjuvant Ovarian Ablation (OA) in the Treatment of Premenopausal Women With Early-Stage Invasive Breast Cancer was reviewed for developmental rigor by methodologists. An ad hoc review panel of experts reviewed the content.
Results The ASCO ad hoc OA guideline review panel concurred that the recommendations are clear, thorough, based on the most relevant scientific evidence in this content area, and present options that will be acceptable to patients. According to the CCO guideline: one, OA should not be routinely added to systemic therapy with chemotherapy, tamoxifen, or the combination of tamoxifen and chemotherapy; two, OA alone is not recommended as an alternative to any other form of systemic therapy, except in the specific case of patients who are candidates for other forms of systemic therapy but who, for some reason, will not receive any other systemic therapy (eg, patients who cannot tolerate other forms of systemic therapy or patients who choose no other form of systemic therapy); and three, when chemical suppression using luteinizing hormone-releasing hormone agonists is the chosen method of OA, in the opinion of the Breast Cancer Disease Site Group, monthly injection is the recommended mode of administration. The mode of administration in nearly all of the available trials has been monthly administration.
Conclusion The ASCO review panel agrees with the recommendations as stated in the CCO guideline, with the qualification that ongoing research studies may alter the recommendations of the panel.
C1 [Griggs, Jennifer J.; Henry, N. Lynn] Univ Michigan Hlth Syst, Ann Arbor, MI USA.
[Griggs, Jennifer J.; Somerfield, Mark R.; Prestrud, Ann Alexis] Amer Soc Clin Oncol, Alexandria, VA 22314 USA.
[Khatcheressian, James L.] Virginia Canc Inst, Richmond, VA USA.
[Anderson, Holly] Breast Canc Coalit Rochester, Rochester, MN USA.
[Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Davidson, Nancy E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
RP Griggs, JJ (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA.
EM guidelines@asco.org
FU AstraZeneca
FX Employment or Leadership Position: None Consultant or Advisory Role:
None Stock Ownership: None Honoraria: None Research Funding: N. Lynn
Henry, AstraZeneca Expert Testimony: None Other Remuneration: None
NR 7
TC 35
Z9 36
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 10
PY 2011
VL 29
IS 29
BP 3939
EP 3942
DI 10.1200/JCO.2011.36.4950
PG 4
WC Oncology
SC Oncology
GA 833LE
UT WOS:000295886200020
PM 21900112
ER
PT J
AU Galsky, MD
Hahn, NM
Rosenberg, J
AF Galsky, Matthew D.
Hahn, Noah M.
Rosenberg, Jonathan
TI Reply to O. Dizdar et al
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID CHEMOTHERAPY; CISPLATIN
C1 [Galsky, Matthew D.] Mt Sinai Sch Med, New York, NY USA.
[Hahn, Noah M.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA.
[Rosenberg, Jonathan] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Galsky, MD (reprint author), Mt Sinai Sch Med, New York, NY USA.
NR 7
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 10
PY 2011
VL 29
IS 29
BP 3945
EP 3946
DI 10.1200/JCO.2011.37.8117
PG 2
WC Oncology
SC Oncology
GA 833LE
UT WOS:000295886200025
ER
PT J
AU Arvold, ND
Hsu, L
Chen, WY
Benzaquen, LR
Weiss, SE
AF Arvold, Nils D.
Hsu, Liangge
Chen, Wendy Y.
Benzaquen, Laura R.
Weiss, Stephanie E.
TI Marantic Endocarditis With Cardioembolic Strokes Mimicking
Leptomeningeal Metastases in Breast Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID NONBACTERIAL THROMBOTIC ENDOCARDITIS; CEREBROSPINAL-FLUID CYTOLOGY;
TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CLINICOPATHOLOGIC CORRELATIONS;
DIAGNOSIS; EMBOLISM; AUTOPSY; SYSTEM; ERA
C1 [Arvold, Nils D.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA.
[Hsu, Liangge; Benzaquen, Laura R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Chen, Wendy Y.; Weiss, Stephanie E.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
RP Arvold, ND (reprint author), Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA.
NR 24
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 10
PY 2011
VL 29
IS 29
BP E743
EP E746
DI 10.1200/JCO.2011.36.4190
PG 4
WC Oncology
SC Oncology
GA 833LE
UT WOS:000295886200001
PM 21788555
ER
PT J
AU O'Hare, AM
Choi, AI
Boscardin, WJ
Clinton, WL
Zawadzki, I
Hebert, PL
Tamura, MK
Taylor, L
Larson, EB
AF O'Hare, Ann M.
Choi, Andy I.
Boscardin, W. John
Clinton, Walter L.
Zawadzki, Ilan
Hebert, Paul L.
Tamura, Manjula Kurella
Taylor, Leslie
Larson, Eric B.
TI LESS IS MORE Trends in Timing of Initiation of Chronic Dialysis in the
United States
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; SURVIVAL; VALIDATION; MORTALITY; HARMFUL; GFR;
AGE
AB Background: During the past decade, a trend has been observed in the United States toward initiation of chronic dialysis at higher levels of estimated glomerular filtration rate. This likely reflects secular trends in the composition of the dialysis population and a tendency toward initiation of dialysis earlier in the course of kidney disease.
Methods: The goal of this study was to generate model-based estimates of the magnitude of changes in the timing of dialysis initiation between 1997 and 2007. We used information from a national registry for end-stage renal disease on estimated glomerular filtration rate at initiation among patients who received their first chronic dialysis treatment in 1997 or 2007. We used information regarding predialysis estimated glomerular filtration rate slope from an integrated health care system.
Results: After accounting for changes in the characteristics of new US dialysis patients from 1997 to 2007, we estimate that chronic dialysis was initiated a mean of 147 days earlier (95% confidence interval, 134-160) in the later compared with the earlier year. Differences in timing were consistent across a range of patient subgroups but were most pronounced for those aged 75 years or older; the mean difference in timing in that subgroup was 233 days (95% confidence interval, 206-267).
Conclusions: Chronic dialysis appears to have been initiated substantially earlier in the course of kidney disease in 2007 compared with 1997. In the absence of strong evidence to suggest that earlier initiation of chronic dialysis is beneficial, these findings call for careful evaluation of contemporary dialysis initiation practices in the United States.
C1 [O'Hare, Ann M.] Univ Washington, Dept Med, Seattle, WA USA.
[Hebert, Paul L.] Univ Washington, Dept Hlth Sci, Seattle, WA USA.
[O'Hare, Ann M.] Vet Affairs VA Med Ctr, Seattle, WA USA.
[O'Hare, Ann M.] Renal Dialysis Unit, Seattle, WA USA.
[Hebert, Paul L.; Taylor, Leslie] VA Puget Sound Healthcare Syst, VA Hlth Serv, Res & Dev Ctr Excellence, Seattle, WA USA.
[O'Hare, Ann M.; Clinton, Walter L.; Zawadzki, Ilan; Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Seattle, WA USA.
[O'Hare, Ann M.; Clinton, Walter L.; Zawadzki, Ilan; Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA USA.
[Choi, Andy I.; Boscardin, W. John] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Choi, Andy I.; Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Tamura, Manjula Kurella] Stanford Univ, Dept Med, San Francisco, CA USA.
[Tamura, Manjula Kurella] VA Palo Alto Healthcare Syst, San Francisco, CA USA.
[Choi, Andy I.] VA Med Ctr, VA No Calif Healthcare Syst, San Francisco, CA USA.
RP O'Hare, AM (reprint author), Vet Affairs Med Ctr, Renal Dialysis Unit, 1660 S Columbian Way, Seattle, WA 98109 USA.
EM ann.ohare@va.gov
RI Kurella Tamura, Manjula/C-8284-2014
OI Kurella Tamura, Manjula/0000-0001-5227-2479
FU American Federation for Aging Research [K23DK080645, K23AG028952];
National Institute on Aging; National Institutes of Health; Beeson
Career Development Award [K23AG28980]
FX Dr O'Hare serves as the principal investigator for an interagency
agreement between the Centers for Disease Control and Prevention and the
Veterans Affairs Puget Sound Healthcare System. Within the past year,
she has received royalties from UpToDate, Inc. Dr Choi was supported by
grant K23DK080645 and Dr Kurella Tamura was supported by grant
K23AG028952 (a Paul B. Beeson Career Development Award) from the
American Federation for Aging Research and the National Institute on
Aging. Dr Larson has received research support from the National
Institutes of Health; royalties from UpToDate, Inc; Springer Publishing
Company; and Elsevier BV; and speaker honoraria from universities and
other nonprofit organizations.; This study was supported by Beeson
Career Development Award K23AG28980 (principal investigator: Dr O'Hare).
NR 32
TC 28
Z9 28
U1 0
U2 2
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 OCT 10
PY 2011
VL 171
IS 18
BP 1663
EP 1669
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 830YL
UT WOS:000295695600012
PM 21987197
ER
PT J
AU Levy, DE
Kang, R
Vogeli, CS
Rigotti, NA
AF Levy, Douglas E.
Kang, Raymond
Vogeli, Christine S.
Rigotti, Nancy A.
TI Smoking Cessation Advice Rates in US Hospitals
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Levy, Douglas E.; Vogeli, Christine S.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
[Levy, Douglas E.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, Boston, MA 02114 USA.
[Levy, Douglas E.; Vogeli, Christine S.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Kang, Raymond] Northwestern Univ, Inst Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Levy, DE (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM dlevy3@partners.org
NR 7
TC 6
Z9 6
U1 0
U2 2
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 OCT 10
PY 2011
VL 171
IS 18
BP 1682
EP 1684
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 830YL
UT WOS:000295695600020
PM 21987201
ER
PT J
AU Yeh, GY
Forman, DE
Stevenson, LW
Wood, MJ
Wayne, PM
McCarthy, EP
Davis, RB
Phillips, RS
AF Yeh, Gloria Y.
Forman, Daniel E.
Stevenson, Lynne Warner
Wood, Malissa J.
Wayne, Peter Michael
McCarthy, Ellen P.
Davis, Roger B.
Phillips, Russell S.
TI Yin and Yang of Tai Chi Exercise reply
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Yeh, Gloria Y.; Wayne, Peter Michael; McCarthy, Ellen P.; Davis, Roger B.; Phillips, Russell S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care,Dept Med, Brookline, MA 02446 USA.
[Yeh, Gloria Y.; Wayne, Peter Michael; Davis, Roger B.; Phillips, Russell S.] Harvard Univ, Sch Med, Div Res & Educ Complementary & Integrat Med Thera, Brookline, MA 02446 USA.
[Forman, Daniel E.; Stevenson, Lynne Warner] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA.
[Wood, Malissa J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
RP Yeh, GY (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care,Dept Med, 1309 Beacon St,2nd Floor, Brookline, MA 02446 USA.
EM gloria_yeh@hms.harvard.edu
NR 4
TC 0
Z9 0
U1 1
U2 5
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 OCT 10
PY 2011
VL 171
IS 18
BP 1685
EP 1686
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 830YL
UT WOS:000295695600024
ER
PT J
AU Etchegaray, JP
Mostoslavsky, R
AF Etchegaray, Jean-Pierre
Mostoslavsky, Raul
TI eNERgizing Pluripotent Gene Transcription
SO CELL STEM CELL
LA English
DT Editorial Material
ID STEM-CELLS; REPAIR; TFIIH; NANOG
C1 [Etchegaray, Jean-Pierre; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
RP Mostoslavsky, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
EM rmostoslavsky@mgh.harvard.edu
NR 10
TC 3
Z9 3
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD OCT 7
PY 2011
VL 9
IS 4
BP 285
EP 286
DI 10.1016/j.stem.2011.09.004
PG 2
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 835MT
UT WOS:000296041200002
PM 21982224
ER
PT J
AU Arnold, K
Sarkar, A
Yram, MA
Polo, JM
Bronson, R
Sengupta, S
Seandel, M
Geijsen, N
Hochedlinger, K
AF Arnold, Katrin
Sarkar, Abby
Yram, Mary Anna
Polo, Jose M.
Bronson, Rod
Sengupta, Sumitra
Seandel, Marco
Geijsen, Niels
Hochedlinger, Konrad
TI Sox2(+) Adult Stem and Progenitor Cells Are Important for Tissue
Regeneration and Survival of Mice
SO CELL STEM CELL
LA English
DT Article
ID SELF-RENEWAL; IN-VITRO; EXPRESSION; MARKER; DIFFERENTIATION; INDUCTION;
SPERMATOGENESIS; IDENTIFICATION; PLURIPOTENCY; MULTIPOTENT
AB The transcription factor Sox2 maintains the pluripotency of early embryonic cells and regulates the formation of several epithelia during fetal development. Whether Sox2 continues to play a role in adult tissues remains largely unknown. We show here that Sox2 marks adult cells in several epithelial tissues where its expression has not previously been characterized, including the stomach, cervix, anus, testes, lens, and multiple glands. Genetic lineage tracing and transplantation experiments demonstrate that Sox2-expressing cells continuously give rise to mature cell types within these tissues, documenting their self-renewal and differentiation potentials. Consistent with these findings, ablation of Sox2(+) cells in mice results in a disruption of epithelial tissue homeostasis and lethality. Developmental fate mapping reveals that Sox2(+) adult stem cells originate from fetal Sox2(+) tissue progenitors. Thus, our results identify Sox2 expression in numerous adult endodermal and ectodermal stem cell compartments, which are critical for normal tissue regeneration and survival.
C1 [Arnold, Katrin; Sarkar, Abby; Yram, Mary Anna; Polo, Jose M.; Hochedlinger, Konrad] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
[Arnold, Katrin; Sarkar, Abby; Yram, Mary Anna; Polo, Jose M.; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Arnold, Katrin; Sarkar, Abby; Yram, Mary Anna; Polo, Jose M.; Hochedlinger, Konrad] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Arnold, Katrin; Sarkar, Abby; Yram, Mary Anna; Polo, Jose M.; Geijsen, Niels; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Arnold, Katrin; Sarkar, Abby; Yram, Mary Anna; Polo, Jose M.; Geijsen, Niels; Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA 02114 USA.
[Arnold, Katrin; Sarkar, Abby; Yram, Mary Anna; Polo, Jose M.; Geijsen, Niels; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Bronson, Rod] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA.
[Sengupta, Sumitra; Seandel, Marco] Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA.
RP Hochedlinger, K (reprint author), Harvard Univ, Howard Hughes Med Inst, 7 Divin Ave, Cambridge, MA 02138 USA.
EM khochedlinger@helix.mgh.harvard.edu
FU Harvard Stem Cell Institute; NIH [R01HD058013-01A1]; Kimmel Foundation
for Cancer Research; V Foundation for Cancer Research; MGH
FX We thank Laura Prickett-Rice and Kat Folz-Donahoe for assistance with
FACS, and Markus Schober, Nimet Maherali, and Matthias Stadtfeld for
helpful discussions and critical reading of the manuscript. K.A. and
K.H. were supported by a Seed Grant from the Harvard Stem Cell
Institute. Additional support to K.H. was from the NIH Director's
Innovator Award R01HD058013-01A1, the Kimmel and V Foundations for
Cancer Research, and MGH startup funds.
NR 46
TC 211
Z9 218
U1 2
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD OCT 7
PY 2011
VL 9
IS 4
BP 317
EP 329
DI 10.1016/j.stem.2011.09.001
PG 13
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 835MT
UT WOS:000296041200010
PM 21982232
ER
PT J
AU Wilkinson, K
Boyd, JD
Glicksman, M
Moore, KJ
El Khoury, J
AF Wilkinson, Kim
Boyd, Justin D.
Glicksman, Marcie
Moore, Kathryn J.
El Khoury, Joseph
TI A High Content Drug Screen Identifies Ursolic Acid as an Inhibitor of
Amyloid beta Protein Interactions with Its Receptor CD36
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ALZHEIMERS-DISEASE; SCAVENGER RECEPTOR; HUMAN BRAIN; CLASS-B;
INFLAMMATION; MICROGLIA; ASTROCYTES; EXPRESSION; MIGRATION; FIBRILS
AB A pathological hallmark of Alzheimer disease (AD) is deposition of amyloid beta (A beta) in the brain. A beta binds to microglia via a receptor complex that includes CD36 leading to production of proinflammatory cytokines and neurotoxic reactive oxygen species and subsequent neurodegeneration. Interruption of A beta binding to CD36 is a potential therapeutic strategy for AD. To identify pharmacologic inhibitors of A beta binding to CD36, we developed a 384-well plate assay for binding of fluorescently labeled A beta to Chinese hamster ovary cells stably expressing human CD36 (CHO-CD36) and screened an Food and Drug Administration-approved compound library. The assay was optimized based on the cells' tolerance to dimethyl sulfoxide, A beta concentration, time required for A beta binding, reproducibility, and signal-to-background ratio. Using this assay, we identified four compounds as potential inhibitors of A beta binding to CD36. These compounds were ursolic acid, ellipticine, zoxazolamine, and homomoschatoline. Of these compounds, only ursolic acid, a naturally occurring pentacyclic triterpenoid, successfully inhibited binding of A beta to CHO-CD36 cells in a dose-dependent manner. The ursolic acid effect reached a plateau at similar to 20 mu M, with a maximal inhibition of 64%. Ursolic acid also blocked binding of A beta to microglial cells and subsequent ROS production. Our data indicate that cell-based high-content screening of small molecule libraries for their ability to block binding of A beta to its receptors is a useful tool to identify novel inhibitors of receptors involved in AD pathogenesis. Our data also suggest that ursolic acid is a potential therapeutic agent for AD via its ability to block A beta-CD36 interactions.
C1 [Wilkinson, Kim; El Khoury, Joseph] Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
[Boyd, Justin D.; Glicksman, Marcie] Brigham & Womens Hosp, Lab Drug Discovery Neurodegenerat, Boston, MA 02139 USA.
[Moore, Kathryn J.] NYU, Leon H Charney Div Cardiol, Dept Med, Med Ctr, New York, NY 10016 USA.
RP El Khoury, J (reprint author), Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
EM jelkhoury@partners.org
OI Moore, kathryn/0000-0003-2505-2547
FU National Institutes of Health through NINDS [NS059005]; National
Institutes of Health through NIAID [AI U24AI082660]; National Institutes
of Health through NIA [AG032349, AG020255]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants NS059005 through the NINDS and AI U24AI082660 through the
NIAID (to J. E. K.), AG032349 through the NIA (to J. E. K. and K. J.
M.), and AG020255 through the NIA (to K. J. M.).
NR 24
TC 34
Z9 34
U1 0
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 OCT 7
PY 2011
VL 286
IS 40
BP 34914
EP 34922
DI 10.1074/jbc.M111.232116
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 827DD
UT WOS:000295406300045
PM 21835916
ER
PT J
AU Shinozaki, S
Choi, CS
Shimizu, N
Yamada, M
Kim, M
Zhang, T
Dong, HH
Kim, YB
Kaneki, M
AF Shinozaki, Shohei
Choi, Cheol Soo
Shimizu, Nobuyuki
Yamada, Marina
Kim, Minhye
Zhang, Ting
Dong, H. Henry
Kim, Young-Bum
Kaneki, Masao
TI Liver-specific Inducible Nitric-oxide Synthase Expression Is Sufficient
to Cause Hepatic Insulin Resistance and Mild Hyperglycemia in Mice
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; SKELETAL-MUSCLE CELLS; AKT/PROTEIN
KINASE-B; S-NITROSYLATION; FASTING HYPERGLYCEMIA; RECEPTOR SUBSTRATE-1;
POSSIBLE INVOLVEMENT; MAMMALIAN TARGET; GENE-EXPRESSION; OB/OB MICE
AB Inducible nitric-oxide synthase (iNOS), a major mediator of inflammation, plays an important role in obesity-induced insulin resistance. Inhibition of iNOS by gene disruption or pharmacological inhibitors reverses or ameliorates obesity-induced insulin resistance in skeletal muscle and liver in mice. It is unknown, however, whether increased expression of iNOS is sufficient to cause insulin resistance in vivo. To address this issue, we generated liver-specific iNOS transgenic (L-iNOS-Tg) mice, where expression of the transgene, iNOS, is regulated under mouse albumin promoter. L-iNOS-Tg mice exhibited mild hyperglycemia, hyperinsulinemia, insulin resistance, and impaired insulin-induced suppression of hepatic glucose output, as compared with wild type (WT) littermates. Insulin-stimulated phosphorylation of insulin receptor substrate-1 (IRS-1) and -2, and Akt was significantly attenuated in liver, but not in skeletal muscle, of L-iNOS-Tg mice relative to WT mice without changes in insulin receptor phosphorylation. Moreover, liver-specific iNOS expression abrogated insulin-stimulated phosphorylation of glycogen synthase kinase-3 beta, forkhead box O1, and mTOR (mammalian target of rapamycin), endogenous substrates of Akt, along with increased S-nitrosylation of Akt relative to WT mice. However, the expression of insulin receptor, IRS-1, IRS-2, Akt, glycogen synthase kinase-3 beta, forkhead box O1, protein-tyrosine phosphatase-1B, PTEN (phosphatase and tensin homolog), and p85 phosphatidylinositol 3-kinase was not altered by iNOS transgene. Hyperglycemia was associated with elevated glycogen phosphorylase activity and decreased glycogen synthase activity in the liver of L-iNOS-Tg mice, whereas phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and proliferator-activated receptor gamma coactivator-1 alpha expression were not altered. These results clearly indicate that selective expression of iNOS in liver causes hepatic insulin resistance along with deranged insulin signaling, leading to hyperglycemia and hyperinsulinemia. Our data highlight a critical role for iNOS in the development of hepatic insulin resistance and hyperglycemia.
C1 [Shinozaki, Shohei; Shimizu, Nobuyuki; Yamada, Marina; Kim, Minhye; Kaneki, Masao] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp,Shriners Hosp Children, Charlestown, MA 02129 USA.
[Choi, Cheol Soo] Gachon Univ Med & Sci, Dept Internal Med, Inchon 406840, South Korea.
[Choi, Cheol Soo] Gachon Univ Med & Sci, Lee Gil Ya Canc & Diabet Inst, Inchon 406840, South Korea.
[Zhang, Ting; Dong, H. Henry] Univ Pittsburgh, Med Ctr, Div Immunogenet, Rangos Res Ctr,Childrens Hosp Pittsburgh, Pittsburgh, PA 15224 USA.
[Kim, Young-Bum] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
[Kim, Young-Bum] Harvard Univ, Sch Med, Boston, MA 02215 USA.
RP Kaneki, M (reprint author), 149 13th St,Rm 6604, Charlestown, MA 02129 USA.
EM mkaneki@helix.mgh.harvard.edu
RI Zhang, Ting/J-5074-2015;
OI Dong, H. Henry/0000-0003-0279-5241
FU National Institutes of Health [R01DK05827, R01DK066301]; American
Diabetes Association [7-08-RA-77, 109-RA-87]; Korea Healthcare
Technology R&D Project, Republic of Korea [A084651]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01DK05827 (to M. K.) and R01DK066301 (to H. H. D.). This
work was also supported by American Diabetes Association Grants
7-08-RA-77 (to Y.-B. K.) and 1-09-RA-87 (to H. H. D.), and Korea
Healthcare Technology R&D Project, Republic of Korea Grant A084651 (to
C. S. C.).
NR 50
TC 27
Z9 28
U1 1
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 7
PY 2011
VL 286
IS 40
BP 34959
EP 34975
DI 10.1074/jbc.M110.187666
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 827DD
UT WOS:000295406300050
PM 21846719
ER
PT J
AU Eng, ET
Smagghe, BJ
Walz, T
Springer, TA
AF Eng, Edward T.
Smagghe, Benoit J.
Walz, Thomas
Springer, Timothy A.
TI Intact alpha(IIb)beta(3) Integrin Is Extended after Activation as
Measured by Solution X-ray Scattering and Electron Microscopy
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GLYCOPROTEIN-IIB; STRUCTURAL BASIS; CONFORMATIONAL REGULATION;
CRYSTAL-STRUCTURE; CELL-ADHESION; BINDING-SITE; OUTSIDE-IN; COMPLEX;
LIGAND; DOMAIN
AB Integrins are bidirectional signaling molecules on the cell surface that have fundamental roles in regulating cell behavior and contribute to cell migration and adhesion. Understanding of the mechanism of integrin signaling and activation has been advanced with truncated ectodomain preparations; however, the nature of conformational change in the full-length intact integrin molecule remains an active area of research. Here we used small angle x-ray scattering and electron microscopy to study detergent-solubilized, intact platelet integrin alpha(IIb)beta(3). In the resting state, the intact alpha(IIb)beta(3) adopted a compact, bent conformation. Upon activation with Mn2+, the average integrin extension increased. Further activation by addition of ligand led to stabilization of the extended state and opening of the headpiece. The observed extension and conformational rearrangement upon activation are consistent with the extension and headpiece opening model of integrin activation.
C1 [Eng, Edward T.; Smagghe, Benoit J.; Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst,CLSB, Boston, MA 02115 USA.
[Eng, Edward T.; Smagghe, Benoit J.; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Walz, Thomas] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
RP Springer, TA (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst,CLSB, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA.
EM springer@idi.harvard.edu
FU National Institutes of Health [HL103526]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant HL103526.
NR 50
TC 27
Z9 27
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 7
PY 2011
VL 286
IS 40
BP 35218
EP 35226
DI 10.1074/jbc.M111.275107
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 827DD
UT WOS:000295406300074
PM 21832081
ER
PT J
AU Abu Dayyeh, BK
Gupta, N
Sherman, KE
de Bakker, PIW
Chung, RT
AF Abu Dayyeh, Barham K.
Gupta, Namrata
Sherman, Kenneth E.
de Bakker, Paul I. W.
Chung, Raymond T.
CA Aids Clinical Trials Grp A5178
TI IL28B Alleles Exert an Additive Dose Effect When Applied to HCV-HIV
Coinfected Persons Undergoing Peginterferon and Ribavirin Therapy
SO PLOS ONE
LA English
DT Article
ID HEPATITIS-C-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; SUSTAINED VIROLOGICAL
RESPONSE; INTERFERON PLUS RIBAVIRIN; AMINO-ACID SUBSTITUTIONS;
COMBINATION THERAPY; INFECTED PATIENTS; GENETIC-VARIATION;
LIVER-DISEASE; GENOTYPE 1B
AB Background: Genetic studies have demonstrated a strong association between single nucleotide polymorphisms (SNPs) at IL28B and response to treatment with peginterferon (PEG) and ribavirin (RBV) in HCV monoinfected persons. We sought to test these associations in a prospective PEG / weight based ribavirin (WBR) treatment trial (ACTG A5178) (National Institution of Health registration number NCT00078403) in persons with HCV-HIV coinfection, and to develop a prediction score.
Methods: We selected subjects enrolled in A5178 who completed at least the first 12 weeks of the trial and had DNA available, and genotyped three SNPs at IL28B (rs12979860, rs12980275, rs8099917). We used multivariate logistic regression analysis to evaluate the association between IL28B SNPs and HCV treatment outcomes and to develop the prediction score.
Results: 231 HCV/HIV coinfected subjects were included. We observed a strong association between IL28B genotype and response to therapy among those with genotypes 1 or 4 (odds ratio for complete early virologic responses (cEVR) and sustained virologic response (SVR) was 2.98 [1.7-5.3] and 3.4 [1.7-6.9], respectively, for each additional copy of the C allele of rs12979860). Differences in frequency of the responder allele explained some of the discrepancy in HCV treatment outcomes between blacks and whites. A simple pretreatment prediction score that incorporates the IL28B genotype and baseline HCV viral load has a 93% negative predictive value (NPV) for SVR.
Conclusions: IL28B SNPs have an additive allele dose effect in predicting HCV treatment outcomes in HCV/HIV coinfected persons and can be incorporated into a simple pretreatment prediction score that could minimize the risk of exposure to PEG/RBV therapy for persons with unfavorable scores.
C1 [Abu Dayyeh, Barham K.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Abu Dayyeh, Barham K.; Chung, Raymond T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Gupta, Namrata; de Bakker, Paul I. W.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Sherman, Kenneth E.] Univ Cincinnati, Dept Internal Med, Cincinnati, OH USA.
[de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA.
[de Bakker, Paul I. W.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[de Bakker, Paul I. W.] Univ Med Ctr, Dept Med Genet, Div Biomed Genet, Utrecht, Netherlands.
RP Abu Dayyeh, BK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
EM rtchung@partners.org
RI de Bakker, Paul/B-8730-2009
OI de Bakker, Paul/0000-0001-7735-7858
FU National Institute of Health [K27 5K24DK078772-04]
FX This work was supported by the National Institute of Health [K27
5K24DK078772-04 to R.T.C.]. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 41
TC 1
Z9 2
U1 0
U2 0
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 OCT 7
PY 2011
VL 6
IS 10
AR e25753
DI 10.1371/journal.pone.0025753
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834OC
UT WOS:000295970300026
ER
PT J
AU Ayrapetov, MK
Xu, C
Sun, YL
Zhu, KY
Parmar, K
D'Andrea, AD
Price, BD
AF Ayrapetov, Marina K.
Xu, Chang
Sun, Yingli
Zhu, Kaya
Parmar, Kalindi
D'Andrea, Alan D.
Price, Brendan D.
TI Activation of Hif1 alpha by the Prolylhydroxylase Inhibitor
Dimethyoxalyglycine Decreases Radiosensitivity
SO PLOS ONE
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTOR; PROLYL HYDROXYLASE INHIBITORS;
GENE-EXPRESSION; DNA-DAMAGE; PROLINE HYDROXYLATION; HISTONE
DEMETHYLASES; HUMAN CANCERS; JMJD2 FAMILY; TUMOR-GROWTH; GAMMA-RAYS
AB Hypoxia inducible factor 1 alpha (Hif1 alpha) is a stress responsive transcription factor, which regulates the expression of genes required for adaption to hypoxia. Hif1 alpha is normally hydroxylated by an oxygen-dependent prolylhydroxylase, leading to degradation and clearance of Hif1 alpha from the cell. Under hypoxic conditions, the activity of the prolylhydroxylase is reduced and Hif1 alpha accumulates. Hif1 alpha is also constitutively expressed in tumor cells, where it is associated with resistance to ionizing radiation. Activation of the Hif1 alpha transcriptional regulatory pathway may therefore function to protect normal cells from DNA damage caused by ionizing radiation. Here, we utilized the prolylhydroxylase inhibitor dimethyloxalylglycine (DMOG) to elevate Hif1 alpha levels in mouse embryonic fibroblasts (MEFs) to determine if DMOG could function as a radioprotector. The results demonstrate that DMOG increased Hif1 alpha protein levels and decreased the sensitivity of MEFs to ionizing radiation. Further, the ability of DMOG to function as a radioprotector required Hif1 alpha, indicating a key role for Hif1 alpha's transcriptional activity. DMOG also induced the Hif1 alpha-dependent accumulation of several DNA damage response proteins, including CHD4 and MTA3 (sub-units of the NuRD deacetylase complex) and the Suv39h1 histone H3 methyltransferase. Depletion of Suv39h1, but not CHD4 or MTA3, reduced the ability of DMOG to protect cells from radiation damage, implicating increased histone H3 methylation in the radioprotection of cells. Finally, treatment of mice with DMOG prior to total body irradiation resulted in significant radioprotection of the mice, demonstrating the utility of DMOG and related prolylhydroxylase inhibitors to protect whole organisms from ionizing radiation. Activation of Hif1a through prolylhydroxylase inhibition therefore identifies a new pathway for the development of novel radiation protectors.
C1 [Ayrapetov, Marina K.; Xu, Chang; Zhu, Kaya; Parmar, Kalindi; D'Andrea, Alan D.; Price, Brendan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02115 USA.
[Sun, Yingli] Chinese Acad Sci, Beijing Inst Genom, Dis Genom & Individualized Med Key Lab, Beijing, Peoples R China.
RP Ayrapetov, MK (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 sunyl@big.ac.cn; kalindi_parmar@dfci.harvard.edu;
brendan_price@dfci.harvard.edu
FU National Cancer Institute (NCI) [CA64585, CA93602]; Associates of the
Joint Center for Radiation Therapy (AJCRT) foundation; National
Institute of Allergy and Infectious Diseases (NIAID) [U19 A1067751]
FX This work was supported by grants from the National Cancer Institute
(NCI) (CA64585 and CA93602), the Associates of the Joint Center for
Radiation Therapy (AJCRT) foundation and by National Institute of
Allergy and Infectious Diseases (NIAID) U19 A1067751 center grant. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 59
TC 12
Z9 12
U1 0
U2 9
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 OCT 7
PY 2011
VL 6
IS 10
AR e26064
DI 10.1371/journal.pone.0026064
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834OC
UT WOS:000295970300056
PM 22016813
ER
PT J
AU Stienen, BMC
Tanaka, A
de Gelder, B
AF Stienen, Bernard M. C.
Tanaka, Akihiro
de Gelder, Beatrice
TI Emotional Voice and Emotional Body Postures Influence Each Other
Independently of Visual Awareness
SO PLOS ONE
LA English
DT Article
ID FACIAL EXPRESSIONS; INFLUENCE RECOGNITION; BODILY EXPRESSIONS;
PERCEPTION; AMYGDALA; FACE; ATTENTION; MASKING; THREAT; FEAR
AB Multisensory integration may occur independently of visual attention as previously shown with compound face-voice stimuli. We investigated in two experiments whether the perception of whole body expressions and the perception of voices influence each other when observers are not aware of seeing the bodily expression. In the first experiment participants categorized masked happy and angry bodily expressions while ignoring congruent or incongruent emotional voices. The onset between target and mask varied from -50 to +133 ms. Results show that the congruency between the emotion in the voice and the bodily expressions influences audiovisual perception independently of the visibility of the stimuli. In the second experiment participants categorized the emotional voices combined with masked bodily expressions as fearful or happy. This experiment showed that bodily expressions presented outside visual awareness still influence prosody perception. Our experiments show that audiovisual integration between bodily expressions and affective prosody can take place outside and independent of visual awareness.
C1 [Stienen, Bernard M. C.; de Gelder, Beatrice] Tilburg Univ, Lab Cognit & Affect Neurosci, NL-5000 LE Tilburg, Netherlands.
[Tanaka, Akihiro] Waseda Inst Adv Study, Tokyo, Japan.
[de Gelder, Beatrice] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[de Gelder, Beatrice] Harvard Univ, Sch Med, Charlestown, MA USA.
RP Stienen, BMC (reprint author), Tilburg Univ, Lab Cognit & Affect Neurosci, NL-5000 LE Tilburg, Netherlands.
EM B.deGelder@uvt.nl
FU Dutch Association of Scientific Research (NWO), Tango; EU
[FDP6-NEST-043403]; MEXT [19001004]; European Commission, under FET-Open
[249858]
FX This project was funded by the Dutch Association of Scientific Research
(NWO), Tango, the EU project COBOL (FDP6-NEST-043403) and by
Grant-in-Aid of MEXT for Specially Promoted Research (no. 19001004). The
project Tango acknowledges the financial support of the Future and
Emerging Technologies (FET) programme within the Seventh Framework
Programme for Research of the European Commission, under FET-Open (grant
number 249858). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 30
TC 12
Z9 12
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 OCT 7
PY 2011
VL 6
IS 10
AR e25517
DI 10.1371/journal.pone.0025517
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834OC
UT WOS:000295970300017
PM 22003396
ER
PT J
AU Hu, XL
Kim, H
Stahl, E
Plenge, R
Daly, M
Raychaudhuri, S
AF Hu, Xinli
Kim, Hyun
Stahl, Eli
Plenge, Robert
Daly, Mark
Raychaudhuri, Soumya
TI Integrating Autoimmune Risk Loci with Gene-Expression Data Identifies
Specific Pathogenic Immune Cell Subsets
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION;
INFLAMMATORY-BOWEL-DISEASE; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCI;
CROHNS-DISEASE; RECEPTOR GENE; B-CELLS; VARIANTS; ITGAM
AB Although genome-wide association studies have implicated many individual loci in complex diseases, identifying the exact causal alleles and the cell types within which they act remains greatly challenging. To ultimately understand disease mechanism, researchers must carefully conceive functional studies in relevant pathogenic cell types to demonstrate the cellular impact of disease-associated genetic variants. This challenge is highlighted in autoimmune diseases, such as rheumatoid arthritis, where any of a broad range of immunological cell types might potentially be impacted by genetic variation to cause disease. To this end, we developed a statistical approach to identify potentially pathogenic cell types in autoimmune diseases by using a gene-expression data set of 223 murine-sorted immune cells from the Immunological Genome Consortium. We found enrichment of transitional B cell genes in systemic lupus erythematosus (p = 5.9 x 10(-6)) and epithelial-associated stimulated dendritic cell genes in Crohn disease (p = 1.6 x 10(-5)). Finally, we demonstrated enrichment of CD4+ effector memory T cell genes within rheumatoid arthritis loci (p < 10(-6)). To further validate the role of CD4+ effector memory T cells within rheumatoid arthritis, we identified 436 loci that were not yet known to be associated with the disease but that had a statistically suggestive association in a recent genome-wide association study (GWAS) meta-analysis (PG WAS < 0.001). Even among these putative loci, we noted a significant enrichment for genes specifically expressed in CD4+ effector memory T cells (p = 1.25 x 10(-4)). These cell types are primary candidates for future functional studies to reveal the role of risk alleles in autoimmunity. Our approach has application in other phenotypes, outside of autoimmunity, where many loci have been discovered and high-quality cell-type-specific gene expression is available.
C1 [Hu, Xinli; Kim, Hyun; Stahl, Eli; Plenge, Robert; Raychaudhuri, Soumya] Harvard Univ, Sch Med, Div Genet, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Hu, Xinli; Kim, Hyun; Stahl, Eli; Plenge, Robert; Raychaudhuri, Soumya] Harvard Univ, Sch Med, Div Rheumatol Immunol & Allergy, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Hu, Xinli; Stahl, Eli; Plenge, Robert; Daly, Mark; Raychaudhuri, Soumya] Broad Inst, Med & Populat Genet Grp, Cambridge, MA 02142 USA.
[Hu, Xinli] Harvard Univ, Hlth Sci & Technol MD Program, Boston, MA 02115 USA.
[Hu, Xinli] MIT, Boston, MA 02115 USA.
[Daly, Mark] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02214 USA.
[Raychaudhuri, Soumya] Partners HealthCare Ctr Personalized Genet Med, Boston, MA 02115 USA.
RP Raychaudhuri, S (reprint author), Harvard Univ, Sch Med, Div Genet, Brigham & Womens Hosp, Boston, MA 02115 USA.
EM soumya@broadinstitute.org
FU National Institutes of Health National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIH-NIAMS) [1K08AR055688]; Harvard
Health Sciences and Technology Program
FX This work benefitted from data assembled by the ImmGen Consortium. This
work was supported in part by the National Institutes of Health National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS)
Development Award (1K08AR055688) and by the Harvard Health Sciences and
Technology Program. We thank Joel Hirschorn, Michael B. Brenner, David
Altshuler, and Lude Franke for helpful discussions.
NR 54
TC 57
Z9 57
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD OCT 7
PY 2011
VL 89
IS 4
BP 496
EP 506
DI 10.1016/j.ajhg.2011.09.002
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 834HV
UT WOS:000295951300004
PM 21963258
ER
PT J
AU Talkowski, ME
Mullegama, SV
Rosenfeld, JA
van Bon, WM
Shen, YP
Repnikova, EA
Gastier-Foster, J
Thrush, DL
Kathiresan, S
Ruderfer, DM
Chiang, C
Hanscom, C
Ernst, C
Lindgren, AM
Morton, CC
An, Y
Astbury, C
Brueton, LA
Lichtenbelt, KD
Ades, LC
Fichera, M
Romano, C
Innis, JW
Williams, CA
Bartholomew, D
Van Allen, MI
Parikh, A
Zhang, LL
Wu, BL
Pyatt, RE
Schwartz, S
Shaffer, LG
de Vries, BBA
Gusella, JF
Elsea, SH
AF Talkowski, Michael E.
Mullegama, Sureni V.
Rosenfeld, Jill A.
van Bon, W. M.
Shen, Yiping
Repnikova, Elena A.
Gastier-Foster, Julie
Thrush, Devon Lamb
Kathiresan, Sekar
Ruderfer, Douglas M.
Chiang, Colby
Hanscom, Carrie
Ernst, Carl
Lindgren, Amelia M.
Morton, Cynthia C.
An, Yu
Astbury, Caroline
Brueton, Louise A.
Lichtenbelt, Klaske D.
Ades, Lesley C.
Fichera, Marco
Romano, Corrado
Innis, Jeffrey W.
Williams, Charles A.
Bartholomew, Dennis
Van Allen, Margot I.
Parikh, Aditi
Zhang, Lilei
Wu, Bai-Lin
Pyatt, Robert E.
Schwartz, Stuart
Shaffer, Lisa G.
de Vries, Bert B. A.
Gusella, James F.
Elsea, Sarah H.
TI Assessment of 2q23.1 Microdeletion Syndrome Implicates MBD5 as a Single
Causal Locus of Intellectual Disability, Epilepsy, and Autism Spectrum
Disorder
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID COMPARATIVE GENOMIC HYBRIDIZATION; SMITH-MAGENIS-SYNDROME;
DNA-SEQUENCING DATA; MENTAL-RETARDATION; WIDE ASSOCIATION; CHROMOSOME
REARRANGEMENTS; GENOMEWIDE ASSOCIATION; BIPOLAR DISORDER; PHENOTYPE;
DELETIONS
AB Persons with neurodevelopmental disorders or autism spectrum disorder (ASD) often harbor chromosomal microdeletions, yet the individual genetic contributors within these regions have not been systematically evaluated. We established a consortium of clinical diagnostic and research laboratories to accumulate a large cohort with genetic alterations of chromosomal region 2q23.1 and acquired 65 subjects with microdeletion or translocation. We sequenced translocation breakpoints; aligned microdeletions to determine the critical region; assessed effects on mRNA expression; and examined medical records, photos, and clinical evaluations. We identified a single gene, methyl-CpG-binding domain 5 (MBD5), as the only locus that defined the critical region. Partial or complete deletion of MBD5 was associated with haploinsufficiency of mRNA expression, intellectual disability, epilepsy, and autistic features. Fourteen alterations, including partial deletions of noncoding regions not typically captured or considered pathogenic by current diagnostic screening, disrupted MBD5 alone. Expression profiles and clinical characteristics were largely indistinguishable between MBD5-specific alteration and deletion of the entire 2q23.1 interval. No copy-number alterations of MBD5 were observed in 7878 controls, suggesting MBD5 alterations are highly penetrant. We surveyed MOOS coding variations among 747 ASD subjects compared to 2043 non-ASD subjects analyzed by whole-exome sequencing and detected an association with a highly conserved methyl-CpG-binding domain missense variant, p.79Gly>Glu (c.236G>A) (p = 0.012). These results suggest that genetic alterations of MBD5 cause features of 2q23.1 microdeletion syndrome and that this epigenetic regulator significantly contributes to ASD risk, warranting further consideration in research and clinical diagnostic screening and highlighting the importance of chromatin remodeling in the etiology of these complex disorders.
C1 [Elsea, Sarah H.] Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA 23298 USA.
[Talkowski, Michael E.; Kathiresan, Sekar; Ruderfer, Douglas M.; Chiang, Colby; Hanscom, Carrie; Ernst, Carl; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Talkowski, Michael E.; Gusella, James F.] Harvard Univ, Harvard Med Sch, Dept Genet, Cambridge, MA 02115 USA.
[Talkowski, Michael E.; Gusella, James F.] Harvard Univ, Harvard Med Sch, Dept Neurol, Cambridge, MA 02115 USA.
[Talkowski, Michael E.; Kathiresan, Sekar; Morton, Cynthia C.; Gusella, James F.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02143 USA.
[Rosenfeld, Jill A.; Shaffer, Lisa G.] PerkinElmer Inc, Signature Genom Labs, Spokane, WA 99207 USA.
[van Bon, W. M.; de Vries, Bert B. A.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 GA Nijmegen, Netherlands.
[Shen, Yiping] Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Shanghai 200127, Peoples R China.
[Shen, Yiping; Wu, Bai-Lin] Childrens Hosp Boston, Dept Lab Med, Boston, MA 02115 USA.
[Shen, Yiping; Wu, Bai-Lin] Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA.
[Kathiresan, Sekar; Wu, Bai-Lin] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Repnikova, Elena A.; Gastier-Foster, Julie; Thrush, Devon Lamb; Astbury, Caroline; Pyatt, Robert E.] Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH 43205 USA.
[Gastier-Foster, Julie; Astbury, Caroline; Pyatt, Robert E.] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA.
[Gastier-Foster, Julie; Thrush, Devon Lamb] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Ruderfer, Douglas M.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Ruderfer, Douglas M.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Ruderfer, Douglas M.] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02143 USA.
[Lindgren, Amelia M.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
[Lindgren, Amelia M.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Wu, Bai-Lin] Fudan Univ, Childrens Hosp, Shanghai 200032, Peoples R China.
[Wu, Bai-Lin] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China.
[Brueton, Louise A.] Birmingham Womens Hosp, Clin Genet Unit, W Midlands Reg Genet Serv, Birmingham B15 2TG, W Midlands, England.
[Lichtenbelt, Klaske D.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CX Utrecht, Netherlands.
[Ades, Lesley C.] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia.
[Fichera, Marco] Ist Ricovero & Cura, Lab Genet Diag, I-94018 Troina, Italy.
[Romano, Corrado] Assoc Oasi Maria Santissima, IRCCS, I-94108 Troina, Italy.
[Innis, Jeffrey W.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Innis, Jeffrey W.] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA.
[Williams, Charles A.] Univ Florida, Coll Med, Dept Pediat, Div Genet & Metab, Gainesville, FL 32611 USA.
[Bartholomew, Dennis] Nationwide Childrens Hosp, Div Mol & Human Genet, Columbus, OH 43205 USA.
[Van Allen, Margot I.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada.
[Parikh, Aditi; Zhang, Lilei] Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA.
[Parikh, Aditi; Zhang, Lilei] Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA.
[Schwartz, Stuart] LabCorp, Res Triangle Pk, NC 27709 USA.
[Elsea, Sarah H.] Virginia Commonwealth Univ, Sch Med, Dept Pediat, Richmond, VA 23298 USA.
RP Elsea, SH (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA 23298 USA.
EM selsea@vcu.edu
RI Fichera, Marco/K-9220-2016; Ruderfer, Douglas/M-5795-2016; Astbury,
Caroline/E-2665-2011; Gastier-Foster, Julie/E-3105-2011; van Bon,
Bregje/D-3720-2013; Romano, Corrado/B-9695-2008; van Bon,
Bregje/Q-2445-2015
OI Fichera, Marco/0000-0002-8225-6880; Ruderfer,
Douglas/0000-0002-2365-386X; Romano, Corrado/0000-0003-1049-0683;
FU Developmental Genome Anatomy Project [GM061354, HD065286]; National
"973" project on Population and Health of China [2010CB529601]; Science
and Technology Council of Shanghai [09JC1402400, 09ZR1404500]; Simons
Foundation Autism Research Initiative; National Institutes of Health
[F32MH087123]; "5 per mille" program
FX We are thankful to all of the subjects and families involved in this
study. We are grateful for the assistance of Jennifer Defant, Santhosh
Girirajan, Stephen Williams, Zalak Shah, and Tracey Oh in the collection
of clinical data and in the preparation of this manuscript. We thank
Pamela Sklar and the International Schizophrenia Consortium for
contributing control data and Nancy J. Van Vranken for patient referral.
We are also grateful to Manuel Rivas for assistance with the Syzygy
analysis. We thank the Fondation Jerome Lejeune (SHE.) for funding
portions of this study, Developmental Genome Anatomy Project(GM061354),
HD065286, National "973" project on Population and Health of China
(2010CB529601), Science and Technology Council of Shanghai (09JC1402400
and 09ZR1404500), and the Simons Foundation Autism Research Initiative.
M.E.T. was supported by a National Institutes of Health National
Research Service Award (F32MH087123). The authors would also like to
thank the NHLBI GO Exome Sequencing Project and its ongoing studies that
produced and provided exome variant calls for comparison: the Lung GO
Sequencing Project (HL-102923), the Women's Health Initiative Sequencing
Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the
Seattle GO Sequencing Project (HL-102926) and the Heart GO Sequencing
Project (HL-103010). Fichera and Romano were supported by a grant from
the "5 per mille" program.
NR 48
TC 90
Z9 90
U1 2
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD OCT 7
PY 2011
VL 89
IS 4
BP 551
EP 563
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 834HV
UT WOS:000295951300009
PM 21981781
ER
PT J
AU Jun, GG
Nicolaou, M
Morrison, MA
Buros, J
Morgan, DJ
Radeke, MJ
Yonekawa, Y
Tsironi, EE
Kotoula, MG
Zacharaki, F
Mollema, N
Yuan, Y
Miller, JW
Haider, NB
Hageman, GS
Kim, IK
Schaumberg, DA
Farrer, LA
DeAngelis, MM
AF Jun, Gyungah
Nicolaou, Michael
Morrison, Margaux A.
Buros, Jacqueline
Morgan, Denise J.
Radeke, Monte J.
Yonekawa, Yoshihiro
Tsironi, Evangelia E.
Kotoula, Maria G.
Zacharaki, Fani
Mollema, Nissa
Yuan, Yang
Miller, Joan W.
Haider, Neena B.
Hageman, Gregory S.
Kim, Ivana K.
Schaumberg, Debra A.
Farrer, Lindsay A.
DeAngelis, Margaret M.
TI Influence of ROBO1 and RORA on Risk of Age-Related Macular Degeneration
Reveals Genetically Distinct Phenotypes in Disease Pathophysiology
SO PLOS ONE
LA English
DT Article
ID COMPLEMENT FACTOR-H; OCULAR ANGIOGENESIS; RETINAL DEVELOPMENT;
GENE-EXPRESSION; AXON GUIDANCE; ASSOCIATION; SMOKING; DRUSEN; ALPHA;
SUSCEPTIBILITY
AB ROBO1 is a strong candidate gene for age-related macular degeneration (AMD) based upon its location under a linkage peak on chromosome 3p12, its expression pattern, and its purported function in a pathway that includes RORA, a gene previously associated with risk for neovascular AMD. Previously, we observed that expression of ROBO1 and RORA is down-regulated among wet AMD cases, as compared to their unaffected siblings. Thus, we hypothesized that contribution of association signals in ROBO1, and interaction between these two genes may be important for both wet and dry AMD. We evaluated association of 19 single nucleotide polymorphisms (SNPs) in ROBO1 with wet and dry stages of AMD in a sibling cohort and a Greek case-control cohort containing 491 wet AMD cases, 174 dry AMD cases and 411 controls. Association signals and interaction results were replicated in an independent prospective cohort (1070 controls, 164 wet AMD cases, 293 dry AMD cases). The most significantly associated ROBO1 SNPs were rs1387665 under an additive model (meta P = 0.028) for wet AMD and rs9309833 under a recessive model (meta P = 6x10(-4)) for dry AMD. Further analyses revealed interaction between ROBO1 rs9309833 and RORA rs8034864 for both wet and dry AMD (interaction P<0.05). These studies were further supported by whole transcriptome expression profile studies from 66 human donor eyes and chromatin immunoprecipitation assays from mouse retinas. These findings suggest that distinct ROBO1 variants may influence the risk of wet and dry AMD, and the effects of ROBO1 on AMD risk may be modulated by RORA variants.
C1 [Jun, Gyungah; Nicolaou, Michael; Buros, Jacqueline; Farrer, Lindsay A.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Morrison, Margaux A.; Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.; DeAngelis, Margaret M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Morrison, Margaux A.; Morgan, Denise J.; Hageman, Gregory S.; DeAngelis, Margaret M.] Univ Utah, Ctr Translat Med, John Moran Eye Ctr, Salt Lake City, UT USA.
[Radeke, Monte J.] Univ Calif Santa Barbara, Neurosci Res Inst, Ctr Study Macular Degenerat, Santa Barbara, CA 93106 USA.
[Yonekawa, Yoshihiro] Weill Cornell Med Coll, New York, NY USA.
[Tsironi, Evangelia E.; Kotoula, Maria G.; Zacharaki, Fani] Univ Thessaly, Larisa, Greece.
[Mollema, Nissa; Yuan, Yang; Haider, Neena B.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Schaumberg, Debra A.] Brigham & Womens Hosp, Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA.
[Jun, Gyungah; Nicolaou, Michael; Buros, Jacqueline; Schaumberg, Debra A.; Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA.
RP Jun, GG (reprint author), Boston Univ, Sch Med, Boston, MA 02118 USA.
EM Margaret.DeAngelis@utah.edu
RI DeAngelis, e/J-7863-2015;
OI Jun, Gyungah/0000-0002-3230-8697; Farrer, Lindsay/0000-0001-5533-4225;
Buros, Jacqueline/0000-0001-9588-4889
FU Thome Memorial Foundation; Bank of America N.A.; Lincy Foundation;
Massachusetts Lions; Friends of the Massachusetts Eye and Ear Infirmary;
Genetics of Age-related Macular Degeneration Fund; Research to Prevent
Blindness; Hope for Vision; National Institutes of Health [EY014458,
EY14104, EY017362, EY017404]; Massachusetts Eye and Ear Infirmary
FX This work was supported by grants from the Thome Memorial Foundation;
Bank of America N.A.; Lincy Foundation; the Massachusetts Lions; Friends
of the Massachusetts Eye and Ear Infirmary; the Massachusetts Eye and
Ear Infirmary; Genetics of Age-related Macular Degeneration Fund;
Unrestricted Grant from Research to Prevent Blindness to the Department
of Ophthalmology and Visual Sciences, University of Utah; Hope for
Vision; and the National Institutes of Health (EY014458, EY14104,
EY017362, EY017404). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 49
TC 10
Z9 10
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 OCT 6
PY 2011
VL 6
IS 10
AR e25775
DI 10.1371/journal.pone.0025775
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834NO
UT WOS:000295968700018
PM 21998696
ER
PT J
AU Nathan, DG
AF Nathan, David G.
TI Guilt by association
SO BLOOD
LA English
DT Editorial Material
ID SICKLE-CELL-DISEASE; PULMONARY-HYPERTENSION
C1 [Nathan, David G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Nathan, DG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 7
TC 4
Z9 4
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 6
PY 2011
VL 118
IS 14
BP 3758
EP 3759
DI 10.1182/blood-2011-08-370338
PG 4
WC Hematology
SC Hematology
GA 832LY
UT WOS:000295807700003
PM 21980046
ER
PT J
AU Sakakibara, K
Saito, N
Sato, T
Suzuki, A
Hasegawa, Y
Friedman, JM
Kufe, DW
VonHoff, DD
Iwami, T
Kawabe, T
AF Sakakibara, Keiichi
Saito, Naoya
Sato, Takuji
Suzuki, Atsushi
Hasegawa, Yoko
Friedman, Jonathan M.
Kufe, Donald W.
VonHoff, Daniel D.
Iwami, Tadahiko
Kawabe, Takumi
TI CBS9106 is a novel reversible oral CRM1 inhibitor with CRM1 degrading
activity
SO BLOOD
LA English
DT Article
ID MULTIPLE-MYELOMA CELLS; ABL TYROSINE KINASE; NF-KAPPA-B; NUCLEAR EXPORT;
NUCLEOCYTOPLASMIC TRANSPORT; LEPTOMYCIN-B; G(2) CHECKPOINT;
LEUKEMIA-CELLS; CANCER; ACTIVATION
AB CRM1 plays an important role in the nuclear export of cargo proteins bearing nuclear exporting signal sequences. Leptomycin B (LMB), a well-known CRM1 inhibitor, possesses strong antitumor properties. However, its toxicity prevents it from being clinically useful. In this study, we demonstrate that a novel compound, CBS9106, inhibits CRM1-dependent nuclear export, causing arrest of the cell cycle and inducing apoptosis in a time-and dose-dependent manner for a broad spectrum of cancer cells, including multiple myeloma cells. CBS9106 reduces CRM1 protein levels significantly without affecting CRM1 mRNA expression. This effect could be reversed by adding bortezomib or LMB. Moreover, CBS9106-biotin allows capture of CRM1 protein by streptavidin beads in a competitive manner with LMB and vice versa. Mass spectrometric analysis shows that CBS9106 reacts with a synthetic CRM1 peptide that contains Cys528 but not with a Cys528 mutant peptide. Oral administration of CBS9106 significantly suppresses tumor growth and prolongs survival in mice bearing tumor xenograft without a significant loss in body weight. A reduced level of CRM1 protein is also observed in tumor xenografts isolated from mice treated with CBS9106. Taken together, these results indicate that CBS9106 is a novel reversible CRM1 inhibitor and a promising clinical candidate. (Blood. 2011;118(14):3922-3931)
C1 [Sakakibara, Keiichi; Saito, Naoya; Sato, Takuji; Suzuki, Atsushi; Hasegawa, Yoko; Friedman, Jonathan M.; Iwami, Tadahiko; Kawabe, Takumi] CanBas Co Ltd, Numazu 4100801, Japan.
[Kufe, Donald W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[VonHoff, Daniel D.] Translat Genom Res Inst TGen, Phoenix, AZ USA.
RP Kawabe, T (reprint author), CanBas Co Ltd, 2-2-1 Otemachi, Numazu 4100801, Japan.
EM takumi@canbas.co.jp
OI friedman, jonathan/0000-0001-6908-5928
NR 35
TC 58
Z9 64
U1 1
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 6
PY 2011
VL 118
IS 14
BP 3922
EP 3931
DI 10.1182/blood-2011-01-333138
PG 10
WC Hematology
SC Hematology
GA 832LY
UT WOS:000295807700024
PM 21841164
ER
PT J
AU Jacquemont, S
Reymond, A
Zufferey, F
Harewood, L
Walters, RG
Kutalik, Z
Martinet, D
Shen, YP
Valsesia, A
Beckmann, ND
Thorleifsson, G
Belfiore, M
Bouquillon, S
Campion, D
de Leeuw, N
de Vries, BBA
Esko, T
Fernandez, BA
Fernandez-Aranda, F
Fernandez-Real, JM
Gratacos, M
Guilmatre, A
Hoyer, J
Jarvelin, MR
Kooy, RF
Kurg, A
Le Caignec, C
Mannik, K
Platt, OS
Sanlaville, D
Van Haelst, MM
Gomez, SV
Walha, F
Wu, BL
Yu, YG
Aboura, A
Addor, MC
Alembik, Y
Antonarakis, SE
Arveiler, B
Barth, M
Bednarek, N
Bena, F
Bergmann, S
Beri, M
Bernardini, L
Blaumeiser, B
Bonneau, D
Bottani, A
Boute, O
Brunner, HG
Cailley, D
Callier, P
Chiesa, J
Chrast, J
Coin, L
Coutton, C
Cuisset, JM
Cuvellier, JC
David, A
de Freminville, B
Delobel, B
Delrue, MA
Demeer, B
Descamps, D
Didelot, G
Dieterich, K
Disciglio, V
Doco-Fenzy, M
Drunat, S
Duban-Bedu, B
Dubourg, C
Moustafa, JSE
Elliott, P
Faas, BHW
Faivre, L
Faudet, A
Fellmann, F
Ferrarini, A
Fisher, R
Flori, E
Forer, L
Gaillard, D
Gerard, M
Gieger, C
Gimelli, S
Gimelli, G
Grabe, HJ
Guichet, A
Guillin, O
Hartikainen, AL
Heron, D
Hippolyte, L
Holder, M
Homuth, G
Isidor, B
Jaillard, S
Jaros, Z
Jimenez-Murcia, S
Helas, GJ
Jonveaux, P
Kaksonen, S
Keren, B
Kloss-Brandstatter, A
Knoers, NVAM
Koolen, DA
Kroisel, PM
Kronenberg, F
Labalme, A
Landais, E
Lapi, E
Layet, V
Legallic, S
Leheup, B
Leube, B
Lewis, S
Lucas, J
MacDermot, KD
Magnusson, P
Marshall, C
Mathieu-Dramard, M
McCarthy, MI
Meitinger, T
Mencarelli, MA
Merla, G
Moerman, A
Mooser, V
Morice-Picard, F
Mucciolo, M
Nauck, M
Ndiaye, NC
Nordgren, A
Pasquier, L
Petit, F
Pfundt, R
Plessis, G
Rajcan-Separovic, E
Ramelli, GP
Rauch, A
Ravazzolo, R
Reis, A
Renieri, A
Richart, C
Ried, JS
Rieubland, C
Roberts, W
Roetzer, KM
Rooryck, C
Rossi, M
Saemundsen, E
Satre, V
Schurmann, C
Sigurdsson, E
Stavropoulos, DJ
Stefansson, H
Tengstrom, C
Thorsteinsdottir, U
Tinahones, FJ
Touraine, R
Vallee, L
van Binsbergen, E
Van der Aa, N
Vincent-Delorme, C
Visvikis-Siest, S
Vollenweider, P
Volzke, H
Vulto-van Silfhout, AT
Waeber, G
Wallgren-Pettersson, C
Witwicki, RM
Zwolinksi, S
Andrieux, J
Estivill, X
Gusella, JF
Gustafsson, O
Metspalu, A
Scherer, SW
Stefansson, K
Blakemore, AIF
Beckmann, JS
Froguel, P
AF Jacquemont, Sebastien
Reymond, Alexandre
Zufferey, Flore
Harewood, Louise
Walters, Robin G.
Kutalik, Zoltan
Martinet, Danielle
Shen, Yiping
Valsesia, Armand
Beckmann, Noam D.
Thorleifsson, Gudmar
Belfiore, Marco
Bouquillon, Sonia
Campion, Dominique
de Leeuw, Nicole
de Vries, Bert B. A.
Esko, Tonu
Fernandez, Bridget A.
Fernandez-Aranda, Fernando
Manuel Fernandez-Real, Jose
Gratacos, Monica
Guilmatre, Audrey
Hoyer, Juliane
Jarvelin, Marjo-Riitta
Kooy, R. Frank
Kurg, Ants
Le Caignec, Cedric
Maennik, Katrin
Platt, Orah S.
Sanlaville, Damien
Van Haelst, Mieke M.
Villatoro Gomez, Sergi
Walha, Faida
Wu, Bai-lin
Yu, Yongguo
Aboura, Azzedine
Addor, Marie-Claude
Alembik, Yves
Antonarakis, Stylianos E.
Arveiler, Benoit
Barth, Magalie
Bednarek, Nathalie
Bena, Frederique
Bergmann, Sven
Beri, Mylene
Bernardini, Laura
Blaumeiser, Bettina
Bonneau, Dominique
Bottani, Armand
Boute, Odile
Brunner, Han G.
Cailley, Dorothee
Callier, Patrick
Chiesa, Jean
Chrast, Jacqueline
Coin, Lachlan
Coutton, Charles
Cuisset, Jean-Marie
Cuvellier, Jean-Christophe
David, Albert
de Freminville, Benedicte
Delobel, Bruno
Delrue, Marie-Ange
Demeer, Benedicte
Descamps, Dominique
Didelot, Gerard
Dieterich, Klaus
Disciglio, Vittoria
Doco-Fenzy, Martine
Drunat, Severine
Duban-Bedu, Benedicte
Dubourg, Christele
Moustafa, Julia S. El-Sayed
Elliott, Paul
Faas, Brigitte H. W.
Faivre, Laurence
Faudet, Anne
Fellmann, Florence
Ferrarini, Alessandra
Fisher, Richard
Flori, Elisabeth
Forer, Lukas
Gaillard, Dominique
Gerard, Marion
Gieger, Christian
Gimelli, Stefania
Gimelli, Giorgio
Grabe, Hans J.
Guichet, Agnes
Guillin, Olivier
Hartikainen, Anna-Liisa
Heron, Delphine
Hippolyte, Loyse
Holder, Muriel
Homuth, Georg
Isidor, Bertrand
Jaillard, Sylvie
Jaros, Zdenek
Jimenez-Murcia, Susana
Helas, Geraldine Joly
Jonveaux, Philippe
Kaksonen, Satu
Keren, Boris
Kloss-Brandstaetter, Anita
Knoers, Nine V. A. M.
Koolen, David A.
Kroisel, Peter M.
Kronenberg, Florian
Labalme, Audrey
Landais, Emilie
Lapi, Elisabetta
Layet, Valerie
Legallic, Solenn
Leheup, Bruno
Leube, Barbara
Lewis, Suzanne
Lucas, Josette
MacDermot, Kay D.
Magnusson, Pall
Marshall, Christian
Mathieu-Dramard, Michele
McCarthy, Mark I.
Meitinger, Thomas
Mencarelli, Maria Antonietta
Merla, Giuseppe
Moerman, Alexandre
Mooser, Vincent
Morice-Picard, Fanny
Mucciolo, Mafalda
Nauck, Matthias
Ndiaye, Ndeye Coumba
Nordgren, Ann
Pasquier, Laurent
Petit, Florence
Pfundt, Rolph
Plessis, Ghislaine
Rajcan-Separovic, Evica
Ramelli, Gian Paolo
Rauch, Anita
Ravazzolo, Roberto
Reis, Andre
Renieri, Alessandra
Richart, Cristobal
Ried, Janina S.
Rieubland, Claudine
Roberts, Wendy
Roetzer, Katharina M.
Rooryck, Caroline
Rossi, Massimiliano
Saemundsen, Evald
Satre, Veronique
Schurmann, Claudia
Sigurdsson, Engilbert
Stavropoulos, Dimitri J.
Stefansson, Hreinn
Tengstrom, Carola
Thorsteinsdottir, Unnur
Tinahones, Francisco J.
Touraine, Renaud
Vallee, Louis
van Binsbergen, Ellen
Van der Aa, Nathalie
Vincent-Delorme, Catherine
Visvikis-Siest, Sophie
Vollenweider, Peter
Voelzke, Henry
Vulto-van Silfhout, Anneke T.
Waeber, Gerard
Wallgren-Pettersson, Carina
Witwicki, Robert M.
Zwolinksi, Simon
Andrieux, Joris
Estivill, Xavier
Gusella, James F.
Gustafsson, Omar
Metspalu, Andres
Scherer, Stephen W.
Stefansson, Kari
Blakemore, Alexandra I. F.
Beckmann, Jacques S.
Froguel, Philippe
TI Mirror extreme BMI phenotypes associated with gene dosage at the
chromosome 16p11.2 locus
SO NATURE
LA English
DT Article
ID COPY NUMBER VARIATION; BODY-MASS INDEX; DEPENDENT PROBE AMPLIFICATION;
CIRCULAR BINARY SEGMENTATION; TIME QUANTITATIVE PCR; HIDDEN-MARKOV
MODEL; SNP GENOTYPING DATA; FAILURE-TO-THRIVE; RELATIVE QUANTIFICATION;
METABOLIC SYNDROME
AB Both obesity and being underweight have been associated with increased mortality(1,2). Underweight, defined as a body mass index (BMI) <= 18.5 kg per m(2) in adults and <= -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive(3-5), feeding and eating disorder and/or anorexia nervosa(6,7). In contrast to obesity, few genetic variants underlying these clinical conditions have been reported(8,9). We previously showed that hemizygosity of a similar to 600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities(10). Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.
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[Reymond, Alexandre; Harewood, Louise; Walha, Faida; Chrast, Jacqueline; Didelot, Gerard; Witwicki, Robert M.] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
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[Kutalik, Zoltan; Valsesia, Armand; Bergmann, Sven; Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland.
[Kutalik, Zoltan; Valsesia, Armand; Bergmann, Sven] Univ Lausanne, Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
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[Valsesia, Armand] Univ Lausanne, Ludwig Inst Canc Res, CH-1015 Lausanne, Switzerland.
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[Kaksonen, Satu] Habilitat Unit Folkhalsan, SF-00250 Helsinki, Finland.
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[Ravazzolo, Roberto] Univ Genoa, G Gaslini Inst, CEBR, I-16126 Genoa, Italy.
[Richart, Cristobal] Univ Rovira & Virgili, Univ Hosp Juan XXIII, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Dept Internal Med,Inst Salud Carlos III, Tarragona 43005, Spain.
[Rieubland, Claudine] Univ Bern, Inselspital, Dept Paediat, Div Human Genet, CH-3010 Bern, Switzerland.
[Roberts, Wendy] Hosp Sick Children, Autism Res Unit, Toronto, ON M5G 1X8, Canada.
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[Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
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[Vollenweider, Peter; Waeber, Gerard] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland.
[Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17475 Greifswald, Germany.
[Wallgren-Pettersson, Carina] Univ Helsinki, Dept Med Genet, Helsinki 00251, Finland.
[Wallgren-Pettersson, Carina] Folkhalsan Inst Genet, Helsinki 00251, Finland.
[Gustafsson, Omar] Oslo Univ Hosp, Dept Psychiat, N-0407 Oslo, Norway.
[Scherer, Stephen W.] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1L7, Canada.
[Froguel, Philippe] Inst Pasteur, Inst Biol, CNRS 8090, F-59800 Lille, France.
[Disciglio, Vittoria] Azienda Osped Univ Senese, UOC Genet Med, Siena, Italy.
[Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-81675 Munich, Germany.
RP Beckmann, JS (reprint author), CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland.
EM Jacques.Beckmann@chuv.ch
RI Koolen, D.A./L-4448-2015; Leeuw, N./L-4480-2015; Pfundt,
Rolph/L-4576-2015; Meitinger, Thomas/O-1318-2015; Vulto-van Silfhout,
Anneke/H-4199-2015; Nordgren, Ann/N-4057-2013; Bernardini,
Laura/H-5360-2016; Kooy, Frank/F-5276-2014; Schurmann,
Claudia/L-1204-2016; Coin, Lachlan/A-9001-2014; Reis, Andre/D-2309-2009;
Visvikis-Siest, Sophie/H-2324-2014; Jimenez-Murcia, Susana/L-9786-2014;
Walters, Robin/E-6069-2010; Beckmann, Jacques S /A-9772-2008; Estivill,
Xavier/E-2957-2012; Howe, Jennifer/I-9013-2012; Scherer, Stephen
/B-3785-2013; Brunner, Han/C-9928-2013; Colaus, PsyColaus/K-6607-2013;
Kronenberg, Florian/B-1736-2008; Rauch, Anita/C-5568-2014; Sigurdsson,
Engilbert/D-2486-2014; Fernandez-Aranda, Fernando/L-9762-2014; Arveiler,
Benoit/M-3721-2014; Estivill, Xavier/A-3125-2013; ROORYCK,
Caroline/M-4565-2014; MORICE-PICARD, Fanny/M-5125-2014; sanlaville,
damien/M-4716-2014; Antonarakis, Stylianos/N-8866-2014; Kurg,
Ants/J-2616-2015; Bonneau, Dominique/K-6110-2015; Le Caignec,
Cedric/K-8467-2015; Isidor, Bertrand/L-2435-2015; Faas,
B.H.W./L-4301-2015; jaillard, sylvie/L-9314-2015
OI Nordgren, Ann/0000-0003-3285-4281; Bernardini,
Laura/0000-0002-3554-2817; Kooy, Frank/0000-0003-2024-0485; Schurmann,
Claudia/0000-0003-4158-9192; Coin, Lachlan/0000-0002-4300-455X; Reis,
Andre/0000-0002-6301-6363; Harewood, Louise/0000-0002-6398-6714;
Visvikis-Siest, Sophie/0000-0001-8104-8425; Jimenez-Murcia,
Susana/0000-0002-3596-8033; Walters, Robin/0000-0002-9179-0321;
Beckmann, Jacques S /0000-0002-9741-1900; Scherer, Stephen
/0000-0002-8326-1999; Kronenberg, Florian/0000-0003-2229-1120; Rauch,
Anita/0000-0003-2930-3163; Sigurdsson, Engilbert/0000-0001-9404-7982;
El-Sayed Moustafa, Julia Sarah/0000-0001-6963-6654; petit,
florence/0000-0002-1368-1023; Esko, Tonu/0000-0003-1982-6569; Gieger,
Christian/0000-0001-6986-9554; Stefansson, Hreinn/0000-0002-9331-6666;
Jarvelin, Marjo-Riitta/0000-0002-2149-0630; yu,
yongguo/0000-0002-4472-0910; Fernandez-Real, Jose
Manuel/0000-0002-7442-9323; Bergmann, Sven/0000-0002-6785-9034;
Fernandez-Aranda, Fernando/0000-0002-2968-9898; Estivill,
Xavier/0000-0002-0723-2256; sanlaville, damien/0000-0001-9939-2849;
Antonarakis, Stylianos/0000-0001-8907-5823; Le Caignec,
Cedric/0000-0002-0598-653X; Isidor, Bertrand/0000-0001-6480-126X;
FU Leenaards Foundation; Jerome Lejeune Foundation; Telethon Action Suisse
Foundation; Swiss National Science Foundation; European Commission
[037627, QLG1-CT-2000-01643]; Ludwig Institute for Cancer Research;
Swiss Institute of Bioinformatics; Imperial College Department of
Medicine; Comprehensive Biomedical Research Centre; Imperial College
Healthcare NHS Trust; National Institute for Health Research; Wellcome
Trust; Medical Research Council; Instituto de Salud Carlos III
(ISCIII)-FIS; German Mental Retardation Network; German Federal Ministry
of Education and Research [NGFNplus 01GS08160]; European Union
[PI081714, PS09/01778, 201413, 245536, HEALTH-2007-2.2.1-10-223423];
Belgian National Fund for Scientific Research, Flanders; Dutch
Organisation for Health Research and Development (ZON-MW) [917-86-319];
Hersenstichting Nederland (B.B.A.d.V.); Chinese National Natural Science
Foundation [81000346]; Simons Foundation Autism Research Initiative;
Autism Speaks; NIH [GM061354, MH071425]; Oesterreichische Nationalbank
(OENB) [13059]; Children's Tumor Foundation; Harvard Medical School;
Fudan University; Chinese National '973' project on Population and
Health [2010CB529601]; Science and Technology Council of Shanghai
[09JC1402400]; Michael Smith Foundation for Health; CIHR [MOP 74502];
Estonian Government [SF0180142s08, SF0180026s09, SF0180027s10];
Helmholtz Zentrum Munich; State of Bavaria; German National Genome
Research Network [01GS0823]; German Federal Ministry of Education and
Research (BMBF); Munich Center of Health Sciences (MC Health,
LMUinnovativ); Genome Canada; McLaughlin Centre; Academy of Finland
[104781, 120315, 129269, 1114194]; University Hospital Oulu; Biocenter;
University of Oulu, Finland [75617]; NHLBI [5R01HL087679-02,
1RL1MH083268-01]; NIH/NIMH [5R01MH63706:02]; ENGAGE project; Medical
Research Council, UK [G0500539, G0600705]; Academy of Finland;
Biocentrum Helsinki; [SAF2008-02278]; [HEALTH-F4-2007-201413]
FX We thank the Vital-IT high-performance computing centre of the Swiss
Institute of Bioinformatics. S.J. is recipient of a bourse de releve
academique de la Faculte de Biologie et Medecine de l'Universite de
Lausanne. This work was supported by the Leenaards Foundation Prize
(S.J., D. M. and A. Reymond), the Jerome Lejeune Foundation (A.
Reymond), the Telethon Action Suisse Foundation (A. Reymond), the Swiss
National Science Foundation (A. Reymond, J.S.B., S. B. and S. E. A.), a
Swiss National Science Foundation Sinergia grant (S.J., D. M., S. B.,
J.S.B. and A. Reymond), the European Commission an EU ploidy Integrated
Project grant 037627 (A. Reymond, S. B., X. E., H. G. B. and S. E. A.),
the Ludwig Institute for Cancer Research (A. V.), the Swiss Institute of
Bioinformatics (S. B. and Z.K.), an Imperial College Department of
Medicine PhD studentship (J.S.E.-S.M), the Comprehensive Biomedical
Research Centre, Imperial College Healthcare NHS Trust, and the National
Institute for Health Research (P. E.), the Wellcome Trust and the
Medical Research Council (A. I. F. B. and P. F.), the Instituto de Salud
Carlos III (ISCIII)-FIS, the German Mental Retardation Network funded
through a grant of the German Federal Ministry of Education and Research
(NGFNplus 01GS08160) (A. Reis), European Union-FEDER (PI081714,
PS09/01778) (F. F. A., M. G. and X. E.), SAF2008-02278 (C. R.), the
Belgian National Fund for Scientific Research, Flanders (N.V.A. and R.
F. K.), the Dutch Organisation for Health Research and Development
(ZON-MW grant 917-86-319) and Hersenstichting Nederland (B.B.A.d.V.),
grant 81000346 from the Chinese National Natural Science Foundation
(Y.G.Y.), the Simons Foundation Autism Research Initiative, Autism
Speaks and NIH grant GM061354 (J.F.G.), and Oesterreichische
Nationalbank (OENB) grant 13059 (A.K.-B.). Y.S. holds a Young
Investigator Award from the Children's Tumor Foundation and a Catalyst
Award from Harvard Medical School. B. L. W. holds a Fudan Scholar
Research Award from Fudan University, a grant from Chinese National
'973' project on Population and Health (2010CB529601) and a grant from
the Science and Technology Council of Shanghai (09JC1402400). E. R. S.
and S. L., recipients of the Michael Smith Foundation for Health
Research Scholar award, acknowledge the CIHR MOP 74502 operational
grant. The Estonian Genome Center of the University of Tartu (EGCUT)
received support from the EU Centre of Excellence in Genomics and FP7
grants 201413 and 245536, and from Estonian Government SF0180142s08,
SF0180026s09 and SF0180027s10 (A. M., K. M. and A. K.). D. S. thanks the
Direction Generale de l'Organisation des Soins from the French Ministry
of Health for their support in the development of several array-CGH
platforms, and the Centres Labellises Anomalies du Development in
France. The Helmholtz Zentrum Munich and the State of Bavaria financed
the KORA study, also supported by the German National Genome Research
Network (NGFN-2 and NGFN Plus: 01GS0823), the German Federal Ministry of
Education and Research (BMBF), and the Munich Center of Health Sciences
(MC Health, LMUinnovativ). CIBEROBN and CIBERESP are initiatives of
ISCIII (Spain). S. W. S. holds the GlaxoSmithKline-Canadian Institutes
of Health Chair in Genetics and Genomics at the University of Toronto
and the Hospital for Sick Children, and is supported by Genome Canada
and the McLaughlin Centre. Funding for deCODE came in part from NIH
grant MH071425 (K. S.), EU grant HEALTH-2007-2.2.1-10-223423 (Project
PsychCNV) and EU grant IMI-JU-NewMeds.; NFBC1966 received financial
supportfrom the Academy of Finland (project grants 104781, 120315,
129269, 1114194, Center of Excellence in Complex Disease Genetics and
SALVE), University Hospital Oulu, Biocenter, University of Oulu, Finland
(75617), the European Commission (EURO-BLCS, Framework 5 award
QLG1-CT-2000-01643), NHLBI grant 5R01HL087679-02 through the STAMPEED
program (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02), ENGAGE project and
grant agreement HEALTH-F4-2007-201413, and the Medical Research Council,
UK (G0500539, G0600705, PrevMetSyn/SALVE). The DNA extractions, sample
quality controls, biobank up-keeping and aliquotting was performed in
the National Public Health Institute, Biomedicum Helsinki, Finland and
supported financially by the Academy of Finland and Biocentrum Helsinki.
We thank M. Hass, Z. Jaros, M. Jussila, M. Koiranen, P. Rantakallio, M.
C. Rudolf, V. Soo, O. Tornwall, S. Vaara, T. Ylitalo and the French DHOS
national CGH network for their help, as well as all participating
patients and clinicians. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 61
TC 165
Z9 170
U1 2
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 6
PY 2011
VL 478
IS 7367
BP 97
EP U111
DI 10.1038/nature10406
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400042
PM 21881559
ER
PT J
AU Ehret, GB
Munroe, PB
Rice, KM
Bochud, M
Johnson, AD
Chasman, DI
Smith, AV
Tobin, MD
Verwoert, GC
Hwang, SJ
Pihur, V
Vollenweider, P
O'Reilly, PF
Amin, N
Bragg-Gresham, JL
Teumer, A
Glazer, NL
Launer, L
Zhao, JH
Aulchenko, Y
Heath, S
Sober, S
Parsa, A
Luan, JA
Arora, P
Dehghan, A
Zhang, F
Lucas, G
Hicks, AA
Jackson, AU
Peden, JF
Tanaka, T
Wild, SH
Rudan, I
Igl, W
Milaneschi, Y
Parker, AN
Fava, C
Chambers, JC
Fox, ER
Kumari, M
Go, MJ
van der Harst, P
Kao, WHL
Sjogren, M
Vinay, DG
Alexander, M
Tabara, Y
Shaw-Hawkins, S
Whincup, PH
Liu, YM
Shi, G
Kuusisto, J
Tayo, B
Seielstad, M
Sim, X
Nguyen, KDH
Lehtimaki, T
Matullo, G
Wu, Y
Gaunt, TR
Onland-Moret, NC
Cooper, MN
Platou, CGP
Org, E
Hardy, R
Dahgam, S
Palmen, J
Vitart, V
Braund, PS
Kuznetsova, T
Uiterwaal, CSPM
Adeyemo, A
Palmas, W
Campbell, H
Ludwig, B
Tomaszewski, M
Tzoulaki, I
Palmer, ND
Aspelund, T
Garcia, M
Chang, YPC
O'Connell, JR
Steinle, NI
Grobbee, DE
Arking, DE
Kardia, SL
Morrison, AC
Hernandez, D
Najjar, S
McArdle, WL
Hadley, D
Brown, MJ
Connell, JM
Hingorani, AD
Day, INM
Lawlor, DA
Beilby, JP
Lawrence, RW
Clarke, R
Hopewell, JC
Ongen, H
Dreisbach, AW
Li, YL
Young, JH
Bis, JC
Kahonen, M
Viikari, J
Adair, LS
Lee, NR
Chen, MH
Olden, M
Pattaro, C
Bolton, JAH
Kottgen, A
Bergmann, S
Mooser, V
Chaturvedi, N
Frayling, TM
Islam, M
Jafar, TH
Erdmann, J
Kulkarni, SR
Bornstein, SR
Grassler, J
Groop, L
Voight, BF
Kettunen, J
Howard, P
Taylor, A
Guarrera, S
Ricceri, F
Emilsson, V
Plump, A
Barroso, IS
Khaw, KT
Weder, AB
Hunt, SC
Sun, YV
Bergman, RN
Collins, FS
Bonnycastle, LL
Scott, LJ
Stringham, HM
Peltonen, L
Perola, M
Vartiainen, E
Brand, SM
Staessen, JA
Wang, TJ
Burton, PR
Artigas, MS
Dong, YB
Snieder, H
Wang, XL
Zhu, HD
Lohman, KK
Rudock, ME
Heckbert, SR
Smith, NL
Wiggins, KL
Doumatey, A
Shriner, D
Veldre, G
Viigimaa, M
Kinra, S
Prabhakaran, D
Tripathy, V
Langefeld, CD
Rosengren, A
Thelle, DS
Corsi, AM
Singleton, A
Forrester, T
Hilton, G
McKenzie, CA
Salako, T
Iwai, N
Kita, Y
Ogihara, T
Ohkubo, T
Okamura, T
Ueshima, H
Umemura, S
Eyheramendy, S
Meitinger, T
Wichmann, HE
Cho, YS
Kim, HL
Lee, JY
Scott, J
Sehmi, JS
Zhang, WH
Hedblad, B
Nilsson, P
Smith, GD
Wong, A
Narisu, N
Stancakova, A
Raffel, LJ
Yao, J
Kathiresan, S
O'Donnell, CJ
Schwartz, SM
Ikram, MA
Longstreth, WT
Mosley, TH
Seshadri, S
Shrine, NRG
Wain, LV
Morken, MA
Swift, AJ
Laitinen, J
Prokopenko, I
Zitting, P
Cooper, JA
Humphries, SE
Danesh, J
Rasheed, A
Goel, A
Hamsten, A
Watkins, H
Bakker, SJL
van Gilst, WH
Janipalli, CS
Mani, KR
Yajnik, CS
Hofman, A
Mattace-Raso, FUS
Oostra, BA
Demirkan, A
Isaacs, A
Rivadeneira, F
Lakatta, EG
Orru, M
Scuteri, A
Ala-Korpela, M
Kangas, AJ
Lyytikainen, LP
Soininen, P
Tukiainen, T
Wurtz, P
Ong, RTH
Dorr, M
Kroemer, HK
Volker, U
Volzke, H
Galan, P
Hercberg, S
Lathrop, M
Zelenika, D
Deloukas, P
Mangino, M
Spector, TD
Zhai, GJ
Meschia, JF
Nalls, MA
Sharma, P
Terzic, J
Kumar, MVK
Denniff, M
Zukowska-Szczechowska, E
Wagenknecht, LE
Fowkes, FGR
Charchar, FJ
Schwarz, PEH
Hayward, C
Guo, XQ
Rotimi, C
Bots, ML
Brand, E
Samani, NJ
Polasek, O
Talmud, PJ
Nyberg, F
Kuh, D
Laan, M
Hveem, K
Palmer, LJ
van der Schouw, YT
Casas, JP
Mohlke, KL
Vineis, P
Raitakari, O
Ganesh, SK
Wong, TY
Tai, ES
Cooper, RS
Laakso, M
Rao, DC
Harris, TB
Morris, RW
Dominiczak, AF
Kivimaki, M
Marmot, MG
Miki, T
Saleheen, D
Chandak, GR
Coresh, J
Navis, G
Salomaa, V
Han, BG
Zhu, XF
Kooner, JS
Melander, O
Ridker, PM
Bandinelli, S
Gyllensten, UB
Wright, AF
Wilson, JF
Ferrucci, L
Farrall, M
Tuomilehto, J
Pramstaller, PP
Elosua, R
Soranzo, N
Sijbrands, EJG
Altshuler, D
Loos, RJF
Shuldiner, AR
Gieger, C
Meneton, P
Uitterlinden, AG
Wareham, NJ
Gudnason, V
Rotter, JI
Rettig, R
Uda, M
Strachan, DP
Witteman, JCM
Hartikainen, AL
Beckmann, JS
Boerwinkle, E
Vasan, RS
Boehnke, M
Larson, MG
Jarvelin, MR
Psaty, BM
Abecasis, GR
Chakravarti, A
Elliott, P
van Duijn, CM
Newton-Cheh, C
Levy, D
Caulfield, MJ
Johnson, T
AF Ehret, Georg B.
Munroe, Patricia B.
Rice, Kenneth M.
Bochud, Murielle
Johnson, Andrew D.
Chasman, Daniel I.
Smith, Albert V.
Tobin, Martin D.
Verwoert, Germaine C.
Hwang, Shih-Jen
Pihur, Vasyl
Vollenweider, Peter
O'Reilly, Paul F.
Amin, Najaf
Bragg-Gresham, Jennifer L.
Teumer, Alexander
Glazer, Nicole L.
Launer, Lenore
Zhao, Jing Hua
Aulchenko, Yurii
Heath, Simon
Sober, Siim
Parsa, Afshin
Luan, Jian'an
Arora, Pankaj
Dehghan, Abbas
Zhang, Feng
Lucas, Gavin
Hicks, Andrew A.
Jackson, Anne U.
Peden, John F.
Tanaka, Toshiko
Wild, Sarah H.
Rudan, Igor
Igl, Wilmar
Milaneschi, Yuri
Parker, Alex N.
Fava, Cristiano
Chambers, John C.
Fox, Ervin R.
Kumari, Meena
Go, Min Jin
van der Harst, Pim
Kao, Wen Hong Linda
Sjogren, Marketa
Vinay, D. G.
Alexander, Myriam
Tabara, Yasuharu
Shaw-Hawkins, Sue
Whincup, Peter H.
Liu, Yongmei
Shi, Gang
Kuusisto, Johanna
Tayo, Bamidele
Seielstad, Mark
Sim, Xueling
Khanh-Dung Hoang Nguyen
Lehtimaki, Terho
Matullo, Giuseppe
Wu, Ying
Gaunt, Tom R.
Onland-Moret, N. Charlotte
Cooper, Matthew N.
Platou, Carl G. P.
Org, Elin
Hardy, Rebecca
Dahgam, Santosh
Palmen, Jutta
Vitart, Veronique
Braund, Peter S.
Kuznetsova, Tatiana
Uiterwaal, Cuno S. P. M.
Adeyemo, Adebowale
Palmas, Walter
Campbell, Harry
Ludwig, Barbara
Tomaszewski, Maciej
Tzoulaki, Ioanna
Palmer, Nicholette D.
Aspelund, Thor
Garcia, Melissa
Chang, Yen-Pei C.
O'Connell, Jeffrey R.
Steinle, Nanette I.
Grobbee, Diederick E.
Arking, Dan E.
Kardia, Sharon L.
Morrison, Alanna C.
Hernandez, Dena
Najjar, Samer
McArdle, Wendy L.
Hadley, David
Brown, Morris J.
Connell, John M.
Hingorani, Aroon D.
Day, Ian N. M.
Lawlor, Debbie A.
Beilby, John P.
Lawrence, Robert W.
Clarke, Robert
Hopewell, Jemma C.
Ongen, Halit
Dreisbach, Albert W.
Li, Yali
Young, J. Hunter
Bis, Joshua C.
Kahonen, Mika
Viikari, Jorma
Adair, Linda S.
Lee, Nanette R.
Chen, Ming-Huei
Olden, Matthias
Pattaro, Cristian
Bolton, Judith A. Hoffman
Koettgen, Anna
Bergmann, Sven
Mooser, Vincent
Chaturvedi, Nish
Frayling, Timothy M.
Islam, Muhammad
Jafar, Tazeen H.
Erdmann, Jeanette
Kulkarni, Smita R.
Bornstein, Stefan R.
Graessler, Juergen
Groop, Leif
Voight, Benjamin F.
Kettunen, Johannes
Howard, Philip
Taylor, Andrew
Guarrera, Simonetta
Ricceri, Fulvio
Emilsson, Valur
Plump, Andrew
Barroso, Ine S.
Khaw, Kay-Tee
Weder, Alan B.
Hunt, Steven C.
Sun, Yan V.
Bergman, Richard N.
Collins, Francis S.
Bonnycastle, Lori L.
Scott, Laura J.
Stringham, Heather M.
Peltonen, Leena
Perola, Markus
Vartiainen, Erkki
Brand, Stefan-Martin
Staessen, Jan A.
Wang, Thomas J.
Burton, Paul R.
Artigas, Maria Soler
Dong, Yanbin
Snieder, Harold
Wang, Xiaoling
Zhu, Haidong
Lohman, Kurt K.
Rudock, Megan E.
Heckbert, Susan R.
Smith, Nicholas L.
Wiggins, Kerri L.
Doumatey, Ayo
Shriner, Daniel
Veldre, Gudrun
Viigimaa, Margus
Kinra, Sanjay
Prabhakaran, Dorairaj
Tripathy, Vikal
Langefeld, Carl D.
Rosengren, Annika
Thelle, Dag S.
Corsi, Anna Maria
Singleton, Andrew
Forrester, Terrence
Hilton, Gina
McKenzie, Colin A.
Salako, Tunde
Iwai, Naoharu
Kita, Yoshikuni
Ogihara, Toshio
Ohkubo, Takayoshi
Okamura, Tomonori
Ueshima, Hirotsugu
Umemura, Satoshi
Eyheramendy, Susana
Meitinger, Thomas
Wichmann, H. -Erich
Cho, Yoon Shin
Kim, Hyung-Lae
Lee, Jong-Young
Scott, James
Sehmi, Joban S.
Zhang, Weihua
Hedblad, Bo
Nilsson, Peter
Smith, George Davey
Wong, Andrew
Narisu, Narisu
Stancakova, Alena
Raffel, Leslie J.
Yao, Jie
Kathiresan, Sekar
O'Donnell, Christopher J.
Schwartz, Stephen M.
Ikram, M. Arfan
Longstreth, W. T., Jr.
Mosley, Thomas H.
Seshadri, Sudha
Shrine, Nick R. G.
Wain, Louise V.
Morken, Mario A.
Swift, Amy J.
Laitinen, Jaana
Prokopenko, Inga
Zitting, Paavo
Cooper, Jackie A.
Humphries, Steve E.
Danesh, John
Rasheed, Asif
Goel, Anuj
Hamsten, Anders
Watkins, Hugh
Bakker, Stephan J. L.
van Gilst, Wiek H.
Janipalli, Charles S.
Mani, K. Radha
Yajnik, Chittaranjan S.
Hofman, Albert
Mattace-Raso, Francesco U. S.
Oostra, Ben A.
Demirkan, Ayse
Isaacs, Aaron
Rivadeneira, Fernando
Lakatta, Edward G.
Orru, Marco
Scuteri, Angelo
Ala-Korpela, Mika
Kangas, Antti J.
Lyytikainen, Leo-Pekka
Soininen, Pasi
Tukiainen, Taru
Wurtz, Peter
Ong, Rick Twee-Hee
Doerr, Marcus
Kroemer, Heyo K.
Voelker, Uwe
Voelzke, Henry
Galan, Pilar
Hercberg, Serge
Lathrop, Mark
Zelenika, Diana
Deloukas, Panos
Mangino, Massimo
Spector, Tim D.
Zhai, Guangju
Meschia, James F.
Nalls, Michael A.
Sharma, Pankaj
Terzic, Janos
Kumar, M. V. Kranthi
Denniff, Matthew
Zukowska-Szczechowska, Ewa
Wagenknecht, Lynne E.
Fowkes, F. Gerald R.
Charchar, Fadi J.
Schwarz, Peter E. H.
Hayward, Caroline
Guo, Xiuqing
Rotimi, Charles
Bots, Michiel L.
Brand, Eva
Samani, Nilesh J.
Polasek, Ozren
Talmud, Philippa J.
Nyberg, Fredrik
Kuh, Diana
Laan, Maris
Hveem, Kristian
Palmer, Lyle J.
van der Schouw, Yvonne T.
Casas, Juan P.
Mohlke, Karen L.
Vineis, Paolo
Raitakari, Olli
Ganesh, Santhi K.
Wong, Tien Y.
Tai, E. Shyong
Cooper, Richard S.
Laakso, Markku
Rao, Dabeeru C.
Harris, Tamara B.
Morris, Richard W.
Dominiczak, Anna F.
Kivimaki, Mika
Marmot, Michael G.
Miki, Tetsuro
Saleheen, Danish
Chandak, Giriraj R.
Coresh, Josef
Navis, Gerjan
Salomaa, Veikko
Han, Bok-Ghee
Zhu, Xiaofeng
Kooner, Jaspal S.
Melander, Olle
Ridker, Paul M.
Bandinelli, Stefania
Gyllensten, Ulf B.
Wright, Alan F.
Wilson, James F.
Ferrucci, Luigi
Farrall, Martin
Tuomilehto, Jaakko
Pramstaller, Peter P.
Elosua, Roberto
Soranzo, Nicole
Sijbrands, Eric J. G.
Altshuler, David
Loos, Ruth J. F.
Shuldiner, Alan R.
Gieger, Christian
Meneton, Pierre
Uitterlinden, Andre G.
Wareham, Nicholas J.
Gudnason, Vilmundur
Rotter, Jerome I.
Rettig, Rainer
Uda, Manuela
Strachan, David P.
Witteman, Jacqueline C. M.
Hartikainen, Anna-Liisa
Beckmann, Jacques S.
Boerwinkle, Eric
Vasan, Ramachandran S.
Boehnke, Michael
Larson, Martin G.
Jarvelin, Marjo-Riitta
Psaty, Bruce M.
Abecasis, Goncalo R.
Chakravarti, Aravinda
Elliott, Paul
van Duijn, Cornelia M.
Newton-Cheh, Christopher
Levy, Daniel
Caulfield, Mark J.
Johnson, Toby
CA Int Consortium Blood Pressure Geno
CARDIoGRAM Consortium
CKDGen Consortium
KidneyGen Consortium
EchoGen Consortium
CHARGE-HF Consortium
TI Genetic variants in novel pathways influence blood pressure and
cardiovascular disease risk
SO NATURE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; HYPERTENSION; METAANALYSIS;
LOCI; POPULATION; RELEVANCE; RECEPTOR; CLONING; HEALTH
AB Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
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[Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17487 Greifswald, Germany.
[Galan, Pilar; Hercberg, Serge] Univ Paris 13, Inst Natl Rech Agron U1125, Inst Natl Sante & Rech Med U557, F-93017 Bobigny, France.
[Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, Imperial Coll Cerebrovasc Unit ICCRU, London W6 8RF, England.
[Terzic, Janos] Univ Split, Fac Med, Split 21000, Croatia.
[Zukowska-Szczechowska, Ewa] Med Univ Silesia, Dept Internal Med Diabetol & Nephrol, PL-41800 Zabrze, Poland.
[Fowkes, F. Gerald R.] Univ Edinburgh, Sch Med, Div Community Hlth Sci, Publ Hlth Sci Sect, Edinburgh EH8 9AG, Midlothian, Scotland.
[Charchar, Fadi J.] Univ Ballarat, Sch Sci & Engn, Ballarat, Vic 3353, Australia.
[Schwarz, Peter E. H.] Tech Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, D-01307 Dresden, Germany.
[Brand, Eva] Univ Hosp Munster, Munster, Germany.
[Polasek, Ozren] Univ Zagreb, Andrija Stampar Sch Publ Hlth, Dept Med Stat Epidemiol & Med Informat, Zagreb 10000, Croatia.
[Nyberg, Fredrik] AstraZeneca R&D, S-43183 Molndal, Sweden.
[Palmer, Lyle J.] Ontario Inst Canc Res, Toronto, ON M5G 1L7, Canada.
[Palmer, Lyle J.] Univ Toronto, Samuel Lunenfeld Inst Med Res, Toronto, ON M5S 1A1, Canada.
[Casas, Juan P.] Univ London London Sch Hyg & Trop Med, Fac Epidemiol & Population Hlth, London WC1E 7HT, England.
[Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20521, Finland.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, Turku 20521, Finland.
[Ganesh, Santhi K.] Univ Michigan, Med Ctr, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Wong, Tien Y.] Singapore Eye Res Inst, Singapore 168751, Singapore.
[Wong, Tien Y.] Natl Univ Singapore, Dept Ophthalmol, Singapore 119074, Singapore.
[Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 119074, Singapore.
[Tai, E. Shyong] Duke Natl Univ Singapore, Grad Sch Med, Singapore 169857, Singapore.
[Rao, Dabeeru C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Morris, Richard W.] UCL, Dept Primary Care & Populat Hlth, London NW3 2PF, England.
[Dominiczak, Anna F.] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland.
[Coresh, Josef] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
[Navis, Gerjan] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, NL-9713 GZ Groningen, Netherlands.
[Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02215 USA.
[Bandinelli, Stefania] ASF, Geriatr Rehabil Unit, I-50100 Florence, Italy.
[Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki 00271, Finland.
[Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki 00014, Finland.
[Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki 60220, Finland.
[Tuomilehto, Jaakko] Hosp Univ La Paz, Red RECAVA Grp RD06 0014 0015, Madrid 28046, Spain.
[Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, I-39100 Bolzano, Italy.
[Elosua, Roberto] CIBER Epidemiol & Salud Publ, Barcelona 08003, Spain.
[Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA.
[Meneton, Pierre] Ctr Rech Cordeliers, Inst Natl Sante & Rech Med U872, F-75006 Paris, France.
[Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, D-17487 Greifswald, Germany.
[Hartikainen, Anna-Liisa] Univ Oulu, Inst Clin Med Obstet & Gynecol, Oulu 90014, Finland.
[Beckmann, Jacques S.] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland.
[Boerwinkle, Eric] Ctr Human Genet, Houston, TX 77030 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Div Epidemiol & Prevent, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu 90014, Finland.
[Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Oulu 90101, Finland.
[Jarvelin, Marjo-Riitta; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC HPA Ctr Environm & Hlth, London W2 1PG, England.
[van Duijn, Cornelia M.] NGI Erasmus Med Ctr, Ctr Med Syst Biol CMSB 1 2, Rotterdam, Netherlands.
RP Chakravarti, A (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD 21205 USA.
EM p.b.munroe@qmul.ac.uk; aravinda@jhmi.edu;
cnewtoncheh@chgr.mgh.harvard.edu; levyd@nhlbi.nih.gov;
m.j.caulfield@qmul.ac.uk
RI Colaus, PsyColaus/K-6607-2013; Okamura, Tomonori/L-1693-2013; Aulchenko,
Yurii/M-8270-2013; Altshuler, David/A-4476-2009; Grobbee,
Diederick/C-7651-2014; Schnabel, Renate/F-6527-2014; Pramstaller,
Peter/C-2357-2008; Cooper, Matthew/J-4420-2014; Willenborg,
Christina/D-2668-2012; Palmer, Lyle/K-3196-2014; Gaunt, Tom/O-3918-2014;
Kronenberg, Florian/B-1736-2008; Rudan, Igor/I-1467-2012; Hadley,
David/I-6902-2012; Heath, Simon/J-4138-2012; Rice, Kenneth/A-4150-2013;
Deloukas, Panos/B-2922-2013; gurrapu, gopi/A-9801-2011; Fuchsberger,
Christian/C-9646-2010; Giallauria, Francesco/B-5681-2013; Cavalieri,
Margherita/G-8053-2012; Johnson, Andrew/G-6520-2013; Kuznetsova,
Tatiana/I-6882-2013; Gale, Daniel/D-5594-2013; Singleton,
Andrew/C-3010-2009; Arora, Pankaj/F-3437-2011; Kottgen,
Anna/D-2920-2012; Lucas, Gavin/D-4346-2012; Spector, Tim/F-6533-2012;
Abecasis, Goncalo/B-7840-2010; Laan, Maris/A-4100-2011; Stark,
Klaus/D-3813-2009; Soininen, Pasi/B-9716-2008; Aspelund,
Thor/C-5983-2008; EHRET, Georg/A-9532-2009; Kivimaki, Mika/B-3607-2012;
Beckmann, Jacques S /A-9772-2008; Erdmann, Jeanette/P-7513-2014;
Hernandez-Fuentes, Maria/B-5011-2010; Maxwell, Patrick/C-5557-2008;
Lyytikainen, Leo-Pekka/C-8544-2016; Shi, Gang/D-3301-2016; Soler
Artigas, Maria/L-6529-2013; Burton, Paul/H-7527-2016; Smith,
Albert/K-5150-2015; Matullo, Giuseppe/K-6383-2016; Bochud,
Murielle/A-3981-2010; mangino, massimo/F-5134-2011; Hayward,
Caroline/M-8818-2016; Schwarz, Peter/B-5127-2013; Wong,
Andrew/M-8899-2016; Eggermann, Thomas/F-3807-2014; Boehm,
Bernhard/F-8750-2015; Bakker, Stephan/J-4023-2015; Onland-Moret, N.
Charlotte/G-9185-2011; Gudnason, Vilmundur/K-6885-2015; Staessen,
Jan/A-1065-2011; Mattace- Raso, Francesco/L-2541-2015; Wilson, James
F/A-5704-2009; Polasek, Ozren/B-6002-2011; Meitinger,
Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Prokopenko,
Inga/H-3241-2014; Konig, Inke/A-4544-2009; Erdmann,
Jeanette/A-4417-2009; Franke, Andre/B-2151-2010; Davey Smith,
George/A-7407-2013; Boban, Mladen/E-2777-2017; Feitosa,
Mary/K-8044-2012; Hicks, Andrew/E-9518-2017;
OI Okamura, Tomonori/0000-0003-0488-0351; Aulchenko,
Yurii/0000-0002-7899-1575; Altshuler, David/0000-0002-7250-4107;
Grobbee, Diederick/0000-0003-4472-4468; Cooper,
Matthew/0000-0003-1139-3682; Willenborg, Christina/0000-0001-5217-6882;
Palmer, Lyle/0000-0002-1628-3055; Gaunt, Tom/0000-0003-0924-3247;
Kronenberg, Florian/0000-0003-2229-1120; Rudan,
Igor/0000-0001-6993-6884; Rice, Kenneth/0000-0001-5779-4495; Deloukas,
Panos/0000-0001-9251-070X; Giallauria, Francesco/0000-0003-4119-9397;
Kuznetsova, Tatiana/0000-0003-3564-7405; Gale,
Daniel/0000-0002-9170-1579; Arora, Pankaj/0000-0003-2420-3550; Laan,
Maris/0000-0002-8519-243X; Stark, Klaus/0000-0002-7832-1942; Aspelund,
Thor/0000-0002-7998-5433; EHRET, Georg/0000-0002-5730-0675; Beckmann,
Jacques S /0000-0002-9741-1900; Adeyemo, Adebowale/0000-0002-3105-3231;
Kumari, Meena/0000-0001-9716-1035; Forouhi, Nita/0000-0002-5041-248X;
Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Watkins,
Hugh/0000-0002-5287-9016; Shrine, Nick/0000-0003-3641-4371; Zgaga,
Lina/0000-0003-4089-9703; Ramachandran, Vasan/0000-0001-7357-5970;
Erdmann, Jeanette/0000-0002-4486-6231; Humphries, Stephen
E/0000-0002-8221-6547; Soranzo, Nicole/0000-0003-1095-3852; Gieger,
Christian/0000-0001-6986-9554; Ziegler, Andreas/0000-0002-8386-5397;
Hernandez-Fuentes, Maria/0000-0002-7558-9441; Maxwell,
Patrick/0000-0002-0338-2679; Lyytikainen, Leo-Pekka/0000-0002-7200-5455;
Soler Artigas, Maria/0000-0002-3213-1107; Smith,
Albert/0000-0003-1942-5845; Bochud, Murielle/0000-0002-5727-0218;
mangino, massimo/0000-0002-2167-7470; Hayward,
Caroline/0000-0002-9405-9550; Schwarz, Peter/0000-0001-6317-7880; Wong,
Andrew/0000-0003-2079-4779; Bakker, Stephan/0000-0003-3356-6791;
Gudnason, Vilmundur/0000-0001-5696-0084; Staessen,
Jan/0000-0002-3026-1637; Wilson, James F/0000-0001-5751-9178; Polasek,
Ozren/0000-0002-5765-1862; Rivadeneira, Fernando/0000-0001-9435-9441;
Prokopenko, Inga/0000-0003-1624-7457; Talmud,
Philippa/0000-0002-5560-1933; Fuchsberger,
Christian/0000-0002-5918-8947; Monsalve, Beatriz
Elena/0000-0002-5994-866X; Johnson, Toby/0000-0002-5998-3270; Ikram,
Mohammad Arfan/0000-0003-0372-8585; MATULLO,
Giuseppe/0000-0003-0674-7757; Felix, Janine/0000-0002-9801-5774; Org,
Elin/0000-0003-1451-9375; Larson, Martin/0000-0002-9631-1254; ELOSUA,
ROBERTO/0000-0001-8235-0095; Sijbrands, Eric/0000-0001-8857-7389; Magi,
Reedik/0000-0002-2964-6011; Kivimaki, Mika/0000-0002-4699-5627; Whincup,
Peter/0000-0002-5589-4107; Franke, Andre/0000-0003-1530-5811; Davey
Smith, George/0000-0002-1407-8314; Feitosa, Mary/0000-0002-0933-2410;
Hicks, Andrew/0000-0001-6320-0411; Alexander,
Myriam/0000-0002-6848-9370; Abecasis, Goncalo/0000-0003-1509-1825;
Seielstad, Mark/0000-0001-5783-1401; Wurtz, Peter/0000-0002-5832-0221;
Seshadri, Sudha/0000-0001-6135-2622; Sternberg,
Michael/0000-0002-1884-5445; Marmot, Michael/0000-0002-2431-6419;
Prabhakaran, Dorairaj/0000-0002-3172-834X; Lawlor, Debbie
A/0000-0002-6793-2262; Tai, E Shyong/0000-0003-2929-8966; Johansson,
Asa/0000-0002-2915-4498; Morris, Richard/0000-0001-7240-4563; Bergmann,
Sven/0000-0002-6785-9034; Kleber, Marcus/0000-0003-0663-7275; Hypponen,
Elina/0000-0003-3670-9399; Dehghan, Abbas/0000-0001-6403-016X; Wain,
Louise/0000-0003-4951-1867
FU NIH/NHLBI
FX A number of the participating studies and authors are members of the
CHARGE and Global BPgen consortia. Many funding mechanisms by NIH/NHLBI,
European and private funding agencies contributed to this work and a
full list is provided in section 21 of the Supplementary Materials.
NR 28
TC 759
Z9 777
U1 22
U2 198
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 6
PY 2011
VL 478
IS 7367
BP 103
EP 109
DI 10.1038/nature10405
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400043
PM 21909115
ER
PT J
AU Jones, CU
Hunt, D
Shipley, WU
AF Jones, Christopher U.
Hunt, Daniel
Shipley, William U.
TI Radiotherapy and Androgen Deprivation for Prostate Cancer REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID RADIATION-THERAPY
C1 [Jones, Christopher U.] Radiol Associates Sacramento, Sacramento, CA USA.
[Hunt, Daniel] Radiat Therapy Oncol Grp, Philadelphia, PA USA.
[Shipley, William U.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Jones, CU (reprint author), Radiol Associates Sacramento, Sacramento, CA USA.
EM jonesc@radiological.com
NR 2
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 6
PY 2011
VL 365
IS 14
BP 1354
EP 1355
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 829KL
UT WOS:000295578700025
ER
PT J
AU Tilson, JK
Kaplan, SL
Harris, JL
Hutchinson, A
Ilic, D
Niederman, R
Potomkova, J
Zwolsman, SE
AF Tilson, Julie K.
Kaplan, Sandra L.
Harris, Janet L.
Hutchinson, Andy
Ilic, Dragan
Niederman, Richard
Potomkova, Jarmila
Zwolsman, Sandra E.
TI Sicily statement on classification and development of evidence-based
practice learning assessment tools
SO BMC MEDICAL EDUCATION
LA English
DT Article
ID EVIDENCE-BASED MEDICINE; EDUCATION; KNOWLEDGE; VALIDATION; CARE;
QUESTIONNAIRE; INSTRUMENTS; STRATEGIES; BELIEFS; QUALITY
AB Background: Teaching the steps of evidence-based practice (EBP) has become standard curriculum for health professions at both student and professional levels. Determining the best methods for evaluating EBP learning is hampered by a dearth of valid and practical assessment tools and by the absence of guidelines for classifying the purpose of those that exist. Conceived and developed by delegates of the Fifth International Conference of Evidence-Based Health Care Teachers and Developers, the aim of this statement is to provide guidance for purposeful classification and development of tools to assess EBP learning.
Discussion: This paper identifies key principles for designing EBP learning assessment tools, recommends a common taxonomy for new and existing tools, and presents the Classification Rubric for EBP Assessment Tools in Education (CREATE) framework for classifying such tools. Recommendations are provided for developers of EBP learning assessments and priorities are suggested for the types of assessments that are needed. Examples place existing EBP assessments into the CREATE framework to demonstrate how a common taxonomy might facilitate purposeful development and use of EBP learning assessment tools.
Summary: The widespread adoption of EBP into professional education requires valid and reliable measures of learning. Limited tools exist with established psychometrics. This international consensus statement strives to provide direction for developers of new EBP learning assessment tools and a framework for classifying the purposes of such tools.
C1 [Tilson, Julie K.] Univ So Calif, Div Biokinesiol & Phys Therapy, Los Angeles, CA 90089 USA.
[Kaplan, Sandra L.] Univ Med & Dent New Jersey, Dept Rehabil & Movement Sci, Doctoral Programs Phys Therapy, Newark, NJ 07103 USA.
[Harris, Janet L.] Univ Sheffield, Sch Hlth & Related Res, Sheffield S10 2TN, S Yorkshire, England.
[Hutchinson, Andy] Natl Inst Hlth & Clin Excellence, Natl Prescribing Ctr, Liverpool, Merseyside, England.
[Ilic, Dragan] Monash Univ, Dept Epidemiol & Prevent Med, Sch Publ Hlth & Prevent Med, Clayton, Vic 3800, Australia.
[Niederman, Richard] Forsyth Inst, Ctr Evidence Based Dent, Boston, MA USA.
[Potomkova, Jarmila] Palacky Univ, Med Lib, CR-77147 Olomouc, Czech Republic.
[Zwolsman, Sandra E.] Univ Amsterdam, Acad Med Ctr, Dept Gen Practice Family Med, NL-1012 WX Amsterdam, Netherlands.
RP Tilson, JK (reprint author), Univ So Calif, Div Biokinesiol & Phys Therapy, Los Angeles, CA 90089 USA.
EM tilson@usc.edu
RI Ilic, Dragan/I-2437-2014;
OI Ilic, Dragan/0000-0001-5127-9185; niederman, richard/0000-0001-6674-1774
NR 50
TC 42
Z9 43
U1 3
U2 34
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6920
J9 BMC MED EDUC
JI BMC Med. Educ.
PD OCT 5
PY 2011
VL 11
AR 78
DI 10.1186/1472-6920-11-78
PG 10
WC Education & Educational Research; Education, Scientific Disciplines
SC Education & Educational Research
GA 851XN
UT WOS:000297305800001
PM 21970731
ER
PT J
AU Suri, P
Rainville, J
Fitzmaurice, GM
Katz, JN
Jamison, RN
Martha, J
Hartigan, C
Limke, J
Jouve, C
Hunter, DJ
AF Suri, Pradeep
Rainville, James
Fitzmaurice, Garrett M.
Katz, Jeffrey N.
Jamison, Robert N.
Martha, Julia
Hartigan, Carol
Limke, Janet
Jouve, Cristin
Hunter, David J.
TI Acute low back pain is marked by variability: An internet-based pilot
study
SO BMC MUSCULOSKELETAL DISORDERS
LA English
DT Article
ID PRIMARY-CARE; EPIDEMIOLOGY; DISABILITY; EPISODE; FEAR
AB Background: Pain variability in acute LBP has received limited study. The objectives of this pilot study were to characterize fluctuations in pain during acute LBP, to determine whether self-reported 'flares' of pain represent discrete periods of increased pain intensity, and to examine whether the frequency of flares was associated with back-related disability outcomes.
Methods: We conducted a cohort study of acute LBP patients utilizing frequent serial assessments and Internet-based data collection. Adults with acute LBP (lasting <= 3 months) completed questionnaires at the time of seeking care, and at both 3-day and 1-week intervals, for 6 weeks. Back pain was measured using a numerical pain rating scale (NPRS), and disability was measured using the Oswestry Disability Index (ODI). A pain flare was defined as 'a period of increased pain lasting at least 2 hours, when your pain intensity is distinctly worse than it has been recently'. We used mixed-effects linear regression to model longitudinal changes in pain intensity, and multivariate linear regression to model associations between flare frequency and disability outcomes.
Results: 42 of 47 participants (89%) reported pain flares, and the average number of discrete flare periods per patient was 3.5 over 6 weeks of follow-up. More than half of flares were less than 4 hours in duration, and about 75% of flares were less than one day in duration. A model with a quadratic trend for time best characterized improvements in pain. Pain decreased rapidly during the first 14 days after seeking care, and leveled off after about 28 days. Patients who reported a pain flare experienced an almost 3-point greater current NPRS than those not reporting a flare (mean difference [SD] 2.70 [0.11]; p < 0.0001). Higher flare frequency was independently associated with a higher final ODI score (beta [SE} 0.28 (0.08); p = 0.002).
Conclusions: Acute LBP is characterized by variability. Patients with acute LBP report multiple distinct flares of pain, which correspond to discrete increases in pain intensity. A higher flare frequency is associated with worse disability outcomes.
C1 [Suri, Pradeep] VA Boston Healthcare Syst, Div PM&R, Boston, MA USA.
[Suri, Pradeep] Spaulding Rehabil Hosp Network, Boston, MA USA.
[Suri, Pradeep; Rainville, James; Martha, Julia; Hartigan, Carol; Limke, Janet; Jouve, Cristin; Hunter, David J.] New England Baptist Hosp, Boston, MA USA.
[Suri, Pradeep; Rainville, James; Hartigan, Carol; Limke, Janet; Jouve, Cristin] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA.
[Fitzmaurice, Garrett M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA 02115 USA.
[Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA.
[Jamison, Robert N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA.
[Jamison, Robert N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Martha, Julia] New England Res Inst, Watertown, MA USA.
[Hunter, David J.] Univ Sydney, No Clin Sch, Sydney, NSW 2006, Australia.
RP Suri, P (reprint author), VA Boston Healthcare Syst, Div PM&R, Boston, MA USA.
EM pradeep.suri@va.gov
RI Hunter, David/A-4622-2010;
OI Hunter, David/0000-0003-3197-752X; Jamison, Robert/0000-0003-1768-0906
FU Rehabilitation Medicine Scientist Training Program (RMSTP); National
Institutes of Health [K12 HD001097]; Australian Research Council;
NIH/NIAMS [K24 AR 02123, P60 AR 47782]; NIH/NIDA [R21 DA024298]
FX Dr. Suri is funded by the Rehabilitation Medicine Scientist Training
Program (RMSTP) and the National Institutes of Health (K12 HD001097). Dr
Hunter is funded by an Australian Research Council Future Fellowship.
Dr. Katz is funded in part by NIH/NIAMS K24 AR 02123 and NIH/NIAMS P60
AR 47782. Dr. Jamison was funded in part by NIH/NIDA R21 DA024298. The
authors would like to thank the study participants for making this
research possible. A portion of this material was presented at the
Association of Academic Physiatrists Annual Meeting, Phoenix, AZ, USA,
April 12-16, 2011.
NR 25
TC 7
Z9 7
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2474
J9 BMC MUSCULOSKEL DIS
JI BMC Musculoskelet. Disord.
PD OCT 5
PY 2011
VL 12
AR 220
DI 10.1186/1471-2474-12-220
PG 9
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 839NQ
UT WOS:000296374700002
PM 21974962
ER
PT J
AU Lee, KY
Gesta, S
Boucher, J
Wang, XL
Kahn, CR
AF Lee, Kevin Y.
Gesta, Stephane
Boucher, Jeremie
Wang, Xiaohui L.
Kahn, C. Ronald
TI The Differential Role of Hif1 beta/Arnt and the Hypoxic Response in
Adipose Function, Fibrosis, and Inflammation
SO CELL METABOLISM
LA English
DT Article
ID INDUCIBLE FACTOR 1-ALPHA; ARYL-HYDROCARBON RECEPTOR; MITOCHONDRIAL
COMPLEX-III; KNOCK-OUT MICE; GENE-EXPRESSION; TISSUE HYPOXIA; 3T3-L1
CELLS; OBESITY; ARNT; ACTIVATION
AB In obesity, adipocytes distant from vasculature become hypoxic and dysfunctional. This hypoxic response is mediated by hypoxia-inducible factors Hif1 alpha, Hif2 alpha, and Hif3 alpha) and their obligate partner, Hif1 beta (Arnt). We show that mice lacking Hif1 beta in fat (FH1 beta KO) are lean, exhibit reduced adipocyte size, and are protected from age- and diet-induced glucose intolerance. There is also reduced Vegf and vascular permeability in FH1 beta KO fat, but diet-induced inflammation and fibrosis is unchanged. Adipocytes from FH1 beta KO mice have reduced glucose uptake due to decreased Glut1 and Glut4, which is mirrored in 3T3-L1 adipocytes with Hif1 beta knockdown. Hif1 beta knockdown cells also fail to respond appropriately to hypoxia with reduced cellular respiration and reduced mitochondrial gene expression. Some, but not all, of these effects are reproduced by Hif1 alpha knockdown. Thus, Hif1 beta/Arnt regulates glucose uptake, mitochondrial gene expression, and vascular permeability to control adipose mass and function, providing a target for obesity therapy.
C1 [Lee, Kevin Y.; Gesta, Stephane; Boucher, Jeremie; Wang, Xiaohui L.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.
RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.
EM c.ronald.kahn@joslin.harvard.edu
FU Joslin Training Grant [T32DK007260]; NIH [DK 60837, DK 82655]; American
Diabetes Association
FX The authors would like to thank Dr. Frank J. Gonzalez (National Cancer
Institute) for the Hif1 beta floxed mice. We are grateful to M. Rourk
and G. Smyth for animal care; C. Cahill (Joslin Diabetes Research &
Endocrinology Center [DERC] Advanced Microscopy Core); and A. Clermont,
M. Poillucci (DERC Physiology Core), H. Li (DERC Specialized Assay
Core), and J. Schroeder (DERC Genomics Core) for technical assistance.
This work was supported by the Joslin Training Grant (T32DK007260), NIH
grants DK 60837 and DK 82655, an American Diabetes Association
mentor-based award, and the Mary K. Iacocca Professorship to C.R.K.
NR 43
TC 25
Z9 26
U1 1
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD OCT 5
PY 2011
VL 14
IS 4
BP 491
EP 503
DI 10.1016/j.cmet.2011.08.006
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 837SN
UT WOS:000296223600009
PM 21982709
ER
PT J
AU Zhou, YF
Eng, ET
Nishida, N
Lu, CF
Walz, T
Springer, TA
AF Zhou, Yan-Feng
Eng, Edward T.
Nishida, Noritaka
Lu, Chafen
Walz, Thomas
Springer, Timothy A.
TI A pH-regulated dimeric bouquet in the structure of von Willebrand factor
SO EMBO JOURNAL
LA English
DT Article
DE biosynthesis; endothelium; platelets; shear flow; Weibel-Palade bodies
ID HUMAN VONWILLEBRAND-FACTOR; WEIBEL-PALADE BODIES; PLATELET GLYCOPROTEIN
IB; FACTOR A1 DOMAIN; ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE; FACTOR
STORAGE; A3 DOMAIN; PROTEIN; MULTIMERIZATION
AB At the acidic pH of the trans-Golgi and Weibel-Palade bodies (WPBs), but not at the alkaline pH of secretion, the C-terminal similar to 1350 residues of von Willebrand factor (VWF) zip up into an elongated, dimeric bouquet. Six small domains visualized here for the first time between the D4 and cystine-knot domains form a stem. The A2, A3, and D4 domains form a raceme with three pairs of opposed, large, flower-like domains. N-terminal VWF domains mediate helical tubule formation in WPBs and template N-terminal disulphide linkage between VWF dimers, to form ultralong VWF concatamers. The dimensions we measure in VWF at pH 6.2 and 7.4, and the distance between tubules in nascent WPB, suggest that dimeric bouquets are essential for correct VWF dimer incorporation into growing tubules and to prevent cross-linking between neighbouring tubules. Further insights into the structure of the domains and flexible segments in VWF provide an overall view of VWF structure important for understanding both the biogenesis of ultralong concatamers at acidic pH and flow-regulated changes in concatamer conformation in plasma at alkaline pH that trigger hemostasis. The EMBO Journal (2011) 30, 4098-4111. doi:10.1038/emboj.2011.297; Published online 19 August 2011
C1 [Springer, Timothy A.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Immune Dis Inst,CLSB,Childrens Hosp,Dept Pathol, Boston, MA 02115 USA.
[Nishida, Noritaka] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan.
[Walz, Thomas] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Cell Biol, Boston, MA 02115 USA.
RP Springer, TA (reprint author), Harvard Univ, Sch Med, Program Cellular & Mol Med, Immune Dis Inst,CLSB,Childrens Hosp,Dept Pathol, 3 Blackfan Circle, Boston, MA 02115 USA.
EM springer@idi.harvard.edu
RI Zhou, Yanfeng/B-3792-2012
FU NIH [HL-48675]
FX This work was supported by NIH Grant HL-48675. TW is an investigator in
the Howard Hughes Medical Institute.
NR 46
TC 36
Z9 36
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD OCT 5
PY 2011
VL 30
IS 19
BP 4098
EP 4111
DI 10.1038/emboj.2011.297
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 834ND
UT WOS:000295967300021
PM 21857647
ER
PT J
AU Souer, JS
Buijze, G
Ring, D
AF Souer, J. Sebastiaan
Buijze, Geert
Ring, David
TI A Prospective Randomized Controlled Trial Comparing Occupational Therapy
with Independent Exercises After Volar Plate Fixation of a Fracture of
the Distal Part of the Radius
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID COLLES FRACTURES; WRIST FRACTURES; PREDICTORS; PHYSIOTHERAPY; PAIN;
DISABILITY
AB Background: The effect of formal occupational therapy on recovery after open reduction and volar plate fixation of a fracture of the distal part of the radius is uncertain. We hypothesized that there would be no difference in wrist function and arm-specific disability six months after open reduction and volar plate fixation of a distal radial fracture between patients who receive formal occupational therapy and those with instructions for independent exercises.
Methods: Ninety-four patients with an unstable distal radial fracture treated with open reduction and volar locking plate fixation were enrolled in a prospective randomized controlled trial comparing exercises done under the supervision of an occupational therapist with surgeon-directed independent exercises. The primary study question addressed combined wrist flexion and extension six months after surgery Secondary study questions addressed wrist motion, grip strength, Gartland and Werley scores, Mayo wrist scores, and DASH (Disabilities of the Arm, Shoulder and Hand) scores at three months and six months after surgery.
Results: There was a significant difference in the mean arc of wrist flexion and extension six months after surgery (118 degrees versus 129 degrees), favoring patients prescribed independent exercises. Three months after surgery, there was a significant difference in mean pinch strength (80% versus 90%), mean grip strength (66% versus 81%), and mean Gartland and Werley scores, favoring patients prescribed independent exercises. At six months, there was a.significant difference in mean wrist extension (55 degrees versus 62 degrees), ulnar deviation (82% versus 93%), mean supination (84 degrees versus 90 degrees), mean grip strength (81% versus 92%), and mean Mayo score, favoring patients prescribed independent exercises. There were no differences in arm-specific disability (DASH score) at any time point.
Conclusions: Prescription of formal occupational therapy does not improve the average motion or disability score after volar locking plate fixation of a fracture of the distal part of the radius.
C1 [Souer, J. Sebastiaan; Buijze, Geert; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
NR 17
TC 22
Z9 22
U1 0
U2 6
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD OCT 5
PY 2011
VL 93A
IS 19
BP 1761
EP 1766
DI 10.2106/JBJS.J.01452
PG 6
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 832OA
UT WOS:000295813100001
PM 22005860
ER
PT J
AU Ziperstein, JC
AF Ziperstein, Joshua C.
TI Je Vais le Faire
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA.
RP Ziperstein, JC (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA.
EM jziperstein@partners.org
NR 0
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 OCT 5
PY 2011
VL 306
IS 13
BP 1418
EP 1419
DI 10.1001/jama.2011.1411
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 828MZ
UT WOS:000295506900001
PM 21972298
ER
PT J
AU Perrin, JM
Kolls, JK
Coury, DL
AF Perrin, James M.
Kolls, Jay K.
Coury, Daniel L.
TI Evidence-Based Practice and Health Advocacy Organizations
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Perrin, James M.] MassGen Hosp Children, Boston, MA USA.
[Kolls, Jay K.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA.
[Coury, Daniel L.] Nationwide Childrens Hosp, Columbus, OH USA.
RP Perrin, JM (reprint author), MassGen Hosp Children, Boston, MA USA.
EM jperrin@partners.org
RI Coury, Daniel/E-2925-2011
NR 5
TC 0
Z9 0
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 OCT 5
PY 2011
VL 306
IS 13
BP 1443
EP 1443
DI 10.1001/jama.2011.1404
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 828MZ
UT WOS:000295506900016
PM 21972304
ER
PT J
AU Rao, SV
Kaltenbach, LA
Weintraub, WS
Roe, MT
Brindis, RG
Rumsfeld, JS
Peterson, ED
AF Rao, Sunil V.
Kaltenbach, Lisa A.
Weintraub, William S.
Roe, Matthew T.
Brindis, Ralph G.
Rumsfeld, John S.
Peterson, Eric D.
TI Prevalence and Outcomes of Same-Day Discharge After Elective
Percutaneous Coronary Intervention Among Older Patients
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID SINGLE-CENTER EXPERIENCE; DAY HOME DISCHARGE; STENT IMPLANTATION;
ANGIOPLASTY; OUTPATIENT; FEASIBILITY; SAFETY; STAY; TRENDS; BOLUS
AB Context Patients undergoing elective percutaneous coronary intervention (PCI) are generally observed overnight in the hospital. The association between same-day discharge of older patients and death or readmission is unclear.
Objective To evaluate the prevalence and outcomes of same-day discharge among older patients undergoing elective PCI in the United States.
Design, Setting, and Participants Multicenter cohort study. Data were from 107 018 patients 65 years or older undergoing elective PCI procedures at 903 sites participating in the CathPCI Registry between November 2004 and December 2008 and were linked with Medicare Part A claims. Patients were divided into 2 groups based on their length of stay after PCI: same-day discharge or overnight stay.
Main Outcome Measures Death or rehospitalization occurring within 2 days and by 30 days after PCI.
Results The prevalence of same-day discharge was 1.25% (95% CI, 1.19%-1.32%; n = 1339 patients) with significant variation across facilities. Patient characteristics were similar between the 2 groups, although same-day discharge patients underwent shorter procedures with less multivessel intervention. There were no significant differences in the rates of death or rehospitalization at 2 days (same-day discharge, 0.37% [95% CI, 0.16%-0.87%] vs overnight stay, 0.50% [95% CI, 0.46%-0.54%]; P = .51) or at 30 days (same-day discharge, 9.63% [95% CI, 8.17%-11.33%] vs overnight stay, 9.70% [95% CI, 9.52%-9.88%]; P = .94). Among patients with adverse outcomes, the median time to death or rehospitalization did not differ significantly between the groups (same-day discharge, 13 days [interquartile range, 7.0-21.0] vs overnight stay, 14 days [interquartile range, 7.0-21.0]; P = .96). After adjustment for patient and procedure characteristics, same-day discharge was not significantly associated with 30-day death or rehospitalization (adjusted odds ratio, 0.95 [95% CI, 0.78-1.16]).
Conclusion Among selected low-risk Medicare patients undergoing elective PCI, same-day discharge is rarely implemented but is not associated with death or rehospitalization compared with overnight observation. JAMA. 2011;306(13):1461-1467
C1 [Rao, Sunil V.; Kaltenbach, Lisa A.; Roe, Matthew T.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC 27705 USA.
[Weintraub, William S.] Christiana Care Hosp, Newark, DE USA.
[Brindis, Ralph G.] No Calif Kaiser Permanente, Oakland, CA USA.
[Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA.
RP Rao, SV (reprint author), Duke Clin Res Inst, 508 Fulton St 111A, Durham, NC 27705 USA.
EM sunil.rao@duke.edu
FU Terumo Medical; Medicines Company; AstraZeneca; Zoll; Ikaria;
sanofi-aventis; Otsuka; Bristol-Myers Squibb; Abbott; Eli Lilly;
Shionogi; Cardionet; Daiichi-Sankyo; Roche; Novartis; Merck-Schering
Plough; American College of Cardiology; American Heart Association;
GlaxoSmithKline; KAI Pharmaceuticals; Orexigen; Helsinn Pharmaceuticals;
Regeneron; Schering Plough/Merck; Johnson Johnson; St Jude Inc; Bayer;
Pfizer; American College of Cardiology Foundation National
Cardiovascular Data Registry (NCDR)
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Rao reported receiving consulting
fees from Terumo Medical, The Medicines Company, AstraZeneca, and Zoll
and research funding from Ikaria, sanofi-aventis, and Terumo Medical. Dr
Weintraub reported receiving research grants from Otsuka, AstraZeneca,
Bristol-Myers Squibb, sanofi-aventis, and Abbott; receiving consultant
fees from Eli Lilly, Bristol-Myers Squibb, Shionogi, sanofi-aventis,
Cardionet, and Daiichi-Sankyo; and providing expert testimony in cases
involving Bayer and Pfizer. Dr Roe reported receiving research funding
from Eli Lilly, Roche, Novartis, Merck-Schering Plough, Bristol-Myers
Squibb, the American College of Cardiology, and the American Heart
Association and consulting fees/honoraria from GlaxoSmithKline, KAI
Pharmaceuticals, Novartis, Eli Lilly, Bristol-Myers Squibb,
sanofi-aventis, Merck, Orexigen, Helsinn Pharmaceuticals, Regeneron, and
AstraZeneca. Dr Rumsfeld reported being chief science officer for the
National Cardiovascular Data Registry. Dr Peterson reported receiving
research grants from Bristol-Myers Squibb, sanofi-aventis, Eli Lilly,
Schering Plough/Merck, Johnson & Johnson, and St Jude Inc and consultant
fees from Bayer and Pfizer. No other disclosures were reported.; This
analysis was funded by the American College of Cardiology. This research
was supported by the American College of Cardiology Foundation National
Cardiovascular Data Registry (NCDR).
NR 25
TC 40
Z9 42
U1 0
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 5
PY 2011
VL 306
IS 13
BP 1461
EP 1467
DI 10.1001/jama.2011.1409
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 828MZ
UT WOS:000295506900025
PM 21972308
ER
PT J
AU Lee, SJ
Walter, LC
AF Lee, Sei J.
Walter, Louise C.
TI Quality Indicators for Older Adults Preventing Unintended Harms
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID PRACTICE GUIDELINES; OF-CARE; CANCER; PERFORMANCE; LESSONS
C1 [Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA.
Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
RP Lee, SJ (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St,Bldg 1,Room 211A, San Francisco, CA 94121 USA.
EM sei.lee@ucsf.edu
FU NCI NIH HHS [R01 CA134425, 1R01CA134425]; NCRR NIH HHS [KL2 RR024130,
KL2 RR024130-02]; NIA NIH HHS [K23 AG040779]
NR 10
TC 19
Z9 19
U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 5
PY 2011
VL 306
IS 13
BP 1481
EP 1482
DI 10.1001/jama.2011.1418
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 828MZ
UT WOS:000295506900028
PM 21972311
ER
PT J
AU Foster, MC
Hwang, SJ
Porter, SA
Massaro, JM
Hoffmann, U
Fox, CS
AF Foster, Meredith C.
Hwang, Shih-Jen
Porter, Stacy A.
Massaro, Joseph M.
Hoffmann, Udo
Fox, Caroline S.
TI Development and reproducibility of a computed tomography-based
measurement of renal sinus fat
SO BMC NEPHROLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; BODY-MASS INDEX; COMMUNITY-BASED POPULATION;
IMPROVING GLOBAL OUTCOMES; CARDIOVASCULAR-DISEASE; LIPID-ACCUMULATION;
METABOLIC SYNDROME; RISK-FACTORS; UNITED-STATES; OBESITY
AB Background: Renal sinus fat may mediate obesity-related vascular disease, although this fat depot has not been assessed in a community-based sample. We sought to develop a protocol to quantify renal sinus fat accumulation using multi-detector computed tomography (MDCT).
Methods: Protocol development was performed in participants in the Framingham Offspring cohort who underwent MDCT. Volumetric renal sinus fat was measured separately within the right and left kidneys, and renal sinus fat area within a single MDCT scan slice was measured in the right kidney. Due to the high correlation of volumetric and single-slice renal sinus fat in the right kidney (Pearson correlation [r] = 0.85, p < 0.0001), we optimized a single-slice protocol to capture renal sinus fat in the right kidney alone. Pearson correlation coefficients were used to compare to assess the correlation of volumetric and single-slice renal sinus fat in the right kidney with other measures of adiposity. Inter-and intra-reader reproducibility was assessed using intra-class correlation coefficients.
Results: Single-slice measurements were obtained in 92 participants (mean age 60 years, 49% women, median renal sinus fat 0.43 cm(2)). Intra- and inter-reader intra-class correlation coefficients were 0.93 and 0.86, respectively. Single-slice renal sinus fat was correlated with body mass index (r = 0.35, p = 0.0006), waist circumference (r = 0.31, p = 0.003), and abdominal visceral fat (r = 0.48, p < 0.0001). Similar correlations were observed for volumetric renal sinus fat in the right kidney.
Conclusions: Measuring renal sinus fat is feasible and reproducible using MDCT scans in a community-based sample.
C1 [Foster, Meredith C.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Foster, Meredith C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Foster, Meredith C.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA.
[Porter, Stacy A.] Harvard Univ, Sch Med, Boston, MA USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol & Metab, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
OI Massaro, Joseph/0000-0002-2682-4812
FU National Heart, Lung and Blood Institute [N01-HC-25195]
FX The Framingham Heart Study is supported by the National Heart, Lung and
Blood Institute (N01-HC-25195). The funding body did not play a role in
the study design, collection, analysis, and interpretation of data, in
the writing of the manuscript, or the decision to submit the manuscript
for publication.
NR 43
TC 4
Z9 4
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2369
J9 BMC NEPHROL
JI BMC Nephrol.
PD OCT 4
PY 2011
VL 12
AR 52
DI 10.1186/1471-2369-12-52
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 946PV
UT WOS:000304366000001
PM 21970591
ER
PT J
AU Yeh, RW
Normand, SLT
Wolf, RE
Jones, PG
Ho, KKL
Cohen, DJ
Cutlip, DE
Mauri, L
Kugelmass, AD
Amin, AP
Spertus, JA
AF Yeh, Robert W.
Normand, Sharon-Lise T.
Wolf, Robert E.
Jones, Philip G.
Ho, Kalon K. L.
Cohen, David J.
Cutlip, Donald E.
Mauri, Laura
Kugelmass, Aaron D.
Amin, Amit P.
Spertus, John A.
TI Predicting the Restenosis Benefit of Drug-Eluting Versus Bare Metal
Stents in Percutaneous Coronary Intervention
SO CIRCULATION
LA English
DT Article
DE coronary intervention; outcome assessment; predictors; restenosis;
stents
ID CARDIOVASCULAR DATA REGISTRY; ACUTE MYOCARDIAL-INFARCTION; BYPASS
GRAFT-SURGERY; ANGIOGRAPHIC PREDICTORS; CLINICAL RESTENOSIS; OUTCOMES;
TRIALS; RISK; IMPLANTATION; SAFETY
AB Background-Drug-eluting stents (DES) for percutaneous coronary intervention decrease the risk of restenosis compared with bare metal stents. However, they are costlier, require prolonged dual antiplatelet therapy, and provide the most benefit in patients at highest risk for restenosis. To assist physicians in targeting DES use in patients at the highest risk for target vessel revascularization (TVR), we developed and validated a model to predict TVR.
Methods and Results-Preprocedural clinical and angiographic data from 27 107 percutaneous coronary intervention hospitalizations between October 1, 2004, and September 30, 2007, in Massachusetts were used to develop prediction models for TVR at 1 year. Models were developed from a two-thirds random sample and validated in the remaining third. The overall rate of TVR was 7.6% (6.7% with DES, 11% with bare metal stents). Significant predictors of TVR included prior percutaneous coronary intervention, emergency or salvage percutaneous coronary intervention, prior coronary bypass surgery, peripheral vascular disease, diabetes mellitus, and angiographic characteristics. The model was superior to a 3-variable model of diabetes mellitus, stent diameter, and stent length (c statistic, 0.66 versus 0.60; P<0.001) and was well calibrated. The predicted number needed to treat with DES to prevent 1 TVR compared with bare metal stents ranged from 6 (95% confidence interval, 5.4-7.6) to 80 (95% confidence interval, 62.7-116.3), depending on patients' clinical and angiographic factors.
Conclusions-A predictive model using commonly collected variables can identify patients who may derive the greatest benefit in TVR reduction from DES. Whether use of the model improves the safety and cost-effectiveness of DES use should be tested prospectively. (Circulation. 2011;124:1557-1564.)
C1 [Yeh, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02144 USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02144 USA.
[Normand, Sharon-Lise T.; Wolf, Robert E.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02144 USA.
[Cohen, David J.; Amin, Amit P.; Spertus, John A.] Univ Missouri, Kansas City, MO USA.
[Cohen, David J.; Amin, Amit P.; Spertus, John A.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA.
[Ho, Kalon K. L.; Cutlip, Donald E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Cardiol, Boston, MA 02144 USA.
[Mauri, Laura] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02144 USA.
[Kugelmass, Aaron D.] Baystate Med Ctr, Dept Med, Div Cardiol, Springfield, MA 01199 USA.
RP Yeh, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, GRB 800, Boston, MA 02144 USA.
EM ryeh@partners.org
FU Massachusetts Data Analysis Center; Massachusetts Department of Public
Health; Boston Scientific; Medtronic; Abbott Vascular; Cordis; Eli
Lilly; Daiichi Sankyo; Bristol Myers Squibb; Sanofi-aventis; National
Heart, Lung, and Blood Institute [HL096624]; American Heart Association
[0875149N]; Lilly; BMS/Sanofi; Amgen; Evaheart
FX Dr Yeh is an investigator for the Harvard Clinical Research Institute
and a consultant for the Kaiser Permanente Division of Research. Dr
Normand is director of the Massachusetts Data Analysis Center,
contracted by the Massachusetts Department of Public Health, and is
funded to collect, validate, analyze, and disseminate evidence of
quality of cardiovascular care at acute care nonfederal hospitals in
Massachusetts. R. E. Wolf is senior programmer for the Massachusetts
Data Analysis Center and is funded to support biostatistical and
programming aspects of the Center. Dr Cohen receives grant support from
Boston Scientific, Medtronic, and Abbott Vascular and has served as a
consultant to Medtronic, Abbott Vascular, and Cordis. Dr Mauri receives
institutional research support from Abbott, Boston Scientific, Cordis,
Medtronic, Eli Lilly, Daiichi Sankyo, Bristol Myers Squibb, and
Sanofi-aventis and has consulted for Cordis and Medtronic. Dr Spertus
has received research grants from the National Heart, Lung, and Blood
Institute (HL096624) and the American Heart Association (0875149N) to
study the impact of prospective risk estimation on the use of DES as a
function of patients' risks for restenosis. Within the past 2 years, he
has also received research grant support from Lilly, BMS/Sanofi, Amgen,
and Evaheart and has consulted for United Healthcare, Gilead, Quest
Diagnostics, and St. Jude Medical. He has patents and an equity position
in Health Outcomes Sciences, which supports the technology to deliver
individualized estimates of patients' outcomes based on multivariable
models. The other authors report no conflicts.
NR 31
TC 30
Z9 34
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 4
PY 2011
VL 124
IS 14
BP 1557
EP U162
DI 10.1161/CIRCULATIONAHA.111.045229
PG 15
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 829UG
UT WOS:000295609200018
PM 21900079
ER
PT J
AU Tanaka, A
Shimada, K
Tearney, GJ
Kitabata, H
Taguchi, H
Fukuda, S
Kashiwagi, M
Kubo, T
Takarada, S
Hirata, K
Mizukoshi, M
Yoshikawa, J
Bouma, BE
Akasaka, T
AF Tanaka, Atsushi
Shimada, Kenei
Tearney, Guillermo J.
Kitabata, Hironori
Taguchi, Haruyuki
Fukuda, Shota
Kashiwagi, Manabu
Kubo, Takashi
Takarada, Shigeho
Hirata, Kumiko
Mizukoshi, Masato
Yoshikawa, Junichi
Bouma, Brett E.
Akasaka, Takashi
TI Conformational Change in Coronary Artery Structure Assessed by Optical
Coherence Tomography in Patients With Vasospastic Angina
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE coronary; imaging; optical coherence tomography; spasm
ID SPASTIC ANGINA; INTRAVASCULAR ULTRASOUND; VARIANT ANGINA; PLAQUE;
ATHEROSCLEROSIS; FEATURES; PECTORIS
AB Objectives The aim of this study was to investigate the conformational change of arterial structure in the vasospastic lesion with optical coherence tomography.
Background Coronary artery spasm plays an important role in the pathogenesis of ischemic heart diseases. The conformational change of each arterial layer during vasospasm has not been studied in detail.
Methods We assessed 19 coronary arteries (10 spasm and 9 nonspasm lesions) with optical coherence tomography during the provocation test for coronary spasm. An intimal bump was defined as 1 or more intimal projections into the lumen that disappeared after the administration of nitroglycerine (NTG). Intimal gathering was defined as a folding/gathering of the intima, resulting in multiple kinks in the luminal contour that resolved after the administration of NTG.
Results The spasm lesion more frequently showed an intimal bump at baseline and intimal gathering during spasm compared with the nonspasm lesion (spasm 80% vs. nonspasm 0%, p < 0.01, spasm 100% vs. nonspasm 0%, p < 0.01, respectively). The spasm lesion demonstrated a thicker maximum media thickness (spasm 0.24 +/- 0.04 mm vs. nonspasm 0.12 +/- 0.03 mm, p < 0.01) at baseline, whereas no differences were observed after the administration of NTG (spasm 0.13 +/- 0.03 mm vs. nonspasm 0.13 +/- 0.02 mm, p = 0.65).
Conclusions Our results suggest that medial contraction occurs even in an asymptomatic state and facilitates the formation of an intimal bump in patients with vasospastic angina. Luminal narrowing during spasm is associated with intimal gathering without alteration of intimal area. (J Am Coll Cardiol 2011;58:1608-13) (C) 2011 by the American College of Cardiology Foundation
C1 [Tanaka, Atsushi; Tearney, Guillermo J.; Bouma, Brett E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Tanaka, Atsushi; Tearney, Guillermo J.; Bouma, Brett E.] Harvard Univ, Sch Med, Boston, MA USA.
[Shimada, Kenei; Taguchi, Haruyuki; Fukuda, Shota; Yoshikawa, Junichi] Osaka Ekisaikai Hosp, Dept Cardiol, Osaka, Japan.
[Tearney, Guillermo J.; Bouma, Brett E.] Harvard Massachusetts Inst Technol Hlth Sci & Tec, Cambridge, MA USA.
[Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kitabata, Hironori; Kashiwagi, Manabu; Kubo, Takashi; Takarada, Shigeho; Hirata, Kumiko; Mizukoshi, Masato; Akasaka, Takashi] Wakayama Med Univ, Dept Cardiovasc Med, Wakayama, Japan.
RP Tanaka, A (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St, Boston, MA 02114 USA.
EM atanaka1@partners.org
FU Terumo Corp.
FX Dr. Tearney is a consultant for Samsung; has performed sponsored
research for the Terumo Corp.; and has received patent licensing and
royalty income from the Terumo Corp. Dr. Bouma has a sponsored research
agreement with and is an inventor on patents licensed to the Terumo
Corp.; and is an inventor on patents licensed to LightLab Imaging. All
other authors have reported that they have no relationships relevant to
the contents of this paper to disclose.
NR 19
TC 24
Z9 24
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD OCT 4
PY 2011
VL 58
IS 15
BP 1608
EP 1613
DI 10.1016/j.jacc.2011.06.046
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 833FP
UT WOS:000295868000009
PM 21958888
ER
PT J
AU Etcoff, NL
Stock, S
Haley, LE
Vickery, SA
House, DM
AF Etcoff, Nancy L.
Stock, Shannon
Haley, Lauren E.
Vickery, Sarah A.
House, David M.
TI Cosmetics as a Feature of the Extended Human Phenotype: Modulation of
the Perception of Biologically Important Facial Signals
SO PLOS ONE
LA English
DT Article
ID PHYSICAL ATTRACTIVENESS; FACES; BEAUTY; COLOR; SEX; AGE; RATIONALITY;
IMPRESSIONS; COMPETENCE; STEREOTYPE
AB Research on the perception of faces has focused on the size, shape, and configuration of inherited features or the biological phenotype, and largely ignored the effects of adornment, or the extended phenotype. Research on the evolution of signaling has shown that animals frequently alter visual features, including color cues, to attract, intimidate or protect themselves from conspecifics. Humans engage in conscious manipulation of visual signals using cultural tools in real time rather than genetic changes over evolutionary time. Here, we investigate one tool, the use of color cosmetics. In two studies, we asked viewers to rate the same female faces with or without color cosmetics, and we varied the style of makeup from minimal (natural), to moderate (professional), to dramatic (glamorous). Each look provided increasing luminance contrast between the facial features and surrounding skin. Faces were shown for 250 ms or for unlimited inspection time, and subjects rated them for attractiveness, competence, likeability and trustworthiness. At 250 ms, cosmetics had significant positive effects on all outcomes. Length of inspection time did not change the effect for competence or attractiveness. However, with longer inspection time, the effect of cosmetics on likability and trust varied by specific makeup looks, indicating that cosmetics could impact automatic and deliberative judgments differently. The results suggest that cosmetics can create supernormal facial stimuli, and that one way they may do so is by exaggerating cues to sexual dimorphism. Our results provide evidence that judgments of facial trustworthiness and attractiveness are at least partially separable, that beauty has a significant positive effect on judgment of competence, a universal dimension of social cognition, but has a more nuanced effect on the other universal dimension of social warmth, and that the extended phenotype significantly influences perception of biologically important signals at first glance and at longer inspection.
C1 [Etcoff, Nancy L.; Haley, Lauren E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Etcoff, Nancy L.; Haley, Lauren E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Stock, Shannon] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Vickery, Sarah A.] Procter & Gamble Cosmet, Procter & Gamble Beauty & Grooming, Hunt Valley, MD USA.
[House, David M.] Boston Univ, Dept Comp Sci, Boston, MA 02215 USA.
RP Etcoff, NL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
EM netcoff@partners.org
FU P&G Beauty and Grooming
FX This study was funded by P&G Beauty and Grooming, where Sarah A. Vickery
is employed as a Principal Scientist. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 41
TC 30
Z9 30
U1 11
U2 64
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 3
PY 2011
VL 6
IS 10
AR e25656
DI 10.1371/journal.pone.0025656
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834EU
UT WOS:000295943000052
PM 21991328
ER
PT J
AU Settles, M
Etzrodt, M
Kosanke, K
Schiemann, M
Zimmermann, A
Meier, R
Braren, R
Huber, A
Rummeny, EJ
Weissleder, R
Swirski, FK
Wildgruber, M
AF Settles, Marcus
Etzrodt, Martin
Kosanke, Katja
Schiemann, Matthias
Zimmermann, Alexander
Meier, Reinhard
Braren, Rickmer
Huber, Armin
Rummeny, Ernst J.
Weissleder, Ralph
Swirski, Filip K.
Wildgruber, Moritz
TI Different Capacity of Monocyte Subsets to Phagocytose Iron-Oxide
Nanoparticles
SO PLOS ONE
LA English
DT Article
ID MR CONTRAST AGENTS; BLOOD MONOCYTES; DENDRITIC CELLS; IN-VITRO; DISEASE;
USPIO; INFLAMMATION; ENDOTHELIUM; EXPRESSION; METASTASES
AB Objective: To explore the capacity of human CD14(+)CD16(++) and CD14(++)CD16(-) monocytes to phagocyte iron-oxide nanoparticles in vitro.
Methods: Human monocytes were labeled with four different magnetic nanoparticle preparations (Ferumoxides, SHU 555C, CLIO-680, MION-48) exhibiting distinct properties and cellular uptake was quantitatively assessed by flow cytometry, fluorescence microscopy, atomic absorption spectrometry and Magnetic Resonance Imaging (MRI). Additionally we determined whether cellular uptake of the nanoparticles resulted in phenotypic changes of cell surface markers.
Results: Cellular uptake differed between the four nanoparticle preparations. However for each nanoparticle tested, CD14(++)CD16(-) monocytes displayed a significantly higher uptake compared to CD14(+)CD16(++) monocytes, this resulted in significantly lower T1 and T2 relaxation times of these cells. The uptake of iron-oxide nanoparticles further resulted in a remarkable shift of expression of cell surface proteins indicating that the labeling procedure affects the phenotype of CD14(+)CD16(++) and CD14(++)CD16(-) monocytes differently.
Conclusion: Human monocyte subsets internalize different magnetic nanoparticle preparations differently, resulting in variable loading capacities, imaging phenotypes and likely biological properties.
C1 [Settles, Marcus; Kosanke, Katja; Meier, Reinhard; Braren, Rickmer; Huber, Armin; Rummeny, Ernst J.; Wildgruber, Moritz] Tech Univ Munich, Klinikum Rechts Isar, Inst Radiol, D-8000 Munich, Germany.
[Etzrodt, Martin; Weissleder, Ralph; Swirski, Filip K.; Wildgruber, Moritz] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA.
[Schiemann, Matthias] Tech Univ Munich, Klinikum Rechts Isar, Inst Med Mikrobiol Immunol & Hyg, D-8000 Munich, Germany.
[Schiemann, Matthias] Helmholtzzentrum Munchen, Clin Cooperat Grp Antigen Specif Immunotherapy, Munich, Germany.
[Zimmermann, Alexander] Tech Univ Munich, Klinikum Rechts Isar, Klin & Poliklin Gefasschirurg, D-8000 Munich, Germany.
RP Settles, M (reprint author), Tech Univ Munich, Klinikum Rechts Isar, Inst Radiol, D-8000 Munich, Germany.
EM moritz.wildgruber@tum.de
RI Meier, Reinhard/B-2882-2014; Etzrodt, Martin/P-3325-2015;
OI Etzrodt, Martin/0000-0003-1928-3904; Meier, Reinhard/0000-0002-2169-4780
FU NHLBI NIH HHS [R01 HL095612]
NR 42
TC 15
Z9 15
U1 0
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 3
PY 2011
VL 6
IS 10
AR e25197
DI 10.1371/journal.pone.0025197
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834EU
UT WOS:000295943000015
PM 21984904
ER
PT J
AU Nery, FG
Matsuo, K
Nicoletti, MA
Monkul, ES
Zunta-Soares, GB
Hatch, JP
Lafer, B
Soares, JC
AF Nery, Fabiano G.
Matsuo, Koji
Nicoletti, Mark A.
Monkul, E. Serap
Zunta-Soares, Giovana B.
Hatch, John P.
Lafer, Beny
Soares, Jair C.
TI Association between prior alcohol use disorders and decreased prefrontal
gray matter volumes in bipolar I disorder patients
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Bipolar disorder; Alcoholism; Comorbidity; Physiopathology; Cerebral
cortex; Magnetic resonance imaging
ID ORBITOFRONTAL CORTEX; BRAIN; ABNORMALITIES; COMORBIDITY; DEPENDENCE;
COCAINE; MRI
AB Up to 50% of bipolar disorder (BD) patients present a lifetime diagnosis of alcohol use disorders (AUD). BD patients with comorbid AUD, even when in remission from the AUD, have a poorer outcome and functional impairment than patients with BD alone. The neurobiological abnormalities that potentially characterize this severe subgroup of BD patients are unknown. Our goal was to investigate gray matter (GM) volume abnormalities in BD I patients with comorbid AUD. Twenty-one BD-AUD patients, 21 BD-nonAUD BD patients, and 25 healthy controls (HC), matched by age, gender, and handedness were studied. The BD-AUD patients were in remission from AUD on average for 6.8 years. 3D SPGR MRIs (TR = 25 ms, TE = 5 ms, slice thickness = 1.5 mm) were acquired from all subjects using a 1.5 T GE Signa Imaging System. We used an optimized voxel-based morphometry protocol to compare GM volumes among the groups. BD-AUD patients presented smaller GM volumes in the left medial frontal and the right anterior cingulate gyri compared to BD-nonAUD patients. BDnon-AUD patients did not present GM volume differences compared to HC. These findings provide evidence for an effect of comorbid AUD on regional brain structure of BD I patients and warrant further research on neurobiological aspects of this prevalent and severe comorbidity. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Nery, Fabiano G.; Monkul, E. Serap; Hatch, John P.; Lafer, Beny] Univ Sao Paulo, Sch Med, Bipolar Disorder Program PROMAN, Dept Psychiat, Sao Paulo, Brazil.
[Nery, Fabiano G.; Matsuo, Koji; Monkul, E. Serap] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Nery, Fabiano G.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Matsuo, Koji] Yamaguchi Univ, Div Neuropsychiat, Dept Neurosci, Grad Sch Med, Yamaguchi, Japan.
[Nicoletti, Mark A.; Zunta-Soares, Giovana B.; Soares, Jair C.] Univ Texas Med Sch, Dept Psychiat & Behav Sci, Houston, TX USA.
[Hatch, John P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthodont, San Antonio, TX 78229 USA.
RP Soares, JC (reprint author), UT Houston Med Sch, Dept Psychiat & Behav Sci, 1300 Moursund St, Houston, TX 77030 USA.
EM jair.c.soares@uth.tmc.edu
RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015
OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999
FU UTHSCSA GCRC [M01-RR-01346]; Krus Endowed Chair in Psychiatry (UTHSCSA);
Veterans Administration (VA Merit Review); KAKENHI-C [21591519]; [MH
01736]; [MH 068662]; [RR 020571]
FX This research was partly supported, by grants MH 01736, MH 068662, RR
020571, UTHSCSA GCRC (M01-RR-01346), the Krus Endowed Chair in
Psychiatry (UTHSCSA), the Veterans Administration (VA Merit Review),
KAKENHI-C 21591519 (to K. Matsuo) and a private donation from Thompson
Mottais family (to PROMAN). E. Serap Monkul is an employee of Eli Lilly
Brazil. The other authors do not have any commercial associations that
might pose a conflict of interest in connection with this manuscript.
NR 32
TC 10
Z9 10
U1 1
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD OCT 3
PY 2011
VL 503
IS 2
BP 136
EP 140
DI 10.1016/j.neulet.2011.08.026
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 836NN
UT WOS:000296118500012
PM 21884753
ER
PT J
AU Tamura, Y
Chiba, Y
Tanioka, T
Shimizu, N
Shinozaki, S
Yamada, M
Kaneki, K
Mori, S
Araki, A
Ito, H
Kaneki, M
AF Tamura, Yoshiaki
Chiba, Yuko
Tanioka, Toshihiro
Shimizu, Nobuyuki
Shinozaki, Shohei
Yamada, Marina
Kaneki, Kentaro
Mori, Seijiro
Araki, Atsushi
Ito, Hideki
Kaneki, Masao
TI NO donor induces Nec-1-inhibitable, but RIP1-independent, necrotic cell
death in pancreatic beta-cells
SO FEBS LETTERS
LA English
DT Article
DE Pancreatic beta-cells; Cell death; NO donor; Necroptosis; Regulated
necrosis; Necrostatin-1; RIP1
ID CYTOKINE-INDUCED APOPTOSIS; NITRIC-OXIDE; KINASE-B; NECROSIS;
NECROSTATIN-1; INJURY; CONTRIBUTES; MICE; INFLAMMATION; NECROPTOSIS
AB Nitric oxide (NO) has been implicated in pancreatic beta-cell death in the development of diabetes. The mechanisms underlying NO-induced beta-cell death have not been clearly defined. Recently, receptor-interacting protein-1 (RIP1)-dependent necrosis, which is inhibited by necrostatin-1, an inhibitor of RIP1, has emerged as a form of regulated necrosis. Here, we show that NO donor-induced beta-cell death was inhibited by necrostatin-1. Unexpectedly, however, RIP1 knockdown neither inhibited cell death nor altered the protective effects of necrostatin-1 in NO donor-treated beta-cells. These results indicate that NO donor induces necrostatin-1-inhibitable necrotic beta-cell death independent of RIP1. Our findings raise the possibility that NO-mediated beta-cell necrosis may be a novel form of signal-regulated necrosis, which play a role in the progression of diabetes. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
C1 [Tamura, Yoshiaki; Chiba, Yuko; Tanioka, Toshihiro; Shimizu, Nobuyuki; Yamada, Marina; Kaneki, Kentaro; Kaneki, Masao] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp,Shriners Hosp Children, Charlestown, MA 02129 USA.
[Tamura, Yoshiaki; Chiba, Yuko; Mori, Seijiro; Araki, Atsushi; Ito, Hideki] Tokyo Metropolitan Geriatr Inst, Itabashi Ku, Tokyo 1730015, Japan.
RP Kaneki, M (reprint author), Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp,Shriners Hosp Children, 149 13th St,Rm 6604, Charlestown, MA 02129 USA.
EM mkaneki@helix.mgh.harvard.edu
FU National Institutes of Health [R01 DK05827]; Microscopy and Image
Analysis Core of Massachusetts General Hospital [P30NS045776]; American
Diabetes Association [7-08-RA-77]
FX We thank Drs. C. Newgard and B. Seed for providing INS-1/832 and
RIP1-deficient Jurkat cells, respectively. We also thank Dr. C. Waeber
for his superb technical assistance. This work was supported by research
grants from the National Institutes of Health to M. K. (R01 DK05827) and
to the Microscopy and Image Analysis Core of Massachusetts General
Hospital (P30NS045776), and from American Diabetes Association to M. K.
(7-08-RA-77).
NR 39
TC 11
Z9 11
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD OCT 3
PY 2011
VL 585
IS 19
BP 3058
EP 3064
DI 10.1016/j.febslet.2011.08.028
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 828AW
UT WOS:000295473600021
PM 21888904
ER
PT J
AU Patti, JA
AF Patti, John A.
TI The Third Rail: Engineering Safe Travel for the Physician Community
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 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD OCT
PY 2011
VL 8
IS 10
BP 671
EP 672
DI 10.1016/j.jacr.2011.08.017
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KE
UT WOS:000306202000001
PM 21962776
ER
PT J
AU Earls, JP
White, RD
Woodard, PK
Abbara, S
Atalay, MK
Carr, JJ
Haramati, LB
Hendel, RC
Ho, VB
Hoffman, U
Khan, AR
Mammen, L
Martin, ET
Rozenshtein, A
Ryan, T
Schoepf, J
Steiner, RM
White, CS
AF Earls, James P.
White, Richard D.
Woodard, Pamela K.
Abbara, Suhny
Atalay, Michael K.
Carr, J. Jeffrey
Haramati, Linda B.
Hendel, Robert C.
Ho, Vincent B.
Hoffman, Udo
Khan, Arfa R.
Mammen, Leena
Martin, Edward T., III
Rozenshtein, Anna
Ryan, Thomas
Schoepf, Joseph
Steiner, Robert M.
White, Charles S.
TI ACR Appropriateness Criteria (R) Chronic Chest Pain-High Probability of
Coronary Artery Disease
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE Appropriateness Criteria; myocardial ischemia; coronary artery disease;
cardiac magnetic resonance imaging; multidetector cardiac CT;
radionuclide single photon-emission CT
ID POSITRON-EMISSION-TOMOGRAPHY; ULTRAFAST COMPUTED-TOMOGRAPHY; TC-99M
SESTAMIBI SPECT; CARDIOVASCULAR MAGNETIC-RESONANCE; VENTRICULAR EJECTION
FRACTION; WALL-MOTION ABNORMALITIES; ELECTRON-BEAM CT;
MYOCARDIAL-PERFUSION; DIAGNOSTIC-ACCURACY; STRESS ECHOCARDIOGRAPHY
AB Imaging is valuable in determining the presence, extent, and severity of myocardial ischemia and the severity of obstructive coronary lesions in patients with chronic chest pain in the setting of high probability of coronary artery disease. Imaging is critical for defining patients best suited for medical therapy or intervention, and findings can be used to predict long-term prognosis and the likely benefit from various therapeutic options. Chest radiography, radionuclide single photon-emission CT, radionuclide ventriculography, and conventional coronary angiography are the imaging modalities historically used in evaluating suspected chronic myocardial ischemia. Stress echocardiography, PET, cardiac MRI, and multidetector cardiac CT have all been more recently shown to be valuable in the evaluation of ischemic heart disease. Other imaging techniques may be helpful in those patients who do not present with signs classic for angina pectoris or in those patients who do not respond as expected to standard management. 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 [Earls, James P.] Fairfax Radiol Consultants, Fairfax, VA USA.
[White, Richard D.] Univ Florida, Coll Med Jacksonville, Jacksonville, FL USA.
[Woodard, Pamela K.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Abbara, Suhny; Hoffman, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Atalay, Michael K.] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA.
[Carr, J. Jeffrey] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Haramati, Linda B.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Hendel, Robert C.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Hendel, Robert C.; Martin, Edward T., III; Ryan, Thomas] Amer Coll Cardiol, Bethesda, MD USA.
[Ho, Vincent B.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Khan, Arfa R.] Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA.
[Mammen, Leena] Adv Radiol Serv, Grand Rapids, MI USA.
[Martin, Edward T., III] Oklahoma Heart Inst, Tulsa, OK USA.
[Rozenshtein, Anna] Columbia Presbyterian Med Ctr, New York, NY 10032 USA.
[Ryan, Thomas] Ohio State Univ, Heart & Vasc Ctr, Columbus, OH 43210 USA.
[Schoepf, Joseph] Med Univ S Carolina, Charleston, SC 29425 USA.
[Steiner, Robert M.] Temple Univ Hlth Syst, Philadelphia, PA USA.
[White, Charles S.] Univ Maryland Hosp, Baltimore, MD 21201 USA.
RP Earls, JP (reprint author), Amer Coll Radiol, Dept Qual & Safety, 1891 Preston White Dr, Reston, VA 20191 USA.
EM jpearls@yahoo.com
RI Carr, John/A-1938-2012;
OI Carr, John/0000-0002-4398-8237; White, Richard D./0000-0002-1133-7819
NR 71
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD OCT
PY 2011
VL 8
IS 10
BP 679
EP 686
DI 10.1016/j.jacr.2011.06.022
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KE
UT WOS:000306202000006
PM 21962781
ER
PT J
AU Thrall, JH
AF Thrall, James H.
TI Unintended Consequences of Health Care Legislation
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE Health care; legislation; Stark laws; Medicare; Medicaid; SGR
AB Unintended consequences of health care legislation threaten the financial and social well-being of the United States. Examples of major legislation resulting in unintended and unforeseen consequences include the Social Security Amendments Acts of 1989 and 1993 (the Stark laws), the Balanced Budget Act of 1997, and the Social Security Amendments Act of 1965 (Medicare and Medicaid). Each of these has had unintended financial and social outcomes. Spending for Medicare and Medicaid now equals an unsustainable 23% of the federal budget. Major reasons for unintended consequences include failure to appreciate the complexity of the issues, the open-ended nature of medical advances with attendant increases in costs, the inducement of change in behaviors in response to legislation, and the moral hazard of people spending other people's money. Actions that should be considered to avoid unintended consequences include more involvement of health professionals in the design of legislation, the inclusion of triggers to target review of legislatively defined programs, and the setting of time limits for sun-setting legislation. The ACR has played an important advocacy role and should continue to offer input to legislators, federal policymakers, and other stakeholders. Many opportunities exist to address the current financial situation by reducing the amount of unnecessary care delivered. Both major US political parties need to find the political will to compromise to chart the way forward. Some level of sacrifice is likely to be necessary from patients and providers and other stakeholders.
C1 [Thrall, James H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Thrall, James H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Radiol FND 216,55 Fruit St, Boston, MA 02114 USA.
EM jthrall@partners.org
NR 15
TC 4
Z9 4
U1 0
U2 2
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 OCT
PY 2011
VL 8
IS 10
BP 687
EP 691
DI 10.1016/j.jacr.2011.06.013
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KE
UT WOS:000306202000007
PM 21962782
ER
PT J
AU Kalra, MK
Singh, S
Thrall, JH
Mahesh, M
AF Kalra, Mannudeep K.
Singh, Sarabjeet
Thrall, James H.
Mahesh, Mahadevappa
TI Pointers for Optimizing Radiation Dose in Abdominal CT Protocols
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Editorial Material
ID TUBE CURRENT MODULATION
C1 [Mahesh, Mahadevappa] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA.
[Kalra, Mannudeep K.; Singh, Sarabjeet; Thrall, James H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Imaging, Boston, MA USA.
RP Mahesh, M (reprint author), Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, 601 N Caroline St, Baltimore, MD 21287 USA.
EM mmahesh@jhmi.edu
NR 8
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD OCT
PY 2011
VL 8
IS 10
BP 731
EP 734
DI 10.1016/j.jacr.2011.06.026
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KE
UT WOS:000306202000016
PM 21962791
ER
PT J
AU Krishnaraj, A
Hawkins, CM
AF Krishnaraj, Arun
Hawkins, C. Matthew
TI Improving Membership Retention Rates Among New Graduates
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Editorial Material
C1 [Krishnaraj, Arun] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
[Hawkins, C. Matthew] Univ Cincinnati, Coll Med, Dept Radiol, Cincinnati, OH 45221 USA.
RP Krishnaraj, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA.
EM akrishnaraj@partners.org
NR 2
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD OCT
PY 2011
VL 8
IS 10
BP 735
EP 736
DI 10.1016/j.jacr.2011.05.013
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KE
UT WOS:000306202000017
PM 21962792
ER
PT J
AU Middeldorp, CM
de Moor, MHM
McGrath, LM
Gordon, SD
Blackwood, DH
Costa, PT
Terracciano, A
Krueger, RF
de Geus, EJC
Nyholt, DR
Tanaka, T
Esko, T
Madden, PAF
Derringer, J
Amin, N
Willemsen, G
Hottenga, JJ
Distel, MA
Uda, M
Sanna, S
Spinhoven, P
Hartman, CA
Ripke, S
Sullivan, PF
Realo, A
Allik, J
Heath, AC
Pergadia, ML
Agrawal, A
Lin, P
Grucza, RA
Widen, E
Cousminer, DL
Eriksson, JG
Palotie, A
Barnett, JH
Lee, PH
Luciano, M
Tenesa, A
Davies, G
Lopez, LM
Hansell, NK
Medland, SE
Ferrucci, L
Schlessinger, D
Montgomery, GW
Wright, MJ
Aulchenko, YS
Janssens, ACJW
Oostra, BA
Metspalu, A
Abecasis, GR
Deary, IJ
Raikkonen, K
Bierut, LJ
Martin, NG
Wray, NR
van Duijn, CM
Smoller, JW
Penninx, BWJH
Boomsma, DI
AF Middeldorp, C. M.
de Moor, M. H. M.
McGrath, L. M.
Gordon, S. D.
Blackwood, D. H.
Costa, P. T.
Terracciano, A.
Krueger, R. F.
de Geus, E. J. C.
Nyholt, D. R.
Tanaka, T.
Esko, T.
Madden, P. A. F.
Derringer, J.
Amin, N.
Willemsen, G.
Hottenga, J-J
Distel, M. A.
Uda, M.
Sanna, S.
Spinhoven, P.
Hartman, C. A.
Ripke, S.
Sullivan, P. F.
Realo, A.
Allik, J.
Heath, A. C.
Pergadia, M. L.
Agrawal, A.
Lin, P.
Grucza, R. A.
Widen, E.
Cousminer, D. L.
Eriksson, J. G.
Palotie, A.
Barnett, J. H.
Lee, P. H.
Luciano, M.
Tenesa, A.
Davies, G.
Lopez, L. M.
Hansell, N. K.
Medland, S. E.
Ferrucci, L.
Schlessinger, D.
Montgomery, G. W.
Wright, M. J.
Aulchenko, Y. S.
Janssens, A. C. J. W.
Oostra, B. A.
Metspalu, A.
Abecasis, G. R.
Deary, I. J.
Raikkonen, K.
Bierut, L. J.
Martin, N. G.
Wray, N. R.
van Duijn, C. M.
Smoller, J. W.
Penninx, B. W. J. H.
Boomsma, D. I.
TI The genetic association between personality and major depression or
bipolar disorder. A polygenic score analysis using genome-wide
association data
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE bipolar disorder; genetic correlation; genome-wide association;
polygenic score analysis; personality-major depression
ID GENOTYPE IMPUTATION; ANXIETY DISORDERS; 5-FACTOR MODEL; TWIN;
POPULATION; HERITABILITY; METAANALYSIS; SAMPLE; SCHIZOPHRENIA;
EPIDEMIOLOGY
AB The relationship between major depressive disorder (MDD) and bipolar disorder (BD) remains controversial. Previous research has reported differences and similarities in risk factors for MDD and BD, such as predisposing personality traits. For example, high neuroticism is related to both disorders, whereas openness to experience is specific for BD. This study examined the genetic association between personality and MDD and BD by applying polygenic scores for neuroticism, extraversion, openness to experience, agreeableness and conscientiousness to both disorders. Polygenic scores reflect the weighted sum of multiple single-nucleotide polymorphism alleles associated with the trait for an individual and were based on a meta-analysis of genome-wide association studies for personality traits including 13 835 subjects. Polygenic scores were tested for MDD in the combined Genetic Association Information Network (GAIN-MDD) and MDD2000+ samples (N = 8921) and for BD in the combined Systematic Treatment Enhancement Program for Bipolar Disorder and Wellcome Trust Case-Control Consortium samples (N = 6329) using logistic regression analyses. At the phenotypic level, personality dimensions were associated with MDD and BD. Polygenic neuroticism scores were significantly positively associated with MDD, whereas polygenic extraversion scores were significantly positively associated with BD. The explained variance of MDD and BD, similar to 0.1%, was highly comparable to the variance explained by the polygenic personality scores in the corresponding personality traits themselves (between 0.1 and 0.4%). This indicates that the proportions of variance explained in mood disorders are at the upper limit of what could have been expected. This study suggests shared genetic risk factors for neuroticism and MDD on the one hand and for extraversion and BD on the other. Translational Psychiatry (2011) 1, e50; doi:10.1038/tp.2011.45; published online 18 October 2011
C1 [Middeldorp, C. M.; de Moor, M. H. M.; de Geus, E. J. C.; Willemsen, G.; Hottenga, J-J; Distel, M. A.; Boomsma, D. I.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands.
[Middeldorp, C. M.; de Moor, M. H. M.; de Geus, E. J. C.; Penninx, B. W. J. H.; Boomsma, D. I.] Neurosci Campus Amsterdam, Amsterdam, Netherlands.
[Middeldorp, C. M.] Univ Amsterdam, Acad Med Ctr, Dept Child & Adolescent Psychiat, NL-1105 AZ Amsterdam, Netherlands.
[Middeldorp, C. M.] GGZ inGeest VU Med Ctr, Dept Child & Adolescent Psychiat, Amsterdam, Netherlands.
[McGrath, L. M.; Ripke, S.; Barnett, J. H.; Lee, P. H.; Smoller, J. W.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Human Genet Res, Boston, MA 02114 USA.
[McGrath, L. M.; Ripke, S.; Barnett, J. H.; Lee, P. H.; Smoller, J. W.] Massachusetts Gen Hosp, Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA.
[Gordon, S. D.; Nyholt, D. R.; Hansell, N. K.; Medland, S. E.; Montgomery, G. W.; Wright, M. J.; Martin, N. G.; Wray, N. R.] Queensland Inst Med Res, Genet Epidemiol Unit, Brisbane, Qld 4006, Australia.
[Blackwood, D. H.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland.
[Costa, P. T.; Terracciano, A.; Tanaka, T.; Ferrucci, L.; Schlessinger, D.] NIA, NIH, Baltimore, MD 21224 USA.
[Krueger, R. F.; Derringer, J.] Univ Minnesota, Dept Psychol, Baltimore, MD USA.
[Esko, T.; Metspalu, A.] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Esko, T.; Metspalu, A.] Estonian Bioctr, Tartu, Estonia.
[Esko, T.; Metspalu, A.] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Madden, P. A. F.; Heath, A. C.; Pergadia, M. L.; Agrawal, A.; Lin, P.; Grucza, R. A.; Bierut, L. J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Amin, N.; Aulchenko, Y. S.; Janssens, A. C. J. W.; van Duijn, C. M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Distel, M. A.; Penninx, B. W. J. H.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Uda, M.; Sanna, S.] Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
[Spinhoven, P.; Penninx, B. W. J. H.] Leiden Univ, Dept Clin Psychol, Leiden, Netherlands.
[Spinhoven, P.; Penninx, B. W. J. H.] Leiden Univ, Dept Psychiat, Leiden, Netherlands.
[Hartman, C. A.; Penninx, B. W. J. H.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands.
[Ripke, S.; Palotie, A.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Sullivan, P. F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Realo, A.; Allik, J.] Univ Tartu, Dept Psychol, EE-50090 Tartu, Estonia.
[Widen, E.; Cousminer, D. L.; Palotie, A.] Univ Helsinki, FIMM, Helsinki, Finland.
[Eriksson, J. G.] Natl Inst Hlth & Welf, Helsinki, Finland.
[Eriksson, J. G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, J. G.] Vasa Cent Hosp, Vaasa, Finland.
[Eriksson, J. G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland.
[Eriksson, J. G.] Folkhalsan Res Ctr, Helsinki, Finland.
[Palotie, A.] Wellcome Trust Sanger Inst, Cambridge, England.
[Palotie, A.] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Palotie, A.] Univ Cent Hosp, Helsinki, Finland.
[Barnett, J. H.] Univ Cambridge, Dept Psychiat, Cambridge, England.
[Luciano, M.; Davies, G.; Lopez, L. M.; Deary, I. J.] Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Tenesa, A.] Western Gen Hosp, MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Oostra, B. A.] Erasmus Univ, Dept Clin Genet, Med Ctr, NL-3000 DR Rotterdam, Netherlands.
[Abecasis, G. R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Raikkonen, K.] Univ Helsinki, Dept Psychol, SF-00100 Helsinki, Finland.
[Penninx, B. W. J. H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
RP Middeldorp, CM (reprint author), Vrije Univ Amsterdam, Dept Biol Psychol, Van der Boechorststr 1, NL-1081 BT Amsterdam, Netherlands.
EM cm.middeldorp@psy.vu.nl
RI Lopez, Lorna/F-7265-2010; Montgomery, Grant/B-7148-2008; Hansell,
Narelle/A-4553-2016; Deary, Ian/C-6297-2009; Nyholt, Dale/C-8384-2013;
terracciano, antonio/B-1884-2008; Aulchenko, Yurii/M-8270-2013; Lin,
P/G-7702-2014; Medland, Sarah/C-7630-2013; Wray, Naomi/C-8639-2015;
Allik, Juri/D-5609-2009; de Geus, Eco/M-9318-2015; Wright,
Margaret/A-4560-2016; Realo, Anu/M-9524-2016; Luciano,
Michelle/F-7277-2010;
OI Montgomery, Grant/0000-0002-4140-8139; Hansell,
Narelle/0000-0002-8229-9741; Aulchenko, Yurii/0000-0002-7899-1575;
Medland, Sarah/0000-0003-1382-380X; Wray, Naomi/0000-0001-7421-3357;
Allik, Juri/0000-0002-8358-4747; de Geus, Eco/0000-0001-6022-2666;
Wright, Margaret/0000-0001-7133-4970; Luciano,
Michelle/0000-0003-0935-7682; Eriksson, Johan/0000-0002-2516-2060;
Middeldorp, Christel/0000-0002-6218-0428; Raikkonen,
Katri/0000-0003-3124-3470
FU Wellcome Trust [076113, 89061/Z/09/Z, 089062/Z/09/Z]; Netherlands
Scientific Organization Centre for Medical Systems Biology (NWO
Genomics) [904-61-090, 904-61-193, 480-04-004, 400-05-717, 912-100-20];
Neuroscience Campus Amsterdam (NCA); EMGO+ Institute; European Union
[EU/WLRT-2001-01254]; ZonMW [10-000-1002]; NIMH [RO1 MH059160, R01
MH-079799]; NESDA; NTR; NWO-SPI [56-464-1419]; Netherlands Organization
for Scientific Research (NWO) (ZonMW) [31160008, VENI-016-115-035,
916-76-125]; Australian National Health and Medical Research Council
[241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981,
496675, 496739, 552485, 552498, 613608]; FP-5 GenomEUtwin Project
[QLG2-CT-2002-01254]; US National Institutes of Health (NIH) [AA07535,
AA10248, AA13320, AA13321, AA13326, AA14041, MH66206, DA12854,
DA019951]; National Health and Medical Research Council (NHMRC);
Australian Research Council; Netherlands Organization for Scientific
Research (NWO) [480-05-003]; Erasmus MC; Netherlands Genomics Initiative
(NGI); NIH Genes, Environment and Health Initiative (GEI) [U01
HG004422]; Gene Environment Association Studies (GENEVA) under GEI; NIH
GEI [U01HG004438]; National Institute on Alcohol Abuse and Alcoholism;
NIH [AA13320, AA13321, DA12854, HHSN268200782096C, AA07728, AA07580,
AA11998]; NIH from the National Institute on Alcohol Abuse and
Alcoholism (NIAAA) [U10AA008401]; National Institute on Drug Abuse
(NIDA); NIH from the National Cancer Institute [P01CA89392]; NIH,
National Institute on Aging [NO1-AG-1-2109]; Academy of Finland [120315,
129287, 1129457, 1216965, 120386, 125876]; European Science Foundation
(EuroSTRESS); Signe and Ane Gyllenberg foundation; Research Into Ageing;
Help the Aged/Age Concern (The Disconnected Mind); Biotechnology and
Biological Sciences Research Council (BBSRC); Engineering and Physical
Sciences Research Council (EPSRC); Economic and Social Research Council
(ESRC); Medical Research Council (MRC); cross-council Lifelong Health
and Wellbeing Initiative; eDIKT initiative; ECOGENE [205419]; Estonian
Government [SF0180142s08]; EU; Estonian Ministry of Science and
Education [SF0180029s08]; Parke-Davis Exchange Fellowship; [201413
ENGAGE]; [212111 BBMRI]
FX This study makes use of data generated by the Wellcome Trust
Case-Control Consortium. A full list of the investigators who
contributed to the generation of the WTCCC data is available from
http://www.wtccc.org.uk. Funding for the WTCCC project was provided by
the Wellcome Trust under award 076113. NESDA/NTR: Funding support was
provided by the Netherlands Scientific Organization (904-61-090,
904-61-193, 480-04-004, 400-05-717, 912-100-20) Centre for Medical
Systems Biology (NWO Genomics), the Neuroscience Campus Amsterdam (NCA)
and the EMGO+ Institute; the European Union (EU/WLRT-2001-01254), ZonMW
(Geestkracht program, 10-000-1002), NIMH (RO1 MH059160) and matching
funds from participating institutes in NESDA and NTR. The NTR controls
in MDD2000+ were genotyped in the Genomics platform (certified service
provider (CSPro(R)) for Illumina) at the LIFE and BRAIN Center, Bonn
(funded by NWO-SPI 56-464-1419). Statistical analyses were carried out
on the Genetic Cluster Computer (http://www.geneticcluster.org), which
is financially supported by the NWO (480-05-003). MHM de Moor and CM
Middeldorp are financially supported by the Netherlands Organization for
Scientific Research (NWO) (ZonMW Addiction program, grant 31160008,
VENI-016-115-035 and VENI grant 916-76-125). MDD2000+/QIMR: Funding was
provided by the Australian National Health and Medical Research Council
(241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981,
496675,496739, 552485, 552498, 613608), the FP-5 GenomEUtwin Project
(QLG2-CT-2002-01254), and the US National Institutes of Health (NIH
grants AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206,
DA12854, DA019951). A portion of the genotyping on which this study was
based (Illumina 370K scans on 4300 individuals) was carried out at the
Center for Inherited Disease Research, Baltimore (CIDR), through an
access award to our late colleague Dr Richard Todd (Psychiatry,
Washington University School of Medicine, St Louis). GW Montgomery is
supported by the National Health and Medical Research Council (NHMRC)
Fellowship Scheme. NRWray and DR Nyholt are supported by the Australian
Research Council Future Fellowship Scheme. The ERF study was supported
by grants from The Netherlands Organization for Scientific Research
(NWO), Erasmus MC and the Netherlands Genomics Initiative
(NGI)-sponsored Center of Medical Systems Biology (CMSB). Funding
support for the Study of Addiction: Genetics and Environment (SAGE) was
provided through the NIH Genes, Environment and Health Initiative (GEI)
(U01 HG004422). SAGE is one of the genome-wide association studies
funded as part of the Gene Environment Association Studies (GENEVA)
under GEI. Assistance with phenotype harmonization and genotype
cleaning, as well as with general study coordination, was provided by
the GENEVA Coordinating Center (U01 HG004446). Assistance with data
cleaning was provided by the National Center for Biotechnology
Information. Support for collection of datasets and samples was provided
by the Collaborative Study on the Genetics of Alcoholism (COGA; U10
AA008401), the Collaborative Genetic Study of Nicotine Dependence
(COGEND; P01 CA089392) and the Family Study of Cocaine Dependence (FSCD;
R01 DA013423, R01 DA019963).; Funding support for genotyping, which was
performed at the Johns Hopkins University Center for Inherited Disease
Research, was provided by the NIH GEI (U01HG004438), the National
Institute on Alcohol Abuse and Alcoholism, the National Institute on
Drug Abuse and the NIH contract 'High throughput genotyping for studying
the genetic contributions to human disease' (HHSN268200782096C). The
Collaborative Study on the Genetics of Alcoholism (COGA) Principal
Investigators: B Porjesz, V Hesselbrock, H Edenberg, L Bierut, includes
10 different centers: University of Connecticut (V Hesselbrock); Indiana
University (HJ Edenberg, J Nurnberger Jr., T Foroud); University of Iowa
(S Kuperman, J Kramer); SUNY Downstate (B Porjesz); Washington
University in St Louis (L Bierut, A Goate, J Rice, K Bucholz);
University of California at San Diego (M Schuckit); Rutgers University
(J Tischfield); Southwest Foundation (L Almasy), Howard University (R
Taylor) and Virginia Commonwealth University (D Dick). A Parsian and M
Reilly are the NIAAA Staff Collaborators. We continue to be inspired by
our memories of Henri Begleiter and Theodore Reich, founding PI and
Co-PI of COGA, and also owe a debt of gratitude to other past organizers
of COGA, including Ting-Kai Li, currently a consultant with COGA, P
Michael Conneally, Raymond Crowe and Wendy Reich, for their critical
contributions. This national collaborative study is supported by NIH
Grant U10AA008401 from the National Institute on Alcohol Abuse and
Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). The
Collaborative Genetic Study of Nicotine Dependence (COGEND) project is a
collaborative research group and part of the NIDA Genetics Consortium.
Lead investigators directing data collection are Laura Bierut, Naomi
Breslau, Dorothy Hatsukami and Eric Johnson. We thank Heidi Kromrei and
Tracey Richmond for their assistance in data collection. In memory of
Theodore Reich, founding Principal Investigator of COGEND, we are
indebted to his leadership in the establishment and nurturing of COGEND
and acknowledge with great admiration his seminal scientific
contributions to the field. COGEND is supported by the NIH grant
P01CA89392 from the National Cancer Institute. SardiNIA: We acknowledge
support from the Intramural Research Program of the NIH, National
Institute on Aging. Funding was provided by the National Institute on
Aging, NIH contract NO1-AG-1-2109 to the SardiNIA ('ProgeNIA') team.
HBCS: We acknowledge financial support from the Academy of Finland
(grant no. 120315 and 129287 to EW, 1129457 and 1216965 to KR, 120386
and 125876 to JGE), the European Science Foundation (EuroSTRESS), the
Wellcome Trust (grant no. 89061/Z/09/Z and 089062/Z/09/Z) and the Signe
and Ane Gyllenberg foundation. NAG/IRPG: This study is supported by NIH
grants DA12854 (to PAFM), AA07728, AA07580, AA11998, AA13320 and AA13321
(to ACH); and grants from the Australian National Health and Medical
Research Council; MLP is supported by DA019951. LBC36: We thank David
Liewald and Paul Redmond for technical assistance; the study Secretary
Paula Davies; Alan Gow, Michelle Taylor, Janie Corley, Caroline Brett
and Caroline Cameron for data collection and data entry; nurses and
staff at the Wellcome Trust Clinical Research Facility, where subjects
were tested and at the genotyping was performed; staff at the Lothian
Health Board and staff at the SCRE Centre, University of Glasgow. The
research was supported by a program grant from Research Into Ageing.;
The research continues with program grants from Help the Aged/Age
Concern (The Disconnected Mind). GWAS funding awarded by the
Biotechnology and Biological Sciences Research Council (BBSRC) to IJD
and AT. ML is a Royal Society of Edinburgh/Lloyds TSB Foundation for
Scotland Personal Research Fellow. The study was conducted within the
University of Edinburgh Centre for Cognitive Ageing and Cognitive
Epidemiology, supported by the (BBSRC), Engineering and Physical
Sciences Research Council (EPSRC), Economic and Social Research Council
(ESRC) and Medical Research Council (MRC), as part of the cross-council
Lifelong Health and Wellbeing Initiative. This work has made use of the
resources provided by the Edinburgh Compute and Data Facility (ECDF)
(http://www.ecdf.ed.ac.uk/). The ECDF is partially supported by the
eDIKT initiative (http://www.edikt.org.uk). BLSA: We acknowledge support
from the Intramural Research Program of the NIH, National Institute on
Aging. We thank Robert McCrae. EGPUT: AM and TE received support from
FP7 grants (201413 ENGAGE, 212111 BBMRI, ECOGENE (no. 205419, EBC)). AM
and TE also received targeted financing from Estonian Government
SF0180142s08 and by EU through the European Regional Development Fund,
in the frame of Centre of Excellence in Genomics. The genotyping of the
Estonian Genome Project samples was performed in Estonian Biocentre
Genotyping Core Facility, AM and TE thank Mari Nelis and Viljo Soo for
their contributions. A Realo and J Allik are supported by a grant from
the Estonian Ministry of Science and Education (SF0180029s08). STEP-BD:
JH Barnett was funded by the Parke-Davis Exchange Fellowship. JW Smoller
and LM McGrath were supported in part by NIMH grant R01 MH-079799 (Dr
Smoller, PI).
NR 62
TC 26
Z9 27
U1 2
U2 28
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD OCT
PY 2011
VL 1
AR e50
DI 10.1038/tp.2011.45
PG 8
WC Psychiatry
SC Psychiatry
GA 971PM
UT WOS:000306216300007
PM 22833196
ER
PT J
AU Terracciano, A
Esko, T
Sutin, AR
de Moor, MHM
Meirelles, O
Zhu, G
Tanaka, T
Giegling, I
Nutile, T
Realo, A
Allik, J
Hansell, NK
Wright, MJ
Montgomery, GW
Willemsen, G
Hottenga, JJ
Friedl, M
Ruggiero, D
Sorice, R
Sanna, S
Cannas, A
Raikkonen, K
Widen, E
Palotie, A
Eriksson, JG
Cucca, F
Krueger, RF
Lahti, J
Luciano, M
Smoller, JW
van Duijn, CM
Abecasis, GR
Boomsma, DI
Ciullo, M
Costa, PT
Ferrucci, L
Martin, NG
Metspalu, A
Rujescu, D
Schlessinger, D
Uda, M
AF Terracciano, A.
Esko, T.
Sutin, A. R.
de Moor, M. H. M.
Meirelles, O.
Zhu, G.
Tanaka, T.
Giegling, I.
Nutile, T.
Realo, A.
Allik, J.
Hansell, N. K.
Wright, M. J.
Montgomery, G. W.
Willemsen, G.
Hottenga, J-J
Friedl, M.
Ruggiero, D.
Sorice, R.
Sanna, S.
Cannas, A.
Raikkonen, K.
Widen, E.
Palotie, A.
Eriksson, J. G.
Cucca, F.
Krueger, R. F.
Lahti, J.
Luciano, M.
Smoller, J. W.
van Duijn, C. M.
Abecasis, G. R.
Boomsma, D. I.
Ciullo, M.
Costa, P. T., Jr.
Ferrucci, L.
Martin, N. G.
Metspalu, A.
Rujescu, D.
Schlessinger, D.
Uda, M.
TI Meta-analysis of genome-wide association studies identifies common
variants in CTNNA2 associated with excitement-seeking
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE catenin cadherin-associated protein alpha 2 (CTNNA2);
excitement-seeking; genome-wide association (GWA); impulsivity;
sensation-seeking
ID ALPHA-N-CATENIN; NETHERLANDS TWIN REGISTER; SENSATION SEEKING;
PERSONALITY-TRAITS; BIPOLAR DISORDER; 5-FACTOR MODEL; IMPULSIVITY; RISK;
GENE; SCHIZOPHRENIA
AB The tendency to seek stimulating activities and intense sensations define excitement-seeking, a personality trait akin to some aspects of sensation-seeking. This trait is a central feature of extraversion and is a component of the multifaceted impulsivity construct. Those who score high on measures of excitement-seeking are more likely to smoke, use other drugs, gamble, drive recklessly, have unsafe/unprotected sex and engage in other risky behaviors of clinical and social relevance. To identify common genetic variants associated with the Excitement-Seeking scale of the Revised NEO Personality Inventory, we performed genome-wide association studies in six samples of European ancestry (N = 7860), and combined the results in a meta-analysis. We identified a genome-wide significant association between the Excitement-Seeking scale and rs7600563 (P = 2 x 10(-8)). This single-nucleotide polymorphism maps within the catenin cadherin-associated protein, alpha 2 (CTNNA2) gene, which encodes for a brain-expressed a-catenin critical for synaptic contact. The effect of rs7600563 was in the same direction in all six samples, but did not replicate in additional samples (N = 5105). The results provide insight into the genetics of excitement-seeking and risk-taking, and are relevant to hyperactivity, substance use, antisocial and bipolar disorders. Translational Psychiatry (2011) 1, e49; doi:10.1038/tp.2011.42; published online 18 October 2011
C1 [Terracciano, A.; Sutin, A. R.; Meirelles, O.; Costa, P. T., Jr.; Ferrucci, L.; Schlessinger, D.] NIA, NIH, US Dept HHS, Baltimore, MD 21224 USA.
[Esko, T.; Realo, A.; Allik, J.; Metspalu, A.] Univ Tartu, EE-50090 Tartu, Estonia.
[Esko, T.; Metspalu, A.] Estonian Bioctr, Tartu, Estonia.
[de Moor, M. H. M.; Willemsen, G.; Hottenga, J-J; Boomsma, D. I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Zhu, G.; Hansell, N. K.; Wright, M. J.; Montgomery, G. W.; Martin, N. G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Giegling, I.; Friedl, M.; Rujescu, D.] Univ Munich, Dept Psychiat, D-8000 Munich, Germany.
[Nutile, T.; Ruggiero, D.; Sorice, R.; Ciullo, M.] CNR, Inst Genet & Biophys A Buzzati Traverso, I-80125 Naples, Italy.
[Sanna, S.; Cannas, A.; Cucca, F.; Uda, M.] CNR, Ist Ric Genet & Biomed, Cagliari, Italy.
[Raikkonen, K.; Lahti, J.] Univ Helsinki, Inst Behav Sci, Helsinki, Finland.
[Widen, E.; Palotie, A.] Univ Helsinki, FIMM, Helsinki, Finland.
[Palotie, A.] Wellcome Trust Sanger Inst, Cambridge, England.
[Eriksson, J. G.] Natl Inst Hlth & Welf, Helsinki, Finland.
[Krueger, R. F.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[Luciano, M.] Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Smoller, J. W.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Human Genet Res, Boston, MA 02114 USA.
[Smoller, J. W.] Massachusetts Gen Hosp, Neurodev Genet Unit, Boston, MA 02114 USA.
[van Duijn, C. M.] ErasmusMC, Dept Epidemiol, Rotterdam, Netherlands.
[Abecasis, G. R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
RP Terracciano, A (reprint author), NIA, NIH, US Dept HHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM Terraccianoa@mail.nih.gov
RI terracciano, antonio/B-1884-2008; Allik, Juri/D-5609-2009; Montgomery,
Grant/B-7148-2008; Hansell, Narelle/A-4553-2016; Wright,
Margaret/A-4560-2016; ruggiero, daniela/K-5638-2016; Realo,
Anu/M-9524-2016; Luciano, Michelle/F-7277-2010;
OI Allik, Juri/0000-0002-8358-4747; Montgomery, Grant/0000-0002-4140-8139;
Hansell, Narelle/0000-0002-8229-9741; Wright,
Margaret/0000-0001-7133-4970; ruggiero, daniela/0000-0003-3898-7827;
Luciano, Michelle/0000-0003-0935-7682; sanna,
serena/0000-0002-3768-1749; Abecasis, Goncalo/0000-0003-1509-1825;
Costa, Paul/0000-0003-4375-1712; NUTILE, TERESA/0000-0001-7062-8352;
Lahti, Jari/0000-0002-4310-5297; Martin, Nicholas/0000-0003-4069-8020
FU NIH, National Institute on Aging; Estonian Ministry of Science and
Education [SF0180029s08]; European Social Fund [3-8.2/60]; Estonian
Government [SF0180142s08]; European Union; Beyond Blue; Borderline
Personality Disorder Research Foundation; National Health and Medical
Research Council [389891]; Academy of Finland; Finnish Diabetes Research
Society; Folkhalsan Research Foundation; Novo Nordisk Foundation; Finska
Lakaresallskapet; Signe and Ane Gyllenberg Foundation; University of
Helsinki; European Science Foundation (EUROSTRESS); Ministry of
Education; Ahokas Foundation; Emil Aaltonen Foundation; [201413];
[212111]; [245536]
FX We thank study subjects for their participation as well as everybody
involved in each of the participating studies. EGCUT authors want to
acknowledge EGCUT personnel, especially Merli Hass, Viljo Soo and Mari
Nelis. EGCUT data analyzes were carried out in part in the High
Performance Computing Center of University of Tartu. Cilento authors
acknowledge Dr Maria Enza Amendola for the test administration and thank
the personnel working in the organization of the study in the villages.
QIMR thanks study participants and acknowledges Nathan Gillespie for
discussion on study design related to NEO collection; Marisa Grimmer,
Romana Leisser and Kim Eldridge for overseeing data collection; Anjali
Henders, Megan Campbell, Lisa Bowdler, Steven Crooks and staff of the
Molecular Epidemiology Laboratory for sample processing and preparation;
and Harry Beeby, David Smyth and Daniel Park for IT support. We
acknowledge Drs Dale R Nyholt and Scott Gordon for their substantial
efforts involving the QC and preparation of the GWA data sets and Dr
Sarah Medland for undertaking the imputation of the GWAS data and
subsequent preparation for analyses. This research was supported in part
by the Intramural Research Program of the NIH, National Institute on
Aging. Anu Realo and Juri Allik were supported by a grant from the
Estonian Ministry of Science and Education (SF0180029s08) and by a
Primus Grant (3-8.2/60) from the European Social Fund. TE and AM
received support from FP7 Grants (201413, 212111, 245536). TE and AM
also received targeted financing from Estonian Government SF0180142s08
and from the European Union through the European Regional Development
Fund, in the frame of Centre of Excellence in Genomics. QIMR received
support from Beyond Blue and the Borderline Personality Disorder
Research Foundation. Genotyping was funded by the National Health and
Medical Research Council (Medical Bioinformatics Genomics Proteomics
Program, 389891). Helsinki Birth Cohort Study has been supported by
grants from the Academy of Finland, the Finnish Diabetes Research
Society, Folkhalsan Research Foundation, Novo Nordisk Foundation, Finska
Lakaresallskapet, Signe and Ane Gyllenberg Foundation, University of
Helsinki, European Science Foundation (EUROSTRESS), Ministry of
Education, Ahokas Foundation and Emil Aaltonen Foundation.
NR 72
TC 20
Z9 20
U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD OCT
PY 2011
VL 1
AR e49
DI 10.1038/tp.2011.42
PG 8
WC Psychiatry
SC Psychiatry
GA 971PM
UT WOS:000306216300006
PM 22833195
ER
PT J
AU Leong, JVB
Boro, MS
Winter, ME
AF Leong, Julie V. B.
Boro, Maureen S.
Winter, Michael E.
TI Vancomycin clearance in overweight and obese patients
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Letter
ID PHARMACOKINETICS
C1 [Leong, Julie V. B.; Boro, Maureen S.] San Francisco VA Med Ctr, Pharm Informat & Pharmacokinet Program, San Francisco, CA 94121 USA.
[Winter, Michael E.] Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA.
RP Leong, JVB (reprint author), San Francisco VA Med Ctr, Pharm Informat & Pharmacokinet Program, 4150 Clement St, San Francisco, CA 94121 USA.
EM maureen.boro@va.gov
NR 4
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC HEALTH-SYSTEM PHARMACISTS
PI BETHESDA
PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA
SN 1079-2082
J9 AM J HEALTH-SYST PH
JI Am. J. Health-Syst. Pharm.
PD OCT 1
PY 2011
VL 68
IS 19
BP 1777
EP 1778
DI 10.2146/ajhp110286
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 941FG
UT WOS:000303948500011
ER
PT J
AU Fagenholz, PJ
de Moya, MA
AF Fagenholz, Peter J.
de Moya, Marc A.
TI Laparoscopic Treatment of Bowel Obstruction Due to a Bezoar in a
Meckel's Diverticulum
SO JSLS-JOURNAL OF THE SOCIETY OF LAPAROENDOSCOPIC SURGEONS
LA English
DT Article
DE Laparoscopy; Bowel obstruction; Meckel's diverticulum; Bezoar
ID INTESTINAL-OBSTRUCTION; PHYTOBEZOAR
AB Background and Objectives: Meckel's diverticulum is a common anomaly of the gastrointestinal tract that may result in gastrointestinal bleeding, diverticulitis, and small bowel obstruction. This report describes the use of laparoscopy to treat a rare complication of Meckel's diverticulum-small bowel obstruction due to phytobezoar impaction. More generally, it provides an example of the feasibility and utility of a laparoscopic approach to small bowel obstructions of unknown causes.
Methods: A 34-year-old male presented to the emergency department complaining of episodic abdominal pain and vomiting. He had no history of abdominal surgery. His vital signs were stable, and his abdomen was distended, but only mildly tender. He had no abdominal wall hernias on examination. Imaging was consistent with small bowel obstruction. He was brought to the operating room where laparoscopy revealed a Meckel's diverticulum with an impacted phytobezoar as the source of obstruction. The diverticulum was resected and the phytobezoar removed laparoscopically.
Results: The patient recovered well and was discharged home on the third postoperative day, tolerating a regular diet.
Conclusions: Phytobezoar impaction in a Meckel's diverticulum causing small bowel obstruction is a rare event. It can be effectively treated laparoscopically. This case provides an example of the potential utility of laparoscopy in treating small bowel obstructions of unclear etiology.
C1 [Fagenholz, Peter J.; de Moya, Marc A.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
EM pfagenholz@partners.org
NR 11
TC 4
Z9 4
U1 0
U2 1
PU SOC LAPAROENDOSCOPIC SURGEONS
PI MIAMI
PA 7330 SW 62 PL, STE 410, MIAMI, FL 33143-4825 USA
SN 1086-8089
J9 JSLS-J SOC LAPAROEND
JI JSLS-J. Soc. Laparoendosc. Surg.
PD OCT-DEC
PY 2011
VL 15
IS 4
BP 562
EP 564
DI 10.4293/108680811X13176785204607
PG 3
WC Surgery
SC Surgery
GA 936RC
UT WOS:000303606700024
PM 22643518
ER
PT J
AU Clair, C
Bitton, A
Meigs, JB
Rigotti, NA
AF Clair, Carole
Bitton, Asaf
Meigs, James B.
Rigotti, Nancy A.
TI Relationships of Cotinine and Self-Reported Cigarette Smoking With
Hemoglobin A(1c) in the US
SO DIABETES CARE
LA English
DT Article
ID BODY-MASS INDEX; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; SERUM COTININE;
ADIPOSE-TISSUE; EPIC-NORFOLK; POPULATION; EXPOSURE; SMOKERS; MEN
AB OBJECTIVE-Whether nicotine leads to a persistent increase in blood glucose levels is not clear. Our objective was to assess the relationship between cotinine, a nicotine metabolite, and glycated hemoglobin (HbA(1c)), an index of recent glycemia.
RESEARCH DESIGN AND METHODS-We used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2008. We limited our analysis to 17,287 adults without diabetes. We created three cotinine categories: <0.05 ng/mL, 0.05-2.99 ng/mL, and >= 3 ng/mL.
RESULTS-Using self-report, 25% of the sample were current smokers, 24% were former smokers, and 51% were nonsmokers. Smokers had a higher mean HbA 1, (5.36% +/- 0.01 SE) compared with never smokers (5.31% +/- 0.01) and former smokers (5.31% +/- 0.01). In a similar manner, mean HbA(1c), was higher among participants with cotinine ng/mL (5.35% +/- 0.01) and participants with cotinine 0.05-2.99 ng/mL (5.34% +/- 0.01) compared with participants with cotinine <0.05 ng/mL (5.29% +/- 0.01). In multivariable-adjusted analysis, we found that both a cotinine ng/mL and self-reported smoking were associated with higher EbA(1c), compared with a cotinine <0.05 ng/mL or not smoking. People with a cotinine level ng/mL had a relative 5% increase in HbAi, compared with people with a cotinine level <0.05 ng/mL, and smokers had a relative 7% increase in HbA(1c) compared with never smokers.
CONCLUSIONS-Our study suggests that cotinine is associated with increased HbAi, in a representative sample of the U.S. population without diabetes.
C1 [Clair, Carole; Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr,Div Gen Med, Boston, MA 02115 USA.
[Bitton, Asaf] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gen Med, Boston, MA 02115 USA.
RP Clair, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr,Div Gen Med, Boston, MA 02115 USA.
EM carole.willi@gmail.com
RI Clair, Carole/D-9786-2014
OI Clair, Carole/0000-0001-5281-0943
FU Swiss National Science Foundation [PBLAP3-127728/1]; SICPA Foundation;
National Institute of Diabetes and Digestive and Kidney Diseases
[K24-DK-080140]; National Heart, Lung, and Blood Institute
[K24-HL-04440]
FX C.C. has received grants from the Swiss National Science Foundation
(PBLAP3-127728/1) and the SICPA Foundation. J.B.M. has received a grant
from the National Institute of Diabetes and Digestive and Kidney
Diseases (K24-DK-080140). N.A.R. has received a grant from the National
Heart, Lung, and Blood Institute (K24-HL-04440).
NR 24
TC 20
Z9 20
U1 0
U2 6
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD OCT
PY 2011
VL 34
IS 10
BP 2250
EP 2255
DI 10.2337/dc11-0710
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 910AG
UT WOS:000301609000022
PM 21836101
ER
PT J
AU Ioannou, GN
Boyko, EJ
AF Ioannou, George N.
Boyko, Edward J.
TI Metformin and Colorectal Cancer Risk in Diabetic Patients
SO DIABETES CARE
LA English
DT Editorial Material
ID BREAST-CANCER; EUROPEAN ASSOCIATION; CONSENSUS ALGORITHM;
MEDICAL-MANAGEMENT; METABOLIC SYNDROME; TYPE-2; THERAPY; HYPERGLYCEMIA;
METAANALYSIS; ADJUSTMENT
C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA USA.
[Ioannou, George N.; Boyko, Edward J.] Univ Washington, Seattle, WA 98195 USA.
[Ioannou, George N.; Boyko, Edward J.] Vet Affaiis Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA USA.
[Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Div Internal Med, Dept Med, Seattle, WA USA.
RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA USA.
EM georgei@medicine.washington.edu
NR 17
TC 7
Z9 7
U1 0
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD OCT
PY 2011
VL 34
IS 10
BP 2336
EP 2337
DI 10.2337/dc11-1447
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 910AG
UT WOS:000301609000040
PM 21949227
ER
PT J
AU Velayos-Baeza, A
Holinski-Feder, E
Neitzel, B
Bader, B
Critchley, EMR
Monaco, AP
Danek, A
Walker, RH
AF Velayos-Baeza, Antonio
Holinski-Feder, Elke
Neitzel, Birgit
Bader, Benedikt
Critchley, Edmund M. R.
Monaco, Anthony P.
Danek, Adrian
Walker, Ruth H.
TI Chorea-Acanthocytosis Genotype in the Original Critchley Kentucky
Neuroacanthocytosis Kindred
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID GENE; PROTEIN; DISEASE
AB Objective: To determine the molecular nature of the neurological disease in the seminal family reported by Critchley et al in the 1960s, characterized by a hyperkinetic movement disorder and the appearance of acanthocytosis on peripheral blood smear. The eponym Levine-Critchley syndrome, subsequently termed neuroacanthocytosis, has been applied to symptomatically similar, but genetically distinct, disorders, resulting in clinical and diagnostic confusion.
Design: DNA analysis.
Setting: Molecular biology research laboratories.
Participants: First- and second-degree relatives of the original Critchley et al proband from Kentucky.
Main Outcome Measures: Mutations in the VPS13A gene.
Results: A mutation was identified in the VPS13A gene, responsible for autosomal recessive chorea-acanthocytosis. Haplotype reconstruction suggested that this mutation was homozygous in the proband.
Conclusion: These findings strongly support the diagnosis of chorea-acanthocytosis as the disorder described in the original report.
C1 [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA.
[Walker, Ruth H.] Mt Sinai Sch Med, New York, NY USA.
[Velayos-Baeza, Antonio; Monaco, Anthony P.] Wellcome Trust Ctr Human Genet, Oxford, England.
[Critchley, Edmund M. R.] Univ Cent Lancashire, Preston PR1 2HE, Lancs, England.
[Holinski-Feder, Elke; Neitzel, Birgit] Med Genet Zentrum, Munich, Germany.
[Bader, Benedikt; Danek, Adrian] Univ Munich, Neurol Klin & Poliklin, Munich, Germany.
RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol 127, Bronx, NY 10468 USA.
EM ruth.walker@mssm.edu
RI Danek, Adrian/G-7339-2011; Monaco, Anthony/A-4495-2010
OI Danek, Adrian/0000-0001-8857-5383; Monaco, Anthony/0000-0001-7480-3197
FU Mary Kinross Charitable Trust and the Chaney family; Wellcome Trust
[075491/Z/04]
FX This work was supported by a grant from the Advocacy for
Neuroacanthocytosis Patients (the Mary Kinross Charitable Trust and the
Chaney family) (Drs Velayos-Baeza and Monaco) and grant 075491/Z/04 from
the Wellcome Trust (Drs Velayos-Baeza and Monaco).
NR 14
TC 1
Z9 1
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD OCT
PY 2011
VL 68
IS 10
BP 1330
EP 1333
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 830YV
UT WOS:000295696700018
PM 21987550
ER
PT J
AU Kinlay, S
AF Kinlay, Scott
TI Grasping the Nettle and Femoral Artery Stenting
SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS
LA English
DT Editorial Material
DE Editorials; peripheral arterial disease; stents; drugeluting stents;
revascularization; clinical trials randomized
ID BARE NITINOL STENTS; BALLOON ANGIOPLASTY; INTERMITTENT CLAUDICATION;
DISEASE; TRIAL; IMPLANTATION; LESIONS; RESTENOSIS; PACLITAXEL
C1 [Kinlay, Scott] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA.
RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Div Cardiovasc, Cardiac Catheterizat Lab, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM scott.kinlay@va.gov
NR 19
TC 2
Z9 2
U1 0
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 OCT
PY 2011
VL 4
IS 5
BP 407
EP 409
DI 10.1161/CIRCINTERVENTIONS.111.965038
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 896EV
UT WOS:000300549100005
PM 22010187
ER
PT J
AU Dake, MD
Ansel, GM
Jaff, MR
Ohki, T
Saxon, RR
Smouse, HB
Zeller, T
Roubin, GS
Burket, MW
Khatib, Y
Snyder, SA
Ragheb, AO
White, JK
Machan, LS
AF Dake, Michael D.
Ansel, Gary M.
Jaff, Michael R.
Ohki, Takao
Saxon, Richard R.
Smouse, H. Bob
Zeller, Thomas
Roubin, Gary S.
Burket, Mark W.
Khatib, Yazan
Snyder, Scott A.
Ragheb, Anthony O.
White, J. King
Machan, Lindsay S.
CA Zilver PTX Investigators
TI Paclitaxel-Eluting Stents Show Superiority to Balloon Angioplasty and
Bare Metal Stents in Femoropopliteal Disease Twelve-Month Zilver PTX
Randomized Study Results
SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE peripheral vascular disease; angioplasty; paclitaxel-eluting stent;
drug-eluting stent
ID SUPERFICIAL FEMORAL-ARTERY; NITINOL STENTS; CLINICAL-TRIALS; OCCLUSIVE
DISEASE; IMPLANTATION; LESIONS; RESTENOSIS; PLACEMENT; PERFORMANCE;
INHIBITION
AB Background-Sustained benefits of drug-eluting stents in femoropopliteal arteries have not been demonstrated. This prospective, multinational, randomized study was designed to compare the 12-month safety and effectiveness of a polymer-free, paclitaxel-coated nitinol drug-eluting stent (DES) with percutaneous transluminal angioplasty (PTA) and provisional bare metal stent (BMS) placement in patients with femoropopliteal peripheral artery disease.
Methods and Results-Patients were randomly assigned to primary DES implantation (n=236) or PTA (n=238). Demographics and lesion characteristics were similar between groups (eg, average lesion length, approximately 65 +/- 40 mm). One hundred twenty patients had acute PTA failure and underwent secondary random assignment to provisional DES (n=61) or BMS (n=59). Primary end points were the 12-month rates of event-free survival and patency in the primary DES and PTA groups. Compared with the PTA group, the primary DES group exhibited superior 12-month event-free survival (90.4% versus 82.6%; P=0.004) and primary patency (83.1% versus 32.8%; P<0.001), satisfying the primary hypotheses. In the secondary evaluations, (1) the primary DES group exhibited superior clinical benefit compared with the PTA group (88.3% versus 75.8%; P<0.001), (2) the provisional DES group exhibited superior primary patency (89.9% versus 73.0%; P=0.01) and superior clinical benefit (90.5% and 72.3%, P=0.009) compared with the provisional BMS group, and (3) the stent fracture rate (both DES and BMS) was 0.9% (4/457).
Conclusions-Femoropopliteal peripheral artery disease treatment with the paclitaxel-eluting stent was associated with superior 12-month outcomes compared with PTA and provisional BMS placement.
C1 [Dake, Michael D.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
[Ansel, Gary M.] MidWest Cardiol Res Fdn, Columbus, OH USA.
[Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ohki, Takao] Jikei Univ Hosp, Tokyo, Japan.
[Saxon, Richard R.] Tri City Med Ctr, Oceanside, CA USA.
[Smouse, H. Bob] OSF St Francis Med Ctr, Peoria, IL USA.
[Machan, Lindsay S.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Zeller, Thomas] Herz Zentrum, Bad Krozingen, Germany.
[Roubin, Gary S.] Lenox Hill Hosp, New York, NY 10021 USA.
[Burket, Mark W.] Univ Toledo, Med Ctr, Toledo, OH 43606 USA.
[Khatib, Yazan] First Coast Cardiovasc, Jacksonville, FL USA.
[Snyder, Scott A.; Ragheb, Anthony O.] MED Inst Inc, W Lafayette, IN USA.
[White, J. King] Christus St Patrick Hosp, Lake Charles, LA USA.
RP Dake, MD (reprint author), Stanford Univ, Sch Med, Dept Cardiothorac Surg, Falk Cardiovasc Res Ctr, 300 Pasteur Dr, Stanford, CA 94305 USA.
EM mddake@stanford.edu
FU Cook Medical; Abbott Vascular; WL Gore; Bristol-Myers Squibb/Sanofi
Pharmaceutical; organization and Cook Group Company
FX The study was sponsored by Cook Medical.; Dr Dake received speaking
honorarium and travel grants from Cook Medical and consulting fees from
Abbott Vascular and WL Gore. Dr Ansel received consulting fees, travel
grants, payment for review activities, lectures, and royalties for a
device unrelated to this study from Cook Medical; he is an advisor for
Cordis Endovascular, Boston Scientific, and Abbott Vascular. Dr Jaff is
a member of VIVA Physicians, Inc, a noncompensated consultant for Boston
Scientific, Abbott Vascular, Cordis Corporation, Covidien, and Medtronic
Vascular, and holds equity investment in Icon Interventional, I.C.
Sciences, Micell Technologies, Nexeon Medical Systems, PQ Bypass Inc,
Primacea, Trireme/TMI, and Vascular Therapies. Dr Jaff has no financial
relationship with Cook Medical. Dr Ohki received travel grants and
payment for the development of educational materials from Cook Medical.
Dr Saxon received consulting fees, travel grants, and payment for review
activities from Cook Medical; he also received consulting fees from WL
Gore and Atheromed and travel grants, payment for the development of
educational materials, and payment for manuscript preparation from WL
Gore and holds stock options in Atheromed. Dr Smouse received consulting
fees from Cook Medical. Dr Machan received travel grants from Cook
Medical and holds stock options in Angiotech Pharmaceuticals. Dr Zeller
received consulting fees and payment for lectures from Cook Medical; he
received consulting fees from Medrad Possis, eV3, CR Bard, Straub
Medical, Ardian, Gore, Cordis Corporation, and Biotronik, and payment
for lectures from Cordis Corporation, eV3, Medtronic Invatec,
Sanofi-Aventi, Medrad Possis, WL Gore, and Pathway Medical and serves on
the board for Medtronic Invatec, Angioslide, and Avidal Vascular. Dr
Roubin received travel grants and royalties for a device not related to
this study from Cook Medical. Dr Burket received consulting fees and
travel grants from Cook Medical; he received consulting fees from Cook
Medical and the IDEV DMSB and lecture fees from Bristol-Myers
Squibb/Sanofi Pharmaceutical. Dr White received travel grants from Cook
Medical. Drs Snyder and Ragheb are paid employees of MED Institute, a
contract research organization and Cook Group Company.
NR 32
TC 221
Z9 235
U1 0
U2 13
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 OCT
PY 2011
VL 4
IS 5
BP 495
EP 504
DI 10.1161/CIRCINTERVENTIONS.111.962324
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 896EV
UT WOS:000300549100017
PM 21953370
ER
PT J
AU Ananthakrishnan, A
Higuchi, L
Huang, E
Khalili, H
Richter, J
Fuchs, C
Chan, A
AF Ananthakrishnan, Ashwin
Higuchi, Leslie
Huang, Edward
Khalili, Hamed
Richter, James
Fuchs, Charles
Chan, Andrew
TI A Prospective Study of Aspirin, Non-steroidal Anti-inflammatory Drug Use
and Risk of Crohn's Disease and Ulcerative Colitis
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 76th Annual Scientific Meeting of the
American-College-of-Gastroenterology
CY OCT 28-NOV 02, 2011
CL Washington, DC
SP Amer Coll Gastroenterol
C1 [Ananthakrishnan, Ashwin; Huang, Edward; Khalili, Hamed; Richter, James; Chan, Andrew] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Higuchi, Leslie] Childrens Hosp Boston, Boston, MA USA.
[Fuchs, Charles] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD OCT
PY 2011
VL 106
SU 2
MA 1224
BP S462
EP S462
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 885II
UT WOS:000299772002068
ER
PT J
AU Bunchorntavakul, C
Siripun, A
Chavalitdhamrong, D
AF Bunchorntavakul, Chalermrat
Siripun, Aroon
Chavalitdhamrong, Disaya
TI Fluvastatin Monotherapy for the Treatment of Patients with Chronic
Hepatitis C: A Randomized Double-Blinded Placebo-Controlled Study
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 76th Annual Scientific Meeting of the
American-College-of-Gastroenterology
CY OCT 28-NOV 02, 2011
CL Washington, DC
SP Amer Coll Gastroenterol
C1 [Bunchorntavakul, Chalermrat; Siripun, Aroon] Rangsit Univ, Fac Med, Rajavithi Hosp, Bangkok, Thailand.
[Chavalitdhamrong, Disaya] Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
NR 0
TC 2
Z9 2
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD OCT
PY 2011
VL 106
SU 2
MA 259
BP S102
EP S103
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 885II
UT WOS:000299772000260
ER
PT J
AU Greenwald, B
Wolfsen, H
Abrams, J
Lightdale, C
Nishioka, N
Johnston, M
Zfass, A
Bhatt, A
Makkar, R
Barthel, J
Dumot, J
AF Greenwald, Bruce
Wolfsen, Herbert
Abrams, Julian
Lightdale, Charles
Nishioka, Norman
Johnston, Mark
Zfass, Alvin
Bhatt, Amit
Makkar, Rohit
Barthel, James
Dumot, John
TI Spray Cryotherapy for Esophageal Cancer: Long-term Results
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 76th Annual Scientific Meeting of the
American-College-of-Gastroenterology
CY OCT 28-NOV 02, 2011
CL Washington, DC
SP Amer Coll Gastroenterol
C1 [Greenwald, Bruce] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Greenwald, Bruce] Greenebaum Canc Ctr, Baltimore, MD USA.
[Wolfsen, Herbert] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA.
[Abrams, Julian; Lightdale, Charles] Columbia Univ, Med Ctr, New York, NY USA.
[Nishioka, Norman] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nishioka, Norman] Harvard Univ, Sch Med, Boston, MA USA.
[Johnston, Mark] Lancaster Gastroenterol Inc, Lancaster, PA USA.
[Zfass, Alvin] Virginia Commonwealth Univ, Richmond, VA USA.
[Bhatt, Amit; Makkar, Rohit] Cleveland Clin, Cleveland, OH 44106 USA.
[Barthel, James] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Dumot, John] Univ Hosp Case Med Ctr, Cleveland, OH USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD OCT
PY 2011
VL 106
SU 2
MA 17
BP S7
EP S7
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 885II
UT WOS:000299772000018
ER
PT J
AU Khalili, H
Higuchi, L
Huang, E
Ananthakrishnan, A
Richter, J
Fuchs, C
Chan, A
AF Khalili, Hamed
Higuchi, Leslie
Huang, Edward
Ananthakrishnan, Ashwin
Richter, James
Fuchs, Charles
Chan, Andrew
TI Geographic Variations and Risk of Crohn's Disease and Ulcerative
Colitis: Results from Two Large Prospective Cohorts
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 76th Annual Scientific Meeting of the
American-College-of-Gastroenterology
CY OCT 28-NOV 02, 2011
CL Washington, DC
SP Amer Coll Gastroenterol
C1 [Khalili, Hamed; Huang, Edward; Ananthakrishnan, Ashwin; Richter, James; Chan, Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Higuchi, Leslie] Childrens Hosp, Boston, MA 02115 USA.
[Fuchs, Charles] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD OCT
PY 2011
VL 106
SU 2
MA 1284
BP S489
EP S489
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 885II
UT WOS:000299772002128
ER
PT J
AU Leung, F
AF Leung, Felix
TI Injection Treatment for Fecal Incontinence (FI) - Review of Impact on
Quality-of-life (QoL) Measures
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 76th Annual Scientific Meeting of the
American-College-of-Gastroenterology
CY OCT 28-NOV 02, 2011
CL Washington, DC
SP Amer Coll Gastroenterol
C1 [Leung, Felix] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA USA.
[Leung, Felix] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD OCT
PY 2011
VL 106
SU 2
MA 1319
BP S503
EP S503
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 885II
UT WOS:000299772002162
ER
PT J
AU Okeke, F
Korsten, M
Shaw, S
Hunt, K
Rosman, A
AF Okeke, Francis
Korsten, Mark
Shaw, Spencer
Hunt, Kristel
Rosman, Alan
TI Safety of Propofol Used as a Rescue Agent During Colonoscopy
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 76th Annual Scientific Meeting of the
American-College-of-Gastroenterology
CY OCT 28-NOV 02, 2011
CL Washington, DC
SP Amer Coll Gastroenterol
C1 [Okeke, Francis; Korsten, Mark; Shaw, Spencer; Hunt, Kristel; Rosman, Alan] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD OCT
PY 2011
VL 106
SU 2
MA 402
BP S157
EP S158
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 885II
UT WOS:000299772000399
ER
PT J
AU Salazar, C
Cardenas, V
Reddy, R
Graham, D
AF Salazar, Cesar
Cardenas, Victor
Reddy, Rita
Graham, David
TI Helicobacter pylori Eradication Using a 14-day Bismuth Quadruple Therapy
Among Hispanic Adults in El Paso, Texas: Preliminary Findings
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 76th Annual Scientific Meeting of the
American-College-of-Gastroenterology
CY OCT 28-NOV 02, 2011
CL Washington, DC
SP Amer Coll Gastroenterol
C1 [Cardenas, Victor] Univ Texas Sch Publ Hlth, El Paso, TX USA.
[Reddy, Rita; Graham, David] DeBakey Vet Affairs Med Ctr, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD OCT
PY 2011
VL 106
SU 2
MA 118
BP S47
EP S48
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 885II
UT WOS:000299772000119
ER
PT J
AU Spiegel, B
Poysophon, P
Snyder, B
Agarwal, N
Yen, L
Hodgkins, P
Cohen, E
Vu, M
Kurzbard, N
Atia, M
Sheen, V
Kaneshiro, M
Fuller, G
Bolus, R
AF Spiegel, Brennan
Poysophon, Poyrung
Snyder, Bradley
Agarwal, Nikhil
Yen, Linette
Hodgkins, Paul
Cohen, Erica
Vu, Michelle
Kurzbard, Nicole
Atia, Mary
Sheen, Victoria
Kaneshiro, Marc
Fuller, Garth
Bolus, Roger
TI Direct Costs and Resource Utilization for Inpatient Diverticulitis
Admissions
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 76th Annual Scientific Meeting of the
American-College-of-Gastroenterology
CY OCT 28-NOV 02, 2011
CL Washington, DC
SP Amer Coll Gastroenterol
C1 [Spiegel, Brennan] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA.
[Snyder, Bradley; Kurzbard, Nicole] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Yen, Linette; Hodgkins, Paul] Shire Dev Inc, Global Hlth Econ Outcomes Res & Epidemiol, Los Angeles, CA USA.
[Agarwal, Nikhil; Cohen, Erica; Vu, Michelle; Atia, Mary; Sheen, Victoria; Kaneshiro, Marc; Fuller, Garth; Bolus, Roger] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ CORE, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD OCT
PY 2011
VL 106
SU 2
MA 1149
BP S428
EP S428
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 885II
UT WOS:000299772001711
ER
PT J
AU Wasan, S
Juillerat, P
Fowler, S
Yajnik, V
Korzenik, J
Pabby, V
Friedman, S
Coukos, J
Barto, A
Pellish, R
Farraye, F
AF Wasan, Sharmeel
Juillerat, Pascal
Fowler, Sharyle
Yajnik, Vijay
Korzenik, Joshua
Pabby, Vikas
Friedman, Sonia
Coukos, Jennifer
Barto, Amy
Pellish, Randall
Farraye, Francis
TI Efficacy and Safety of Natalizumab in Crohn's Disease Patients Treated
at Five Academic Boston Hospitals
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 76th Annual Scientific Meeting of the
American-College-of-Gastroenterology
CY OCT 28-NOV 02, 2011
CL Washington, DC
SP Amer Coll Gastroenterol
C1 [Wasan, Sharmeel; Coukos, Jennifer; Farraye, Francis] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Juillerat, Pascal; Fowler, Sharyle; Yajnik, Vijay; Korzenik, Joshua] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pabby, Vikas; Friedman, Sonia] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Barto, Amy] Lahey Clin Fdn, Burlington, MA USA.
[Pellish, Randall] Univ Massachusetts, Worcester, MA 01605 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD OCT
PY 2011
VL 106
SU 2
MA 1249
BP S473
EP S473
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 885II
UT WOS:000299772002093
ER
PT J
AU Lin, CW
Warram, JH
Veng-Pedersen, P
AF Lin, C. W.
Warram, J. H.
Veng-Pedersen, P.
TI A Bayesian population analysis of the development of type 2 diabetes in
the offspring of diabetic parents
SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
LA English
DT Article
DE Bayesian analysis; Disease development; Type 2 diabetes; Glucose;
Insulin; HOMA-IR; Body mass index
ID INSULIN SECRETORY DYSFUNCTION; GLUCOSE-TOLERANCE; RISK-FACTORS;
BETA-CELL; RESISTANCE; MELLITUS; NIDDM; MODEL; PROGRESSION; DISEASE
AB Disease progression of type 2 diabetes (T2D) has received considerable attention, but little is known about the disease development of T2D. The purposes of this study were to identify disease development variables (DDV) for development of T2D and to compare corresponding models for disease development. All subjects included in this study were the offspring of diabetic parents and were followed up to 25 years. Repeated fasting blood samples were collected during the follow-up. Longitudinal data of four DDVs, namely fasting blood glucose (FBG), fasting serum insulin (FSI), homeostatic model assessment of insulin resistance (HOMA-IR) and body mass index (BMI) were recorded and compared. According to the diabetes status at the end of the follow-up, the data analysis involved a progressor group of 25 subjects, and a non-progressor group of 127 subjects. The temporal changes in the four DDVs over the time course of the disease development were evaluated by a single-slope and a dual-slope population-based Bayesian model. A dual-slope model based on FBG was found to be the best disease development model. For non-progressors, the FBG baseline stayed at 69.2 [66.5, 72.1] mg/dl (Bayes estimate [95% Bayesian credible set]) and increased with age by a rate of 0.227 mg/dl [0.149, 0.3] per year. For the progressors, the FBG increase with age the same rate as non-progressors and started to have an additional increase of 2.27 [0.505, 4.52] mg/dl per year, starting 8.73 [-10.8, -6.93] years before the diagnosis of T2D. No significant longitudinal increasing or decreasing temporal pattern was found for FSI, HOMA-IR and BMI by the population-based Bayesian approach. The proposed model, which enables a quantitative, time-based evaluation of the development of T2D in this higher risk population, may be used to quantify the effect of interventions/prevention strategies such as drug treatment and lifestyle changes.
C1 [Lin, C. W.; Veng-Pedersen, P.] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA.
[Warram, J. H.] Joslin Diabet Ctr, Sect Epidemiol & Genet, Boston, MA 02215 USA.
RP Veng-Pedersen, P (reprint author), Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA.
EM veng@uiowa.edu
NR 35
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1567-567X
J9 J PHARMACOKINET PHAR
JI J. Pharmacokinet. Pharmacodyn.
PD OCT
PY 2011
VL 38
IS 5
BP 563
EP 579
DI 10.1007/s10928-011-9208-2
PG 17
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 890VB
UT WOS:000300172600003
PM 21833670
ER
PT J
AU Alexander, KA
Dovydaitis, T
Beacham, B
Bohinski, JM
Brawner, BM
Clements, CP
Everett, JS
Gomes, MM
Harner, H
McDonald, CC
Pinkston, E
Sommers, MS
AF Alexander, Kamila A.
Dovydaitis, Tiffany
Beacham, Barbara
Bohinski, Julia M.
Brawner, Bridgette M.
Clements, Carla P.
Everett, Janine S.
Gomes, Melissa M.
Harner, Holly
McDonald, Catherine C.
Pinkston, Esther
Sommers, Marilyn S.
TI Learning Health Equity Frameworks within a Community of Scholars
SO JOURNAL OF NURSING EDUCATION
LA English
DT Article
AB Scholars in nursing science have long espoused the concept of health equity without specifically using the term or dialoguing about the social determinants of health and social justice. This article describes the development, implementation, and evaluation of a doctoral and postdoctoral seminar collective entitled "Health Equity: Conceptual, Linguistic, Methodological, and Ethical Issues." The course enabled scholars-in-training to consider the construct and its nuances and frame a personal philosophy of health equity. An example of how a group of emerging scholars can engage in the important, but difficult, discourse related to health equity is provided. The collective provided a forum for debate, intellectual growth, and increased insight for students and faculty. The lessons learned by all participants have the potential to enrich doctoral and postdoctoral scientific training in nursing science and may serve as a model for other research training programs in the health sciences.
C1 [Alexander, Kamila A.; Dovydaitis, Tiffany; Beacham, Barbara; Bohinski, Julia M.; Brawner, Bridgette M.; Clements, Carla P.; Everett, Janine S.; McDonald, Catherine C.; Pinkston, Esther; Sommers, Marilyn S.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA.
[Harner, Holly] LaSalle Univ, MPH Program, Sch Nursing & Hlth Sci, Philadelphia, PA USA.
[Gomes, Melissa M.] Virginia Commonwealth Univ, Sch Nursing, Richmond, VA USA.
RP Alexander, KA (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, 418 Curie Blvd,Room 233L, Philadelphia, PA 19104 USA.
EM kamilaa@nursing.upenn.edu
FU National Institute of Nursing Research [T32NR007100, F31NR011524,
2R01NR005352, F31NR011106, F31NR011107]; University of Pennsylvania
FX This work was supported by the Ruth L. Kirschstein NRSA Pre & Post
doctoral Fellowship at the University of Pennsylvania School of Nursing,
Research on Vulnerable Women, Children and Families T32NR007100 from the
National Institute of Nursing Research. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institute of Nursing Research or the
National Institutes of Health. This work was also supported by Award
Number F31NR011524 (to Barbara Beacham) from the National Institute of
Nursing Research; Offices of the Provost and School of Nursing Dean from
the University of Pennsylvania (to Bridgette M. Brawner); Diversity
Supplement to 2R01NR005352 (to Carla Clements) from the National
Institute of Nursing Research; Award Number F31NR011106 (to Janine S.
Everett) from the National Institute of Nursing Research; and Award
Number F31NR011107 (to Catherine C. McDonald) from the National
Institute of Nursing Research.
NR 13
TC 2
Z9 2
U1 0
U2 4
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0148-4834
J9 J NURS EDUC
JI J. Nurs. Educ.
PD OCT
PY 2011
VL 50
IS 10
BP 569
EP 574
DI 10.3928/01484834-20110630-05
PG 6
WC Nursing
SC Nursing
GA 884VK
UT WOS:000299736700005
PM 21710960
ER
PT J
AU Mirkovic, J
Lau, C
McGee, S
Crum, C
Badizadegan, K
Feld, M
Stier, E
AF Mirkovic, Jelena
Lau, Condon
McGee, Sasha
Crum, Christopher
Badizadegan, Kamran
Feld, Michael
Stier, Elizabeth
TI Detecting high-grade squamous intraepithelial lesions in the cervix with
quantitative spectroscopy and per-patient normalization
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID VIVO LIGHT-SCATTERING; IN-VIVO; FLUORESCENCE SPECTROSCOPY; REFLECTANCE
SPECTROSCOPY; OPTICAL-DETECTION; PRECANCER; NEOPLASIA; TISSUE; PATTERNS;
SPECTRA
AB This study develops a spectroscopic algorithm for detection of cervical high grade squamous intraepithelial lesions (HSILs). We collected reflectance and fluorescence spectra with the quantitative spectroscopy probe to measure nine spectroscopic parameters from 43 patients undergoing standard colposcopy with directed biopsy. We found that there is improved accuracy for distinguishing HSIL from non-HSIL (low grade SIL and normal tissue) when we "normalized" spectroscopy parameters by dividing the values extracted from each clinically determined suspicious site by the corresponding value extracted from a clinically normal squamous site from the same patient. The "normalized" scattering parameter (A) at 700nm, best distinguished HSIL from non-HSIL with sensitivity and specificity of 89% and 79% suggesting that a simple, monochromatic instrument measuring only A may accurately detect HSIL. (C) 2011 Optical Society of America
C1 [Mirkovic, Jelena; Lau, Condon; McGee, Sasha; Feld, Michael] MIT, George R Harrison Spect Lab, Cambridge, MA 02179 USA.
[Mirkovic, Jelena; Crum, Christopher] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Badizadegan, Kamran] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Stier, Elizabeth] Boston Med Ctr, Dept Obstet & Gynecol, Boston, MA 02118 USA.
RP Mirkovic, J (reprint author), MIT, George R Harrison Spect Lab, 77 Massachusetts Ave, Cambridge, MA 02179 USA.
EM jedza@alum.mit.edu
RI Mirkovic, Jelena/A-6253-2013;
OI LAU, Condon/0000-0002-6569-5814
FU National Institutes of Health [R01 CA097966]; Laser Biomedical Research
Center [P41 RR02594]
FX We thank Chung-Chieh Yu and Jonathan Nazemi for valuable discussions
about data modeling. We thank Jonathan Nazemi and Luis Galindo for the
engineering assistance, and Victoria Feng for the technical assistance.
We finally thank Teresa Darragh and Antonio de las Morenas for their
valuable contribution to the pathology evaluation. This research was
funded by the National Institutes of Health grant R01 CA097966 and the
Laser Biomedical Research Center grant P41 RR02594.
NR 36
TC 4
Z9 4
U1 0
U2 3
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD OCT 1
PY 2011
VL 2
IS 10
BP 2917
EP 2925
PG 9
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 886FN
UT WOS:000299838800017
PM 22025992
ER
PT J
AU Westmoreland, SV
Annamalai, L
Lentz, MR
Ratai, EM
Assaf, B
Boisvert, K
Huynh, T
Vallender, EJ
Miller, GM
Madras, BK
Gonzalez, RG
AF Westmoreland, Susan V.
Annamalai, Lakshmanan
Lentz, Margaret R.
Ratai, Eva-Marie
Assaf, Basel
Boisvert, Karen
Thanhthao Huynh
Vallender, Eric J.
Miller, Gregory M.
Madras, Bertha K.
Gonzalez, R. Gilberto
TI Growth-associated protein-43 and ephrin B3 induction in the brain of
adult SIV-infected rhesus macaques
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Article
DE Rhesus; Macaque; SIV; GAP-43; Ephrin B3; Neuronal injury; Synaptophysin;
Plasticity; Microglia
ID IMMUNODEFICIENCY-VIRUS ENCEPHALITIS; GLUTAMATE TRANSPORT; NEOCORTICAL
DAMAGE; IN-VIVO; GAP-43; INJURY; EXPRESSION; MODEL; HIV; PLASTICITY
AB Understanding the mechanisms of neuronal regeneration and repair in the adult central nervous system is a vital area of research. Using a rhesus lentiviral encephalitis model, we sought to determine whether recovery of neuronal metabolism after injury coincides with the induction of two important markers of synaptodendritic repair: growth-associated protein-43 (GAP-43) and ephrin B3. We examined whether the improvement of neuronal metabolism with combined anti-retroviral therapy (cART) after simian immunodeficiency virus (SIV) infection in rhesus macaques involved induction of GAP-43, also known as neuromodulin, and ephrin B3, both implicated in axonal pathfinding during neurodevelopment and regulation of synapse formation, neuronal plasticity, and repair in adult brain. We utilized magnetic resonance spectroscopy to demonstrate improved neuronal metabolism in vivo in adult SIV-infected cART animals compared to untreated and uninfected controls. We then assessed levels of GAP-43, ephrin B3, and synaptophysin, a presynaptic marker, in three brain regions important for cognitive function, cortex, hippocampus, and putamen, by quantitative real-time RT-PCR and immunohistochemistry. Here we demonstrate that (1) GAP-43 mRNA and protein are induced with SIV infection, (2) GAP-43 protein is higher in the hippocampus outer molecular layer in SIV-infected animals that received cART compared to those that did not, and (3) activated microglia and infiltrating SIV-infected macrophages express abundant ephrin B3, an important axonal guidance molecule. We propose a model whereby SIV infection triggers events that lead to induction of GAP-43 and ephrin B3, and that short-term cART results in increased magnitude of repair mechanisms especially in the hippocampus, a region known for high levels of adult plasticity.
C1 [Westmoreland, Susan V.; Annamalai, Lakshmanan; Assaf, Basel; Boisvert, Karen] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Comparat Pathol, Southborough, MA 01772 USA.
[Vallender, Eric J.; Miller, Gregory M.; Madras, Bertha K.] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Neurosci, Southborough, MA 01772 USA.
[Thanhthao Huynh] Tufts Cummings Sch Vet Med, North Grafton, MA USA.
[Lentz, Margaret R.; Ratai, Eva-Marie; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Lentz, Margaret R.; Ratai, Eva-Marie; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Neuroradiol Div, Charlestown, MA USA.
RP Westmoreland, SV (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Comparat Pathol, Southborough, MA 01772 USA.
EM Susan_westmoreland@hms.harvard.edu
RI Vallender, Eric/A-2450-2008
OI Vallender, Eric/0000-0003-3506-0540
FU NEPRC [RR00168, R01NS050041, DA025697]; NEPRC Microscopy and Primate
Genetics Cores
FX We would like to thank Dr. Larry Benowitz for supplying the anti-GAP-43
antibody and protocol, Ron Desrosiers for supplying the virus inoculum
SIVmac251, Keith Reimann for providing anti-CD8 cM-T807, Raymond
Schinazi for supplying Racivir (RCV), and Norbert Bischofberger of
Gilead Sciences for providing PMPA. In addition, we thank Elizabeth
Curran, Michael O'Connell, and Doug Pauley for pathology assistance, and
Drs. Prabhat Sehgal, Angela Carville, and Elisabeth Moeller for
veterinary expertise. We also thank Hayley Dirscherl, Alexis Denysyk,
Heather Knight, and Karen Boisvert Dalecki for their contribution with
immunohistochemistry and Hong Yang for real-time PCR contribution. This
work was supported by RR00168 (NEPRC Base Grant), R01NS050041 (RGG),
DA025697 (GMM), and the NEPRC Microscopy and Primate Genetics Cores.
NR 47
TC 1
Z9 2
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
EI 1538-2443
J9 J NEUROVIROL
JI J. Neurovirol.
PD OCT
PY 2011
VL 17
IS 5
BP 455
EP 468
DI 10.1007/s13365-011-0047-0
PG 14
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 876QG
UT WOS:000299122000006
PM 21789725
ER
PT J
AU McGuire, JL
Fridman, V
Wuthrich, C
Koralnik, IJ
Jacobs, D
AF McGuire, Jennifer L.
Fridman, Vera
Wuethrich, Christian
Koralnik, Igor J.
Jacobs, Dina
TI Progressive multifocal leukoencephalopathy associated with isolated
CD8+T-lymphocyte deficiency mimicking tumefactive MS
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Article
ID JC VIRUS; CEREBROSPINAL-FLUID; MULTIPLE-SCLEROSIS; IMMUNODEFICIENCY;
IMMUNOSUPPRESSION; INFECTION
C1 [McGuire, Jennifer L.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19146 USA.
[McGuire, Jennifer L.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Fridman, Vera] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Wuethrich, Christian; Koralnik, Igor J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Viral Pathogenesis, Boston, MA 02215 USA.
[Wuethrich, Christian; Koralnik, Igor J.] Beth Israel Deaconess Med Ctr, Dept Neurol, Div Neurovirol, Boston, MA 02215 USA.
[Jacobs, Dina] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
RP McGuire, JL (reprint author), Childrens Hosp Philadelphia, Div Neurol, 34th St & Civ Ctr Blvd, Philadelphia, PA 19146 USA.
EM mcguirej@email.chop.edu
FU NIH [T32-NS061779, R01 NS 041198, 047029, K24 NS 060950]; Philadelphia
Foundation; Biogen Idec
FX Dr. McGuire received support from NIH grant T32-NS061779 and from the L.
Morton Morley Funds of The Philadelphia Foundation. Dr. Koralnik has
received honoraria from Bristol-Myers Squibb, Ono Pharmaceuticals, Merck
Serono, Anti-sense, and Alnylam, and is supported in part by NIH grants
R01 NS 041198 and 047029 and K24 NS 060950 and a research grant from
Biogen Idec. Dr. Jacobs has received honoraria from Biogen Idec, Teva
Pharmaceuticals, and Serono. The content is the sole responsibility of
the authors and does not necessarily represent the official views of the
National Institutes of Health.
NR 23
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD OCT
PY 2011
VL 17
IS 5
BP 500
EP 503
DI 10.1007/s13365-011-0045-2
PG 4
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 876QG
UT WOS:000299122000011
PM 21786075
ER
PT J
AU Bailey, RR
Stuckey, DR
Norman, BA
Duggan, AP
Bacon, KM
Connor, DL
Lee, I
Muder, RR
Lee, BY
AF Bailey, Rachel R.
Stuckey, Dianna R.
Norman, Bryan A.
Duggan, Andrew P.
Bacon, Kristina M.
Connor, Diana L.
Lee, Ingi
Muder, Robert R.
Lee, Bruce Y.
TI Home-Based Preoperative Chlorhexidine Bathing Cloths to Prevent Surgical
Site Infection Reply
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Letter
C1 [Bailey, Rachel R.] Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA 15213 USA.
[Bailey, Rachel R.; Stuckey, Dianna R.; Bacon, Kristina M.; Connor, Diana L.; Lee, Bruce Y.] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15213 USA.
[Bailey, Rachel R.; Stuckey, Dianna R.; Bacon, Kristina M.; Connor, Diana L.; Lee, Bruce Y.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Norman, Bryan A.; Duggan, Andrew P.] Univ Pittsburgh, Dept Ind Engn, Pittsburgh, PA 15213 USA.
[Lee, Ingi] Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA.
[Lee, Ingi] Univ Penn, Sch Med, Ctr Evidence Based Practice, Philadelphia, PA 19104 USA.
[Muder, Robert R.] Vet Affairs Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA USA.
RP Bailey, RR (reprint author), Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, Sect Decis Sci & Clin Syst Modeling, 3520 Forbes Ave,1st Floor, Pittsburgh, PA 15213 USA.
EM RRB16@pitt.edu
NR 6
TC 0
Z9 0
U1 0
U2 3
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 OCT
PY 2011
VL 32
IS 10
BP 1047
EP 1048
DI 10.1086/662024
PG 2
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 876BX
UT WOS:000299083100016
ER
PT J
AU Kopeikina, KJ
Carlson, GA
Pitstick, R
Ludvigson, AE
Peters, A
Luebke, JI
Koffie, RM
Frosch, MP
Hyman, BT
Spires-Jones, TL
AF Kopeikina, Katherine J.
Carlson, George A.
Pitstick, Rose
Ludvigson, Adam E.
Peters, Alan
Luebke, Jennifer I.
Koffie, Robert M.
Frosch, Matthew P.
Hyman, Bradley T.
Spires-Jones, Tara L.
TI Tau Accumulation Causes Mitochondrial Distribution Deficits in Neurons
in a Mouse Model of Tauopathy and in Human Alzheimer's Disease Brain
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID AXONAL-TRANSPORT; NEURODEGENERATIVE DISEASES; NEUROFIBRILLARY TANGLES;
AMYLOID-BETA; SYNAPTIC MITOCHONDRIA; ENDOPLASMIC-RETICULUM; OXIDATIVE
STRESS; SENILE PLAQUES; DYSFUNCTION; OLIGOMERS
AB Neurofibrillary tangles (NFT), intracellular inclusions of abnormal fibrillar forms of naicrotubule associated protein tau, accumulate in Alzheimer's disease (AD) and other tauopathies and are believed to cause neuronal dysfunction, but the mechanism of tau-mediated toxicity are uncertain. Tau overexpression in cell culture impairs localization and trafficking of organelles. Here we tested the hypothesis that, in the intact brain, changes in mitochondrial distribution occur secondary to pathological changes in tau. Array tomography, a high-resolution imaging technique, was used to examine mitochondria in the reversible transgenic (rTg)4510, a regulatable transgenic, mouse model and AD brain tissue. Mitochondrial distribution is progressively disrupted with age in rTg4510 brain, particularly in somata and neurites containing Alz50-positive tau aggregates. Suppression of soluble tau expression with doxycycline resulted in complete recovery of mitochondrial distribution, despite the continued presence of aggregated tau. The effect on mitochondrial distribution occurs without concomitant alterations in neuropil mitochondrial size, as assessed by both array tomography and electron microscopy. Similar mitochondrial localization alterations were also observed in human AD tissue in Alz50+ neurons, confirming the relevance of tau to mitochondrial trafficking observed in this animal model. Because abnormalities reverted to normal if soluble tau was suppressed in rTg4510 mice, even in the continued presence of fibrillar tau inclusions, we suggest that soluble tau plays an important role in mitochondrial abnormalities, which likely contribute to neuronal dysfunction in AD. (Am J Pathol 2011, 179: 2071-2082; DOI: 10.1016/j.ajpath.2011.07.004)
C1 [Kopeikina, Katherine J.; Koffie, Robert M.; Frosch, Matthew P.; Hyman, Bradley T.; Spires-Jones, Tara L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA.
[Kopeikina, Katherine J.; Ludvigson, Adam E.; Peters, Alan; Luebke, Jennifer I.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA.
[Carlson, George A.; Pitstick, Rose] McLaughlin Res Inst, Great Falls, MT USA.
RP Spires-Jones, TL (reprint author), MGH Neurol, 114 16th St, Charlestown, MA 02129 USA.
EM tspires@partners.org
OI Luebke, Jennifer/0000-0003-1399-6073; Spires-Jones,
Tara/0000-0003-2530-0598
FU National Institute of Health [AG08487, T32AG000277, AG026249,
K99AG33670, P50AG05134]; Alzheimer's Association
FX Supported by National Institute of Health Grants AG08487, T32AG000277,
AG026249, K99AG33670, P50AG05134 and the Alzheimer's Association Zenith
Award.
NR 60
TC 67
Z9 71
U1 0
U2 17
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 OCT
PY 2011
VL 179
IS 4
BP 2071
EP 2082
DI 10.1016/j.ajpath.2011.07.004
PG 12
WC Pathology
SC Pathology
GA 865JO
UT WOS:000298307400046
PM 21854751
ER
PT J
AU Cheunsuchon, P
Zhou, YL
Zhang, X
Lee, H
Chen, WD
Nakayama, Y
Rice, KA
Hedley-Whyte, ET
Swearingen, B
Klibanski, A
AF Cheunsuchon, Pornsuk
Zhou, Yunli
Zhang, Xun
Lee, Hang
Chen, Wendy
Nakayama, Yuki
Rice, Kimberley A.
Hedley-Whyte, E. Tessa
Swearingen, Brooke
Klibanski, Anne
TI Silencing of the Imprinted DLK1-MEG3 Locus in Human Clinically
Nonfunctioning Pituitary Adenomas
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; INHIBITS ADIPOCYTE DIFFERENTIATION; UNIPARENTAL
DISOMY; CANCER CELLS; EXPRESSION; MICRORNA; PROTEIN; REGION; DLK1;
HYPERMETHYLATION
AB DLK1-MEG3 is an imprinted locus consisting of multiple maternally expressed noncoding RNA genes and paternally expressed protein-coding genes. The expression of maternally expressed gene 3 (MEG3) is selectively lost in clinically nonfunctioning adenomas (NFAs) of gonadotroph origin; however, expression status of other genes at this locus in human pituitary adenomas has not previously been reported. Using quantitative real-time RT-PCR, we evaluated expression of 24 genes from the DLK1-MEG3 locus in 44 human pituitary adenomas (25 NFAs, 7 ACTH-secreting, 7 GH-secreting, and 5 PRL-secreting adenomas) and 10 normal pituitaries. The effects on cell proliferation of five miRNAs whose expression was lost in NFAs were investigated by flow cytometry analysis. We found that 18 genes, including 13 miRNAs at the DLK1-MEG3 locus, were significantly down-regulated in human NFAs. In ACTH-secreting and PRL-secreting adenomas, 12 and 7 genes were significantly down-regulated, respectively; no genes were significantly down-regulated in GH-secreting tumors. One of the five miRNAs tested induced cell cycle arrest at the G2/M phase in PDFS cells derived from a human NFA. Our data indicate that the DLK1-MEG3 locus is silenced in NFAs. The growth suppression by miRNAs in PDFS cells is consistent with the hypothesis that the DLK1-MEG3 locus plays a tumor suppressor role in human NFAs. (Am J Pathol 2011, 179:2120-2130; DOI: 10.1016/j.ajpath.2011.07.002)
C1 [Cheunsuchon, Pornsuk; Zhou, Yunli; Zhang, Xun; Chen, Wendy; Nakayama, Yuki; Rice, Kimberley A.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Swearingen, Brooke] Massachusetts Gen Hosp, Div Neurosurg, Boston, MA 02114 USA.
RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA.
EM aklibanski@partners.org
RI Cheunsuchon, Pornsuk/O-7915-2015
OI Cheunsuchon, Pornsuk/0000-0001-8851-3553
FU NIH [R01-DK40947]; Guthart Family Foundation; Jarislowsky Foundation
FX Supported by grants from the NIH (R01-DK40947 to A.K.), the Guthart
Family Foundation, and the Jarislowsky Foundation.
NR 51
TC 32
Z9 36
U1 0
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 OCT
PY 2011
VL 179
IS 4
BP 2120
EP 2130
DI 10.1016/j.ajpath.2011.07.002
PG 11
WC Pathology
SC Pathology
GA 865JO
UT WOS:000298307400051
PM 21871428
ER
PT J
AU Jia, HB
Li, N
Gao, GR
Wang, XD
Sun, M
Wu, J
Liu, F
Yin, L
Zhang, MM
Hu, SN
Hou, JB
Yu, B
Zhang, S
Zhang, SS
Jang, IK
AF Jia Haibo
Li Ning
Gao Guangren
Wang Xuedong
Sun Meng
Wu Jian
Liu Fang
Yin Li
Zhang Maomao
Hu Sining
Hou Jingbo
Yu Bo
Zhang Shuo
Zhang Shaosong
Jang Ik-kyung
TI DIFFERENT VESSEL RESPONSE BETWEEN CHRONIC TOTAL OCCLUSIONS AND NON-CTO
LESION AFTER SIROLIMUS-ELUTING STENT IMPLANTATION: A SERIAL OPTICAL
COHERENCE TOMOGRAPHY STUDY
SO HEART
LA English
DT Meeting Abstract
CT 22nd Great Wall International Congress of Cardiology/Asia Pacific Heart
Congress (GWICC and APHF)
CY OCT 13-16, 2011
CL China Int Conf Ctr Sci & Technol (CICCST), Beijing, PEOPLES R CHINA
SP Chinese Med Soc Cardiovasc Dis (CMSCD), Comm Cardio-Cerebral Vasc Dis GSC & CHRS, Chinese Coll Cardiovasc Phys (CCCP)
HO China Int Conf Ctr Sci & Technol (CICCST)
C1 [Jia Haibo; Li Ning; Gao Guangren; Wang Xuedong; Wu Jian; Liu Fang; Yin Li; Zhang Maomao; Hu Sining; Hou Jingbo; Yu Bo; Zhang Shuo] Harbin Med Coll, Affiliated Hosp 2, Dept Cardiol, Key Labs Educ Minist Myocardial Ischemia Mech & T, Harbin, Peoples R China.
[Sun Meng] Harbin Med Coll, Dept Biostat, Harbin, Peoples R China.
[Jang Ik-kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
J9 HEART
JI Heart
PD OCT
PY 2011
VL 97
SU 3
DI 10.1136/heartjnl-2011-300867.434
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 866AV
UT WOS:000298352900434
ER
PT J
AU Tucker, JD
AF Tucker, Joseph D.
TI The social context of sexual HIV prevention among female sex workers in
China
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
ID RISK
C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Tucker, JD (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
EM jtucker4@partners.org
FU FIC NIH HHS [K01 TW008200, 1K01TW008200-01A1]; NICHD NIH HHS [R24
HD056670-01]
NR 11
TC 6
Z9 6
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD OCT
PY 2011
VL 40
IS 5
BP 1421
EP 1422
DI 10.1093/ije/dyr021
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 842XK
UT WOS:000296634900034
PM 21324942
ER
PT J
AU Folmer, RL
Billings, CJ
Diedesch-Rouse, AC
Gallun, FJ
Lew, HL
AF Folmer, Robert L.
Billings, Curtis J.
Diedesch-Rouse, Anna C.
Gallun, Frederick J.
Lew, Henry L.
TI Electrophysiological assessments of cognition and sensory processing in
TBI: Applications for diagnosis, prognosis and rehabilitation
SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY
LA English
DT Review
DE Event-related potentials; Evoked potentials; EP; ERP; TBI; Traumatic
brain injury
ID TRAUMATIC BRAIN-INJURY; EVENT-RELATED POTENTIALS; SOMATOSENSORY-EVOKED
POTENTIALS; CLOSED-HEAD-INJURY; CONTINGENT NEGATIVE VARIATION;
TEMPORAL-PARIETAL LESIONS; AUDITORY ODDBALL TASK; SUBJECTS OWN NAME;
MISMATCH NEGATIVITY; COMATOSE PATIENTS
AB Traumatic brain injuries are often associated with damage to sensory and cognitive processing pathways. Because evoked potentials (EPs) and event-related potentials (ERPs) are generated by neuronal activity, they are useful for assessing the integrity of neural processing capabilities in patients with traumatic brain injury (TBI). This review of somatosensory, auditory and visual ERPs in assessments of TBI patients is provided with the hope that it will be of interest to clinicians and researchers who conduct or interpret electrophysiological evaluations of this population. Because this article reviews ERP studies conducted in three different sensory modalities, involving patients with a wide range of TBI severity ratings and circumstances, it is difficult to provide a coherent summary of findings. However, some general trends emerge that give rise to the following observations and recommendations: 1) bilateral absence of somatosensory evoked potentials (SEPs) is often associated with poor clinical prognosis and outcome; 2) the presence of normal ERPs does not guarantee favorable outcome; 3) ERPs evoked by a variety of sensory stimuli should be used to evaluate TBI patients, especially those with severe injuries; 4) time since onset of injury should be taken into account when conducting ERP evaluations of TBI patients or interpreting results; 5) because sensory deficits (e.g., vision impairment or hearing loss) affect ERP results, tests of peripheral sensory integrity should be conducted in conjunction with ERP recordings; and 6) patients' state of consciousness, physical and cognitive abilities to respond and follow directions should be considered when conducting or interpreting ERP evaluations. Published by Elsevier B.V.
C1 [Folmer, Robert L.; Billings, Curtis J.; Diedesch-Rouse, Anna C.; Gallun, Frederick J.] Portland VA Med Ctr, NCRAR, Portland, OR 97239 USA.
[Folmer, Robert L.; Billings, Curtis J.; Gallun, Frederick J.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA.
[Lew, Henry L.] DVBIC, Rockville, MD USA.
[Lew, Henry L.] VCU, Sch Med, Dept Phys Med & Rehabil, Richmond, VA USA.
RP Folmer, RL (reprint author), Portland VA Med Ctr, NCRAR, 3710 SM US Vet Hosp Rd, Portland, OR 97239 USA.
EM Robert.Folmer@va.gov
RI Gallun, Frederick/G-3792-2012
OI Gallun, Frederick/0000-0002-4145-2199
FU VA RR&D National Center for Rehabilitative Auditory Research
FX Preparation of this manuscript was supported by the VA RR&D National
Center for Rehabilitative Auditory Research, located in the Portland VA
Medical Center, Portland, Oregon.
NR 93
TC 18
Z9 18
U1 1
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-8760
J9 INT J PSYCHOPHYSIOL
JI Int. J. Psychophysiol.
PD OCT
PY 2011
VL 82
IS 1
SI SI
BP 4
EP 15
DI 10.1016/j.ijpsycho.2011.03.005
PG 12
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 859PZ
UT WOS:000297889600002
PM 21419179
ER
PT J
AU Carlson, BA
Yoo, MH
Conrad, M
Gladyshev, VN
Hatfield, DL
Park, JM
AF Carlson, Bradley A.
Yoo, Min-Hyuk
Conrad, Marcus
Gladyshev, Vadim N.
Hatfield, Dolph L.
Park, Jin Mo
TI Protein kinase-regulated expression and immune function of thioredoxin
reductase 1 in mouse macrophages
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Thioredoxin reductase; Macrophage; Lipopolysaccharide; VSIG4;
Selenoprotein
ID NF-KAPPA-B; GENE-EXPRESSION; SELENOPROTEINS; SELENOCYSTEINE; ACTIVATION;
APOPTOSIS; RESPONSES; SELENIUM; MICE
AB Macrophages exposed to lipopolysaccharide (LPS) exhibit radical changes in mRNA and protein profiles. This shift in gene expression is geared not only to activate immune effector and regulatory mechanisms, but also to adjust the immune cell's metabolism to new physiological demands. However, it remains largely unknown whether immune function and metabolic state are mutually regulatory and, if so, how they are mechanistically interrelated in macrophages. Selenium, a dietary trace element exerting pleiotropic effects on immune homeostasis, and selenium-containing proteins (selenoproteins) may play a role in such coordination. We examined the incorporation of radiolabeled selenium into protein during LPS stimulation, and identified thioredoxin reductase 1 (TR1) as the only LPS-inducible selenoprotein in macrophages. TR1 induction occurred at the transcriptional level and depended on the intracellular signaling pathways mediated by p38 MAP kinase and I kappa B kinase. Macrophage-specific ablation of TR1 in mice resulted in a drastic decrease in the expression of VSIG4, a B7 family protein known to suppress T cell activation. These results reveal TR1 as both a regulator and a regulated target in the macrophage gene expression network, and suggest a link between selenium metabolism and immune signaling. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Carlson, Bradley A.; Yoo, Min-Hyuk; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Conrad, Marcus] Helmholtz Zentrum Munchen, Inst Dev Genet, D-85764 Neuherberg, Germany.
[Conrad, Marcus] DZNE German Ctr Neurodegenerat Dis, Munich, Germany.
[Gladyshev, Vadim N.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Park, Jin Mo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA.
[Park, Jin Mo] Harvard Univ, Sch Med, Boston, MA 02129 USA.
RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hatfield@mail.nih.gov; jmpark@cbrc2.mgh.harvard.edu
RI Gladyshev, Vadim/A-9894-2013;
OI Conrad, Marcus/0000-0003-1140-5612
FU National Institutes of Health (NIH), National Cancer Institute (NCI);
Center for Cancer Research; NCI; NIH [AI074957, GM065204]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute (NCI),
and Center for Cancer Research, and in addition, a specific grant from
the Office of Dietary Supplements, NCI, NIH, and NIH grants AI074957
(J.M.P.) and GM065204 (V.N.G.).
NR 22
TC 2
Z9 2
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD OCT-NOV
PY 2011
VL 49
IS 1-2
BP 311
EP 316
DI 10.1016/j.molimm.2011.09.001
PG 6
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 862TU
UT WOS:000298117800036
PM 21943784
ER
PT J
AU Declercq, E
Young, R
Cabral, H
Ecker, J
AF Declercq, Eugene
Young, Robin
Cabral, Howard
Ecker, Jeffrey
TI Is a Rising Cesarean Delivery Rate Inevitable?: Trends in Industrialized
Countries, 1987 to 2007
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
ID LABOR
AB Cesarean delivery rates now exceed 30% in several industrialized countries.
The substantial increase in rates of cesarean delivery in the past decade appears to be due in large part to a broadening of the indications for a primary cesarean together with an increase in scheduled repeat cesareans.
This study examined current cesarean rates in industrialized countries and assessed changes over time in the trends toward increasing rates. Cesarean delivery rates per 1000 live births were followed from 1987 to 2007 in 22 industrialized countries. For comparability between countries, the inclusion criteria were 50,000 or more births annually and a per capita gross domestic product of at least 10,000 US dollars in 2007. A Poisson regression model was used to evaluate changes in cesarean delivery rates for each country over time. The investigators examined overall cesarean delivery rates, absolute changes in rates, and changes in trend lines for the rates during the study period (1987-2007).
Of the 21 countries, 11 reported overall cesarean rates of more than 25% in 2007; 4 had rates more than 30%: Italy (39%), Portugal (35%), the United States (32%), and Switzerland (32%). Between 1992 and 2007, rates increased by more than 2-fold in the Czech Republic, Ireland, Austria, and Hungary. A comparison of cesarean rates across time periods showed that 14 countries (led by the United States, Canada, and Australia) experienced greater rate increases during the period 1998 to 2002 compared with the period 1993 to 1997. An analysis comparing trends from 2003 to 2007 with 1998 to 2002 showed that the rate increases slowed down in 18 countries across these 2 periods.
These findings suggest that despite the continuing rise in cesarean delivery rates among industrialized countries between 1987 and 2007, the rate of increase may be slowing down.
C1 [Declercq, Eugene] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
Osteoarthrit & Arthrit Ctr Outcomes Res, Boston, MA USA.
Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Declercq, E (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
NR 6
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD OCT
PY 2011
VL 66
IS 10
BP 603
EP 605
DI 10.1097/OGX.0b013e31823d8618
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 863EQ
UT WOS:000298146000004
ER
PT J
AU Caronia, LM
Martin, C
Welt, CK
Sykiotis, GP
Quinton, R
Thambundit, A
Avbelj, M
Dhruvakumar, S
Plummer, L
Hughes, VA
Seminara, SB
Boepple, PA
Sidis, Y
Crowley, WF
Martin, KA
Hall, JE
Pitteloud, N
AF Caronia, Lisa M.
Martin, Cecilia
Welt, Corrine K.
Sykiotis, Gerasimos P.
Quinton, Richard
Thambundit, Apisadaporn
Avbelj, Magdalena
Dhruvakumar, Sadhana
Plummer, Lacey
Hughes, Virginia A.
Seminara, Stephanie B.
Boepple, Paul A.
Sidis, Yisrael
Crowley, William F., Jr.
Martin, Kathryn A.
Hall, Janet E.
Pitteloud, Nelly
TI A Genetic Basis for Functional Hypothalamic Amenorrhea
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
AB Functional hypothalamic amenorrhea, a frequent cause of female infertility, is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency triggered by stressors, such as excessive exercise, nutritional deficits (weight loss, eating disorders), or psychological distress. These stressors suppress the hypothalamic-pituitary-gonadal axis (HPA) by inhibiting hypothalamic secretion of GnRH. Idiopathic hypogonadotropic hypogonadism is a congenital form of GnRH deficiency, with multiple genetic defects accounting for about 40% of the cases. It is unknown whether the variable susceptibility of women with hypothalamic amenorrhea to stressors reflects a genetic predisposition.
This study tests the hypothesis that mutations in genes associated with idiopathic hypogonadotropic hypogonadism are causally related to the susceptibility to GnRH deficiency among women with hypothalamic amenorrhea. Genomic DNA from peripheral blood samples of 55 women with hypothalamic amenorrhea was analyzed for the presence of the known coding sequence of genes associated with idiopathic hypogonadotropic hypogonadism.
Among 7 of the 55 women with hypothalamic amenorrhea, 6 heterozygous mutations were identified: fibroblast growth factor receptor 1 gene contained 2 mutant variants (G260E and R756H), prokineticin receptor 2 gene (PROKR2) also had 2 variants (R85H and L173R), the GnRH receptor gene had 1 variant (R262Q), and the Kallmann syndrome 1 sequence gene also had 1 (V371I). A cohort of 422 control women with normal menstrual cycles contained no rare sequence variants. In vitro studies characterized the fibroblast growth factor receptor 1 gene mutants G260E and R756H, and the PROKR2 mutant R85H as loss-of-function mutations; previously, the PROKR2 mutant L173R and the GnRH receptor gene mutant R262Q had been reported as loss-of-function mutants.
These findings show that genes mutated in patients with idiopathic hypogonadotropic hypogonadism are also mutated in those with hypothalamic amenorrhea. These mutations may account in part for the variable susceptibility of women to stressors leading to hypothalamic amenorrhea.
C1 [Caronia, Lisa M.] Massachusetts Gen Hosp, Harvard Ctr Reprod Endocrine Sci, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
Royal Victoria Infirm, Dept Endocrinol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
Univ Lausanne, CHU Vaudois, Div Endocrine, Lausanne, Switzerland.
RP Caronia, LM (reprint author), Massachusetts Gen Hosp, Harvard Ctr Reprod Endocrine Sci, Boston, MA 02114 USA.
RI PITTELOUD, Nelly/K-2709-2014;
OI Welt, Corrine/0000-0002-8219-5504; Avbelj Stefanija,
Magdalena/0000-0002-0836-5114; Sykiotis, Gerasimos/0000-0002-9565-4941
NR 2
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD OCT
PY 2011
VL 66
IS 10
BP 618
EP 619
DI 10.1097/OGX.0b013e31822f94c4
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 863EQ
UT WOS:000298146000011
ER
PT J
AU Yao, YL
Danna, CH
Zemp, FJ
Titov, V
Ciftci, ON
Przybylski, R
Ausubel, FM
Kovalchuk, I
AF Yao, Youli
Danna, Cristian H.
Zemp, Franz J.
Titov, Viktor
Ciftci, Ozan Nazim
Przybylski, Roman
Ausubel, Frederick M.
Kovalchuk, Igor
TI UV-C-Irradiated Arabidopsis and Tobacco Emit Volatiles That Trigger
Genomic Instability in Neighboring Plants
SO PLANT CELL
LA English
DT Article
ID SYSTEMIC ACQUIRED-RESISTANCE; ULTRAVIOLET-B RADIATION; SALICYLIC-ACID;
JASMONIC ACID; CELL-DEATH; RECOMBINATION FREQUENCY; SIGNAL-TRANSDUCTION;
GENE-TRANSCRIPTION; METHYL SALICYLATE; MOSAIC-VIRUS
AB We have previously shown that local exposure of plants to stress results in a systemic increase in genome instability. Here, we show that UV-C-irradiated plants produce a volatile signal that triggers an increase in genome instability in neighboring nonirradiated Arabidopsis thaliana plants. This volatile signal is interspecific, as UV-C-irradiated Arabidopsis plants transmit genome destabilization to naive tobacco (Nicotiana tabacum) plants and vice versa. We report that plants exposed to the volatile hormones methyl salicylate (MeSA) or methyl jasmonate (MeJA) exhibit a similar level of genome destabilization as UV-C-irradiated plants. We also found that irradiated Arabidopsis plants produce MeSA and MeJA. The analysis of mutants impaired in the synthesis and/or response to salicylic acid (SA) and/or jasmonic acid showed that at least one other volatile compound besides MeSA and MeJA can communicate interplant genome instability. The NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (npr1) mutant, defective in SA signaling, is impaired in both the production and the perception of the volatile signals, demonstrating a key role for NPR1 as a central regulator of genome stability. Finally, various forms of stress resulting in the formation of necrotic lesions also generate a volatile signal that leads to genomic instability.
C1 [Yao, Youli; Titov, Viktor; Kovalchuk, Igor] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada.
[Danna, Cristian H.; Ausubel, Frederick M.] Univ Hartford, Dept Genet, Sch Med, Boston, MA 02114 USA.
[Danna, Cristian H.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Zemp, Franz J.] Univ Calgary, Dept Med Sci, Calgary, AB T2N 4N1, Canada.
[Ciftci, Ozan Nazim; Przybylski, Roman] Univ Lethbridge, Dept Chem & Biochem, Lethbridge, AB T1K 3M4, Canada.
RP Kovalchuk, I (reprint author), Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada.
EM igor.kovalchuk@uleth.ca
FU Natural Sciences and Engineering Research Council of Canada; Alberta
Agriculture Research Institute; Human Frontiers Scientific Program;
National Institutes of Health [R37 GM48707]; National Science Foundation
[MCB-0519898]
FX Financial support was provided by The Natural Sciences and Engineering
Research Council of Canada, Alberta Agriculture Research Institute, and
Human Frontiers Scientific Program grants to I. K. and by National
Institutes of Health Grant R37 GM48707 and National Science Foundation
Grant MCB-0519898 awarded to F.M.A.
NR 53
TC 16
Z9 16
U1 4
U2 24
PU AMER SOC PLANT BIOLOGISTS
PI ROCKVILLE
PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA
SN 1040-4651
J9 PLANT CELL
JI Plant Cell
PD OCT
PY 2011
VL 23
IS 10
BP 3842
EP 3852
DI 10.1105/tpc.111.089003
PG 11
WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology
SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology
GA 863OU
UT WOS:000298175900022
PM 22028460
ER
PT J
AU Woods, DL
Phillips, LR
Martin, JL
AF Woods, Diana Lynn
Phillips, Linda R.
Martin, Jennifer L.
TI Biological Basis for Sleep Disturbance and Behavioral Symptoms in
Dementia A Biobehavioral Model
SO RESEARCH IN GERONTOLOGICAL NURSING
LA English
DT Article
ID NURSING-HOME RESIDENTS; MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E
GENOTYPE; CORTISOL SECRETORY ACTIVITY; PITUITARY-ADRENAL AXIS;
LONG-TERM-CARE; ALZHEIMERS-DISEASE; SALIVARY CORTISOL; PSYCHOLOGICAL
SYMPTOMS; APOE GENOTYPE
AB Behavioral symptoms and sleep disturbance occur in more than 56% of older adults with mild to moderate dementia and are challenging and costly. This article proposes a biobehavioral causal model to explain sleep disturbances and behavioral symptoms in dementia (BSD) based on an integrative science perspective using the life cycle model of stress (chronic stress) integrating genetic, neuroendocrine, and personality factors. The model proposes that: (a) BSD are an outcome of sleep disturbance; (b) hypothalamic-pituitary-adrenal (HPA) axis dysregulation is key to sleep disturbances and BSD; (c) genotype influences response to stress hormones; (d) HPA is influenced by genotype; (e) trait anxiety moderates the relationship between HPA axis and BSD and/or sleep disturbances; and (f) trait anxiety is influenced by genotype. Examining these relationships simultaneously will advance our theoretical understanding of BSD and sleep disturbances, potentially providing a basis for the design of targeted interventions and prevention strategies with an understanding of risk.
C1 [Woods, Diana Lynn; Phillips, Linda R.] Univ Calif Los Angeles, Sch Nursing, Ctr Adv Gerontol Nursing Sci, Los Angeles, CA 90095 USA.
[Martin, Jennifer L.] Univ Calif Los Angeles, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA.
[Martin, Jennifer L.] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA.
RP Woods, DL (reprint author), Univ Calif Los Angeles, Sch Nursing, Ctr Adv Gerontol Nursing Sci, 700 Tiverton Ave,Box 956919, Los Angeles, CA 90095 USA.
EM lwoods@sonnet.ucla.edu
FU University of California, Los Angeles, School of Nursing; National
Institute on Aging [K23 AG028452]
FX The authors disclose that they have no significant financial interests
in any product or class of products discussed directly or indirectly in
this activity. The authors acknowledge pilot study support from the
University of California, Los Angeles, School of Nursing, Intramural
Grant (D. L. Woods) and National Institute on Aging grant K23 AG028452
(L.R. Phillips).
NR 125
TC 3
Z9 3
U1 3
U2 8
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 1940-4921
J9 RES GERONTOL NURS
JI Res. Gerontol. Nurs.
PD OCT
PY 2011
VL 4
IS 4
BP 281
EP 293
DI 10.3928/19404921-20110302-01
PG 13
WC Nursing
SC Nursing
GA 864YL
UT WOS:000298276300007
PM 21417189
ER
PT J
AU Kehinde, JO
Pope, C
Amella, EJ
AF Kehinde, Julius Oluwole
Pope, Charlene
Amella, Elaine J.
TI Methodological Issues in Fall Prevention Research Involving Older Adults
in Long-Term Care Facilities
SO RESEARCH IN GERONTOLOGICAL NURSING
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIAL; NURSING-HOME RESIDENTS; RISK
ASSESSMENT-TOOL; TAI-CHI; STRATEGIES; PEOPLE; COSTS; INTERVENTION;
PROGRAMS; CLUSTER
AB The purpose of this study was to conduct a systematic review of the current fall prevention literature, examining methodological issues resulting from variations in fall definitions, methods of data collection, and standards for reporting fall rates in studies involving older adults in long-term care settings. This systematic review used the five stages of Whittemore and Knafl's review methodology to extract data from the databases, summarize, and synthesize the findings of the 10 studies included. The Critical Appraisal Skill Program checklist for randomized controlled trials criteria was used to appraise the methodological quality of the studies. Inconsistencies in fall definitions, methods of data collection, and standards for reporting fall rates were apparent across the studies reviewed. Standardized approaches to defining falls, collecting data, and reporting fall rates are necessary to interpret, make comparisons among, and disseminate the findings of studies.
C1 [Kehinde, Julius Oluwole; Pope, Charlene; Amella, Elaine J.] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA.
[Pope, Charlene] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
RP Kehinde, JO (reprint author), Med Univ S Carolina, Coll Nursing, 99 Jonathan Lucas St, Charleston, SC 29425 USA.
EM jok31@musc.edu
OI Amella, Elaine/0000-0003-4114-429X
NR 56
TC 1
Z9 1
U1 3
U2 14
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 1940-4921
J9 RES GERONTOL NURS
JI Res. Gerontol. Nurs.
PD OCT
PY 2011
VL 4
IS 4
BP 294
EP 304
DI 10.3928/19404921-20110503-02
PG 11
WC Nursing
SC Nursing
GA 864YL
UT WOS:000298276300008
PM 21598864
ER
PT J
AU Siek, KA
Khan, DU
Ross, SE
Haverhals, LM
Meyers, J
Cali, SR
AF Siek, Katie A.
Khan, Danish U.
Ross, Stephen E.
Haverhals, Leah M.
Meyers, Jane
Cali, Steven R.
TI Designing a Personal Health Application for Older Adults to Manage
Medications: A Comprehensive Case Study
SO JOURNAL OF MEDICAL SYSTEMS
LA English
DT Article
DE Older adults; Personal Health Records; Personal Health Applications;
Participatory design; Medication management; Interdisciplinary design
ID NONADHERENCE; CARE; HOSPITALIZATION; ADHERENCE; DISEASE; HOME
AB Older adults with multiple chronic conditions often go through care transitions where they move between care facilities or providers during their treatment. These transitions are often uncoordinated and can imperil patients by omitted, duplicative, or contradictory care plans. Older adults sometimes feel overwhelmed with the new responsibility of coordinating the care plan with providers and changing their medication regimes. In response, we developed a Lesser General Public License (LGPL) open source, web-based Personal Health Application (PHA) using an iterative participatory design process that provided older adults and their caregivers the ability to manage their personal health information. In this paper, we document the PHA design process from low-fidelity prototypes to high-fidelity prototypes over the course of six user studies. Our findings establish the imperative need for interdisciplinary research and collaboration among all stakeholders to create effective PHAs. We conclude with design guidelines that encourage researchers to gradually increase functionality as users become more proficient.
C1 [Siek, Katie A.; Khan, Danish U.; Meyers, Jane] Univ Colorado Boulder, Dept Comp Sci, Boulder, CO 80309 USA.
[Ross, Stephen E.] Univ Colorado Denver, Div Gen Internal Med, Denver, CO 80202 USA.
[Haverhals, Leah M.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA.
[Cali, Steven R.] Univ Colorado Denver, Denver, CO 80217 USA.
RP Siek, KA (reprint author), Univ Colorado Boulder, Dept Comp Sci, 430 UCB, Boulder, CO 80309 USA.
EM ksiek@cs.colorado.edu; khand@colorado.edu; Steve.Ross@ucdenver.edu;
leah.haverhals@gmail.com; meyersjk@colorado.edu; stevecali@gmail.com
FU Robert Wood Johnson Foundation [RWJ59880]
FX We thank our participants and expert review panel for their valuable
feedback. We also thank the reviewers for their insightful and
constructive comments. This research was funded by the Robert Wood
Johnson Foundation Project HealthDesign Grant RWJ59880 (PI Stephen E.
Ross).
NR 41
TC 22
Z9 22
U1 4
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0148-5598
J9 J MED SYST
JI J. Med. Syst.
PD OCT
PY 2011
VL 35
IS 5
SI SI
BP 1099
EP 1121
DI 10.1007/s10916-011-9719-9
PG 23
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA 859DZ
UT WOS:000297856600040
PM 21562730
ER
PT J
AU Sayegh, RR
Madsen, KA
Adler, JD
Johnson, MA
Mathews, MK
AF Sayegh, Rony R.
Madsen, Kimberly A.
Adler, Jason D.
Johnson, Mary A.
Mathews, Michaela K.
TI Diffuse retinal injury from a non-penetrating TASER dart
SO DOCUMENTA OPHTHALMOLOGICA
LA English
DT Article
DE Electrical injury; Electroretinogram; Eye; Ocular injury; Retinal
detachment; TASER; Trauma
ID OCULAR INJURY; CATARACT
AB To describe a non-penetrating TASER gun injury resulting in a small exudative retinal detachment but significant visual acuity and retinal function loss as demonstrated by electroretinography (ERG). A 39-year-old man presented to the emergency department with a TASER barb embedded in his right lower lid. A complete clinical ophthalmologic examination and surgical extrication were performed, as well as radiologic imaging and Ganzfeld electroretinography. No scleral penetration was observed on surgical exploration. Retinal examination showed a peripheral exudative detachment. Subsequent follow-up revealed progressive resolution of the detachment and improvement in visual acuity. The ERG showed a 63-70% decrease in rod a- and b-waves, while isolated cone responses were reduced by only 10%, with a minimal increase in implicit time. This case shows that periocular TASER injuries, even if apparently superficial, may result in significant ocular damage. ERG may be useful in the diagnosis of visual loss attributed to disturbance in photoreceptor function, in the absence of anatomically evident damage.
C1 [Sayegh, Rony R.; Madsen, Kimberly A.; Johnson, Mary A.; Mathews, Michaela K.] Univ Maryland, Sch Med, Dept Ophthalmol & Visual Sci, Baltimore, MD 21201 USA.
[Sayegh, Rony R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Adler, Jason D.] Univ Maryland, Sch Med, Dept Emergency Med, Baltimore, MD 21201 USA.
RP Mathews, MK (reprint author), Univ Maryland, Sch Med, Dept Ophthalmol & Visual Sci, Baltimore, MD 21201 USA.
EM mmath002@umaryland.edu
RI Sayegh, Rony/G-8777-2013
OI Sayegh, Rony/0000-0002-0119-4201
FU Research to Prevent Blindness; National Institutes of Health
[1KO8EY016357-01A2]
FX This work was supported in part by a grant from Research to Prevent
Blindness (MAJ) and by National Institutes of Health grant
#1KO8EY016357-01A2 (MKM).
NR 11
TC 5
Z9 5
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0012-4486
J9 DOC OPHTHALMOL
JI Doc. Ophthalmol.
PD OCT
PY 2011
VL 123
IS 2
BP 135
EP 139
DI 10.1007/s10633-011-9287-9
PG 5
WC Ophthalmology
SC Ophthalmology
GA 859BW
UT WOS:000297850200008
PM 21909993
ER
PT J
AU Cibulskis, K
Lawrence, M
Sivachenko, A
Sougnez, C
Nickerson, E
McKenna, A
Ramos, A
Stojanov, P
Hodis, E
Zou, L
Imielinski, M
Saksena, G
Drier, Y
Bass, A
Garraway, L
Meyerson, M
Getz, G
AF Cibulskis, K.
Lawrence, M.
Sivachenko, A.
Sougnez, C.
Nickerson, E.
McKenna, A.
Ramos, A.
Stojanov, P.
Hodis, E.
Zou, L.
Imielinski, M.
Saksena, G.
Drier, Y.
Bass, A.
Garraway, L.
Meyerson, M.
Getz, G.
TI Landscape of Somatic Alterations in Cancer and Their Relationship to the
Environment
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 42nd Annual Meeting of the Environmental-Mutagen-Society on
Environmental Impacts on the Genome and Epigenome - Mechanisms and Risks
CY OCT 15-19, 2011
CL Montreal, CANADA
SP Environm Mutagen Soc
C1 [Cibulskis, K.; Lawrence, M.; Sivachenko, A.; Sougnez, C.; Nickerson, E.; McKenna, A.; Ramos, A.; Stojanov, P.; Hodis, E.; Zou, L.; Imielinski, M.; Saksena, G.; Drier, Y.; Bass, A.; Garraway, L.; Meyerson, M.; Getz, G.] Broad Inst & Harvard, Cambridge, MA USA.
[Bass, A.; Garraway, L.; Meyerson, M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD OCT
PY 2011
VL 52
SU 1
BP S24
EP S24
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 860DU
UT WOS:000297929800047
ER
PT J
AU Horga, G
Bernacer, J
Dusi, N
Entis, J
Chu, KW
Hazlett, EA
Haznedar, MM
Kemether, E
Byne, W
Buchsbaum, MS
AF Horga, Guillermo
Bernacer, Javier
Dusi, Nicola
Entis, Jonathan
Chu, Kingwai
Hazlett, Erin A.
Haznedar, M. Mehmet
Kemether, Eileen
Byne, William
Buchsbaum, Monte S.
TI Correlations between ventricular enlargement and gray and white matter
volumes of cortex, thalamus, striatum, and internal capsule in
schizophrenia
SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
LA English
DT Article
DE Cerebral spinal fluid; Sulcal enlargement; Myelin; Fronto-thalamic
connectivity
ID SCHIZOTYPAL PERSONALITY-DISORDER; CORTICAL BRODMANNS AREAS; GLUCOSE
METABOLIC-RATE; COMPREHENSIVE ASSESSMENT; HEALTHY-INDIVIDUALS; BRAIN;
SIZE; MEDIODORSAL; PULVINAR; ABNORMALITIES
AB Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI (patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.
C1 [Buchsbaum, Monte S.] Univ Calif San Diego, Dept Psychiat, NeuroPET Ctr, San Diego, CA 92121 USA.
[Buchsbaum, Monte S.] Univ Calif San Diego, Dept Radiol, NeuroPET Ctr, San Diego, CA 92121 USA.
[Horga, Guillermo; Entis, Jonathan; Chu, Kingwai; Kemether, Eileen] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[Horga, Guillermo] Hosp Clin Barcelona, Dept Psychiat, Schizophrenia Clin Program, E-08036 Barcelona, Spain.
[Bernacer, Javier] Univ Navarra, Clin Univ, Lab Funct Neuromorphol, Pamplona 31008, Spain.
[Dusi, Nicola] Univ Verona, Policlin Giambattista Rossi, Dept Publ Hlth & Community Med, Sect Psychiat & Clin Psychol, I-37134 Verona, Italy.
[Hazlett, Erin A.; Haznedar, M. Mehmet; Byne, William] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY 10468 USA.
RP Buchsbaum, MS (reprint author), Univ Calif San Diego, Dept Psychiat, NeuroPET Ctr, 11388 Sorrento Valley Rd,Suite 100, San Diego, CA 92121 USA.
EM mbuchsbaum@ucsd.edu
RI Bernacer, Javier/P-5810-2014; Horga, Guillermo/M-8036-2016
OI Bernacer, Javier/0000-0002-4341-9763; Horga,
Guillermo/0000-0002-9049-9786
NR 47
TC 17
Z9 18
U1 0
U2 8
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0940-1334
J9 EUR ARCH PSY CLIN N
JI Eur. Arch. Psych. Clin. Neurosci.
PD OCT
PY 2011
VL 261
IS 7
BP 467
EP 476
DI 10.1007/s00406-011-0202-x
PG 10
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 856EH
UT WOS:000297619700003
PM 21431919
ER
PT J
AU Quackenbush, J
AF Quackenbush, J.
TI Driving discovery through data integration and analysis
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 5th European-Organisation-for-Research-and-Treatment-of-Cancer
(EORTC)/National-Cancer-Institute
(NCI)/American-Society-of-Clinical-Oncology (ASCO) Annual Meeting on
Molecular Markers in Cancer
CY OCT 27-29, 2011
CL Brussels, BELGIUM
SP European Org Res & Treatment Canc (EORTC), Natl Canc Inst (NCI), Amer Soc Clin Oncol (ASCO)
C1 [Quackenbush, J.] Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD OCT
PY 2011
VL 47
SU 4
BP S4
EP S4
PG 1
WC Oncology
SC Oncology
GA 853UT
UT WOS:000297451900017
ER
PT J
AU DeAngelo, DJ
AF DeAngelo, Daniel J.
TI Chronic Myelogenous Leukemia Preface
SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA
LA English
DT Editorial Material
C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA.
RP DeAngelo, DJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Adult Leukemia Program, 450 Brookline Ave, Boston, MA 02115 USA.
EM Daniel_Deangelo@dfci.harvard.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8588
J9 HEMATOL ONCOL CLIN N
JI Hematol. Oncol. Clin. North Am.
PD OCT
PY 2011
VL 25
IS 5
BP IX
EP X
DI 10.1016/j.hoc.2011.10.001
PG 2
WC Oncology; Hematology
SC Oncology; Hematology
GA 858ST
UT WOS:000297823700001
PM 22054737
ER
PT J
AU Stolzmann, P
Alkadhi, H
Scheffel, H
Plass, A
Leschka, S
Falk, V
Kozerke, S
Wyss, C
Donati, OF
AF Stolzmann, Paul
Alkadhi, Hatem
Scheffel, Hans
Plass, Andre
Leschka, Sebastian
Falk, Volkmar
Kozerke, Sebastian
Wyss, Christophe
Donati, Olivio F.
TI Combining cardiac magnetic resonance and computed tomography coronary
calcium scoring: added value for the assessment of morphological
coronary disease?
SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
LA English
DT Article
DE Coronary artery disease; Calcium scoring; Cardiac magnetic resonance
imaging; Coronary catheterization
ID AMERICAN-HEART-ASSOCIATION; ELECTRON-BEAM TOMOGRAPHY; ARTERY-DISEASE;
CLINICAL CARDIOLOGY; NUCLEAR-CARDIOLOGY; STRESS PERFUSION; PROGNOSTIC
VALUE; CT ANGIOGRAPHY; RISK-FACTORS; K-SPACE
AB To investigate prospectively, in patients with suspicion of coronary artery disease (CAD), the added value of coronary calcium scoring (CS) as adjunct to cardiac magnetic resonance (CMR) for the diagnosis of morphological coronary stenosis in comparison to catheter angiography (CA). Sixty consecutive patients (8 women; 64 +/- 10 years) referred to CA underwent CMR (1.5 T) including perfusion and late gadolinium-enhancement imaging as well as CS with computed tomography. Diagnostic performance was evaluated for CMR and CS separately, and for both methods combined, with CA as reference standard. Best CS threshold combined with a specificity >90% to predict significant stenosis in patients without abnormalities on CMR was determined from receiver operator characteristics (ROC) analysis. Abnormal CMR results were considered to indicate significant stenosis regardless of CS; CS above threshold reclassified patients to have CAD regardless of CMR. CA identified 104/960 (11%) coronary segments with coronary artery stenosis >50% in 36/60 (60%) patients. ROC revealed an area-under-the-curve of 0.83 (95% CI: 0.68-0.99) with the best CS threshold of 495 Agatston score (sensitivity 50%). CMR depicted 128/960 (13%) myocardial segments with abnormalities in 31/60 (52%) patients. Sensitivity, specificity, negative (NPV) and positive predictive value (PPV) of CMR were 78, 88, 72 and 90%. When adding CS to CMR, sensitivity and NPV increased to 89 and 83%, while specificity and PPV slightly decreased to 83 and 89%. Accuracy of the combined approach (87%) was significantly (P < 0.05) higher than that of CMR (82%) alone. Adding CS to CMR improves the accuracy for the detection of morphological CAD.
C1 [Stolzmann, Paul; Alkadhi, Hatem] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Stolzmann, Paul; Alkadhi, Hatem] Harvard Univ, Sch Med, Boston, MA USA.
[Stolzmann, Paul; Alkadhi, Hatem; Scheffel, Hans; Leschka, Sebastian; Donati, Olivio F.] Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland.
[Plass, Andre; Falk, Volkmar] Univ Zurich Hosp, Cardiovasc Surg Clin, CH-8091 Zurich, Switzerland.
[Kozerke, Sebastian] Univ Zurich, Zurich, Switzerland.
[Kozerke, Sebastian] ETH, Inst Biomed Engn, Zurich, Switzerland.
[Wyss, Christophe] Univ Zurich Hosp, Dept Cardiol, CH-8091 Zurich, Switzerland.
RP Stolzmann, P (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
EM pstolzmann@partners.org
RI Kozerke, Sebastian/J-3209-2015
OI Kozerke, Sebastian/0000-0003-3725-8884
NR 31
TC 4
Z9 4
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1569-5794
J9 INT J CARDIOVAS IMAG
JI Int. J. Cardiovasc. Imaging
PD OCT
PY 2011
VL 27
IS 7
BP 969
EP 977
DI 10.1007/s10554-010-9738-5
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 858ZB
UT WOS:000297841600008
PM 21052842
ER
PT J
AU Yoon, YE
Chang, HJ
Cho, I
Jeon, KH
Chun, EJ
Choi, SI
Bae, HJ
Rivera, JJ
Nasir, K
Blumenthal, RS
Lim, TH
AF Yoon, Yeonyee E.
Chang, Hyuk-Jae
Cho, Iksung
Jeon, Ki-Hyun
Chun, Eun-Ju
Choi, Sang-il
Bae, Hee-Jun
Rivera, Juan J.
Nasir, Khurram
Blumenthal, Roger S.
Lim, Tae-Hwan
TI Incidence of subclinical coronary atherosclerosis in patients with
suspected embolic stroke using cardiac computed tomography
SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
LA English
DT Article
DE Stroke; Coronary artery disease; Cardiac computed tomography; Diagnosis
ID TRANSIENT ISCHEMIC ATTACK; HEALTH-CARE PROFESSIONALS; ARTERY-DISEASE;
CEREBROVASCULAR-DISEASE; SCIENTIFIC STATEMENT; DIAGNOSTIC-ACCURACY;
CLINICAL CARDIOLOGY; RISK-EVALUATION; ANGIOGRAPHY; ASSOCIATION
AB The purpose of this study was to investigate the incidence of subclinical coronary artery disease (CAD) in patients with suspected acute embolic stroke or transient ischemic attack (TIA) using 64-row multi-slice computed tomography (MSCT) and to examine its association with conventional risk stratification. We consecutively enrolled 175 patients (66 +/- 13 years, 50% men) suspected to have had embolic stroke/TIA clinically or radiologically, and underwent 64-row MSCT to evaluate for a possible cardiac source of embolism. Both coronary artery calcium scoring (CACS) and coronary CT angiography (CCTA) were concurrently performed based on standard scanning protocols. Patients with a history of angina or documented CAD, and those with significant carotid stenosis were excluded. Atherosclerotic plaques were indentified in 105 (60%) individuals; 37 (21%) had occult CAD of >= 50% diameter stenosis on CCTA. Subjects with and without >= 50% occult CAD on CCTA had similar prevalence of cardiovascular risk factors. Thirty out of 175 (17%) individuals with >= 50% occult CAD would have missed further cardiac testing based on the American Heart association and the American Stroke Association guideline. However, these numbers would be reduced to 2% (4/175) using CACS. In logistic regression analysis, only CACS independently predicted the presence >= 50% occult CAD evidenced by CCTA. Subclinical CAD, including >= 50% stenotic disease, is highly prevalent in patients who had suffered a suspected embolic stroke. The current guideline for further cardiac testing may have limited value to identify patients with >= 50% CAD in this patient population, which can be improved by adopting CACS.
C1 [Chang, Hyuk-Jae] Severance Cardiovasc Hosp, Div Cardiol, Seoul 120752, South Korea.
[Yoon, Yeonyee E.; Cho, Iksung; Jeon, Ki-Hyun] Seoul Natl Univ, Bundang Hosp, Cardiovasc Ctr, Div Cardiol, Songnam, South Korea.
[Chun, Eun-Ju; Choi, Sang-il] Seoul Natl Univ, Bundang Hosp, Dept Radiol, Songnam, South Korea.
[Bae, Hee-Jun] Seoul Natl Univ, Bundang Hosp, Dept Neurol, Songnam, South Korea.
[Rivera, Juan J.; Nasir, Khurram; Blumenthal, Roger S.] Johns Hopkins Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA.
[Rivera, Juan J.] S Beach Prevent Cardiol, Miami Beach, FL USA.
[Nasir, Khurram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA.
[Lim, Tae-Hwan] Ulsan Univ Hosp, Dept Radiol, Seoul, South Korea.
RP Chang, HJ (reprint author), Severance Cardiovasc Hosp, Div Cardiol, 250 Seongsan No, Seoul 120752, South Korea.
EM hjchang@yuhs.ac
FU Ministry of Health, Welfare and Family Affairs, Republic of Korea
[A060171]
FX This study was supported by a grant (A060171) of the Korea Health 21 R&D
project, Ministry of Health, Welfare and Family Affairs, Republic of
Korea.
NR 34
TC 7
Z9 7
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1569-5794
J9 INT J CARDIOVAS IMAG
JI Int. J. Cardiovasc. Imaging
PD OCT
PY 2011
VL 27
IS 7
BP 1035
EP 1044
DI 10.1007/s10554-010-9743-8
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 858ZB
UT WOS:000297841600016
PM 21063781
ER
PT J
AU Choudhry, N
Orlin, A
Bilaniuk, L
Maguire, AM
AF Choudhry, Netan
Orlin, Anton
Bilaniuk, Larissa
Maguire, Albert M.
TI Cerebroretinal microangiopathy with occlusive telangiectasia and
multisytemic manifestations
SO JOURNAL OF AAPOS
LA English
DT Article
ID CALCIFICATIONS; CYSTS
AB Cerebroretinal microangiopathy with calcification and cysts is a multisystem autosomal-recessive disorder in which there is an obliterative angiopathy of small vessels, primarily in the brain, retina, and gastrointestinal tract. We present the case of a 14-year-old boy with cerebroretinal microangiopathy with calcification and cysts illustrating the classic occlusive retinal telangiectasias. His condition was diagnosed using multiple imaging modalities, including upper gastrointestinal endoscopy of the upper gastrointestinal tract, magnetic resonance imaging, optical coherence tomography, and fluorescein angiography.
C1 [Choudhry, Netan] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02141 USA.
[Choudhry, Netan; Orlin, Anton; Maguire, Albert M.] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA.
[Bilaniuk, Larissa] Childrens Hosp Philadelphia, Dept Ophthalmol, Philadelphia, PA 19104 USA.
RP Choudhry, N (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 12th Floor,243 Charles St, Boston, MA 02141 USA.
EM netan.choudhry@gmail.com
NR 5
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1091-8531
J9 J AAPOS
JI J. AAPOS
PD OCT
PY 2011
VL 15
IS 5
BP 502
EP 503
DI 10.1016/j.jaapos.2011.05.014
PG 2
WC Ophthalmology; Pediatrics
SC Ophthalmology; Pediatrics
GA 856PZ
UT WOS:000297657200026
PM 22108368
ER
PT J
AU Baraghis, E
Devor, A
Fang, QQ
Srinivasan, VJ
Wu, WC
Lesage, F
Ayata, C
Kasischke, KA
Boas, DA
Sakadzic, S
AF Baraghis, Edward
Devor, Anna
Fang, Qianqian
Srinivasan, Vivek J.
Wu, Weicheng
Lesage, Frederic
Ayata, Cenk
Kasischke, Karl A.
Boas, David A.
Sakadzic, Sava
TI Two-photon microscopy of cortical NADH fluorescence intensity changes:
correcting contamination from the hemodynamic response
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE nicotinamide adenine dinucleotide fluorescence; two-photon laser
scanning microscopy; brain imaging; correction algorithms; Monte Carlo
simulations; optical scattering; hemoglobin absorption
ID PYRIDINE-NUCLEOTIDE FLUORESCENCE; IN-VIVO; OPTICAL-PROPERTIES; TISSUE
FLUORESCENCE; INTRACELLULAR NADH; BRAIN CORTEX; BLOOD-VOLUME;
SCATTERING; HEMATOCRIT; NM
AB Quantification of nicotinamide adenine dinucleotide (NADH) changes during functional brain activation and pathological conditions provides critical insight into brain metabolism. Of the different imaging modalities, two-photon laser scanning microscopy (TPLSM) is becoming an important tool for cellular-resolution measurements of NADH changes associated with cellular metabolic changes. However, NADH fluorescence emission is strongly absorbed by hemoglobin. As a result, in vivo measurements are significantly affected by the hemodynamics associated with physiological and pathophysiological manipulations. We model NADH fluorescence excitation and emission in TPLSM imaging based on precise maps of cerebral microvasculature. The effects of hemoglobin optical absorption and optical scattering from red blood cells, changes in blood volume and hemoglobin oxygen saturation, vessel size, and location with respect to imaging location are explored. A simple technique for correcting the measured NADH fluorescence intensity changes is provided, with the utilization of a parallel measurement of a physiologically inert fluorophore. The model is applied to TPLSM measurements of NADH fluorescence intensity changes in rat somatosensory cortex during mild hypoxia and hyperoxia. The general approach of the correction algorithm can be extended to other TPLSM measurements, where changes in the optical properties of the tissue confound physiological measurements, such as the detection of calcium dynamics. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3633339]
C1 [Baraghis, Edward; Lesage, Frederic] Ecole Polytech, Dept Genie Elect, Montreal, PQ H3C 3A7, Canada.
[Devor, Anna] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92093 USA.
[Devor, Anna] Univ Calif San Diego, Dept Radiol, San Diego, CA 92093 USA.
[Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neurovasc Res Lab, Charlestown, MA 02129 USA.
[Ayata, Cenk] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA.
[Ayata, Cenk] Massachusetts Gen Hosp, Dept Neurol, Neurosci Intens Care Unit, Boston, MA 02114 USA.
[Kasischke, Karl A.] Univ Rochester, Med Ctr, Dept Neurol, Ctr Neural Dev & Dis, Rochester, NY 14642 USA.
RP Sakadzic, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 149 13th St,Room 2301, Charlestown, MA 02129 USA.
EM sava@nmr.mgh.harvard.edu
FU U.S. National Institute of Health [R01-NS057476, S10-RR022428,
P01-NS055104, K99NS067050]; American Heart Association [11SDG7600037,
11IRG5440002]
FX We thank M. A. Yaseen and G. Boas for critically reading the manuscript
and support from U.S. National Institute of Health Grants No.
R01-NS057476, No. S10-RR022428, No. P01-NS055104, and No. K99NS067050,
as well as American Heart Association Grants No. 11SDG7600037 and No.
11IRG5440002.
NR 47
TC 8
Z9 8
U1 1
U2 6
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD OCT
PY 2011
VL 16
IS 10
AR 106003
DI 10.1117/1.3633339
PG 13
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 853ZV
UT WOS:000297465200010
PM 22029350
ER
PT J
AU Wang, Q
Grozdanic, SD
Harper, MM
Hamouche, N
Kecova, H
Lazic, T
Yu, CX
AF Wang, Qi
Grozdanic, Sinisa D.
Harper, Matthew M.
Hamouche, Nicolas
Kecova, Helga
Lazic, Tatjana
Yu, Chenxu
TI Exploring Raman spectroscopy for the evaluation of glaucomatous retinal
changes
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE glaucoma; raman spectroscopy; retinal ganglion cells; detection; support
vector machine
ID FLUORESCENCE; MICROSCOPY; SPECTRA; MODELS; EYE
AB Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and subsequent loss of visual function. Early detection of glaucoma is critical for the prevention of permanent structural damage and irreversible vision loss. Raman spectroscopy is a technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, we explored the potential of using Raman spectroscopy for detection of glaucomatous changes in vitro. Raman spectroscopic imaging was conducted on retinal tissues of dogs with hereditary glaucoma and healthy control dogs. The Raman spectra were subjected to multivariate discriminant analysis with a support vector machine algorithm, and a classification model was developed to differentiate disease tissues versus healthy tissues. Spectroscopic analysis of 105 retinal ganglion cells (RGCs) from glaucomatous dogs and 267 RGCs from healthy dogs revealed spectroscopic markers that differentiated glaucomatous specimens from healthy controls. Furthermore, the multivariate discriminant model differentiated healthy samples and glaucomatous samples with good accuracy [healthy 89.5% and glaucomatous 97.6% for the same breed (Basset Hounds); and healthy 85.0% and glaucomatous 85.5% for different breeds (Beagles versus Basset Hounds)]. Raman spectroscopic screening can be used for in vitro detection of glaucomatous changes in retinal tissue with a high specificity. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3642010]
C1 [Wang, Qi; Yu, Chenxu] Iowa State Univ, Dept Agr & Biosyst Engn, Ames, IA 50011 USA.
[Grozdanic, Sinisa D.; Harper, Matthew M.; Kecova, Helga; Lazic, Tatjana] US Dept Vet Affairs, Ctr Prevent & Treatment Visual Loss, Iowa City, IA 52246 USA.
[Hamouche, Nicolas] McFarland Clin Eye Ctr, Ames, IA 50011 USA.
RP Yu, CX (reprint author), Iowa State Univ, Dept Agr & Biosyst Engn, 3224 NSRIC, Ames, IA 50011 USA.
EM chenxuyu@iastate.edu
FU U.S. Department of Veterans Affairs Center for Prevention and Treatment
of Visual Loss
FX This study has been supported by the U.S. Department of Veterans Affairs
Center for Prevention and Treatment of Visual Loss.
NR 31
TC 3
Z9 3
U1 0
U2 8
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
EI 1560-2281
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD OCT
PY 2011
VL 16
IS 10
AR 107006
DI 10.1117/1.3642010
PG 9
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 853ZV
UT WOS:000297465200028
PM 22029368
ER
PT J
AU Belmatoug, N
Burlina, A
Giraldo, P
Hendriksz, CJ
Kuter, DJ
Mengel, E
Pastores, GM
AF Belmatoug, Nadia
Burlina, Alberto
Giraldo, Pilar
Hendriksz, Chris J.
Kuter, David J.
Mengel, Eugen
Pastores, Gregory M.
TI Gastrointestinal disturbances and their management in miglustat-treated
patients
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Review
ID DISEASE TYPE-C; I GAUCHER-DISEASE; N-BUTYL-DEOXYNOJIRIMYCIN;
CLINICAL-EXPERIENCE; DISACCHARIDASE ACTIVITIES; BUTYLDEOXYNOJIRIMYCIN;
THERAPY; TRIAL; BIOSYNTHESIS; INHIBITOR
AB Miglustat (Zavesca (R)) is approved for the oral treatment of adult patients with mild to moderate type 1 Gaucher disease (GD1) for whom enzyme replacement therapy is unsuitable, and for the treatment of progressive neurological manifestations in adult and paediatric patients with Niemann-Pick disease type C (NP-C). Gastrointestinal disturbances such as diarrhoea, flatulence and abdominal pain/discomfort have consistently been reported as the most frequent adverse events associated with miglustat during clinical trials and in real-world clinical practice settings. These adverse events are generally mild or moderate in severity, occurring mostly during the initial weeks of therapy. The mechanism underlying these gastrointestinal disturbances is the inhibition by miglustat of intestinal disaccharidase enzymes (mainly sucrase and maltase), leading to suboptimal hydrolysis of carbohydrates and subsequent osmotic diarrhoea and altered colonic fermentation. Transient decreases in body weight, which are often observed during initial miglustat therapy, are considered likely due to gastrointestinal carbohydrate malabsorption and associated negative caloric balance. While most cases of diarrhoea resolve spontaneously during continued miglustat therapy, diarrhoea also responds well to anti-propulsive medications such as loperamide. Dietary modifications such as reduced consumption of dietary sucrose, maltose and lactose have been shown to improve the gastrointestinal tolerability of miglustat and reduce the magnitude of any changes in body weight, particularly if initiated at or before the start of therapy. Miglustat dose escalation at treatment initiation may also reduce gastrointestinal disturbances. This article discusses these aspects in detail, and provides practical recommendations on how to optimize the gastrointestinal tolerability of miglustat.
C1 [Pastores, Gregory M.] NYU Langone Med Ctr, Dept Neurol, Neurogenet Unit, New York, NY 10016 USA.
[Belmatoug, Nadia] Beaujon Hosp, Reference Ctr Lysosomal Dis, Clichy, France.
[Burlina, Alberto] Univ Hosp Padova, Div Metab Dis, Padua, Italy.
[Giraldo, Pilar] CIBERER, Miguel Servet Hosp, Zaragoza, Spain.
[Hendriksz, Chris J.] Birmingham Childrens Hosp NHS Fdn Trust, Birmingham, W Midlands, England.
[Kuter, David J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mengel, Eugen] Johannes Gutenberg Univ Mainz, Mainz, Germany.
RP Pastores, GM (reprint author), NYU Langone Med Ctr, Dept Neurol, Neurogenet Unit, 403 E 34th St,2nd Floor, New York, NY 10016 USA.
EM gregory.pastores@med.nyu.edu
FU Actelion Pharmaceuticals Ltd.
FX Matthew Reilly, PhD, associated with InTouch Medical Ltd. provided
medical writing assistance in the preparation of this manuscript, funded
by Actelion Pharmaceuticals Ltd.
NR 40
TC 24
Z9 25
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-8955
J9 J INHERIT METAB DIS
JI J. Inherit. Metab. Dis.
PD OCT
PY 2011
VL 34
IS 5
BP 991
EP 1001
DI 10.1007/s10545-011-9368-7
PG 11
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 857UZ
UT WOS:000297749500003
PM 21779792
ER
PT J
AU Azarova, AM
Gautam, G
George, RE
AF Azarova, Anna M.
Gautam, Gargi
George, Rani E.
TI Emerging importance of ALK in neuroblastoma
SO SEMINARS IN CANCER BIOLOGY
LA English
DT Review
DE Neuroblastoma; ALK; Tyrosine kinase receptor; Targeted therapy;
Crizotinib; Drug resistance; Point mutations; Small molecule inhibitors;
Combination treatment
ID ANAPLASTIC LYMPHOMA KINASE; RECEPTOR TYROSINE KINASE; SMALL-MOLECULE
INHIBITOR; NON-HODGKINS-LYMPHOMA; LUNG-CANCER CELLS; GROWTH-FACTOR;
C-MET; CRYSTAL-STRUCTURE; NEURONAL DIFFERENTIATION;
DROSOPHILA-MELANOGASTER
AB Since the original descriptions of gain-of function mutations in anaplastic lymphoma kinase (ALK), interest in the role of this receptor tyrosine kinase in neuroblastoma development and as a potential therapeutic target has escalated. As a group, the activating point mutations in full-length ALK, found in approximately 8% of all neuroblastoma tumors, are distributed evenly across different clinical stages. However, the most frequent somatic mutation, F1174L, is associated with amplification of the MYCN oncogene. This combination of features appears to confer a worse prognosis than MYCN amplification alone, suggesting a cooperative effect on neuroblastoma formation by these two proteins. Indeed. F1174L has shown more potent transforming activity in vivo than the second most common activating mutation. R1275Q, and is responsible for innate and acquired resistance to crizotinib, a clinically relevant ALK inhibitor that will soon be commercially available. These advances cast ALK as a bona fide oncoprotein in neuroblastoma and emphasize the need to understand ALK-mediated signaling in this tumor. This review addresses many of the current issues surrounding the role of ALK in normal development and neuroblastoma pathogenesis, and discusses the prospects for clinically effective targeted treatments based on ALK inhibition. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Azarova, Anna M.; Gautam, Gargi; George, Rani E.] Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA.
[Azarova, Anna M.; Gautam, Gargi; George, Rani E.] Harvard Univ, Childrens Hosp Boston, Sch Med, Boston, MA 02115 USA.
[Gautam, Gargi] Karolinska Inst, Karolinska Hosp, Dept Woman & Child Hlth, Childhood Canc Res Unit, SE-17176 Stockholm, Sweden.
RP George, RE (reprint author), Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, 450 Brookline Ave, Boston, MA 02115 USA.
EM rani_george@dfci.harvard.edu
FU Sydney Kimmel Translational Research Scholar Award, Friends for Life
Neuroblastoma Fund [1 R01 CA148688-01A1]
FX Sydney Kimmel Translational Research Scholar Award (REG), 1 R01
CA148688-01A1 (REG), Friends for Life Neuroblastoma Fund (AA).
NR 78
TC 44
Z9 51
U1 0
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-579X
J9 SEMIN CANCER BIOL
JI Semin. Cancer Biol.
PD OCT
PY 2011
VL 21
IS 4
BP 267
EP 275
DI 10.1016/j.semcancer.2011.09.005
PG 9
WC Oncology
SC Oncology
GA 853RZ
UT WOS:000297444700007
PM 21945349
ER
PT J
AU D'Adamo, DR
AF D'Adamo, David R.
TI Integrating Novel Therapies Into the Treatment of Sarcoma: A
Multidisciplinary Approach-Introduction
SO SEMINARS IN ONCOLOGY
LA English
DT Editorial Material
C1 Dana Farber Canc Inst, Sarcoma & Bone Canc Treatment Ctr, Boston, MA 02115 USA.
RP D'Adamo, DR (reprint author), Dana Farber Canc Inst, Sarcoma & Bone Canc Treatment Ctr, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD OCT
PY 2011
VL 38
IS 5
SU 3
BP S1
EP S2
DI 10.1053/j.seminoncol.2011.09.002
PG 2
WC Oncology
SC Oncology
GA 857LK
UT WOS:000297719800001
PM 22055967
ER
PT J
AU D'Adamo, DR
AF D'Adamo, David R.
TI Appraising the Current Role of Chemotherapy for the Treatment of Sarcoma
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID SOFT-TISSUE SARCOMAS; EUROPEAN-OSTEOSARCOMA-INTERGROUP; PHASE-II TRIAL;
PRIMITIVE NEUROECTODERMAL TUMOR; RANDOMIZED COOPERATIVE TRIAL;
GEMCITABINE PLUS DOCETAXEL; HIGH-DOSE METHOTREXATE; ADJUVANT
CHEMOTHERAPY; ONCOLOGY-GROUP; NEOADJUVANT CHEMOTHERAPY
AB Sarcomas are a heterogeneous group of relatively rare mesenchymal neoplasms. They can be grouped into two general categories: soft tissue sarcoma (STS) and primary bone sarcoma, which are treated differently. Because sarcomas are relatively rare and complex with a wide variety of different histopathologic subtypes, evaluation by multidisciplinary teams who have expertise in the field is recommended. Treatment guidelines for the use of chemotherapy in patients with STS and bone sarcoma have been published by the National Comprehensive Cancer Network. The role of adjuvant chemotherapy in resected STS remains controversial. Although chemotherapy improves disease-free survival, the long-term overall survival benefit remains unproven. Chemotherapy is typically used as palliative treatment for most subtypes of metastatic STS. In contrast, chemotherapy has a proven role in the treatment of primary bone tumors and Ewing sarcoma, but it has not demonstrated efficacy in the treatment of chondrosarcoma. The standard chemotherapy regimens used in sarcoma are associated with significant toxicity, including long-term complications. Less intense and less toxic regimens are the focus of ongoing clinical research. Newer cytotoxic agents with an improved safety profile, such as trabectedin and palifosfamide, are currently in development. Future research needs to focus on identification of subpopulations of patients that are most likely to benefit from chemotherapy. Semin Oncol 38:S19-S29 (C) 2011 Elsevier Inc. All rights reserved.
C1 Dana Farber Canc Inst, Sarcoma & Bone Canc Treatment Ctr, Boston, MA 02215 USA.
RP D'Adamo, DR (reprint author), Dana Farber Canc Inst, Sarcoma & Bone Canc Treatment Ctr, 450 Brookline Ave, Boston, MA 02215 USA.
EM david_dadamo@dfci.harvard.edu
FU Novartis; Genentech; Bayer; Merck Co. Inc.
FX Dr D'Adamo has received consulting fees from Novartis and Genentech. He
has performed contracted research for Bayer and Genentech.; Publication
of this article was supported by an educational grant from Merck & Co.
Inc.
NR 87
TC 36
Z9 37
U1 1
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 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD OCT
PY 2011
VL 38
IS 5
SU 3
BP S19
EP S29
DI 10.1053/j.seminoncol.2011.09.004
PG 11
WC Oncology
SC Oncology
GA 857LK
UT WOS:000297719800003
PM 22055968
ER
PT J
AU Neuhaus, V
Jupiter, JB
AF Neuhaus, V.
Jupiter, J. B.
TI Current Concepts Review: Carpal Injuries - Fractures, Ligaments,
Dislocations
SO ACTA CHIRURGIAE ORTHOPAEDICAE ET TRAUMATOLOGIAE CECHOSLOVACA
LA English
DT Review
DE carpal; concepts; current; dislocations; fractures; injuries; ligaments;
review
ID ACUTE SCAPHOID FRACTURES; PERILUNATE DISLOCATIONS; CONSERVATIVE
TREATMENT; DISPLACED FRACTURES; OPERATIVE TREATMENT; OPEN REDUCTION;
NONUNION; SCREW; RADIOGRAPHY; MANAGEMENT
AB An overview about current concepts in treating carpal injuries is presented. These injuries are more commonly seen in young, active individuals after a fall on an outstretched hand. Conventional radiographs and a thorough examination are important. The scaphoid is the most affected bone. Scaphoid fractures can be classified in accordance to OTA, AO, and other classification systems, but mostly to Herbert. It can be treated non-operatively if undisplaced, however a percutaneous internal fixation can be discussed to achieve earlier return to work and shorter time to union, but hazarding the consequences of an operation. Unstable, proximal pole, or delayed diagnosed scaphoid fractures should be treated surgically. Nonunion is seen in 5 - 40% of scaphoid fractures depending mainly on displacement and localization of the fracture. The gold standard in non-osteoarthritic scaphoid nonunion is debridement of the nonunion site, bone grafting, realignment, stable fixation and rehabilitation. The treatment of scaphoid-nonunion advanced collapse is more complex. Proximal row carpectomy or arthrodesis (four-corner or complete wrist) can be mandatory. Other carpal bone fractures are rare. Perilunate dislocations are also uncommon but can be disabling. They usually originate in high-energy trauma. The Mayfield stages help to understand the injury pattern. Open reduction through both volar and dorsal approaches, repair of the volar capsule as well as volar and dorsal ligaments, and internal fixation is commonly the standard treatment. However osteoarthritis and carpal instability are often encountered.
C1 [Jupiter, J. B.] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA.
RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM jjupiter1@partners.org
NR 48
TC 4
Z9 4
U1 1
U2 4
PU GALEN SRO
PI PRAGUE 5
PA NA BELIDLE 34, PRAGUE 5, 150 00, CZECH REPUBLIC
SN 0001-5415
J9 ACTA CHIR ORTHOP TR
JI Acta Chir. Orthop. Traumatol. Cechoslov.
PD OCT
PY 2011
VL 78
IS 5
BP 395
EP 403
PG 9
WC Orthopedics
SC Orthopedics
GA 853MK
UT WOS:000297430200002
PM 22094152
ER
PT J
AU Hanseeuw, BJ
Van Leemput, K
Kavec, M
Grandin, C
Seron, X
Ivanoiu, A
AF Hanseeuw, B. J.
Van Leemput, K.
Kavec, M.
Grandin, C.
Seron, X.
Ivanoiu, A.
TI Mild Cognitive Impairment: Differential Atrophy in the Hippocampal
Subfields
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID ALZHEIMERS-DISEASE; SEGMENTATION; MRI
AB BACKGROUND AND PURPOSE: Hippocampus volumetry is a useful surrogate marker for the diagnosis of Alzheimer disease, but it seems insufficiently sensitive for the aMCI stage. We postulated that some hippocampus subfields are specifically atrophic in aMCI and that measuring hippocampus subfield volumes will improve sensitivity of MR imaging to detect aMCI.
MATERIALS AND METHODS: We evaluated episodic memory and hippocampus subfield volume in 15 patients with aMCI and 15 matched controls. After segmentation of the whole hippocampus from clinical MR imaging, we applied a new computational method allowing fully automated segmentation of the hippocampus subfields. This method used a Bayesian modeling approach to infer segmentations from the imaging data.
RESULTS: In comparison with controls, subiculum and CA2-3 were significantly atrophic in patients with aMCI, whereas total hippocampus volume and other subfields were not. Total hippocampus volume in controls was age-related, whereas episodic memory was the main explanatory variable for both the total hippocampus volume and the subfields that were atrophic in patients with aMCI. Segmenting subfields increases sensitivity to diagnose aMCI from 40% to 73%.
CONCLUSIONS: Measuring CA2-3 and subiculum volumes allows a better detection of aMCI.
C1 [Hanseeuw, B. J.; Ivanoiu, A.] St Luc Univ Hosp, Dept Neurol, Brussels, Belgium.
[Grandin, C.] St Luc Univ Hosp, Dept Radiol, Brussels, Belgium.
[Hanseeuw, B. J.; Grandin, C.; Seron, X.; Ivanoiu, A.] Catholic Univ Louvain, Inst Neurosci, B-1200 Brussels, Belgium.
[Van Leemput, K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA USA.
[Van Leemput, K.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[Van Leemput, K.] Aalto Univ, Sch Sci & Technol, Espoo, Finland.
[Kavec, M.] Erasmus Univ Hosp, Dept Radiol, Brussels, Belgium.
RP Hanseeuw, BJ (reprint author), Clin Univ St Luc, Serv Neurol, Ave Hippocrate, B-101200 Brussels, Belgium.
EM bernard.hanseeuw@uclouvain.be
RI Van Leemput, Koen/A-9197-2009;
OI Van Leemput, Koen/0000-0001-6466-5309; Hanseeuw,
Bernard/0000-0002-3102-6778
FU Belgian Foundation for Scientific Research (FNRS); Academy of Finland
[133611]; National Institutes of Health [R01NS052585, R01EB006758,
R01EB009051, P41RR014075]; Massachusetts General Hospital (Executive
Committee on Research Formulaic Bridge Support) [2010A055663]
FX Funding for this study was provided by the Belgian Foundation for
Scientific Research (FNRS). K. Van Leemput was supported in part by the
Academy of Finland (grant 133611), the National Institutes of Health
(R01NS052585, R01EB006758, R01EB009051, P41RR014075), and Massachusetts
General Hospital (Executive Committee on Research Formulaic Bridge
Support/Proposal 2010A055663).
NR 17
TC 52
Z9 52
U1 1
U2 9
PU AMER SOC NEURORADIOLOGY
PI OAK BROOK
PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA
SN 0195-6108
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD OCT
PY 2011
VL 32
IS 9
BP 1658
EP 1661
DI 10.3174/ajnr.A2589
PG 4
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 849RL
UT WOS:000297142700017
PM 21835940
ER
PT J
AU Gupta, R
Mehndiratta, A
Mitha, AP
Grasruck, M
Leidecker, C
Ogilvy, C
Brady, TJ
AF Gupta, R.
Mehndiratta, A.
Mitha, A. P.
Grasruck, M.
Leidecker, C.
Ogilvy, C.
Brady, T. J.
TI Temporal Resolution of Dynamic Angiography Using Flat Panel Volume CT:
In Vivo Evaluation of Time-Dependent Vascular Pathologies
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID ARTERIOVENOUS-MALFORMATION MODEL; SACCULAR ANEURYSMS; SCANNER; RUPTURE;
DESIGN
AB BACKGROUND AND PURPOSE: Recently introduced fpVCT scanners can capture volumetric (4D) time-varying projections enabling whole-organ dynamic CTA imaging. The main objective of this study was to assess the temporal resolution of dynamic CTA in discriminating various phases of rapid and slow time-dependent neurovascular pathologies in animal models.
MATERIALS AND METHODS: Animal models were created to assess phasic blood flow, subclavian steal phenomena, saccular aneurysms, and neuroperfusion under protocols approved by the SRAC. Animals with progressively increasing heart rate Macaca sylvanus (similar to 100 bpm), Oryctolagus cuniculus (NZW rabbit) (similar to 150 bpm), Rattus norvegicus (similar to 300 bpm), Mus musculus (similar to 500 bpm) were imaged to challenge the temporal resolution of the system. FpVCT, a research prototype with a 25 x 25 x 18 cm coverage, was used for dynamic imaging with the gantry rotation time varying from 3 to 5 seconds. Volumetric datasets with 50% temporal overlap were reconstructed; 4D datasets were analyzed by using the Leonardo workstation.
RESULTS: Dynamic imaging by using fpVCT was capable of demonstrating the following phenomena: 1) subclavian steal in rabbits (Delta T congruent to 3-4 seconds); 2) arterial, parenchymal, and venous phases of blood flow in mice (Delta T congruent to 2 seconds), rabbits (Delta T congruent to 3-4 seconds), and Macaca sylvanus (Delta T congruent to 3-4 seconds); 3) sequential enhancement of the right and left side of the heart in Macaca sylvanus and white rabbits (Delta T congruent to 2 seconds); and 4) different times of the peak opacification of cervical and intracranial arteries, venous sinuses, and the jugular veins in these animals (smallest, Delta T congruent to 1.5-2 seconds). The perfusion imaging in all animals tested was limited due to the fast transit time through the brain and the low contrast resolution of fpVCT.
CONCLUSIONS: Dynamic imaging by using fpVCT can distinguish temporal processes separated by >1.5 seconds. Neurovascular pathologies with a time constant >1.5 seconds can be evaluated noninvasively by using fpVCT.
C1 [Gupta, R.; Mehndiratta, A.; Brady, T. J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Mitha, A. P.; Ogilvy, C.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Mehndiratta, A.] Univ Oxford, Inst Biomed Engn, Oxford, England.
[Grasruck, M.; Leidecker, C.] Siemens Med Solut, Forchheim, Germany.
RP Gupta, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA.
EM rgupta1@partners.org
FU Siemens Medical Solutions; Center for Integration of Medicine and
Innovative Technology consortium; Radiological Society of North America
Research and Education Foundation; Alberta Heritage Fund for Medical
Research Clinical Fellowship Award; American Association of Neurological
Surgeons/Congress of Neurological Surgeons Resident Research; Siemens
Medical Solutions, Erlangen, Germany; Massachusetts General Hospital,
Boston, Massachusetts; Siemens Healthcare; Siemens AG; Healthcare
Sector; National Institutes of Health
FX Financial Relationships and Grant Information: T.J.B. was partially
supported by an educational grant from Siemens Medical Solutions. R.G.
was funded by a grant from the Center for Integration of Medicine and
Innovative Technology consortium and the Radiological Society of North
America Research and Education Foundation. A.P.M. was supported by an
Alberta Heritage Fund for Medical Research Clinical Fellowship Award and
an American Association of Neurological Surgeons/Congress of
Neurological Surgeons Resident Research Award in Cerebrovascular
Disease. M.G. and C.L. are employees of Siemens Medical Solutions,
Germany. The other authors did not receive any financial support in
conjunction with the generation of this submission. Other than these
financial relationships, the authors have no personal or institutional
financial interest in drugs, materials, or devices described in this
submission.; Rajiv Gupta, Research Support (including provision of
equipment or materials) Siemens Medical Solutions, Erlangen, Germany,
Details. The scanner was purchased from Siemens Medical Solutions. Two
of the coauthors are employees of Siemens Medical Solutions. Amit
Mehndiratta, Research Support (including provision of equipment or
materials) Massachusetts General Hospital, Boston, Massachusetts,
Details: The work submitted to the American Journal of Neuradiology was
part of my research fellowship at Massachusetts General Hospital.
Michael Grasruck, Research Support (including provision of equipment or
materials). Employee of Siemens Healthcare, Other Financial Interests.
Employee of Siemens Healthcare. Christianne Leidecker, Research Support
(including provision of equipment or materials). Siemens AG, Healthcare
Sector, Details Employee, Christopher S. Ogilvy, Research Support
(including provision of equipment or materials) National Institutes of
Health, Consultant Mizuho America, Actelion Pharmaceuticals, Toshiba,
Details: Mizuho: $14 000; Actelion: $4500; Toshiba: $5000.
NR 15
TC 3
Z9 3
U1 1
U2 5
PU AMER SOC NEURORADIOLOGY
PI OAK BROOK
PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA
SN 0195-6108
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD OCT
PY 2011
VL 32
IS 9
BP 1688
EP 1696
DI 10.3174/ajnr.A2586
PG 9
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 849RL
UT WOS:000297142700022
PM 21835945
ER
PT J
AU Abdel-Bakky, MS
Hammad, MA
Walker, LA
Ashfaq, MK
AF Abdel-Bakky, Mohamed Sadek
Hammad, Mohamed A.
Walker, Larry A.
Ashfaq, Mohammad K.
TI Silencing of tissue factor by antisense deoxyoligonucleotide prevents
monocrotaline/LPS renal injury in mice
SO ARCHIVES OF TOXICOLOGY
LA English
DT Article
DE Tissue factor antisense; Monocrotaline; Lipopolysaccharide; Renal
toxicity
ID PYRROLIZIDINE ALKALOID MONOCROTALINE; RESPIRATORY-DISTRESS-SYNDROME;
ISCHEMIA-REPERFUSION INJURY; FACTOR CYTOPLASMIC DOMAIN;
TUMOR-NECROSIS-FACTOR; FACTOR VIIA; ENDOTHELIAL-CELLS; FACTOR
EXPRESSION; TGF-BETA; ACTIVATION
AB Tissue factor (TF) is involved in monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity. It is not known whether MCT/LPS can cause renal toxicity and whether TF is involved in this toxicity. Thus, the present study was undertaken to investigate the potential renal toxicity after MCT/LPS co-treatment and the involvement of TF in this toxicity. MCT was delivered to ND4 male mice (200 mg/kg) per os followed 4 h later by treatment with LPS ip (6 mg/kg) to investigate its effect on kidney. We injected TF antisense oligonucleotide (TF-AS) intravenously (i.v) in mice prior to LPS treatment, to block TF, and measured their blood urea nitrogen (BUN), creatinine (CRE), alkaline phosphatase (ALP), and potassium. In MCT/LPS co-treated group, fibrin was detected on the glomerular capillary lumina, distal tubules of renal cortex, and the necrotic tubules of renal medulla. An elevation of BUN, creatinine, and the BUN/creatinine ratio was seen in mice with MCT/LPS co-treatment, compared to animals receiving LPS or MCT alone. Simultaneously, an aggressive tubular necrosis was seen in the medullary tubules in the same group which may account for the oliguria observed in these animals. Fourfold inductions in the plasma TF level was detected at 10 h after MCT/LPS co-treatment which increased to 18-fold at 24 h. Increased blood level of leptin, interleukin-6 (IL-6) and downregulation of tubular chemokine (C-X-C motif) ligand 16 (CXCL16) are characteristic features in MCT/LPS co-treated animal. On the other hand, mice injected with TF-AS in the presence of MCT/LPS co-treatment showed no elevation of the blood BUN, creatinine, potassium, and normal levels of the proinflammatory molecules. TF-AS injection significantly prevented glomerular and tubular fibrin deposition, tubular necrosis, and improvement of the animal survivability. Renal toxicity involving TF can be prevented successfully by the use of TF-AS.
C1 [Abdel-Bakky, Mohamed Sadek; Hammad, Mohamed A.; Walker, Larry A.; Ashfaq, Mohammad K.] Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA.
[Hammad, Mohamed A.; Walker, Larry A.] Univ Mississippi, Dept Pharmacol, Sch Pharm, University, MS 38677 USA.
[Abdel-Bakky, Mohamed Sadek] Al Azhar Univ, Fac Pharm, Cairo, Egypt.
[Hammad, Mohamed A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA.
RP Ashfaq, MK (reprint author), Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA.
EM mkashfaq@olemiss.edu
OI HAMMAD, MOHAMED/0000-0002-9684-2506
FU United States Department of Agriculture, Agricultural Research Service
[58-6408-2-0009]; US Food and Drug Administration [5U01FD002071-09,
1U01FD003871-011]
FX The authors wish to thank Mr. Rajnish Sahu (NCNPR, University of
Mississippi) for his help in the use of fluorescent microscope. This
work was supported in part by the United States Department of
Agriculture, Agricultural Research Service, Specific Cooperative
agreement [58-6408-2-0009] and US Food and Drug Administration
[5U01FD002071-09 and 1U01FD003871-011].
NR 54
TC 8
Z9 8
U1 0
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5761
J9 ARCH TOXICOL
JI Arch. Toxicol.
PD OCT
PY 2011
VL 85
IS 10
BP 1245
EP 1256
DI 10.1007/s00204-011-0663-8
PG 12
WC Toxicology
SC Toxicology
GA 852LI
UT WOS:000297359000008
PM 21327618
ER
PT J
AU Basher, F
Bunni, M
Amani, Z
Zhang, X
Nowling, TK
AF Basher, Fahmin
Bunni, Marlene
Amani, Zainab
Zhang, Xian
Nowling, Tamara K.
TI Effects of Altering Fli1 Levels in Lupus T Cells on Disease Expression
and T Cell Function in the MRL/Lpr Mouse Model.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Basher, Fahmin; Bunni, Marlene; Amani, Zainab; Zhang, Xian; Nowling, Tamara K.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Zhang, Xian; Nowling, Tamara K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2363
BP S921
EP S921
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502749
ER
PT J
AU Bernstein, EJ
Isakova, T
Sullivan, ME
Chibnik, LB
Bazari, H
Wolf, M
Kay, J
AF Bernstein, Elana J.
Isakova, Tamara
Sullivan, Mary E.
Chibnik, Lori B.
Bazari, Hasan
Wolf, Myles
Kay, Jonathan
TI Hypophosphatemia Is Associated with Nephrogenic Systemic Fibrosis: A
Case-Control Study
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Bernstein, Elana J.] Hosp Special Surg, New York, NY 10021 USA.
[Isakova, Tamara; Wolf, Myles] Univ Miami, Miami, FL USA.
[Sullivan, Mary E.; Bazari, Hasan] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Chibnik, Lori B.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Kay, Jonathan] Univ Massachusetts, Sch Med, Worcester, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2309
BP S902
EP S902
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502695
ER
PT J
AU Brown, AG
Hirsch, R
Laor, T
Francis, KA
Hannon, MJ
Kwoh, CK
AF Brown, Amanda G.
Hirsch, Raphael
Laor, Tal
Francis, Kimberly A.
Hannon, Michael J.
Kwoh, C. Kent
TI Patients with Juvenile Idiopathic Arthritis and Rheumatoid Arthritis in
"Physician Determined Clinical Remission" Have Evidence of Persistent
Inflammation Revealed by 3T MRI
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Brown, Amanda G.; Hirsch, Raphael; Francis, Kimberly A.] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA.
[Laor, Tal] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Laor, Tal] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Hannon, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Kwoh, C. Kent] VA Pittsburgh Healthcare, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 958
BP S376
EP S376
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621501153
ER
PT J
AU Chang, AY
Ghazi, E
Okawa, J
Werth, VP
AF Chang, Aileen Y.
Ghazi, Elizabeth
Okawa, Joyce
Werth, Victoria P.
TI Disease Activity and Quality of Life in Refractory Cutaneous Lupus
Erythematosus Patients Initiated on Immunosuppressive Therapy
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Chang, Aileen Y.; Okawa, Joyce; Werth, Victoria P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Chang, Aileen Y.; Okawa, Joyce; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Ghazi, Elizabeth] UMDNJ Robert Wood Johnson Med Sch, Piscataway, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 617
BP S239
EP S239
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621500613
ER
PT J
AU Chung, SA
Brown, EE
Williams, AH
Bhangale, T
Ramos, PS
Ziegler, JT
Freedman, BI
Kimberly, RP
Vyse, TJ
Gregersen, PK
Jacob, CO
Alarcon-Riquelme, ME
Tsao, BP
Harley, JB
Behrens, TW
Petri, M
Kamboh, MI
Demirci, FY
Manzi, S
Criswell, LA
Moser, KL
Gaffney, PM
Graham, RR
Langefeld, CD
AF Chung, Sharon A.
Brown, Elizabeth E.
Williams, Adrienne H.
Bhangale, Tushar
Ramos, Paula S.
Ziegler, Julie T.
Freedman, Barry I.
Kimberly, Robert P.
Vyse, Timothy J.
Gregersen, Peter K.
Jacob, Chaim O.
Alarcon-Riquelme, Marta E.
Tsao, Betty P.
Harley, John B.
Behrens, Timothy W.
Petri, M.
Kamboh, M. Ilyas
Demirci, F. Yesim
Manzi, Susan
Criswell, Lindsey A.
Moser, Kathy L.
Gaffney, Patrick M.
Graham, Robert R.
Langefeld, Carl D.
TI Lupus Nephritis Susceptibility Markers in PDGRFA-GSX2, SLC5A11, ID4, and
HAS2-SNTB1 Regions Identified From a Meta-Analysis of Genome Wide
Association Studies of Women with Systemic Lupus Erythematosus
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Chung, Sharon A.; Criswell, Lindsey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Brown, Elizabeth E.; Kimberly, Robert P.] Univ Alabama, Birmingham, AL USA.
[Williams, Adrienne H.; Ramos, Paula S.; Ziegler, Julie T.; Freedman, Barry I.; Langefeld, Carl D.] Wake Forest Sch Med, Winston Salem, NC USA.
[Bhangale, Tushar; Behrens, Timothy W.; Graham, Robert R.] Genentech Inc, San Francisco, CA 94080 USA.
[Vyse, Timothy J.] Kings Coll London, London WC2R 2LS, England.
[Gregersen, Peter K.] Feinstein Inst Med Res, Manhasset, NY USA.
[Jacob, Chaim O.] Univ So Calif, Los Angeles, CA USA.
[Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta de Andalucia, Oklahoma Med Res Fdn, Ctr Genom & Oncol Res, Oklahoma City, OK 73104 USA.
[Tsao, Betty P.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Harley, John B.] Med Ctr, US Dept Vet Affairs, Cincinnati, OH USA.
[Petri, M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Kamboh, M. Ilyas; Demirci, F. Yesim] Univ Pittsburgh, Pittsburgh, PA USA.
[Manzi, Susan] Allegheny Singer Res Inst, Pittsburgh, PA 15212 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2479
BP S967
EP S967
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621503050
ER
PT J
AU Davids, ML
Do, H
Tomasson, G
Davis, JC
Hoffman, GS
McCune, WJ
Specks, U
St Clair, EW
Stone, JH
Merkel, PA
Spiera, RF
AF Davids, Morgana L.
Do, Huong
Tomasson, Gunnar
Davis, John C.
Hoffman, Gary S.
McCune, W. Joseph
Specks, Ulrich
St Clair, E. William
Stone, John H.
Merkel, Peter A.
Spiera, Robert F.
TI Mental Health As a Predictor of Disease Flare in Granulomatosis with
Polyangiitis (Wegener's Granulomatosis)
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Davids, Morgana L.; Do, Huong; Spiera, Robert F.] Hosp Special Surg, New York, NY 10021 USA.
[Tomasson, Gunnar] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Davis, John C.] Genentech Inc, San Francisco, CA 94080 USA.
[Hoffman, Gary S.] Cleveland Clin, Cleveland, OH 44106 USA.
[McCune, W. Joseph] Univ Michigan, Ann Arbor, MI 48109 USA.
[Specks, Ulrich] Mayo Clin, Rochester, MN USA.
[St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA.
[Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2371
BP S924
EP S925
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502757
ER
PT J
AU Davis, LA
Pointer, LM
Wolff, RK
Reimold, AM
Kerr, GS
Mikuls, TR
Cannon, GW
Caplan, L
AF Davis, Lisa A.
Pointer, Lauren M.
Wolff, Roger K.
Reimold, Andreas M.
Kerr, Gail S.
Mikuls, Ted R.
Cannon, Grant W.
Caplan, Liron
TI Association of Medicaons and Rheumatoid Arthritis Susceptibility
Polymorphism with Lipid Profiles in Patients with Rheumatoid Arthritis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Davis, Lisa A.] Univ Colorado, Sch Med, Aurora, CO USA.
[Pointer, Lauren M.] Denver Vet Affairs Med Ctr, Denver, CO USA.
[Wolff, Roger K.] Univ Utah, Salt Lake City, UT USA.
[Reimold, Andreas M.] Univ Texas SW, Dallas, TX USA.
[Kerr, Gail S.] Washington DC VA, Washington, DC USA.
[Kerr, Gail S.] Georgetown Univ, Washington, DC USA.
[Wolff, Roger K.] Dallas VA, Dallas, TX USA.
[Mikuls, Ted R.] Omaha VA, Omaha, NE USA.
[Mikuls, Ted R.] Univ Nebraska, Omaha, NE 68182 USA.
[Cannon, Grant W.] Salt Lake City VA, Salt Lake City, UT USA.
[Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA.
[Caplan, Liron] Denver VA, Aurora, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 1181
BP S460
EP S461
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621501375
ER
PT J
AU Davis, TE
Kis-Toth, K
Szanto, A
Miller, LC
Tsokos, GC
AF Davis, Trevor E.
Kis-Toth, Katalin
Szanto, Attila
Miller, Laurie C.
Tsokos, George C.
TI Methylprednisolone Modulates MicroRNA and Gene Expression in Human
CD4(+) T Cells: A Novel Mechanism of Anti-Inflammatory Action
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Davis, Trevor E.; Kis-Toth, Katalin; Tsokos, George C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Szanto, Attila; Tsokos, George C.] Harvard Univ, Sch Med, Boston, MA USA.
[Davis, Trevor E.] Tufts Med Ctr, Floating Hosp Children, Boston, MA USA.
[Szanto, Attila] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Szanto, Attila/B-2198-2012
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2331
BP S910
EP S910
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502717
ER
PT J
AU Deng, Y
Zhao, J
Tan, W
Kaufman, KM
Brown, EE
Edberg, JC
Kamen, DL
Gilkeson, GS
Jacob, CO
Scofield, RH
Kimberly, RP
Langefeld, CD
Alarcon-Riquelme, ME
Harley, JB
Vyse, TJ
Gaffney, PM
Moser, KL
James, JA
Chen, JY
Mikuls, TR
Shadick, NA
Weinblatt, ME
Bridges, SL
Paulus, HE
Tsao, BP
AF Deng, Yun
Zhao, Jian
Tan, Wenfeng
Kaufman, Kenneth M.
Brown, Elizabeth E.
Edberg, Jeffrey C.
Kamen, Diane L.
Gilkeson, Gary S.
Jacob, Chaim O.
Scofield, Robert H.
Kimberly, Robert P.
Langefeld, Carl D.
Alarcon-Riquelme, Marta E.
Harley, John B.
Vyse, Timothy J.
Gaffney, Patrick M.
Moser, Kathy L.
James, Judith A.
Chen, Ji-Yih
Mikuls, Ted R.
Shadick, Nancy A.
Weinblatt, Michael E.
Bridges, S. Louis, Jr.
Paulus, Harold E.
Tsao, Betty P.
CA PROFILE Investigators
BIOLUPUS GENLES
TI Association of a Functional Variant in TLR7 with Systemic Lupus
Erythematosus and Rheumatoid Arthritis in Multiple Ancestries
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Deng, Yun; Zhao, Jian; Tan, Wenfeng; Paulus, Harold E.; Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Kaufman, Kenneth M.; Scofield, Robert H.; Alarcon-Riquelme, Marta E.; Gaffney, Patrick M.; Moser, Kathy L.; BIOLUPUS GENLES] US Dept Vet Affairs, Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Med Ctr, Oklahoma City, OK USA.
[Brown, Elizabeth E.; Edberg, Jeffrey C.; Kimberly, Robert P.; PROFILE Investigators] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA.
[Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA.
[Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA.
[Scofield, Robert H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.
[Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA.
[Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta de Andalucia, Ctr Genom & Oncol Res, Granada, Spain.
[Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.
[Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England.
[Vyse, Timothy J.] Kings Coll London, Div Mol Med & Immunol, London WC2R 2LS, England.
[Chen, Ji-Yih] Chang Gung Mem Hosp, Div Allergy Immunol & Rheumatol, Taipei 10591, Taiwan.
[Mikuls, Ted R.] Omaha VA, Omaha, NE USA.
[Mikuls, Ted R.] Univ Nebraska, Omaha, NE 68182 USA.
[Shadick, Nancy A.; Weinblatt, Michael E.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Bridges, S. Louis, Jr.] Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA.
RI Zhao, Jian/E-6292-2012
NR 0
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 634
BP S246
EP S247
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621500630
ER
PT J
AU Dillon, SP
Kao, L
Kaufman, KM
Ice, JA
Omdal, R
Mariette, X
Witte, T
Illei, GG
Rischmueller, M
Nordmark, G
Jonsson, R
Herlenius, MW
Vyse, TJ
Brennan, MT
Rybicki, BA
Ng, WF
Segal, BM
Rhodus, NL
Merrill, JT
Montgomery, CG
Lessard, CJ
Harley, JB
Moser, KL
Gaffney, PM
Scofield, RH
AF Dillon, Skyler P.
Kao, Lydia
Kaufman, Kenneth M.
Ice, John A.
Omdal, Roald
Mariette, Xavier
Witte, Torsten
Illei, Gabor G.
Rischmueller, Maureen
Nordmark, Gunnel
Jonsson, Roland
Herlenius, Marie Wahren
Vyse, Timothy J.
Brennan, Michael T.
Rybicki, Benjamin A.
Ng, Wan-Fai
Segal, Barbara M.
Rhodus, Nelson L.
Merrill, Joan T.
Montgomery, Courtney G.
Lessard, Christopher J.
Harley, John B.
Moser, Kathy L.
Gaffney, Patrick M.
Scofield, R. Hal
TI Triple X Syndrome (47,XXX) Increases the Risk and Accelerates the Onset
of Systemic Lupus Erythematosus and Sjogren's Syndrome: Support for a
Gene-Dose Effect From the X Chromosome
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Dillon, Skyler P.; Kao, Lydia] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Omdal, Roald] Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
[Mariette, Xavier] Univ Paris 11, Le Kremlin Bicetre, France.
[Witte, Torsten] Hannover Med Sch, Hannover, Germany.
[Illei, Gabor G.] NIDCR, NIH, Bethesda, MD USA.
[Rischmueller, Maureen] Queen Elizabeth Hosp, Adelaide, SA, Australia.
[Nordmark, Gunnel] Uppsala Univ, Rheumatol Sect, Dept Med Sci, Uppsala, Sweden.
[Herlenius, Marie Wahren] CMM L8204 Karolinska Hosp, Stockholm, Sweden.
[Jonsson, Roland] Univ Bergen, Bergen, Norway.
[Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England.
[Vyse, Timothy J.] Kings Coll London, Div Mol Med & Immunol, London WC2R 2LS, England.
[Brennan, Michael T.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Rybicki, Benjamin A.] Henry Ford Hlth Syst, Detroit, MI USA.
[Ng, Wan-Fai] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Rhodus, Nelson L.] Univ Minnesota, Minneapolis, MN USA.
[Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.
[Moser, Kathy L.; Gaffney, Patrick M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK USA.
RI Witte, Torsten/B-5783-2016
NR 0
TC 2
Z9 2
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 643
BP S251
EP S251
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621500639
ER
PT J
AU Ding, YN
Hsu, HC
Mountz, JD
AF Ding, Yanna
Hsu, Hui-Chen
Mountz, John D.
TI Identification of a CD62L(hi)CD44(low) T-FH Precursor Capable of
Developing into An IL21(hi) IL17(hi) Mature T-FH in Autoimmune BXD2
Mice.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Ding, Yanna; Hsu, Hui-Chen; Mountz, John D.] Univ Alabama, Birmingham, AL USA.
[Mountz, John D.] Birmingham VAMC, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2362
BP S920
EP S921
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502748
ER
PT J
AU Domsic, RT
Lucas, M
Wisniewski, SR
Kwoh, CK
Fine, MJ
Medsger, TA
AF Domsic, Robyn T.
Lucas, Mary
Wisniewski, Stephen R.
Kwoh, C. Kent
Fine, Michael J.
Medsger, Thomas A.
TI Development and Internal Validation of a Two-Year Mortality Risk
Prediction Rule in Early Diffuse Systemic Sclerosis Patients
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Domsic, Robyn T.; Lucas, Mary; Wisniewski, Stephen R.; Kwoh, C. Kent; Fine, Michael J.; Medsger, Thomas A.] Univ Pittsburgh, Pittsburgh, PA USA.
[Kwoh, C. Kent; Fine, Michael J.] VA Pittsburgh Healthcare, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2485
BP S969
EP S970
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621503056
ER
PT J
AU Drouin, EE
Seward, RJ
Yao, CX
Katchar, K
McHugh, G
Strle, K
Costello, CE
Steere, AC
AF Drouin, Elise E.
Seward, Robert J.
Yao, Chunxiang
Katchar, Kianoosh
McHugh, Gail
Strle, Klemen
Costello, Catherine E.
Steere, Allen C.
TI A Novel Human Autoantigen Induces T and B Cell Responses in Patients
with Antibiotic-Refractory Lyme Arthritis.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Drouin, Elise E.; Katchar, Kianoosh; McHugh, Gail; Strle, Klemen; Steere, Allen C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Seward, Robert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Drouin, Elise E.; Katchar, Kianoosh; McHugh, Gail; Strle, Klemen; Steere, Allen C.] Harvard Univ, Sch Med, Boston, MA USA.
[Seward, Robert J.; Yao, Chunxiang; Costello, Catherine E.] Boston Univ, Sch Med, Boston, MA 02118 USA.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2344
BP S914
EP S914
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502730
ER
PT J
AU Galasso, JA
AF Galasso, Janine A.
TI What Is the Health Literacy and Numeracy in a Rheumatology Veterans
Population?
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Galasso, Janine A.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 1551
BP S606
EP S606
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621501745
ER
PT J
AU Ghazi, E
Kling, MA
Propert, K
Okawa, J
Werth, VP
AF Ghazi, Elizabeth
Kling, Mitchel A.
Propert, Kathleen
Okawa, Joyce
Werth, Victoria P.
TI Increased Depression and Anxiety Symptoms in a Group of Dermatomyositis
Patients
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Ghazi, Elizabeth] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA.
[Kling, Mitchel A.; Okawa, Joyce; Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Okawa, Joyce; Werth, Victoria P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
NR 0
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 249
BP S92
EP S92
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621500249
ER
PT J
AU Gross, RL
Schwartzman-Morris, JS
Krathen, M
Reed, G
Chang, H
Saunders, KC
Fisher, MC
Putterman, C
Mease, PJ
Gottlieb, AB
Broder, AR
AF Gross, Rachel L.
Schwartzman-Morris, Julie S.
Krathen, Michael
Reed, George
Chang, Hong
Saunders, Katherine C.
Fisher, Mark C.
Putterman, Chaim
Mease, Philip J.
Gottlieb, Alice B.
Broder, Anna R.
TI The Risk of Malignancy in a Large Cohort of Patients with Psoriatic
Arthritis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Gross, Rachel L.; Schwartzman-Morris, Julie S.; Putterman, Chaim; Broder, Anna R.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Krathen, Michael; Chang, Hong; Gottlieb, Alice B.] Tufts Med Ctr, Boston, MA USA.
[Reed, George] Univ Massachusetts, Worcester, MA 01605 USA.
[Saunders, Katherine C.] CORRONA Inc, Southborough, MA USA.
[Fisher, Mark C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mease, Philip J.] Seattle Rheumatol Associate, Seattle, WA USA.
NR 1
TC 3
Z9 3
U1 1
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 509
BP S195
EP S195
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621500509
ER
PT J
AU Hu, XL
Kim, H
Stahl, EA
Plenge, RM
Daly, M
Raychaudhuri, S
AF Hu, Xinli
Kim, Hyun
Stahl, Eli A.
Plenge, Robert M.
Daly, Mark
Raychaudhuri, Soumya
TI Integrative Analyses Demonstrate That Rheumatoid Arthritis Risk Loci
Impact Genes with CD4+Effector Memory T-Cell Function
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Hu, Xinli; Kim, Hyun; Stahl, Eli A.; Plenge, Robert M.; Raychaudhuri, Soumya] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Daly, Mark] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2156
BP S840
EP S841
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502542
ER
PT J
AU Hughes, T
Adler, A
Merrill, JT
Kelly, JA
Kaufman, K
Williams, A
Langefeld, CD
Gilkeson, GS
Sanchez, E
Martin, J
Gaffney, PM
Moser, KL
Vyse, TJ
Alarcon-Riquelme, ME
James, JA
Scofield, RH
Harley, JB
Richardson, BC
Sawalha, AH
AF Hughes, Travis
Adler, Adam
Merrill, J. T.
Kelly, Jennifer A.
Kaufman, Kenneth
Williams, Adrienne
Langefeld, Carl D.
Gilkeson, Gary S.
Sanchez, Elena
Martin, Javier
Gaffney, Patrick M.
Moser, Kathy L.
Vyse, Tomothy J.
Alarcon-Riquelme, Marta E.
James, Judith A.
Scofield, Robert H.
Harley, John B.
Richardson, Bruce C.
Sawalha, Amr H.
CA Elizabeth E Brown PROFILE
TI Sex-Specific Genetic Architecture of Systemic Lupus Erythematosus
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta de Andalucia, Oklahoma Med Res Fdn, Ctr Genom & Oncol Res, Oklahoma City, OK USA.
[Williams, Adrienne] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA.
[Martin, Javier] Inst Parasitol & Biomed Lopez Neyra CSIC, Granada, Spain.
[Elizabeth E Brown PROFILE] Univ Alabama, Birmingham, AL USA.
[Vyse, Tomothy J.] Kings Coll London, Guys Hosp, London WC2R 2LS, England.
[James, Judith A.; Scofield, Robert H.] Univ Oklahoma, Hlth Sci Ctr, US Dept Vet Affairs, Arthritis & Clin Immunol Res Program,Oklahoma Med, Oklahoma City, OK USA.
[Scofield, Robert H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.
[Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.
[Richardson, Bruce C.] Univ Michigan, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 157
BP S57
EP S57
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621500158
ER
PT J
AU Hwang, YG
Lim, FC
Wu, Q
Yang, PA
Fisher, G
Hunter, G
Hsu, HC
Mountz, JD
AF Hwang, Yong Gil
Lim, Fei Chu
Wu, Qi
Yang, PingAr
Fisher, Gordon
Hunter, Gary
Hsu, Hui-Chen
Mountz, John D.
TI A Novel Role for Vitamin D in Immunosenescence: Is Enough Too Much for
Naive CD8 T Cells?
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Fisher, Gordon] Univ Alabama, Dept Nutr Sci, Birmingham, AL USA.
[Hunter, Gary] Univ Alabama, Dept Human Studies, Birmingham, AL USA.
[Mountz, John D.] Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2348
BP S915
EP S916
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502734
ER
PT J
AU Kariuki, S
Franek, BS
Kumar, AA
Kumabe, M
Kaufman, KM
Anaya, JM
Alarcon-Riquelme, ME
Bae, SC
Brown, EE
Freedman, BI
Gilkeson, GS
Jacob, CO
James, JA
Kimberly, RP
Martin, J
Merrill, JT
Pons-Estel, B
Tsao, BP
Vyse, TJ
Langefeld, CD
Harley, JB
Moser, KL
Gaffney, PM
Skol, AD
Niewold, TB
AF Kariuki, Silvia
Franek, Beverly S.
Kumar, Akaash A.
Kumabe, Marissa
Kaufman, Kenneth M.
Anaya, Juan-Manuel
Alarcon-Riquelme, Marta E.
Bae, Sang-Cheol
Brown, Elizabeth E.
Freedman, Barry I.
Gilkeson, Gary S.
Jacob, Chaim O.
James, Judith A.
Kimberly, Robert P.
Martin, Javier
Merrill, Joan T.
Pons-Estel, Bernardo
Tsao, Betty P.
Vyse, Timothy J.
Langefeld, Carl D.
Harley, John B.
Moser, Kathy L.
Gaffney, Patrick M.
Skol, Andrew D.
Niewold, Timothy B.
TI Genetic Associations with Serologic Autoimmunity in a Large
Multi-Ancestral Systemic Lupus Erythematosus Cohort
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Kariuki, Silvia; Franek, Beverly S.; Kumar, Akaash A.; Kumabe, Marissa; Skol, Andrew D.; Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA.
[Kaufman, Kenneth M.; Moser, Kathy L.; Gaffney, Patrick M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA.
[Kaufman, Kenneth M.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA.
[Anaya, Juan-Manuel] Univ Rosario, Corp Invest Biol, Bogota, Colombia.
[Alarcon-Riquelme, Marta E.] Oklahoma Med Res Fdn, Granada, Spain.
[Alarcon-Riquelme, Marta E.] Ctr Genom & Invest Oncol Pfizer Univ Granada Junt, Granada, Spain.
[Alarcon-Riquelme, Marta E.] BIOLUPUS Network, Oklahoma City, OK USA.
[Alarcon-Riquelme, Marta E.] GENLES Network, Oklahoma City, OK USA.
[Bae, Sang-Cheol] Hanyang Univ, Hosp Rheumat Dis, CRCRA, Seoul 133791, South Korea.
[Brown, Elizabeth E.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA.
[Freedman, Barry I.; Langefeld, Carl D.] Wake Forest Sch Med, Winston Salem, NC USA.
[Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA.
[Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA.
[James, Judith A.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA.
[James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Martin, Javier] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain.
[Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England.
[Vyse, Timothy J.] Kings Coll London, Div Mol Med & Immunol, London WC2R 2LS, England.
[Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.
[Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
RI Anaya, Juan-Manuel/J-1960-2016
OI Anaya, Juan-Manuel/0000-0002-6444-1249
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 633
BP S246
EP S246
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621500629
ER
PT J
AU Kaufman, KM
Kelly, JA
Hughes, T
Adler, A
Sanchez, E
Ojwang, JO
Langefeld, CD
Ziegler, JT
James, JA
Brown, EE
Kimberly, RP
Edberg, JC
Criswell, LA
Chang, DM
Gilkeson, GS
Niewold, TB
Bae, SC
Alarcon-Riquelme, ME
Jacob, CO
Moser, KL
Gaffney, PM
Harley, JB
Sawalha, AH
Tsao, BP
AF Kaufman, Kenneth M.
Kelly, Jennifer A.
Hughes, Travis
Adler, Adam
Sanchez, Elena
Ojwang, Joshua O.
Langefeld, Carl D.
Ziegler, Julie T.
James, Judith A.
Brown, Elizabeth E.
Kimberly, Robert P.
Edberg, Jeffrey C.
Criswell, Lindsey A.
Chang, Deh-Ming
Gilkeson, Gary S.
Niewold, Timothy B.
Bae, Sang-Cheol
Alarcon-Riquelme, Marta E.
Jacob, Chaim O.
Moser, Kathy L.
Gaffney, Patrick M.
Harley, John B.
Sawalha, Amr H.
Tsao, Betty P.
TI Fine Mapping of Xq28: Both MECP2/IRAK1 and NAA10/RENBP Contribute to
Risk for SLE in Multiple Ancestral Groups
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Kaufman, Kenneth M.; Moser, Kathy L.; Gaffney, Patrick M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA.
[Kaufman, Kenneth M.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA.
[Langefeld, Carl D.; Ziegler, Julie T.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Brown, Elizabeth E.; Edberg, Jeffrey C.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA.
[Criswell, Lindsey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Chang, Deh-Ming] Natl Def Med Ctr, Taipei, Taiwan.
[Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA.
[Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA.
[Bae, Sang-Cheol] Hanyang Univ, Hosp Rheumat Dis, CRCRA, Seoul 133791, South Korea.
[Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta de Andalucia GENYO, Ctr Genom & Invest Oncol, Granada, Spain.
[Alarcon-Riquelme, Marta E.] BIOLUPUS Network, Oklahoma City, OK USA.
[Alarcon-Riquelme, Marta E.] GENLES Network, Oklahoma City, OK USA.
[Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA.
[Harley, John B.] Cincinnato Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 642
BP S250
EP S251
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621500638
ER
PT J
AU Khosroshahi, A
Carruthers, M
Deshpande, V
Unizony, S
Bloch, DB
Stone, JH
AF Khosroshahi, Arezou
Carruthers, Mollie
Deshpande, Vikram
Unizony, Sebastian
Bloch, Donald B.
Stone, John H.
TI Rituximab for the Treatment of IgG4-Related Disease: Lessons From Ten
Consecutive Patients
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Khosroshahi, Arezou; Carruthers, Mollie; Deshpande, Vikram; Unizony, Sebastian; Bloch, Donald B.; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 1740
BP S683
EP S683
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502126
ER
PT J
AU Khosroshahi, A
Hasserjian, RP
Sainani, NI
Deshpande, V
Stone, JH
AF Khosroshahi, Arezou
Hasserjian, Robert P.
Sainani, Nisha I.
Deshpande, Vikram
Stone, John H.
TI A Clinicopathologic Study of Retroperitoneal Fibrosis and Its
Association with Immunoglobulin G4-Related Disease
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Khosroshahi, Arezou; Hasserjian, Robert P.; Sainani, Nisha I.; Deshpande, Vikram; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 1713
BP S672
EP S672
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502099
ER
PT J
AU Kwoh, CK
Hannon, MJ
Green, SM
Guermazi, A
Boudreau, RM
AF Kwoh, C. Kent
Hannon, Michael J.
Green, Stephanie M.
Guermazi, Ali
Boudreau, Robert M.
TI A Screening Tool for Knee Osteoarthritis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Hannon, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Kwoh, C. Kent] VA Pittsburgh Healthcare, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Guermazi, Ali] Boston Med Ctr, Boston, MA USA.
NR 0
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2079
BP S810
EP S810
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502465
ER
PT J
AU Kwoh, CK
Guermazi, A
Hannon, MJ
Boudreau, RM
Green, SM
Jakicic, JM
Roemer, F
AF Kwoh, C. Kent
Guermazi, Ali
Hannon, Michael J.
Boudreau, Robert M.
Green, Stephanie M.
Jakicic, John M.
Roemer, Frank
TI Identification of Magnetic Resonance Imaging Morphologic Features
Associated with Different Knee Pain Patterns
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Hannon, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Kwoh, C. Kent] VA Pittsburgh Healthcare, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA.
[Guermazi, Ali] Boston Med Ctr, Boston, MA USA.
[Roemer, Frank] Boston Univ, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 959
BP S376
EP S376
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621501154
ER
PT J
AU Lessard, CJ
Adrianto, I
Ice, JA
Kelly, JA
Li, H
Wiley, GB
Rasmussen, A
Alarcon-Riquelme, ME
Anaya, JM
Bae, SC
Brown, EE
Jacob, CO
James, JA
Martin, J
Niewold, TB
Pons-Estel, B
Tsao, BP
Vyse, TJ
Harley, JB
Wakeland, E
Kaufman, KM
Montgomery, C
Langefeld, CD
Gaffney, PM
Moser, KL
AF Lessard, Christopher J.
Adrianto, Indra
Ice, John A.
Kelly, Jennifer A.
Li, He
Wiley, Graham B.
Rasmussen, Astrid
Alarcon-Riquelme, Marta E.
Anaya, Juan-Manuel
Bae, Sang-Cheol
Brown, Elizabeth E.
Jacob, Chaim O.
James, Judith A.
Martin, Javier
Niewold, Timothy B.
Pons-Estel, Bernardo
Tsao, Betty P.
Vyse, Timothy J.
Harley, John B.
Wakeland, Edward
Kaufman, Kenneth M.
Montgomery, Courtney
Langefeld, Carl D.
Gaffney, Patrick M.
Moser, Kathy L.
TI A Large-Scale, Multi-Racial Replication Study Identifies Novel Systemic
Lupus Erythematosus Susceptibility Loci At IRF8, TMEM39A, and
IKZF3/ZPBP2
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta Andalucia, Oklahoma Med Res Fdn, Ctr Genom & Oncol Res, Oklahoma City, OK USA.
[Anaya, Juan-Manuel] Univ Rosario, Corp Invest Biol, Bogota, Colombia.
[Bae, Sang-Cheol] Hanyang Univ, Hosp Rheumat Dis, CRCRA, Seoul 133791, South Korea.
[Brown, Elizabeth E.] Univ Alabama, Birmingham, AL USA.
[Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA.
[James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Martin, Javier] Inst Parasitol & Biomed Lopez Neyra CSIC, Granada, Spain.
[Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA.
[Tsao, Betty P.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England.
[Vyse, Timothy J.] Kings Coll London, Div Mol Med, London WC2R 2LS, England.
[Vyse, Timothy J.] Kings Coll London, Div Immunol, London WC2R 2LS, England.
[Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Harley, John B.] Med Ctr, US Dept Vet Affairs, Cincinnati, OH USA.
[Wakeland, Edward] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Kaufman, Kenneth M.; Gaffney, Patrick M.; Moser, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA.
[Kaufman, Kenneth M.] Med Ctr, US Dept Vet Affairs, Oklahoma City, OK USA.
[Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
RI Adrianto, Indra/D-4214-2013; Anaya, Juan-Manuel/J-1960-2016
OI Adrianto, Indra/0000-0002-9973-3057; Anaya,
Juan-Manuel/0000-0002-6444-1249
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2475
BP S965
EP S965
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621503046
ER
PT J
AU Lessard, CJ
Adrianto, I
Ice, JA
Kelly, JA
Jonsson, R
Illei, GG
Rischmueller, M
Nordmark, G
Mariette, X
Miceli-Richard, C
Herlenius, MW
Witte, T
Brennan, MT
Omdal, R
Gaffney, PM
Lessard, JA
Ng, WF
Rhodus, NL
Segal, BM
Scofield, RH
James, JA
Anaya, JM
Harley, JB
Montgomery, C
Moser, KL
AF Lessard, Christopher J.
Adrianto, Indra
Ice, John A.
Kelly, Jennifer A.
Jonsson, Roland
Illei, Gabor G.
Rischmueller, Maureen
Nordmark, Gunnel
Mariette, Xavier
Miceli-Richard, Corinne
Herlenius, Marie Wahren
Witte, Torsten
Brennan, Michael T.
Omdal, Roald
Gaffney, Patrick M.
Lessard, James A.
Ng, Wan-Fai
Rhodus, Nelson L.
Segal, Barbara M.
Scofield, R. Hal
James, Judith A.
Anaya, Juan-Manuel
Harley, John B.
Montgomery, Courtney
Moser, Kathy L.
TI Large-Scale, High-Density Genotyping Performed by the Sjogren's Genetics
Network Using the ImmunoChip Identifies PRKRA as a Novel Sjogren's
Syndrome Susceptibility Locus and Confirms Associations with IRF5, BLK
and MHC
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Gaffney, Patrick M.; Moser, Kathy L.] Oklahoma Med Res Fdn, Arthritis & Clin Immunol Res Program, Oklahoma City, OK 73104 USA.
[Jonsson, Roland] Univ Bergen, Bergen, Norway.
[Illei, Gabor G.] NIDCR, NIH 10 1N110, Bethesda, MD USA.
[Rischmueller, Maureen] Queen Elizabeth Hosp, Adelaide, SA, Australia.
[Nordmark, Gunnel] Uppsala Univ, Rheumatol Sect, Dept Med Sci, Uppsala, Sweden.
[Mariette, Xavier; Miceli-Richard, Corinne] Bicetre Univ Hosp, Le Kremlin Bicetre, France.
[Herlenius, Marie Wahren] Karolinska Inst, Stockholm, Sweden.
[Witte, Torsten] Hannover Med Sch, Hannover, Germany.
[Brennan, Michael T.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Omdal, Roald] Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
[Lessard, James A.] Valley Bone& Joint Clin, Grand Forks, ND USA.
[Ng, Wan-Fai] Newcastle Univ, Inst Cellular Med, Musculoskeletal Res Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Rhodus, Nelson L.] Univ Minnesota, Minneapolis, MN USA.
[Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Anaya, Juan-Manuel] Univ Rosario Corp Invest Biol, Bogota, Colombia.
[Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.
RI Adrianto, Indra/D-4214-2013; Witte, Torsten/B-5783-2016; Anaya,
Juan-Manuel/J-1960-2016
OI Adrianto, Indra/0000-0002-9973-3057; Anaya,
Juan-Manuel/0000-0002-6444-1249
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 773
BP S303
EP S304
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621500769
ER
PT J
AU Lessard, CJ
Ice, JA
Adrianto, I
Kelly, JA
Jonsson, R
Illei, GG
Rischmueller, M
Nordmark, G
Mariette, X
Miceli-Richard, C
Herlenius, MW
Witte, T
Brennan, MT
Omdal, R
Vyse, TJ
Lessard, JA
Ng, WF
Rhodus, NL
Segal, BM
Scofield, RH
Anaya, JM
Harley, JB
Montgomery, CG
Moser, KL
AF Lessard, Christopher J.
Ice, John A.
Adrianto, Indra
Kelly, Jennifer A.
Jonsson, Roland
Illei, Gabor G.
Rischmueller, Maureen
Nordmark, Gunnel
Mariette, Xavier
Miceli-Richard, Corinne
Herlenius, Marie Wahren
Witte, Torsten
Brennan, Michael T.
Omdal, Roald
Vyse, Timothy J.
Lessard, James A.
Ng, Wan-Fai
Rhodus, Nelson L.
Segal, Barbara M.
Scofield, R. Hal
Anaya, Juan-Manuel
Harley, John B.
Montgomery, Courtney G.
Moser, Kathy L.
CA Benjamin A Rybicki ACCESS
TI A High-Density Genome-Wide Association Study by the Sjogren's Genetics
Network Identifies Five Novel Susceptibility Loci for Primary Sjogren's
Syndrome and Confirms Association with MHC, IRF5, and BLK
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Lessard, Christopher J.; Ice, John A.; Adrianto, Indra; Kelly, Jennifer A.; Scofield, R. Hal; Montgomery, Courtney G.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA.
[Jonsson, Roland] Univ Bergen, Bergen, Norway.
[Illei, Gabor G.] NIDCR, NIH, Bethesda, MD USA.
[Rischmueller, Maureen] Queen Elizabeth Hosp, Adelaide, SA, Australia.
[Nordmark, Gunnel] Uppsala Univ, Rheumatol Sect, Dept Med Sci, Uppsala, Sweden.
[Mariette, Xavier; Miceli-Richard, Corinne] Bicetre Univ Hosp, Le Kremlin Bicetre, France.
[Herlenius, Marie Wahren] Karolinska Inst, Stockholm, Sweden.
[Witte, Torsten] Hannover Med Sch, D-3000 Hannover, Germany.
[Brennan, Michael T.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Omdal, Roald] Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
[Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England.
[Vyse, Timothy J.] Kings Coll London, Div Mol Med & Immunol, London WC2R 2LS, England.
[Lessard, James A.] Valley Bone & Joint Clin, Grand Forks, ND USA.
[Ng, Wan-Fai] Newcastle Univ, Inst Cellular Med, Musculoskeletal Res Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Rhodus, Nelson L.] Univ Minnesota, Minneapolis, MN USA.
[Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Benjamin A Rybicki ACCESS] Henry Ford Hosp, Detroit, MI 48202 USA.
[Anaya, Juan-Manuel] Univ Rosario Corp Invest Biol, Bogota, Colombia.
[Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.
[Moser, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA.
RI Adrianto, Indra/D-4214-2013; Witte, Torsten/B-5783-2016; Anaya,
Juan-Manuel/J-1960-2016
OI Adrianto, Indra/0000-0002-9973-3057; Anaya,
Juan-Manuel/0000-0002-6444-1249
NR 0
TC 1
Z9 1
U1 1
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 481
BP S184
EP S184
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621500481
ER
PT J
AU Li, H
Hsu, HC
Li, J
Wu, Q
Yang, PA
Cua, D
Mountz, JD
AF Li, Hao
Hsu, Hui-Chen
Li, Jun
Wu, Qi
Yang, PingAr
Cua, Daniel
Mountz, John D.
TI IL-23 Upregulates IRF5 and Polarizes Inflammatory M1 Macrophages to
Promote Inflammation in a Mouse Model of Arthritis.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Li, Hao; Hsu, Hui-Chen; Li, Jun; Wu, Qi; Yang, PingAr; Mountz, John D.] Univ Alabama, Birmingham, AL USA.
[Cua, Daniel] Merck Res Lab, Palo Alto, CA USA.
[Mountz, John D.] Birmingham VAMC, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2097
BP S816
EP S817
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502483
ER
PT J
AU Li, J
Hsu, HC
Yang, P
Wu, Q
Mountz, JD
AF Li, Jun
Hsu, Hui-Chen
Yang, PingAr
Wu, Qi
Mountz, John D.
TI Fucosylation Inhibitor, 2-D-Gal, Promotes Human Synovial Fibroblast
Apoptosis and Is a Potent Suppressor of Arthritis in a TNF-alpha Tg
Mouse Model In Vivo
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Li, Jun; Hsu, Hui-Chen; Yang, PingAr; Wu, Qi; Mountz, John D.] Univ Alabama, Birmingham, AL USA.
[Mountz, John D.] Birmingham VAMC, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2248
BP S879
EP S880
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502634
ER
PT J
AU Li, J
Hsu, HC
Yang, P
Wu, Q
Li, H
Mountz, JD
AF Li, Jun
Hsu, Hui-Chen
Yang, PingAr
Wu, Qi
Li, Hao
Mountz, John D.
TI Rebalancing the IL-23/Th17 Axis and Regulatory T Cells in Arthritis by
Depleting IRF5(+) IL-23(+) M1 Macrophages Using An Anti-Human DR5
Antibody
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Li, Jun; Hsu, Hui-Chen; Yang, PingAr; Wu, Qi; Li, Hao; Mountz, John D.] Univ Alabama, Birmingham, AL USA.
[Mountz, John D.] Birmingham VAMC, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 2246
BP S878
EP S879
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502632
ER
PT J
AU Liu, M
Wang, LW
Bongartz, T
Hawse, JR
Markovic, SN
Schaid, DJ
Goss, PE
Ingle, JN
Weinshilboum, RM
AF Liu, Mohan
Wang, Liewei
Bongartz, Tim
Hawse, John R.
Markovic, Svetomir N.
Schaid, Daniel J.
Goss, Paul E.
Ingle, James N.
Weinshilboum, Richard M.
TI Musculoskeletal Inflammation and Estrogens: T-Cell Leukemia 1A (TCL1A)
Gene-Dependent Regulation of Inflammatory Cytokines
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Liu, Mohan; Wang, Liewei; Bongartz, Tim; Hawse, John R.; Markovic, Svetomir N.; Schaid, Daniel J.; Ingle, James N.; Weinshilboum, Richard M.] Mayo Clin, Rochester, MN USA.
[Goss, Paul E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 1676
BP S655
EP S656
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502062
ER
PT J
AU Maxwell, JL
Felson, DT
Niu, JB
Wise, B
Nevitt, MC
Singh, J
Frey-Law, L
Neogi, T
AF Maxwell, Jessica L.
Felson, David T.
Niu, Jingbo
Wise, Barton
Nevitt, Michael C.
Singh, Jasvinder
Frey-Law, Laura
Neogi, Tuhina
TI Does Important Improvement in Function After Knee Replacement Guarantee
Good Absolute Function
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Felson, David T.; Niu, Jingbo; Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Wise, Barton] Ctr Hlth Aging UC Davis, Sacramento, CA USA.
[Nevitt, Michael C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Singh, Jasvinder] Univ Alabama, Birmingham, AL USA.
[Singh, Jasvinder] Birmingham VA Med Ctr, Birmingham, AL USA.
[Frey-Law, Laura] Univ Iowa, Iowa City, IA USA.
NR 0
TC 0
Z9 0
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 1541
BP S602
EP S602
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621501735
ER
PT J
AU Mohan, N
Hannon, MJ
Kwoh, CK
AF Mohan, Niveditha
Hannon, Michael J.
Kwoh, C. Kent
TI Correlation of Bony Enlargements with Radiological Findings in Hand
Osteoarthritis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Mohan, Niveditha] Univ Pittsburgh, Arth Inst, Pittsburgh, PA USA.
[Hannon, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Kwoh, C. Kent] VA Pittsburgh Healthcare, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 962
BP S377
EP S377
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621501157
ER
PT J
AU Mohan, N
Hannon, MJ
Kwoh, CK
AF Mohan, Niveditha
Hannon, Michael J.
Kwoh, C. Kent
TI Correlation of Hand Pain and Radiological Findings in Hand
Osteoarthritis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Mohan, Niveditha] Univ Pittsburgh, Arth Inst, Pittsburgh, PA USA.
[Hannon, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Kwoh, C. Kent] VA Pittsburgh Healthcare, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 963
BP S377
EP S378
PG 2
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621501158
ER
PT J
AU Monach, PA
Warner, RL
Tomasson, G
Specks, U
Stone, JH
Ding, L
Fervenza, F
Fessler, BJ
Hoffman, GS
Ikle, D
Kallenberg, CGM
Krischer, J
Langford, CA
Mueller, M
Seo, P
St Clair, EW
Spiera, R
Tchao, N
Ytterberg, SR
Johnson, KJ
Merkel, PA
AF Monach, Paul A.
Warner, Roscoe L.
Tomasson, Gunnar
Specks, Ulrich
Stone, John H.
Ding, Linna
Fervenza, Fernando
Fessler, Barri J.
Hoffman, Gary S.
Ikle, David
Kallenberg, Cees G. M.
Krischer, Jeffrey
Langford, Carol A.
Mueller, Mark
Seo, Philip
St Clair, E. William
Spiera, Robert
Tchao, Nadia
Ytterberg, Steven R.
Johnson, Kent J.
Merkel, Peter A.
TI Serum Proteins Reflecting Inflammation, Injury, and Repair As Biomarkers
of Disease Activity in ANCA-Associated Vasculitis.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Tomasson, Gunnar; Merkel, Peter A.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Warner, Roscoe L.; Johnson, Kent J.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Specks, Ulrich; Fervenza, Fernando; Ytterberg, Steven R.] Mayo Clin, Rochester, MN USA.
[Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ding, Linna] NIAID, Bethesda, MD 20892 USA.
[Fessler, Barri J.] Univ Alabama Birmingham, Birmingham, AL USA.
[Hoffman, Gary S.] Cleveland Clin Found A50, Cleveland, OH USA.
[Ikle, David] Rho, Chapel Hill, NC USA.
[Kallenberg, Cees G. M.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Krischer, Jeffrey] Univ S Florida, Tampa, FL USA.
[Langford, Carol A.] Cleveland Clin, Cleveland, OH 44106 USA.
[Mueller, Mark] US FDA, Bethesda, MD 20014 USA.
[Seo, Philip] Johns Hopkins Vasculitis Ctr, Baltimore, MD USA.
[St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA.
[Spiera, Robert] Hosp Special Surg, New York, NY 10021 USA.
[Tchao, Nadia] Immune Tolerance Network, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 792
BP S312
EP S312
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621500788
ER
PT J
AU Munroe, ME
Guthridge, JM
Kamen, DL
Norris, JM
Moser, KL
Niewold, TB
Gilkeson, GS
Karp, DR
Weisman, MH
Ishimori, ML
Wallace, DJ
Harley, JB
James, JA
AF Munroe, Melissa E.
Guthridge, Joel M.
Kamen, Diane L.
Norris, Jill M.
Moser, Kathy L.
Niewold, Timothy B.
Gilkeson, Gary S.
Karp, David R.
Weisman, Michael H.
Ishimori, Mariko L.
Wallace, Daniel J.
Harley, John B.
James, Judith A.
TI Altered Soluble Mediators of Inflammation At Baseline in Individuals Who
Subsequently Transition to Systemic Lupus Erythematosus: Early Studies
From the Lupus Autoimmunity in Relatives (LAUREL) Study
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Munroe, Melissa E.; Guthridge, Joel M.; Moser, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA.
[Kamen, Diane L.] Med Univ SC, Charleston, SC USA.
[Norris, Jill M.] Univ Colorado Denver, Aurora, CO USA.
[Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA.
[Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA.
[Karp, David R.] UT SW Med Ctr, Dallas, TX USA.
[Weisman, Michael H.; Ishimori, Mariko L.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Wallace, Daniel J.] Cedars Sinai UCLA, Los Angeles, CA USA.
[Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.
[James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 1663
BP S650
EP S650
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621502049
ER
PT J
AU Neogi, T
Niu, JB
Felson, DT
Nevitt, MC
Zhang, YQ
Frey-Law, L
Maxwell, JL
Singh, J
AF Neogi, Tuhina
Niu, Jingbo
Felson, David T.
Nevitt, Michael C.
Zhang, Yuqing
Frey-Law, Laura
Maxwell, Jessica L.
Singh, Jasvinder
TI Time-Course and Extent of Pain and Function Improvements Post-Knee
Replacement: The Multicenter Osteoarthritis Study
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT 75th Annual Scientific Meeting of the
American-College-of-Rheumatology/46th Annual Scientific Meeting of the
Association-of-Rheumatology-Health-Professionals
CY NOV 04-09, 2011
CL Chicago, IL
SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals
C1 [Neogi, Tuhina; Niu, Jingbo; Felson, David T.; Zhang, Yuqing; Maxwell, Jessica L.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Nevitt, Michael C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Frey-Law, Laura] Univ Iowa, Iowa City, IA USA.
[Singh, Jasvinder] Univ Alabama, Birmingham, AL USA.
[Singh, Jasvinder] Birmingham VA Med Ctr, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2011
VL 63
IS 10
SU S
MA 742
BP S289
EP S289
PG 1
WC Rheumatology
SC Rheumatology
GA 856EV
UT WOS:000297621500738
ER
EF