FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Morone, NE
Greco, CM
Rollman, BL
Moore, CG
Lane, B
Morrow, L
Glynn, NW
Delaney, J
Albert, SM
Weiner, DK
AF Morone, Natalia E.
Greco, Carol M.
Rollman, Bruce L.
Moore, Charity G.
Lane, Bridget
Morrow, Lisa
Glynn, Nancy W.
Delaney, Jill
Albert, Steven M.
Weiner, Debra K.
TI The design and methods of the aging successfully with pain study
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Low back pain; Older adult; Mindfulness; Meditation; Randomized clinical
trial
ID LOW-BACK-PAIN; LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE BATTERY;
SELF-REPORTED DISABILITY; STRESS REDUCTION PROGRAM; MINDFULNESS
MEDITATION; OLDER-ADULTS; PSYCHOMETRIC PROPERTIES; SUBSEQUENT
DISABILITY; CANCER OUTPATIENTS
AB Chronic low back pain (CLBP) is widespread among older adults (>= 65 years) and is often treated inadequately. With a rapidly growing aging population, CLBP will increase and so will the demand for treatment. We believe that mind-body therapies can help to meet this demand. We present the methodology of a randomized, controlled clinical trial of 300 individuals with CLBP aged 65 years or older. The specific aims are, 1) to determine the effectiveness of a mindfulness meditation program in increasing function and reducing pain among older adults with CLBP, and 2) to evaluate the impact of mindfulness meditation on neuropsychological performance in older adults with CLBP. The intervention program is modeled on the Mindfulness-Based Stress Reduction Program (MBSR) and the control is adapted from the 10 Keys (TM) to Healthy Aging. We will measure self-reported and objectively measured physical function and include a variety of measures to assess pain intensity and pain interference and psychological function. Our primary hypothesis is that the MBSR program will be more effective than the 10 Keys (TM) program in increasing function and decreasing pain. The proposed study represents the first large, well-controlled, comprehensive examination of the effects of a mind-body program on older adults with chronic pain. Published by Elsevier Inc.
C1 [Morone, Natalia E.; Rollman, Bruce L.; Moore, Charity G.; Lane, Bridget; Delaney, Jill] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Ctr Res Hlth Care, Pittsburgh, PA USA.
[Morone, Natalia E.; Weiner, Debra K.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
[Morone, Natalia E.; Rollman, Bruce L.; Moore, Charity G.; Weiner, Debra K.] Univ Pittsburgh, Sch Med, Clin & Translat Sci Inst, Pittsburgh, PA USA.
[Weiner, Debra K.] Univ Pittsburgh, Sch Med, Div Geriatr, Pittsburgh, PA USA.
[Greco, Carol M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Ctr Integrat Med,Med Ctr Shadyside, Pittsburgh, PA USA.
[Glynn, Nancy W.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Weiner, Debra K.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA.
[Albert, Steven M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA 15261 USA.
RP Morone, NE (reprint author), 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA.
EM moronene@upmc.edu
OI Moore, Charity/0000-0002-0060-0124; Albert, Steven/0000-0001-6786-9956;
Glynn, Nancy/0000-0003-2265-0162
FU National Institute on Aging [R01 AG034078-01]
FX This work was supported by a grant from the National Institute on Aging
R01 AG034078-01. Clinical trials.gov identifier: NCT01405716. The
contents do not represent the views of the Department of Veterans
Affairs or the United States Government.
NR 51
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Z9 7
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAR
PY 2012
VL 33
IS 2
BP 417
EP 425
DI 10.1016/j.cct.2011.11.012
PG 9
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 901JA
UT WOS:000300962000022
PM 22115971
ER
PT J
AU Lowery, JT
Marcus, A
Kinney, A
Bowen, D
Finkelstein, DM
Horick, N
Garrett, K
Haile, R
Sandler, R
Ahnen, DJ
AF Lowery, Jan T.
Marcus, Al
Kinney, Anita
Bowen, Deborah
Finkelstein, Dianne M.
Horick, Nora
Garrett, Kathleen
Haile, Robert
Sandler, Robert
Ahnen, Dennis J.
TI The Family Health Promotion Project (FHPP): Design and baseline data
from a randomized trial to increase colonoscopy screening in high risk
families
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Colonoscopy; High risk; Intervention; Randomized trial
ID NONPOLYPOSIS COLORECTAL-CANCER; COLON-CANCER; OLDER-ADULTS; BEHAVIOR;
SURVEILLANCE; RELATIVES; BARRIERS; MODEL; INDIVIDUALS; BELIEFS
AB Colorectal cancer (CRC) is a significant cause of mortality and morbidity in the United States, much of which could be prevented through adequate screening. Consensus guidelines recommend that high-risk groups initiate screening earlier with colonoscopy and more frequently than average risk persons. However, a large proportion of high risk individuals do not receive regular colonoscopic screening. The Family Health Promotion Project (FHPP) is a randomized-controlled trial to test the effectiveness of a telephone-based counseling intervention to increase adherence to risk-appropriate colonoscopy screening in high risk individuals. Unaffected members of CRC families from two national cancer family registries were enrolled (n = 632) and randomized to receive either a single session telephone counseling intervention using Motivational Interviewing techniques or a minimal mail-out intervention. The primary endpoint, rate of colonoscopy screening, was assessed at 6, 12 and 24 months post-enrollment. In this paper, we describe the research design and telephone counseling intervention of the FHPP trial, and report baseline data obtained from the two high risk cohorts recruited into this trial. Results obtained at baseline confirm the need for interventions to promote colonoscopy screening among these high risk individuals, as well as highlighting several key opportunities for intervention, including increasing knowledge about risk-appropriate screening guidelines, and providing both tailored risk information and barriers counseling. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Lowery, Jan T.; Marcus, Al; Garrett, Kathleen; Ahnen, Dennis J.] Univ Colorado, Ctr Canc, Div Canc Prevent & Control, Aurora, CO 80045 USA.
[Lowery, Jan T.] Univ Colorado, Colorado Sch Publ Hlth, Aurora, CO 80045 USA.
[Kinney, Anita] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA.
[Kinney, Anita] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Bowen, Deborah] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA.
[Finkelstein, Dianne M.; Horick, Nora] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Finkelstein, Dianne M.; Horick, Nora] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Haile, Robert] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Sandler, Robert] Univ N Carolina, Chapel Hill, NC USA.
[Ahnen, Dennis J.] Univ Colorado, Sch Med, Aurora, CO 80045 USA.
[Ahnen, Dennis J.] Vet Adm Med Ctr, Dept Med, Aurora, CO USA.
RP Lowery, JT (reprint author), Univ Colorado, Ctr Canc, Div Canc Prevent & Control, Anschutz Med Campus,Bldg 500,MS F-538,POB 6508, Aurora, CO 80045 USA.
EM jan.lowery@ucdenver.edu
FU National Cancer Institute [5R01CA68099]
FX Funded by National Cancer Institute, Grant #5R01CA68099.
NR 51
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Z9 8
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAR
PY 2012
VL 33
IS 2
BP 426
EP 435
DI 10.1016/j.cct.2011.11.005
PG 10
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 901JA
UT WOS:000300962000023
PM 22101228
ER
PT J
AU Grover, S
Ashley, SW
Raut, CP
AF Grover, Shilpa
Ashley, Stanley W.
Raut, Chandrajit P.
TI Small intestine gastrointestinal stromal tumors
SO CURRENT OPINION IN GASTROENTEROLOGY
LA English
DT Review
DE endoscopy; gastrointestinal stromal tumor; imatinib; sunitinib; surgery
ID TYROSINE-KINASE INHIBITOR; FINE-NEEDLE-ASPIRATION; GUIDED TRUCUT BIOPSY;
PHASE-II TRIAL; IMATINIB MESYLATE; C-KIT; GERMLINE MUTATION; IN-VITRO;
DIFFERENTIAL-DIAGNOSIS; SUBEPITHELIAL MASSES
AB Purpose of review
To review the contemporary management of gastrointestinal stromal tumor (GIST), including endoscopy, surgery, and systemic therapy, highlighting the aspects unique to small intestinal tumors.
Recent findings
Tumor size, mitotic count, and site of origin are the three key prognostic factors, with mitotic count being the single strongest predictor of recurrence. Tumors arising in the small bowel have worse prognosis than those of comparable size and mitotic count arising in other organs. Endoscopy and endoscopic ultrasound-guided, fine-needle aspiration are key components in the diagnosis of GIST. The role of endoscopy in surveillance and resection remain investigational. Surgery, either open or laparoscopic, remains the only curative option, but recurrence rates are high. Adjuvant therapy with imatinib mesylate improves recurrence-free survival rates and may improve overall survival (OS) with longer duration of treatment. Neoadjuvant imatinib may play an important role in the management of patients with locally advanced disease. For patients with advanced disease, first-line imatinib and second-line sunitinib malate have improved progression-free and OS rates. Systemic treatment should be continued life-long or until treatment failure.
Summary
Advances in the last decade have dramatically changed the management and prognosis of patients with primary and advanced GIST.
C1 [Ashley, Stanley W.; Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Grover, Shilpa] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA.
[Grover, Shilpa; Ashley, Stanley W.; Raut, Chandrajit P.] Harvard Univ, Sch Med, Boston, MA USA.
[Grover, Shilpa; Ashley, Stanley W.; Raut, Chandrajit P.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Raut, CP (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
EM craut@partners.org
NR 117
TC 18
Z9 22
U1 3
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0267-1379
J9 CURR OPIN GASTROEN
JI Curr. Opin. Gastroenterol.
PD MAR
PY 2012
VL 28
IS 2
BP 113
EP 123
DI 10.1097/MOG.0b013e32834ec154
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 898SW
UT WOS:000300763100004
PM 22157511
ER
PT J
AU Friedman, ES
Davis, LL
Zisook, S
Wisniewski, SR
Trivedi, MH
Fava, M
Rush, AJ
AF Friedman, Edward S.
Davis, Lori L.
Zisook, Sidney
Wisniewski, Stephen R.
Trivedi, Madhukar H.
Fava, Maurizio
Rush, A. John
CA CO-MED Study Team
TI Baseline depression severity as a predictor of single and combination
antidepressant treatment outcome: Results from the CO-MED trial
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Depression; Abuse; Suicide; Combination treatment severity; Response;
Remission
ID MEASUREMENT-BASED CARE; STAR-ASTERISK-D; DIAGNOSTIC SCREENING
QUESTIONNAIRE; REPORT QIDS-SR; SELF-REPORT; MAJOR DEPRESSION; QUICK
INVENTORY; PSYCHOMETRIC EVALUATION; PSYCHIATRIC-DISORDERS;
CLINICAL-PRACTICE
AB The objective of this manuscript is to report associations between baseline depressive severity and (1) baseline sociodemographic and clinical characteristics, (2) treatment outcomes, and (3) differential outcomes for three treatment groups. Six hundred and sixty-five outpatients with nonpsychotic, major depressive disorder were prospectively randomized to treatment with either a selective serotonin reuptake inhibitor (SSRI) monotherapy (escitalopram plus placebo) or one of two antidepressant medication combinations (bupropion-sustained release plus escitalopram, or venlafaxine-extended release plus mirtazapine). For purposes of these analyses, participants were divided into four groups based on baseline severity by the 16-item Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR16) total score: mild (0-10) [N=81], moderate (11-15) [N=238], severe (16-20) [N=260] and very severe (21-27) [N=67]. Treatment outcomes at 12 and 28 weeks were compared among the four severity groups. A history of childhood neglect and/or abuse was strongly associated with the severity of adult depression (1/2 of participants in the very severe group versus 1/5-1/4 of those in the mild group reported abuse and/or neglect). The degree of suicidality (e.g., 15/.4% of the very severe group ever attempted suicide versus none in the mild group), the number of suicide attempts (e.g., mean of .41 +/- 1.99 suicide attempts in the severe group versus 0.0 +/- 0.0 in the mild group) and severity of suicidality (e.g., 9.2% of participants in very severe group had a plan or made a gesture versus 5.6% in moderate group and none in the mild group) were increased in more severe groups. Participants with a greater baseline depressive severity reported significantly more psychiatric comorbidities (e.g. [at p<.05] increased rates of agoraphobia, bulimia, generalized anxiety, hypocondriasis, panic disorder, post-traumatic stress disorder, social phobia and somatoform disorder, with 23.9% of participants in the very severe group having reported four or more psychiatric disorders versus 1.2% of the mild group). Combination medication treatments were no more effective in treating severe depressions than was SSRI monotherapy. Remission (61.7% of participants in the mild group achieved remission versus 28.4% in the very severe group) is more difficult to achieve in more severe groups than is response (48.8% of participants in the mild group achieved response versus 58.2% in the very severe group) (p<.03). These data may help us to understand the impact of baseline features on antidepressant medication effectiveness and to inform the personalization of depression treatment across the spectrum of depressive severity. (C) 2011 Elsevier B.V. and ECNP. All rights reserved.
C1 [Friedman, Edward S.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA.
[Davis, Lori L.] VA Med Ctr, Res & Dev Serv, Tuscaloosa, AL USA.
[Davis, Lori L.] Univ Alabama, Sch Med, Dept Psychiat, Birmingham, AL USA.
[Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Zisook, Sidney] VA San Diego Hlth Care Syst, San Diego, CA USA.
[Wisniewski, Stephen R.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Rush, A. John] Duke NUS, Off Clin Sci, Singapore, Singapore.
RP Friedman, ES (reprint author), 3811 OHara St, Pittsburgh, PA 15213 USA.
EM friedmane@upmc.edu
OI Wisniewski, Stephen/0000-0002-3877-9860; Rush,
Augustus/0000-0003-2004-2382
FU NIMH [MH-9008, NO1MH90003]; Aspect Medical Systems; AstraZeneca;
Bristol-Myers Squibb; Cyberonics; Indevus; Medtronics; Northstar;
Novartis; Pfizer; Sanofi-Aventis; Wyeth-Ayerst; Repligen; Abbott
Laboratories, Inc.; Bristol-Myers Squibb Company (BMS); Eisai
Pharmaceuticals; Janssen; VA, NIMH, Shire; Southwestern Oncology Group,
Department of Defense (DoD); American Foundation for Suicide Prevention;
Department of Veterans Affairs; PamLab; Advanced Neuromodulation
Systems; Best Practice Project Management; Bristol-Myers Squibb/Otsuka;
Forest Pharmaceuticals; Gerson Lehrman Group; GlaxoSmithKline; Jazz
Pharmaceuticals; Magellan Health Services; Merck Company; Neuronetics;
Novartis Pharmaceuticals; Ono Pharmaceuticals; Organon; Otsuka
Pharmaceuticals; Transcept Pharmaceuticals; Urban Institute; Cyberonics
Inc.; Stanley Medical Research Institute; Forest Laboratories; Otsuka;
Guilford Publications; Healthcare Technology Systems
FX The authors are entirely responsible for the scientific content of this
paper. This study was supported and funded by NIMH grant MH-9008. We
would also like to acknowledge the editorial support of Jon Kilner, MS,
MA (Pittsburgh, PA). We acknowledge the administrative support of the
Research and Development Services at the participating VA Medical
Centers.; Edward S. Friedman M.D. has received grant/research support
from Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb,
Cyberonics, Indevus, Medtronics, Northstar, Novartis, Pfizer,
Sanofi-Aventis, Wyeth-Ayerst, Repligen; and has served on the speakers
bureaus or Advisory Boards for AstraZeneca, Eli Lilly, GlaxoSmithKline,
Pfizer, Wyeth-Ayerst, Bristol-Myers Squibb. Royalties: Springer.; Lori
L. Davis M.D. Research support (no personal income received from these
grants): Abbott Laboratories, Inc.; AstraZeneca; Bristol-Myers Squibb
Company (BMS); Eisai Pharmaceuticals; Janssen; VA, NIMH, Shire;
AstraZeneca; Southwestern Oncology Group, Department of Defense (DoD).
Advisory/Consulting: Cyberonics; Abbott; Shire; Constella; Eli Lilly.
Speaking: Abbott Laboratories; Cyberonics; Sanofi-Aventis; AstraZeneca.
Equity Holdings (exclude mutual funds/blinded trusts): Pfizer (until
2009). Royalty/patent, other income: None.; Sidney Zisook, M.D. has
received grant support from National Institute of Mental Health,
American Foundation for Suicide Prevention, the Department of Veterans
Affairs and PamLab.; John Rush, M.D., has received consultant fees from
Advanced Neuromodulation Systems, AstraZeneca, Best Practice Project
Management, Bristol-Myers Squibb/Otsuka, Cyberonics, Forest
Pharmaceuticals, Gerson Lehrman Group, GlaxoSmithKline, Jazz
Pharmaceuticals, Magellan Health Services, Merck & Company, Neuronetics,
Novartis Pharmaceuticals, Ono Pharmaceuticals, Organon, Otsuka
Pharmaceuticals, Pamlab, Pfizer, Transcept Pharmaceuticals, Urban
Institute and Wyeth-Ayerst; speaking fees from Cyberonics Inc., Forest
Laboratories, GlaxoSmithKline and Otsuka; royalties from Guilford
Publications, and Healthcare Technology Systems, and research support
from National Institute of Mental Health and the Stanley Medical
Research Institute. He has owned shares of stock in Pfizer.; This study
was supported and funded by NIMH grant NO1MH90003.
NR 46
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U1 1
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD MAR
PY 2012
VL 22
IS 3
BP 183
EP 199
DI 10.1016/j.euroneuro.2011.07.010
PG 17
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 902BK
UT WOS:000301013400002
PM 21920711
ER
PT J
AU Vallet, S
Witzens-Harig, M
Jaeger, D
Podar, K
AF Vallet, Sonia
Witzens-Harig, Mathias
Jaeger, Dirk
Podar, Klaus
TI Update on immunomodulatory drugs (IMiDs) in hematologic and solid
malignancies
SO EXPERT OPINION ON PHARMACOTHERAPY
LA English
DT Review
DE angiogenesis; birth defects; cereblon; immunomodulation; lenalidomide;
multiple myeloma; myelodysplastic syndromes; pomalidomide; thalidomide
ID DIAGNOSED MULTIPLE-MYELOMA; LOW-DOSE DEXAMETHASONE; STEM-CELL
TRANSPLANTATION; NATURAL-KILLER-CELL; PHASE-II TRIAL; LENALIDOMIDE PLUS
DEXAMETHASONE; SINGLE-AGENT LENALIDOMIDE; NECROSIS-FACTOR-ALPHA;
NON-HODGKINS-LYMPHOMA; MYELODYSPLASTIC SYNDROMES
AB Introduction: Thalidomide and its analogs [small molecule immunomodulatory drugs (IMiDs (R))] are among the most successful new therapeutic agents of recent years. Thalidomide is now an integral part of multiple myeloma (MM) therapy. Lenalidomide has been approved for the treatment of patients with relapsed MM and 5q-myelodysplastic syndromes (MDS). Currently, more than 400 clinical trials are evaluating the activity of lenalidomide, alone or in combination with other conventional or novel therapies, in newly diagnosed MM and 5q-MDS. Based on their broad range of actions within the tumor microenvironment, IMiDs are currently also evaluated in a wide variety of additional hematologic and solid malignancies.
Areas covered: This paper reviews the historic development of thalidomide and its derivatives and presents novel insights into their mode of action. Moreover, it discusses up-to-date clinical trials investigating IMiDs and potential future research and therapeutic perspectives in MM and other malignancies.
Expert opinion: Although IMiDs have emerged as powerful agents for the treatment of hematologic and solid tumors, more preclinical and clinical studies are urgently needed both to increase our knowledge of their mechanisms of action, and to optimize their clinical use, in order to further improve the patient's quality of life and survival.
C1 [Vallet, Sonia; Witzens-Harig, Mathias; Jaeger, Dirk; Podar, Klaus] Heidelberg Univ, Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
[Vallet, Sonia; Witzens-Harig, Mathias; Jaeger, Dirk; Podar, Klaus] German Canc Res Ctr, Heidelberg, Germany.
[Witzens-Harig, Mathias] Heidelberg Univ, Dept Hematol & Oncol, Heidelberg, Germany.
[Podar, Klaus] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
[Podar, Klaus] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA.
RP Podar, K (reprint author), Heidelberg Univ, Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
NR 186
TC 7
Z9 7
U1 3
U2 7
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-6566
J9 EXPERT OPIN PHARMACO
JI Expert Opin. Pharmacother.
PD MAR
PY 2012
VL 13
IS 4
BP 473
EP 494
DI 10.1517/14656566.2012.656091
PG 22
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 894UB
UT WOS:000300451400003
PM 22324734
ER
PT J
AU Souter, I
Dimitriadis, I
Thatcher, ML
Petrozza, JC
Wright, DL
AF Souter, Irene
Dimitriadis, Irene
Thatcher, Maria L.
Petrozza, John C.
Wright, Diane L.
TI The Prognostic Significance of An Elevated Day-3 FSH in Young Women (<=
35 Years) Undergoing In-Vitro Fertilization (IVF)
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Pacific-Coast-Reproductive-Society
CY APR 18-22, 2012
CL CA
SP Pacific Coast Reproduct Soc
C1 [Souter, Irene; Dimitriadis, Irene; Thatcher, Maria L.; Petrozza, John C.; Wright, Diane L.] Massachusetts Gen Hosp, Fertil Ctr, Dept Ob Gyn, Boston, MA 02114 USA.
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 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD MAR
PY 2012
VL 97
IS 3
SU S
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 900GX
UT WOS:000300876000030
ER
PT J
AU Chang, TE
Jing, YH
Yeung, AS
Brenneman, SK
Kalsekar, I
Hebden, T
McQuade, R
Baer, L
Kurlander, JL
Watkins, AK
Siebenaler, JA
Fava, M
AF Chang, Trina E.
Jing, Yonghua
Yeung, Albert S.
Brenneman, Susan K.
Kalsekar, Iftekhar
Hebden, Tony
McQuade, Robert
Baer, Lee
Kurlander, Jonathan L.
Watkins, Angela K.
Siebenaler, Jean A.
Fava, Maurizio
TI Effect of communicating depression severity on physician prescribing
patterns: findings from the Clinical Outcomes in MEasurement-based
Treatment (COMET) trial
SO GENERAL HOSPITAL PSYCHIATRY
LA English
DT Article
DE Depressive disorder; Primary health care; Self-report; Questionnaires;
Prescribing pattern
ID STAR-ASTERISK-D; COMORBIDITY SURVEY REPLICATION; PRIMARY-CARE;
COLLABORATIVE CARE; RANDOMIZED-TRIAL; UNITED-STATES; DOUBLE-BLIND;
AUGMENTATION; DISORDER; PSYCHIATRISTS
AB Objective: In this secondary analysis from the Clinical Outcomes in MEasurement-based Treatment trial (COMET), we evaluated whether providing primary care physicians with patient-reported feedback regarding depression severity affected pharmacological treatment patterns.
Method: Intervention-arm physicians received their patients' 9-item Patient Health Questionnaire scores monthly. Odds of having no change in antidepressant treatment during the 6-month study period were calculated. Relationships between depression symptom status (partial or nonresponse) at month 3 and treatment changes in months 3 through 6 were assessed.
Results: Among 503 intervention and 412 usual care (UC) patients with major depressive disorder, most received antidepressant monotherapy at baseline (79.4% UC vs. 88.4% intervention; P=.047). Few switched their baseline antidepressant (17.4%), increased their dose (12.4%) or augmented with a second medication (2%). Odds of having no change in antidepressant therapy did not differ significantly between study arms (odds ratio 1.21; 95% confidence interval 0.78-1.88; P=.392). Few month 3 partial or nonresponders had a regimen change over the following 3 months; the study arms did not differ significantly (partial responders: 4.1% UC vs. 7.7% intervention; P=.429; nonresponders: 14.6% UC vs. 15.9% intervention; P=.888).
Conclusions: Among depressed patients treated in primary care, little active management was observed. The lack of treatment modification for the majority of partial and nonresponders was notable. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Chang, Trina E.; Yeung, Albert S.; Baer, Lee; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA.
[Chang, Trina E.; Baer, Lee; Fava, Maurizio] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA 02114 USA.
[Jing, Yonghua; Kalsekar, Iftekhar; Hebden, Tony] Bristol Myers Squibb Co, Plainsboro, NJ 08536 USA.
[Brenneman, Susan K.; Kurlander, Jonathan L.; Watkins, Angela K.] OptumInsight, Eden Prairie, MN 55344 USA.
[McQuade, Robert] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ 08540 USA.
[Siebenaler, Jean A.] OptumInsight, Cincinnati, OH 45069 USA.
RP Chang, TE (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA.
EM techang@partners.org
FU Bristol-Myers Squibb (Princeton, NJ); Otsuka Pharmaceutical Co, Ltd
(Tokyo, Japan); Bristol-Myers Squibb
FX This study was funded by Bristol-Myers Squibb (Princeton, NJ) and Otsuka
Pharmaceutical Co, Ltd (Tokyo, Japan). The authors thank Elizabeth J.
Davis, PhD (medical writing, OptumInsight), Mia Eisenbart (OptumInsight
Site Management Center), Ross Baker, PhD (Otsuka Pharmaceutical), Edward
Kim, MD (formerly of Bristol-Myers Squibb), Kurt Kroenke, MD
(Regenstrief Institute, Inc.; Indiana University School of Medicine),
and Michael Klinkman, MS, MD (University of Michigan Department of
Family Medicine). Dr. Chang has received research support from companies
with an interest in depression treatment. Drs. Jing, Kalsekar, and
Hebden are employees of Bristol-Myers Squibb. Drs. Yeung and Baer have
no institutional or financial relationships that pose a conflict of
interest. Dr. Brenneman, Mr. Kurlander, Ms. Watkins, and Dr. Siebenaler
are employees of OptumInsight (formerly Innovus), an independent
research organization contracted by Bristol-Myers Squibb to conduct the
study. Dr. McQuade is an employee of Otsuka. Pharmaceutical Co, Ltd. Dr.
Fava has received research support from or served as a consultant to
companies with an interest in depression treatment. Presented in part at
NCDEU 2011, Boca Raton, June 13-16, 2011.
NR 36
TC 16
Z9 16
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0163-8343
J9 GEN HOSP PSYCHIAT
JI Gen. Hosp. Psych.
PD MAR-APR
PY 2012
VL 34
IS 2
BP 105
EP 112
DI 10.1016/j.genhosppsych.2011.12.003
PG 8
WC Psychiatry
SC Psychiatry
GA 902ET
UT WOS:000301022100001
PM 22264654
ER
PT J
AU Sadasivam, S
Duan, SH
DeCaprio, JA
AF Sadasivam, Subhashini
Duan, Shenghua
DeCaprio, James A.
TI The MuvB complex sequentially recruits B-Myb and FoxM1 to promote
mitotic gene expression
SO GENES & DEVELOPMENT
LA English
DT Article
DE DREAM complex; Myb-MuvB complex; B-Myb; FoxM1; ChIP sequencing; cell
cycle
ID CELL-CYCLE PROGRESSION; REPRESSOR COMPLEX; TRANSCRIPTIONAL NETWORK;
TERMINAL DOMAIN; DREAM COMPLEX; G(2)/M GENES; S-PHASE; PROTEIN;
PHOSPHORYLATION; IDENTIFICATION
AB Cell cycle progression is dependent on two major waves of gene expression. Early cell cycle gene expression occurs during G1/S to generate factors required for DNA replication, while late cell cycle gene expression begins during G2 to prepare for mitosis. Here we demonstrate that the MuvB complex-comprised of LIN9, LIN37, LIN52, LIN54, and RBBP4-serves an essential role in three distinct transcription complexes to regulate cell cycle gene expression. The MuvB complex, together with the Rb-like protein p130, E2F4, and DP1, forms the DREAM complex during quiescence and represses expression of both early and late genes. Upon cell cycle entry, the MuvB complex dissociates from p130/DREAM, binds to B-Myb, and reassociates with the promoters of late genes during S phase. MuvB and B-Myb are required for the subsequent recruitment of FoxM1 to late gene promoters during G2. The MuvB complex remains bound to FoxM1 during peak late cell cycle gene expression, while B-Myb binding is lost when it undergoes phosphorylation-dependent, proteasome-mediated degradation during late S phase. Our results reveal a novel role for the MuvB complex in recruiting B-Myb and FoxM1 to promote late cell cycle gene expression and in regulating cell cycle gene expression from quiescence through mitosis.
C1 [Sadasivam, Subhashini; DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Sadasivam, Subhashini; DeCaprio, James A.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02215 USA.
[Duan, Shenghua] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02215 USA.
RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM james_decaprio@dfci.harvard.edu
FU Public Health Service [P01CA050661, RO1CA93804, R01CA63113]; Susan F.
Smith Center for Women's Cancers, Dana-Farber Cancer Institute
FX We thank Eric McIntush (Bethyl Laboratories) for antibodies. We thank
the Microarray Core and the Center for Cancer Computational Biology
(CCCB) at Dana-Farber Cancer Institute for excellent assistance with
expression profiling and ChIP-seq, respectively. We thank all members of
the DeCaprio laboratory, N. Dyson (Massachusetts General Hospital), and
W. Tansey (Vanderbilt University) for discussions. We thank N. Dyson and
W. Wei (Beth Israel Deaconess Medical Center) for critically reading the
manuscript. S. D. thanks S. Bentink and B. Haibe-Kains (Dana-Farber
Cancer Institute) for discussions. We thank M. Correll (CCCB) for
critically reviewing the bioinformatics analysis presented here. We
thank Dustin Holloway (CCCB) for the bioinformatics analysis on FoxM1
and CHR motifs. This work was supported in part by Public Health Service
grants P01CA050661, RO1CA93804, and R01CA63113 to J.A.D., and a research
grant from the Susan F. Smith Center for Women's Cancers, Dana-Farber
Cancer Institute to S. S. S. S. designed and performed all of the
experiments, analyzed data, and wrote the paper; S. D. performed
bioinformatics analysis and helped with generating Figures 2 and 3; and
J.A.D. designed experiments, gave conceptual advice, and wrote the
paper.
NR 55
TC 79
Z9 82
U1 0
U2 6
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
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD MAR 1
PY 2012
VL 26
IS 5
BP 474
EP 489
DI 10.1101/gad.181933.111
PG 16
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 904KZ
UT WOS:000301196100007
PM 22391450
ER
PT J
AU Graham-Jones, P
Jain, SH
Friedman, CP
Marcotte, L
Blumenthal, D
AF Graham-Jones, Pierce
Jain, Sachin H.
Friedman, Charles P.
Marcotte, Leah
Blumenthal, David
TI The Need To Incorporate Health Information Technology Into Physicians'
Education And Professional Development
SO HEALTH AFFAIRS
LA English
DT Article
AB Nationwide, as physicians and health care systems adopt electronic health records, health information technology is becoming integral to the practice of medicine. But current medical education and professional development curricula do not systematically prepare physicians to use electronic health records and the data these systems collect. We detail how training in meaningful use of electronic health records could be incorporated into physician training, from medical school, through licensure and board certification, to continuing medical education and the maintenance of licensure and board certification. We identify six near-term opportunities for professional organizations to accelerate the integration of health information technology into their requirements.
C1 [Graham-Jones, Pierce] US Dept HHS, Beacon Community Program, Off Natl Coordinator Hlth Informat Technol, Washington, DC 20201 USA.
[Jain, Sachin H.] Harvard Univ, Sch Business, Inst Strategy & Competitiveness, Boston, MA 02163 USA.
[Friedman, Charles P.] Univ Michigan, Sch Informat, Hlth Informat Program, Ann Arbor, MI 48109 USA.
[Friedman, Charles P.] Univ Michigan, Sch Publ Hlth, Hlth Informat Program, Ann Arbor, MI 48109 USA.
[Marcotte, Leah] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Blumenthal, David] Partners HealthCare Syst, Massachusetts Gen Hosp, Boston, MA USA.
[Blumenthal, David] Harvard Univ, Sch Med, Boston, MA USA.
RP Graham-Jones, P (reprint author), US Dept HHS, Beacon Community Program, Off Natl Coordinator Hlth Informat Technol, Washington, DC 20201 USA.
EM pierce.graham-jones@hhs.gov
NR 22
TC 17
Z9 17
U1 0
U2 16
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD MAR
PY 2012
VL 31
IS 3
BP 481
EP 487
DI 10.1377/hlthaff.2011.0423
PG 7
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 904UQ
UT WOS:000301223800004
PM 22392658
ER
PT J
AU Zen, AL
Whooley, MA
Zhao, SJ
Cohen, BE
AF Zen, Angelica L.
Whooley, Mary A.
Zhao, Shoujun
Cohen, Beth E.
TI Post-Traumatic Stress Disorder is Associated With Poor Health Behaviors:
Findings From the Heart and Soul Study
SO HEALTH PSYCHOLOGY
LA English
DT Article
DE posttraumatic stress disorder; health behaviors; smoking; physical
activity; medication adherence
ID PHYSICAL-ACTIVITY; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE;
MEDICATION ADHERENCE; DEPRESSIVE SYMPTOMS; CONSTRUCT-VALIDITY; PROBLEM
DRINKING; RISK; NONADHERENCE; VETERANS
AB Objective: Posttraumatic stress disorder (PTSD) results in substantial disability, including increased risk of cardiovascular disease (CVD). Poor health behaviors are major risk factors for initial and recurrent CVD events. Therefore, this study investigated whether PTSD is associated with poor health behaviors in patients with CVD. Method: Cross-sectional study of 1,022 men and women with CVD. PTSD was assessed with the Computerized Diagnostic Interview Schedule for DSM-IV. Physical activity, medication adherence and smoking history were determined by self-report questionnaires. Multivariate logistic and linear regression models were used to evaluate the association of PTSD with health behaviors. Results: Of the 1,022 participants, 95 (9%) had PTSD. PTSD was associated with significantly higher rates of physical inactivity in terms of overall exercise (OR 1.6, 95% CI [1.0-2.6]; p = .049), light exercise (OR 1.7, 95% CI [1.0-2.9]; p = .045), and self-rated level of exercise compared to others of their age and sex (OR 1.8, 95% CI [1.0-3.0]; p = .047). Participants with PTSD were more likely to report medication nonadherence, including forgetting medications (OR 1.8, 95% CI [1.0-3.3]; p = .04) or skipping medications (OR 1.7, 95% CI [1.1-2.9]; p = .03). Participants with PTSD also reported a greater smoking history (beta 6.4 pack years, 95% CI [1.8-10.9]; p = .006), which remained significant after adjustment for depression and income. Conclusions: Among patients with heart disease, those with PTSD were more likely to report physical inactivity, medication nonadherence and smoking. The majority of these associations were explained by adjustment for comorbid depression and lower income.
C1 [Whooley, Mary A.; Cohen, Beth E.] San Francisco VA Med Ctr, Dept Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA.
[Zen, Angelica L.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Whooley, Mary A.; Cohen, Beth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Zhao, Shoujun] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA.
RP Cohen, BE (reprint author), San Francisco VA Med Ctr, Dept Vet Affairs Med Ctr, Gen Internal Med Sect, Box 111A1, San Francisco, CA 94121 USA.
EM beth.cohen@va.gov
RI Schueter, nicos/A-3625-2014
FU NIH/NHLBI [K23 HL 094765-01]; Department of Defense/NCIRE
[DAMD17-03-1-0532, W81XWH-05-2-0094]; Irene Perstein Foundation;
Department of Veterans Affairs, Washington, DC; National Heart Lung and
Blood Institute, Bethesda, MD [R01 HL079235]; American Federation for
Aging Research, New York, NY; Robert Wood Johnson Foundation, Princeton,
NJ; Ischemia Research and Education Foundation, South San Francisco, CA;
Nancy Kirwan Heart Research Fund, San Francisco, CA
FX The authors do not have any conflicts of interest. Preliminary data for
this article was presented as an abstract at the American Geriatrics
Society, 2010 meeting. Dr. Cohen was supported by NIH/NHLBI grant K23 HL
094765-01, Department of Defense/NCIRE grant DAMD17-03-1-0532,
W81XWH-05-2-0094, and a grant from the Irene Perstein Foundation. The
Heart and Soul Study was funded by the Department of Veterans Affairs,
Washington, DC, the National Heart Lung and Blood Institute (R01
HL079235), Bethesda, MD, the American Federation for Aging Research
(Paul Beeson Scholars Program), New York, NY, the Robert Wood Johnson
Foundation (Faculty Scholars Program), Princeton, NJ, the Ischemia
Research and Education Foundation, South San Francisco, CA, and the
Nancy Kirwan Heart Research Fund, San Francisco, CA. The contents of
this work are solely the responsibility of the authors and do not
necessarily represent the official views of any of these funding
agencies. The funding organizations were not involved in the design and
conduct of the study; collection, management, analysis, and
interpretation of the data; or preparation, review, or approval of the
manuscript.
NR 43
TC 51
Z9 51
U1 1
U2 12
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0278-6133
J9 HEALTH PSYCHOL
JI Health Psychol.
PD MAR
PY 2012
VL 31
IS 2
BP 194
EP 201
DI 10.1037/a0025989
PG 8
WC Psychology, Clinical; Psychology
SC Psychology
GA 907BM
UT WOS:000301392800009
PM 22023435
ER
PT J
AU Shi, Y
Meeker, WQ
AF Shi, Ying
Meeker, William Q.
TI Bayesian Methods for Accelerated Destructive Degradation Test Planning
SO IEEE TRANSACTIONS ON RELIABILITY
LA English
DT Article
DE Compromise plan; general equivalence theorem; large-sample
approximation; log-location-scale distribution; optimum plan
ID OPTIMAL EXPERIMENTAL-DESIGN
AB Accelerated Destructive Degradation Tests (ADDTs) provide timely product reliability information in practical applications. This paper describes Bayesian methods for ADDT planning under a class of nonlinear degradation models with one accelerating variable. We use a Bayesian criterion based on the estimation precision of a specified failure-time distribution quantile at use conditions to find optimum test plans. A large-sample approximation for the posterior distribution provides a useful simplification to the planning criterion. The general equivalence theorem (GET) is used to verify the global optimality of the numerically optimized test plans. Optimum plans usually provide insight for constructing compromise plans which tend to be more robust, and practically useful. We present a numerical example with a log-location-scale distribution to illustrate the Bayesian test planning methods, and to investigate the effects of the prior distribution and sample size on test planning results.
C1 [Shi, Ying] San Francisco VA Med Ctr, No Calif Inst Res & Educ, San Francisco, CA 94121 USA.
[Meeker, William Q.] Iowa State Univ, Dept Stat, Ames, IA 50011 USA.
RP Shi, Y (reprint author), San Francisco VA Med Ctr, No Calif Inst Res & Educ, San Francisco, CA 94121 USA.
EM ying.shi2@va.gov; wqmeeker@iastate.edu
NR 16
TC 17
Z9 19
U1 3
U2 24
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9529
J9 IEEE T RELIAB
JI IEEE Trans. Reliab.
PD MAR
PY 2012
VL 61
IS 1
BP 245
EP 253
DI 10.1109/TR.2011.2170115
PG 9
WC Computer Science, Hardware & Architecture; Computer Science, Software
Engineering; Engineering, Electrical & Electronic
SC Computer Science; Engineering
GA 904LP
UT WOS:000301198500028
ER
PT J
AU Palacios, E
Franke, M
Munoz, M
Hurtado, R
Dallman, R
Chalco, K
Guerra, D
Mestanza, L
Llaro, K
Bonilla, C
Sebastian, J
Bayona, J
Lyzigos, M
Anger, H
Shin, S
AF Palacios, E.
Franke, M.
Munoz, M.
Hurtado, R.
Dallman, R.
Chalco, K.
Guerra, D.
Mestanza, L.
Llaro, K.
Bonilla, C.
Sebastian, J.
Bayona, J.
Lyzigos, M.
Anger, H.
Shin, S.
TI HIV-positive patients treated for multidrug-resistant tuberculosis:
clinical outcomes in the HAART era
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Article
DE HIV; multidrug-resistant tuberculosis; resource-poor settings;
antiretroviral therapy; clinical outcomes
ID NEW-YORK-CITY; VIRUS-INFECTED PATIENTS; ANTIRETROVIRAL THERAPY;
DRUG-RESISTANCE; ADVERSE EVENTS; RISK-FACTORS; SURVIVAL; PREDICTORS;
TARGETS; IMPACT
AB SETTING: Multidrug-resistant tuberculosis (MDR-TB) and the human immunodeficiency virus (HIV) pose two of the greatest threats to global tuberculosis (TB) control. Given expanding global access to antiretroviral therapy (ART) and second-line TB drugs, more data are needed on experiences treating MDR-TB and HIV co-infection in resource-poor settings.
OBJECTIVE: To describe the clinical characteristics, management, outcomes, and factors associated with survival among HIV-positive individuals receiving treatment for MDR-TB.
DESIGN: This was a retrospective case series of 52 HIV-positive individuals receiving treatment for MDR-TB in Lima, Peru. We used Cox proportional hazards regression models to identify risk factors for mortality.
RESULTS: A total of 31 (57%) of the cohort died on treatment, with the majority of deaths due to MDR-TB. Low baseline weight predicted a three-fold increased rate of death (aHR 3.1, 95%CI 1.5-6.7), while individuals receiving highly active ART experienced a significantly lower rate of death compared to those who were not (aHR 0.4, 95 %CI 0.2-0.9).
CONCLUSION: Early ART is likely a key component of effective MDR-TB management in co-infected individuals.
C1 [Shin, S.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA.
[Palacios, E.; Munoz, M.; Chalco, K.; Guerra, D.; Mestanza, L.; Llaro, K.; Bayona, J.; Anger, H.] Socios Salud, Sucursal Peru, Lima, Peru.
[Franke, M.; Shin, S.] Harvard Univ, Sch Med, Boston, MA USA.
[Hurtado, R.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
[Dallman, R.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA.
[Bonilla, C.] Minist Salud, Natl TB Program, Lima, Peru.
[Sebastian, J.] Minist Salud, Peruvian HIV Program, Lima, Peru.
[Lyzigos, M.] Univ Michigan, Sch Med, Ann Arbor, MI USA.
RP Shin, S (reprint author), Brigham & Womens Hosp, Div Global Hlth Equ, 7th Floor,FXB Bldg,651 Huntington Ave, Boston, MA 02115 USA.
EM sshin@partners.org
NR 40
TC 23
Z9 23
U1 0
U2 6
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
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD MAR
PY 2012
VL 16
IS 3
BP 348
EP 354
DI 10.5588/ijtld.11.0473
PG 7
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA 903DY
UT WOS:000301097500012
PM 22640448
ER
PT J
AU Camargo, CA
AF Camargo, Carlos A., Jr.
TI Potter Stewart and the definition of anaphylaxis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Editorial Material
DE Anaphylaxis
ID EMERGENCY-DEPARTMENT VISITS; REPEAT EPINEPHRINE TREATMENTS; ALLERGIC
REACTIONS; FOOD; MULTICENTER; ORGANIZATION
C1 [Camargo, Carlos A., Jr.] Harvard Univ, Div Rheumatol Allergy & Immunol, Dept Med, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Camargo, CA (reprint author), Harvard Univ, Div Rheumatol Allergy & Immunol, Dept Med, Massachusetts Gen Hosp,Med Sch, 326 Cambridge St,Suite 410, Boston, MA 02114 USA.
EM ccamargo@partners.org
NR 16
TC 3
Z9 3
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
BP 753
EP 754
DI 10.1016/j.jaci.2012.01.030
PG 2
WC Allergy; Immunology
SC Allergy; Immunology
GA 904IW
UT WOS:000301189300021
PM 22285277
ER
PT J
AU Walsh, J
Arora, M
Hosenfeld, C
Ladabaum, U
Kuppermann, M
Knight, SJ
AF Walsh, Judith
Arora, Millie
Hosenfeld, Christina
Ladabaum, Uri
Kuppermann, Miriam
Knight, Sara J.
TI Preferences for Genetic Testing to Identify Hereditary Colorectal
Cancer: Perspectives of High-Risk Patients, Community Members, and
Clinicians
SO JOURNAL OF CANCER EDUCATION
LA English
DT Article
DE Colorectal cancer screening; Preferences; Focus groups
ID BREAST-CANCER; COLON-CANCER; ATTITUDES; KNOWLEDGE; SUSCEPTIBILITY;
PERCEPTIONS; WOMEN; INDIVIDUALS; ASSOCIATION; RELATIVES
AB The aim of this study was to establish key characteristics that patients, consumers, and health professionals value regarding genetic testing (GT) and personalized medicine using the example of GT for hereditary Lynch syndrome. We conducted a series of focus groups with individuals recruited from a clinic that follows those at high risk for hereditary cancer, individuals recruited from the community, physicians, and genetic counselors. Participants were presented with clinical scenarios about Lynch syndrome testing and asked to identify characteristics that they perceived as important in making decisions about GT. Forty-two participants (19 community members, 8 high-risk and cancer patients, 3 genetic counselors, and 8 physicians) participated. Among community members and patients, the most frequently discussed considerations were the personal impact of GT and family impact, respectively. Among physicians, the most frequently discussed topic was the characteristics of genomic services (e.g., test invasiveness); among genetic counselors, the most frequently discussed topic was evidence and recommendations. A variety of test characteristics were important in decision making about GT. High-risk patients, community members, and health care providers had different priorities. Health care professionals should be aware of differences between their own considerations about GT and those that are important to patients.
C1 [Walsh, Judith] UCSF Womens Hlth Clin Res Ctr, San Francisco, CA 94115 USA.
[Walsh, Judith; Arora, Millie] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA.
[Hosenfeld, Christina] Univ Calif San Francisco, Dept Pharm, San Francisco, CA USA.
[Ladabaum, Uri] Stanford Univ, Div Gastroenterol, Palo Alto, CA 94304 USA.
[Kuppermann, Miriam] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA.
[Kuppermann, Miriam] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Knight, Sara J.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA.
RP Walsh, J (reprint author), UCSF Womens Hlth Clin Res Ctr, 1635 Divisadero Suite 600, San Francisco, CA 94115 USA.
EM Judith.Walsh@ucsf.edu
NR 26
TC 8
Z9 8
U1 3
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-8195
J9 J CANCER EDUC
JI J. Cancer Educ.
PD MAR
PY 2012
VL 27
IS 1
BP 112
EP 119
DI 10.1007/s13187-011-0286-z
PG 8
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
Occupational Health
GA 895IU
UT WOS:000300490600019
PM 22131063
ER
PT J
AU Pagan, JA
Brown, CJ
Asch, DA
Armstrong, K
Bastida, E
Guerra, C
AF Pagan, Jose A.
Brown, Cynthia J.
Asch, David A.
Armstrong, Katrina
Bastida, Elena
Guerra, Carmen
TI Health Literacy and Breast Cancer Screening among Mexican American Women
in South Texas
SO JOURNAL OF CANCER EDUCATION
LA English
DT Article
DE Mammography; Mexican American; Health literacy
ID HISPANIC WOMEN; MAMMOGRAPHY; DISPARITIES; LATINAS; CARE
AB Breast cancer is the main cause of cancer deaths for Hispanic women. This study analyzes the role of functional health literacy on mammography screening behavior and adherence of Hispanic women. Survey data from 722 Mexican American women age 40 and over residing in the Lower Rio Grande Valley of Texas in 2008 were used to estimate logistic regression models to assess the role of functional health literacy on mammography screening behavior and adherence. About 51% of survey respondents had a functional health literacy level deemed as inadequate or marginally functional. After adjusting for other factors, women with adequate health literacy levels were more likely to report to have ever had a mammogram (odds ratio [OR] = 2.92; 95% confidence interval [CI] = 1.62-5.28), to have had a mammogram within the last 2 years (OR = 1.70; 95% CI = 1.14-2.53) or to have had one within the last year (OR = 2.30; 95% CI = 1.54-3.43), compared to women with inadequate or marginally adequate functional health literacy levels. Inadequate/marginal functional health literacy is strongly associated with lower mammography screening. Large improvements in breast cancer control in this population may come from either basic advances in health literacy or by tailored approaches to help women with low literacy navigate local health care systems.
C1 [Pagan, Jose A.] Univ N Texas, Hlth Sci Ctr, Sch Publ Hlth, Dept Hlth Management & Policy, Ft Worth, TX 76107 USA.
[Pagan, Jose A.; Asch, David A.; Armstrong, Katrina] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Brown, Cynthia J.] Univ Texas Pan Amer, Coll Business Adm, Dept Econ & Finance, Edinburg, TX 78541 USA.
[Asch, David A.; Armstrong, Katrina; Guerra, Carmen] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Bastida, Elena] Florida Int Univ, Robert Stempel Coll Publ Hlth & Social Work, Dept Hlth Promot & Dis Prevent, Miami, FL 33199 USA.
RP Pagan, JA (reprint author), Univ N Texas, Hlth Sci Ctr, Sch Publ Hlth, Dept Hlth Management & Policy, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA.
EM jose.pagan@unthsc.edu
OI Asch, David/0000-0002-7970-286X
NR 23
TC 13
Z9 13
U1 2
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-8195
J9 J CANCER EDUC
JI J. Cancer Educ.
PD MAR
PY 2012
VL 27
IS 1
BP 132
EP 137
DI 10.1007/s13187-011-0239-6
PG 6
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
Occupational Health
GA 895IU
UT WOS:000300490600021
PM 21573944
ER
PT J
AU Lopez-Jimenez, F
Kramer, VC
Masters, B
Stuart, PW
Mullooly, C
Hinshaw, L
Haas, L
Warwick, K
AF Lopez-Jimenez, Francisco
Kramer, Valerie Carroll
Masters, Barbara
Stuart, Patricia (Mickey) W.
Mullooly, Cathy
Hinshaw, Ling
Haas, Linda
Warwick, Kathy
TI Recommendations for Managing Patients With Diabetes Mellitus in
Cardiopulmonary Rehabilitation AN AMERICAN ASSOCIATION OF CARDIOVASCULAR
AND PULMONARY REHABILITATION STATEMENT
SO JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION
LA English
DT Article
DE cardiopulmonary rehabilitation; diabetes mellitus; scientific review;
blood glucose monitoring; exercise
ID CORONARY-ARTERY-DISEASE; CARDIAC REHABILITATION; GLYCEMIC CONTROL;
MYOCARDIAL-INFARCTION; SCIENTIFIC STATEMENT; PREVENTION PROGRAMS;
METABOLIC SYNDROME; HEART-ASSOCIATION; BETA-BLOCKER; TASK-FORCE
AB Diabetes mellitus is a highly prevalent condition in patients participating in cardiopulmonary rehabilitation. However, research and subsequent guidelines specifically applicable to patients with diabetes, participating in cardiopulmonary rehabilitation, are limited. Recognizing this limitation, the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) initiated this statement, with the goal of developing a template that incorporated recommendations provided in the AACVPR Core Components and the American Association of Diabetes Educators 7 Self-Care Behaviors. This statement describes key processes regarding evaluation, interventions, and expected outcomes in each of the core components for the management of patients with diabetes in a cardiopulmonary rehabilitation program.
C1 [Lopez-Jimenez, Francisco; Hinshaw, Ling] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[Kramer, Valerie Carroll] Northwestern Univ, Evanston Hosp, NorthShore Univ HealthSyst, Evanston, IL 60201 USA.
[Masters, Barbara] Protestant Mem Med Ctr, Belleville, IL USA.
[Stuart, Patricia (Mickey) W.] Diabet Educ & Etc LLC, Vicksburg, MS USA.
[Mullooly, Cathy] Novo Nordisk Inc, Boston, MA USA.
[Haas, Linda] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Haas, Linda] VHA Off Nursing Serv, Washington, DC USA.
[Warwick, Kathy] Profess Nutr Consultants LLC, Jackson, MS USA.
RP Kramer, VC (reprint author), 709 Newgate, Prospect Heights, IL 60070 USA.
EM valeriekramer@comcast.net
OI Hinshaw, Ling/0000-0002-6103-8294
NR 47
TC 7
Z9 8
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1932-7501
J9 J CARDIOPULM REHABIL
JI J. Cardiopulm. Rehabil. Prev.
PD MAR-APR
PY 2012
VL 32
IS 2
BP 101
EP 112
DI 10.1097/HCR.0b013e31823be0bc
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 901EG
UT WOS:000300943900006
PM 22198371
ER
PT J
AU Banerji, V
Frumm, SM
Ross, KN
Li, LS
Schinzel, AC
Hahn, CK
Kakoza, RM
Chow, KT
Ross, L
Alexe, G
Tolliday, N
Inguilizian, H
Galinsky, I
Stone, RM
DeAngelo, DJ
Roti, G
Aster, JC
Hahn, WC
Kung, AL
Stegmaier, K
AF Banerji, Versha
Frumm, Stacey M.
Ross, Kenneth N.
Li, Loretta S.
Schinzel, Anna C.
Hahn, Cynthia K.
Kakoza, Rose M.
Chow, Kwan T.
Ross, Linda
Alexe, Gabriela
Tolliday, Nicola
Inguilizian, Haig
Galinsky, Ilene
Stone, Richard M.
DeAngelo, Daniel J.
Roti, Giovanni
Aster, Jon C.
Hahn, William C.
Kung, Andrew L.
Stegmaier, Kimberly
TI The intersection of genetic and chemical genomic screens identifies
GSK-3 alpha as a target in human acute myeloid leukemia
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID GLYCOGEN-SYNTHASE KINASE-3; NF-KAPPA-B; THERAPEUTIC TARGET; CELL-GROWTH;
STEM-CELLS; LITHIUM; INHIBITION; GSK-3; AML; NEUTROPENIA
AB Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Long-term survival of patients with AML has changed little over the past decade, necessitating the identification and validation of new AML targets. Integration of genomic approaches with small-molecule and genetically based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. Here, we identified a role for glycogen synthase kinase 3 alpha (GSK-3 alpha) in AML by performing 2 independent small-molecule library screens and an shRNA screen for perturbations that induced a differentiation expression signature in AML cells. GSK-3 is a serine-threonine kinase involved in diverse cellular processes, including differentiation, signal transduction, cell cycle regulation, and proliferation. We demonstrated that specific loss of GSK-3 alpha induced differentiation in AML by multiple measurements, including induction of gene expression signatures, morphological changes, and cell surface markers consistent with myeloid maturation. GSK-3 alpha-specific suppression also led to impaired growth and proliferation in vitro, induction of apoptosis, loss of colony formation in methylcellulose, and anti-AML activity in vivo. Although the role of GSK-3 beta has been well studied in cancer development, these studies support a role for GSK-3 alpha in AML.
C1 [Banerji, Versha; Frumm, Stacey M.; Li, Loretta S.; Hahn, Cynthia K.; Kakoza, Rose M.; Chow, Kwan T.; Ross, Linda; Alexe, Gabriela; Inguilizian, Haig; Roti, Giovanni; Kung, Andrew L.; Stegmaier, Kimberly] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Banerji, Versha; Frumm, Stacey M.; Li, Loretta S.; Hahn, Cynthia K.; Kakoza, Rose M.; Chow, Kwan T.; Ross, Linda; Alexe, Gabriela; Inguilizian, Haig; Roti, Giovanni; Kung, Andrew L.; Stegmaier, Kimberly] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Ross, Kenneth N.; Schinzel, Anna C.; Tolliday, Nicola; Hahn, William C.; Stegmaier, Kimberly] Broad Inst MIT, Cambridge, MA USA.
[Ross, Kenneth N.; Schinzel, Anna C.; Tolliday, Nicola; Hahn, William C.; Stegmaier, Kimberly] Harvard Univ, Cambridge, MA 02138 USA.
[Schinzel, Anna C.; Galinsky, Ilene; Stone, Richard M.; DeAngelo, Daniel J.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
RP Stegmaier, K (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM kimberly_stegmaier@dfci.harvard.edu
FU National Cancer Institute [R01 CA140292]; American Cancer Society; ASH
Fellow Scholar Award in Clinical/Translational Research; Howard Hughes
Medical Institute; Smith Family New Investigator Award; Boston
Foundation; CancerCare Manitoba; CancerCare Manitoba Foundation;
University of Manitoba; Terry Fox Foundation through National Cancer
Institute of Canada
FX We thank Serena Silver, Jen Grenier, and David Root for RNAi screening
guidance and the Chemical Biology Platform at the Broad Institute. We
thank all of the patients who contributed invaluable primary samples. We
thank Alexandre Puissant, Annie Carlton, and Jacob Berchuck for their
technical advice and assistance. This work was supported by the National
Cancer Institute (R01 CA140292) (to K. Stegmaier), the American Cancer
Society (to K. Stegmaier), an ASH Fellow Scholar Award in
Clinical/Translational Research (to K. Stegmaier), Howard Hughes Medical
Institute (to K. Stegmaier and L.S. Li), a Smith Family New Investigator
Award supported by the Richard Allan Barry Fund at the Boston Foundation
(to K. Stegmaier), CancerCare Manitoba (to V. Banerji), CancerCare
Manitoba Foundation (to V. Banerji), the University of Manitoba (to V.
Banerji), and the Terry Fox Foundation through an award from the
National Cancer Institute of Canada (to V. Banerji).
NR 48
TC 34
Z9 36
U1 2
U2 13
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD MAR
PY 2012
VL 122
IS 3
BP 935
EP 947
DI 10.1172/JCI46465
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 902EN
UT WOS:000301021500019
PM 22326953
ER
PT J
AU Lengerova, M
Kocmanova, I
Racil, Z
Hrncirova, K
Pospisilova, S
Mayer, J
Najvar, LK
Wiederhold, NP
Kirkpatrick, WR
Patterson, TF
AF Lengerova, Martina
Kocmanova, Iva
Racil, Zdenek
Hrncirova, Kristyna
Pospisilova, Sarka
Mayer, Jiri
Najvar, Laura K.
Wiederhold, Nathan P.
Kirkpatrick, William R.
Patterson, Thomas F.
TI Detection and Measurement of Fungal Burden in a Guinea Pig Model of
Invasive Pulmonary Aspergillosis by Novel Quantitative Nested Real-Time
PCR Compared with Galactomannan and (1,3)-beta-D-Glucan Detection
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID BRONCHOALVEOLAR LAVAGE FLUID; EXPERIMENTAL MURINE ASPERGILLOSIS;
ENZYME-IMMUNOASSAY; FUMIGATUS; DIAGNOSIS; SERUM; DNA; SEQUENCE; RELEASE
AB We developed and assessed the diagnostic value of a novel quantitative nested real-time (QNRT) PCR assay targeting the internal transcribed spacer region of ribosomal DNA (rDNA) in a guinea pig model of invasive pulmonary aspergillosis. Groups of 5 immunosuppressed animals that were infected using an aerosol chamber with Aspergillus fumigatus conidia were humanely terminated 1 h postinoculation and at days 3, 5, 7, and 11 postchallenge, and lung tissue, bronchoalveolar lavage (BAL) fluid, whole blood, and serum samples were collected. The QNRT PCR results obtained with the serum and BAL fluid were compared to those achieved with galactomannan and (1 -> 3)-beta-D-glucan assays. High fungal burden levels were detected by QNRT PCR in both lung tissue and BAL fluid in all infected animals at each time point, and the sensitivity of each assay in BAL fluid was 100% by day 3 and remained so through the remainder of the study. The sensitivity of detection of fungi in whole blood and serum samples was significantly lower, and some samples remained negative by all three assays despite the advanced stage of the infection. From these data, we can conclude that this novel QNRT PCR method was highly sensitive for the detection of A. fumigatus from different types of samples in this model. In addition, BAL fluid samples appeared to be the most suitable for the early diagnosis of invasive pulmonary aspergillosis. When testing serum, the use of a combination of available assays may increase the possibility of early detection of this opportunistic mycosis.
C1 [Lengerova, Martina; Kocmanova, Iva; Racil, Zdenek; Hrncirova, Kristyna; Pospisilova, Sarka; Mayer, Jiri] Masaryk Univ, Dept Internal Med Hematooncol, Fac Med, Brno, Czech Republic.
[Lengerova, Martina; Kocmanova, Iva; Racil, Zdenek; Hrncirova, Kristyna; Pospisilova, Sarka; Mayer, Jiri] Univ Hosp Brno, Brno, Czech Republic.
[Lengerova, Martina; Pospisilova, Sarka; Mayer, Jiri] Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic.
[Najvar, Laura K.; Wiederhold, Nathan P.; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Najvar, Laura K.; Kirkpatrick, William R.; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA.
RP Lengerova, M (reprint author), Masaryk Univ, Dept Internal Med Hematooncol, Fac Med, Brno, Czech Republic.
EM mlengerova@fnbrno.cz
RI Lengerova, Martina/E-1038-2012; Pospisilova, Sarka/D-7200-2012
FU Ministry of Health of the Czech Republic [NS10442-3/2009,
NS10441-3/2009]; Ministry of Industry and Trade of the Czech Republic
[FR-TI2/254]; NIH/NIAID [N01-AI-30041]
FX This study was supported in part by grants from the Ministry of Health
of the Czech Republic (NS10442-3/2009, NS10441-3/2009), the Ministry of
Industry and Trade of the Czech Republic (FR-TI2/254), and NIH/NIAID
contract N01-AI-30041.
NR 28
TC 17
Z9 20
U1 3
U2 20
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAR
PY 2012
VL 50
IS 3
BP 602
EP 608
DI 10.1128/JCM.05356-11
PG 7
WC Microbiology
SC Microbiology
GA 901WB
UT WOS:000300997800011
PM 22189110
ER
PT J
AU Campbell, JD
Lewis, JS
McElmeel, ML
Fulcher, LC
Jorgensen, JH
AF Campbell, Jennifer D.
Lewis, James S., II
McElmeel, M. Leticia
Fulcher, Letitia C.
Jorgensen, James H.
TI Detection of Favorable Oral Cephalosporin-Clavulanate Interactions by In
Vitro Disk Approximation Susceptibility Testing of Extended-Spectrum-
Beta-Lactamase-Producing Members of the Enterobacteriaceae
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID ESCHERICHIA-COLI; PHARMACOKINETICS; COMBINATION; VOLUNTEERS; ACID;
COMMUNITY; EMERGENCE
AB Extended-spectrum-beta-lactamase (ESBL)-producing members of the Enterobacteriaceae are often resistant to multiple drug classes, making therapy of urinary infections with oral antibiotics difficult. Previously it was shown that amoxicillin-clavulanate can provide clavulanate inhibition of ESBLs and protect an oral cephalosporin present in combination when tested by broth microdilution. This study has shown that disk approximation testing could detect favorable cephalosporin-clavulanate interactions among a group of 101 previously characterized members of the Enterobacteriaceae with CTX-M, SHV, or TEM ESBLs.
C1 [McElmeel, M. Leticia; Fulcher, Letitia C.; Jorgensen, James H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
[Campbell, Jennifer D.] S Texas Vet Healthcare Syst, San Antonio, TX USA.
[Campbell, Jennifer D.; Lewis, James S., II] Univ Texas Austin, Coll Pharm, Pharmacotherapy Div, Austin, TX 78712 USA.
[Campbell, Jennifer D.; Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA.
[Lewis, James S., II] Univ Hlth Syst, San Antonio, TX USA.
RP Jorgensen, JH (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
EM jorgensen@uthscsa.edu
NR 18
TC 5
Z9 5
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAR
PY 2012
VL 50
IS 3
BP 1023
EP 1026
DI 10.1128/JCM.06248-11
PG 4
WC Microbiology
SC Microbiology
GA 901WB
UT WOS:000300997800070
PM 22170910
ER
PT J
AU Issa, NC
Koo, S
Lynch, RC
Gay, C
Hammond, SP
Baden, LR
Ghobrial, IM
Finkelman, MA
Marty, FM
AF Issa, Nicolas C.
Koo, Sophia
Lynch, Robert C.
Gay, Charline
Hammond, Sarah P.
Baden, Lindsey R.
Ghobrial, Irene M.
Finkelman, Malcolm A.
Marty, Francisco M.
TI Serum Galactomannan and (1 -> 3)-beta-D-Glucan Assays for Patients with
Multiple Myeloma and Waldenstrom's Macroglobulinemia
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID INVASIVE FUNGAL-INFECTIONS; BETA-D-GLUCAN; EARLY-DIAGNOSIS;
ASPERGILLOSIS; EPIDEMIOLOGY; RECIPIENTS; LEUKEMIA; PLASMA
AB We assessed the performance of galactomannan and (1 -> 3)-beta-D-glucan in 29 serum samples from patients with multiple myeloma and Waldenstrom's macroglobulinemia without invasive fungal disease to address issues of false positivity and uninterpretable results previously reported among patients with these conditions. Galactomannan and (1 -> 3)-beta-D-glucan assays were not falsely elevated in any patient. (1 -> 3)-beta-D-glucan assay results were uninterpretable in 24% of patients. Patients with IgG levels of >2,000 mg/dl had higher odds of uninterpretable (1 -> 3)-beta-D-glucan results.
C1 [Issa, Nicolas C.; Koo, Sophia; Lynch, Robert C.; Gay, Charline; Hammond, Sarah P.; Baden, Lindsey R.; Ghobrial, Irene M.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Issa, Nicolas C.; Koo, Sophia; Hammond, Sarah P.; Baden, Lindsey R.; Ghobrial, Irene M.; Marty, Francisco M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Issa, Nicolas C.; Koo, Sophia; Hammond, Sarah P.; Baden, Lindsey R.; Ghobrial, Irene M.; Marty, Francisco M.] Harvard Univ, Sch Med, Boston, MA USA.
[Finkelman, Malcolm A.] Associates Cape Cod Inc, E Falmouth, MA USA.
RP Issa, NC (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA.
EM nissa@partners.org
OI Koo, Sophia/0000-0002-4973-7439
NR 21
TC 2
Z9 3
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAR
PY 2012
VL 50
IS 3
BP 1054
EP 1056
DI 10.1128/JCM.06295-11
PG 3
WC Microbiology
SC Microbiology
GA 901WB
UT WOS:000300997800078
PM 22170932
ER
PT J
AU Wortzel, HS
Strom, LA
Anderson, AC
Maa, EH
Spitz, M
AF Wortzel, Hal S.
Strom, Laura A.
Anderson, Alan C.
Maa, Edward H.
Spitz, Mark
TI Disrobing Associated with Epileptic Seizures and Forensic Implications
SO JOURNAL OF FORENSIC SCIENCES
LA English
DT Article
DE forensic science; forensic medicine; forensic psychiatry; seizures;
epilepsy; behavioral medicine
ID VIOLENCE
AB Little is known about the clinical aspects and medico-legal consequences of disrobing in the context of epileptic seizures. Seizure-related disrobing may occur either as an ictal automatism or during the postictal period. Some patients may experience a seizure while already in the unclothed state, engage in ictal wandering, and thereby appear in public in the nude. Two cases involving disrobing associated with seizures captured via video-monitored electroencephalography are offered. An additional case reveals the legal consequences endured by one patient who experienced a nocturnal seizure and began wandering in an unclothed state. Collectively, these cases illustrate the medical reality of seizure-related disrobing and the related adverse effects on patients quality of life. Disrobing associated with epileptic seizures carries the potential for serious legal consequences if not properly identified as an ictal phenomenon.
C1 [Wortzel, Hal S.] Denver Vet Hosp, VISN MIRECC 19, Denver, CO 80220 USA.
[Wortzel, Hal S.; Anderson, Alan C.] Dept Psychiat, Neurobehav Disorders Program, Aurora, CO 80045 USA.
[Strom, Laura A.; Anderson, Alan C.; Maa, Edward H.; Spitz, Mark] Dept Neurol, Aurora, CO 80045 USA.
[Strom, Laura A.; Anderson, Alan C.; Maa, Edward H.; Spitz, Mark] Denver Vet Hosp, Div Neurol, Denver, CO 80220 USA.
RP Wortzel, HS (reprint author), Denver VA Hosp, VISN MIRECC 19, 1055 Clermont St, Denver, CO 80220 USA.
EM hal.wortzel@ucdenver.edu
NR 10
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-1198
J9 J FORENSIC SCI
JI J. Forensic Sci.
PD MAR
PY 2012
VL 57
IS 2
BP 550
EP 552
DI 10.1111/j.1556-4029.2011.01995.x
PG 3
WC Medicine, Legal
SC Legal Medicine
GA 897XY
UT WOS:000300696400039
PM 22150773
ER
PT J
AU Hoshida, Y
Fuchs, BC
Tanabe, KK
AF Hoshida, Yujin
Fuchs, Bryan C.
Tanabe, Kenneth K.
TI Genomic risk of hepatitis C-related hepatocellular carcinoma
SO JOURNAL OF HEPATOLOGY
LA English
DT Editorial Material
ID GROWTH-FACTOR GENE; FUNCTIONAL POLYMORPHISM; SUSCEPTIBILITY LOCUS; WIDE
ASSOCIATION; CIRRHOSIS; PROGRESSION; FIBROSIS
AB To identify the genetic susceptibility factor(s) for hepatitis C virus-induced hepatocellular carcinoma (HCV-induced HCC), we conducted a genome-wide association study using 432,703 autosomal SNPs in 721 individuals with HCV-induced HCC (cases) and 2890 HCV-negative controls of Japanese origin. Eight SNPs that showed possible association (P < 1 x 10(-5)) in the genome-wide association study were further genotyped in 673 cases and 2596 controls. We found a previously unidentified locus in the 5' flanking region of MICA on 6p21.33 (rs2596542, P(combined) = 4.21 x 10(-13), odds ratio = 1.39) to be strongly associated with HCV-induced HCC. Subsequent analyses using individuals with chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC susceptibility (P = 0.61) but is significantly associated with progression from CHC to HCC (P = 3.13 x 10(-8)). We also found that the risk allele of rs2596542 was associated with lower soluble MICA protein levels in individuals with HCV-induced HCC (P = 1.38 x 10(-13)). (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
C1 [Hoshida, Yujin] Broad Inst Massachusetts Inst Technol, Canc Program, Cambridge, MA USA.
[Hoshida, Yujin] Harvard Univ, Cambridge, MA 02138 USA.
[Fuchs, Bryan C.; Tanabe, Kenneth K.] Harvard Med Sch, Boston, MA USA.
[Fuchs, Bryan C.; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA USA.
RP Hoshida, Y (reprint author), Broad Inst Massachusetts Inst Technol, Canc Program, Cambridge, MA USA.
EM hoshida@broadinstitute.org; ktanabe@partners.org
NR 11
TC 10
Z9 10
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD MAR
PY 2012
VL 56
IS 3
BP 729
EP 730
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 904TQ
UT WOS:000301221200032
PM 21963516
ER
PT J
AU Madaras-Kelly, KJ
Remington, RE
Fan, VS
Sloan, KL
AF Madaras-Kelly, Karl J.
Remington, Richard E.
Fan, Vincent S.
Sloan, Kevin L.
TI Predicting antibiotic resistance to community-acquired pneumonia
antibiotics in culture-positive patients with healthcare-associated
pneumonia
SO JOURNAL OF HOSPITAL MEDICINE
LA English
DT Article
ID IN-VITRO ACTIVITY; STAPHYLOCOCCUS-AUREUS; RISK-FACTORS; INFECTION;
FLUOROQUINOLONE; SUSCEPTIBILITY; COLONIZATION; GUIDELINES; MANAGEMENT;
BACTERIA
AB OBJECTIVE: To develop and validate a model to predict resistance to community-acquired pneumonia antibiotics (CAP-resistance) among patients with healthcare-associated pneumonia (HCAP), and to compare the model's predictive performance to a model including only guideline-defined criteria for HCAP. DESIGN: Retrospective cohort study. SETTING: Six Veterans Affairs Medical Centers in the northwestern United States. PATIENTS: Culture-positive inpatients with HCAP. MEASUREMENTS: Patients were identified based upon guideline-defined criteria for HCAP. Relevant cultures obtained within 48 hours of admission were assessed to determine bacteriology and antibiotic susceptibility. Medical records for the year preceding admission were assessed to develop predictive models of CAP-resistance with logistic regression. The predictive performance of cohort-developed and guideline-defined models was compared. RESULTS: CAP-resistant organisms were identified in 118 of 375 culture-positive patients. Of guideline-defined criteria, CAP-resistance was associated (odds ratio (OR) [95% confidence interval (CI)]) with: admission from nursing home (2.6 [1.6-4.4]); recent antibiotic exposure (1.7 [1.0-2.8]); and prior hospitalization (1.6 [1.0-2.6]). In the cohort-developed model, CAP-resistance was associated with: admission from nursing home or recent nursing home discharge (2.3 [1.4-3.8]); positive methicillin-resistant Staphylococcus aureus (MRSA) history within 90 days of admission (6.4 [2.6-17.8]) or 91-365 days (2.3 [0.9-5.9]); cephalosporin exposure (1.8 [1.12.9]); recent infusion therapy (1.9 [1.0-3.5]); diabetes (1.7 [1.0-2.8]); and intensive care unit (ICU) admission (1.6 [1.0-2.6]). Area under the receiver operating characteristic curve (aROC [95% CI]) for the cohort-developed model (0.71 [0.65-0.77]) was significantly higher than for the guideline-defined model (0.63 [0.57-0.69]) (P = 0.01). CONCLUSIONS: Select guideline-defined criteria predicted CAP-resistance. A cohort-developed model based primarily on prior MRSA history, nursing home residence, and specific antibiotic exposures provided improved prediction of CAP-resistant organisms in HCAP. Journal of Hospital Medicine 2012; 7: 195-202 (C) 2011 Society of Hospital Medicine.
C1 [Madaras-Kelly, Karl J.] Vet Affairs Med Ctr, Clin Pharm Serv 119A, Boise, ID 83702 USA.
[Remington, Richard E.] Vet Affairs Med Ctr, Res Serv, Boise, ID 83702 USA.
[Fan, Vincent S.] Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA USA.
[Madaras-Kelly, Karl J.; Remington, Richard E.] Idaho State Univ, Coll Pharm, Dept Pharm Practice & Adm Sci, Meridian, ID USA.
[Fan, Vincent S.] Univ Washington, Sch Med, Dept Pulm & Crit Care Med, Seattle, WA USA.
RP Madaras-Kelly, KJ (reprint author), Vet Affairs Med Ctr, Clin Pharm Serv 119A, 500 W Ft St, Boise, ID 83702 USA.
EM KMK@pharmacy.isu.edu
FU Idaho State University [RO3AI074894-01A2]; Department of Veterans
Affairs; National Institutes of Health
FX Karl J. Madaras-Kelly is employed full time by Idaho State University.
The National Institute of Allergy and Infectious Diseases provided
salary support for this study paid through Idaho State University (grant
RO3AI074894-01A2). The National Institute of Allergy and Infectious
Diseases provided payment for statistical services on this study to
Richard E. Remington, sub-contracted through Idaho State University
(grant RO3AI074894-01A2). Vincent S. Fan is employed full time by the
Department of Veterans Affairs, and receives grant support unrelated to
the study from the Department of Veterans Affairs and the National
Institutes of Health. He serves as a consultant for Uptake Medical
Corporation. Kevin L. Sloan has no conflicts of interest to report.
NR 31
TC 15
Z9 16
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1553-5592
J9 J HOSP MED
JI J. Hosp. Med.
PD MAR
PY 2012
VL 7
IS 3
BP 195
EP 202
DI 10.1002/jhm.942
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 901QY
UT WOS:000300983100006
PM 22038859
ER
PT J
AU Freund, K
Weckmann, MT
Casarett, DJ
Swanson, K
Brooks, MK
Broderick, A
AF Freund, Katherine
Weckmann, Michelle T.
Casarett, David J.
Swanson, Kristi
Brooks, Mary Kay
Broderick, Ann
TI Hospice eligibility in patients who died in a tertiary care center
SO JOURNAL OF HOSPITAL MEDICINE
LA English
DT Article
DE communication; palliative care; patient education
ID END-OF-LIFE; PALLIATIVE CARE; NURSING-HOMES; NEAR-DEATH; DISCUSSIONS;
HEALTH; CANCER; LENGTH; EXPENDITURES; ASSOCIATIONS
AB BACKGROUND: Hospice is a service that patients, families, and physicians find beneficial, yet a majority of patients die without receiving hospice care. Little is known about how many hospitalized patients are hospice eligible at the time of hospitalization. METHODS: Retrospective chart review was used to examine all adult deaths (n = 688) at a tertiary care center during 2009. Charts were selected for full review if the death was nontraumatic and the patient had a hospital admission within 12 months of the terminal admission. The charts were examined for hospice eligibility based on medical criteria, evidence of a hospice discussion, and hospice enrollment. RESULTS: Two hundred nine patients had an admission in the year preceding the terminal admission and a nontraumatic death. Sixty percent were hospice eligible during the penultimate admission. Hospice discussions were documented in 14% of the hospice-eligible patients. Patients who were hospice eligible had more subspecialty consults on the penultimate admission compared to those not hospice eligible (P = 0.016), as well as more overall hospitalizations in the 12 months preceding their terminal admission (P = 0.0003), and fewer days between their penultimate admission and death (P = 0.001). CONCLUSION: The majority of terminally ill inpatients did not have a documented discussion of hospice with their care provider. Educating physicians to recognize the stepwise decline of most illnesses and hospice admission criteria will facilitate a more informed decision-making process for patients and their families. A consistent commitment to offer hospice earlier than the terminal admission would increase access to community or home-based care, potentially increasing quality of life. Journal of Hospital Medicine 2012; 7: 218-223. (C) 2011 Society of Hospital Medicine.
C1 [Weckmann, Michelle T.; Swanson, Kristi] Univ Iowa, Carver Coll Med, Dept Family Med, Iowa City, IA 52242 USA.
[Weckmann, Michelle T.] Univ Iowa, Carver Coll Med, Dept Psychiat, Iowa City, IA 52242 USA.
[Casarett, David J.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Casarett, David J.] Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, Ctr Bioeth, Inst Aging, Philadelphia, PA USA.
[Brooks, Mary Kay] Univ Iowa Hosp & Clin, Off Clin Qual Safety & Performance Improvement, Iowa City, IA 52242 USA.
[Broderick, Ann] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA.
RP Weckmann, MT (reprint author), Univ Iowa, Carver Coll Med, Dept Family Med, 01102 PFP, Iowa City, IA 52242 USA.
EM michelle-weckmann@uiowa.edu
FU University of Iowa Carver College of Medicine [NIH 2-T35-HL007485-31]
FX Support for this research was provided by the University of Iowa Carver
College of Medicine, Medical Student Summer Research Fellowship Program
(NIH 2-T35-HL007485-31). None of the authors have any financial
conflicts of interest to report.
NR 30
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U1 3
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1553-5592
J9 J HOSP MED
JI J. Hosp. Med.
PD MAR
PY 2012
VL 7
IS 3
BP 218
EP 223
DI 10.1002/jhm.975
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 901QY
UT WOS:000300983100009
PM 22086609
ER
PT J
AU Nikolaou, VA
Stratigos, AJ
Flaherty, KT
Tsao, H
AF Nikolaou, Vasiliki A.
Stratigos, Alexander J.
Flaherty, Keith T.
Tsao, Hensin
TI Melanoma: New Insights and New Therapies
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Review
ID STAGE IV MELANOMA; PHASE-II TRIAL; METASTATIC MELANOMA;
MALIGNANT-MELANOMA; IMATINIB MESYLATE; THERAPEUTIC TARGET; ANTISENSE
THERAPY; CLINICAL-EFFICACY; TUMOR PROGRESSION; INDUCED APOPTOSIS
AB Metastatic melanoma has historically been considered as one of the most therapeutically challenging malignancies. However, for the first time after decades of basic research and clinical investigation, new drugs have produced major clinical responses. The discovery of BRAF mutations in melanoma created the first opportunity to develop oncogene-directed therapy in this disease and led to the development of compounds that inhibit aberrant BRAF activity. A decade later, vemurafenib, an orally available and well-tolerated selective BRAF inhibitor, ushered in a new era of molecular treatments for advanced disease. Additional targets have been identified, and novel agents that impact on various signaling pathways or modulate the immune system hold the promise of a whole new therapeutic landscape for patients with metastatic melanoma. One of the major thrusts in melanoma therapy is now focused on understanding and targeting the network of signal transduction pathways and on attacking elements that underlie the tumor's propensity for growth and chemoresistance. In this article, we review the novel targeted anticancer approaches that are under consideration in melanoma treatment.
C1 [Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, MGH Canc Ctr, Dept Dermatol, Boston, MA 02114 USA.
[Nikolaou, Vasiliki A.; Stratigos, Alexander J.] Univ Athens, Sch Med, Andreas Sygros Hosp, Dermatooncol Unit,Dept Dermatol, GR-11527 Athens, Greece.
RP Tsao, H (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, MGH Canc Ctr, Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA.
EM htsao@partners.org
FU Cephalon; National Institutes of Health [K24 CA149202]; American Skin
Association; Melanoma Research Alliance; MGH
FX K.T.F. has been a consultant at Roche/Genentech and GlaxoSmithKline.
H.T. has been a consultant for Genentech, SciBASE, and Quest, and has
received research funding from Cephalon. There is no conflict with the
publicly reported research in this article. The other authors state no
conflict of interest.; This scholarly activity was made possible in part
by grants from the National Institutes of Health (K24 CA149202 to H.T.),
the American Skin Association (to H.T.), and the Melanoma Research
Alliance (to K.T.F and H.T.), and by generous donors to the MGH
Millennium Melanoma Fund on behalf of melanoma research.
NR 88
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U1 2
U2 33
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAR
PY 2012
VL 132
IS 3
BP 854
EP 863
DI 10.1038/jid.2011.421
PN 2
PG 10
WC Dermatology
SC Dermatology
GA 893RW
UT WOS:000300374100013
PM 22217739
ER
PT J
AU Zhu, YC
Chabriat, H
Godin, O
Dufouil, C
Rosand, J
Greenberg, SM
Smith, EE
Tzourio, C
Viswanathan, A
AF Zhu, Yi-Cheng
Chabriat, Hugues
Godin, Ophelia
Dufouil, Carole
Rosand, Jonathan
Greenberg, Steven M.
Smith, Eric E.
Tzourio, Christophe
Viswanathan, Anand
TI Distribution of white matter hyperintensity in cerebral hemorrhage and
healthy aging
SO JOURNAL OF NEUROLOGY
LA English
DT Article
DE Intercerebral hemorrhage; White matter hyperintensity; Cerebral amyloid
angiopathy
ID LOBAR INTRACEREBRAL HEMORRHAGE; AMYLOID ANGIOPATHY; COGNITIVE DECLINE;
LESIONS; DISEASE; MRI; POPULATION; VOLUMES; RISK
AB We compared the severity of white matter T2-hyperintensities (WMH) in the frontal lobe and occipital lobe using a visual MRI score in 102 patients with lobar intracerebral hemorrhage (ICH) diagnosed with possible or probable cerebral amyloid angiopathy (CAA), 99 patients with hypertension-related deep ICH, and 159 normal elderly subjects from a population-based cohort. The frontal-occipital (FO) gradient was used to describe the difference in the severity of WMH between the frontal lobe and occipital lobe. A higher proportion of subjects with obvious occipital dominant WMH (FO gradient a parts per thousand currency signa'2) was found among patients with lobar ICH than among healthy elderly subjects (FO gradient a parts per thousand currency signa'2: 13.7 vs. 5.7%, p = 0.03). Subjects with obvious occipital dominant WMH were more likely to have more WMH (p = 0.0006) and a significantly higher prevalence of the apolipoprotein E epsilon 4 allele (45.8% vs. 19.4%, p = 0.04) than those who had obvious frontal dominant WMH. This finding is consistent with the relative predilection of CAA for posterior brain regions, and suggests that white matter lesions may preferentially occur in areas of greatest vascular pathology.
C1 [Greenberg, Steven M.; Smith, Eric E.; Viswanathan, Anand] Harvard Univ, Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Dept Neurol,Stroke Res Ctr,Med Sch, Boston, MA 02114 USA.
[Zhu, Yi-Cheng] Beijing Union Med Coll Hosp, Dept Neurol, Beijing, Peoples R China.
[Zhu, Yi-Cheng; Chabriat, Hugues] CHU Lariboisiere, Assistance Publ Hop Paris, Dept Neurol, INSERM,U740, Paris, France.
[Zhu, Yi-Cheng; Godin, Ophelia; Dufouil, Carole; Tzourio, Christophe] INSERM, Neuroepidemiol U708, Paris, France.
[Godin, Ophelia; Dufouil, Carole; Tzourio, Christophe] Univ Paris 06, Paris, France.
[Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Viswanathan, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Dept Neurol,Stroke Res Ctr,Med Sch, 175 Cambridge St,Suite 300, Boston, MA 02114 USA.
EM aviswanathan1@partners.org
RI Dufouil, Carole/J-4968-2012; Tzourio, christophe/B-4015-2009; Chabriat,
Hugues/G-5699-2010;
OI Tzourio, christophe/0000-0002-6517-2984; Chabriat,
Hugues/0000-0001-8436-6074; Smith, Eric/0000-0003-3956-1668
FU French Chinese Foundation for Science and Applications (FFCSA); China
Scholarship Council (CSC); Association de Recherche en Neurologie
Vasculaire (ARNEVA); EISAI; French National Research Agency (ANR);
Sanofi-Synthelabo; Merck-Sharp; Dohm; Lundbeck; Servier; Johnson and
Johnson
FX Yi-Cheng Zhu is funded by the French Chinese Foundation for Science and
Applications (FFCSA), the China Scholarship Council (CSC), and the
Association de Recherche en Neurologie Vasculaire (ARNEVA). Carole
Dufouil has received consulting fees from EISAI. Christophe Tzourio has
received investigator initiated research funding from the French
National Research Agency (ANR) and has received fees from
Sanofi-Synthelabo for participation on a data safety monitoring board
and from Merck-Sharp & Dohm for participation on a scientific committee.
Hugues Chabriat has already received fees from Eisai, Lundbeck, Servier
and Johnson and Johnson companies for participating on data safety and
scientific committees in studies unrelated to the present study.
NR 19
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U1 0
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
J9 J NEUROL
JI J. Neurol.
PD MAR
PY 2012
VL 259
IS 3
BP 530
EP 536
DI 10.1007/s00415-011-6218-3
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 904GW
UT WOS:000301183500017
PM 21877206
ER
PT J
AU Duhaime, AC
Holshouser, B
Hunter, JV
Tong, K
AF Duhaime, Ann-Christine
Holshouser, Barbara
Hunter, Jill V.
Tong, Karen
TI Common Data Elements for Neuroimaging of Traumatic Brain Injury:
Pediatric Considerations
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE CT; common data elements; MRI; pediatrics; traumatic brain injury
ID CLOSED HEAD-INJURY; THERAPEUTIC PROCEDURES; WHITE-MATTER; MATURATION;
CHILDREN; CT; ADOLESCENCE; GUIDELINES; MANAGEMENT; CHILDHOOD
AB As part of the Traumatic Brain Injury Common Data Elements project, a large-scale effort to define common data elements across a variety of domains, including neuroimaging, special considerations for pediatric patients were introduced. This article is an extension of that initial work, in which pediatric-specific pathoanatomical entities, technical considerations, interpretation paradigms, and safety considerations were reviewed. The goal of this review was to outline differences and specific information relevant to optimal performance and proper interpretation of neuroimaging in pediatric patients with traumatic brain injury. The long-range goal of this project is to facilitate data sharing as well as to provide critical infrastructure for potential clinical trials in this major public health area.
C1 [Duhaime, Ann-Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Holshouser, Barbara] Loma Linda Univ, Sch Med, Dept Radiol, Loma Linda, CA USA.
[Hunter, Jill V.] Texas Childrens Hosp, Baylor Coll Med, Dept Neuroradiol, Houston, TX 77030 USA.
[Tong, Karen] Loma Linda Univ, Med Ctr, Loma Linda, CA USA.
RP Duhaime, AC (reprint author), Massachusetts Gen Hosp, 15 Parkman St,Wang 331, Boston, MA 02114 USA.
EM aduhaime@partners.org
FU National Institutes of Health (National Institute of Neurological
Disorders and Stroke; NIH/NINDS); United States Department of
Education/National Institute on Disability and Rehabilitation Research
(DOE/NIDRR)
FX We gratefully acknowledge the valuable contributions of Ramona Hicks for
providing the impetus as well as the organization and format for this
project and for assistance with manuscript preparation. This project was
jointly supported by the National Institutes of Health (National
Institute of Neurological Disorders and Stroke; NIH/NINDS) and the
United States Department of Education/National Institute on Disability
and Rehabilitation Research (DOE/NIDRR).
NR 27
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U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD MAR
PY 2012
VL 29
IS 4
BP 629
EP 633
DI 10.1089/neu.2011.1927
PG 5
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 901SQ
UT WOS:000300987500002
PM 21671798
ER
PT J
AU Miller, AC
Odenkirchen, J
Duhaime, AC
Hicks, R
AF Miller, A. Cate
Odenkirchen, Joanne
Duhaime, Ann-Christine
Hicks, Ramona
TI Common Data Elements for Research on Traumatic Brain Injury: Pediatric
Considerations
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE assessment tools; bioinformatics; CDE; clinical trials; database;
meta-analysis; pediatrics; rehabilitation; research; TBI
ID PSYCHOLOGICAL HEALTH; OUTCOME MEASURES; WORKING GROUP; RECOMMENDATIONS
AB Traumatic brain injury (TBI) is a significant global health problem, with a notably high incidence in children and adolescents. Despite the prevalence of TBI and the disabilities that often follow, research on which to base effective treatment is limited by several challenges, including but not limited to the complexity and heterogeneity of TBI. Even when rigorous methods are employed, the utility of the research may be limited by difficulties in comparing findings across studies resulting from the use of different measures to assess similar TBI study variables. Standardization of definitions and data elements is an important step toward accelerating the process of data sharing that will ultimately lead to a stronger evidence base for treatment advances. To address this need, recommendations for common data elements (CDEs) for research on TBI were developed through a 2009 national initiative. To ensure that the TBI CDE recommendations are relevant to pediatric populations, the National Institute on Disability and Rehabilitation Research (NIDRR) and the National Institute of Neurological Disorders and Stroke (NINDS) called for a review of the original recommendations. Following the process used for the original initiative, multidisciplinary work groups composed of pediatric TBI experts were formed (Demographics and Clinical Assessment; Biomarkers; Neuroimaging; and Outcomes Assessment). Recommendations for modifications and additions to the original CDEs were developed by the work groups, vetted at a 2010 workshop and further refined in preparation for publication. The pediatric considerations for TBI CDEs are described in a series of articles in this journal. This article describes the efforts leading to this pediatric CDE initiative and the CDE review and development process. It concludes with general recommendations for future iterations of the CDE initiative.
C1 [Miller, A. Cate] US Dept Educ, Natl Inst Disabil & Rehabil Res, Washington, DC 20202 USA.
[Odenkirchen, Joanne; Hicks, Ramona] NINDS, NIH, Bethesda, MD 20892 USA.
[Duhaime, Ann-Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Miller, AC (reprint author), US Dept Educ, Natl Inst Disabil & Rehabil Res, 400 Maryland Ave SW, Washington, DC 20202 USA.
EM cate.miller@ed.gov
FU National Institute for Disability and Rehabilitation Research of the
United States Department of Education (NIDRR/DoE); National Institute of
Neurological Disorders and Stroke of the National Institutes of Health
(NINDS/NIH)
FX We gratefully acknowledge the working group members and chairpersons for
their dedication of time and expertise to this initiative. Support for
the workshop came from the National Institute for Disability and
Rehabilitation Research of the United States Department of Education
(NIDRR/DoE) and the National Institute of Neurological Disorders and
Stroke of the National Institutes of Health (NINDS/NIH)
NR 14
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U2 5
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD MAR
PY 2012
VL 29
IS 4
BP 634
EP 638
DI 10.1089/neu.2011.1932
PG 5
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 901SQ
UT WOS:000300987500003
PM 22091862
ER
PT J
AU Hunter, JV
Wilde, EA
Tong, KA
Holshouser, BA
AF Hunter, Jill V.
Wilde, Elisabeth A.
Tong, Karen A.
Holshouser, Barbara A.
TI Emerging Imaging Tools for Use with Traumatic Brain Injury Research
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE adults; children; CT; MRI; neuroimaging; TBI
ID DIFFUSE AXONAL INJURY; MAGNETIC-RESONANCE-SPECTROSCOPY;
CEREBRAL-BLOOD-FLOW; CONTROLLED CORTICAL IMPACT; PROTON MR SPECTROSCOPY;
COMMON DATA ELEMENTS; WHITE-MATTER INJURY; CENTRAL-NERVOUS-SYSTEM;
WORKING-MEMORY LOAD; SEVERE HEAD TRAUMA
AB This article identifies emerging neuroimaging measures considered by the inter-agency Pediatric Traumatic Brain Injury (TBI) Neuroimaging Workgroup. This article attempts to address some of the potential uses of more advanced forms of imaging in TBI as well as highlight some of the current considerations and unresolved challenges of using them. We summarize emerging elements likely to gain more widespread use in the coming years, because of 1) their utility in diagnosis, prognosis, and understanding the natural course of degeneration or recovery following TBI, and potential for evaluating treatment strategies; 2) the ability of many centers to acquire these data with scanners and equipment that are readily available in existing clinical and research settings; and 3) advances in software that provide more automated, readily available, and cost-effective analysis methods for large scale data image analysis. These include multi-slice CT, volumetric MRI analysis, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), arterial spin tag labeling (ASL), functional MRI (fMRI), including resting state and connectivity MRI, MR spectroscopy (MRS), and hyperpolarization scanning. However, we also include brief introductions to other specialized forms of advanced imaging that currently do require specialized equipment, for example, single photon emission computed tomography (SPECT), positron emission tomography (PET), encephalography (EEG), and magnetoencephalography (MEG)/magnetic source imaging (MSI). Finally, we identify some of the challenges that users of the emerging imaging CDEs may wish to consider, including quality control, performing multi-site and longitudinal imaging studies, and MR scanning in infants and children.
C1 [Hunter, Jill V.] Texas Childrens Hosp, Dept Pediat Radiol, Houston, TX 77030 USA.
[Hunter, Jill V.; Wilde, Elisabeth A.] Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA.
[Hunter, Jill V.; Wilde, Elisabeth A.] Baylor Coll Med, Dept Phys Med Rehabil & Neurol, Houston, TX 77030 USA.
[Wilde, Elisabeth A.] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA.
[Tong, Karen A.; Holshouser, Barbara A.] Loma Linda Univ, Sch Med, Dept Radiol, Loma Linda, CA USA.
RP Hunter, JV (reprint author), Texas Childrens Hosp, Dept Pediat Radiol, 6621 Fannin St,W1120, Houston, TX 77030 USA.
EM jhunter@bcm.edu
FU National Institutes of Health (National Institute of Neurological
Disorders and Stroke; NIH/NINDS); United States Department of
Education/National Institute on Disability and Rehabilitation Research
(DOE/NIDRR); Department of Veterans' Affairs; United States Department
of Defense
FX This project was jointly supported by the National Institutes of Health
(National Institute of Neurological Disorders and Stroke; NIH/NINDS),
the United States Department of Education/National Institute on
Disability and Rehabilitation Research (DOE/NIDRR), the Department of
Veterans' Affairs, and the United States Department of Defense.
NR 196
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U1 7
U2 38
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD MAR
PY 2012
VL 29
IS 4
BP 654
EP 671
DI 10.1089/neu.2011.1906
PG 18
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 901SQ
UT WOS:000300987500005
PM 21787167
ER
PT J
AU McCauley, SR
Wilde, EA
Anderson, VA
Bedell, G
Beers, SR
Campbell, TF
Chapman, SB
Ewing-Cobbs, L
Gerring, JP
Gioia, GA
Levin, HS
Michaud, LJ
Prasad, MR
Swaine, BR
Turkstra, LS
Wade, SL
Yeates, KO
AF McCauley, Stephen R.
Wilde, Elisabeth A.
Anderson, Vicki A.
Bedell, Gary
Beers, Sue R.
Campbell, Thomas F.
Chapman, Sandra B.
Ewing-Cobbs, Linda
Gerring, Joan P.
Gioia, Gerard A.
Levin, Harvey S.
Michaud, Linda J.
Prasad, Mary R.
Swaine, Bonnie R.
Turkstra, Lyn S.
Wade, Shari L.
Yeates, Keith O.
TI Recommendations for the Use of Common Outcome Measures in Pediatric
Traumatic Brain Injury Research
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE children; infants; outcome assessment, TBI
ID CLOSED-HEAD-INJURY; VERBAL-LEARNING-TEST; QUALITY-OF-LIFE;
TEST-CHILDRENS VERSION; DIFFICULTIES-QUESTIONNAIRE SDQ; MOTOR FUNCTION
MEASURE; PORTLAND ADAPTABILITY INVENTORY; FUNCTIONAL INDEPENDENCE
MEASURE; BEHAVIOR RATING INVENTORY; POST-CONCUSSIVE SYMPTOMS
AB This article addresses the need for age-relevant outcome measures for traumatic brain injury (TBI) research and summarizes the recommendations by the inter-agency Pediatric TBI Outcomes Workgroup. The Pediatric Workgroup's recommendations address primary clinical research objectives including characterizing course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements (CDE) Workgroups, the Pediatric TBI Outcomes Workgroup adopted the standard three-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in pediatric TBI from each identified domain including academics, adaptive and daily living skills, family and environment, global outcome, health-related quality of life, infant and toddler measures, language and communication, neuropsychological impairment, physical functioning, psychiatric and psychological functioning, recovery of consciousness, social role participation and social competence, social cognition, and TBI-related symptoms. In the second tier, supplemental measures were recommended for consideration in TBI research focusing on specific topics or populations. In the third tier, emerging measures included important instruments currently under development, in the process of validation, or nearing the point of published findings that have significant potential to be superior to measures in the core and supplemental lists and may eventually replace them as evidence for their utility emerges.
C1 [McCauley, Stephen R.] Baylor Coll Med, Cognit Neurosci Lab, Dept Phys Med & Rehabil, Houston, TX 77030 USA.
[McCauley, Stephen R.; Wilde, Elisabeth A.; Levin, Harvey S.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[McCauley, Stephen R.; Levin, Harvey S.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[McCauley, Stephen R.; Wilde, Elisabeth A.; Levin, Harvey S.] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA.
[Wilde, Elisabeth A.] Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA.
[Anderson, Vicki A.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
[Bedell, Gary] Tufts Univ, Dept Occupat Therapy, Medford, MA 02155 USA.
[Beers, Sue R.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Campbell, Thomas F.] Univ Texas Dallas, Callier Ctr Commun Disorders, Commun Disorders Sch Behav & Brain Sci, Dallas, TX 75235 USA.
[Chapman, Sandra B.] Univ Texas Dallas, Ctr BrainHlth Behav & Brain Sci, Dallas, TX 75235 USA.
[Ewing-Cobbs, Linda; Prasad, Mary R.] Univ Texas Hlth Sci Ctr Houston, Childrens Learning Inst, Houston, TX USA.
[Ewing-Cobbs, Linda; Prasad, Mary R.] Univ Texas Hlth Sci Ctr Houston, Dept Psychiat & Behav Sci, Houston, TX USA.
[Gerring, Joan P.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
[Gerring, Joan P.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Gioia, Gerard A.] George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20052 USA.
[Gioia, Gerard A.] George Washington Univ, Sch Med, Dept Psychiat, Washington, DC 20052 USA.
[Michaud, Linda J.; Wade, Shari L.] Univ Cincinnati, Dept Phys Med & Rehabil, Cincinnati, OH USA.
[Michaud, Linda J.; Wade, Shari L.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA.
[Michaud, Linda J.; Wade, Shari L.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Swaine, Bonnie R.] Univ Montreal, Ecole Readaptat, Ctr Interdisciplinary Rehabil Res CRIR, Montreal, PQ, Canada.
[Turkstra, Lyn S.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA.
[Turkstra, Lyn S.] Univ Wisconsin, Dept Communicat Disorders & Neurol Surg, Madison, WI USA.
[Yeates, Keith O.] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA.
[Yeates, Keith O.] Nationwide Childrens Hosp, Res Inst, Ctr Biobehav Hlth, Columbus, OH USA.
RP McCauley, SR (reprint author), Baylor Coll Med, Cognit Neurosci Lab, Dept Phys Med & Rehabil, 1709 Dryden Rd,Suite 1200,BCM635, Houston, TX 77030 USA.
EM mccauley@bcm.edu
OI Yeates, Keith/0000-0001-7680-2892
FU National Institutes of Health (National Institute of Neurological
Disorders and Stroke; NIH/NINDS); United States Department of
Education/National Institute on Disability and Rehabilitation Research
(DOE/NIDRR)
FX This project was jointly supported by the National Institutes of Health
(National Institute of Neurological Disorders and Stroke; NIH/NINDS) and
the United States Department of Education/National Institute on
Disability and Rehabilitation Research (DOE/NIDRR).
NR 298
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U1 9
U2 32
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD MAR
PY 2012
VL 29
IS 4
BP 678
EP 705
DI 10.1089/neu.2011.1838
PG 28
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 901SQ
UT WOS:000300987500007
PM 21644810
ER
PT J
AU Subramanian, A
Timberlake, M
Mittakanti, H
Lara, M
Brandt, ML
AF Subramanian, Anuradha
Timberlake, Matthew
Mittakanti, Harsha
Lara, Michael
Brandt, Mary L.
TI Novel Educational Approach for Medical Students: Improved Retention
Rates Using Interactive Medical Software Compared with Traditional
Lecture-Based Format
SO JOURNAL OF SURGICAL EDUCATION
LA English
DT Article
DE web-based; surgical education; interactive tool
AB BACKGROUND: Mannequin and computer-based simulators are useful for the practice of patient management, physical procedures, and competency. However, they are ineffective in teaching clinical medicine. StepStone Interactive Medical Software (SS) is a web-based medical learning modality that provides the user with a highly focused set of evaluative and interventional tasks to treat memorable virtual patients in a visual case-based format.
OBJECTIVE: To determine whether the SS learning modality is superior to traditional lecture format in medical student learning and retention.
METHODS: After Institutional Review Board (IRB) approval was obtained and the consents were signed, 30 third-year medical students were assigned randomly to 2 groups of 15 students each: The control group received two 30-minute PowerPoint lectures (Microsoft Corporation, Redmond, Washington) about torsades de pointes (TdP) and pulseless electrical activity (PEA), and the SS group was given 1 hour to review 2 SS cases teaching TdP and PEA. A preintervention test was given to assess their baseline knowledge. An immediate postintervention test was given to both groups. Twenty-two clays later, a long-term retention test was administered. The results were analyzed using a Student t test for continuous variables.
RESULTS: The mean scores for the preintervention test in the control and SS groups were 44.9 +/- 3% and 44.1 +/- 2%, respectively (p = 0.41). The mean scores for the postintervention test in the control and SS groups were 61.7 +/- 2% and 86.7 +/- 2%, respectively (p < 0.001). Improvement from baseline knowledge was calculated, and the mean improvement was 16.8 +/- 3% in the control group and 42.5 +/- 2% in the SS group (p < 0.001). The long-term retention test revealed the mean scores of 55.8 +/- 3% in the control group and 70.1 +/- 3% in the SS group (p < 0.001). Long-term improvement from baseline knowledge was calculated and the control group improved by 10.9 +/- 4%, whereas the SS group improved by 26 +/- 3% (p = 0.002).
CONCLUSIONS: The SS learning modality demonstrated a significant improvement in student learning retention compared to traditional didactic lecture format. SS is an effective web-based medical education tool. (J Surg 69:253-256. (C) 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)
C1 [Subramanian, Anuradha] Baylor Coll Med, Michael E DeBakey Dept Surg, VA Med Ctr, Houston, TX 77030 USA.
RP Subramanian, A (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, VA Med Ctr, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA.
EM asubrama@bcm.edu
NR 6
TC 13
Z9 13
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1931-7204
J9 J SURG EDUC
JI J. Surg. Educ.
PD MAR-APR
PY 2012
VL 69
IS 2
BP 253
EP 256
DI 10.1016/j.jsurg.2011.12.007
PG 4
WC Education, Scientific Disciplines; Surgery
SC Education & Educational Research; Surgery
GA 906AD
UT WOS:000301316400023
PM 22365876
ER
PT J
AU Hammerness, PG
AF Hammerness, Paul G.
TI Cardiovascular Events and Methylphenidate Use in Taiwan Reply
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Letter
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; YOUNG-ADULTS; CHILDREN;
ADOLESCENTS
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Hammerness, PG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM phammerness@partners.org
NR 5
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 MAR
PY 2012
VL 51
IS 3
BP 325
EP 326
DI 10.1016/j.jaac.2011.12.012
PG 2
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 902IG
UT WOS:000301031200012
ER
PT J
AU Niewczas, MA
Gohda, T
Skupien, J
Smiles, AM
Walker, WH
Rosetti, F
Cullere, X
Eckfeldt, JH
Doria, A
Mayadas, TN
Warram, JH
Krolewski, AS
AF Niewczas, Monika A.
Gohda, Tomohito
Skupien, Jan
Smiles, Adam M.
Walker, William H.
Rosetti, Florencia
Cullere, Xavier
Eckfeldt, John H.
Doria, Alessandro
Mayadas, Tanya N.
Warram, James H.
Krolewski, Andrzej S.
TI Circulating TNF Receptors 1 and 2 Predict ESRD in Type 2 Diabetes
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; CORONARY-HEART-DISEASE; FACTOR-ALPHA;
INFLAMMATORY CYTOKINES; RENAL-FUNCTION; RISK; MELLITUS; MARKERS;
NEPHROPATHY; WOMEN
AB Levels of proinflammatory cytokines associate with risk for developing type 2 diabetes but whether chronic inflammation contributes to the development of diabetic complications, such as ESRD, is unknown. In the 1990s, we recruited 410 patients with type 2 diabetes for studies of diabetic nephropathy and recorded their characteristics at enrollment. During 12 years of follow-up, 59 patients developed ESRD (17 per 1000 patient-years) and 84 patients died without ESRD (24 per 1000 patient-years). Plasma markers of systemic inflammation, endothelial dysfunction, and the TNF pathway were measured in the study entry samples. Of the examined markers, only TNF receptors 1 and 2 (TNFR1 and TNFR2) associated with risk for ESRD. These two markers were highly correlated, but ESRD associated more strongly with TNFR1. The cumulative incidence of ESRD for patients in the highest TNFR1 quartile was 54% after 12 years but only 3% for the other quartiles (P<0.001). In Cox proportional hazard analyses, TNFR1 predicted risk for ESRD even after adjustment for clinical covariates such as urinary albumin excretion. Plasma concentration of TNFR1 outperformed all tested clinical variables with regard to predicting ESRD. Concentrations of TNFRs moderately associated with death unrelated to ESRD. In conclusion, elevated concentrations of circulating TNFRs in patients with type 2 diabetes at baseline are very strong predictors of the subsequent progression to ESRD in subjects with and without proteinuria.
C1 [Niewczas, Monika A.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA.
[Niewczas, Monika A.; Gohda, Tomohito; Skupien, Jan; Doria, Alessandro; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Niewczas, Monika A.] Med Univ Warsaw, Dept Immunol Transplantol & Internal Dis, Warsaw, Poland.
[Gohda, Tomohito] Juntendo Univ, Sch Med, Dept Internal Med, Div Nephrol, Tokyo 113, Japan.
[Rosetti, Florencia; Cullere, Xavier; Mayadas, Tanya N.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA.
[Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA.
EM andrzej.krolewski@joslin.harvard.edu
FU Juvenile Diabetes Research Foundation [1-2008-1018, 3-2009-397];
National Institutes of Health [DK041526, DK067638, DK077111]; American
Diabetes Association mentor-based fellowship [7-03-MN-28]; Uehara
Memorial Foundation; Yasuhiko Tomino, Juntendo University, Tokyo, Japan;
CONACYT Fundacion Mexico
FX This study was supported by a Juvenile Diabetes Research Foundation
research grant (1-2008-1018) and grants from the National Institutes of
Health (DK041526 and DK067638) to ASK.; an American Diabetes Association
mentor-based fellowship (7-03-MN-28) to MAN.; a grant from the Uehara
Memorial Foundation and a personal grant from Yasuhiko Tomino, Juntendo
University, Tokyo, Japan, to T.G.; a Juvenile Diabetes Research
Foundation fellowship grant (3-2009-397) to J.S.; grants from the
National Institutes of Health to T.N.M. (DK077111 and HL065095) and X.C.
(KO1 AR054984); and a graduate student fellowship from CONACYT Fundacion
Mexico en Harvard to F.R.
NR 36
TC 125
Z9 130
U1 3
U2 10
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAR
PY 2012
VL 23
IS 3
BP 507
EP 515
DI 10.1681/ASN.2011060627
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 904OD
UT WOS:000301206900018
PM 22266663
ER
PT J
AU Gohda, T
Niewczas, MA
Ficociello, LH
Walker, WH
Skupien, J
Rosetti, F
Cullere, X
Johnson, AC
Crabtree, G
Smiles, AM
Mayadas, TN
Warram, JH
Krolewski, AS
AF Gohda, Tomohito
Niewczas, Monika A.
Ficociello, Linda H.
Walker, William H.
Skupien, Jan
Rosetti, Florencia
Cullere, Xavier
Johnson, Amanda C.
Crabtree, Gordon
Smiles, Adam M.
Mayadas, Tanya N.
Warram, James H.
Krolewski, Andrzej S.
TI Circulating TNF Receptors 1 and 2 Predict Stage 3 CKD in Type 1 Diabetes
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; SERUM CYSTATIN-C; RENAL-FUNCTION DECLINE;
FOLLOW-UP; ALPHA; NEPHROPATHY; GENERATION; KIDNEY; CELLS; RISK
AB Elevated plasma concentrations of TNF receptors 1 and 2 (TNFR1 and TNFR2) predict development of ESRD in patients with type 2 diabetes without proteinuria, suggesting these markers may contribute to the pathogenesis of renal decline. We investigated whether circulating markers of the TNF pathway determine GFR loss among patients with type 1 diabetes. We followed two cohorts comprising 628 patients with type 1 diabetes, normal renal function, and no proteinuria. Over 12 years, 69 patients developed estimated GFR less than 60 mL/min per 1.73 m(2) (16 per 1000 person-years). Concentrations of TNFR1 and TNFR2 were strongly associated with risk for early renal decline. Renal decline was associated only modestly with total TNF alpha concentration and appeared unrelated to free TNFa. The cumulative incidence of estimated GFR less than 60 mL/min per 1.73 m(2) for patients in the highest TNFR2 quartile was 60% after 12 years compared with 5%-19% in the remaining quartiles. In Cox proportional hazards analysis, patients with TNFR2 values in the highest quartile were threefold more likely to experience renal decline than patients in the other quartiles (hazard ratio, 3.0; 95% confidence interval, 1.7-5.5). The risk associated with high TNFR1 values was slightly less than that associated with high TNFR2 values. TNFR levels were unrelated to baseline free TNF alpha level and remained stable over long periods within an individual. In conclusion, early GFR loss in patients with type 1 diabetes without proteinuria is strongly associated with circulating TNF receptor levels but not TNF alpha levels (free or total).
C1 [Krolewski, Andrzej S.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA.
[Gohda, Tomohito; Niewczas, Monika A.; Ficociello, Linda H.; Skupien, Jan; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Gohda, Tomohito] Juntendo Univ, Sch Med, Dept Internal Med, Div Nephrol, Tokyo 113, Japan.
[Niewczas, Monika A.] Med Univ Warsaw, Dept Immunol Transplantol & Internal Dis, Warsaw, Poland.
[Rosetti, Florencia; Cullere, Xavier; Mayadas, Tanya N.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA.
RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA.
EM andrzej.krolewski@joslin.harvard.edu
FU JDRF [1-2008-1018, 3-2009-397]; National Institutes of Health [DK077111,
HL065095, DK041526, DK067638]; Uehara Memorial Foundation; Yasuhiko
Tomino (Juntendo University, Tokyo, Japan); American Diabetes
Association [7-03-MN-28]; CONACyT Fundacion Mexico
FX This study was supported by JDRF Research Grant 1-2008-1018 and Grants
DK041526 and DK067638 from the National Institutes of Health to A.S.K.,
a grant from the Uehara Memorial Foundation to T.G., a personal grant
from Yasuhiko Tomino (Juntendo University, Tokyo, Japan) to T.G., an
American Diabetes Association mentor-based fellowship (7-03-MN-28) to
M.A.N., a JDRF fellowship grant (3-2009-397) to J.S., National
Institutes of Health Grants DK077111 and HL065095 to T.N.M. and KO1
AR054984 to X.C., and a graduate student fellowship from CONACyT
Fundacion Mexico en Harvard to F.R.
NR 35
TC 99
Z9 102
U1 3
U2 5
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAR
PY 2012
VL 23
IS 3
BP 516
EP 524
DI 10.1681/ASN.2011060628
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 904OD
UT WOS:000301206900019
PM 22266664
ER
PT J
AU Roth, AJ
Brown, MC
Smith, RN
Badhwar, AK
Parente, O
Chung, HC
Bunch, DO
McGregor, JG
Hogan, SL
Hu, YC
Yang, JJ
Berg, EA
Niles, J
Jennette, JC
Preston, GA
Falk, RJ
AF Roth, Aleeza J.
Brown, Michael C.
Smith, Rex Neal
Badhwar, Anshul K.
Parente, Oscar
Chung, Hyun Chul
Bunch, Donna O'Dell
McGregor, JulieAnne G.
Hogan, Susan L.
Hu, Yichun
Yang, Jia-Jin
Berg, Elisabeth A.
Niles, John
Jennette, J. Charles
Preston, Gloria A.
Falk, Ronald J.
TI Anti-LAMP-2 Antibodies Are Not Prevalent in Patients With Antineutrophil
Cytoplasmic Autoantibody Glomerulonephritis
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CRESCENTIC GLOMERULONEPHRITIS; SYSTEMIC VASCULITIS; ANCA; GRANULOCYTES;
PATHOGENESIS; H-LAMP-2
AB Lysosomal membrane protein 2 (LAMP-2) is a target of antineutrophil cytoplasmic autoantibodies (ANCA) in addition to the more commonly known targets proteinase 3 and myeloperoxidase. The prevalence of anti-LAMP-2 antibodies and their relationship to disease in ANCA glomerulonephritis are not well described. We measured anti-LAMP-2 reactivity in 680 sera samples (two academic centers) from patients with ANCA glomerulonephritis (n=329); those with ANCA-negative glomerulonephritis (n=104); those with fimbriated, gram-negative Escherichia coli urinary tract infection (n=104); disease controls (n=19); and healthy volunteers (n=124). With levels in healthy controls used to define a reference range, anti-LAMP-2 reactivity was present in 21% of ANCA sera from two of the centers; reactivity was present in 16% of the control group with urinary tract infection. Western blotting and immunofluorescence microscopy did not verify positivity. Titers of anti-myeloperoxidase and anti-proteinase 3 antibodies were 1500-fold and 10,000-fold higher than anti-LAMP-2 titers, respectively. There was no correlation between anti-LAMP-2 antibodies and disease activity. Furthermore, Wistar Kyoto rats injected with anti-LAMP-2 antibodies did not develop glomerulonephritis. In conclusion, antibodies that react with LAMP-2 may exist at very low titers in a minority of patients with ANCA disease. These data do not support a mechanistic relationship between anti-LAMP-2 antibodies and ANCA glomerulonephritis.
C1 [Roth, Aleeza J.; Brown, Michael C.; Badhwar, Anshul K.; Parente, Oscar; Chung, Hyun Chul; Bunch, Donna O'Dell; McGregor, JulieAnne G.; Hogan, Susan L.; Hu, Yichun; Yang, Jia-Jin; Berg, Elisabeth A.; Jennette, J. Charles; Preston, Gloria A.; Falk, Ronald J.] Univ N Carolina, Kidney Ctr, Dept Med, Div Nephrol & Hypertens, Chapel Hill, NC 27599 USA.
[Roth, Aleeza J.; Jennette, J. Charles; Preston, Gloria A.; Falk, Ronald J.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
[Smith, Rex Neal; Niles, John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Roth, AJ (reprint author), Univ N Carolina, Kidney Ctr, Dept Med, Div Nephrol & Hypertens, CB 7155,5009 Burnett Womack Bldg, Chapel Hill, NC 27599 USA.
EM ajroth@med.unc.edu
FU National Institute of Diabetes and Digestive and Kidney
Diseases/National Institutes of Health [2PO1DK]; National Institutes of
Health Training from the National Institute for Environmental Health
Sciences [T32 ES 07017]; Howard Hughes Medical Institute (HHMI); HHMI
through the Med
FX This work was supported by National Institute of Diabetes and Digestive
and Kidney Diseases/National Institutes of Health Grant 2PO1DK, National
Institutes of Health Training Grant T32 ES 07017 from the National
Institute for Environmental Health Sciences, and the Howard Hughes
Medical Institute (HHMI) Med into Grad Scholar, supported in part by a
grant to the University of North Carolina at Chapel Hill from HHMI
through the Med into Grad Initiative.
NR 15
TC 58
Z9 66
U1 1
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAR
PY 2012
VL 23
IS 3
BP 545
EP 555
DI 10.1681/ASN.2011030273
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 904OD
UT WOS:000301206900022
PM 22021709
ER
PT J
AU Lombardi, JV
Cambria, RP
Nienaber, CA
Chiesa, R
Teebken, O
Lee, A
Mossop, P
Bharadwaj, P
AF Lombardi, Joseph V.
Cambria, Richard P.
Nienaber, Christoph A.
Chiesa, Roberto
Teebken, Omke
Lee, Anthony
Mossop, Peter
Bharadwaj, Priya
CA STABLE Investigators
TI Prospective multicenter clinical trial (STABLE) on the endovascular
treatment of complicated type B aortic dissection using a composite
device design
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT Vascular Annual Meeting of the Society-for-Vascular-Surgery
(SVS)/Plenary Session of William Von Liebig Forum/36th Annual Spring
Meeting of the Peripheral-Vascular-Surgery-Society
CY JUN 15-18, 2011
CL Chicago, IL
SP Soc Vasc Surg (SVS), Peripheral Vasc Surg Soc
ID STENT-GRAFT PLACEMENT; ANEURYSM REPAIR; INTERNATIONAL REGISTRY;
MANAGEMENT; DISEASES; SOCIETY
AB Objective: This study evaluates the safety and effectiveness of a unique composite thoracic endovascular aneurysm repair (TEVAR) construct (proximal stent graft and distal bare metal stent) for the treatment of patients with complicated type B aortic dissection (cTBAD).
Methods: In this prospective, single-arm, multicenter study, patients with cTBAD were treated with an endovascular system consisting of proximal TX2 thoracic stent grafts and distal bare metal dissection stents (Zenith Dissection Endovascular System; Cook Medical, Bloomington, Ind). Indications for enrollment were branch vessel malperfusion, impending rupture, aortic diameter >= 40 mm, rapid aortic expansion, and persistent pain or hypertension despite maximum medical therapy. One-year follow-up results, including clinical and radiographic (computerized tomography [ CT] and X-ray) evaluation, were available for this report.
Results: Ten centers enrolled 40 patients (70% men; mean age 58 years old) between December 2007 and August 2009. The onset of symptoms was acute (<= 14 days) in 24 patients (60%), subacute (15-30 days) in six patients (15%), and chronic (31-90 days) in 10 patients (25%); the overall mean time from symptom onset to treatment was 20 days (range, 0-78 days). A majority of patients (77.5%; 31 of 40 patients) presented with impending aortic rupture (indicated by periaortic effusion/hematoma) or branch vessel malperfusion. Seven combinations of stent grafts and dissection stents were used, and all devices were successfully deployed and patent. The 30-day mortality rate was 5% (2 of 40); two deaths occurred after 30 days, leading to a 1-year survival rate of 90%. Two deaths, occurring at 11 and 81 days postprocedure, respectively, were secondary to aortic rupture. Morbidity occurring within 30 days included stroke (7.5%), transient ischemic attack (2.5%), paraplegia (2.5%), retrograde progression of dissection (5%), and renal failure (12.5%). Additional morbidity after 30 days included one case of retrograde progression of dissection and one case of renal failure. None of the patients with renal failure became dialysis-dependent. Four patients (10%) underwent secondary interventions within 1 year. Favorable aortic remodeling was observed during the course of follow-up, indicated by an increase in the true lumen size and a concomitant decrease in the false lumen size along the dissected aorta, with completely thrombosed thoracic false lumen observed in 31% of patients at 12 months as compared to 0% at baseline.
Conclusions: Initial data with a composite TEVAR construct have demonstrated favorable clinical and anatomic results. Continued enrollment and long-term data are needed to assess the overall effectiveness of this treatment strategy. (J Vasc Surg 2012; 55: 629-40.)
C1 [Lombardi, Joseph V.] Cooper Univ Hosp, Div Vasc & Endovasc Surg, Dept Surg, Camden, NJ 08103 USA.
[Cambria, Richard P.] Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA.
[Nienaber, Christoph A.] Univ Hosp Rostock, Clin Internal Med, Rostock, Germany.
[Chiesa, Roberto] Hosp San Raffaele, I-20132 Milan, Italy.
[Teebken, Omke] Hannover Med Sch, Dept Cardiac Thorac Transplantat & Vasc Surg, D-3000 Hannover, Germany.
[Lee, Anthony] Christine E Lynn Heart & Vasc Inst, Boca Raton, FL USA.
[Mossop, Peter] St Vincents Hosp Melbourne, Dept Med Imaging, Fitzroy, Vic, Australia.
[Bharadwaj, Priya] MED Inst, W Lafayette, IN USA.
RP Lombardi, JV (reprint author), Cooper Univ Hosp, Div Vasc & Endovasc Surg, Dept Surg, 3 Cooper Plaza,Suite 411, Camden, NJ 08103 USA.
EM lombardi-joseph@cooperhealth.edu
NR 22
TC 63
Z9 69
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD MAR
PY 2012
VL 55
IS 3
BP 629
EP U319
DI 10.1016/j.jvs.2011.10.022
PG 14
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 901DE
UT WOS:000300941100001
PM 22169668
ER
PT J
AU Bechara, CF
Barshes, NR
Lin, PH
Kougias, P
AF Bechara, Carlos F.
Barshes, Neal R.
Lin, Peter H.
Kougias, Panagiotis
TI Recanalization of flush iliac occlusions with the assistance of a
contralateral iliac occlusive balloon
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID RECONSTRUCTION; MANAGEMENT
AB Treating flush iliac artery occlusion by endovascular means can be very challenging and is a cause of technical failure requiring open surgical intervention. We describe a simple endovascular technique that can be valuable in increasing technical success and avoiding the use of a re-entry device. The technique involves placing an occlusive contralateral iliac artery balloon to assist in recanalizing a flush iliac artery occlusion. (J Vasc Surg 2012;55:872-4.)
C1 Baylor Coll Med, Div Vasc & Endovasc Therapy, Michael E DeBakey Dept Surg, Houston, TX 77030 USA.
Michael E DeBakey VA Med Ctr, Houston, TX USA.
RP Bechara, CF (reprint author), DeBakey VA Med Ctr, 2002 Holcombe Blvd,112, Houston, TX 77030 USA.
EM bechara@bcm.edu
NR 9
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD MAR
PY 2012
VL 55
IS 3
BP 872
EP 874
DI 10.1016/j.jvs.2011.10.029
PG 3
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 901DE
UT WOS:000300941100038
PM 22169670
ER
PT J
AU Goodney, PP
Fisher, ES
Cambria, RP
AF Goodney, Philip P.
Fisher, Elliott S.
Cambria, Richard P.
TI Roles for specialty societies and vascular surgeons in accountable care
organizations
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID QUALITY IMPROVEMENT PROGRAM; PERIPHERAL ARTERIAL-DISEASE; ABDOMINAL
AORTIC-ANEURYSM; CRITICAL LIMB ISCHEMIA; NORTHERN NEW-ENGLAND;
MEDICARE-POPULATION; CAROTID-ENDARTERECTOMY; PRACTICE GUIDELINES;
AMERICAN-COLLEGE; LOWER-EXTREMITY
AB With the passage of the Affordable Care Act, accountable care organizations (ACOs) represent a new paradigm in healthcare payment reform. Designed to limit growth in spending while preserving quality, these organizations aim to incant physicians to lower costs by returning a portion of the savings realized by cost-effective, evidence-based care back to the ACO. In this review, first, we will explore the development of ACOs within the context of prior attempts to control Medicare spending, such as the sustainable growth rate and managed care organizations. Second, we describe the evolution of ACOs, the demonstration projects that established their feasibility, and their current organizational structure. Third, because quality metrics are central to the use and implementation of ACOs, we describe current efforts to design, collect, and interpret quality metrics in vascular surgery. And fourth, because a "seat at the table" will be an important key to success for vascular surgeons in these efforts, we discuss how vascular surgeons can participate and lead efforts within ACOs. (J Vasc Surg 2012;55:875-82.)
C1 [Goodney, Philip P.] Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, Hanover, NH USA.
[Goodney, Philip P.; Fisher, Elliott S.] Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA.
[Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Goodney, PP (reprint author), Dartmouth Hitchcock Med Ctr, 1 Med Ctr Dr, Lebanon, NH 03766 USA.
EM philip.goodney@hitchcock.org
FU NHLBI [1K08HL05676-01]; AVA/ACS
FX Dr Goodney was supported by a K08 Award (1K08HL05676-01) from the NHLBI,
and a AVA/ACS Supplemental Award.
NR 62
TC 10
Z9 10
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD MAR
PY 2012
VL 55
IS 3
BP 875
EP 882
DI 10.1016/j.jvs.2011.10.116
PG 8
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 901DE
UT WOS:000300941100039
PM 22370029
ER
PT J
AU Sperling, R
Salloway, S
Brooks, DJ
Tampieri, D
Barakos, J
Fox, NC
Raskind, M
Sabbagh, M
Honig, LS
Porsteinsson, AP
Lieberburg, I
Arrighi, HM
Morris, KA
Lu, Y
Liu, E
Gregg, KM
Brashear, HR
Kinney, GG
Black, R
Grundman, M
AF Sperling, Reisa
Salloway, Stephen
Brooks, David J.
Tampieri, Donatella
Barakos, Jerome
Fox, Nick C.
Raskind, Murray
Sabbagh, Marwan
Honig, Lawrence S.
Porsteinsson, Anton P.
Lieberburg, Ivan
Arrighi, H. Michael
Morris, Kristen A.
Lu, Yuan
Liu, Enchi
Gregg, Keith M.
Brashear, H. Robert
Kinney, Gene G.
Black, Ronald
Grundman, Michael
TI Amyloid-related imaging abnormalities in patients with Alzheimer's
disease treated with bapineuzumab: a retrospective analysis
SO LANCET NEUROLOGY
LA English
DT Article
ID CEREBRAL MICROBLEEDS; ANGIOPATHY; BETA; INFLAMMATION; PREVALENCE;
EPSILON-4; PROTEIN; TRIALS; BRAIN; MODEL
AB Background Amyloid-related imaging abnormalities (ARIA) have been reported in patients with Alzheimer's disease treated with bapineuzumab, a humanised monoclonal antibody against amyloid beta. ARIA include MRI signal abnormalities suggestive of vasogenic oedema and sulcal effusions (ARIA-E) and microhaemorrhages and haemosiderin deposits (ARIA-H). Our aim was to investigate the incidence of ARIA during treatment with bapineuzumab, and evaluate associated risk factors.
Methods Two neuroradiologists independently reviewed 2572 fluid-attenuated inversion recovery (FLAIR) MRI scans from 262 participants in two phase 2 studies of bapineuzumab and an open-label extension study. Readers were masked to the patient's treatment, APOE epsilon 4 genotype, medical history, and demographics. Patients were included in risk analyses if they had no evidence of ARIA-E in their pre-treatment MRI, had received bapineuzumab, and had at least one MRI scan after treatment. We used Kaplan-Meier survival analysis to examine the distribution of incident ARIA-E from the start of bapineuzumab treatment and proportional hazards regression models to assess risk factors associated with ARIA.
Findings 210 patients were included in the risk analyses. 36 patients (17%) developed ARIA-E during treatment with bapineuzumab; 15 of these ARIA-E cases (42%) had not been detected previously. 28 of these patients (78%) did not report associated symptoms. Adverse events, reported in eight symptomatic patients, included headache, confusion, and neuropsychiatric and gastrointestinal symptoms. Incident ARIA-H occurred in 17 of the patients with ARIA-E (47%), compared with seven of 177 (4%) patients without ARIA-E. 13 of the 15 patients in whom ARIA were detected in our study received additional treatment infusions while ARIA-E were present, without any associated symptoms. Occurrence of ARIA-E increased with bapineuzumab dose (hazard ratio [HR] 2.24 per 1 mg/kg increase in dose, 95% CI 1.40-3.62; p=0.0008) and presence of APOE epsilon 4 alleles (HR 2.55 per allele, 95% CI 1.57-4.12; p=0.0001).
Interpretation ARIA consist of a spectrum of imaging findings with variable clinical correlates, and some patients with ARIA-E remain asymptomatic even if treatment is continued. The increased risk of ARIA among APOE e4 carriers, its association with high bapineuzumab dose, and its timecourse in relation to dosing suggest an association between ARIA and alterations in vascular amyloid burden.
C1 [Sperling, Reisa] Harvard Univ, Sch Med, Brigham & Womens Hosp,Ctr Alzheimer Res & Treatme, Memory Disorders Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Salloway, Stephen] Butler Hosp, Providence, RI 02906 USA.
[Brooks, David J.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Ctr Neurosci, London, England.
[Tampieri, Donatella] McGill Univ, Montreal, PQ, Canada.
[Barakos, Jerome] Calif Pacific Med Ctr, Francisco, CA USA.
[Fox, Nick C.] UCL, Inst Neurol, London, England.
[Raskind, Murray] VA Med Ctr, Seattle, WA USA.
[Sabbagh, Marwan] Cleo Roberts Ctr Clin Res, Sun Hlth Res Inst, Sun City, AZ USA.
[Honig, Lawrence S.] Columbia Univ, New York, NY USA.
[Porsteinsson, Anton P.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Lieberburg, Ivan] Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA.
[Arrighi, H. Michael; Morris, Kristen A.; Lu, Yuan; Liu, Enchi; Gregg, Keith M.; Brashear, H. Robert; Kinney, Gene G.; Grundman, Michael] Janssen Alzheimer Immunotherapy Res & Dev, San Francisco, CA USA.
[Black, Ronald] Pifzer, Collegeville, PA USA.
[Grundman, Michael] Global R&D Partners, San Diego, CA USA.
RP Sperling, R (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Ctr Alzheimer Res & Treatme, Memory Disorders Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA.
EM reisa@rics.bwh.harvard.edu
RI Fox, Nick/B-1319-2009;
OI Fox, Nick/0000-0002-6660-657X; Brooks, David/0000-0003-2602-2518
FU Elan Corporation; Janssen Alzheimer Immunotherapy; Wyeth
Pharmaceuticals; Pfizer; Celgene Corporation; Ceregene; Bayer AG; Baxter
International; Bristol-Myers Squibb; Eli Lilly and Company; Janssen
Alzheimer Immunotherapy Research and Development; Avid
Radiopharmaceuticals; Genentech; Eisai; Hoffmann-La Roche; Medivation;
Toyama Chemical Co; Elan Corporation (South San Francisco, CA, USA
FX Elan Corporation, Janssen Alzheimer Immunotherapy, Wyeth
Pharmaceuticals, and Pfizer.; RS has served as a study investigator and
a consultant for Janssen Alzheimer Immunotherapy Research and
Development, and for Pfizer, and has received honoraria for
participation in symposia. She has also served as a consultant or site
investigator or both for Bristol-Myers Squibb, Roche, Elan, Biogen-IDEC,
Avid, and Bayer. SS has served as a consultant and study investigator
for Janssen Alzheimer Immunotherapy Research and Development, Pfizer,
and Elan Corporation phase 2 and 3 studies of bapineuzumab. DT provides
review of MRI images for Janssen Alzheimer Immunotherapy Research and
Development. JB serves as a neuroradiological consultant to SYNARC, an
imaging contract research organisation contracted by both sponsor
companies; he also serves as a consultant to Janssen Alzheimer
Immunotherapy Research and Development for non-clinical research
activities. NCF has provided consulting or image analysis services or
both to Elan Corporation, Janssen Alzheimer Immunotherapy Research and
Development, Pfizer, Wyeth Pharmaceuticals, AstraZeneca, Bristol-Myers
Squibb, Eli Lilly and Company, GE Healthcare, Lundbec.k A/S, and IXICO.
MR serves as consultant to Janssen Alzheimer Immunotherapy Research and
Development. MS participates in a consulting and advisory capacity for
Eli Lilly and Company, Amerisciences, Takeda Pharmaceuticals, Eisai,
Pfizer, and GlaxoSmithKline, and receives royalties from Wiley and
AmeriSciences. He receives contracting fees and grants from Celgene
Corporation, Ceregene, Bayer AG, Baxter International, Bristol-Myers
Squibb, Eli Lilly and Company, Pfizer, Janssen Alzheimer Immunotherapy
Research and Development, Avid Radiopharmaceuticals, Genentech, and
Eisai. LSH serves on the study steering committee and has acted as a
consultant for Janssen Alzheimer Immunotherapy Research and Development,
but receives less than US$10000 yearly for such consulting activities.
APP has received grant and research support from Baxter International,
Bristol-Myers Squibb, Eisai, Elan Corporation, Genentech, Hoffmann-La
Roche, Janssen Alzheimer Immunotherapy Research and Development,
Medivation, Pfizer, and Toyama Chemical Co. He has also served as a
consultant and participated on advisory boards for Elan Corporation,
Janssen Alzheimer Immunotherapy Research and Development, Medivation,
Pfizer, Transition Therapeutics, and Toyama Chemical Co. He is also a
member of the speakers' bureau for Forest Laboratories. RB is an
employee of and receives stock and stock options from Pfizer. H MA, KAM,
YL, EL, KMG, HRB, and GGK are employees of Janssen Alzheimer
lmmunotherapy Research and Development. IL, H MA, ICAM, YL, EL, KMG, and
GGK are stockholders in Elan Corporation. MG is a consultant to Janssen
Alzheimer Immunotherapy Research and Development and is a stockholder in
Elan Corporation. DJB declares no conflicts of interest.; This study was
sponsored by Elan Corporation (South San Francisco, CA, USA; Janssen
Alzheimer Immunotherapy acquired the Alzheimer Immunotherapy Program
from Elan Corporation in September, 2009) and Wyeth Pharmaceuticals
(Collegeville, PA, USA; which was acquired by Pfizer in October, 2009).
We thank Lorna Fang for her contributions to the analytic programming,
and Selena Scaglione and Mark McGovern for their contributions to study
operation and management. Editorial support was provided by Elizabeth
Yepez (Phase Five Communications; New York, NY, USA), and was funded by
Janssen Alzheimer Immunotherapy Research and Development. Her
involvement consisted of manuscript formatting only, and no contribution
was made to content.
NR 27
TC 149
Z9 152
U1 6
U2 28
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD MAR
PY 2012
VL 11
IS 3
BP 241
EP 249
DI 10.1016/S1474-4422(12)70015-7
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 902BZ
UT WOS:000301014900012
PM 22305802
ER
PT J
AU Smith, EE
Schneider, JA
Wardlaw, JM
Greenberg, SM
AF Smith, Eric E.
Schneider, Julie A.
Wardlaw, Joanna M.
Greenberg, Steven M.
TI Cerebral microinfarcts: the invisible lesions
SO LANCET NEUROLOGY
LA English
DT Review
ID SMALL VESSEL DISEASE; CORTICAL WATERSHED MICROINFARCTS; APPARENT
DIFFUSION-COEFFICIENT; WHITE-MATTER LESIONS; AMYLOID ANGIOPATHY;
ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; ISCHEMIC-STROKE; BLOOD-PRESSURE;
PATHOLOGICAL CORRELATION
AB The association between small but still visible lacunar infarcts and cognitive decline has been established by population-based radiological and pathological studies. Microscopic examination of brain sections shows even smaller but substantially more numerous microinfarcts, the focus of this Review. These lesions often result from small vessel pathologies such as arteriolosclerosis or cerebral amyloid angiopathy. They typically go undetected in clinical radiological correlation studies that rely on conventional structural MRI, although the largest acute microinfarcts can be detected by diffusion-weighted imaging. In view of their high numbers and widespread distribution, microinfarcts could directly disrupt important cognitive networks and thus account for some of the neurological dysfunction associated with lesions visible on conventional MRI such as lacunar infarcts and white matter hyperintensities. Standardised neuropathological assessment criteria and the development of non-invasive means of detection during life would be major steps towards understanding the causes and consequences of otherwise macroscopically invisible microinfarcts.
C1 [Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Kistler Stroke Res Ctr, Boston, MA 02114 USA.
[Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada.
[Schneider, Julie A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Dept Pathol, Chicago, IL 60612 USA.
[Schneider, Julie A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
[Wardlaw, Joanna M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol CCACE, Edinburgh, Midlothian, Scotland.
[Wardlaw, Joanna M.] Scottish Imaging Network Platform Sci Excellence, Edinburgh, Midlothian, Scotland.
RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Kistler Stroke Res Ctr, 175 Cambridge St, Boston, MA 02114 USA.
EM sgreenberg@partners.org
OI Smith, Eric/0000-0003-3956-1668
FU Alberta Innovates Health Solutions; Alberta Heritage Fund for Medical
Research; Canadian Institutes of Health Research; Scottish Funding
Council; National Institutes of Health for the study of microinfarcts in
cerebral amyloid angiopathy [2R01 AG26484-01]
FX No external funding was obtained for this Review. EES receives salary
support from Alberta Innovates Health Solutions (funded by the Alberta
Heritage Fund for Medical Research) and the Canadian Institutes of
Health Research. JMW receives partial funding support from the Scottish
Funding Council. SMG receives salary support from the National
Institutes of Health including for the study of microinfarcts in
cerebral amyloid angiopathy (2R01 AG26484-01). SMG had full access to
all the data and had the final responsibility for the decision to submit
for publication. We thank Chunhui Yang for contributions to figure 1;
Eric Jouvent and Hugues Chabriat for contributing figure 2; Dorothea
Strozyk, Joe Verghese, and Richard O'Brien for contributing unpublished
data used in table 1 and figure 4; and Chelsea Kidwell for providing
details of her studies presented at the 2010 International Stroke
Conference and published in abstract form.
NR 95
TC 138
Z9 145
U1 7
U2 43
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD MAR
PY 2012
VL 11
IS 3
BP 272
EP 282
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA 902BZ
UT WOS:000301014900015
PM 22341035
ER
PT J
AU Reddy, MM
Fernandes, MS
Deshpande, A
Weisberg, E
Inguilizian, HV
Abdel-Wahab, O
Kung, AL
Levine, RL
Griffin, JD
Sattler, M
AF Reddy, M. M.
Fernandes, M. S.
Deshpande, A.
Weisberg, E.
Inguilizian, H. V.
Abdel-Wahab, O.
Kung, A. L.
Levine, R. L.
Griffin, J. D.
Sattler, M.
TI The JAK2V617F oncogene requires expression of inducible
phosphofructokinase/fructose-bisphosphatase 3 for cell growth and
increased metabolic activity
SO LEUKEMIA
LA English
DT Article
DE myeloid neoplasia; tyrosine kinase oncogene; signal transduction;
PFKFB3; JAK2
ID FRUCTOSE 2,6-BISPHOSPHATE; CANCER-CELLS; TRANSCRIPTION FACTORS;
6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE;
6-PHOSPHOFRUCTO-2-KINASE; INHIBITION; MYC; PATHWAY; FAMILY; PFKFB3
AB Myeloproliferative neoplasms are characterized by overproduction of myeloid lineage cells with frequent acquisition of oncogenic JAK2V617F kinase mutations. The molecular mechanisms that regulate energy requirements in these diseases are poorly understood. Transformed cells tend to rely on fermentation instead of more efficient oxidative phosphorylation for energy production. Our data in JAK2V617F-transformed cells show that growth and metabolic activity were strictly dependent on the presence of glucose. Uptake of glucose and cell surface expression of the glucose transporter Glut1 required the oncogenic tyrosine kinase. Importantly, JAK2V617F as well as active STAT5 increased the expression of the inducible rate-limiting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), which controls glycolytic flux through 6-phosphofructo-1-kinase. PFKFB3 was required for JAK2V617F-dependent lactate production, oxidative metabolic activity and glucose uptake. Targeted knockdown of PFKFB3 also limited cell growth under normoxic and hypoxic conditions and blocked in vivo tumor formation in mice. Overall, these data suggest that inducible PFKFB3 is required for increased growth, metabolic activity and is regulated through active JAK2 and STAT5. Novel therapies that specifically block PFKFB3 activity or expression would, therefore, be expected to inhibit JAK2/STAT5-dependent malignancies and related cancers. Leukemia (2012) 26, 481-489; doi:10.1038/leu.2011.225; published online 23 August 2011
C1 [Reddy, M. M.; Fernandes, M. S.; Deshpande, A.; Weisberg, E.; Griffin, J. D.; Sattler, M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Reddy, M. M.; Fernandes, M. S.; Deshpande, A.; Weisberg, E.; Griffin, J. D.; Sattler, M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Reddy, M. M.; Fernandes, M. S.; Deshpande, A.; Weisberg, E.; Griffin, J. D.; Sattler, M.] Harvard Univ, Sch Med, Boston, MA USA.
[Inguilizian, H. V.; Kung, A. L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02215 USA.
[Abdel-Wahab, O.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Abdel-Wahab, O.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA.
[Kung, A. L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
RP Sattler, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM martin_sattler@dfci.harvard.edu
OI Abdel-Wahab, Omar/0000-0002-3907-6171; Kung, Andrew/0000-0002-9091-488X
FU National Institutes of Health [CA134660-03]
FX This study was supported in part by the National Institutes of Health
grant (CA134660-03, MS). RLL is a Geoffrey Beene Junior Chair.
NR 35
TC 12
Z9 12
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD MAR
PY 2012
VL 26
IS 3
BP 481
EP 489
DI 10.1038/leu.2011.225
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA 905RK
UT WOS:000301290300014
PM 21860432
ER
PT J
AU Fan, AP
Benner, T
Bolar, DS
Rosen, BR
Adalsteinsson, E
AF Fan, Audrey P.
Benner, Thomas
Bolar, Divya S.
Rosen, Bruce R.
Adalsteinsson, Elfar
TI Phase-based regional oxygen metabolism (PROM) using MRI
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE cerebral metabolic rate of oxygen; cerebral venous oxygen saturation;
cerebral blood flow; MR susceptometry
ID CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY;
MAGNETIC-SUSCEPTIBILITY; HIGH-FIELD; OXIDATIVE-METABOLISM;
RELAXATION-TIME; BRAIN; CORTEX; SUSCEPTOMETRY; VALIDATION
AB Venous oxygen saturation (Yv) in cerebral veins and the cerebral metabolic rate of oxygen (CMRO2) are important indicators for brain function and disease. Although MRI has been used for global measurements of these parameters, currently there is no recognized technique to quantify regional Yv and CMRO2 using noninvasive imaging. This article proposes a technique to quantify CMRO2 from independent MRI estimates of Yv and cerebral blood flow. The approach uses standard gradient-echo and arterial spin labeling acquisitions to make these measurements. Using MR susceptometry on gradient-echo phase images, Yv was quantified for candidate vein segments in gray matter that approximate a long cylinder parallel to the main magnetic field. Local cerebral blood flow for the identified vessel was determined from a corresponding region in the arterial spin labeling perfusion map. Fick's principle of arteriovenous difference was then used to quantify CMRO2 locally around each vessel. Application of this method in young, healthy subjects provided gray matter averages of 59.6% +/- 2.3% for Yv, 51.7 +/- 6.4 mL/100 g/min for cerebral blood flow, and 158 +/- 18 mu ol/100 g/min for CMRO2 (mean +/- SD, n = 12), which is consistent with values previously reported by positron emission tomography and MRI. Magn Reson Med, 2012. (c) 2011 Wiley Periodicals, Inc.
C1 [Fan, Audrey P.; Bolar, Divya S.; Adalsteinsson, Elfar] MIT, Elect Res Lab, Dept Elect Engn & Comp Sci, Magnet Resonance Imaging Grp, Cambridge, MA 02139 USA.
[Benner, Thomas; Bolar, Divya S.; Rosen, Bruce R.; Adalsteinsson, Elfar] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Fan, Audrey P.; Bolar, Divya S.; Rosen, Bruce R.; Adalsteinsson, Elfar] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA.
RP Fan, AP (reprint author), MIT, Elect Res Lab, Dept Elect Engn & Comp Sci, Magnet Resonance Imaging Grp, 32 Vassar St,Room 36-792, Cambridge, MA 02139 USA.
EM apfan@mit.edu
FU NIH [T90-DA022759, T32-GM07753, R01-EB007942]; Siemens Healthcare;
Siemens Healthcare, Siemens-MIT Alliance
FX Grant sponsor: NIH; Grant numbers: T90-DA022759, T32-GM07753,
R01-EB007942; Grant sponsor: Siemens Healthcare; Grant sponsor: Siemens
Healthcare, Siemens-MIT Alliance.
NR 45
TC 41
Z9 44
U1 0
U2 7
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 MAR
PY 2012
VL 67
IS 3
BP 669
EP 678
DI 10.1002/mrm.23050
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 897UO
UT WOS:000300683900011
PM 21713981
ER
PT J
AU Cummings, DE
Bloom, SR
Rubino, F
AF Cummings, David E.
Bloom, Stephen R.
Rubino, Francesco
TI At the heart of the benefits of bariatric surgery
SO NATURE MEDICINE
LA English
DT Editorial Material
ID MORTALITY; WEIGHT; OBESE
AB Obesity is associated with an increased risk of cardiovascular events, thus weight loss would be expected to have a beneficial effect on cardiovascular disease. This view is supported by a recent paper that used participants from the ongoing Swedish Obese Subjects (SOS) study, a nonrandomized, prospective study to investigate the effects of bariatric surgery on cardiovascular disease(1). Individuals who underwent bariatric surgery had a significantly reduced number of total and fatal cardiovascular events compared with matched obese controls who did not undergo surgery. Surprisingly, the reduction in cardiovascular events was not related to the baseline body mass index (BMI) or the weight loss experienced by the treated patients. We asked three experts how this study affects understanding of the relationship between weight loss, metabolic and cardiovascular disease, as well as how bariatric surgery may mediate its effects on human health.
C1 [Cummings, David E.] Univ Washington, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA.
[Cummings, David E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Bloom, Stephen R.] Imperial Coll London Hammersmith, London, England.
[Rubino, Francesco] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA.
RP Cummings, DE (reprint author), Univ Washington, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA.
NR 12
TC 1
Z9 1
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD MAR
PY 2012
VL 18
IS 3
BP 358
EP 359
DI 10.1038/nm0312-358
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 905IF
UT WOS:000301264800034
PM 22395701
ER
PT J
AU Lipson, D
Capelletti, M
Yelensky, R
Otto, G
Parker, A
Jarosz, M
Curran, JA
Balasubramanian, S
Bloom, T
Brennan, KW
Donahue, A
Downing, SR
Frampton, GM
Garcia, L
Juhn, F
Mitchell, KC
White, E
White, J
Zwirko, Z
Peretz, T
Nechushtan, H
Soussan-Gutman, L
Kim, J
Sasaki, H
Kim, HR
Park, SI
Ercan, D
Sheehan, CE
Ross, JS
Cronin, MT
Janne, PA
Stephens, PJ
AF Lipson, Doron
Capelletti, Marzia
Yelensky, Roman
Otto, Geoff
Parker, Alex
Jarosz, Mirna
Curran, John A.
Balasubramanian, Sohail
Bloom, Troy
Brennan, Kristina W.
Donahue, Amy
Downing, Sean R.
Frampton, Garrett M.
Garcia, Lazaro
Juhn, Frank
Mitchell, Kathy C.
White, Emily
White, Jared
Zwirko, Zac
Peretz, Tamar
Nechushtan, Hovav
Soussan-Gutman, Lior
Kim, Jhingook
Sasaki, Hidefumi
Kim, Hyeong Ryul
Park, Seung-il
Ercan, Dalia
Sheehan, Christine E.
Ross, Jeffrey S.
Cronin, Maureen T.
Jaenne, Pasi A.
Stephens, Philip J.
TI Identification of new ALK and RET gene fusions from colorectal and lung
cancer biopsies
SO NATURE MEDICINE
LA English
DT Article
ID MUTATIONS; SENSITIVITY; CARCINOMAS; ACTIVATION; INHIBITOR; GEFITINIB;
ERLOTINIB; CETUXIMAB; PATHWAYS; TUMORS
AB Applying a next-generation sequencing assay targeting 145 cancer-relevant genes in 40 colorectal cancer and 24 non-small cell lung cancer formalin-fixed paraffin-embedded tissue specimens identified at least one clinically relevant genomic alteration in 59% of the samples and revealed two gene fusions, C2orf44-ALK in a colorectal cancer sample and KIF5B-RET in a lung adenocarcinoma. Further screening of 561 lung adenocarcinomas identified 11 additional tumors with KIF5B-RET gene fusions (2.0%; 95% CI 0.8-3.1%). Cells expressing oncogenic KIF5B-RET are sensitive to multi-kinase inhibitors that inhibit RET.
C1 [Lipson, Doron; Yelensky, Roman; Otto, Geoff; Parker, Alex; Jarosz, Mirna; Curran, John A.; Balasubramanian, Sohail; Bloom, Troy; Brennan, Kristina W.; Donahue, Amy; Downing, Sean R.; Frampton, Garrett M.; Garcia, Lazaro; Juhn, Frank; Mitchell, Kathy C.; White, Emily; White, Jared; Zwirko, Zac; Ross, Jeffrey S.; Cronin, Maureen T.; Stephens, Philip J.] Fdn Med, Cambridge, MA USA.
[Capelletti, Marzia; Ercan, Dalia; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
[Peretz, Tamar; Nechushtan, Hovav] Hadassah Hebrew Univ Med Ctr, Sharett Inst Oncol, Jerusalem, Israel.
[Soussan-Gutman, Lior] Oncotest Teva Pharmaceut Ind, Petah Tiqwa, Israel.
[Kim, Jhingook] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Thorac Surg, Seoul, South Korea.
[Sasaki, Hidefumi] Nagoya City Univ, Dept Oncol Immunol & Surg 2, Grad Sch Med Sci, Nagoya, Aichi, Japan.
[Kim, Hyeong Ryul; Park, Seung-il] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Thorac Surg, Seoul, South Korea.
[Sheehan, Christine E.; Ross, Jeffrey S.] Albany Med Ctr, Dept Pathol, Albany, NY USA.
RP Stephens, PJ (reprint author), Fdn Med, Cambridge, MA USA.
EM mcronin@foundationmedicine.com; pjanne@partners.org;
pstephens@foundationmedicine.com
FU Dana Farber/Harvard Cancer Center Lung Cancer SPORE [P50 CA090578];
Cammarata Family Foundation; Dana-Farber Cancer Institute; Japan Society
for the Promotion of Science (JSPS) [23659674, 21390394, 21591820]
FX We would like to thank M. Hawryluk for his help in preparing this
manuscript. This work is supported by the Dana Farber/Harvard Cancer
Center Lung Cancer SPORE P50 CA090578 (P.A.J.), the Cammarata Family
Foundation Research Fund (M. C. and P.A.J.), the Nirenberg Fellowship at
the Dana-Farber Cancer Institute (M. C. and P.A.J.) and the Japan
Society for the Promotion of Science (JSPS), grant references 23659674,
21390394 and 21591820 (H.S.).
NR 20
TC 366
Z9 383
U1 10
U2 59
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD MAR
PY 2012
VL 18
IS 3
BP 382
EP 384
DI 10.1038/nm.2673
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 905IF
UT WOS:000301264800038
PM 22327622
ER
PT J
AU Lu, MJ
Wan, M
Leavens, KF
Chu, QW
Monks, BR
Fernandez, S
Ahima, RS
Ueki, K
Kahn, CR
Birnbaum, MJ
AF Lu, Mingjian
Wan, Min
Leavens, Karla F.
Chu, Qingwei
Monks, Bobby R.
Fernandez, Sully
Ahima, Rexford S.
Ueki, Kohjiro
Kahn, C. Ronald
Birnbaum, Morris J.
TI Insulin regulates liver metabolism in vivo in the absence of hepatic Akt
and Foxo1
SO NATURE MEDICINE
LA English
DT Article
ID FORKHEAD TRANSCRIPTION FACTOR; PROTEIN-KINASE-B; MTOR COMPLEX 1;
GLUCOSE-PRODUCTION; GENE-EXPRESSION; LIPID-METABOLISM; MICE LACKING;
FACTOR FKHR; GROWTH; PHOSPHORYLATION
AB Considerable data support the idea that forkhead box O1 (Foxo1) drives the liver transcriptional program during fasting and is then inhibited by thymoma viral proto-oncogene 1 (Akt) after feeding. Here we show that mice with hepatic deletion of Akt1 and Akt2 were glucose intolerant, insulin resistant and defective in their transcriptional response to feeding in the liver. These defects were normalized with concomitant liver-specific deletion of Foxo1. Notably, in the absence of both Akt and Foxo1, mice adapted appropriately to both the fasted and fed state, and insulin suppressed hepatic glucose production normally. A gene expression analysis revealed that deletion of Akt in liver led to the constitutive activation of Foxo1-dependent gene expression, but again, concomitant ablation of Foxo1 restored postprandial regulation, preventing the inhibition of the metabolic response to nutrient intake caused by deletion of Akt. These results are inconsistent with the canonical model of hepatic metabolism in which Akt is an obligate intermediate for proper insulin signaling. Rather, they show that a major role of hepatic Akt is to restrain the activity of Foxo1 and that in the absence of Foxo1, Akt is largely dispensable for insulin-and nutrient-mediated hepatic metabolic regulation in vivo.
C1 [Lu, Mingjian; Wan, Min; Leavens, Karla F.; Chu, Qingwei; Monks, Bobby R.; Fernandez, Sully; Ahima, Rexford S.; Birnbaum, Morris J.] Univ Penn, Inst Diabet Obes & Metab, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Ueki, Kohjiro] Univ Tokyo, Dept Diabet & Metab Dis, Grad Sch Med, Tokyo, Japan.
[Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA.
RP Birnbaum, MJ (reprint author), Univ Penn, Inst Diabet Obes & Metab, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM birnbaum@mail.med.upenn.edu
OI Birnbaum, Morris/0000-0001-9972-8680
FU NIH [P30 DK19525]; US National Institutes of Health [RO1 DK56886];
diabetes training grant [T32 DK007314]
FX The authors would like to thank M. Magnuson (Vanderbilt University) for
providing the antibody to Gck and D. Accili (Columbia University) for
sharing the Foxo1loxP/loxP mice. We are grateful to J. Schug,
who helped with the microarray data analysis and generated the heat map
and the density plot. The Functional Genomics Core and the Transgenic,
Knockout, Mouse Phenotyping and Biomarker Cores of the University of
Pennsylvania Diabetes and Endocrinology Research Center (NIH grant P30
DK19525) were instrumental in this work. This work was supported by the
US National Institutes of Health grant RO1 DK56886 (M. J. B.) and the
diabetes training grant T32 DK007314 (M.L.).
NR 59
TC 100
Z9 104
U1 2
U2 20
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD MAR
PY 2012
VL 18
IS 3
BP 388
EP U254
DI 10.1038/nm.2686
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 905IF
UT WOS:000301264800040
PM 22344295
ER
PT J
AU Sugimoto, H
LeBleu, VS
Bosukonda, D
Keck, P
Taduri, G
Bechtel, W
Okada, H
William, C
Bey, P
Rusckowski, M
Tampe, B
Tampe, D
Kanasaki, K
Zeisberg, M
Kalluri, R
AF Sugimoto, Hikaru
LeBleu, Valerie S.
Bosukonda, Dattatreyamurty
Keck, Peter
Taduri, Gangadhar
Bechtel, Wibke
Okada, Hirokazu
Carlson, William, Jr.
Bey, Philippe
Rusckowski, Mary
Tampe, Bjoern
Tampe, Desiree
Kanasaki, Keizo
Zeisberg, Michael
Kalluri, Raghu
TI Activin-like kinase 3 is important for kidney regeneration and reversal
of fibrosis
SO NATURE MEDICINE
LA English
DT Article
ID BONE MORPHOGENETIC PROTEIN-7; TO-MESENCHYMAL TRANSITION;
GROWTH-FACTOR-BETA; DIABETIC-NEPHROPATHY; RENAL FIBROSIS; TRANSFORMING
GROWTH-FACTOR-BETA-2; CRYSTAL-STRUCTURE; TISSUE FIBROSIS; EXPRESSION;
PROGRESSION
AB Molecules associated with the transforming growth factor beta (TGF-beta) superfamily, such as bone morphogenic proteins (BMPs) and TGF-beta, are key regulators of inflammation, apoptosis and cellular transitions. Here we show that the BMP receptor activin-like kinase 3 (Alk3) is elevated early in diseased kidneys after injury. We also found that its deletion in the tubular epithelium leads to enhanced TGF-beta 1-Smad family member 3 (Smad3) signaling, epithelial damage and fibrosis, suggesting a protective role for Alk3-mediated signaling in the kidney. A structure-function analysis of the BMP-Alk3-BMP receptor, type 2 (BMPR2) ligand-receptor complex, along with synthetic organic chemistry, led us to construct a library of small peptide agonists of BMP signaling that function through the Alk3 receptor. One such peptide agonist, THR-123, suppressed inflammation, apoptosis and the epithelial-to-mesenchymal transition program and reversed established fibrosis in five mouse models of acute and chronic renal injury. THR-123 acts specifically through Alk3 signaling, as mice with a targeted deletion for Alk3 in their tubular epithelium did not respond to therapy with THR-123. Combining THR-123 and the angiotensin-converting enzyme inhibitor captopril had an additive therapeutic benefit in controlling renal fibrosis. Our studies show that BMP signaling agonists constitute a new line of therapeutic agents with potential utility in the clinic to induce regeneration, repair and reverse established fibrosis.
C1 [Sugimoto, Hikaru; LeBleu, Valerie S.; Taduri, Gangadhar; Bechtel, Wibke; Okada, Hirokazu; Kanasaki, Keizo; Zeisberg, Michael; Kalluri, Raghu] Beth Israel Deaconess Med Ctr, Dept Med, Div Matrix Biol, Boston, MA 02215 USA.
[Bosukonda, Dattatreyamurty; Keck, Peter; Carlson, William, Jr.] Thrasos Innovat Inc, Montreal, PQ, Canada.
[Carlson, William, Jr.; Bey, Philippe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA.
[Rusckowski, Mary] Univ Massachusetts, Div Nucl Med, Dept Radiol, Coll Med, Worcester, MA 01605 USA.
[Tampe, Bjoern; Tampe, Desiree; Zeisberg, Michael; Kalluri, Raghu] Univ Gottingen, Goettingen Univ Med Ctr, Dept Nephrol & Rheumatol, D-3400 Gottingen, Germany.
[Kalluri, Raghu] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Boston, MA USA.
[Kalluri, Raghu] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Kalluri, R (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Matrix Biol, Boston, MA 02215 USA.
EM rkalluri@bidmc.harvard.edu
RI LeBleu, Valerie /E-2991-2015; Kalluri, Raghu/E-2677-2015
OI Kalluri, Raghu/0000-0002-2190-547X
FU US National Institutes of Health [DK55001, DK061688, DK081576, DK074558,
CA155370 CA163191, CA125550, CA151925]; Else Kroner-Memorial-Stipend
[P58/05//EKMS 05/59]; Research Training Grant in Gastroenterology
[2T32DK007760-11]; Research Training Grant in Cardiovascular Biology
[5T32HL007374-30]
FX This study was supported by US National Institutes of Health grants
DK55001, DK061688, DK081576, DK074558, CA155370 CA163191, CA125550,
CA151925 and the Else Kroner-Memorial-Stipend P58/05//EKMS 05/59 (M.Z.).
V. S. L. is funded from the Research Training Grant in Gastroenterology
(2T32DK007760-11). H. S. is funded by the Research Training Grant in
Cardiovascular Biology (5T32HL007374-30). Mice with the
Alk3flox/flox allele (Alk3f/f) were kindly
provided by Y. Mishina, US National Institutes of Health under a
material transfer agreement. gamma GT-Cre mice, NP-1 cells and the
polyclonal antibody to FSP1 were provided by E. Neilson, Vanderbilt
University Medical Center. We thank S. McGoohan for his technical
assistance.
NR 40
TC 83
Z9 88
U1 3
U2 24
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD MAR
PY 2012
VL 18
IS 3
BP 396
EP U264
DI 10.1038/nm.2629
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 905IF
UT WOS:000301264800041
PM 22306733
ER
PT J
AU White, YAR
Woods, DC
Takai, Y
Ishihara, O
Seki, H
Tilly, JL
AF White, Yvonne A. R.
Woods, Dori C.
Takai, Yasushi
Ishihara, Osamu
Seki, Hiroyuki
Tilly, Jonathan L.
TI Oocyte formation by mitotically active germ cells purified from ovaries
of reproductive-age women
SO NATURE MEDICINE
LA English
DT Article
ID EMBRYONIC STEM-CELLS; ADULT MAMMALIAN OVARIES; FEMALE INFERTILITY;
GENE-EXPRESSION; BONE-MARROW; TRANSPLANTATION; MOUSE; MICE; OOGENESIS;
PROTEIN
AB Germline stem cells that produce oocytes in vitro and fertilization-competent eggs in vivo have been identified in and isolated from adult mouse ovaries. Here we describe and validate a fluorescence-activated cell sorting-based protocol that can be used with adult mouse ovaries and human ovarian cortical tissue to purify rare mitotically active cells that have a gene expression profile that is consistent with primitive germ cells. Once established in vitro, these cells can be expanded for months and can spontaneously generate 35- to 50-mu m oocytes, as determined by morphology, gene expression and haploid (1n) status. Injection of the human germline cells, engineered to stably express GFP, into human ovarian cortical biopsies leads to formation of follicles containing GFP-positive oocytes 1-2 weeks after xenotransplantation into immunodeficient female mice. Thus, ovaries of reproductive-age women, similar to adult mice, possess rare mitotically active germ cells that can be propagated in vitro as well as generate oocytes in vitro and in vivo.
C1 [White, Yvonne A. R.; Woods, Dori C.; Tilly, Jonathan L.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA.
[White, Yvonne A. R.; Woods, Dori C.; Tilly, Jonathan L.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
[Takai, Yasushi; Ishihara, Osamu; Seki, Hiroyuki] Saitama Med Univ, Saitama Med Ctr, Dept Obstet & Gynecol, Saitama, Japan.
RP Tilly, JL (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA.
EM jtilly@partners.org
FU US National Institute on Aging [NIH R37-AG012279]; Henry and Vivian
Rosenberg Philanthropic Fund; Sea Breeze Foundation; Vincent Memorial
Hospital; NIH [F32-AG034809]
FX The authors thank L. Prickett-Rice and K. Folz-Donahue of the Harvard
Stem Cell Institute Flow Cytometry Core Facility and J. Groeneweg for
expert technical assistance. We also thank J. R. Mann and K. J.
MacLaughlin for the provision of TgOG2 transgenic mice. This work was
supported by a Method to Extend Research in Time (MERIT) Award from the
US National Institute on Aging (NIH R37-AG012279), the Henry and Vivian
Rosenberg Philanthropic Fund, the Sea Breeze Foundation and Vincent
Memorial Hospital Research Funds. This work was conducted while D. C. W.
was supported in part by a Ruth L. Kirschstein National Research Service
Award (NIH F32-AG034809).
NR 50
TC 219
Z9 234
U1 12
U2 102
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD MAR
PY 2012
VL 18
IS 3
BP 413
EP U176
DI 10.1038/nm.2669
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 905IF
UT WOS:000301264800043
PM 22366948
ER
PT J
AU Eichhorn, PJA
Rodon, L
Gonzalez-Junca, A
Dirac, A
Gili, M
Martinez-Saez, E
Aura, C
Barba, I
Peg, V
Prat, A
Cuartas, I
Jimenez, J
Garcia-Dorado, D
Sahuquillo, J
Bernards, R
Baselga, J
Seoane, J
AF Eichhorn, Pieter J. A.
Rodon, Laura
Gonzalez-Junca, Alba
Dirac, Annette
Gili, Maguei
Martinez-Saez, Elena
Aura, Claudia
Barba, Ignasi
Peg, Vicente
Prat, Aleix
Cuartas, Isabel
Jimenez, Jose
Garcia-Dorado, David
Sahuquillo, Juan
Bernards, Rene
Baselga, Jose
Seoane, Joan
TI USP15 stabilizes TGF-beta receptor I and promotes oncogenesis through
the activation of TGF-beta signaling in glioblastoma
SO NATURE MEDICINE
LA English
DT Article
ID E3 UBIQUITIN LIGASE; GROWTH-FACTOR-BETA; GLIOMA; SMURF2; DEGRADATION;
PATHWAY; SMAD7; GENETICS; TARGETS; BIOLOGY
AB In advanced cancer, including glioblastoma, the transforming growth factor beta (TGF-beta) pathway acts as an oncogenic factor and is considered to be a therapeutic target. Using a functional RNAi screen, we identified the deubiquitinating enzyme ubiquitin-specific peptidase 15 (USP15) as a key component of the TGF-beta signaling pathway. USP15 binds to the SMAD7-SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) complex and deubiquitinates and stabilizes type I TGF-beta receptor (T beta R-I), leading to an enhanced TGF-beta signal. High expression of USP15 correlates with high TGF-beta activity, and the USP15 gene is found amplified in glioblastoma, breast and ovarian cancer. USP15 amplification confers poor prognosis in individuals with glioblastoma. Downregulation or inhibition of USP15 in a patient-derived orthotopic mouse model of glioblastoma decreases TGF-beta activity. Moreover, depletion of USP15 decreases the oncogenic capacity of patient-derived glioma-initiating cells due to the repression of TGF-beta signaling. Our results show that USP15 regulates the TGF-beta pathway and is a key factor in glioblastoma pathogenesis.
C1 [Seoane, Joan] Vall dHebron Univ Hosp, VHIO, Barcelona, Spain.
[Dirac, Annette; Bernards, Rene] Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands.
[Dirac, Annette; Bernards, Rene] Netherlands Canc Inst, Ctr Biomed Genet, Amsterdam, Netherlands.
[Martinez-Saez, Elena; Barba, Ignasi; Peg, Vicente; Garcia-Dorado, David; Sahuquillo, Juan] Vall dHebron Univ Hosp, VHIR, Barcelona, Spain.
[Prat, Aleix] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Baselga, Jose; Seoane, Joan] Univ Autonoma Barcelona, Cerdanyola Del Valless, Spain.
[Baselga, Jose] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA.
[Seoane, Joan] ICREA, Barcelona, Spain.
RP Seoane, J (reprint author), Vall dHebron Univ Hosp, VHIO, Barcelona, Spain.
EM jseoane@vhio.net
RI Barba, Ignasi/H-5104-2013; Prat, Aleix/P-8561-2014; Sahuquillo,
Juan/B-3577-2008;
OI Prat, Aleix/0000-0003-2377-540X; Sahuquillo, Juan/0000-0003-0713-5875;
Peg, Vicente/0000-0002-5203-6166; Martinez-Saez,
Elena/0000-0001-6004-5364
FU Medical Oncology department; Neurosurgery department; Pathology
department of the Vall d'Hebron Hospital; Instituto Carlos III
[CM09/143, FIS (PI070648)]; Red Tematica de Investigacion Cooperativa en
Enfermedades Cardiovasculares (RECAVA, ISCIII); European Research
Council [ERC 205819]; Ministry of Science and Innovation
[CSD2009-00080]; Asociacion Espanola Contra el Cancer (AECC)
FX We thank A. Saez-Border as and A. Arias for technical support. We also
thank the Medical Oncology department, the Neurosurgery department and
the Pathology department of the Vall d'Hebron Hospital for support. E.
M. S. is supported by the Instituto Carlos III (CM09/143). I. B. and
D.G.-D. were supported by the Red Tematica de Investigacion Cooperativa
en Enfermedades Cardiovasculares (RECAVA, ISCIII). This work was
supported by the European Research Council grant (ERC 205819), Instituto
Carlos III grant FIS (PI070648), Ministry of Science and Innovation
grant Consolider Ingenio 2010 program (CSD2009-00080) and the Asociacion
Espanola Contra el Cancer (AECC) grant.
NR 37
TC 112
Z9 117
U1 2
U2 26
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD MAR
PY 2012
VL 18
IS 3
BP 429
EP U192
DI 10.1038/nm.2619
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 905IF
UT WOS:000301264800045
PM 22344298
ER
PT J
AU Rugge, M
Fassan, M
Graham, DY
AF Rugge, Massimo
Fassan, Matteo
Graham, David Y.
TI Secondary prevention of gastric cancer
SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
LA English
DT Editorial Material
ID STOMACH; DIAGNOSIS
AB The natural history of 'epidemic' intestinal-type gastric cancer provides consistent data that enable clinicians to design multidisciplinary strategies for secondary prevention. A recent paper by Dinis-Ribeiro et al. reports guidelines for the management of patients with precancerous stomach lesions.
C1 [Rugge, Massimo; Fassan, Matteo] Univ Padua, Dept Med, Surg Pathol & Cytopathol Unit, I-35121 Padua, PD, Italy.
[Graham, David Y.] Baylor Coll Med, Div Digest Dis, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
RP Rugge, M (reprint author), Univ Padua, Dept Med, Surg Pathol & Cytopathol Unit, Via Aristide Gabelli 61, I-35121 Padua, PD, Italy.
EM massimo.rugge@unipd.it
RI Fassan, Matteo/F-5152-2012; Rugge, Massimo/K-7525-2016
OI Fassan, Matteo/0000-0001-6515-5482;
NR 10
TC 16
Z9 16
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5045
J9 NAT REV GASTRO HEPAT
JI Nat. Rev. Gastroenterol. Hepatol.
PD MAR
PY 2012
VL 9
IS 3
BP 128
EP 129
DI 10.1038/nrgastro.2012.19
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 905PM
UT WOS:000301284700002
PM 22330815
ER
PT J
AU Li, HM
Pink, MD
Murphy, JG
Stein, A
Dell'Acqua, ML
Hogan, PG
AF Li, Huiming
Pink, Matthew D.
Murphy, Jonathan G.
Stein, Alexander
Dell'Acqua, Mark L.
Hogan, Patrick G.
TI Balanced interactions of calcineurin with AKAP79 regulate
Ca2+-calcineurin-NFAT signaling
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID NMDA RECEPTOR ACTIVATION; PROTEIN-KINASE-A; ANCHORING PROTEIN;
SELECTIVE-INHIBITION; CARDIAC-HYPERTROPHY; LIVING CELLS; COMPLEX; NFAT;
PEPTIDE; AFFINITY
AB In hippocampal neurons, the scaffold protein AKAP79 recruits the phosphatase calcineurin to L-type Ca2+ channels and couples Ca2+ influx to activation of calcineurin and of its substrate, the transcription factor NFAT. Here we show that an IAIIIT anchoring site in human AKAP79 binds the same surface of calcineurin as the PxIxIT recognition peptide of NFAT, albeit more strongly. A modest decrease in calcineurin-AKAP affinity due to an altered anchoring sequence is compatible with NFAT activation, whereas a further decrease impairs activation. Counterintuitively, increasing calcineurin-AKAP affinity increases recruitment of calcineurin to the scaffold but impairs NFAT activation; this is probably due to both slower release of active calcineurin from the scaffold and sequestration of active calcineurin by 'decoy' AKAP sites. We propose that calcineurin-AKAP79 scaffolding promotes NFAT signaling by balancing strong recruitment of calcineurin with its efficient release to communicate with NFAT.
C1 [Li, Huiming; Hogan, Patrick G.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
[Li, Huiming; Hogan, Patrick G.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Li, Huiming] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Pink, Matthew D.; Murphy, Jonathan G.; Dell'Acqua, Mark L.] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA.
[Pink, Matthew D.; Murphy, Jonathan G.; Dell'Acqua, Mark L.] Univ Colorado, Sch Med, Program Neurosci, Aurora, CO USA.
[Stein, Alexander] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Stein, Alexander] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Hogan, Patrick G.] La Jolla Inst Allergy & Immunol, La Jolla, CA USA.
RP Hogan, PG (reprint author), Childrens Hosp, Immune Dis Inst, 300 Longwood Ave, Boston, MA 02115 USA.
EM Mark.DellAcqua@ucdenver.edu; phogan@liai.org
RI Stein, Alexander/I-4950-2012;
OI Stein, Alexander/0000-0002-2696-0611; Dell'Acqua,
Mark/0000-0003-3798-3461
FU National Center for Research Resources at the US National Institutes of
Health [RR15-301]; US DOE [DE-AC02-06CH11357]; US National Institutes of
Health [AI40127, MH080291, AI090428]; Pacific Mountain Affiliate;
[T32NS007083]; [T32HD041697]
FX We are grateful to the Department of Neurobiology, Harvard Medical
School, for use of its spectrofluorometer, and to S. Lehrer, Boston
Biomedical Research Institute, for access to the stopped-flow
instrument. Diffraction data were collected at the Advanced Photon
Source on Northeastern Collaborative Access Team beamline 24-ID-C, which
is supported by award RR15-301 from the National Center for Research
Resources at the US National Institutes of Health. Use of the Advanced
Photon Source, an Office of Science User Facility operated for the US
Department of Energy (DOE) Office of Science by Argonne National
Laboratory, was supported by the US DOE under Contract No.
DE-AC02-06CH11357. We thank A. Sorkin, University of Pittsburgh, for
providing the tandem YFP-CFP construct. The work was supported by US
National Institutes of Health grants AI40127 (to A. Rao and P.G.H.),
MH080291 (to M.L.D.) and AI090428 (to H.L.). M.D.P. was supported in
part by T32NS007083 and by an American Heart Association Predoctoral
Fellowship from the Pacific Mountain Affiliate. J.G.M. was supported in
part by T32HD041697.
NR 48
TC 54
Z9 56
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD MAR
PY 2012
VL 19
IS 3
BP 337
EP U100
DI 10.1038/nsmb.2238
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 904GI
UT WOS:000301181900011
PM 22343722
ER
PT J
AU Dolga, A
Perocchi, F
Doti, N
Meissner, L
Tobaben, S
Grohm, J
Zischka, H
Plesnila, N
Culmsee, C
AF Dolga, A.
Perocchi, F.
Doti, N.
Meissner, L.
Tobaben, S.
Grohm, J.
Zischka, H.
Plesnila, N.
Culmsee, C.
TI Mitochondrial SK2/K(Ca)2.2 channels mediate neuroprotective effects
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 78th Annual Congress of the
German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology
(DGPT)
CY MAR 19-22, 2012
CL Dresden, GERMANY
SP German Soc Expt & Clin Pharmacol & Toxicol (DGPT)
C1 [Dolga, A.; Tobaben, S.; Grohm, J.; Culmsee, C.] Univ Marburg, Inst Pharmakol & Klin Pharm, D-35043 Marburg, Germany.
[Perocchi, F.] Harvard Univ, Sch Med, Boston, MA USA.
[Perocchi, F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Doti, N.] CNR, Inst Biostruct & Bioimaging, I-80125 Naples, Italy.
[Meissner, L.; Plesnila, N.] Univ Munich, Sch Med, Inst Stroke & Dementia Res, Munich, Germany.
[Zischka, H.] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Munich, Germany.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD MAR
PY 2012
VL 385
SU 1
MA 091
BP 22
EP 22
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 898YY
UT WOS:000300779500092
ER
PT J
AU Hamann, M
Kuschka, J
Gioioso, V
Sharma, N
Richter, A
AF Hamann, M.
Kuschka, J.
Gioioso, V
Sharma, N.
Richter, A.
TI Investigations of the cholinergic neurotransmitter system in DYT1 mice
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 78th Annual Congress of the
German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology
(DGPT)
CY MAR 19-22, 2012
CL Dresden, GERMANY
SP German Soc Expt & Clin Pharmacol & Toxicol (DGPT)
C1 [Hamann, M.; Kuschka, J.; Richter, A.] Free Univ Berlin, Dept Vet Med, Inst Pharmacol & Toxicol, D-14195 Berlin, Germany.
[Gioioso, V; Sharma, N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD MAR
PY 2012
VL 385
SU 1
MA 140
BP 33
EP 33
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 898YY
UT WOS:000300779500141
ER
PT J
AU Shin, JH
Hoh, DJ
Kalfas, IH
AF Shin, John H.
Hoh, Daniel J.
Kalfas, Iain H.
TI Iliac Screw Fixation Using Computer-Assisted Computer Tomographic Image
Guidance: Technical Note
SO NEUROSURGERY
LA English
DT Article
DE Iliac screw; Image guidance; Navigation
AB BACKGROUND: Iliac screw fixation is a powerful tool used by spine surgeons to achieve fusion across the lumbosacral junction for a number of indications, including deformity, tumor, and pseudarthrosis. Complications associated with screw placement are related to blind trajectory selection and excessive soft tissue dissection.
OBJECTIVE: To describe the technique of iliac screw fixation using computed tomographic (CT)-based image guidance.
METHODS: Intraoperative registration and verification of anatomic landmarks are performed with the use of a preoperatively acquired CT of the lumbosacral spine. With the navigation probe, the ideal starting point for screw placement is selected while visualizing the intended trajectory and target on a computer screen. Once the starting point is selected and marked with a burr, a drill guide is docked within this point and the navigation probe re-inserted, confirming the trajectory. The probe is then removed and the high-speed drill reinserted within the drill guide. Drilling is performed to a depth measured on the computer screen and a screw is placed.
RESULTS: Confirmation of accurate placement of iliac screws can be performed with standard radiographs.
CONCLUSION: CT-guided navigation allows for 3-dimensional visualization of the pelvis and minimizes complications associated with soft-tissue dissection and breach of the ilium during screw placement.
C1 [Shin, John H.] Harvard Univ, Dept Neurosurg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Hoh, Daniel J.] Univ Florida, Dept Neurosurg, Gainesville, FL USA.
[Kalfas, Iain H.] Cleveland Clin, Ctr Spine Hlth, Dept Neurosurg, Cleveland, OH 44106 USA.
RP Shin, JH (reprint author), Harvard Univ, Dept Neurosurg, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,WAC 745, Boston, MA 02114 USA.
EM shin.john@mgh.harvard.edu
NR 10
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Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD MAR
PY 2012
VL 70
SU 1
AR ons16
DI 10.1227/NEU.0b013e318230517a
PG 5
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 904VY
UT WOS:000301228100003
ER
PT J
AU Heffernan-Stroud, LA
Helke, KL
Jenkins, RW
De Costa, AM
Hannun, YA
Obeid, LM
AF Heffernan-Stroud, L. A.
Helke, K. L.
Jenkins, R. W.
De Costa, A-M
Hannun, Y. A.
Obeid, L. M.
TI Defining a role for sphingosine kinase 1 in p53-dependent tumors
SO ONCOGENE
LA English
DT Article
DE ceramide; sphingosine-1-phosphate; p53; sphingosine kinase; cancer;
senescence
ID PROGRAMMED CELL-DEATH; CERAMIDE-INDUCED APOPTOSIS; TANDEM
MASS-SPECTROMETRY; BIOACTIVE SPHINGOLIPIDS; QUANTITATIVE-ANALYSIS;
GENOTOXIC STRESS; HIGH EXPRESSION; DOWN-REGULATION; MICE DEFICIENT;
CYCLE ARREST
AB p53 is a crucial tumor suppressor that is mutated or deleted in a majority of cancers. Exactly how p53 prevents tumor progression has proved elusive for many years; however, this information is crucial to define targets for chemotherapeutic development that can effectively restore p53 function. Bioactive sphingolipids have recently emerged as important regulators of proliferative, apoptotic and senescent cellular processes. In this study, we demonstrate that the enzyme sphingosine kinase 1 (SK1), a critical enzyme in the regulation of the key bioactive sphingolipids ceramide, sphingosine and sphingosine-1-phosphate (S1P), serves as a key downstream target for p53 action. Our results show that SK1 is proteolysed in response to genotoxic stress in a p53-dependent manner. p53 null mice display elevation of SK1 levels and a tumor-promoting dysregulation of bioactive sphingolipids in which the anti-growth sphingolipid ceramide is decreased and the pro-growth sphingolipid S1P is increased. Importantly, deletion of SK1 in p53 null mice completely abrogated thymic lymphomas in these mice and prolonged their life span by similar to 30%. Deletion of SK1 also significantly attenuated the formation of other cancers in p53 heterozygote mice. The mechanism of p53 tumor suppression by loss of SK1 is mediated by elevations of sphingosine and ceramide, which in turn were accompanied by increased expression of cell cycle inhibitors and tumor cell senescence. Thus, targeting SK1 may restore sphingolipid homeostasis in p53-dependent tumors and provide insights into novel therapeutic approaches to cancer. Oncogene (2012) 31, 1166-1175; doi:10.1038/onc.2011.302; published online 18 July 2011
C1 [Obeid, L. M.] Med Univ S Carolina, Dept Med, Charleston, SC 29403 USA.
[Heffernan-Stroud, L. A.; Obeid, L. M.] Med Univ S Carolina, Dept Mol & Cellular Biol & Pathobiol, Charleston, SC 29403 USA.
[Helke, K. L.] Med Univ S Carolina, Dept Comparat Med Lab Anim Resources, Charleston, SC 29403 USA.
[Jenkins, R. W.; Hannun, Y. A.; Obeid, L. M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29403 USA.
[De Costa, A-M] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29403 USA.
[Obeid, L. M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St, Charleston, SC 29403 USA.
EM obeidl@musc.edu
OI obeid, lina/0000-0002-0734-0847; Helke, Kris/0000-0001-9746-0764
FU Biomedical Laboratory Research and Development Service of the VA Office
of Research and Development [I01BX000156]; NIH/NIGMS [R01 GM062887];
NIH/NCI [P01 CA097132-project 3, P01 CA097132-project 1]; American Heart
Association [AHA 081509E]; NIH MSTP [GM08716]; MUSC Hollings Cancer
Center Abney Foundation; NIH/NIEHS [T32 ES012878, F30ES017379]; NCI
[IPO1CA097132, P30 CA 138313]; NIH/NCRR SC COBRE [P20 RR017677]; NIH
[C06 RR018823]; National Center for Research Resources
FX This work was supported, in part, by Award Number I01BX000156 from the
Biomedical Laboratory Research and Development Service of the VA Office
of Research and Development, NIH/NIGMS R01 GM062887, NIH/NCI P01
CA097132-project 3 (to LMO). NIH/NCI P01 CA097132-project 1 (to YAH).
American Heart Association Pre-Doctoral Fellowship AHA 081509E (to RWJ),
NIH MSTP Training Grant GM08716 (to RWJ, AMDC, LAHS), MUSC Hollings
Cancer Center Abney Foundation Scholarship (to RWJ, LAHS), NIH/NIEHS TG
T32 ES012878, and NIH/NIEHS National Research Service Award Individual
Predoctoral Fellowship F30ES017379 (to LAHS). Liquid chromatography-mass
spectrometry analysis of sphingolipids was performed by Lipidomics
Shared Resource, MUSC (Methods 2006, 39: 82-91) supported by NCI Grants:
IPO1CA097132 and P30 CA 138313 and NIH/NCRR SC COBRE Grant P20 RR017677
as specified in Supplementary Information. Laboratory space in the CRI
building of MUSC was supported by the NIH, Grant C06 RR018823 from the
Extramural Research Facilities Program of the National Center for
Research Resources. Refer to Supplementary Information for individual
acknowledgements and the VA disclaimer.
NR 72
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Z9 21
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD MAR
PY 2012
VL 31
IS 9
BP 1166
EP 1175
DI 10.1038/onc.2011.302
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 901EW
UT WOS:000300945900009
PM 21765468
ER
PT J
AU Helman, E
Naxerova, K
Kohane, IS
AF Helman, E.
Naxerova, K.
Kohane, I. S.
TI DNA hypermethylation in lung cancer is targeted at
differentiation-associated genes
SO ONCOGENE
LA English
DT Article
DE Hypermethylation; development; non-small cell lung cancer; gene
expression
ID TUMOR-SUPPRESSOR GENE; CPG-ISLAND METHYLATION; EMBRYONIC STEM-CELLS;
EARLY EVENT; GENOME; MARKERS; GERM; HYPOMETHYLATION; CARDIOMYOCYTES;
RETINOBLASTOMA
AB Aberrant DNA hypermethylation of tumor suppressor genes is thought to be an early event in tumorigenesis. Many studies have reported the methylation status of individual genes with known involvement in cancer, but an unbiased assessment of the biological function of the collective of hypermethylated genes has not been conducted so far. Based on the observation that a variety of human cancers recapitulate developmental gene expression patterns ( that is activate genes normally expressed in early development and suppress late developmental genes), we hypothesized that the silencing of differentiation-associated genes in cancer could be attributed in part to DNA hypermethylation. To this end, we investigated the developmental expression patterns of genes with hypermethylated CpG islands in primary human lung carcinomas and lung cancer cell lines. We found that DNA hypermethylation primarily affects genes that are expressed in late stages of murine lung development. Gene ontology characterization of these genes shows that they are almost exclusively involved in morphogenetic differentiation processes. Our results indicate that DNA hypermethylation in cancer functions as a selective silencing mechanism of genes that are required for the maintenance of a differentiated state. The process of cellular de-differentiation that is evident on both the microscopic and transcriptional level in cancer might at least partly be mediated by these epigenetic events. Our observations provide a mechanistic explanation for induction of differentiation upon treatment with DNA methyltransferase inhibitors. Oncogene (2012) 31, 1181-1188; doi:10.1038/onc.2011.307; published online 1 August 2011
C1 [Kohane, I. S.] Childrens Hosp, Informat Program, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA.
[Naxerova, K.] Harvard Univ, Sch Med, Boston, MA USA.
[Naxerova, K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA.
RP Kohane, IS (reprint author), Childrens Hosp, Informat Program, Harvard Mit Div Hlth Sci & Technol, 300 Longwood Ave,Enders 6L, Boston, MA 02115 USA.
EM Isaac_Kohane@hms.harvard.edu
RI Kohane, Isaac Kohane/K-3716-2012;
OI Kohane, Isaac Kohane/0000-0003-2192-5160; Naxerova,
Kamila/0000-0001-7744-5110
NR 49
TC 12
Z9 12
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR
PY 2012
VL 31
IS 9
BP 1181
EP 1188
DI 10.1038/onc.2011.307
PG 8
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 901EW
UT WOS:000300945900011
PM 21804601
ER
PT J
AU Singh, JP
Ellenbogen, KA
Desai, NR
Mcalister, FA
AF Singh, Jagmeet P.
Ellenbogen, Kenneth A.
Desai, Nihar R.
Mcalister, Finlay A.
TI ICDs, Guidelines, and National Registries: Opportunities to Enhance
Quality of Patient Care
SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY
LA English
DT Editorial Material
ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; HEART-FAILURE;
COST-EFFECTIVENESS; AMIODARONE; THERAPY
C1 [Singh, Jagmeet P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA.
[Ellenbogen, Kenneth A.] VCU Sch Med, Div Cardiol, Richmond, VA USA.
[Desai, Nihar R.] Brigham & Womens Hosp, Div Cardiol, Div Cardiovasc Med, Boston, MA 02115 USA.
[Mcalister, Finlay A.] Univ Alberta Hosp, Div Internal Med, Edmonton, AB T6G 2B7, Canada.
RP Singh, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA.
EM jsingh@partners.org
RI McAlister, Finlay/C-4151-2013
NR 17
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0147-8389
J9 PACE
JI PACE-Pacing Clin. Electrophysiol.
PD MAR
PY 2012
VL 35
IS 3
BP 253
EP 258
DI 10.1111/j.1540-8159.2011.03300.x
PG 6
WC Cardiac & Cardiovascular Systems; Engineering, Biomedical
SC Cardiovascular System & Cardiology; Engineering
GA 902PB
UT WOS:000301049300010
PM 22268567
ER
PT J
AU Shalaby, A
Brumberg, G
El-Saed, A
Saba, S
AF Shalaby, Alaa
Brumberg, Genevieve
El-Saed, Aiman
Saba, Samir
TI Mood Disorders and Outcome in Patients Receiving Cardiac
Resynchronization Therapy
SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY
LA English
DT Article
DE depression; anxiety; cardiac resynchronization therapy; mortality; heart
failure
ID CHRONIC HEART-FAILURE; DEPRESSIVE SYMPTOMS; CARDIOVERTER-DEFIBRILLATORS;
MYOCARDIAL-INFARCTION; RISK; MORTALITY; ANXIETY; PREVALENCE; PREDICTORS;
ARRHYTHMIAS
AB Background: Mood disorders (MD) have been demonstrated to influence outcome in cardiac disease in general and specifically in chronic heart failure (HF). Little is known about their possible effect on response to cardiac resynchronization therapy (CRT).
Objective: To evaluate the influence of MD on CRT response. Methods: We conducted a retrospective chart review of all cardiac CRT-D (CRT defibrillator) recipients (N = 153) at the Veterans Affairs Pittsburgh Healthcare System from beginning of 2004 through end of 2006. All-cause death and HF-related hospitalizations (HFH), individually and combined, were sought through 2009.
Results: During a mean follow-up time of 31.4 +/- 14.7 months, there were 48 (31.4%) deaths and 55 (35.9%) HFHs in HF patients having New York Heart Association class of 2.9 +/- 0.3, left ventricular ejection fraction (LVEF) of 25.8 +/- 9.1%, left ventricular end-diastolic diameter (LVEDD) of 61.6 +/- 11.6 mm, and QRS of 152 +/- 30.5 ms. A total of 65 (42.5%) patients had MD (depression, anxiety, or posttraumatic stress disorder). Compared to others, patients in the MD group were at a significantly higher risk of HFH alone (47.7% vs 27.3%, P = 0.009) or when combined with death (58.5% vs 39.8%, P = 0.022) but not death alone (35.4% vs 28.4%, P = 0.36). The significant predictive effect of MD on HFH alone and when combined with death shown in univariate analysis was not attenuated after adjustment for age, ejection fraction, etiology of cardiomyopathy, cumulative number of any shocks, smoking, and evidence of postimplantation echocardiographic improvement.
Conclusions: MD in patients with advanced but stable HF receiving CRT-D therapy was a predictor of HFH alone or when combined with death but not mortality alone. (PACE 2012; 35: 294-301)
C1 [Shalaby, Alaa; Brumberg, Genevieve; El-Saed, Aiman; Saba, Samir] Univ Pittsburgh, Med Ctr, Vet Affairs Pittsburgh Hlth Syst, Div Cardiol,Cardiovasc Inst, Pittsburgh, PA 15240 USA.
RP Shalaby, A (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Div Cardiol, 111C Univ Dr, Pittsburgh, PA 15240 USA.
EM Alaa.Shalaby@va.gov
NR 39
TC 6
Z9 6
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0147-8389
J9 PACE
JI PACE-Pacing Clin. Electrophysiol.
PD MAR
PY 2012
VL 35
IS 3
BP 294
EP 301
DI 10.1111/j.1540-8159.2011.03304.x
PG 8
WC Cardiac & Cardiovascular Systems; Engineering, Biomedical
SC Cardiovascular System & Cardiology; Engineering
GA 902PB
UT WOS:000301049300015
PM 22229659
ER
PT J
AU Hermanrud, CE
Pathiraja, V
Matar, A
Duran-Struuck, R
Crepeau, RL
Srinivasan, S
Sachs, DH
Huang, CA
Wang, ZR
AF Hermanrud, Christina E.
Pathiraja, Vimukthi
Matar, Abraham
Duran-Struuck, Raimon
Crepeau, Rebecca L.
Srinivasan, Srimathi
Sachs, David H.
Huang, Christene A.
Wang, Zhirui
TI Expression and purification of non-N-glycosylated porcine interleukin 3
in yeast Pichia pastoris
SO PROTEIN EXPRESSION AND PURIFICATION
LA English
DT Article
DE Porcine IL3; Pichia pastoris expression; Purification; Glycosylation;
Mobilization
ID HEMATOPOIETIC-CELL TRANSPLANTATION; LARGE-ANIMAL-MODEL; PROGENITOR
CELLS; MIXED CHIMERISM; MINIATURE SWINE; GLYCOPROTEINS; MOBILIZATION;
IMMUNOTOXIN; ENGRAFTMENT; TOLERANCE
AB Yeast Pichia pastoris has been widely utilized to express heterologous recombinant proteins. P. pastoris expressed recombinant porcine interleukin 3 (IL3) has been used for porcine stem cell mobilization in allo-hematopoietic cell transplantation models and pig-to-primate xeno-hematopoietic cell transplantation models in our lab for many years. Since the yeast glycosylation mechanism is not exactly the same as those of other mammalian cells, P. pastoris expressed high-mannose glycoprotein porcine IL3 has been shown to result in a decreased serum half-life. Previously this was avoided by separation of the non-glycosylated porcine IL3 from the mixture of expressed glycosylated and non-glycosylated porcine IL3. However, this process was very inefficient and lead to a poor yield following purification. To overcome this problem, we engineered a non-N-glycosylated version of porcine IL3 by replacing the four potential N-glycosylation sites with four alanines. The codon-optimized non-N-glycosylated porcine IL3 gene was synthesized and expressed in P. pastoris. The expressed non-N-glycosylated porcine IL3 was captured using Ni-Sepharose 6 fast flow resin and further purified using strong anion exchange resin Poros 50 HQ. In vivo mobilization studies performed in our research facility demonstrated that the non-N-glycosylated porcine IL3 still keeps the original stem cell mobilization function. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Hermanrud, Christina E.; Pathiraja, Vimukthi; Matar, Abraham; Duran-Struuck, Raimon; Crepeau, Rebecca L.; Srinivasan, Srimathi; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA.
[Hermanrud, Christina E.; Pathiraja, Vimukthi; Matar, Abraham; Duran-Struuck, Raimon; Crepeau, Rebecca L.; Srinivasan, Srimathi; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] Harvard Univ, Sch Med, Boston, MA 02129 USA.
[Hermanrud, Christina E.; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] MGH DF HCC Recombinant Prot Express & Purificat C, Boston, MA USA.
RP Wang, ZR (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-6113,13th St, Boston, MA 02129 USA.
EM zhirui.wang@tbrc.mgh.harvard.edu
FU National Institutes of Health [R01A1084657-02]; Dana Farber/Harvard
Cancer Center
FX This work was supported by National Institutes of Health (R01A1084657-02
to CAH); and Dana Farber/Harvard Cancer Center Core development grant.
NR 16
TC 1
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U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-5928
J9 PROTEIN EXPRES PURIF
JI Protein Expr. Purif.
PD MAR
PY 2012
VL 82
IS 1
BP 70
EP 74
DI 10.1016/j.pep.2011.11.011
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 900WZ
UT WOS:000300923700011
PM 22154875
ER
PT J
AU Berry, RB
Kushida, CA
Kryger, MH
Soto-Calderon, H
Staley, B
Kuna, ST
AF Berry, Richard B.
Kushida, Clete A.
Kryger, Meir H.
Soto-Calderon, Haideliza
Staley, Bethany
Kuna, Samuel T.
TI Respiratory Event Detection by a Positive Airway Pressure Device
SO SLEEP
LA English
DT Article
DE CPAP; autoCPAP; APAP
ID OBSTRUCTIVE SLEEP-APNEA; TREATING ADULT PATIENTS; PRACTICE PARAMETERS;
TITRATING PRESSURES; HYPOPNEA SYNDROME; POLYSOMNOGRAPHY; CPAP;
DIAGNOSIS; EFFICACY; UPDATE
AB Study Objectives: Compare automatic event detection (AED) of respiratory events using a positive airway pressure (PAP) device with manual scoring of polysomnography (PSG) during PAP treatment of obstructive sleep apnea (OSA).
Design: Prospective PSGs of patients using a PAP device.
Setting: Six academic and private sleep disorders centers.
Patients: A total of 148 PSGs from 115 participants with OSA (apnea-hypopnea index [AH I] >= 15 events/hr) were analyzed.
Interventions: A signal generated by the PAP device identifying the AED of respiratory events based on airflow was recorded during PSG.
Measurements and Results: The PSGs were manually scored without visualization of the AED signal and scoring of a hypopnea required a >= 4% oxygen desaturation. The apnea index (AI), hypopnea index (HI), and AH I by manual score and PAP AED were compared. A customized computer program compared individual events by manual scoring and AED to determine the true positive, false positive, false negative, or true negative events and found a sensitivity of 0.58 and a specificity of 0.98. The AH I, AI, and HI by the two methods were highly correlated. Bland-Altman analysis showed better agreement for AI than HI. Using a manually scored AH I of >= 10 events/hr to denote inadequate treatment, an AED AHI >= 10 events/hr had a sensitivity of 0.58 and a specificity of 0.94.
Conclusions: An AHI < 10 events/hr by PAP AED is usually associated with good treatment efficacy. Differences between manually scored and AED events were primarily due to different criteria for hypopnea detection.
C1 [Berry, Richard B.] Univ Florida, Dept Med, Gainesville, FL 32610 USA.
[Kushida, Clete A.] Stanford Univ, Redwood City, CA USA.
[Kryger, Meir H.] Gaylord Sleep Med, Wallingford, CT USA.
[Soto-Calderon, Haideliza; Staley, Bethany; Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Soto-Calderon, Haideliza; Staley, Bethany; Kuna, Samuel T.] Univ Penn, Philadelphia, PA 19104 USA.
RP Berry, RB (reprint author), Univ Florida, Dept Med, Box 100225 HSC, Gainesville, FL 32610 USA.
EM sleep_doc@msn.com
FU Philips-Respironics; Ventus Medical; ResMed; Dymedix; Ventus to Gaylord
Hospital
FX This study was sponsored by Philips-Respironics. Dr. Berry has received
research support from Philips-Respironics and Ventus Medical via grant
to the University of Florida and ResMed via grant to North Florida
Foundation for Research and Education (Gainesville VAMC). Dr. Kushida
has received research support from Philips-Respironics and ResMed via
grants to Stanford and royalties from patent licensed to
Philips-Respironics. Dr. Kryger has received research support from
Philips-Respironics, ResMed, Dymedix, and Ventus to Gaylord Hospital.
Dr. Kuna has received research support from Philips-Respironics. The
other authors have indicated no financial conflicts of interest.
NR 14
TC 17
Z9 20
U1 0
U2 2
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
J9 SLEEP
JI Sleep
PD MAR 1
PY 2012
VL 35
IS 3
BP 361
EP 367
DI 10.5665/sleep.1696
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 901GG
UT WOS:000300950400010
PM 22379242
ER
PT J
AU Grandner, MA
Martin, JL
Patel, NP
Jackson, NJ
Gehrman, PR
Pien, G
Perlis, ML
Xie, DW
Sha, DH
Weaver, T
Gooneratne, NS
AF Grandner, Michael A.
Martin, Jennifer L.
Patel, Nirav P.
Jackson, Nicholas J.
Gehrman, Philip R.
Pien, Grace
Perlis, Michael L.
Xie, Dawei
Sha, Daohang
Weaver, Terri
Gooneratne, Nalaka S.
TI Age and Sleep Disturbances Among American Men And Women: Data From the
US Behavioral Risk Factor Surveillance System
SO SLEEP
LA English
DT Article
DE Aging; sleep quality; fatigue; epidemiology; depression
ID WORK HOURS RECOMMENDATIONS; OLDER-ADULTS; DAYTIME SLEEPINESS;
PROSPECTIVE COHORT; HEALTH; INSOMNIA; ADOLESCENT; COMPLAINTS; DISORDERS;
POPULATION
AB Study Objective: Explore the prevalence of sleep-related complaints across age groups, examining effects of sex, general health, and depressed mood.
Design: Cross-sectional analysis of data from the 2006 Behavioral Risk Factor Surveillance System (BRFSS).
Setting: Epidemiologic.
Participants: Complete-case analysis included 155,877 participants who responded to questions related to Self-Reported Sleep Disturbance (SLEEPDIST) and Self-Reported Tiredness/Lack of Energy (TIREDNESS).
Interventions: None.
Measurements and Results: Outcomes were self-reported complaints in response to survey questions assessing SLEEPDIST and TIREDNESS, dichotomized as reporting a complaint < 6 versus >= 6 nights or days, respectively, in a 2-wk period. Predictors were age, general health, and depressed mood. All analyses were adjusted for race/ethnicity, income, education, and time since last medical checkup. Across all age groups, women reported more SLEEPDIST and TIREDNESS. Poor general health, mild depressed mood, and moderate/severe depressed mood were associated with SLEEPDIST and TIREDNESS. Both SLEEPDIST and TIREDNESS generally declined across the life span, with fewest endorsements in respondents older than 80 yr. For SLEEPDIST, odds ratios (ORs, reference = 80+) declined from age 18-54 yr, rose slightly, and then declined again after age 59 yr in men. The pattern was similar for women, except a more marked rise was noted from age 40-59 yr. The pattern was similar for TIREDNESS.
Conclusions: Advancing age was not associated with increased Self-Reported Sleep Disturbance or Self-Reported Tiredness/Lack of Energy. These results suggest that the often-reported increase in sleep problems with age is a nonlinear phenomenon, mediated by factors other than physiologic aging.
C1 [Grandner, Michael A.; Jackson, Nicholas J.; Pien, Grace] Univ Penn, Ctr Sleep & Circadian Neurobiol, Dept Med, Div Sleep Med, Philadelphia, PA 19104 USA.
[Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Martin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA.
[Gehrman, Philip R.; Perlis, Michael L.] Univ Penn, Div Pulm & Crit Care Med, Dept Med, Philadelphia, PA 19104 USA.
[Pien, Grace] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Xie, Dawei; Sha, Daohang] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Weaver, Terri] Univ Illinois, Chicago Coll Nursing, Biobehav & Hlth Sci Dept, Chicago, IL USA.
[Gooneratne, Nalaka S.] Univ Penn, Div Geriatr Med, Dept Med, Philadelphia, PA 19104 USA.
RP Grandner, MA (reprint author), Univ Penn, Ctr Sleep & Circadian Neurobiol, Dept Med, Div Sleep Med, 3624 Market St,Suite 205, Philadelphia, PA 19104 USA.
EM Grand-ner@upenn.edu
FU University of Pennsylvania Center for Sleep and Circadian Neurobiology
[T32HL007713, K23AG028452, R21AG31390]; Boehringer Ingelheim;
Sanofi-Aventis; Pharma; Actelion; Takeda; Gerson Lehman; Clinical
Advisors; LEK; MedaCorp; Respironics Respiratory and Sleep Research
Foundation; Cephalon, Inc.
FX This work was supported by T32HL007713, K23AG028452 (to Dr. Martin),
R21AG31390 (to Dr. Gooneratne) as well as funding for Biostatistical
Support from the University of Pennsylvania Center for Sleep and
Circadian Neurobiology. The authors thank Allan Pack, MB, ChB, PhD for
guidance and other support. Also, the authors thank the BRFSS
participants and the Centers for Disease Control and Prevention for
collecting these data and making them available.; This was not an
industry supported study. Dr. Patel has received research support from
Boehringer Ingelheim unrelated to this study. Dr. Pien has the use of
equipment on loan from Respironics unrelated to this study. Dr. Perlis
has consulted for Gerson Lehrman Group, Clinical Advisors, Meda
Corp/Leerink Swann, Actelion, SleepEasily, Sanofi-Aventis, L.E.K.
Consulting LLC. He has received research support from Sanofi-Aventis,
Pharma, and Cephalon and had speaking honoraria from Sanofi-Aventis,
AASM, UR, and Internet Didactic Services. He has received salary and
distributions from Actelion, Takeda, Gerson Lehman, Clinical Advisors,
LEK, and MedaCorp. Dr. Weaver has received research equipment from
Respironics, Inc. and Protech; grant support from Respironics
Respiratory and Sleep Research Foundation, Cephalon, Inc. She has
consulted for Apnex Medical, Inc., and Cephalon, Inc. and has FOSQ
license Agreements with Sanofi-Aventis Pharmaceutical, Merck 7 Co.,
Inc., Sleep Solutions, N.V. Organon, Apnex Medical, Inc., Ventus
medical, GlaxoSmithKline, and Respironics. The other authors have
indicated no financial conflicts of interest.
NR 54
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Z9 45
U1 2
U2 17
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
J9 SLEEP
JI Sleep
PD MAR 1
PY 2012
VL 35
IS 3
BP 395
EP 406
DI 10.5665/sleep.1704
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 901GG
UT WOS:000300950400014
PM 22379246
ER
PT J
AU Turvey, CL
Zulman, DM
Nazi, KM
Wakefield, BJ
Woods, SS
Hogan, TP
Weaver, FM
McInnes, K
AF Turvey, Carolyn L.
Zulman, Donna M.
Nazi, Kim M.
Wakefield, Bonnie J.
Woods, Susan S.
Hogan, Timothy P.
Weaver, Frances M.
McInnes, Keith
TI Transfer of Information from Personal Health Records: A Survey of
Veterans Using My HealtheVet
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE e-health; medical records; telehealth
ID RANDOMIZED-TRIAL; MEDICAL-RECORD; SATISFACTION; SERVICES
AB Objective: Personal health records provide patients with ownership of their health information and allow them to share information with multiple healthcare providers. However, the usefulness of these records relies on patients understanding and using their records appropriately. My HealtheVet is a Web-based patient portal containing a personal health record administered by the Veterans Health Administration. The goal of this study was to explore veterans' interest and use of My HealtheVet to transfer and share information as well as to identify opportunities to increase veteran use of the My HealtheVet functions. Materials and Methods: Two waves of data were collected in 2010 through an American Customer Satisfaction Index Web-based survey. A random sample of veterans usingMy HealtheVet was invited to participate in the survey conducted on the My HealtheVet portal through a Web-based pop-up browser window. Results: Wave One results (n = 25,898) found that 41% of veterans reported printing information, 21% reported saving information electronically, and only 4% ever sent information from My HealtheVet to another person. In Wave Two (n = 18,471), 30% reported self-entering medication information, with 18% sharing this information with their Veterans Affairs (VA) provider and 9.6% sharing with their non-VA provider. Conclusion: Although veterans are transferring important medical information from their personal health records, increased education and awareness are needed to increase use. Personal health records have the potential to improve continuity of care. However, more research is needed on both the barriers to adoption as well as the actual impact on patient health outcomes and well-being.
C1 [Turvey, Carolyn L.; Wakefield, Bonnie J.] Iowa City VA Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat CA, Iowa City, IA 52246 USA.
[Turvey, Carolyn L.] Iowa City VA Hlth Care Syst, VA Off Rural Hlth, Vet Rural Hlth Resource Ctr Cent Reg, Iowa City, IA 52246 USA.
[Turvey, Carolyn L.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Zulman, Donna M.] Univ Michigan, Robert Wood Johnson Fdn Clin Scholars Program, Ann Arbor, MI 48109 USA.
[Zulman, Donna M.] VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA.
[Nazi, Kim M.] US Dept Vet Affairs, Vet & Consumers Hlth Informat Off, Washington, DC USA.
[Wakefield, Bonnie J.] Univ Missouri, Sinclair Sch Nursing, Columbia, MO USA.
[Woods, Susan S.] Portland VA Med Ctr, Portland, OR USA.
[Hogan, Timothy P.] Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA.
[Hogan, Timothy P.] Edward Hines Jr VA Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL USA.
[Hogan, Timothy P.] Edward Hines Jr VA Hosp, eHlth Qual Enhancement Res Initiat, Hines, IL USA.
[Hogan, Timothy P.] Loyola Univ Chicago, Stritch Sch Med, Program Hlth Serv Res, Maywood, IL USA.
[Weaver, Frances M.] Loyola Univ, Stritch Sch Med, Dept Med, Chicago, IL 60611 USA.
[McInnes, Keith] ENRM Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[McInnes, Keith] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
RP Turvey, CL (reprint author), Iowa City VA Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat CA, 601 Highway 6 W 152,Suite 40, Iowa City, IA 52246 USA.
EM carolyn-turvey@va.gov
FU Department of Veteran Affairs, Health Services Research and Development
Service through the eHealth QUERI; CADRE Center; Veterans Rural Health
Resource Center-Central Region, VA Office of Rural Health
FX Dr. Turvey is a Research Health Science Specialist in the Comprehensive
Access & Delivery Research and Evaluation (CADRE) Center, Iowa City VA
Health Care System. The work reported here was supported by the
Department of Veteran Affairs, Health Services Research and Development
Service through the eHealth QUERI, the CADRE Center, and the Veterans
Rural Health Resource Center-Central Region, VA Office of Rural Health.
The views expressed in this article are those of the authors and do not
necessarily represent the views of the Department of Veterans Affairs.
NR 13
TC 9
Z9 9
U1 1
U2 12
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 MAR
PY 2012
VL 18
IS 2
BP 109
EP 114
DI 10.1089/tmj.2011.0109
PG 6
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 902MB
UT WOS:000301041200006
PM 22304439
ER
PT J
AU Nambudiri, VE
Landrum, MB
Lamont, EB
McNeil, BJ
Bozeman, SR
Freedland, SJ
Keating, NL
AF Nambudiri, Vinod E.
Landrum, Mary Beth
Lamont, Elizabeth B.
McNeil, Barbara J.
Bozeman, Samuel R.
Freedland, Stephen J.
Keating, Nancy L.
TI Understanding Variation in Primary Prostate Cancer Treatment Within the
Veterans Health Administration
SO UROLOGY
LA English
DT Article
ID AFFAIRS MEDICAL-CENTERS; RADICAL PROSTATECTOMY; GEOGRAPHIC-VARIATION;
OF-LIFE; MEN; OUTCOMES; TRENDS; CARE; SERVICES; THERAPY
AB OBJECTIVE To examine the variation in prostate cancer treatment in the Veterans Health Administration (VHA)-a national, integrated delivery system. We also compared the care for older men in the VHA with that in fee-for-service Medicare.
METHODS We used data from the Veterans Affairs Central Cancer Registry linked with administrative data and Surveillance, Epidemiology, and End Results-Medicare data to identify men with local or regional prostate cancer diagnosed during 2001 to 2004. We used multinomial logistic and hierarchical regression models to examine the patient, tumor, and facility characteristics associated with treatment in the VHA and, among older patients, used propensity score methods to compare primary therapy between the VHA and fee-for-service Medicare.
RESULTS The rates of radical prostatectomy and radiotherapy varied substantially across VHA facilities. Among the VHA patients, older age, black race/ethnicity, and greater comorbidity were associated with receiving neither radical prostatectomy nor radiotherapy. Facilities with more black patients with prostate cancer had lower rates of radical prostatectomy, and those with less availability of external beam radiotherapy had lower radiotherapy rates. The adjusted rates of radiotherapy (39.7% vs 52.0%) and radical prostatectomy (12.1% vs 15.8%) were lower and the rates of receiving neither treatment greater (48.2% vs 32.2%) in the VHA versus fee-for-service Medicare (P < .001).
CONCLUSIONS In the VHA, the treatment rates varied substantially across facilities, and black men received less aggressive prostate cancer treatment than white men, suggesting factors other than patient preferences influence the treatment decisions. Also, primary prostate cancer therapy for older men is less aggressive in the VHA than in fee-for-service Medicare. UROLOGY 79: 537-545, 2012. (C) 2012 Elsevier Inc.
C1 [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Div Adult Oncol, Boston, MA 02114 USA.
ABT Associates Inc, Cambridge, MA 02138 USA.
Durham Vet Affairs Med Ctr, Durham, NC USA.
Duke Univ, Duke Prostate Ctr, Dept Surg, Div Urol, Durham, NC USA.
Duke Univ, Dept Pathol, Durham, NC 27706 USA.
RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
EM keating@hcp.med.harvard.edu
FU Department of Veterans Affairs through the Office of Policy and
Planning; Prostate Cancer Foundation
FX This work was funded by the Department of Veterans Affairs through the
Office of Policy and Planning. The efforts of Drs. Freedland and Keating
were also funded, in part, by the Prostate Cancer Foundation.
NR 30
TC 17
Z9 17
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
J9 UROLOGY
JI Urology
PD MAR
PY 2012
VL 79
IS 3
BP 537
EP 545
DI 10.1016/j.urology.2011.11.013
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 903XB
UT WOS:000301154400019
PM 22245306
ER
PT J
AU Prisciandaro, JJ
DeSantis, SM
Chiuzan, C
Brown, DG
Brady, KT
Tolliver, BK
AF Prisciandaro, James J.
DeSantis, Stacia M.
Chiuzan, Cody
Brown, Delisa G.
Brady, Kathleen T.
Tolliver, Bryan K.
TI Impact of Depressive Symptoms on Future Alcohol Use in Patients with
Co-Occurring Bipolar Disorder and Alcohol Dependence: A Prospective
Analysis in an 8-Week Randomized Controlled Trial of Acamprosate
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Bipolar Disorder; Alcohol; Alcoholism; Comorbidity; Craving; Dependence;
Depression; Drinking; Mania; Relapse
ID SUBSTANCE USE DISORDERS; TREATMENT ENHANCEMENT PROGRAM; HIDDEN
MARKOV-MODELS; ACUTE MANIA; STEP-BD; ABUSE; SCALE; HOSPITALIZATION;
PARTICIPANTS; DISTINCTION
AB Background: Bipolar disorders and alcohol use disorders commonly co-occur, yet little is known about the proximal impact of bipolar symptoms on alcohol use in patients with this comorbidity. The present study examined the impact of depressive symptoms and alcohol craving on proximal alcohol use in patients with co-occurring bipolar disorder and alcohol dependence.
Methods: Data were collected during an 8-week randomized controlled trial of acamprosate for individuals with co-occurring bipolar disorder and alcohol dependence (n = 30). Depressive symptoms and alcohol craving were assessed biweekly using the Montgomery Asberg Depression Rating Scale (MADRS) and the Obsessive Compulsive Drinking Scale (OCDS), respectively. Daily alcohol use data were available via administration of the Time-line Follow-back interview at baseline and at subsequent weekly study visits. Correlational analyses and hidden Markov modeling were used to examine the prospective relationships between depressive symptoms, alcohol craving, and alcohol use.
Results: Depressive symptoms and alcohol craving were significantly correlated with proximal (i. e., 1 week later) alcohol use across a variety of alcohol consumption summary measures. In hidden Markov models, depressive symptoms (OR = 1.3, 95% credible interval = [1.1, 1.5]) and alcohol craving (OR = 1.6, 95% credible interval = [1.4, 1.9]) significantly predicted transitioning from a light to a heavy drinking state, or remaining in a heavy drinking state.
Conclusions: The results from the present study suggest that depressive symptoms and alcohol craving increase proximal risk for alcohol use in individuals with co-occurring bipolar and alcohol use disorders.
C1 [Prisciandaro, James J.; Brown, Delisa G.; Brady, Kathleen T.; Tolliver, Bryan K.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, Charleston, SC 29425 USA.
[DeSantis, Stacia M.; Chiuzan, Cody] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA.
[Brady, Kathleen T.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA.
RP Prisciandaro, JJ (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, 67 President St,MSC861, Charleston, SC 29425 USA.
EM priscian@musc.edu
FU Forest Laboratories, Inc.; NIDA [T32 DA007288]
FX This study was funded by an investigator-initiated research grant to BKT
from Forest Laboratories, Inc.; Forest Laboratories 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 study
for publication. JJP was supported by NIDA T32 DA007288.
NR 40
TC 14
Z9 14
U1 3
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD MAR
PY 2012
VL 36
IS 3
BP 490
EP 496
DI 10.1111/j.1530-0277.2011.01645.x
PG 7
WC Substance Abuse
SC Substance Abuse
GA 897PC
UT WOS:000300663900012
PM 21933201
ER
PT J
AU Agrawal, A
Freedman, ND
Cheng, YC
Lin, P
Shaffer, JR
Sun, Q
Taylor, K
Yaspan, B
Cole, JW
Cornelis, MC
DeSensi, RS
Fitzpatrick, A
Heiss, G
Kang, JH
O'Connell, J
Bennett, S
Bookman, E
Bucholz, KK
Caporaso, N
Crout, R
Dick, DM
Edenberg, HJ
Goate, A
Hesselbrock, V
Kittner, S
Kramer, J
Nurnberger, JI
Qi, L
Rice, JP
Schuckit, M
van Dam, RM
Boerwinkle, E
Hu, F
Levy, S
Marazita, M
Mitchell, BD
Pasquale, LR
Bierut, LJ
AF Agrawal, Arpana
Freedman, Neal D.
Cheng, Yu-Ching
Lin, Peng
Shaffer, John R.
Sun, Qi
Taylor, Kira
Yaspan, Brian
Cole, John W.
Cornelis, Marilyn C.
DeSensi, Rebecca S.
Fitzpatrick, Annette
Heiss, Gerardo
Kang, Jae H.
O'Connell, Jeffrey
Bennett, Siiri
Bookman, Ebony
Bucholz, Kathleen K.
Caporaso, Neil
Crout, Richard
Dick, Danielle M.
Edenberg, Howard J.
Goate, Alison
Hesselbrock, Victor
Kittner, Steven
Kramer, John
Nurnberger, John I., Jr.
Qi, Lu
Rice, John P.
Schuckit, Marc
van Dam, Rob M.
Boerwinkle, Eric
Hu, Frank
Levy, Steven
Marazita, Mary
Mitchell, Braxton D.
Pasquale, Louis R.
Bierut, Laura J.
CA GENEVA Consortium
TI Measuring alcohol consumption for genomic meta-analyses of alcohol
intake: opportunities and challenges
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID U-SHAPED CURVE; WIDE ASSOCIATION; GENETIC INFLUENCES;
ENVIRONMENTAL-INFLUENCES; GENOMEWIDE ASSOCIATION; DIETARY PATTERNS;
SMOKING-BEHAVIOR; CANCER RISK; DEPENDENCE; MORTALITY
AB Whereas moderate drinking may have health benefits, excessive alcohol consumption causes many important acute and chronic diseases and is the third leading contributor to preventable death in the United States. Twin studies suggest that alcohol-consumption patterns are heritable (50%); however, multiple genetic variants of modest effect size are likely to contribute to this heritable variation. Genome-wide association studies provide a tool for discovering genetic loci that contribute to variations in alcohol consumption. Opportunities exist to identify susceptibility loci with modest effect by meta-analyzing together multiple studies. However, existing studies assessed many different aspects of alcohol use, such as typical compared with heavy drinking, and these different assessments can be difficult to reconcile. In addition, many studies lack the ability to distinguish between lifetime and recent abstention or to assess the pattern of drinking during the week, and a variety of such concerns surround the appropriateness of developing a common summary measure of alcohol intake. Combining such measures of alcohol intake can cause heterogeneity and exposure misclassification, cause a reduction in power, and affect the magnitude of genetic association signals. In this review, we discuss the challenges associated with harmonizing alcohol-consumption data from studies with widely different assessment instruments, with a particular focus on large-scale genetic studies. Am J Clin Nutr 2012; 95: 539-47.
C1 [Agrawal, Arpana] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Freedman, Neal D.; Caporaso, Neil] NCI, Bethesda, MD 20892 USA.
[Cheng, Yu-Ching; Cole, John W.; O'Connell, Jeffrey; Kittner, Steven; Mitchell, Braxton D.] Univ Maryland, Bethesda, MD USA.
[Shaffer, John R.; DeSensi, Rebecca S.; Marazita, Mary] Univ Pittsburgh, Pittsburgh, PA USA.
[Sun, Qi; Cornelis, Marilyn C.; Qi, Lu; van Dam, Rob M.; Hu, Frank] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Kang, Jae H.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Taylor, Kira] Univ Louisville, Louisville, KY 40292 USA.
[Heiss, Gerardo] Univ N Carolina, Chapel Hill, NC USA.
[Yaspan, Brian] Vanderbilt Univ, Nashville, TN USA.
[Fitzpatrick, Annette; Bennett, Siiri] Univ Washington, GENEVA Coordinating Ctr, Seattle, WA 98195 USA.
[Fitzpatrick, Annette; Bennett, Siiri; Bookman, Ebony] NHGRI, Morrisville, NC USA.
[Crout, Richard] W Virginia Univ, Morgantown, WV 26506 USA.
[Dick, Danielle M.] Virginia Commonwealth Univ, Richmond, VA USA.
[Edenberg, Howard J.; Nurnberger, John I., Jr.] Indiana Univ, Indianapolis, IN 46204 USA.
[Hesselbrock, Victor] Univ Connecticut, Farmington, CT USA.
[Kramer, John; Levy, Steven] Univ Iowa, Iowa City, IA USA.
[Schuckit, Marc] Univ Calif San Diego, San Diego, CA 92103 USA.
[Boerwinkle, Eric] Univ Texas Houston, Houston, TX USA.
[Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Agrawal, A (reprint author), Washington Univ, Sch Med, Dept Psychiat, 660 S Euclid,CB 8134, St Louis, MO 63110 USA.
EM arpana@wustl.edu
RI van Dam, Rob/F-9674-2010; Lin, P/G-7702-2014; Freedman,
Neal/B-9741-2015;
OI van Dam, Rob/0000-0002-7354-8734; Freedman, Neal/0000-0003-0074-1098;
Nurnberger, John/0000-0002-7674-1767; Edenberg,
Howard/0000-0003-0344-9690; Mitchell, Braxton/0000-0003-4920-4744
FU NIH Genes, Environment and Health Initiative (GEI) [U01 HG004422]; Gene,
Environment Association Studies (GENEVA) under GEI; Johns Hopkins
University Center for Inherited Disease Research by NIH GEI
[U01HG004438]; National Institute on Alcohol Abuse and Alcoholism;
National Institute on Drug Abuse; NIH [HHSN268200782096C];
ABMRF/Foundation for Alcohol Research; Boston Obesity Nutrition Research
Center [DK46200, U01HG004399, NIH R01 HL71981, K99HL098459]; American
Heart Association Scientist Development Award; Canadian Institutes of
Health Research (MCC); National Institutes of Dental and Craniofacial
Research (NIDCR) as part of the trans-NIH GEI [U01-DE018903]; NIDCR
[R01-DE 014899, R01-DE09551, R01-DE12101]; Iowa Fluoride Study; Iowa
Bone Development Study; NIDCR through CIDR's NIH; NHLBI; National Heart,
Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; Office of
Research and Development; Medical Research Service and the Baltimore
Geriatrics Research, Education and Clinical Center of the Department of
Veterans Affairs; National Institute of Neurological Disorders and
Stroke; NIH Office of Research on Women's Health [R01 NS45012, U01
NS069208-01]; National Human Genome Research Institute [U01 HG004436];
NHGRI [U01HG004728, NEI R01EY015473]; NIH GEI [U01HG04424];
[K02DA21237]; [DA23668]; [T32 AG000262]
FX The Study of Addiction: Genetics and Environment (SAGE): supported by
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 and with the 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 the collection of data
sets 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). 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 NIH contract "High throughput genotyping
for studying the genetic contributions to human disease"
(HHSN268200782096C). LJB was supported by K02DA21237. AA receives
support from the DA23668 and ABMRF/Foundation for Alcohol Research. NHS
and HPFS: the Pilot and Feasibility program were sponsored by the Boston
Obesity Nutrition Research Center (DK46200; QS), U01HG004399 (FH), NIH
R01 HL71981 and K99HL098459 (QS), American Heart Association Scientist
Development Award (LQ), and the Canadian Institutes of Health Research
(MCC). Dental Caries: Study: "Dental Caries: Whole Genome Association
and Gene Environment Studies" 1-U01-DE018903, PI Marazita. (Included in
the alcohol cross-study were the Levy (IOWA) and Marazita (PITT) study
populations so the acknowledgements below reflect only those studies.)
Funding support for the GWAS was provided by the National Institutes of
Dental and Craniofacial Research (NIDCR) as part of the trans-NIH GEI
(U01-DE018903). Data and samples were provided by the Center for Oral
Health Research in Appalachia (a collaboration of the University of
Pittsburgh and West Virginia University funded by NIDCR R01-DE 014899)
and the Iowa Fluoride Study and the Iowa Bone Development Study, funded
by NIDCR R01-DE09551 and R01-DE12101, respectively. Genotyping was done
by the Johns Hopkins University Center for Inherited Disease Research
(CIDR), which is fully funded through a federal contract from the NIH to
The Johns Hopkins University (contract number HHSN268200782096C). Funds
for this project's genotyping were provided by the NIDCR through CIDR's
NIH contract. Assistance with phenotype harmonization and genotype
cleaning, as well as with general study coordination, was provided by
the GENEVA Coordinating Center (U01-HG004446). Atherosclerosis Risk in
Communities Study: supported by NHLBI Cardiovascular Epidemiology
Training Grant (UNC) (National Research Service Award) to KT; carried
out as a collaborative study supported by National Heart, Lung, and
Blood Institute contracts HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C.; GEOS:
supported in part 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 (SK and JWC); the
National Institute of Neurological Disorders and Stroke and the NIH
Office of Research on Women's Health (R01 NS4512 and U01 NS069208-01)
(SK); the National Human Genome Research Institute (U01 HG004436) (BDM,
SK, and JO); and grant T32 AG000262 (Y-CC). GLAUGEN: supported by grants
NHGRI U01HG004728 and NEI R01EY015473 to LRP (Research to Prevent
Blindness Physician Scientist Award). Genotyping was performed at the
Broad Institute of MIT and Harvard, with funding support from the NIH
GEI (U01HG04424). The GENEVA Coordinating Center (U01HG004446) provided
assistance with genotype cleaning.
NR 74
TC 16
Z9 16
U1 2
U2 14
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAR
PY 2012
VL 95
IS 3
BP 539
EP 547
DI 10.3945/ajcn.111.015545
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 897HK
UT WOS:000300638700003
PM 22301922
ER
PT J
AU Dalrymple, LS
Katz, R
Kestenbaum, B
de Boer, IH
Fried, L
Sarnak, MJ
Shlipak, MG
AF Dalrymple, Lorien S.
Katz, Ronit
Kestenbaum, Bryan
de Boer, Ian H.
Fried, Linda
Sarnak, Mark J.
Shlipak, Michael G.
TI The Risk of Infection-Related Hospitalization With Decreased Kidney
Function
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Renal disease; chronic kidney disease; infection; clinical epidemiology
ID GLOMERULAR-FILTRATION-RATE; SERUM CYSTATIN-C; STAGE RENAL-DISEASE;
CARDIOVASCULAR EVENTS; DEATH; CREATININE; MORBIDITY; DIALYSIS; DEFECTS;
ADULTS
AB Background: Moderate kidney disease may predispose to infection. We sought to determine whether decreased kidney function, estimated by serum cystatin C level, was associated with the risk of infection-related hospitalization in older individuals.
Study Design: Cohort study.
Setting & Participants: 5,142 Cardiovascular Health Study (CHS) participants with measured serum creatinine and cystatin C and without estimated glomerular filtration rate (eGFR) <15 mL/min/1.73m(2) at enrollment.
Predictor: The primary exposure of interest was eGFR using serum cystatin C level (eGFR(SCysC)).
Outcome: Infection-related hospitalizations during a median follow-up of 11.5 years.
Results: In adjusted analyses, eGFR(SCysC) categories of 60-89, 45-59, and 15-44 mL/min/1.73 m(2) were associated with 16%, 37%, and 64% greater risk of all-cause infection-related hospitalization, respectively, compared with eGFRSCysC >= 90 mL/min/1.73 m2. When cause-specific infection was examined, eGFR(SCysC) of 15-44 mL/min/1.73 m2 was associated with an 80% greater risk of pulmonary and 160% greater risk of genitourinary infection compared with eGFR(SCysC) >= 90 mL/min/1.73 m(2).
Limitations: No measures of urinary protein, study limited to principal discharge diagnosis.
Conclusions: Lower kidney function, estimated using cystatin C level, was associated with a linear and graded risk of infection-related hospitalization. These findings highlight that even moderate degrees of decreased kidney function are associated with clinically significant higher risks of serious infection in older individuals. Am J Kidney Dis. 59(3): 356-363. (C) 2012 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Dalrymple, Lorien S.] Univ Calif Davis, Dept Med, Davis, CA 95616 USA.
[Katz, Ronit] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Kestenbaum, Bryan; de Boer, Ian H.] Univ Washington, Dept Med, Seattle, WA USA.
[Fried, Linda] VA Pittsburgh Hlth Care Syst, Renal Sect, Pittsburgh, PA USA.
[Fried, Linda] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA.
[Fried, Linda] Univ Pittsburgh, Dept Epidemiol, Sch Med, Pittsburgh, PA 15261 USA.
[Sarnak, Mark J.] Tufts Med Ctr, Dept Med, Boston, MA USA.
[Shlipak, Michael G.] Vet Affairs Med Ctr, Med Serv, Gen Internal Med Sect, San Francisco, CA 94121 USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Dalrymple, LS (reprint author), Div Nephrol, 4150 V St,Ste 3500, Sacramento, CA 95817 USA.
EM lorien.dalrymple@ucdmc.ucdavis.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [HL080295]; National
Institute of Neurological Disorders and Stroke; National Institute on
Aging [AG-023629, AG-15928, AG-20098, AG-027058, AG-027002]; National
Center for Research [UL1 RR024146]; NHLBI; [N01-HC-85239];
[N01-HC-85079]; [N01-HC-85080]; [N01-HC-85081]; [N01-HC-85082];
[N01-HC-85083]; [N01-HC-85084]; [N01-HC-85085]; [N01-HC-85086];
[N01-HC-35129]; [N01 HC-15103]; [N01 HC-55222]; [N01-HC-75150];
[N01-HC-45133]
FX This research was supported by contracts N01-HC-85239, N01-HC-85079
through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222,
N01-HC-75150, N01-HC-45133, and grant HL080295 from the National Heart,
Lung, and Blood Institute (NHLBI), with additional contribution from the
National Institute of Neurological Disorders and Stroke. Additional
support was provided through AG-023629, AG-15928, AG-20098, AG-027058,
and AG-027002 from the National Institute on Aging and UL1 RR024146 from
the National Center for Research. The CHS was funded through contracts
with NHLBI and included substantial NHLBI involvement in the design and
conduct of the study and the collection and management of the data. The
funding source was not involved in data analysis, interpretation of the
data, preparation, review, or approval of the manuscript. The contents
are solely the responsibility of the authors and do not necessarily
represent the official view of the National Institutes of Health. A full
list of principal CHS investigators and institutions can be found at
www.chs-nhlbi.org/pi.htm.
NR 25
TC 20
Z9 20
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD MAR
PY 2012
VL 59
IS 3
BP 356
EP 363
DI 10.1053/j.ajkd.2011.07.012
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 898WE
UT WOS:000300772300009
PM 21906862
ER
PT J
AU Greenblatt, MB
Sargent, JL
Farina, G
Tsang, K
Lafyatis, R
Glimcher, LH
Whitfield, ML
Aliprantis, AO
AF Greenblatt, Matthew B.
Sargent, Jennifer L.
Farina, Giuseppina
Tsang, Kelly
Lafyatis, Robert
Glimcher, Laurie H.
Whitfield, Michael L.
Aliprantis, Antonios O.
TI Interspecies Comparison of Human and Murine Scleroderma Reveals IL-13
and CCL2 as Disease Subset-Specific Targets
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; GENE-EXPRESSION ANALYSIS;
SYSTEMIC-SCLEROSIS; RHEUMATOID-ARTHRITIS; PULMONARY-FIBROSIS; SKIN
FIBROSIS; HOST DISEASE; SERUM-LEVELS; T-CELLS; INTERLEUKIN-13
AB Development of personalized treatment regimens is hampered by lack of insight into how individual animal models reflect subsets of human disease, and autoimmune and inflammatory conditions have proven resistant to such efforts. Scleroderma is a lethal autoimmune disease characterized by fibrosis, with no effective therapy. Comparative gene expression profiling showed that murine sclerodermatous graft-versus-host disease (sclGVHD) approximates an inflammatory subset of scleroderma estimated at 17% to 36% of patients analyzed with diffuse, 28% with limited, and 100% with localized scleroderma. Both scIGVHD and the inflammatory subset demonstrated IL-13 cytokine pathway activation. Host dermal myeloid cells and graft T cells were identified as sources of IL-13 in the model, and genetic deficiency of either IL-13 or IL-4R alpha, an IL-13 signal transducer, protected the host from disease. To identify therapeutic targets, we explored the intersection of genes coordinately up-regulated in sclGVHD, the human inflammatory subset, and IL-13 treated fibroblasts; we identified chemokine CCL2 as a potential target. Treatment with anti-CCL2 antibodies prevented sclGVHD. Last, we showed that IL-13 pathway activation in scleroderma patients correlated with clinical skin scores, a marker of disease severity. Thus, an inflammatory subset of scleroderma is driven by IL-13 and may benefit from IL-13 or CCL2 blockade. This approach serves as a model for personalized translational medicine, in which well-characterized animal models are matched to molecularly stratified patient subsets. (Am J Pathol 2012, 180:1080-1094; DOI: 10.1016/j.ajpath.2011.11.024)
C1 [Greenblatt, Matthew B.; Tsang, Kelly; Glimcher, Laurie H.; Aliprantis, Antonios O.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Sargent, Jennifer L.; Whitfield, Michael L.] Dartmouth Med Sch, Dept Genet, Hanover, NH 03755 USA.
[Farina, Giuseppina; Lafyatis, Robert] Boston Univ, Sch Med, Dept Med, Div Rheumatol, Boston, MA 02118 USA.
[Glimcher, Laurie H.; Aliprantis, Antonios O.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Glimcher, Laurie H.; Aliprantis, Antonios O.] Harvard Univ, Sch Med, Boston, MA USA.
[Glimcher, Laurie H.] Harvard Univ, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Glimcher, Laurie H.] MIT, Boston, MA USA.
RP Aliprantis, AO (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 651 Huntington Ave,FXB 205, Boston, MA 02115 USA.
EM michael.L.whitfield@dartmouth.edu; aaliprantis@partners.org
OI Farina, Giuseppina Alessandra/0000-0002-3948-6920
FU Scleroderma Research Foundation; Arthritis Foundation; Burroughs
Wellcome Fund; NIH National Institute of Arthritis and Musculoskeletal
and Skin Diseases [K08AR054859]; NIAMS [U01AR055063, R01AR051089];
Scleroderma Foundation
FX Supported by grants from the Scleroderma Research Foundation (M.L.W.,
A.O.A. and L.H.G.), a Hulda Irene Duggan Arthritis Investigator Award
from the Arthritis Foundation (M.L.W.), a Career Award for Medical
Scientists from the Burroughs Wellcome Fund (A.O.A.), by an NIH National
Institute of Arthritis and Musculoskeletal and Skin Diseases grant
K08AR054859 (A.O.A), NIAMS grants U01AR055063 (R.L.) and R01AR051089
(R.L.), and by Scleroderma Foundation support (G.F.).
NR 57
TC 35
Z9 35
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD MAR
PY 2012
VL 180
IS 3
BP 1080
EP 1094
DI 10.1016/j.ajpath.2011.11.024
PG 15
WC Pathology
SC Pathology
GA 902EU
UT WOS:000301022200021
PM 22245215
ER
PT J
AU Anderson, S
Oyama, TT
Lindsley, JN
Schutzer, WE
Beard, DR
Gattone, VH
Komers, R
AF Anderson, Sharon
Oyama, Terry T.
Lindsley, Jessie N.
Schutzer, William E.
Beard, Douglas R.
Gattone, Vincent H., II
Komers, Radko
TI 2-Hydroxyestradiol slows progression of experimental polycystic kidney
disease
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE gender; estrogen; mammalian target of rapamycin 2; hydroxyestradiol p21;
hypoxia-inducible factor-1 alpha
ID HAN-SPRD RATS; ACTIVATED PROTEIN-KINASE; EPITHELIAL-CELL PROLIFERATION;
RENAL-DISEASE; SIGNALING PATHWAY; INHIBITION SLOWS; CYSTIC-DISEASE; MTOR
PATHWAY; CANCER CELLS; GROWTH
AB Anderson S, Oyama TT, Lindsley JN, Schutzer WE, Beard DR, Gattone VH 2nd, Komers R. 2-Hydroxyestradiol slows progression of experimental polycystic kidney disease. Am J Physiol Renal Physiol 302: F636-F645, 2012. First published December 7, 2011; doi: 10.1152/ajprenal.00265.2011.-Male gender is a risk factor for progression of polycystic kidney disease (PKD). 17 beta-Estradiol (E2) protects experimentally, but clinical use is limited by adverse effects. Novel E2 metabolites provide many benefits of E2 without stimulating the estrogen receptor, and thus may be safer. We hypothesized that E2 metabolites are protective in a model of PKD. Studies were performed in male control Han:SPRD rats, and in cystic males treated with orchiectomy, 2-methoxyestradiol, 2-hydroxyestradiol (2-OHE), or vehicle, from age 3 to 12 wk. Cystic rats exhibited renal functional impairment (similar to 50% decrease in glomerular filtration and renal plasma flow rates, P < 0.05) and substantial cyst development (20.5 +/- 2.0% of cortex area). 2-OHE was the most effective in limiting cysts (6.0 +/- 0.7% of cortex area, P < 0.05 vs. vehicle-treated cystic rats) and preserving function, in association with suppression of proliferation, apoptosis, and angiogenesis markers. Downregulation of p21 expression and increased expression of Akt, the mammalian target of rapamycin (mTOR), and some of its downstream effectors were significantly reversed by 2-OHE. Thus, 2-OHE limits disease progression in a cystic rodent model. Mechanisms include reduced renal cell proliferation, apoptosis, and angiogenesis. These effects may be mediated, at least in part, by preservation of p21 and suppression of Akt and mTOR. Estradiol metabolites may represent a novel, safe intervention to slow progression of PKD.
C1 [Anderson, Sharon; Oyama, Terry T.; Lindsley, Jessie N.; Schutzer, William E.; Komers, Radko] Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97239 USA.
[Anderson, Sharon] Portland VA Med Ctr, Med Serv, Portland, OR USA.
[Schutzer, William E.; Beard, Douglas R.] Portland VA Med Ctr, Res Serv, Portland, OR USA.
[Gattone, Vincent H., II] Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN USA.
RP Anderson, S (reprint author), Oregon Hlth & Sci Univ, Div Nephrol, CH12R,3303 SW Bond St, Portland, OR 97239 USA.
EM anderssh@ohsu.edu
FU National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases [DK 078807]; Polycystic Kidney Research
Foundation
FX These studies were supported by grants from the National Institutes of
Health/National Institute of Diabetes and Digestive and Kidney Diseases
(DK 078807) and the Polycystic Kidney Research Foundation.
NR 76
TC 5
Z9 5
U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD MAR
PY 2012
VL 302
IS 5
BP F636
EP F645
DI 10.1152/ajprenal.00265.2011
PG 10
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 901BG
UT WOS:000300936100014
PM 22160773
ER
PT J
AU Martin, TR
Snapp, DL
Tomita, DM
AF Martin, Thomas R.
Snapp, Deborah L.
Tomita, Diane M.
TI The Parker B. Francis Fellowship Program Analysis of 31 Years of Career
Development Support
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE research training; fellowship support; survey; career development
ID ORGANIZATIONAL-CLIMATE; MEDICAL-SCHOOL; RESPONSE RATES; WOMEN FACULTY
AB Rationale: The Parker B. Francis (PBF) Fellowship Program has supported more than 750 M.D., M.D./Ph.D., and Ph.D. fellows since 1976, but there is little information about the effectiveness of the program in fostering successful careers and producing important research.
Objectives: To survey all past PBF Fellows to obtain information about their productivity and career pathways.
Methods: We obtained e-mail addresses for 526 (74%) of the 712 PBF awardees from 1976 to 2006, then sent an e-mail survey to the 526 past fellows and received 365 replies (69% response rate, 49% overall). Survey questions addressed time in research, areas of research, current position and responsibilities, and research funding.
Measurements and Main Results: Seventy percent of the 365 respondents spend 25% or greater effort in research and 56% report 50% or more effort in research. Respondents have published an average of 2.7 peer-reviewed publications per year, totaling more than 15,678 peer-reviewed publications, of which 1,875 appeared in high-impact journals. Respondents have received more than $1.8 billion in direct research funding since their PBF Fellowships began. Ph.D. awardees spend more time in research than M.D. awardees, and current research effort did not differ by gender. PBF awardees have become prominent leaders in universities, the National Institutes of Health, health care, and industry.
Conclusions: The PBF Program has been highly successful in producing a large number of scientific and clinical leaders in pulmonary and critical care medicine. The results provide comprehensive data about the success of this career development program and provide a model for programs designed to build the workforce in pulmonary and critical care medicine.
C1 [Martin, Thomas R.] Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
[Martin, Thomas R.] VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA USA.
RP Martin, TR (reprint author), Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
EM trmartin@u.washington.edu
FU Francis Family Foundation, Kansas City, MO; Francis Family Foundation
FX Supported by the Francis Family Foundation, Kansas City, MO.; The
authors thank the Francis Family members and the Francis Family
Foundation Board of Directors for their steadfast support of the Parker
B. Francis Fellowship Program and the Parker B. Francis Council of
Scientific Advisors for advice during the preparation of this report.
The data in this report reflect the leadership of the past Scientific
Directors of the PBF Program, S. Marsh Tenney, M.D., Donald F. Tierney,
M.D. and Joseph D. Brain, Sc.D.
NR 10
TC 2
Z9 2
U1 0
U2 3
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 MAR 1
PY 2012
VL 185
IS 5
BP 479
EP 485
DI 10.1164/rccm.201108-1390PP
PG 7
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 900AG
UT WOS:000300858400008
PM 22095548
ER
PT J
AU Kraft, S
Faquin, WC
Krane, JF
AF Kraft, Stefan
Faquin, William C.
Krane, Jeffrey F.
TI HPV-associated Neuroendocrine Carcinoma of the Oropharynx: A Rare New
Entity With Potentially Aggressive Clinical Behavior
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE human papillomavirus; head and neck cancer; squamous cell carcinoma;
neuroendocrine carcinoma; oropharynx
ID SQUAMOUS-CELL-CARCINOMA; HUMAN-PAPILLOMAVIRUS DNA; TRANSCRIPTION
FACTOR-I; NECK-CANCER; UTERINE CERVIX; IMMUNOHISTOCHEMICAL ANALYSIS;
ADENOSQUAMOUS CARCINOMA; UNDIFFERENTIATED CARCINOMA; FAVORABLE
PROGNOSIS; TONSILLAR CARCINOMA
AB High-grade neuroendocrine carcinoma of the head and neck is an aggressive neoplasm which rarely arises in the oropharynx. Here we report a series of 8 oropharyngeal neuroendocrine carcinomas associated with both human papillomavirus (HPV) infection and tobacco exposure. The tumor occurred predominantly in male patients (6 of 8) at a mean age of 59 years. Histologically, these cases were all classified as poorly differentiated neuroendocrine carcinoma (small cell carcinoma) with high mitotic activity [mean 53.3 mitoses per 10 HPF], necrosis, high nuclear-to-cytoplasmic ratio, and nuclear molding. One case also exhibited a moderately differentiated component, and one other case had a component of squamous cell carcinoma with basaloid features. Neuroendocrine differentiation was confirmed by immunoreactivity for synaptophysin and/or chromogranin A in all cases. P63 staining was negative, except in 1 case. Seven of the 8 cases showed strong and diffuse p16 expression, a surrogate marker for high-risk HPV infection. HPV infection was confirmed in 6 of these 7 cases by HPV in situ hybridization and/or polymerase chain reaction analysis. HPV subtypes 16, 18, and 33 were identified in 1 case each by polymerase chain reaction testing. Six of the 7 patients for whom clinical history was available presented with advanced disease (4 with regional lymph node metastases, 1 with distant metastases, and 1 with distant and locoregional metastases). Disease recurred in 5 of the 6 patients with available clinical follow-up, with 3 developing distant metastases to brain, bones, lung, pleura, adrenal glands, and pancreas. These 3 cases were all from the HPV-positive group. In summary, neuroendocrine carcinoma of the oropharynx represents a rare novel HPV-associated entity with high-grade histologic features and aggressive clinical behavior.
C1 [Kraft, Stefan; Krane, Jeffrey F.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Kraft, Stefan; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Krane, JF (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM jkrane@partners.org
NR 74
TC 28
Z9 29
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD MAR
PY 2012
VL 36
IS 3
BP 321
EP 330
PG 10
WC Pathology; Surgery
SC Pathology; Surgery
GA 902KY
UT WOS:000301038200001
PM 22301491
ER
PT J
AU Khor, TS
Alfaro, EE
Ooi, EMM
Li, Y
Srivastava, A
Fujita, H
Do, YP
Kumarasinghe, MP
Lawyers, GY
AF Khor, Tze Sheng
Alfaro, Eduardo E.
Ooi, Esther M. M.
Li, Yuan
Srivastava, Amitabh
Fujita, Hiroshi
Do, Youn Park
Kumarasinghe, Marian Priyanthi
Lawyers, Gregory Yves
TI Divergent Expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in Dysplasia
and Intramucosal Adenocarcinomas With Intestinal and Foveolar
Morphology: Is This Evidence of Distinct Gastric and Intestinal Pathways
to Carcinogenesis in Barrett Esophagus?
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE Barrett esophagus; foveolar dysplasia; adenomatous dysplasia; hybrid
dysplasia; intramucosal adenocarcinoma; immunophenotype; mucin core
peptide expression; CDX-2
ID COLUMNAR-LINED ESOPHAGUS; IMMUNOHISTOCHEMICAL-DEMONSTRATION; GOBLET
CELLS; METAPLASIA; DIAGNOSIS; EPITHELIUM; CANCER; DIFFERENTIATION;
SURVEILLANCE; HISTOGENESIS
AB Dysplasia in Barrett esophagus has been recognized to be morphologically heterogenous, featuring adenomatous, foveolar, and hybrid phenotypes. Recent studies have suggested a tumor suppressor role for CDX-2 in the metaplasia-dysplasia-carcinoma sequence. The phenotypic stability and role of CDX-2 in the neoplastic progression of different types of dysplasias have not been evaluated. Thirty-eight endoscopic mucosal resections with dysplasia and/or intramucosal carcinoma (IMC) arising in Barrett esophagus were evaluated for the expression of MUC5AC, MUC6, MUC2, CD 10, and CDX-2. The background mucosa was also evaluated. The results were correlated with morphologic classification and clinicopathologic parameters. Of 38 endoscopic mucosal resections, 23 had IMC and dysplasia, 8 had IMC only, and 7 had dysplasia only. Among dysplastic lesions, 73% were foveolar, 17% were adenomatous, and 10% were hybrid. Twenty of 23 cases with dysplasia and adjacent IMC showed an identical immunophenotype of dysplasia and IMC comprising 16 gastric, 3 intestinal, and I mixed immunophenotype. Three cases showed discordance of dysplasia and IMC immunophenotype. These findings suggest that most Barrett-related IMC cases are either gastric or intestinal, with phenotypic stability during progression supporting separate gastric and intestinal pathways of carcinogenesis. CDX-2 showed gradual downregulation of expression during progression in adenomatous dysplasia but not in foveolar or hybrid dysplasia, supporting a tumor suppressor role, at least in the intestinal pathway. CDX-2 was also found to be expressed to a greater degree in intestinal metaplasia compared with non-intestinalized columnar metaplasia. Consistent with CDX-2 as a tumor suppressor, this suggests that non-intestinalized columnar metaplasia may be an unstable intermediate state at risk for neoplastic progression.
C1 [Khor, Tze Sheng; Alfaro, Eduardo E.; Ooi, Esther M. M.; Li, Yuan; Fujita, Hiroshi; Lawyers, Gregory Yves] Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA.
[Srivastava, Amitabh] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Srivastava, Amitabh; Lawyers, Gregory Yves] Harvard Univ, Sch Med, Boston, MA USA.
[Khor, Tze Sheng; Kumarasinghe, Marian Priyanthi] Univ Western Australia, PathW Lab Med, Perth, WA 6009, Australia.
[Ooi, Esther M. M.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Alfaro, Eduardo E.] Univ Costa Rica, Hosp Mexico, Dept Pathol, San Jose, Costa Rica.
[Li, Yuan] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Pathol, Beijing 100730, Peoples R China.
[Li, Yuan] Peking Union Med Coll, Beijing 100730, Peoples R China.
[Fujita, Hiroshi] Kagoshima Univ, Grad Sch Med & Dent Sci, Kagoshima Univ Hosp, Dept Gastroenterol, Kagoshima 890, Japan.
[Do, Youn Park] Pusan Natl Univ, Pusan Natl Univ Hosp, Med Res Inst, Sch Med,Dept Pathol, Pusan, South Korea.
RP Lawyers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, 55 Fruit St, Boston, MA 02114 USA.
EM glauwers@partners.org
RI Ooi, Esther/B-3257-2011
OI Ooi, Esther/0000-0002-2097-633X
FU National Research and Development Program for Cancer Control [0920050];
Ministry for Health, Welfare and Family affairs, Republic of Korea; A&A
Saw Medical Research Fellowship; National Health and Medical Research
Council of Australia
FX Funding for immunohistochemistry for this study was supported by a Grant
(0920050) from the National Research and Development Program for Cancer
Control, Ministry for Health, Welfare and Family affairs, Republic of
Korea. T.S.K. is supported by an A&A Saw Medical Research Fellowship.
E.M.M.O. is supported by a National Health and Medical Research Council
of Australia Postdoctoral Research Fellowship. For the remaining authors
none were declared.
NR 39
TC 28
Z9 31
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD MAR
PY 2012
VL 36
IS 3
BP 331
EP 342
PG 12
WC Pathology; Surgery
SC Pathology; Surgery
GA 902KY
UT WOS:000301038200002
PM 22261707
ER
PT J
AU Kao, CS
Idrees, MT
Young, RH
Ulbright, TM
AF Kao, Chia-Sui
Idrees, Muhammad T.
Young, Robert H.
Ulbright, Thomas M.
TI Solid Pattern Yolk Sac Tumor: A Morphologic and lmmunohistochemical
Study of 52 Cases
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE testis; mediastinum; yolk sac tumor; solid pattern
ID GERM-CELL TUMORS; ENDODERMAL SINUS TUMOR; EMBRYONAL CARCINOMA;
DIFFERENTIAL-DIAGNOSIS; ALPHA-FETOPROTEIN; SEMINOMA; OVARY; CHILDREN;
IMMUNOHISTOCHEMISTRY; MARKER
AB Yolk sac tumors may exhibit numerous patterns. One that has received little attention overall, yet is not uncommon, is a solid pattern, which is especially prone to misinterpretation, usually as seminoma, in biopsy specimens from metastatic or mediastinal sites. This distinction is of critical importance as the 2 tumors are treated differently. To determine features useful in the diagnosis of solid yolk sac tumor we reviewed 52 germ cell tumors (28 testicular primaries, 21 metastases from the testis, and 3 mediastinal primaries) that had a yolk sac tumor component with foci of solid growth, defined as a sheet-like arrangement of tumor cells occupying > 2 mm(2) and with no or only rare microcysts. Solid yolk sac tumor was almost always associated with other patterns, most commonly microcystic/reticular (75%), glandular (35%) myxoid (25%). The solid foci consisted of sheets of cells with usually abundant cytoplasm that was mostly (85%) pale to clear and frequently had intercellular basement membrane deposits (75%), rare microcysts (67%), significant nuclear pleomorphism (65%), and hyaline globules (65%). In 2 cases (4%), the cells were small with scant cytoplasm (blastema-like variant). A myxoid background (39%), lymphocytic infiltrate (17%), and an applique pattern (8%) were sometimes observed. On immunostaining, AE1/AE3 cytokeratin and glypican 3 provided the most intense and diffuse reactivity for solid yolk sac tumor, whereas a-fetoprotein was negative in 38%. CD117 stained 59%, whereas only rare cells in I case (3%) were weakly reactive for podoplanin; OCT3/4 was uniformly negative. We conclude that solid yolk sac tumor can generally be recognized by careful morphologic evaluation, especially its association with other yolk sac tumor patterns, the presence of intercellular band-like deposits of basement membrane, occasional microcysts, nuclear pleomorphism, intracellular hyaline globules, and usual absence of lymphocytes. In difficult cases a concise immunohistochemical panel consisting of AE1/AE3, glypican 3, and OCT3/4 distinguishes solid yolk sac tumor from other neoplasms. alpha-fetoprotein stains are commonly negative or weak and focal in solid yolk sac tumor and cannot be solely relied on for diagnosis. Common CD117 positivity in solid pattern yolk sac tumors makes it an unreliable discriminator between yolk sac tumor and seminoma.
C1 [Kao, Chia-Sui; Idrees, Muhammad T.; Ulbright, Thomas M.] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA.
[Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Lab, Boston, MA USA.
RP Ulbright, TM (reprint author), Indiana Univ, Hlth Pathol Lab, Room 4014,350 W 11th St, Indianapolis, IN 46202 USA.
EM tulbrigh@iupui.edu
NR 50
TC 21
Z9 28
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD MAR
PY 2012
VL 36
IS 3
BP 360
EP 367
PG 8
WC Pathology; Surgery
SC Pathology; Surgery
GA 902KY
UT WOS:000301038200005
PM 22261704
ER
PT J
AU Baron, DM
Yu, BL
Lei, C
Bagchi, A
Beloiartsev, A
Stowell, CP
Steinbicker, AU
Malhotra, R
Bloch, KD
Zapol, WM
AF Baron, David M.
Yu, Binglan
Lei, Chong
Bagchi, Aranya
Beloiartsev, Arkadi
Stowell, Christopher P.
Steinbicker, Andrea U.
Malhotra, Rajeev
Bloch, Kenneth D.
Zapol, Warren M.
TI Pulmonary Hypertension in Lambs Transfused with Stored Blood Is
Prevented by Breathing Nitric Oxide
SO ANESTHESIOLOGY
LA English
DT Article
ID SICKLE-CELL-DISEASE; ENDOTHELIAL DYSFUNCTION; STORAGE LESION;
S-NITROSOHEMOGLOBIN; FREE HEMOGLOBIN; BANKED BLOOD; AWAKE LAMBS;
HEMOLYSIS; SHEEP; VASOCONSTRICTION
AB Background: During extended storage, erythrocytes undergo functional changes. These changes reduce the viability of erythrocytes leading to release of oxyhemoglobin, a potent scavenger of nitric oxide. We hypothesized that transfusion of ovine packed erythrocytes (PRBC) stored for prolonged periods would induce pulmonary vasoconstriction in lambs, and that reduced vascular nitric oxide concentrations would increase this vasoconstrictor effect.
Methods: We developed a model of autologous stored blood transfusion in lambs (n = 36). Leukoreduced blood was stored for either 2 days (fresh PRBC) or 40 days (stored PRBC). Fresh or stored PRBC were transfused into donors instrumented for awake hemodynamic measurements. Hemodynamic effects of PRBC transfusion were also studied after infusion of N-G-nitro-L-arginine methyl-ester (25 mg/kg) or during inhalation of nitric oxide (80 ppm).
Results: Cell-free hemoglobin levels were higher in the supernatant of stored PRBC than in supernatant of fresh PRBC (Mean +/- SD, 148 +/- 20 vs. 41 +/- 13 mg/dl, respectively, P < 0.001). Pulmonary artery pressure during transfusion of stored PRBC transiently increased from 13 +/- 1 to 18 +/- 1 mmHg (P < 0.001) and was associated with increased plasma hemoglobin concentrations. N-G-intro-L-arginine methyl-ester potentiated the increase in pulmonary arterial pressure induced by transfusing stored PRBC, whereas inhalation of nitric oxide prevented the vasoconstrictor response.
Conclusions: Our results suggest that patients with reduced vascular nitric oxide levels because of endothelial dysfunction may be more susceptible to adverse effects of transfusing blood stored for prolonged periods. These patients might benefit from transfusion of fresh PRBC, when available, or inhaled nitric oxide supplementation to prevent the pulmonary hypertension associated with transfusion of stored PRBC.
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Zapol, WM (reprint author), Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Thier 503, Boston, MA 02114 USA.
EM wzapol@partners.org
OI Malhotra, Rajeev/0000-0003-0120-4630
FU Eleanor and Miles Shore 50th Anniversary Fellowship (Boston,
Massachusetts); German Research Foundation (Bonn, Germany) [SW 119/3-1];
National Institutes of Health (Bethesda, Maryland) [T32, HL074352];
American Heart Association (Dallas, Texas); Ikaria
FX Received from Massachusetts General Hospital and Harvard Medical School,
Boston, Massachusetts. Submitted for publication August 2, 2011.
Accepted for publication November 21, 2011. Supported by funds of the
Department of Anesthesia, Critical Care, and Pain Medicine,
Massachusetts General Hospital, Boston, Massachusetts. Dr. Yu was
supported by the Eleanor and Miles Shore 50th Anniversary Fellowship
(Boston, Massachusetts). Dr. Steinbicker was supported by grant No. SW
119/3-1 from the German Research Foundation (Bonn, Germany). Dr.
Malhotra was supported by a National Institutes of Health T32 grant
(Bethesda, Maryland) and a Fellow-to-Faculty Transition Award from the
American Heart Association (Dallas, Texas). Dr. Bloch was supported by a
National Institutes of Health R01 grant No. HL074352 (Bethesda,
Maryland). Dr. Zapol receives royalties from patents on inhaled nitric
oxide licensed by Massachusetts General Hospital to Linde Corporation,
Munich, Germany, and Ikaria Corporation, Clinton, New Jersey. Dr. Bloch
has received grants from Ikaria to study inhaled nitric oxide. Drs.
Zapol and Yu have applied for a U.S. patent entitled "Attenuation of
artificial oxygen carrier-induced vasoconstriction," Provisional Patent
Application 60/864,734. The remaining authors report no conflicts of
interest.
NR 47
TC 28
Z9 32
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD MAR
PY 2012
VL 116
IS 3
BP 637
EP 647
DI 10.1097/ALN.0b013e318246ef77
PG 11
WC Anesthesiology
SC Anesthesiology
GA 898UE
UT WOS:000300766700019
PM 22293717
ER
PT J
AU Wong, VM
Wenk, JF
Zhang, ZH
Cheng, GM
Acevedo-Bolton, G
Burger, M
Saloner, DA
Wallace, AW
Guccione, JM
Ratcliffe, MB
Ge, L
AF Wong, Vincent M.
Wenk, Jonathan F.
Zhang, Zhihong
Cheng, Guangming
Acevedo-Bolton, Gabriel
Burger, Mike
Saloner, David A.
Wallace, Arthur W.
Guccione, Julius M.
Ratcliffe, Mark B.
Ge, Liang
TI The Effect of Mitral Annuloplasty Shape in Ischemic Mitral
Regurgitation: A Finite Element Simulation
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID DILATED CARDIOMYOPATHY; LEFT-VENTRICLE; WALL STRESS; VALVE; REPAIR;
MODEL; RECONSTRUCTION; PATHOGENESIS; HYPERTROPHY; DIMENSIONS
AB Background. Undersized mitral annuloplasty (MA) is the preferred surgical treatment for chronic ischemic mitral regurgitation. However, the preferred shape of undersized MA is unclear.
Methods. A previously described finite element model of the left ventricle with mitral valve based on magnetic resonance images of a sheep with chronic ischemic mitral regurgitation after posterolateral myocardial infarction was used. Saddle-shape (Edwards Physio II) and asymmetric (IMR ETlogix) MA rings were digitized and meshed. Virtual annuloplasty was performed using virtual sutures to attach the MA ring. Left ventricular diastole and systole were performed before and after virtual MA of each type.
Results. Both types of MA reduced the septolateral dimension of the mitral annulus and abolished mitral regurgitation. The asymmetric MA was associated with lower virtual suture force in the P2 region but higher force in P1 and P3 regions. Although both types of MA reduced fiber stress at the left ventricular base, fiber stress reduction after asymmetric MA was slightly greater. Neither type of MA affected fiber stress at the left ventricular equator or apex. Although both types of MA increased leaflet curvature and reduced leaflet stress, stress reduction with saddle-shape MA was slightly greater. Both MA types reduced stress on the mitral chordae.
Conclusions. The effects of saddle-shape and asymmetric MA rings are similar. Finite element simulations are a powerful tool that may reduce the need for animal and clinical trials. (Ann Thorac Surg 2012; 93: 776-82) (C) 2012 by The Society of Thoracic Surgeons
C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA USA.
Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA.
Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA.
Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA.
Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
Livermore Software Technol Corp, Livermore, CA USA.
Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA.
EM mark.ratcliffe@va.gov
FU NIH [R01-HL-084431, R01-HL-077921, 86400]
FX We thank Edwards Lifesciences for providing samples of the annuloplasty
rings used in this work. This study was supported by NIH grants
R01-HL-084431 (M.B.R.) and R01-HL-077921 and 86400 (J.M.G.).
NR 39
TC 22
Z9 23
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD MAR
PY 2012
VL 93
IS 3
BP 776
EP 782
DI 10.1016/j.athoracsur.2011.08.080
PG 7
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 899RB
UT WOS:000300832700028
PM 22245588
ER
PT J
AU Lanuti, M
Sharma, A
Willers, H
Digumarthy, SR
Mathisen, DJ
Shepard, JAO
AF Lanuti, Michael
Sharma, Amita
Willers, Henning
Digumarthy, Subba R.
Mathisen, Douglas J.
Shepard, Jo-Anne O.
TI Radiofrequency Ablation for Stage I Non-Small Cell Lung Cancer:
Management of Locoregional Recurrence
SO ANNALS OF THORACIC SURGERY
LA English
DT Article; Proceedings Paper
CT 47th Annual Meeting of the Society-of-Thoracic-Surgeons
CY JAN 31-FEB 02, 2011
CL San Diego, CA
SP Soc Thorac Surg
ID BODY RADIATION-THERAPY; THERMAL ABLATION; RISK PATIENTS; TUMORS;
RADIOTHERAPY; OUTCOMES; SAFETY
AB Background. This study characterizes the management of locoregional recurrence (LRR) in patients with highrisk stage I non- small cell lung cancer (NSCLC) treated with lung radiofrequency ablation (RFA).
Methods. Consecutive patients with biopsy-proven stage I NSCLC underwent computed tomography-guided lung RFA from December 2003 to 2010. All patients were deemed medically inoperable or refused an operation. RFA was performed with curative intent.
Results. Fifty-five ablations were performed in 45 patients (age, 51 to 89 years) with stage I NSCLC. At a median follow-up of 32 months, LRR occurred in 21 (38%) within a mean of 12 +/- 10 (range, 1-44) months from RFA. Recurrence was observed locally in the tumor bed in 18 (33%), in regional nodes in 4 (7%), and distant in 2 (4%). The mean maximal tumor diameter was 2.3 +/- 1.3 (range, 0.7 to 4.5) cm. In tumors exceeding 3 cm, 10 (80%) were associated with LRR. Recurrent lesions were treated with repeat RFA (5), radiotherapy (8), chemoradiotherapy (5), and chemotherapy (2). Local control was achieved by repeat RFA in 2 of 5 (40%) or by radiotherapy in 8 lesions (100%), with 2 regional nodal failures (median follow-up, 40 +/- 13 months). Overall survival among patients who did or did not experience LRR was similar (32% to 35%). Repeat RFA was not associated with any significant complications or procedure-related 30-day mortality.
Conclusions. Lung RFA is associated with increased rates of local failure in tumors exceeding 3 cm and in contact with larger segmental vessels. Patients with local failure can be promptly salvaged with SBRT or repeat RFA, without detriment to overall survival. (Ann Thorac Surg 2012;93:921-8) (C) 2012 by The Society of Thoracic Surgeons
C1 [Lanuti, Michael] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Thorac Surg,Div Thorac Radiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Lanuti, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Thorac Surg,Div Thorac Radiol, 55 Fruit St,Blake 1570, Boston, MA 02114 USA.
EM mlanuti@partners.org
NR 22
TC 31
Z9 36
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD MAR
PY 2012
VL 93
IS 3
BP 921
EP 928
DI 10.1016/j.athoracsur.2011.11.043
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 899RB
UT WOS:000300832700059
PM 22296982
ER
PT J
AU Wivagg, CN
Hung, DT
AF Wivagg, Carl N.
Hung, Deborah T.
TI Resuscitation-Promoting Factors Are Required for beta-Lactam Tolerance
and the Permeability Barrier in Mycobacterium tuberculosis
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID ESCHERICHIA-COLI; HYDROLASES
AB Mycobacterial resuscitation-promoting factors (RPFs) have been of great interest since the discovery that they promote the growth of nonculturable Mycobacterium tuberculosis cells. Yet, their precise role in mycobacterial survival and infection has remained elusive. We performed a chemical screen to identify molecules that show preferential killing of a Mycobacterium tuberculosis mutant lacking RPFs over wild-type bacilli and found that the mutant has enhanced sensitivity to the beta-lactam class of antibiotics. By monitoring beta-lactam diffusion across the mycobacterial outer membrane, we found that the RPFs are required to maintain the outer membrane integrity, as their deletion results in an increase in outer membrane permeability.
C1 [Wivagg, Carl N.; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA.
[Hung, Deborah T.] Broad Inst, Infect Dis Initiat, Cambridge, MA USA.
[Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
RP Hung, DT (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA.
EM hung@molbio.mgh.harvard.edu
NR 9
TC 4
Z9 4
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD MAR
PY 2012
VL 56
IS 3
BP 1591
EP 1594
DI 10.1128/AAC.06027-11
PG 4
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 897DN
UT WOS:000300623300059
PM 22155826
ER
PT J
AU Ballen, KK
Koreth, J
Chen, YB
Dey, BR
Spitzer, TR
AF Ballen, Karen K.
Koreth, John
Chen, Yi-Bin
Dey, Bimalangshu R.
Spitzer, Thomas R.
TI Selection of optimal alternative graft source: mismatched unrelated
donor, umbilical cord blood, or haploidentical transplant
SO BLOOD
LA English
DT Review
ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION;
VERSUS-HOST-DISEASE; ACUTE-LEUKEMIA; HEMATOLOGIC MALIGNANCIES;
ALLOGENEIC TRANSPLANTATION; ANTITHYMOCYTE GLOBULIN; PERIPHERAL-BLOOD;
POSTTRANSPLANTATION CYCLOPHOSPHAMIDE; LYMPHOPROLIFERATIVE DISEASE
AB Only 30% of patients who require an allogeneic hematopoietic cell transplant will have an HLA-matched sibling donor. A search for an unrelated donor will be undertaken for patients without a matched family donor. However, many patients, particularly patients of diverse racial and ethnic backgrounds, may not be able to rapidly identify a suitably matched unrelated donor. Three alternative graft sources, umbilical cord blood (UCB), haploidentical (haplo)-related donor, and mis-matched unrelated donor (MMUD) are available. UCB is associated with decreased GVHD, but hematologic recovery and immune reconstitution are slow. Haplo-HCT is characterized by donor availability for transplantation and after transplantation adoptive cellular immunotherapy but may be complicated by a high risk of graft failure and relapse. A MMUD transplant may also be an option, but GVHD may be of greater concern. Phase 2 studies have documented advances in HLAtyping, GVHD prophylaxis, and infection prevention, which have improved survival. The same patient evaluated in different transplant centers may be offered MMUD, UCB, or haplo-HCT depending on center preference. In this review, we discuss the rationale for donor choice and the need of phase 3 studies to help answer this important question. (Blood. 2012; 119(9): 1972-1980)
C1 [Ballen, Karen K.; Chen, Yi-Bin; Dey, Bimalangshu R.; Spitzer, Thomas R.] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA.
[Koreth, John] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, 0 Emerson,Suite 118, Boston, MA 02114 USA.
EM kballen@partners.org
FU Advisory Board of Millennium
FX Conflict-of-interest disclosure: J.K. acquired research funding and is
on the Advisory Board of Millennium. The remaining authors declare no
competing financial interests.
NR 93
TC 70
Z9 75
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 MAR 1
PY 2012
VL 119
IS 9
BP 1972
EP 1980
DI 10.1182/blood-2011-11-354563
PG 9
WC Hematology
SC Hematology
GA 901GA
UT WOS:000300949500006
PM 22210876
ER
PT J
AU Tai, YT
Horton, HM
Kong, SY
Pong, E
Chen, H
Cemerski, S
Bernett, MJ
Nguyen, DHT
Karki, S
Chu, SY
Lazar, GA
Munshi, NC
Desjarlais, JR
Anderson, KC
Muchhal, US
AF Tai, Yu-Tzu
Horton, Holly M.
Kong, Sun-Young
Pong, Erik
Chen, Hsing
Cemerski, Saso
Bernett, Matthew J.
Nguyen, Duc-Hanh T.
Karki, Sher
Chu, Seung Y.
Lazar, Greg A.
Munshi, Nikhil C.
Desjarlais, John R.
Anderson, Kenneth C.
Muchhal, Umesh S.
TI Potent in vitro and in vivo activity of an Fc-engineered humanized
anti-HM1.24 antibody against multiple myeloma via augmented effector
function
SO BLOOD
LA English
DT Article
ID DEPENDENT CELLULAR CYTOTOXICITY; C-RECEPTOR POLYMORPHISMS; METASTATIC
BREAST-CANCER; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; XENOGRAFT
MODELS; LUNG-CANCER; TUMOR-CELLS; IMMUNOTHERAPY; ANTIGEN
AB HM1.24, an immunologic target for multiple myeloma (MM) cells, has not been effectively targeted with therapeutic monoclonal antibodies (mAbs). In this study, we investigated in vitro and in vivo anti-MM activities of XmAb5592, a humanized anti-HM1.24 mAb with Fc-domain engineered to significantly enhance Fc gamma R binding and associated immune effector functions. XmAb5592 increased antibody-dependent cellular cytotoxicity (ADCC) several fold relative to the anti-HM1.24 IgG1 analog against both MM cell lines and primary patient myeloma cells. XmAb5592 also augmented antibody dependent cellular phagocytosis (ADCP) by macrophages. Natural killer (NK) cells became more activated by XmAb5592 than the IgG1 analog, evidenced by increased cell surface expression of granzyme B-dependent CD107a and MM cell lysis, even in the presence of bone marrow stromal cells. XmAb5592 potently inhibited tumor growth in mice bearing human MM xenografts via Fc gamma R-dependent mechanisms, and was significantly more effective than the IgG1 analog. Lenalidomide synergistically enhanced in vitro ADCC against MM cells and in vivo tumor inhibition induced by XmAb5592. A single dose of 20 mg/kg XmAb5592 effectively depleted both blood and bone marrow plasma cells in cynomolgus monkeys. These results support clinical development of XmAb5592, both as a monotherapy and in combination with lenalidomide, to improve patient outcome of MM. (Blood. 2012; 119(9): 2074-2082)
C1 [Horton, Holly M.; Pong, Erik; Chen, Hsing; Cemerski, Saso; Bernett, Matthew J.; Nguyen, Duc-Hanh T.; Karki, Sher; Chu, Seung Y.; Lazar, Greg A.; Desjarlais, John R.; Muchhal, Umesh S.] Xencor Inc, Monrovia, CA 91016 USA.
[Tai, Yu-Tzu; Kong, Sun-Young; Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA.
[Tai, Yu-Tzu; Kong, Sun-Young; Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA.
[Kong, Sun-Young] Natl Canc Ctr, Res Inst & Hosp, Goyang, South Korea.
[Munshi, Nikhil C.] Boston Vet Adm Healthcare Syst, W Roxbury, MA USA.
RP Muchhal, US (reprint author), Xencor Inc, 111 W Lemon Ave, Monrovia, CA 91016 USA.
EM umuchhal@xencor.com
FU NCI NIH HHS [P01 CA078378, P01 CA155258, R01 CA050947, P50 CA100707]
NR 50
TC 28
Z9 28
U1 3
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 1
PY 2012
VL 119
IS 9
BP 2074
EP 2082
DI 10.1182/blood-2011-06-364521
PG 9
WC Hematology
SC Hematology
GA 901GA
UT WOS:000300949500017
PM 22246035
ER
PT J
AU LaCasce, AS
Vandergrift, JL
Rodriguez, MA
Abel, GA
Crosby, AL
Czuczman, MS
Nademanee, AP
Blayney, DW
Gordon, LI
Millenson, M
Vanderplas, A
Lepisto, EM
Zelenetz, AD
Niland, J
Friedberg, JW
AF LaCasce, Ann S.
Vandergrift, Jonathan L.
Rodriguez, Maria A.
Abel, Gregory A.
Crosby, Allison L.
Czuczman, Myron S.
Nademanee, Auayporn P.
Blayney, Douglas W.
Gordon, Leo I.
Millenson, Michael
Vanderplas, Ann
Lepisto, Eva M.
Zelenetz, Andrew D.
Niland, Joyce
Friedberg, Jonathan W.
TI Comparative outcome of initial therapy for younger patients with mantle
cell lymphoma: an analysis from the NCCN NHL Database
SO BLOOD
LA English
DT Article
ID PROGRESSION-FREE SURVIVAL; INTERNATIONAL PROGNOSTIC INDEX; PROSPECTIVE
RANDOMIZED-TRIAL; EUROPEAN MCL NETWORK; IMMUNOCHEMOTHERAPY;
TRANSPLANTATION; RITUXIMAB; MULTICENTER; SUPERIOR; MIPI
AB Few randomized trials have compared therapies in mantle cell lymphoma (MCL), and the role of aggressive induction is unclear. The National Comprehensive Cancer Network (NCCN) Non-Hodgkin Lymphoma (NHL) Database, a prospective cohort study collecting clinical, treatment, and outcome data at 7 NCCN centers, provides a unique opportunity to compare the effectiveness of initial therapies in MCL. Patients younger than 65 diagnosed between 2000 and 2008 were included if they received RHCVAD (rituximab fractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone), RCHOP+HDT/ASCR (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone + high-dose therapy/autologous stem cell rescue), RHCVAD+HDT/ASCR, or RCHOP. Clinical parameters were similar for patients treated with RHCVAD (n = 83, 50%), RCHOP+HDT/ASCR (n = 34, 20%), RCHOP (n = 29, 17%), or RHCVAD+HDT/ASCR (n = 21, 13%). Overall, 70 (42%) of the 167 patients progressed and 25 (15%) expired with a median follow-up of 33 months. There was no difference in progression-free survival (PFS) between aggressive regimens (P > .57), which all demonstrated superior PFS compared with RCHOP (P < .004). There was no difference in overall survival (OS) between the RHCVAD and RCHOP+HDT/ASCR (P = .98). RCHOP was inferior to RHCVAD and RCHOP+HDT/ASCR, which had similar PFS and OS. Despite aggressive regimens, the median PFS was 3 to 4 years. Future trials should focus on novel agents rather than comparing current approaches. (Blood. 2012; 119(9): 2093-2099)
C1 [LaCasce, Ann S.; Abel, Gregory A.; Crosby, Allison L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Vandergrift, Jonathan L.; Lepisto, Eva M.] Natl Comprehens Canc Network, Ft Washington, MD USA.
[Rodriguez, Maria A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Nademanee, Auayporn P.; Vanderplas, Ann; Niland, Joyce] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Blayney, Douglas W.] Stanford Canc Ctr, Stanford, CA USA.
[Gordon, Leo I.] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA.
[Millenson, Michael] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Friedberg, Jonathan W.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA.
RP LaCasce, AS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM ann_lacasce@dfci.harvard.edu
OI Zelenetz, Andrew/0000-0003-1403-6883; Gordon, Leo/0000-0003-1666-7064
NR 23
TC 45
Z9 47
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 1
PY 2012
VL 119
IS 9
BP 2093
EP 2099
DI 10.1182/blood-2011-07-369629
PG 7
WC Hematology
SC Hematology
GA 901GA
UT WOS:000300949500019
PM 22234679
ER
PT J
AU Tsao, S
Yao, M
Tsao, H
Henry, FP
Zhao, Y
Kochevar, JJ
Redmond, RW
Kochevar, IE
AF Tsao, S.
Yao, M.
Tsao, H.
Henry, F. P.
Zhao, Y.
Kochevar, J. J.
Redmond, R. W.
Kochevar, I. E.
TI Light-activated tissue bonding for excisional wound closure: a
split-lesion clinical trial
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Article
ID PROSPECTIVE RANDOMIZED-TRIAL; CELL CARCINOMA; PORCINE SKIN; INCISIONS;
GUIDELINES; ADHESIVE; CARE; SURGERY; REPAIR; SCARS
AB Background Apposition of wound edges by sutures provides a temporary scaffold and tension support for healing. We have developed a novel tissue-sealing technology, photoactivated tissue bonding (PTB), which immediately crosslinks proteins between tissue planes, thereby sealing on a molecular scale.
Objectives To determine the effectiveness of PTB for superficial closure of skin excisions and to compare the results with standard epidermal suturing.
Methods A split-lesion, paired comparison study of 31 skin excisions was performed. Following deep closure with absorbable sutures, one-half of each wound was superficially closed with nonabsorbable nylon sutures while the other half was stained with Rose Bengal dye and treated with green light. Overall appearance and scar characteristics were rated at 2 weeks and 6 months in a blinded manner by three dermatologists viewing photographs, by two onsite physicians and by patients.
Results At 2 weeks, neither sutured nor PTB-treated segments showed dehiscence; however, PTB-sealed segments showed less erythema than sutured segments as determined by photographic (P = 0.001) and onsite evaluations (P = 0.005). Overall appearance after PTB was judged better than after sutures (P = 0.002). At 6 months, scars produced by PTB were deemed superior to scars resulting from sutures in terms of appearance (P < 0.001), width (P = 0.002) and healing (P = 0.003). Patients were more satisfied with the appearance of the PTB-sealed wound half after 2 weeks and 6 months (P = 0.013 and P = 0.003, respectively).
Conclusions A novel molecular suturing technique produces effective wound sealing and less scarring than closure with nylon interrupted epidermal sutures. Comparisons with better suturing techniques are warranted.
C1 [Tsao, S.; Yao, M.; Tsao, H.; Redmond, R. W.; Kochevar, I. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Yao, M.; Tsao, H.; Henry, F. P.; Redmond, R. W.; Kochevar, I. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Zhao, Y.; Kochevar, J. J.] Kochevar Res Associates, Boston, MA USA.
RP Kochevar, IE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
EM kochevar@helix.mgh.harvard.edu
OI Henry, Francis P./0000-0003-4170-7806
FU Dermatology Foundation; U.S. Department of Defense [FA9550-04-1-0079]
FX This study was supported by grants from the Dermatology Foundation and
the U.S. Department of Defense Medical Free Electron Program
(FA9550-04-1-0079). The laser was initially on loan from IRIDEX
Corporation and was purchased during the study.
NR 25
TC 15
Z9 17
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-0963
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD MAR
PY 2012
VL 166
IS 3
BP 555
EP 563
DI 10.1111/j.1365-2133.2011.10710.x
PG 9
WC Dermatology
SC Dermatology
GA 897ZG
UT WOS:000300701900032
PM 22032650
ER
PT J
AU Shu, XO
Long, JR
Lu, W
Li, C
Chen, WY
Delahanty, R
Cheng, J
Cai, H
Zheng, Y
Shi, JJ
Gu, K
Wang, WJ
Kraft, P
Gao, YT
Cai, QY
Zheng, W
AF Shu, Xiao Ou
Long, Jirong
Lu, Wei
Li, Chun
Chen, Wendy Y.
Delahanty, Ryan
Cheng, Jiarong
Cai, Hui
Zheng, Ying
Shi, Jiajun
Gu, Kai
Wang, Wen-Jing
Kraft, Peter
Gao, Yu-Tang
Cai, Qiuyin
Zheng, Wei
TI Novel Genetic Markers of Breast Cancer Survival Identified by a
Genome-Wide Association Study
SO CANCER RESEARCH
LA English
DT Article
ID ESTROGEN-RECEPTOR; SUSCEPTIBILITY LOCI; MUTATION CARRIERS;
SYNUCLEIN-GAMMA; RISK; POLYMORPHISMS; CHEMOTHERAPY; EXPRESSION; PROTEIN;
POPULATION
AB Only two genome-wide association studies (GWAS) have been conducted to date to identify potential markers for total mortality after diagnosis of breast cancer. Here, we report the identification of two single-nucleotide polymorphisms (SNP) associated with total mortality from a two-stage GWAS conducted among 6,110 Shanghai-resident Chinese women with tumor-node-metastasis (TNM) stage I to IV breast cancer. The discovery stage included 1,950 patients and evaluated 613,031 common SNPs. The top 49 associations were evaluated in an independent replication stage of 4,160 Shanghai patients with breast cancer. A consistent and highly significant association with total mortality was documented for SNPs rs3784099 and rs9934948. SNP rs3784099, located in the RAD51L1 gene, was associated with total morality in both the discovery stage (P = 1.44 x 10(-8)) and replication stage (P = 0.06; P-combined 1.17 x 10(-7)). Adjusted HRs for total mortality were 1.41 [95% confidence interval (CI), 1.18-1.68] for the AG genotype and 2.64 (95% CI, 1.74-4.03) for the AA genotype, when compared with the GG genotype. The variant C allele of rs9934948, located on chromosome 16, was associated with a similarly elevated risk of total mortality (P-combined = 5.75 x 10(-6)). We also observed this association among 1,145 patients with breast cancer of European ancestry from the Nurses' Health Study (NHS; P = 0.006); the association was highly significant in a combined analysis of NHS and Chinese data (P = 1.39 x 10(-7)). Similar associations were observed for these two SNPs with breast cancer-specific mortality. This study provides strong evidence suggesting that the RAD51L1 gene and a chromosome 16 locus influence breast cancer prognosis. Cancer Res; 72(5); 1182-9. (C) 2012 AACR.
C1 [Shu, Xiao Ou; Long, Jirong; Delahanty, Ryan; Cai, Hui; Shi, Jiajun; Cai, Qiuyin; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Dept Med,Div Epidemiol, Nashville, TN 37203 USA.
[Shu, Xiao Ou; Long, Jirong; Delahanty, Ryan; Cai, Hui; Shi, Jiajun; Cai, Qiuyin; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA.
[Li, Chun] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37203 USA.
[Lu, Wei; Zheng, Ying; Gu, Kai; Wang, Wen-Jing] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China.
[Cheng, Jiarong; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Chen, Wendy Y.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Chen, Wendy Y.] Harvard Univ, Sch Med, Boston, MA USA.
[Chen, Wendy Y.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Shu, XO (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Dept Med,Div Epidemiol, 2525 W End Ave,Suite 600,IMPH, Nashville, TN 37203 USA.
EM xiao-ou.shu@vanderbilt.edu
RI Li, Chun/B-8388-2012
FU U.S. NIH/National Cancer Institute [R01CA118229, R01CA124558,
R01CA064277, R01CA090899]; U.S. Department of Defense (DOD) [BC011118,
BC050791]; Vanderbilt-Ingram Cancer Center [P30 CA68485]
FX This work was supported by the U.S. NIH/National Cancer Institute (grant
numbers: R01CA118229 to X.O. Shu and R01CA124558, R01CA064277, and
R01CA090899 to W. Zheng), as well as the U.S. Department of Defense
(DOD) Breast Cancer Research Program (Idea Awards BC011118 to X.O. Shu
and BC050791 to Q. Cai). Sample preparation and discovery stage
genotyping were conducted at the Survey and Biospecimen and Microarray
Shared Resources, which are supported, in part, by the Vanderbilt-Ingram
Cancer Center (P30 CA68485).
NR 39
TC 33
Z9 34
U1 0
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 1
PY 2012
VL 72
IS 5
BP 1182
EP 1189
DI 10.1158/0008-5472.CAN-11-2561
PG 8
WC Oncology
SC Oncology
GA 901TG
UT WOS:000300989100017
PM 22232737
ER
PT J
AU Hirata, H
Hinoda, Y
Ueno, K
Nakajima, K
Ishii, N
Dahiya, R
AF Hirata, Hiroshi
Hinoda, Yuji
Ueno, Koji
Nakajima, Koichi
Ishii, Nobuhisa
Dahiya, Rajvir
TI MicroRNA-1826 directly targets beta-catenin (CTNNB1) and MEK1 (MAP2K1)
in VHL-inactivated renal cancer
SO CARCINOGENESIS
LA English
DT Article
ID CELL CARCINOMA; KIDNEY CANCER; IN-VIVO; THERAPY; EXPRESSION;
THERAPEUTICS; INHIBITOR; PATHWAY; GROWTH
AB The aim of this project is to identify new therapeutic microRNAs (miRNAs) for von Hippel-Lindau (VHL)-inactivated renal cancer cells. We initially identified several potential miRNAs targeting CTNNB1 and MEK1 using several targets scan algorithms. Only miR-1826 was found to target CTNNB1 and MEK1. Therefore, we focused on miRNA-1826 and performed 3' untranslated region (UTR) luciferase assay, functional analyses and association study between miR-1826 expression and renal cancer patient outcomes. miR-1826 expression was significantly lower in renal cancer tissues compared with non-neoplastic areas and lower expression was significantly associated with overall shorter survival and earlier recurrence after radical nephrectomy. Following miR-1826 transfection, 3' UTR luciferase activity and protein expression of beta-catenin and MEK1 were significantly downregulated in renal cancer cells. Introduction of miR-1826 also inhibited renal cancer cell proliferation, invasion and migration. Additionally, miR-1826 promoted apoptosis and G(1) arrest in VHL-inactivated renal cancer cells. Knockdowns of CTNNB1 and MEK1 by small interfering RNAs reproduced the tumor-suppressive effect of miR-1826. Our data suggest that the miR-1826 plays an important role as a tumor suppressor by downregulating beta-catenin and MEK1 in VHL-inactivated renal cancers.
C1 [Hirata, Hiroshi; Ueno, Koji; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA 94121 USA.
[Hirata, Hiroshi; Ueno, Koji; Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94121 USA.
[Hinoda, Yuji] Yamaguchi Univ, Grad Sch Med, Dept Oncol & Lab Med, Yamaguchi 7558505, Japan.
[Nakajima, Koichi; Ishii, Nobuhisa] Toho Univ, Dept Urol, Fac Med, Tokyo 1438540, Japan.
RP Dahiya, R (reprint author), Vet Affairs Med Ctr, Dept Urol, Urol Res Ctr 112F, 4150 Clement St, San Francisco, CA 94121 USA.
EM rdahiya@urology.ucsf.edu
FU National Institutes of Health [RO1CA130860, RO1CA160079, RO1CA138642,
T32-DK07790, 1I01BX001123]; VA Research Enhancement Award Program
(REAP); Merit Review grants; Yamada Science Foundation
FX This study was supported by grants (RO1CA130860, RO1CA160079,
RO1CA138642, T32-DK07790, 1I01BX001123) from the National Institutes of
Health, VA Research Enhancement Award Program (REAP), Merit Review
grants and Yamada Science Foundation.
NR 29
TC 29
Z9 33
U1 2
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD MAR
PY 2012
VL 33
IS 3
BP 501
EP 508
DI 10.1093/carcin/bgr302
PG 8
WC Oncology
SC Oncology
GA 901SW
UT WOS:000300988100004
PM 22180573
ER
PT J
AU Becker, JR
Robinson, TY
Sachidanandan, C
Kelly, AE
Coy, S
Peterson, RT
MacRae, CA
AF Becker, Jason R.
Robinson, Tamara Y.
Sachidanandan, Chetana
Kelly, Amy E.
Coy, Shannon
Peterson, Randall T.
MacRae, Calum A.
TI In vivo natriuretic peptide reporter assay identifies chemical modifiers
of hypertrophic cardiomyopathy signalling
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Natriuretic peptides; Hypertrophy; Heart development; Heart failure;
Hypertrophic cardiomyopathy
ID CHRONIC HEART-FAILURE; MUSCLE-CELL-LINE; EXPRESSION; ZEBRAFISH;
PATHWAYS; GENE; ANF
AB Despite increased understanding of the fundamental biology regulating cardiomyocyte hypertrophy and heart failure, it has been challenging to find novel chemical or genetic modifiers of these pathways. Traditional cell-based methods do not model the complexity of an intact cardiovascular system and mammalian models are not readily adaptable to chemical or genetic screens. Our objective was to create an in vivo model suitable for chemical and genetic screens for hypertrophy and heart failure modifiers
Using the developing zebrafish, we established that the cardiac natriuretic peptide genes (nppa and nppb), known markers of cardiomyocyte hypertrophy and heart failure, were induced in the embryonic heart by pathological cardiac stimuli. This pathological induction was distinct from the developmental regulation of these genes. We created a luciferase-based transgenic reporter line that accurately modelled the pathological induction patterns of the zebrafish nppb gene. Utilizing this reporter line, we were able to show remarkable conservation of pharmacological responses between the larval zebrafish heart and adult mammalian models.
By performing a focused screen of chemical agents, we were able to show a distinct response of a genetic model of hypertrophic cardiomyopathy to the histone deacetylase inhibitor, Trichostatin A, and the mitogen-activated protein kinase kinase 1/2 inhibitor, U0126. We believe this in vivo reporter line will offer a unique approach to the identification of novel chemical or genetic regulators of myocardial hypertrophy and heart failure.
C1 [Becker, Jason R.; Robinson, Tamara Y.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN 37232 USA.
[Sachidanandan, Chetana; Peterson, Randall T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
[Kelly, Amy E.; Coy, Shannon; MacRae, Calum A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA.
RP Becker, JR (reprint author), Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, 2220 Pierce Ave,340 PRB, Nashville, TN 37232 USA.
EM jason.becker@vanderbilt.edu
FU NIH [T32HL007208]; Massachusetts General Hospital Hypertrophic
Cardiomyopathy Center; British Heart Foundation
FX This work was supported by NIH T32HL007208 and Vanderbilt Physician
Scientist Development Program award to J.R.B. Massachusetts General
Hospital Hypertrophic Cardiomyopathy Center and British Heart Foundation
grants to C.A.M.
NR 22
TC 15
Z9 16
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAR 1
PY 2012
VL 93
IS 3
BP 463
EP 470
DI 10.1093/cvr/cvr350
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 899BZ
UT WOS:000300789300013
PM 22198505
ER
PT J
AU Verma, A
Matsunaga, J
Artiushin, S
Pinne, M
Houwers, DJ
Haake, DA
Stevenson, B
Timoney, JF
AF Verma, Ashutosh
Matsunaga, James
Artiushin, Sergey
Pinne, Marija
Houwers, Dirk J.
Haake, David A.
Stevenson, Brian
Timoney, John F.
TI Antibodies to a Novel Leptospiral Protein, LruC, in the Eye Fluids and
Sera of Horses with Leptospira-Associated Uveitis
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID EQUINE RECURRENT UVEITIS; SURFACE-EXPOSED LIPOPROTEIN; OUTER-MEMBRANE;
SIGNAL PEPTIDES; INTERROGANS; PATHOGENESIS; PREDICTION; IDENTIFICATION;
INFECTION; FAMILY
AB Screening of an expression library of Leptospira interrogans with eye fluids from uveitic horses resulted in identification of a novel protein, LruC. LruC is located in the inner leaflet of the leptospiral outer membrane, and an lruC gene was detected in all tested pathogenic L. interrogans strains. LruC-specific antibody levels were significantly higher in eye fluids and sera of uveitic horses than healthy horses. These findings suggest that LruC may play a role in equine leptospiral uveitis.
C1 [Verma, Ashutosh; Artiushin, Sergey; Timoney, John F.] Univ Kentucky, Dept Vet Sci, MH Gluck Equine Res Ctr, Lexington, KY 40546 USA.
[Matsunaga, James; Pinne, Marija] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA.
[Matsunaga, James; Pinne, Marija; Haake, David A.] UCLA Sch Med, Dept Med, Los Angeles, CA USA.
[Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA.
[Verma, Ashutosh; Stevenson, Brian] Univ Kentucky, Coll Med, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40506 USA.
[Houwers, Dirk J.] Univ Utrecht, Fac Vet Med, Dept Infect Dis & Immunol, Vet Microbiol Diagnost Ctr, Utrecht, Netherlands.
RP Verma, A (reprint author), Univ Kentucky, Coll Med, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40506 USA.
FU Keeneland Endowment; Paul Mellon Fellowship; Public Health Service from
National Institute of Allergy and Infectious Diseases [AI-34431]; VA
FX This work was supported by the Keeneland Endowment. A. Verma was funded
by a Paul Mellon Fellowship in Equine Studies. The support of Public
Health Service grant AI-34431 (to D. A. H.) from the National Institute
of Allergy and Infectious Diseases and VA Medical Research Funds (to D.
A. H. and J. M.) is also acknowledged.
NR 39
TC 9
Z9 9
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD MAR
PY 2012
VL 19
IS 3
BP 452
EP 456
DI 10.1128/CVI.05524-11
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 899UF
UT WOS:000300841200026
PM 22237897
ER
PT J
AU Nardi, V
Song, Y
Santamaria-Barria, JA
Cosper, AK
Lam, Q
Faber, AC
Boland, GM
Yeap, BY
Bergethon, K
Scialabba, VL
Tsao, H
Settleman, J
Ryan, DP
Borger, DR
Bhan, AK
Hoang, MP
Iafrate, AJ
Cusack, JC
Engelman, JA
Dias-Santagata, D
AF Nardi, Valentina
Song, Youngchul
Santamaria-Barria, Juan A.
Cosper, Arjola K.
Lam, Quynh
Faber, Anthony C.
Boland, Genevieve M.
Yeap, Beow Y.
Bergethon, Kristin
Scialabba, Vanessa L.
Tsao, Hensin
Settleman, Jeffrey
Ryan, David P.
Borger, Darrell R.
Bhan, Atul K.
Hoang, Mai P.
Iafrate, Anthony J.
Cusack, James C.
Engelman, Jeffrey A.
Dias-Santagata, Dora
TI Activation of PI3K Signaling in Merkel Cell Carcinoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; LARGE T-ANTIGEN;
POLYOMAVIRUS INFECTION; RAPAMYCIN INHIBITOR; ANTITUMOR-ACTIVITY; CANCER;
SKIN; MUTATIONS; NVP-BEZ235; TUMORS
AB Purpose: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor, often metastatic at presentation, for which current chemotherapeutic regimens are largely ineffective. As its pathogenesis is still unknown, we hypothesized that deregulation of signaling pathways commonly activated in cancer may contribute to MCC tumorigenesis and may provide insights into targeted therapy approaches for this malignancy.
Experimental Design: We retrospectively profiled 60 primary MCC samples using a SNaPshot-based tumor genotyping assay to screen for common mutations in 13 cancer genes.
Results: We identified mutations in 9 (15%) MCC primary tumors, including mutations in TP53 (3 of 60) and activating mutations in the PIK3CA gene (6 of 60). Sanger sequencing of the primary MCC tumors detected one additional PIK3CA mutation (R19K) that had not been previously described in cancer. Merkel cell polyoma virus (MCPyV) was detected in 38 (66%) MCC cases and patients with MCPyV-positive cancers showed a trend toward better survival. With one exception, the presence of MCPyV and activating mutations in PIK3CA appeared mutually exclusive. We observed that signaling through the PI3K/pAKT pathway was active in one MCPyV-positive and in all MCPyV-negative MCC cell lines, as evidenced by AKT phosphorylation. Importantly, the presence of a PIK3CA-activating mutation was associated with sensitivity to treatment with ZST474, a specific phosphoinositide 3-kinase (PI3K) inhibitor, and to NVP-BEZ235, a dual PI3K/mTOR inhibitor, targeted agents under active clinical development.
Conclusions: PI3K pathway activation may drive tumorigenesis in a subset of MCC and screening these tumors for PIK3CA mutations could help identify patients who may respond to treatment with PI3K pathway inhibitors. Clin Cancer Res; 18(5); 1227-36. (C)2012 AACR.
C1 [Nardi, Valentina; Lam, Quynh; Bergethon, Kristin; Scialabba, Vanessa L.; Bhan, Atul K.; Hoang, Mai P.; Iafrate, Anthony J.; Dias-Santagata, Dora] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Santamaria-Barria, Juan A.; Boland, Genevieve M.; Cusack, James C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Song, Youngchul; Cosper, Arjola K.; Faber, Anthony C.; Yeap, Beow Y.; Settleman, Jeffrey; Ryan, David P.; Borger, Darrell R.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Yeap, Beow Y.; Tsao, Hensin; Settleman, Jeffrey; Ryan, David P.; Borger, Darrell R.; Bhan, Atul K.; Hoang, Mai P.; Iafrate, Anthony J.; Cusack, James C.; Engelman, Jeffrey A.; Dias-Santagata, Dora] Harvard Univ, Sch Med, Boston, MA USA.
RP Dias-Santagata, D (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,GRJ-1028A, Boston, MA 02114 USA.
EM ddiassantagata@partners.org
FU [P30 CA06516]
FX This study was supported by grant no. P30 CA06516 (B.Y. Yeap). The costs
of publication of this article were defrayed in part by the payment of
page charges. This article must therefore be hereby marked advertisement
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
NR 56
TC 32
Z9 32
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 1
PY 2012
VL 18
IS 5
BP 1227
EP 1236
DI 10.1158/1078-0432.CCR-11-2308
PG 10
WC Oncology
SC Oncology
GA 902LW
UT WOS:000301040700007
PM 22261808
ER
PT J
AU Riester, M
Taylor, JM
Feifer, A
Koppie, T
Rosenberg, JE
Downey, RJ
Bochner, BH
Michor, F
AF Riester, Markus
Taylor, Jennifer M.
Feifer, Andrew
Koppie, Theresa
Rosenberg, Jonathan E.
Downey, Robert J.
Bochner, Bernard H.
Michor, Franziska
TI Combination of a Novel Gene Expression Signature with a Clinical
Nomogram Improves the Prediction of Survival in High-Risk Bladder Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID RADICAL CYSTECTOMY; CARCINOMA; ASSOCIATION; PERFORMANCE; MICROARRAYS;
CLASSIFIER; GENERATION; THERAPY; STAGE
AB Purpose: We aimed to validate and improve prognostic signatures for high-risk urothelial carcinoma of the bladder.
Experimental Design: We evaluated microarray data from 93 patients with bladder cancer managed by radical cystectomy to determine gene expression patterns associated with clinical and prognostic variables. We compared our results with published bladder cancer microarray data sets comprising 578 additional patients and with 49 published gene signatures from multiple cancer types. Hierarchical clustering was utilized to identify subtypes associated with differences in survival. We then investigated whether the addition of survival-associated gene expression information to a validated postcystectomy nomogram utilizing clinical and pathologic variables improves prediction of recurrence.
Results: Multiple markers for muscle invasive disease with highly significant expression differences in multiple data sets were identified, such as fibronectin 1 (FN1), NNMT, POSTN, and SMAD6. We identified signatures associated with pathologic stage and the likelihood of developing metastasis and death from bladder cancer, as well as with two distinct clustering subtypes of bladder cancer. Our novel signature correlated with overall survival in multiple independent data sets, significantly improving the prediction concordance of standard staging in all data sets [mean Delta C-statistic: 0.14; 95% confidence interval (CI), 0.01-0.27; P < 0.001]. Tested in our patient cohort, it significantly enhanced the performance of a postoperative survival nomogram (Delta C-statistic: 0.08, 95% CI, -0.04-0.20; P < 0.005).
Conclusions: Prognostic information obtained from gene expression data can aid in posttreatment prediction of bladder cancer recurrence. Our findings require further validation in external cohorts and prospectively in a clinical trial setting. Clin Cancer Res; 18(5); 1323-33. (C)2012 AACR.
C1 [Riester, Markus; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Riester, Markus; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Rosenberg, Jonathan E.] Dana Farber Canc Inst, Bladder Canc Ctr, Boston, MA 02215 USA.
[Taylor, Jennifer M.; Feifer, Andrew; Bochner, Bernard H.] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA.
[Downey, Robert J.] Mem Sloan Kettering Canc Ctr, Dept Surg, Thorac Serv, New York, NY 10021 USA.
[Koppie, Theresa] Univ Calif Davis, Dept Urol, Sacramento, CA 95817 USA.
RP Michor, F (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA.
EM michor@jimmy.harvard.edu
OI Rosenberg, Jonathan/0000-0003-2637-4249; Riester,
Markus/0000-0002-4759-8332
FU NCI initiative [U54CA143798]; NIH [T32 CA82088]
FX This work was supported from the NCI initiative to found Physical
Science Oncology Centers (U54CA143798; M. Riester, F. Michor) and an
NRSA training grant T32 CA82088 from the NIH (J.M. Taylor).
NR 39
TC 52
Z9 53
U1 0
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 1
PY 2012
VL 18
IS 5
BP 1323
EP 1333
DI 10.1158/1078-0432.CCR-11-2271
PG 11
WC Oncology
SC Oncology
GA 902LW
UT WOS:000301040700016
PM 22228636
ER
PT J
AU Azim, HA
Michiels, S
Bedard, PL
Singhal, SK
Criscitiello, C
Ignatiadis, M
Haibe-Kains, B
Piccart, MJ
Sotiriou, C
Loi, S
AF Azim, Hatem A., Jr.
Michiels, Stefan
Bedard, Philippe L.
Singhal, Sandeep K.
Criscitiello, Carmen
Ignatiadis, Michail
Haibe-Kains, Benjamin
Piccart, Martine J.
Sotiriou, Christos
Loi, Sherene
TI Elucidating Prognosis and Biology of Breast Cancer Arising in Young
Women Using Gene Expression Profiling
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MOLECULAR PORTRAITS; SIGNATURE; SUBTYPES; SURVIVAL; STROMA; POPULATION;
AGE; CLASSIFICATION; METASTASIS; PREDICTOR
AB Purpose: Breast cancer in young women is associated with poor prognosis. We aimed to define the role of gene expression signatures in predicting prognosis in young women and to understand biological differences according to age.
Experimental Design: Patients were assigned to molecular subtypes [estrogen receptor (ER)(+)/HER2(-); HER2(+), ER-/HER2(-))] using a three-gene classifier. We evaluated whether previously published proliferation, stroma, and immune-related gene signatures added prognostic information to Adjuvant! online and tested their interaction with age in a Cox model for relapse-free survival (RFS). Furthermore, we evaluated the association between candidate age-related genes or gene sets with age in an adjusted linear regression model.
Results: A total of 3,522 patients (20 data sets) were eligible. Patients aged 40 years or less had a higher proportion of ER-/HER2(-) tumors (P < 0.0001) and were associated with poorer RFS after adjustment for breast cancer subtype, tumor size, nodal status, and histologic grade and stratification for data set and treatment modality (HR = 1.34, 95% CI 1.10-1.63, P = 0.004). The proliferation gene signatures showed no significant interaction with age in ER+/HER2(-) tumors after adjustment for Adjuvant! online. Further analyses suggested that breast cancer in the young is enriched with processes related to immature mammary epithelial cells (luminal progenitors, mammary stem, c-kit, RANKL) and growth factor signaling in two independent cohorts (n = 1,188 and 2,334).
Conclusions: Proliferation-related prognostic gene signatures can aid treatment decision-making for young women. However, breast cancer arising at a young age seems to be biologically distinct beyond subtype distribution. Separate therapeutic approaches such as targeting RANKL or mammary stem cells could therefore be needed. Clin Cancer Res; 18(5); 1341-51. (C)2012 AACR.
C1 [Azim, Hatem A., Jr.; Michiels, Stefan; Singhal, Sandeep K.; Criscitiello, Carmen; Ignatiadis, Michail; Sotiriou, Christos; Loi, Sherene] Univ Libre Brussels, Breast Canc Translat Res Lab BCTL JC Heuson, Inst Jules Bordet, B-1000 Brussels, Belgium.
[Piccart, Martine J.] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium.
[Bedard, Philippe L.] Univ Toronto, Princess Margaret Hosp, Div Med Oncol & Hematol, Toronto, ON, Canada.
[Haibe-Kains, Benjamin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Computat Biol & Funct Genom Lab, Boston, MA 02115 USA.
RP Loi, S (reprint author), Univ Libre Brussels, Breast Canc Translat Res Lab BCTL JC Heuson, Inst Jules Bordet, Blvd Waterloo 125, B-1000 Brussels, Belgium.
EM sherene.loi@bordet.be
RI Haibe-Kains, Benjamin/D-3702-2011; Michiels, Stefan/L-1516-2013; Loi,
Sherene/H-1979-2016;
OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Michiels,
Stefan/0000-0002-6963-2968; Loi, Sherene/0000-0001-6137-9171
FU ESMO
FX H.A. Azim Jr is supported by an ESMO translational research grant.
NR 49
TC 87
Z9 88
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 1
PY 2012
VL 18
IS 5
BP 1341
EP 1351
DI 10.1158/1078-0432.CCR-11-2599
PG 11
WC Oncology
SC Oncology
GA 902LW
UT WOS:000301040700018
PM 22261811
ER
PT J
AU Rosenberg, JE
Chen, MH
Nguyen, PL
Braccioforte, MH
Moran, BJ
D'Amico, AV
AF Rosenberg, Jonathan E.
Chen, Ming-Hui
Nguyen, Paul L.
Braccioforte, Michelle H.
Moran, Brian J.
D'Amico, Anthony V.
TI Hormonal Therapy or External-Beam Radiation With Brachytherapy and the
Risk of Death From Prostate Cancer in Men With Intermediate Risk
Prostate Cancer
SO CLINICAL GENITOURINARY CANCER
LA English
DT Article
DE Androgen deprivation therapy; Brachytherapy; External-beam radiotherapy;
Hormonal therapy; Prostate cancer
ID RANDOMIZED CONTROLLED-TRIAL; ANDROGEN SUPPRESSION; DOSE-ESCALATION;
ADENOCARCINOMA; RADIOTHERAPY
AB Supplemental androgen suppression therapy may lower the risk of prostate-cancer-specific mortality in men with intermediate-risk prostate cancer who are undergoing brachytherapy. Prospective validation in a randomized controlled trial is needed.
Purpose: To determine whether external-beam radiotherapy (EBRT) improves disease control compared with supplemental androgen suppression therapy (AST) in men with intermediate-risk prostate cancer who are being treated with brachytherapy. Patients and Methods: A total of 807 men with intermediate-risk prostate cancer (T2bNXM0, Gleason <= 7, prostate-specific antigen [PSA] <20 ng/mL; or cT1c-T2bNXM0, Gleason 7) were consecutively treated with either AST and brachytherapy or EBRT and brachytherapy, between 1997 and 2007, and were followed up until September 21, 2007. A Fine and Gray competing risks multivariable regression model was used to assess whether AST or radiotherapy dose escalation reduced the risk of prostate-cancer specific mortality (PCSM) when adjusting for age, PSA, Gleason score, and tumor category. Results: Treatment with brachytherapy and with EBRT was associated with a significant increase in the risk of PCSM compared with brachytherapy and AST (adjusted hazard ratio [HR] 4.027 [95% CI, 1.168-13.89]; P = .027) after adjusting for age and prostate cancer prognostic factors. A Gleason score of 4+3 and increasing PSA were associated with worse PCSM (adjusted HR 8.882 [95% CI, 1.095-72.04]; P = .041; and adjusted HR 8.029 [95% CI, 2.38-28.8]; P = .0014, respectively). Conclusion: Supplemental AST use compared with EBRT is associated with a lower risk of PCSM in men with intermediate-risk PC undergoing brachytherapy. Prospective validation in a randomized controlled trial is needed. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Rosenberg, Jonathan E.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA.
[Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA.
[Nguyen, Paul L.; D'Amico, Anthony V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Braccioforte, Michelle H.; Moran, Brian J.] Prostate Canc Fdn Chicago, Westmont, IL USA.
RP Rosenberg, JE (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney Sr,D1230, Boston, MA 02115 USA.
EM jonathan_rosenberg@dfci.harvard.edu
NR 14
TC 1
Z9 1
U1 0
U2 0
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1558-7673
J9 CLIN GENITOURIN CANC
JI Clin. Genitourin. Cancer
PD MAR
PY 2012
VL 10
IS 1
BP 21
EP 25
DI 10.1016/j.clgc.2011.10.003
PG 5
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 902KG
UT WOS:000301036400004
PM 22130293
ER
PT J
AU McGlone, SM
Bailey, RR
Zimmer, SM
Popovich, MJ
Tian, Y
Ufberg, P
Muder, RR
Lee, BY
AF McGlone, S. M.
Bailey, R. R.
Zimmer, S. M.
Popovich, M. J.
Tian, Y.
Ufberg, P.
Muder, R. R.
Lee, B. Y.
TI The economic burden of Clostridium difficile
SO CLINICAL MICROBIOLOGY AND INFECTION
LA English
DT Article
DE Burden; Clostridium difficile; cost; economics; stochastic model
ID INTENSIVE-CARE-UNIT; HYPERVIRULENT STRAIN; COST-EFFECTIVENESS;
RISK-FACTORS; DISEASE; INFECTION; COLECTOMY; DIARRHEA; COLITIS;
MORTALITY
AB lthough Clostridium difficile (C. difficile) is the leading cause of infectious diarrhoea in hospitalized patients, the economic burden of this major nosocomial pathogen for hospitals, third-party payers and society remains unclear. We developed an economic computer simulation model to determine the costs attributable to healthcare-acquired C. difficile infection (CDI) from the hospital, third-party payer and societal perspectives. Sensitivity analyses explored the effects of varying the cost of hospitalization, C. difficile-attributable length of stay, and the probability of initial and secondary recurrences. The median cost of a case ranged from $9179 to $11 456 from the hospital perspective, $8932 to $11 679 from the third-party payor perspective, and $13 310 to $16 464 from the societal perspective. Most of the costs incurred were accrued during a patients primary CDI episode. Hospitals with an incidence of 4.1 CDI cases per 100 000 discharges would incur costs =$3.2 million (hospital perspective); an incidence of 10.5 would lead to costs =$30.6 million. Our model suggests that the annual US economic burden of CDI would be =$496 million (hospital perspective), =$547 million (third-party payer perspective) and =$796 million (societal perspective). Our results show that C. difficile infection is indeed costly, not only to third-party payers and the hospital, but to society as well. These results are consistent with current literature citing C. difficile as a costly disease.
C1 [McGlone, S. M.; Bailey, R. R.; Popovich, M. J.; Tian, Y.; Ufberg, P.; Lee, B. Y.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15213 USA.
[McGlone, S. M.; Bailey, R. R.; Popovich, M. J.; Tian, Y.; Ufberg, P.; Lee, B. Y.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Zimmer, S. M.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA.
[Muder, R. R.] VA Pittsburgh Hlth Syst, Div Infect Dis, Pittsburgh, PA USA.
RP McGlone, SM (reprint author), Univ Pittsburgh, Sch Med, Dept Biomed Informat, 3520 Forbes Ave,1st Floor, Pittsburgh, PA 15213 USA.
EM smm168@pitt.edu
OI Slayton, Rachel/0000-0003-4699-8040
FU National Institute General Medical Sciences Models of Infectious Disease
Agent Study (MIDAS) [5U54GM088491-02]; Pennsylvania Department of Health
(DOH)
FX This study was supported by the National Institute General Medical
Sciences Models of Infectious Disease Agent Study (MIDAS) (grant number
5U54GM088491-02) and the Pennsylvania Department of Health (DOH). The
funders had no role in the design and conduct of the study, collection,
management, analysis and interpretation of the data, and preparation,
review or approval of the manuscript.
NR 45
TC 87
Z9 91
U1 2
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1198-743X
J9 CLIN MICROBIOL INFEC
JI Clin. Microbiol. Infect.
PD MAR
PY 2012
VL 18
IS 3
BP 282
EP 289
DI 10.1111/j.1469-0691.2011.03571.x
PG 8
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 899SX
UT WOS:000300837600019
PM 21668576
ER
PT J
AU David, CM
AF David, Charlene M.
TI Clinical Nurse Specialist Practice in Fall Prevention: Comparing,
Sharing, and Improving
SO CLINICAL NURSE SPECIALIST
LA English
DT Meeting Abstract
C1 [David, Charlene M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 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 0887-6274
J9 CLIN NURSE SPEC
JI Clin. Nurse Spec.
PD MAR-APR
PY 2012
VL 26
IS 2
BP E12
EP E12
PG 1
WC Nursing
SC Nursing
GA 897FS
UT WOS:000300632600033
ER
PT J
AU Valdez, C
Richardson, J
Holmquist, J
Tjoelker, R
AF Valdez, Christine
Richardson, Jenny
Holmquist, Jennifer
Tjoelker, Rita
TI Back to the Future: Building a Clinical Nurse Specialist Residency
Program
SO CLINICAL NURSE SPECIALIST
LA English
DT Meeting Abstract
C1 [Valdez, Christine; Richardson, Jenny; Holmquist, Jennifer; Tjoelker, Rita] Portland VA Med Ctr, Portland, OR USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0887-6274
J9 CLIN NURSE SPEC
JI Clin. Nurse Spec.
PD MAR-APR
PY 2012
VL 26
IS 2
BP E6
EP E6
PG 1
WC Nursing
SC Nursing
GA 897FS
UT WOS:000300632600015
ER
PT J
AU Polyak, K
AF Polyak, Kornelia
TI On Chromatin Remodeling in Mammary Gland Differentiation and Breast
Tumorigenesis
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Editorial Material
ID MAPS; PLURIPOTENT; CELLS
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
RP Polyak, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM kornelia_polyak@dfci.harvard.edu
NR 11
TC 1
Z9 1
U1 0
U2 0
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD MAR
PY 2012
VL 4
IS 3
AR a013417
DI 10.1101/cshperspect.a013417
PG 2
WC Cell Biology
SC Cell Biology
GA 901EJ
UT WOS:000300944200013
ER
PT J
AU Bromley, E
AF Bromley, Elizabeth
TI The Texture of the Real: Experimentation and Experience in Schizophrenia
SO CULTURE MEDICINE AND PSYCHIATRY
LA English
DT Article
DE Cognition; Reductionism; Stigma; Schizophrenia; Neuroscience
ID MENTAL-ILLNESS; SOCIOLOGY; COGNITION; MATRICS; PSYCHOLOGY; SCIENCE;
BRAIN; SELF; NEUROCOGNITION; CONSTRUCTION
AB The dominance of the neurosciences in psychiatric research raises questions about the relationship between research practices and the lived experience of mental illness. Here, I use data from a group of researchers focusing on neurocognition in schizophrenia to explore the problem of representation in psychiatric research and the forms that neuroscientific evidence assumes for those who produce it. These researchers grappled with the complexity of schizophrenia not by narrowing disease concepts to biological facts but by referencing measurement techniques to generate new versions of schizophrenia. By linking experimental findings to inchoate concepts of personhood and social experience, I found that they reframed and reinforced cultural values, including that those with schizophrenia are destined to a debased and deficient existence. I argue that cognition has emerged as an essential feature of schizophrenia not only because of its representational utility but also because of the ontological work the concept performs. In closing, I present some implications for the neurobiological and social sciences.
C1 [Bromley, Elizabeth] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Ctr Hlth Serv & Soc, Los Angeles, CA 90024 USA.
[Bromley, Elizabeth] Desert Pacific Mental Illness Res Educ & Clin Ctr, W Los Angeles VA Healthcare Ctr, Los Angeles, CA USA.
RP Bromley, E (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Ctr Hlth Serv & Soc, Los Angeles, CA 90024 USA.
EM ebromley@mednet.ucla.edu
NR 93
TC 1
Z9 1
U1 6
U2 12
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0165-005X
J9 CULT MED PSYCHIAT
JI Cult. Med. Psychiatr.
PD MAR
PY 2012
VL 36
IS 1
BP 154
EP 174
DI 10.1007/s11013-011-9241-z
PG 21
WC Anthropology; Psychiatry; Social Sciences, Biomedical
SC Anthropology; Psychiatry; Biomedical Social Sciences
GA 899WQ
UT WOS:000300847700011
PM 22183201
ER
PT J
AU Galanopoulou, AS
Buckmaster, PS
Staley, KJ
Moshe, SL
Perucca, E
Engel, J
Loscher, W
Noebels, JL
Pitkanen, A
Stables, J
White, HS
O'Brien, TJ
Simonato, M
AF Galanopoulou, Aristea S.
Buckmaster, Paul S.
Staley, Kevin J.
Moshe, Solomon L.
Perucca, Emilio
Engel, Jerome, Jr.
Loescher, Wolfgang
Noebels, Jeffrey L.
Pitkanen, Asla
Stables, James
White, H. Steve
O'Brien, Terence J.
Simonato, Michele
CA Amer Epilepsy Soc Basic Sci Comm
Int League Epilepsy Working Grp
TI Identification of new epilepsy treatments: Issues in preclinical
methodology
SO EPILEPSIA
LA English
DT Article
DE Antiseizure drug; Antiepileptogenesis; Disease modification;
Comorbidities; Biomarkers
ID TEMPORAL-LOBE EPILEPSY; INFANTILE SPASMS; ANTIEPILEPTIC DRUGS;
PERSISTENT SEIZURES; FUTURE-DIRECTIONS; FEBRILE SEIZURES; ANIMAL-MODEL;
RODENT MODEL; MOUSE MODEL; EPILEPTOGENESIS
AB Preclinical research has facilitated the discovery of valuable drugs for the symptomatic treatment of epilepsy. Yet, despite these therapies, seizures are not adequately controlled in a third of all affected individuals, and comorbidities still impose a major burden on quality of life. The introduction of multiple new therapies into clinical use over the past two decades has done little to change this. There is an urgent demand to address the unmet clinical needs for: (1) new symptomatic antiseizure treatments for drug-resistant seizures with improved efficacy/tolerability profiles, (2) disease-modifying treatments that prevent or ameliorate the process of epileptogenesis, and (3) treatments for the common comorbidities that contribute to disability in people with epilepsy. New therapies also need to address the special needs of certain subpopulations, that is, age- or gender-specific treatments. Preclinical development in these treatment areas is complex due to heterogeneity in presentation and etiology, and may need to be formulated with a specific seizure, epilepsy syndrome, or comorbidity in mind. The aim of this report is to provide a framework that will help define future guidelines that improve and standardize the design, reporting, and validation of data across preclinical antiepilepsy therapy development studies targeting drug-resistant seizures, epileptogenesis, and comorbidities.
C1 [Galanopoulou, Aristea S.; Moshe, Solomon L.] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Saul R Korey Dept Neurol, Lab Dev Epilepsy,Montefiore Einstein Epilepsy Man, Bronx, NY 10461 USA.
[Buckmaster, Paul S.] Stanford Univ, Dept Comparat Med & Neurol, Stanford, CA 94305 USA.
[Buckmaster, Paul S.] Stanford Univ, Dept Neurol Sci, Stanford, CA 94305 USA.
[Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA USA.
[Moshe, Solomon L.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA.
[Perucca, Emilio] Univ Pavia, Dept Internal Med & Therapeut, Clin Pharmacol Unit, I-27100 Pavia, Italy.
[Perucca, Emilio] IRCCS C Mondino Fdn, Natl Neurol Inst, Pavia, Italy.
[Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA.
[Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA.
[Loescher, Wolfgang] Univ Vet Med, Dept Pharmacol Toxicol & Pharm, Hannover, Germany.
[Noebels, Jeffrey L.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Pitkanen, Asla] Univ Eastern Finland, AI Virtanen Inst Mol Sci, Epilepsy Res Lab, Kuopio, Finland.
[Pitkanen, Asla] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.
[Stables, James] NINDS, ASP, NIH, Bethesda, MD 20892 USA.
[White, H. Steve] Univ Utah, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA.
[O'Brien, Terence J.] Univ Melbourne, Dept Med, Royal Melbourne Hosp, Parkville, Vic 3052, Australia.
[O'Brien, Terence J.] Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Parkville, Vic, Australia.
[Simonato, Michele] Univ Ferrara, Dept Clin & Expt Med, Pharmacol Sect, I-44100 Ferrara, Italy.
[Simonato, Michele] Univ Ferrara, Ctr Neurosci, I-44100 Ferrara, Italy.
[Simonato, Michele] Natl Inst Neurosci, Palermo, Italy.
RP Galanopoulou, AS (reprint author), Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Saul R Korey Dept Neurol, Lab Dev Epilepsy,Montefiore Einstein Epilepsy Man, 1410 Pelham Pkwy S,Kennedy Ctr Rm 306, Bronx, NY 10461 USA.
EM aristea.galanopoulou@einstein.yu.edu
RI French, Jacqueline/G-6795-2013; O'Brien, Terence/L-8102-2013;
OI Noebels, Jeffrey /0000-0002-2887-0839; French,
Jacqueline/0000-0003-2242-8027; O'Brien, Terence/0000-0002-7198-8621
FU NIH NINDS/NICHD [NS62947]; Johnson Johnson; Novartis; NIH [R01 NS20253,
R01-NS43209, 2UO1-NS45911, P01 NS02808, R01 NS33310, U01 NS42372];
Heffer Family Foundation; Eisai; GlaxoSmithKline; Bial; Pfizer; UCB
Pharma; Upsher-Smith; Vertex; Italian Ministry of Health; Italian
Ministry for University and Research; Italian Medicines Agency; European
Commission of the EU; NeuroAdjuvants, Inc.; Janssen-Cilag;
Sanofi-Synthelabo; Chiesi Pharmaceuticals (Italy); Schering-Plough
FX ASG has received research support from NIH NINDS/NICHD grant NS62947
(PI) and recent research grant by Johnson & Johnson. ASG has also
received consultancy fees from Novartis and royalties from Morgan and
Claypool Life Sciences. PSB has nothing to disclose. KJS has nothing to
disclose. SLM has received research support from NIH: R01 NS20253 (PI),
R01-NS43209 (Investigator), 2UO1-NS45911 (Investigator), and the Heffer
Family Foundation. SLM is serving on the Editorial Board of Neurobiology
of Disease, Epileptic Disorders, Brain and Development, and
Physiological Research and has received a consultancy fee from Eisai and
speaker's fee and travel from GlaxoSmithKline. EP received speaker's or
consultancy fees and/or research grants from Bial, Eisai,
GlaxoSmithKline, Johnson & Johnson, Novartis, Pfizer, Pfizer, UCB
Pharma, Upsher-Smith, and Vertex. EP receives research support from the
Italian Ministry of Health, the Italian Ministry for University and
Research, the Italian Medicines Agency, and the European Commission of
the EU. EP also serves on the editorial boards of Acta Neurologica
Scandinavica, CNS Drugs, Epileptic Disorders, Epilepsy Research,
Seizure, Lancet Neurology, Expert Reviews in Neurotherapeutics, Clinical
Pharmacokinetics, Therapeutic Advances in Drug Safety, Frontiers in
Clinical Trials and Pharmacotherapy, and Clinical Drug Investigation.
JEJr has received research funding from NIH grants P01 NS02808, R01
NS33310, U01 NS42372, honoraria from Medtronic, Eisai, Johnson &
Johnson, Lippincottand royalties from Medlink, Wolters-Kluwer,
Blackwell, and Elsevier. WL has nothing to disclose. JLN has nothing to
disclose. AP has nothing to disclose. JS has nothing to disclose. HSW
has served as a paid consultant to Johnson & Johnson Pharmaceutical
Research and Development, GlaxoSmithKline, Valeant Pharmaceuticals, Eli
Lilly & Co., and Upsher-Smith Laboratories, Inc., is a member of the UCB
Pharma Speakers Bureau, the NeuroTherapeutics Scientific Advisory Board,
has received research funding from NeuroAdjuvants, Inc., and is one of
two scientific cofounders of NeuroAdjuvants, Inc., Salt Lake City, UT.
TJO'B has received unrestricted research grants from UCB Pharma
Janssen-Cilag, Sanofi-Synthelabo, and Novartis. TJO'B has received
speaking honorarium from UCB Pharma Janssen-Cilag, Sanofi-Synthelabo,
and SciGen. MS has received research funding from GlaxoSmithKline,
Chiesi Pharmaceuticals (Italy), Sanofi-Synthelabo, and Schering-Plough.
We confirm that we have read the Journal's position on issues relating
to ethical publication. This statement is consistent with these
guidelines
NR 61
TC 85
Z9 87
U1 1
U2 24
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD MAR
PY 2012
VL 53
IS 3
BP 571
EP 582
DI 10.1111/j.1528-1167.2011.03391.x
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA 899TF
UT WOS:000300838400023
PM 22292566
ER
PT J
AU Beinart, R
Danik, S
Palacios, I
Barrett, C
Inglessis, I
Agnihotri, A
Passeri, J
AF Beinart, Roy
Danik, Stephan
Palacios, Igor
Barrett, Conor
Inglessis, Ignacio
Agnihotri, Arvind
Passeri, Jonathan
TI Ventricular tachycardia following trans-apical aortic valve replacement
SO EUROPACE
LA English
DT Article
AB Transcatheter aortic valve replacement (TAVR) is a relatively new procedure for high-risk patients with severe aortic stenosis. We report a case of a new left ventricular outflow tract ventricular tachycardia following TAVR.
C1 [Beinart, Roy; Danik, Stephan; Palacios, Igor; Barrett, Conor; Inglessis, Ignacio; Agnihotri, Arvind; Passeri, Jonathan] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA.
RP Passeri, J (reprint author), Massachusetts Gen Hosp, Ctr Heart, YAW 5D,55 Fruit St, Boston, MA 02114 USA.
EM jpasseri@partners.org
NR 3
TC 2
Z9 2
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1099-5129
J9 EUROPACE
JI Europace
PD MAR
PY 2012
VL 14
IS 3
BP 450
EP 452
DI 10.1093/europace/eur324
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 898EC
UT WOS:000300717700028
PM 22016303
ER
PT J
AU Zuniga, J
Buendia-Roldan, I
Zhao, Y
Jimenez, L
Torres, D
Romo, J
Ramirez, G
Cruz, A
Vargas-Alarcon, G
Sheu, CC
Chen, F
Su, L
Tager, AM
Pardo, A
Selman, M
Christiani, DC
AF Zuniga, J.
Buendia-Roldan, I.
Zhao, Y.
Jimenez, L.
Torres, D.
Romo, J.
Ramirez, G.
Cruz, A.
Vargas-Alarcon, G.
Sheu, C-C.
Chen, F.
Su, L.
Tager, A. M.
Pardo, A.
Selman, M.
Christiani, D. C.
TI Genetic variants associated with severe pneumonia in A/H1N1 influenza
infection
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
DE A/H1N1; genetic susceptibility; influenza; Mexicans; single-nucleotide
polymorphisms; viral pneumonia
ID GENOME-WIDE ASSOCIATION; H1N1 VIRUS-INFECTION; A H1N1; COMPLEMENT;
RECEPTOR; SUSCEPTIBILITY; DISEASE; C1Q
AB The A/H1N1 influenza strain isolated in Mexico in 2009 caused severe pulmonary illness in a small number of exposed individuals. Our objective was to determine the influence of genetic factors on their susceptibility.
We carried out a case-control association study genotyping 91 patients with confirmed severe pneumonia from A/H1N1 infection and 98 exposed but asymptomatic household contacts, using the HumanCVD BeadChip (Illumina, San Diego, CA, USA).
Four risk single-nucleotide polymorphisms were significantly (p < 0.0001) associated with severe pneumonia: rs1801274 (Fc fragment of immunoglobulin G, low-affinity IIA, receptor (FCGR2A) gene, chromosome 1; OR 2.68, 95% CI 1.69-4.25); rs9856661 (gene unknown, chromosome 3; OR 2.62, 95% CI 1.64-4.18); rs8070740 (RPA interacting protein (RPAIN) gene, chromosome 17; OR 2.67, 95% CI 1.63-4.39); and rs3786054 (complement component 1, q subcomponent binding protein (C1QBP) gene, chromosome 17; OR 3.13, 95% CI 1.89-5.17). All SNP associations remained significant after adjustment for sex and comorbidities. The SNPs on chromosome 17 were in linkage disequilibrium.
These findings revealed that gene polymorphisms located in chromosomes 1 and 17 might influence susceptibility to development of severe pneumonia in A/H1N1 infection. Two of these SNPs are mapped within genes (FCGR2A, C1QBP) involved in the handling of immune complexes and complement activation, respectively, suggesting that these genes may confer risk due to increased activation of host immunity.
C1 [Zhao, Y.; Sheu, C-C.; Chen, F.; Su, L.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Zuniga, J.; Buendia-Roldan, I.; Jimenez, L.; Torres, D.; Romo, J.; Ramirez, G.; Cruz, A.; Selman, M.] Univ Nacl Autonoma Mexico, Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Mexico City 04510, DF, Mexico.
[Vargas-Alarcon, G.] Univ Nacl Autonoma Mexico, Inst Nacl Cardiol, Mexico City 04510, DF, Mexico.
[Pardo, A.] Univ Nacl Autonoma Mexico, Fac Ciencias, Mexico City 04510, DF, Mexico.
[Tager, A. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02115 USA.
[Tager, A. M.; Christiani, D. C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA.
[Sheu, C-C.] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Div Pulm & Crit Care Med, Kaohsiung, Taiwan.
RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 677 Huntington Ave, Boston, MA 02115 USA.
EM dchris@hsph.harvard.edu
FU National Council of Science and Technology of Mexico (Mexico City,
Mexico) (CONACYT) [127002]; National Institutes of Health (Bethesda, MD,
USA) [ES00002, HL060710, HL095732]
FX This study was supported by grants from the National Council of Science
and Technology of Mexico (Mexico City, Mexico) (CONACYT grant number
127002), and National Institutes of Health (Bethesda, MD, USA) (grant
numbers ES00002, HL060710 and HL095732).
NR 30
TC 33
Z9 34
U1 1
U2 8
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
J9 EUR RESPIR J
JI Eur. Resp. J.
PD MAR
PY 2012
VL 39
IS 3
BP 604
EP 610
DI 10.1183/09031936.00020611
PG 7
WC Respiratory System
SC Respiratory System
GA 900JS
UT WOS:000300883800015
PM 21737555
ER
PT J
AU Taylor, AM
Humphries, JM
White, RM
Murphey, RD
Burns, CE
Zon, LI
AF Taylor, Alison M.
Humphries, Jessica M.
White, Richard M.
Murphey, Ryan D.
Burns, Caroline E.
Zon, Leonard I.
TI Hematopoietic defects in rps29 mutant zebrafish depend upon p53
activation
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID DIAMOND-BLACKFAN ANEMIA; RIBOSOMAL-PROTEIN S19; ERYTHROPOIESIS;
DEFICIENCY; GENE; IDENTIFICATION; ABNORMALITIES; DISRUPTION; MUTATIONS;
REVEALS
AB Disruption of ribosomal proteins is associated with hematopoietic phenotypes in cell culture and animal models. Mutations in ribosomal proteins are seen in patients with Diamond Blackfan anemia, a rare congenital disease characterized by red cell aplasia and distinctive craniofacial anomalies. A zebrafish screen uncovered decreased hematopoietic stem cells in embryos with mutations in ribosomal protein rps29. Here, we determined that rps29(-/-) embryos also have red blood cell defects and increased apoptosis in the head. As the p53 pathway has been shown to play a role in other ribosomal protein mutants, we studied the genetic relationship of rps29 and p53. Transcriptional profiling revealed that genes upregulated in the rps29 mutant are enriched for genes upregulated by p53 after irradiation. p53 mutation near completely rescues the rps29 morphological and hematopoietic phenotypes, demonstrating that p53 mediates the effects of rps29 knockdown. We also identified neuronal gene orthopedia protein a (otpa) as one whose expression correlates with rps29 expression, suggesting that levels of expression of some genes are dependent on rps29 levels. Together, our studies demonstrate a role of p53 in mediating the cellular defects associated with rps29 and establish a role for rps29 and p53 in hematopoietic stem cells and red blood cell development. (C) 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
C1 [Zon, Leonard I.] Harvard Univ, Sch Med, Childrens Hosp Boston, Stem Cell Program, Boston, MA 02115 USA.
[Taylor, Alison M.; Humphries, Jessica M.; White, Richard M.; Murphey, Ryan D.; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Taylor, Alison M.; Humphries, Jessica M.; White, Richard M.; Murphey, Ryan D.; Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Taylor, Alison M.; Humphries, Jessica M.; White, Richard M.; Murphey, Ryan D.; Burns, Caroline E.; Zon, Leonard I.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Burns, Caroline E.] Massachusetts Gen Hosp, Charlestown, MA USA.
RP Zon, LI (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Stem Cell Program, 1 Blackfan St,Karp Bldg,7th Floor, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
FU National Institutes of Health Cell and Developmental Biology Training
[GM07226]; Howard Hughes Medical Institute (Chevy Chase, MD, USA);
National Heart, Lung, and Blood Institute (Bethesda, MD, USA) [5U01
HL10001-02]
FX A.M.T. was supported in part by National Institutes of Health Cell and
Developmental Biology Training Grant GM07226. L.I.Z. is supported by the
Howard Hughes Medical Institute (Chevy Chase, MD, USA), and this work
was funded by National Heart, Lung, and Blood Institute (Bethesda, MD,
USA) grant 5U01 HL10001-02.
NR 36
TC 27
Z9 27
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD MAR
PY 2012
VL 40
IS 3
BP 228
EP 237
DI 10.1016/j.exphem.2011.11.007
PG 10
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 899GY
UT WOS:000300805600006
PM 22120640
ER
PT J
AU Keating, A
Pineda, R
AF Keating, Anne
Pineda, Roberto, II
TI Trichosporon asahii Keratitis in a Patient With a Type I Boston
Keratoprosthesis and Contact Lens
SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE
LA English
DT Article
DE Fungal keratitis; Trichosporon; Boston keratoprosthesis; Contact lens
ID FUNGAL KERATITIS
AB Purpose: The aim of the study was to report a case of Trichosporon asahii in a patient with a type I Boston keratoprosthesis and contact lens with review of the literature.
Methods: A case report and literature review are provided.
Results: A 70-year-old monocular South Asian man with light perception vision and dense corneal scarring from previously failed amniotic membrane grafting and one failed corneal transplant was evaluated for a keratoprosthesis for visual rehabilitation. Three months after undergoing uneventful implantation of a type I Boston keratoprosthesis and placement of a therapeutic contact lens, he was found on routine follow-up to have a corneal infiltrate that was culture positive for T. asahii. The fungal keratitis was successfully treated with topical amphotericin B and oral ketoconazole.
Conclusions: Contact lens wear is a known risk factor for fungal keratitis. Trichosporon is an uncommon agent of fungal keratitis. We report the first known case of fungal keratitis caused by T. asahii in a patient with a keratoprosthesis and contact lens.
C1 [Keating, Anne; Pineda, Roberto, II] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
RP Keating, A (reprint author), 7th Floor,243 Charles St, Boston, MA 02114 USA.
EM keat0026@gmail.com
NR 6
TC 2
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1542-2321
J9 EYE CONTACT LENS
JI Eye Contact Lens-Sci. Clin. Pra.
PD MAR
PY 2012
VL 38
IS 2
BP 130
EP 132
DI 10.1097/ICL.0b013e31822c3703
PG 3
WC Ophthalmology
SC Ophthalmology
GA 898YB
UT WOS:000300777200010
PM 21876439
ER
PT J
AU Provenzale, D
AF Provenzale, Dawn
TI A Guide for Success as a Clinical Investigator
SO GASTROENTEROLOGY
LA English
DT Editorial Material
C1 [Provenzale, Dawn] Duke Univ, Med Ctr, Durham, NC 27705 USA.
[Provenzale, Dawn] US Dept Vet Affairs, Durham, NC USA.
RP Provenzale, D (reprint author), Duke Univ, Med Ctr, 508 Fulton St 152, Durham, NC 27705 USA.
EM dawn.provenzale@dm.duke.edu
NR 5
TC 4
Z9 4
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 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2012
VL 142
IS 3
BP 418
EP 421
DI 10.1053/j.gastro.2012.01.009
PG 4
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 898XC
UT WOS:000300774700013
PM 22266151
ER
PT J
AU Ananthakrishnan, AN
Khalili, H
Higuchi, LM
Bao, Y
Korzenik, JR
Giovannucci, EL
Richter, JM
Fuchs, CS
Chan, AT
AF Ananthakrishnan, Ashwin N.
Khalili, Hamed
Higuchi, Leslie M.
Bao, Ying
Korzenik, Joshua R.
Giovannucci, Edward L.
Richter, James M.
Fuchs, Charles S.
Chan, Andrew T.
TI Higher Predicted Vitamin D Status Is Associated With Reduced Risk of
Crohn's Disease
SO GASTROENTEROLOGY
LA English
DT Article
DE Ultraviolet Exposure; Nutrition; Inflammatory Bowel Disease; IBD
ID INFLAMMATORY-BOWEL-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; RECEPTOR GENE
POLYMORPHISM; COLORECTAL-CANCER; 25-HYDROXYVITAMIN-D LEVELS;
1,25-DIHYDROXYVITAMIN D-3; ULCERATIVE-COLITIS; ALPHA-TOCOPHEROL;
UNITED-STATES; D DEFICIENCY
AB BACKGROUND & AIMS: Vitamin D influences innate immunity, which is believed to be involved in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). However, data examining vitamin D status in relation to risk of CD and UC are lacking. METHODS: We conducted a prospective cohort study of 72,719 women (age, 40-73 y) enrolled in the Nurses' Health Study. In 1986, women completed an assessment of diet and lifestyle, from which a 25-hydroxy vitamin D [25(OH) D] prediction score was developed and validated against directly measured levels of plasma 25(OH) D. Through 2008, we confirmed reported diagnoses of incident CD or UC through medical record review. We used Cox proportional hazards modeling to examine the hazard ratio (HR) for incident CD or UC after adjusting for potential confounders. RESULTS: During 1,492,811 person-years of follow-up evaluation, we documented 122 incident cases of CD and 123 cases of UC. The median predicted 25(OH) D level was 22.3 ng/mL in the lowest and 32.2 ng/mL in the highest quartiles. Compared with the lowest quartile, the multivariate-adjusted HR associated with the highest quartile of vitamin D was 0.54 (95% confidence interval [CI], 0.30-.99) for CD (P-trend = .02) and 0.65 (95% CI, 0.34-1.25) for UC (P-trend = .17). Compared with women with a predicted 25(OH) D level less than 20 ng/mL, the multivariate-adjusted HR was 0.38 (95% CI, 0.15-0.97) for CD and 0.57 (95% CI, 0.19-1.70) for UC for women with a predicted 25(OH) D level greater than 30 ng/mL. There was a significant inverse association between dietary and supplemental vitamin D and UC, and a nonsignificant reduction in CD risk. CONCLUSIONS: Higher predicted plasma levels of 25(OH) D significantly reduce the risk for incident CD and nonsignificantly reduce the risk for UC in women.
C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Div Gastroenterol, Boston, MA 02114 USA.
[Ananthakrishnan, Ashwin N.; Khalili, Hamed; Higuchi, Leslie M.; Bao, Ying; Korzenik, Joshua R.; Richter, James M.; Fuchs, Charles S.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA.
[Higuchi, Leslie M.] Childrens Hosp Boston, Div Gastroenterol & Nutr, Boston, MA USA.
[Bao, Ying; Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Div Gastroenterol, 55 Fruit St,GRJ 722, Boston, MA 02114 USA.
EM achan@partners.org
FU American Gastroenterological Association; IBD Working Group; Broad
Foundation; National Institutes of Health [R01 CA137178, P01 CA87969,
P30 DK043351, K08 DK064256]; Procter and Gamble; Warner Chilcott
FX This work was supported by a Research Scholars Award of the American
Gastroenterological Association (A.N.A.), the IBD Working Group (H. K.),
the Broad Medical Research Program of the Broad Foundation (A. T. C),
and the National Institutes of Health (R01 CA137178, P01 CA87969, P30
DK043351, and K08 DK064256).; These authors disclose the following:
Joshua Korzenik has been a consultant for Procter and Gamble, Shire
Pharmaceuticals, CytokinePharma, and receives research support from
Procter and Gamble and Warner Chilcott; James Richter is a consultant
for Policy Analysis, Inc; and Andrew Chan has served as a consultant for
Bayer HealthCare and Millennium Pharmaceuticals. The remaining authors
disclose no conflicts.
NR 49
TC 122
Z9 131
U1 3
U2 25
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2012
VL 142
IS 3
BP 482
EP 489
DI 10.1053/j.gastro.2011.11.040
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 898XC
UT WOS:000300774700026
PM 22155183
ER
PT J
AU Liao, GX
Detre, C
Berger, SB
Engel, P
Malefyt, RD
Herzog, RW
Bhan, AK
Terhorst, C
AF Liao, Gongxian
Detre, Cynthia
Berger, Scott B.
Engel, Pablo
Malefyt, Rene de Waal
Herzog, Roland W.
Bhan, Atul K.
Terhorst, Cox
TI Glucocorticoid-Induced Tumor Necrosis Factor Receptor Family-Related
Protein Regulates CD4(+)T Cell-Mediated Colitis in Mice
SO GASTROENTEROLOGY
LA English
DT Article
DE TNF; Immune Regulation; Inflammation; IBD
ID (GITR)-GITR LIGAND PATHWAY; T-CELLS; DENDRITIC CELLS; INTESTINAL
INFLAMMATION; MURINE MACROPHAGE; CUTTING EDGE; GITR; IMMUNITY;
EXPRESSION; MUCOSAL
AB BACKGROUND & AIMS: The glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR; also called TNFRSF18 or CD357) regulates the T cell-mediated immune response and is present on surfaces of regulatory T (Treg) cells and activated CD4(+) T cells. We investigated the roles of GITR in the development of colitis in mice. METHODS: Chronic enterocolitis was induced by the transfer of wild-type or GITR(-/-) CD4(+) T cells to GITR(-/-) x Rag(-/-) or Rag(-/-) mice. We determined the severity of colitis by using the disease activity index; measured levels of inflammatory cytokines, T cells, and dendritic cells; and performed histologic analysis of colon samples. RESULTS: Transfer of nonfractionated CD4(+) cells from wild-type or GITR(-/-) donors induced colitis in GITR(-/-) x Rag(-/-) but not in Rag(-/-) mice. Among mice with transfer-induced colitis, the percentage of Treg and T-helper (Th) 17 cells was reduced but that of Th1 cells increased. Treg cells failed to prevent colitis in GITR(-/-) x Rag(-/-) recipients; this was not the result of aberrant function of GITR(-/-) Treg or T effector cells but resulted from an imbalance between the numbers of tolerogenic CD103(+) and PDCA1(+) plasmacytoid dendritic cells in GITR(-/-) mice. This imbalance impaired Treg cell development and expanded the Th1 population in GITR(-/-) x Rag(-/-) mice following transfer of nonfractionated CD4(+) cells. CONCLUSIONS: GITR is not required on the surface of Treg and T effector cells to induce colitis in mice; interactions between GITR and its ligand are not required for induction of colitis. GITR instead appears to control dendritic cell and monocyte development; in its absence, mice develop aggravated chronic enterocolitis via an imbalance of colitogenic Th1 cells and Treg cells.
C1 [Liao, Gongxian; Detre, Cynthia; Berger, Scott B.; Terhorst, Cox] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Immunol, Boston, MA 02115 USA.
[Bhan, Atul K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Engel, Pablo] Univ Barcelona, Sch Med, Dept Cell Biol Immunol & Neurosci, Immunol Unit, Barcelona, Spain.
[Malefyt, Rene de Waal] Merck Res Labs, Palo Alto, CA USA.
[Herzog, Roland W.] Univ Florida, Canc & Genet Res Ctr, Gainesville, FL USA.
RP Liao, GX (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Immunol, Boston, MA 02115 USA.
EM gliao@bidmc.harvard.edu
FU National Institutes of Health [P01 HL078810, R01 DK-52510, PHS
5T32AI7512-24]
FX Supported by the National Institutes of Health (P01 HL078810 and R01
DK-52510 to C. T. and PHS 5T32AI7512-24 to G.L.)
NR 32
TC 10
Z9 10
U1 0
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2012
VL 142
IS 3
BP 582
EP U256
DI 10.1053/j.gastro.2011.11.031
PG 18
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 898XC
UT WOS:000300774700037
PM 22155173
ER
PT J
AU Jakobiec, FA
Zakka, FR
Townsend, DJ
AF Jakobiec, Frederick A.
Zakka, Fouad R.
Townsend, Daniel J.
TI Pleomorphic basal cell carcinoma of the eyelid with true ductular
differentiation
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
C1 [Jakobiec, Frederick A.; Zakka, Fouad R.] David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA.
[Jakobiec, Frederick A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Jakobiec, Frederick A.; Zakka, Fouad R.; Townsend, Daniel J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Jakobiec, FA (reprint author), David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA.
EM Fred_Jakobiec@meei.harvard.edu
NR 10
TC 2
Z9 2
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD MAR
PY 2012
VL 250
IS 3
BP 451
EP 454
DI 10.1007/s00417-011-1836-0
PG 4
WC Ophthalmology
SC Ophthalmology
GA 902LH
UT WOS:000301039100018
PM 22037988
ER
PT J
AU Hoogeveen-Westerveld, M
Ekong, R
Povey, S
Karbassi, I
Batish, SD
den Dunnen, JT
van Eeghen, A
Thiele, E
Mayer, K
Dies, K
Wen, L
Thompson, C
Sparagana, SP
Davies, P
Aalfs, C
van den Ouweland, A
Halley, D
Nellist, M
AF Hoogeveen-Westerveld, Marianne
Ekong, Rosemary
Povey, Sue
Karbassi, Izabela
Batish, Sat Dev
den Dunnen, Johan T.
van Eeghen, Agnies
Thiele, Elizabeth
Mayer, Karin
Dies, Kira
Wen, Li
Thompson, Catherine
Sparagana, Steven P.
Davies, Peter
Aalfs, Cora
van den Ouweland, Ans
Halley, Dicky
Nellist, Mark
TI Functional assessment of TSC1 missense variants identified in
individuals with tuberous sclerosis complex
SO HUMAN MUTATION
LA English
DT Article
DE TSC1; TSC2; tuberous sclerosis complex; hamartin; tuberin
ID CELL-GROWTH; GENE; MUTATIONS; HAMARTIN
AB Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 or TSC2 genes. The TSC1 and TSC2 gene products, TSC1 and TSC2, form a complex that inhibits the mammalian target of rapamycin (mTOR) complex 1 (TORC1). Previously, we demonstrated that pathogenic amino acid substitutions in the N-terminal domain of TSC1 (amino acids 50224) are destabilizing. Here we investigate an additional 21 unclassified TSC1 variants. Our functional assessment identified four substitutions (p.L61R, p.G132D, p.F158S, and p.R204P) between amino acids 50 and 224 that reduced TSC1 stability and prevented the TSC1-TSC2-dependent inhibition of TORC1. In four cases (20%), our functional assessment did not agree with the predictions of the SIFT amino acid substitution analysis software. Our new data confirm our previous finding that the N-terminal region of TSC1 is essential for TSC1 function. Hum Mutat 33:476479, 2012. (C) 2011 Wiley Periodicals, Inc.
C1 [Hoogeveen-Westerveld, Marianne; van den Ouweland, Ans; Halley, Dicky; Nellist, Mark] Erasmus MC, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands.
[Ekong, Rosemary; Povey, Sue] UCL, Res Dept Genet Evolut & Environm, London WC1E 6BT, England.
[Karbassi, Izabela; Batish, Sat Dev] Athena Diagnost Inc, Worcester, MA USA.
[den Dunnen, Johan T.] Leiden Univ Med Ctr, Dept Human & Clin Genet, NL-2333 ZC Leiden, Netherlands.
[van Eeghen, Agnies; Thiele, Elizabeth] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Mayer, Karin] Ctr Human Genet & Lab Med, D-82152 Martinsried, Germany.
[Dies, Kira] Childrens Hosp Boston, Dept Neurol, Boston, MA USA.
[Wen, Li] Cent S Univ, Inst Reprod & Stem Cell Engn, Changsha 410078, Hunan, Peoples R China.
[Thompson, Catherine; Sparagana, Steven P.] Texas Scottish Rite Hosp Children, Dept Neurol, Dallas, TX 75219 USA.
[Sparagana, Steven P.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Davies, Peter] Cardiff Univ, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales.
[Aalfs, Cora] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands.
RP Nellist, M (reprint author), Erasmus MC, Dept Clin Genet, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands.
EM m.nellist@erasmusmc.nl
FU U.S. Department of Defense Congressionally Directed Medical Research
Program [TS060052]; Tuberous Sclerosis Alliance
FX The U.S. Department of Defense Congressionally Directed Medical Research
Program (TS060052); The Tuberous Sclerosis Alliance.
NR 16
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U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD MAR
PY 2012
VL 33
IS 3
BP 476
EP 479
DI 10.1002/humu.22007
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 898AB
UT WOS:000300706000006
PM 22161988
ER
PT J
AU Fuhlbrigge, A
Peden, D
Apter, AJ
Boushey, HA
Camargo, CA
Gern, J
Heymann, PW
Martinez, FD
Mauger, D
Teague, WG
Blaisdell, C
AF Fuhlbrigge, Anne
Peden, David
Apter, Andrea J.
Boushey, Homer A.
Camargo, Carlos A., Jr.
Gern, James
Heymann, Peter W.
Martinez, Fernando D.
Mauger, David
Teague, William G.
Blaisdell, Carol
TI Asthma outcomes: Exacerbations
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma exacerbations; severity of acute asthma; systemic steroids in
asthma; urgent asthma care
ID RANDOMIZED CONTROLLED-TRIAL; METERED-DOSE INHALER; MILD PERSISTENT
ASTHMA; EXHALED NITRIC-OXIDE; INNER-CITY CHILDREN; BUDESONIDE/FORMOTEROL
COMBINATION THERAPY; POORLY CONTROLLED ASTHMA; BROMIDE PLUS FENOTEROL;
AMBIENT AIR-POLLUTION; DRY POWDER INHALER
AB Background: The goals of asthma treatment include preventing recurrent exacerbations. Yet there is no consensus about the terminology for describing or defining "exacerbation" or about how to characterize an episode's severity.
Objective: National Institutes of Health institutes and other federal agencies convened an expert group to propose how asthma exacerbation should be assessed as a standardized asthma outcome in future asthma clinical research studies.
Methods: We used comprehensive literature reviews and expert opinion to compile a list of asthma exacerbation outcomes and classified them as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at a National Institutes of Health-organized workshop in March 2010 and finalized in September 2011.
Results: No dominant definition of "exacerbation" was found. The most widely used definitions included 3 components, all related to treatment, rather than symptoms: (1) systemic use of corticosteroids, (2) asthma-specific emergency department visits or hospitalizations, and (3) use of short-acting beta-agonists as quick-relief (sometimes referred to as "rescue" or "reliever") medications.
Conclusions: The working group participants propose that the definition of "asthma exacerbation" be "a worsening of asthma requiring the use of systemic corticosteroids to prevent a serious outcome." As core outcomes, they propose inclusion and separate reporting of several essential variables of an exacerbation. Furthermore, they propose the development of a standardized, component-based definition of "exacerbation" with clear thresholds of severity for each component. (J Allergy Clin Immunol 2012; 129: S34-48.)
C1 [Blaisdell, Carol] NHLBI, DLD, NIH, Bethesda, MD 20892 USA.
[Fuhlbrigge, Anne] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Peden, David] Univ N Carolina, Chapel Hill, NC USA.
[Apter, Andrea J.] Univ Penn, Philadelphia, PA 19104 USA.
[Boushey, Homer A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Gern, James] Univ Wisconsin, Madison, WI 53706 USA.
[Heymann, Peter W.; Teague, William G.] Univ Virginia, Charlottesville, VA USA.
[Martinez, Fernando D.] Univ Arizona, Tucson, AZ USA.
[Mauger, David] Penn State Univ, Hershey, PA USA.
RP Blaisdell, C (reprint author), NHLBI, DLD, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM blaisdellcj@nhlbi.nih.gov
FU National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Environmental
Health Sciences; Agency for Healthcare Research and Quality; Merck
Childhood Asthma Network; Robert Wood Johnson Foundation; US
Environmental Protection Agency; NIH/NIAID; MedImmune; Aquinox
Pharmaceuticals; GlaxoSmithKline; Genentech; Sanofi-Aventis; Centocor;
Boehringer Ingelheim; Biota; Theraclone; NIH; Novartis; NIH/NHLBI;
American Lung Association
FX The Asthma Outcomes workshop was funded by contributions from the
National Institute of Allergy and Infectious Diseases; the National
Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the National Institute
of Environmental Health Sciences; the Agency for Healthcare Research and
Quality; and the Merck Childhood Asthma Network, as well as by a grant
from the Robert Wood Johnson Foundation. Contributions from the National
Heart, Lung, and Blood Institute; the National Institute of Allergy and
Infectious Diseases; the Eunice Kennedy Shriver National Institute of
Child Health and Human Development; the National Institute of
Environmental Health Sciences; and the US Environmental Protection
Agency funded the publication of this article and all other articles in
this supplement.; Disclosure of potential conflict of interest: A.
Fuhlbrigge is on the Merck Respiratory Advisory Board and is a
consultant for the Lovelace Respiratory and Research Institute. D. Peden
has received research support from the NIH/NIAID, MedImmune, the US
Environmental Protection Agency, and Aquinox Pharmaceuticals. A. J.
Apter has received research support from the NHLBI and is on the AAAAI
Board of Directors. H. A. Boushey has provided ad-hoc consultation for
Kalobics; is on the Pharmaxis advisory committee; is on the ad-hoc
advisory committee for Merck and GlaxoSmithKline; has provided
consultation for Genentech and Johnson & Johnson; and has received
research support from GlaxoSmithKline and Genentech. C. A. Camargo, Jr,
is a consultant for Dey, Genentech, Merck, Novartis, and Pfizer; and has
received research support from GlaxoSmithKline and Sanofi-Aventis. J.
Gern is on the Scientific Advisory Board and has stock options in 3V
Biosciences, and has received consulting fees from Centocor, Boehringer
Ingelheim, GlaxoSmithKline, Biota, MedImmune, and Theraclone. P. W.
Heymann has received research support from the NIH and Novartis. F. D.
Martinez has consulted for MedImmune and received lecture honorarium
from Abbott. W. G. Teague is a speaker for Merck and Genentech, and has
received research support from the NIH/NHLBI and the American Lung
Association. C. Blaisdell is on the American Academy of Pediatrics
Executive Board and is an abstract reviewer for the Pediatric Academic
Society. The rest of the authors declare that they have no relevant
conflicts of interest.
NR 138
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U1 2
U2 14
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
SU S
BP S34
EP S48
DI 10.1016/j.jaci.2011.12.983
PG 15
WC Allergy; Immunology
SC Allergy; Immunology
GA 901OL
UT WOS:000300976600004
PM 22386508
ER
PT J
AU Raddi, G
Morado, DR
Yan, J
Haake, DA
Yang, XF
Liu, J
AF Raddi, Gianmarco
Morado, Dustin R.
Yan, Jie
Haake, David A.
Yang, X. Frank
Liu, Jun
TI Three-Dimensional Structures of Pathogenic and Saprophytic Leptospira
Species Revealed by Cryo-Electron Tomography
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID BORRELIA-BURGDORFERI; ELECTRON TOMOGRAPHY; FLAGELLAR MOTOR; CELLULAR
ARCHITECTURE; PERIPLASMIC FLAGELLA; TREPONEMA-PRIMITIA; FINE-STRUCTURE;
MOTILITY; INTERROGANS; BACTERIA
AB Leptospira interrogans is the primary causative agent of the most widespread zoonotic disease, leptospirosis. An in-depth structural characterization of L. interrogans is needed to understand its biology and pathogenesis. In this study, cryo-electron tomography (cryo-ET) was used to compare pathogenic and saprophytic species and examine the unique morphological features of this group of bacteria. Specifically, our study revealed a structural difference between the cell envelopes of L. interrogans and Leptospira biflexa involving variations in the lipopolysaccharide (LPS) layer. Through cryo-ET and subvolume averaging, we determined the first three-dimensional (3-D) structure of the flagellar motor of leptospira, with novel features in the flagellar C ring, export apparatus, and stator. Together with direct visualization of chemoreceptor arrays, DNA packing, periplasmic filaments, spherical cytoplasmic bodies, and a unique "cap" at the cell end, this report provides structural insights into these fascinating Leptospira species.
C1 [Yang, X. Frank] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN USA.
[Raddi, Gianmarco; Morado, Dustin R.; Liu, Jun] Univ Texas Med Sch Houston, Dept Pathol & Lab Med, Houston, TX USA.
[Yan, Jie] Zhejiang Univ, Coll Med, Dept Med Microbiol & Parasitol, Hangzhou 310003, Zhejiang, Peoples R China.
[Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA.
[Haake, David A.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Haake, David A.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA.
[Haake, David A.] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA USA.
RP Yang, XF (reprint author), Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN USA.
EM xfyang@iupui.edu; jun.liu.1@uth.tmc.edu
FU National Institute of Allergy and Infectious Diseases (NIAID)
[R01AI087946, 5R01AI034431]; Welch Foundation [AU-1714]; VA
FX This work was supported in part by grants R01AI087946 (to J. Liu) and
5R01AI034431 (to D. A. Haake) from the National Institute of Allergy and
Infectious Diseases (NIAID), by grant AU-1714 from the Welch Foundation
(to J. Liu), and by VA Medical Research funds (to D. A. Haake).
NR 50
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U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD MAR
PY 2012
VL 194
IS 6
BP 1299
EP 1306
DI 10.1128/JB.06474-11
PG 8
WC Microbiology
SC Microbiology
GA 899WI
UT WOS:000300846900003
PM 22228733
ER
PT J
AU Cole, LW
Kesselheim, JC
Kesselheim, AS
AF Cole, Lindsay W.
Kesselheim, Jennifer C.
Kesselheim, Aaron S.
TI Ethical Issues in New Drug Prescribing
SO JOURNAL OF BIOETHICAL INQUIRY
LA English
DT Article
DE Pharmaceutical marketing; Adverse event; Randomized controlled trial;
Food and drug administration; Pharmaceutical industry
ID OFF-LABEL; PHYSICIANS; INDUSTRY; PERSPECTIVE; BEHAVIOR; EVENTS
AB We use the format of a hypothetical case study to review issues related to pharmaceutical product approval and physician prescribing practices. In this case, a new FDA-approved drug is recommended for a patient who subsequently experiences an adverse event that may or may not be related to the prescription. This case raises a number of ethical and legal considerations physicians routinely face when deciding whether to recommend such drugs for their patients. Despite the need for ongoing observation by the regulatory apparatus, physicians should be cognizant of the limitations of the drug approval system and the post-approval prescription drug surveillance system. We discuss physicians' ethical obligations when faced with a newly approved drug, including seeking out independent sources of learning, reporting adverse effects, and notifying patients about limitations in available knowledge about therapeutic recommendations.
C1 [Kesselheim, Aaron S.] Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02120 USA.
[Cole, Lindsay W.] Harvard Univ, Sch Med, Boston, MA USA.
[Kesselheim, Jennifer C.] Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Kesselheim, Aaron S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA USA.
RP Kesselheim, AS (reprint author), Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA.
EM akesselheim@partners.org
FU Agency for Healthcare Research and Quality [K08HS18465-01]; Robert Wood
Johnson Foundation
FX Dr. Aaron Kesselheim is supported by a career development award from the
Agency for Healthcare Research and Quality (K08HS18465-01) and a Robert
Wood Johnson Foundation Investigator Award in Health Policy Research.
The authors report no potential conflicts of interest.
NR 36
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U1 1
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1176-7529
J9 J BIOETHIC INQ
JI J. Bioethical Inq.
PD MAR
PY 2012
VL 9
IS 1
BP 77
EP 83
DI 10.1007/s11673-011-9342-y
PG 7
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 898WW
UT WOS:000300774100010
PM 23180203
ER
PT J
AU Roche-Labarbe, N
Fenoglio, A
Aggarwal, A
Dehaes, M
Carp, SA
Franceschini, MA
Grant, PE
AF Roche-Labarbe, Nadege
Fenoglio, Angela
Aggarwal, Alpna
Dehaes, Mathieu
Carp, Stefan A.
Franceschini, Maria Angela
Grant, Patricia Ellen
TI Near-infrared spectroscopy assessment of cerebral oxygen metabolism in
the developing premature brain
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE brain hemodynamic development; cerebral oxygen consumption; diffuse
correlation spectroscopy; frequency-domain near-infrared spectroscopy;
premature neonates
ID DIFFUSE CORRELATION SPECTROSCOPY; BLOOD-FLOW; PRETERM INFANTS;
OPTICAL-PROPERTIES; NEWBORN-INFANTS; VISUAL-CORTEX; QUANTIFICATION;
HEMODYNAMICS; ABSORPTION; SCATTERING
AB Little is known about cerebral blood flow, cerebral blood volume (CBV), oxygenation, and oxygen consumption in the premature newborn brain. We combined quantitative frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation (SO2) and CBV with diffusion correlation spectroscopy measures of cerebral blood flow index (BFix) to determine the relationship between these measures, gestational age at birth (GA), and chronological age. We followed 56 neonates of various GA once a week during their hospital stay. We provide absolute values of SO2 and CBV, relative values of BFix, and relative cerebral metabolic rate of oxygen (rCMRO(2)) as a function of postmenstrual age (PMA) and chronological age for four GA groups. SO2 correlates with chronological age (r = -0.54, P value <= 0.001) but not with PMA (r = -0.07), whereas BFix and rCMRO(2) correlate better with PMA (r = 0.37 and 0.43, respectively, P value <= 0.001). Relative CMRO2 during the first month of life is lower when GA is lower. Blood flow index and rCMRO(2) are more accurate biomarkers of the brain development than SO2 in the premature newborns. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 481-488; doi: 10.1038/jcbfm.2011.145; published online 26 October 2011
C1 [Roche-Labarbe, Nadege; Carp, Stefan A.; Franceschini, Maria Angela] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Fenoglio, Angela; Dehaes, Mathieu; Grant, Patricia Ellen] Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA 02115 USA.
[Aggarwal, Alpna; Grant, Patricia Ellen] Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA.
RP Roche-Labarbe, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM nadege@nmr.mgh.harvard.edu
RI Roche-Labarbe, Nadege/N-9101-2015
OI Roche-Labarbe, Nadege/0000-0002-5010-0400
FU NIH [R01 HD042908, P41-RR14075, R21-HD058725]; National Center for
Research Resources [UL1RR025758]
FX This work was supported by NIH Grant R01 HD042908, P41-RR14075, and
R21-HD058725 and by Clinical Translational Science Award UL1RR025758 to
Harvard University and Brigham and Women's Hospital from the National
Center for Research Resources.
NR 40
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U1 4
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD MAR
PY 2012
VL 32
IS 3
BP 481
EP 488
DI 10.1038/jcbfm.2011.145
PG 8
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 901FN
UT WOS:000300948200010
PM 22027937
ER
PT J
AU Mbye, LH
Keles, E
Tao, LY
Zhang, J
Chung, J
Larvie, M
Koppula, R
Lo, EH
Whalen, MJ
AF Mbye, Lamin H.
Keles, Eyup
Tao, Luyang
Zhang, Jimmy
Chung, Joonyong
Larvie, Mykol
Koppula, Rajani
Lo, Eng H.
Whalen, Michael J.
TI Kollidon VA64, a membrane-resealing agent, reduces histopathology and
improves functional outcome after controlled cortical impact in mice
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE blood-brain barrier; edema; Kollidon VA64; mice; plasmalemma; traumatic
brain injury
ID TRAUMATIC BRAIN-INJURY; SURFACTANT POLOXAMER-188; MECHANICAL TRAUMA;
PRENATAL EXPOSURE; CELL-DEATH; PERMEABILITY; NEURONS; DAMAGE;
EPILEPTOGENESIS; RECOVERY
AB Loss of plasma membrane integrity is a feature of acute cellular injury/death in vitro and in vivo. Plasmalemma-resealing agents are protective in acute central nervous system injury models, but their ability to reseal cell membranes in vivo has not been reported. Using a mouse controlled cortical impact (CCI) model, we found that propidium iodide-positive (PI+) cells pulse labeled at 6, 24, or 48 hours maintained a degenerative phenotype and disappeared from the injured brain by 7 days, suggesting that plasmalemma permeability is a biomarker of fatal cellular injury after CCI. Intravenous or intracerebroventricular administration of Kollidon VA64, poloxamer P188, or polyethylene glycol 8000 resealed injured cell membranes in vivo (P < 0.05 versus vehicle or poloxamer P407). Kollidon VA64 (1 mmol/L, 500 mu L) administered intravenously to mice 1 hour after CCI significantly reduced acute cellular degeneration, chronic brain tissue damage, brain edema, blood-brain barrier damage, and postinjury motor deficits (all P < 0.05 versus vehicle). However, VA64 did not rescue pulse-labeled PI+ cells from eventual demise. We conclude that PI permeability within 48 hours of CCI is a biomarker of eventual cell death/loss. Kollidon VA64 reduces secondary damage after CCI by mechanisms other than or in addition to resealing permeable cells. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 515-524; doi: 10.1038/jcbfm.2011.158; published online 16 November 2011
C1 [Mbye, Lamin H.; Keles, Eyup; Zhang, Jimmy; Chung, Joonyong; Koppula, Rajani; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA.
[Mbye, Lamin H.; Keles, Eyup; Zhang, Jimmy; Chung, Joonyong; Koppula, Rajani; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA.
[Tao, Luyang] Soochow Univ, Inst Forens Sci, Suzhou, Peoples R China.
[Larvie, Mykol; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA.
[Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
RP Whalen, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Charlestown, MA 02129 USA.
EM mwhalen@partners.org
FU NINDS [5RO1NS061255]; Nature Science Foundation of China
FX This study was supported by NINDS 5RO1NS061255 (MJW) and the Nature
Science Foundation of China (LT).
NR 36
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U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD MAR
PY 2012
VL 32
IS 3
BP 515
EP 524
DI 10.1038/jcbfm.2011.158
PG 10
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 901FN
UT WOS:000300948200013
PM 22086196
ER
PT J
AU Klein, KP
Hannum, WH
Fields, HW
Proffit, WR
AF Klein, Katherine P.
Hannum, Wallace H.
Fields, Henry W.
Proffit, William R.
TI Interactive Distance Learning in Orthodontic Residency Programs:
Problems and Potential Solutions
SO JOURNAL OF DENTAL EDUCATION
LA English
DT Article
DE dental education; distance education; orthodontic education;
orthodontics
ID EDUCATION
AB Sharing resources through distance education has been proposed as one way to deal with a lack of full-time faculty members and maintain high-quality content in orthodontic residency programs. To keep distance education for orthodontic residents cost-effective while retaining interaction, a blended approach was developed that combines observation of web-based seminars with live post-seminar discussions. To evaluate this approach, a grant from the American Association of Orthodontists (AAO) opened free access during the 2009-10 academic year to twenty-five recorded seminars in four instructional sequences to all sixty-three orthodontic programs in the United States and Canada. The only requirement was to also participate in the evaluation. Just over half (52 percent) of the U.S. programs chose to participate; the primary reason for participating was because faculty members wanted their residents to have exposure to other faculty members and ideas. The non-participating programs cited technical and logistical problems and their own ability to teach these subjects satisfactorily as reasons. Although participating distant faculty members and residents were generally pleased with the experience, problems in both educational and technical aspects were observed. Educationally, the biggest problem was lack of distant resident preparation and expectation of a lecture rather than a seminar. Technically, the logistics of scheduling distant seminars and uneven quality of the audio and video recordings were the major concerns of both residents and faculty members. Proposed solutions to these educational and technical problems are discussed.
C1 [Proffit, William R.] Univ N Carolina, Sch Dent, Dept Orthodont, Chapel Hill, NC 27599 USA.
[Klein, Katherine P.] Massachusetts Gen Hosp, Div Dent, Boston, MA 02114 USA.
[Hannum, Wallace H.] Univ N Carolina, Sch Educ, Chapel Hill, NC 27599 USA.
[Fields, Henry W.] Ohio State Univ, Coll Dent, Div Orthodont, Columbus, OH 43210 USA.
RP Proffit, WR (reprint author), Univ N Carolina, Sch Dent, Dept Orthodont, CB 7450, Chapel Hill, NC 27599 USA.
EM william_proffit@dentistry.unc.edu
NR 11
TC 1
Z9 2
U1 0
U2 2
PU AMER DENTAL EDUCATION ASSOC
PI WASHINGTON
PA 1400 K STREET, NW, STE 1100, WASHINGTON, DC 20005 USA
SN 0022-0337
J9 J DENT EDUC
JI J. Dent. Educ.
PD MAR
PY 2012
VL 76
IS 3
BP 322
EP 329
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 902KO
UT WOS:000301037200007
PM 22383600
ER
PT J
AU Horton, E
Wright, R
Barbosa, FC
Plummer, L
Kaina, J
Buck, C
Jiang, N
Quinton, R
Crowley, WF
Balasubramanian, R
AF Horton, Edward
Wright, Rohanna
Barbosa, Flavia Costa
Plummer, Lacey
Kaina, Jennifer
Buck, Cassandra
Jiang, Ning
Quinton, Richard
Crowley, William F., Jr.
Balasubramanian, Ravikumar
TI LOW SPINAL BONE MINERAL DENSITY IN MEN WITH ISOLATED GNRH DEFICIENCY IS
RELATED TO THE DEGREE OF PUBERTAL ACTIVATION OF
HYPOTHALAMO-PITUITARY-GONADAL AXIS
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
C1 [Horton, Edward; Barbosa, Flavia Costa; Plummer, Lacey; Kaina, Jennifer; Buck, Cassandra; Jiang, Ning; Crowley, William F., Jr.; Balasubramanian, Ravikumar] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA.
[Wright, Rohanna; Quinton, Richard] Royal Victoria Infirm, Dept Endocrinol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
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 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2012
VL 60
IS 3
BP 618
EP 618
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 898YL
UT WOS:000300778200014
ER
PT J
AU Buonanno, F
Meng, R
Feeney, K
Cao, J
Lo, EH
Elia, M
Thayer, M
Ning, MM
AF Buonanno, Ferdinando
Meng, Ran
Feeney, Kathleen
Cao, Jing
Lo, Eng H.
Elia, Mikaela
Thayer, Molly
Ning, MingMing
TI ANTIPHOSPHOLIPID ANTIBODY ELEVATION IS ASSOCIATED WITH "SILENT STROKES"
IN PATIENTS WITH PATENT FORAMEN OVALE
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
C1 [Ning, MingMing] Harvard Univ, Sch Med, Mass Gen Hosp, 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 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2012
VL 60
IS 3
BP 619
EP 619
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 898YL
UT WOS:000300778200018
ER
PT J
AU Lewkowitz-Shpuntoff, H
Balasubramanian, R
Chavan, N
Kaina, J
Dwyer, A
Seminara, S
Plummer, L
Hayes, F
Crowley, WF
Pitteloud, N
AF Lewkowitz-Shpuntoff, Hilana
Balasubramanian, Ravikumar
Chavan, Niraj
Kaina, Jennifer
Dwyer, Andrew
Seminara, Stephanie
Plummer, Lacey
Hayes, Francis
Crowley, William F., Jr.
Pitteloud, Nelly
TI FUNCTIONAL GONADOTROPIN-RELEASING HORMONE DEFICIENCY IN MEN
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lewkowitz-Shpuntoff, Hilana] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Dwyer, Andrew; Pitteloud, Nelly] CHU Vaudois, CH-1011 Lausanne, Switzerland.
RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014
OI Dwyer, Andrew/0000-0002-7023-6794;
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 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2012
VL 60
IS 3
BP 619
EP 619
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 898YL
UT WOS:000300778200017
ER
PT J
AU Chou, SH
Feske, SK
Simmons, SL
Orzell, S
Du, R
Marckmann, A
Lo, EH
Ning, MM
AF Chou, Sherry H.
Feske, Steven K.
Simmons, Suzanne L.
Orzell, Susannah
Du, Rose
Marckmann, Andrea
Lo, Eng H.
Ning, MingMing
TI ELEVATED CEREBROSPINAL FLUID METALLOPROTEINASE-9 IS ASSOCIATED WITH POOR
6-MONTH OUTCOME FOLLOWING SUBARACHNOID HEMORRHAGE
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
C1 [Chou, Sherry H.; Feske, Steven K.; Simmons, Suzanne L.; Orzell, Susannah; Du, Rose; Ning, MingMing] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Chou, Sherry H.; Marckmann, Andrea; Lo, Eng H.; Ning, MingMing] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Chou, Sherry H.; Feske, Steven K.; Du, Rose; Lo, Eng H.; Ning, MingMing] Harvard Univ, Sch Med, Boston, MA USA.
RI Du, Rose/I-5402-2012
OI Du, Rose/0000-0003-2641-6496
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 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2012
VL 60
IS 3
BP 620
EP 620
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 898YL
UT WOS:000300778200022
ER
PT J
AU Funkhouser, WK
Lubin, IM
Monzon, FA
Zehnbauer, BA
Evans, JP
Ogino, S
Nowak, JA
AF Funkhouser, William K., Jr.
Lubin, Ira M.
Monzon, Federico A.
Zehnbauer, Barbara A.
Evans, James P.
Ogino, Shuji
Nowak, Jan A.
TI Relevance, Pathogenesis, and Testing Algorithm for Mismatch
Repair-Defective Colorectal Carcinomas A Report of the Association for
Molecular Pathology
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Article
ID ISLAND METHYLATOR PHENOTYPE; SPORADIC COLON-CANCER; REVISED BETHESDA
GUIDELINES; POPULATION-BASED SAMPLE; TUMOR MICROSATELLITE-INSTABILITY;
FRAMESHIFT-INDUCED NEOPEPTIDES; COST-EFFECTIVENESS ANALYSIS; MLH1
PROMOTER METHYLATION; HNPCC MUTATION CARRIERS; BRAF V600E MUTATION
AB Loss-of-function defects in DNA mismatch repair (MMR), which manifest as high levels of microsatellite instability (MSI), occur in approximately 15% of all colorectal carcinomas (CRCs). This molecular subset of CRC characterizes patients with better stage-specific prognoses who experience no benefit from 5-fluorouracil chemotherapy. Most MMR-deficient (dMMR) CRCs are sporadic, but 15% to 20% are due to inherited predisposition (Lynch syndrome). High penetrance of CRCs in germline MMR gene mutation carriers emphasizes the importance of accurate diagnosis of Lynch syndrome carriers. Family-based (Amsterdam), patient/family-based (Bethesda), morphology-based, microsatellite-based, and IHC-based screening,criteria do not individually detect all germline mutation carriers. These limitations support the use of multiple concurrent tests and the screening of all patients with newly diagnosed CRC. This approach is resource intensive but would increase detection of inherited and de novo germline mutations to guide family screening. Although CRC prognosis and prediction of 5-fluorouracil response arc: similar in both the Lynch and sporadic dMMR subgroups, these subgroups differ significantly with regard to the implications for family members. We recommend that new CRCs should be classified into sporadic MMR-proficient, sporadic dMMR, or Lynch dMMR subgroups. The concurrent use of MSI testing, MMR protein IHC, and BRAF c.1799T>A mutation analysis would detect almost all dMMR CRCs, would classify 94% of all new CRCs into these MMR subgroups, and would guide secondary molecular testing of the remainder. (J moL Diagn, 2012, 14:91-103; DOI:10.1016/j.jmoldx.2011.11.001)
C1 [Funkhouser, William K., Jr.] Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
[Funkhouser, William K., Jr.; Lubin, Ira M.; Monzon, Federico A.] Univ N Carolina, Mismatch Repair Defect CRC Working Grp, Assoc Mol Pathol Clin Practice Comm, Chapel Hill, NC 27599 USA.
[Evans, James P.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Lubin, Ira M.; Zehnbauer, Barbara A.] Ctr Dis Control & Prevent, Div Lab Sci & Stand, Atlanta, GA USA.
[Monzon, Federico A.] Methodist Hosp, Dept Pathol, Houston, TX 77030 USA.
[Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ogino, Shuji] Dana Farber Canc Inst, Canc Epidemiol Pmgram, Boston, MA 02115 USA.
[Ogino, Shuji] Harvard Canc Ctr, Boston, MA USA.
[Nowak, Jan A.] Northshore Univ HealthSyst, Evanston, IL USA.
RP Funkhouser, WK (reprint author), Univ N Carolina, Sch Med, Dept Pathol & Lab Med, CB 7525,Brinkhous Bullitt Bldg, Chapel Hill, NC 27599 USA.
EM bill_funkhouser@med.unc.edu
NR 130
TC 57
Z9 57
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD MAR
PY 2012
VL 14
IS 2
BP 91
EP 103
DI 10.1016/j.jmoldx.2011.11.001
PG 13
WC Pathology
SC Pathology
GA 901ZF
UT WOS:000301007700001
PM 22260991
ER
PT J
AU Kolasinski, J
Stagg, CJ
Chance, S
Esiri, M
Chang, E
Palace, JA
McNab, JA
Jenkinson, M
Miller, K
Johansen-Berg, H
AF Kolasinski, J.
Stagg, C. J.
Chance, S.
Esiri, M.
Chang, E.
Palace, J. A.
McNab, J. A.
Jenkinson, M.
Miller, K.
Johansen-Berg, H.
TI COMPARISON OF HISTOLOGICAL AND DIFFUSION-WEIGHTED MRI TECHNIQUES IN THE
ANALYSIS OF POST MORTEM MULTIPLE SCLEROSIS BRAINS
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-of-British-Neurologists
CY 2011
CL Gateshead, ENGLAND
SP Assoc British Neurologists
C1 Univ Oxford, Ctr Funct Magnet Resonance Imaging Brain, Oxford OX1 2JD, England.
Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
Massachusetts Gen Hosp, AA Martinos Ctr, Boston, MA 02114 USA.
EM jkolasinski@me.com
NR 0
TC 0
Z9 0
U1 2
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD MAR
PY 2012
VL 83
IS 3
DI 10.1136/jnnp-2011-301993.181
PG 1
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 897AE
UT WOS:000300612200183
ER
PT J
AU Matilde, L
Eichler, F
Hornemann, T
Murphy, SM
Polke, J
Bull, K
Houlden, H
Reilly, MM
AF Matilde, L.
Eichler, F.
Hornemann, T.
Murphy, S. M.
Polke, J.
Bull, K.
Houlden, H.
Reilly, M. M.
TI HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY TYPE 1: CORRELATION OF
SEVERITY AND PLASMA ATYPICAL DEOXY-SPHYNGOID BASES
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-of-British-Neurologists
CY 2011
CL Gateshead, ENGLAND
SP Assoc British Neurologists
C1 UCL Inst Neurol, MRC Ctr Neuromuscular Dis, London, England.
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
Univ Zurich Hosp, Inst Clin Chem, Zurich, Switzerland.
EM m.laura@ion.ucl.ac.uk
RI Reilly, Mary/C-8482-2013; Houlden, Henry/C-1532-2008
OI Houlden, Henry/0000-0002-2866-7777
NR 0
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 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD MAR
PY 2012
VL 83
IS 3
DI 10.1136/jnnp-2011-301993.16
PG 1
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 897AE
UT WOS:000300612200017
ER
PT J
AU Salgado, C
Neff, T
Frazier, L
Vargas, SO
VanderVeen, D
AF Salgado, Cristian
Neff, Tobias
Frazier, Lindsay
Vargas, Sara O.
VanderVeen, Deborah
TI An Unusual Case of Congenital Primitive Neuroectodermal Tumor With
Ocular Metastasis
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Article
DE Ewing; PNET; medical oncology; tumors; brain
ID EWING SARCOMA FAMILY; MULTIPLE METASTASES
AB Primitive neuroectodermal tumor (PNET) is most common in the second decade of life. Congenital PNET is very rare. Ocular metastasis of PNET is likewise exceedingly rare; with only 5 previously published cases. We report an unusual congenital PNET of the face, which metastasized to subcutis, eyes, and brain. The primary tumor responded to chemotherapy (vincristine/doxorubicin/cyclophosphamide) with metachronous progression of ocular lesions. A therapeutic trial of intraocular bevacizumab showed no efficacy on intraocular lesions. Eventually the patient developed cerebral metastasis, and second line therapy with topotecan/cyclophosphamide was initiated. The tumor progressed and the patient died after acute herniation.
C1 [Neff, Tobias; Frazier, Lindsay] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA.
[Salgado, Cristian; VanderVeen, Deborah] Childrens Hosp Boston, Dept Ophthalmol, Boston, MA 02115 USA.
[Vargas, Sara O.] Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA.
[Neff, Tobias; Frazier, Lindsay] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Salgado, Cristian] Pontificia Univ Catolica, Santiago, Chile.
RP Neff, T (reprint author), Childrens Hosp Boston, Div Hematol Oncol, 300 Longwood Ave,Karp Res Bldg Rb08005E, Boston, MA 02115 USA.
EM Tobias.Neff@tch.harvard.edu
OI Neff, Tobias/0000-0002-0188-8393
NR 14
TC 2
Z9 3
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1077-4114
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD MAR
PY 2012
VL 34
IS 2
BP E69
EP E71
DI 10.1097/MPH.0b013e318221ca9b
PG 3
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 898HH
UT WOS:000300730900008
PM 22052164
ER
PT J
AU Robinson, A
Kardos, M
Kimball, AB
AF Robinson, Amanda
Kardos, Marisa
Kimball, Alexandra B.
TI Physician Global Assessment (PGA) and Psoriasis Area and Severity Index
(PASI): Why do both? A systematic analysis of randomized controlled
trials of biologic agents for moderate to severe plaque psoriasis
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
DE Physician Global Assessment; Psoriasis Area and Severity Index;
psoriasis severity assessment tools
ID PLACEBO-CONTROLLED TRIAL; INTERLEUKIN-12/23 MONOCLONAL-ANTIBODY;
OPEN-LABEL EXTENSION; TO-SEVERE PSORIASIS; PHASE-III TRIAL;
DOUBLE-BLIND; INFLIXIMAB INDUCTION; EFALIZUMAB THERAPY;
CLINICAL-RESPONSE; 50 MG
AB Background: Although there are many psoriasis assessment tools currently published, one of the unmet needs in psoriasis research remains consensus about the single best validated and reproducible assessment tool.
Objectives: In this systematic review we sought to determine the degree of correlation between two commonly used psoriasis assessment tools, the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA).
Methods: Randomized controlled systemic trials in moderate to severe psoriasis were reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We recorded and compared the percent of patients achieving both 75% reduction in PASI score (PASI 75) and PGA 0 or 1 (clear or almost clear) at 8 to 16 weeks, 17 to 24 weeks, and greater than 24 weeks of treatment with the investigational drug.
Results: Our literature review yielded 30 randomized controlled trials using biologic agents in moderate to severe psoriasis. We found that the two assessment tools correlate very tightly except at the lower bounds of therapeutic efficacy. The r(2) values for the correlation between PASI 75 and a score of clear or almost clear on the PGA were 0.9157 at 8 to 16 weeks and 0.892 at 17 to 24 weeks.
Limitations: Limitations of our study include the small number of randomized controlled trials publishing the percent of patients achieving 75% reduction in PASI score and a score of clear or almost clear on the PGA after 24 weeks of therapy. In addition, our results are not generalizable beyond the patients with moderate to severe plaque psoriasis.
Conclusion: The two assessment tools are substantially redundant and either alone is a sufficient tool for assessing psoriasis severity in patients with moderate to severe disease. Because the PASI is better validated and more detailed, it remains the score of choice for clinical trials, but the simpler PGA may be well suited for community-based outcomes projects. (J Am Acad Dermatol 2012;66:369-75.)
C1 [Robinson, Amanda; Kardos, Marisa; Kimball, Alexandra B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Kardos, Marisa] Tufts Univ, Sch Med, Medford, MA 02155 USA.
[Kimball, Alexandra B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Kimball, AB (reprint author), CURTIS, 50 Staniford St,Suite 240, Boston, MA 02114 USA.
EM harvardskinstudies@partners.org
FU National Psoriasis Foundation/USA
FX Funding sources: National Psoriasis Foundation/USA.
NR 41
TC 64
Z9 65
U1 1
U2 4
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 MAR
PY 2012
VL 66
IS 3
BP 369
EP 375
DI 10.1016/j.jaad.2011.01.022
PG 7
WC Dermatology
SC Dermatology
GA 901CJ
UT WOS:000300939000012
PM 22041254
ER
PT J
AU Murrell, DF
Daniel, BS
Joly, P
Borradori, L
Amagai, M
Hashimoto, T
Caux, F
Marinovic, B
Sinha, AA
Hertl, M
Bernard, P
Sirois, D
Cianchini, G
Fairley, JA
Jonkman, MF
Pandya, AG
Rubenstein, D
Zillikens, D
Payne, AS
Woodley, D
Zambruno, G
Aoki, V
Pincelli, C
Diaz, L
Hall, RP
Meurer, M
Mascaro, JM
Schmidt, E
Shimizu, H
Zone, J
Swerlick, R
Mimouni, D
Culton, D
Lipozencic, J
Bince, B
Grando, SA
Bystryn, JC
Werth, VP
AF Murrell, Dedee F.
Daniel, Benjamin S.
Joly, Pascal
Borradori, Luca
Amagai, Masayuki
Hashimoto, Takashi
Caux, Frederic
Marinovic, Branka
Sinha, Animesh A.
Hertl, Michael
Bernard, Philippe
Sirois, David
Cianchini, Giuseppe
Fairley, Janet A.
Jonkman, Marcel F.
Pandya, Amit G.
Rubenstein, David
Zillikens, Detlef
Payne, Aimee S.
Woodley, David
Zambruno, Giovanna
Aoki, Valeria
Pincelli, Carlo
Diaz, Luis
Hall, Russell P.
Meurer, Michael
Mascaro, Jose M., Jr.
Schmidt, Enno
Shimizu, Hiroshi
Zone, John
Swerlick, Robert
Mimouni, Daniel
Culton, Donna
Lipozencic, Jasna
Bince, Benjamin
Grando, Sergei A.
Bystryn, Jean-Claude
Werth, Victoria P.
TI Definitions and outcome measures for bullous pemphigoid: Recommendations
by an international panel of experts
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Review
DE bullous pemphigoid; consensus; definitions; outcome measures; severity
score
ID TOPICAL CORTICOSTEROIDS
AB Our scientific knowledge of bullous pemphigoid (BP) has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in BP. A major obstacle in sharing multicenter-based evidences for therapeutic efforts is the lack of generally accepted definitions for the clinical evaluation of patients with BP. Common terms and end points of BP are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. These recommendations from the International Pemphigoid Committee represent 2 years of collaborative efforts to attain mutually acceptable common definitions for BP and proposes a disease extent score, the BP Disease Area Index. These items should assist in the development of consistent reporting of outcomes in future BP reports and studies. (J Am Acad Dermatol 2012;66:479-85.)
C1 [Murrell, Dedee F.; Daniel, Benjamin S.] Univ New S Wales, St George Hosp, Dept Dermatol, Sydney, NSW, Australia.
[Joly, Pascal] Univ Rouen, Rouen Univ Hosp, Dermatol Clin, Dept Dermatol,INSERM,U905, F-76821 Mont St Aignan, France.
[Borradori, Luca] Univ Hosp Bern, Dept Dermatol, Bern, Switzerland.
[Amagai, Masayuki] Keio Univ, Sch Med, Tokyo, Japan.
[Hashimoto, Takashi] Kurume Univ, Sch Med, Kurume, Fukuoka, Japan.
[Caux, Frederic] Univ Paris 08, Dept Dermatol, Bobigny, France.
[Marinovic, Branka; Lipozencic, Jasna] Univ Zagreb, Hosp Ctr & Sch Med, Dept Dermatol & Venereol, Zagreb 41000, Croatia.
[Sinha, Animesh A.] SUNY Buffalo, Dept Dermatol, Buffalo, NY 14260 USA.
[Hertl, Michael] Univ Hosp, Dept Dermatol, Marburg, Germany.
[Sirois, David] NYU, Coll Dent, Dept Oral Med, New York, NY 10003 USA.
[Cianchini, Giuseppe] IRCCS, Inst Dermopat Immacolata, Immunodermatol Dept, Rome, Italy.
[Zambruno, Giovanna] IRCCS, Inst Dermopat Immacolata, Lab Mol & Cell Biol, Rome, Italy.
[Fairley, Janet A.] Univ Iowa, Dept Dermatol, Iowa City, IA USA.
[Fairley, Janet A.] Dept Vet Affairs Med Ctr, Iowa City, IA 52242 USA.
[Jonkman, Marcel F.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands.
[Rubenstein, David; Diaz, Luis; Culton, Donna] Univ N Carolina, Dept Dermatol, Chapel Hill, NC 27514 USA.
[Pandya, Amit G.] Univ Texas SW Med Ctr Dallas, Dallas, TX USA.
[Zillikens, Detlef; Schmidt, Enno] Univ Lubeck, Dept Dermatol, Lubeck, Germany.
[Woodley, David] Univ So Calif, Dept Dermatol, Keck Sch Med, Los Angeles, CA 90089 USA.
[Payne, Aimee S.; Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA.
[Aoki, Valeria] Univ Sao Paulo, Dept Dermatol, BR-05508 Sao Paulo, Brazil.
[Pincelli, Carlo] Univ Modena & Reggio Emilia, Inst Dermatol, Sch Biosci & Biotechnol, Modena, Italy.
[Hall, Russell P.] Duke Med Ctr, Div Dermatol, Durham, NC USA.
[Shimizu, Hiroshi] Hokkaido Univ, Grad Sch Med, Dept Dermatol, Sapporo, Hokkaido, Japan.
[Meurer, Michael] Tech Univ Dresden, Carl Gustav Carus Med Sch, Dresden, Germany.
[Mascaro, Jose M., Jr.] Univ Barcelona, Dept Dermatol, E-08007 Barcelona, Spain.
[Zone, John] Univ Utah, Dept Dermatol, Salt Lake City, UT 84112 USA.
[Bince, Benjamin] Jose R Reyes Mem Med Ctr, Dept Dermatol, Manila, Philippines.
[Swerlick, Robert] Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA.
[Bystryn, Jean-Claude] NYU, Med Ctr, New York, NY 10003 USA.
[Mimouni, Daniel] Rabin Med Ctr, Dept Dermatol, Petah Tiqwa, Israel.
[Bernard, Philippe] Robert Debre Univ Hosp, Dept Dermatol, Reims, France.
[Grando, Sergei A.] Univ Calif Irvine, Dept Biol Chem, Dept Dermatol, Ctr Canc, Irvine, CA 92717 USA.
[Grando, Sergei A.] Univ Calif Irvine, Res Inst, Inst Immunol, Irvine, CA USA.
[Werth, Victoria P.] Philadelphia Dept Vet Affairs Med Ctr, Philadelphia, PA USA.
RP Murrell, DF (reprint author), Univ New S Wales, St George Hosp, Dept Dermatol, Sydney, NSW, Australia.
EM d.murrell@unsw.edu.au
RI Cianchini, Giuseppe/I-8877-2012; Amagai, Masayuki/K-5325-2013; Schmidt,
Enno/C-4008-2009; Jonkman, Marcel/H-4647-2011; Pincelli,
Carlo/A-7288-2012; Aoki, Valeria/H-1415-2012;
OI Amagai, Masayuki/0000-0003-3314-7052; Schmidt, Enno/0000-0002-1206-8913;
Pincelli, Carlo/0000-0003-4416-2637; Marinovic,
Branka/0000-0001-8441-5016; Hashimoto, Takashi/0000-0002-0144-3255
FU International Pemphigus and Pemphigoid Foundation; National Institutes
of Health [K24-AR 02207]
FX The International Pemphigus and Pemphigoid Foundation generously
supported renting rooms at the American Academy of Dermatology and
audiovisual equipment; the European Society for Dermatological Research
and European Academy of Dermatology provided meeting rooms. This report
was supported in part by a grant from the National Institutes of Health
(K24-AR 02207) to Dr Werth.
NR 10
TC 59
Z9 62
U1 6
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 MAR
PY 2012
VL 66
IS 3
BP 479
EP 485
DI 10.1016/j.jaad.2011.06.032
PG 7
WC Dermatology
SC Dermatology
GA 901CJ
UT WOS:000300939000026
PM 22056920
ER
PT J
AU Levy, C
Hutt, E
Pointer, L
AF Levy, Cari
Hutt, Evelyn
Pointer, Lauren
TI Site of Death Among Veterans Living in Veterans Affairs Nursing Homes
SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION
LA English
DT Article
DE Site of death; nursing home; veterans; hospice; end-of-life
ID HOSPICE CARE; LIFE; END; MORTALITY; RESIDENTS; TURNOVER; SERVICES;
QUALITY; BENEFIT; INDEX
AB Objectives: To determine predictors of dying in VA nursing homes, community living centers (CLCs), compared with dying in a hospital.
Design: Retrospective cohort study.
Setting: VA CLCs.
Participants: Included were 7408 CLC decedents from FY2005 to FY2007.
Measurements: Outcome: Site of death obtained from VA Vital Statistics files. Predictors of Death Site: VA-MDS variables defining patient demographics, functional status, cognitive status, major diagnostic categories, and care planning documentation.
Analysis: Logistic regression was used to estimate the odds ratio of death in the CLC relative to the hospital for patient and facility characteristics.
Results: Among decedents, 87% died in the CLC and 13% in a hospital. More than half of all decedents were neither enrolled in hospice nor designated as having end-stage disease. The strongest predictor of site of death in a CLC relative to a hospital was being enrolled in hospice (OR = 20.94; 95% CI: 12.38, 35.44). A designation of end-stage disease increased the odds of death in a CLC by 3.9 times (95% CI: 2.78, 5.47) compared with death in a hospital. Advance directive rates in CLCs were high (73.4%); having any advance directive increased the odds of death in a CLC by 1.57 times (95% CI: 1.35, 1.82).
Conclusion: Recognition of end-stage disease and documentation of advance directives are powerful determinants of site of death for CLC residents. Receipt of hospice care in a CLC is a strong predictor of site of death in a CLC even in the absence of collaboration with community-based hospice and financial incentives to avoid hospitalization. Copyright (C) 2012 - American Medical Directors Association, Inc.
C1 [Levy, Cari; Hutt, Evelyn] Univ Colorado Denver, Div Hlth Care Policy & Res, Denver Vet Affairs Med Ctr, Denver, CO 80220 USA.
RP Levy, C (reprint author), Univ Colorado Denver, Div Hlth Care Policy & Res, Denver Vet Affairs Med Ctr, 1055 Clermont,Mailstop 151, Denver, CO 80220 USA.
EM cari.levy@va.gov
FU Veterans Affairs Career Development Award
FX This research was funded by a Veterans Affairs Career Development Award.
NR 26
TC 5
Z9 5
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-8610
J9 J AM MED DIR ASSOC
JI J. Am. Med. Dir. Assoc.
PD MAR
PY 2012
VL 13
IS 3
BP 199
EP 201
DI 10.1016/j.jamda.2011.08.004
PG 3
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 898IE
UT WOS:000300734700004
PM 21945536
ER
PT J
AU Akins, CW
AF Akins, Cary W.
TI The ethical dilemma of Thoracic Surgery recertification
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA.
RP Akins, CW (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Cox 648,55 Fruit St, Boston, MA 02114 USA.
EM cakins@partners.org
NR 2
TC 4
Z9 4
U1 0
U2 0
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 MAR
PY 2012
VL 143
IS 3
BP 521
EP 522
DI 10.1016/j.jtcvs.2011.12.015
PG 3
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 897BX
UT WOS:000300617300003
PM 22244565
ER
PT J
AU Yarbrough, WM
Mukherjee, R
Ikonomidis, JS
Zile, MR
Spinale, FG
AF Yarbrough, William M.
Mukherjee, Rupak
Ikonomidis, John S.
Zile, Michael R.
Spinale, Francis G.
TI Myocardial remodeling with aortic stenosis and after aortic valve
replacement: Mechanisms and future prognostic implications
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID LEFT-VENTRICULAR HYPERTROPHY; HYPERTENSIVE HEART-DISEASE; OVERLOADED
HUMAN HEART; C-REACTIVE PROTEIN; GROWTH-FACTOR-BETA; MATRIX
METALLOPROTEINASES; PRESSURE-OVERLOAD; DIASTOLIC DYSFUNCTION; TISSUE
INHIBITOR; NATRIURETIC PEPTIDE
AB Aortic valve stenosis is a common cause of left ventricular pressure overload, a pathologic process that elicits myocyte hypertrophy and alterations in extracellular matrix composition, both of which contribute to increases in left ventricular stiffness. However, clinical and animal studies suggest that increased myocardial extracellular matrix fibrillar collagen content occurs later in the time course of left ventricular pressure overload at a time coincident with severe abnormalities in diastolic function followed by the development of symptomatic heart failure. Aortic valve replacement remains the most effective treatment for elimination of chronic pressure overload secondary to aortic stenosis but has traditionally been recommended only after the onset of clinical symptoms. Long-termfollow-up of patients with symptomatic aortic stenosis after aortic valve replacement suggests that valve replacement may not result in complete reversal of the maladaptive changes that occur within the myocardial extracellular matrix secondary to the pressure overload state. To the contrary, residual left ventricular extracellular matrix abnormalities such as these are likely responsible for persistent abnormalities in diastolic function and increased morbidity and mortality after aortic valve replacement. Defining the mechanisms and pathways responsible for regulating the myocardial extracellular matrix during the natural history of aortic stenosis may provide a means by which to detect crucial structural milestones and thereby permit more precise identification of the development of maladaptive left ventricular remodeling. (J Thorac Cardiovasc Surg 2012;143:656-64)
C1 [Yarbrough, William M.; Mukherjee, Rupak; Ikonomidis, John S.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Dept Med, Charleston, SC 29425 USA.
[Zile, Michael R.] Med Univ S Carolina, Div Cardiol, Dept Med, Charleston, SC 29425 USA.
[Zile, Michael R.; Spinale, Francis G.] Ralph H Johnson Vet Assoc Med Ctr, Charleston, SC USA.
RP Spinale, FG (reprint author), Strom Thurmond Res Ctr, 114 Doughty St,Suite 625, Charleston, SC 29425 USA.
EM wilburnm@musc.edu
FU American Association for Thoracic Surgery; National Institutes of Health
[HL 57952]; Veterans' Affairs Health Administration
FX This work was supported by the Third Edward D. Churchill Research
Scholarship (American Association for Thoracic Surgery), a National
Institutes of Health Supplement award (HL 57952), and the Veterans'
Affairs Health Administration.
NR 58
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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 MAR
PY 2012
VL 143
IS 3
BP 656
EP 664
DI 10.1016/j.jtcvs.2011.04.044
PG 9
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 897BX
UT WOS:000300617300024
PM 21762938
ER
PT J
AU Tolpin, DA
Collard, CD
Lee, VV
Virani, SS
Allison, PM
Elayda, MA
Pan, W
AF Tolpin, Daniel A.
Collard, Charles D.
Lee, Vei-Vei
Virani, Salim S.
Allison, Paul M.
Elayda, MacArthur A.
Pan, Wei
TI Subclinical changes in serum creatinine and mortality after coronary
artery bypass grafting
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; GELATINASE-ASSOCIATED
LIPOCALIN; CARDIAC-SURGERY; CARDIOTHORACIC SURGERY; BIOMARKER; OUTCOMES;
IMPACT; STRATIFICATION; SEVERITY
AB Background: Changes in postoperative serum creatinine levels have been used to define acute renal injury in patients undergoing cardiac surgery with cardiopulmonary bypass. It remains unclear, however, whether subclinical increases in serum creatinine that do not meet current Acute Kidney Injury Network or RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria for acute renal injury are predictive of mortality after cardiac surgery.
Methods: Multivariate logistic regression was performed in a retrospective cohort of 3914 consecutive patients undergoing primary, isolated coronary artery bypass grafting with cardiopulmonary bypass to determine whether postoperative serum creatinine change independently predicts 30-day all-cause mortality in patients with normal renal function and with varying levels of preoperative renal insufficiency. To control further for selection bias, multivariate logistic regression was performed on a propensity-matched cohort (n = 2042) to determine whether subclinical increases in serum creatinine predict mortality.
Results: Negative change in serum creatinine was associated with reduced 30-day all-cause mortality. Even subclinical increases in serum creatinine were associated with increased mortality relative to patients with negative changes in serum creatinine (odds ratio, 3.93; 95% confidence interval, 1.68-9.22; P <.01). After propensity matching, subclinical increases in serum creatinine were still associated with increased mortality (odds ratio, 4.13; 95% confidence interval, 1.37-12.45; P = .01).
Conclusions: Subclinical increases in serum creatinine that do not meet acute renal injury criteria are independently associated with 30-day all-cause mortality in patients with normal renal function or preoperative renal insufficiency undergoing coronary artery bypass grafting. (J Thorac Cardiovasc Surg 2012;143:682-8)
C1 [Tolpin, Daniel A.; Collard, Charles D.; Pan, Wei] St Lukes Episcopal Hosp, Texas Heart Inst, Div Cardiovasc Anesthesiol, Houston, TX 77030 USA.
[Lee, Vei-Vei; Elayda, MacArthur A.] St Lukes Episcopal Hosp, Texas Heart Inst, Div Biostat & Epidemiol, Houston, TX 77030 USA.
[Tolpin, Daniel A.; Collard, Charles D.; Pan, Wei] Baylor Coll Med, Dept Anesthesiol, Houston, TX 77030 USA.
[Virani, Salim S.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA.
[Allison, Paul M.] St Lukes Episcopal Hosp, Dept Pathol, Chem Coagulat & Blood Donor Ctr, Houston, TX 77030 USA.
RP Pan, W (reprint author), St Lukes Episcopal Hosp, Texas Heart Inst, Div Cardiovasc Anesthesiol, 6720 Bertner Ave,Room 0520, Houston, TX 77030 USA.
EM wpan@heart.thi.tmc.edu
OI Virani, Salim/0000-0001-9541-6954
NR 23
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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 MAR
PY 2012
VL 143
IS 3
BP 682
EP +
DI 10.1016/j.jtcvs.2011.09.044
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 897BX
UT WOS:000300617300027
PM 22054657
ER
PT J
AU Prigerson, HG
AF Prigerson, Holly G.
TI Mind over menopausal symptoms in women with breast cancer
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID PREVALENCE; THERAPY
C1 Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA.
RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA.
EM Holly_Prigerson@dfci.harvard.edu
NR 8
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD MAR
PY 2012
VL 13
IS 3
BP 227
EP 229
DI 10.1016/S1470-2045(11)70381-3
PG 4
WC Oncology
SC Oncology
GA 900IO
UT WOS:000300880600023
PM 22340964
ER
PT J
AU Cheung, AM
Tile, L
Cardew, S
Pruthi, S
Robbins, J
Tomlinson, G
Kapral, MK
Khosla, S
Majumdar, S
Erlandson, M
Scher, J
Hu, HX
Demaras, A
Lickley, L
Bordeleau, L
Elser, C
Ingle, J
Richardson, H
Goss, PE
AF Cheung, Angela M.
Tile, Lianne
Cardew, Savannah
Pruthi, Sandhya
Robbins, John
Tomlinson, George
Kapral, Moira K.
Khosla, Sundeep
Majumdar, Sharmila
Erlandson, Marta
Scher, Judy
Hu, Hanxian
Demaras, Alice
Lickley, Lavina
Bordeleau, Louise
Elser, Christine
Ingle, James
Richardson, Harriet
Goss, Paul E.
TI Bone density and structure in healthy postmenopausal women treated with
exemestane for the primary prevention of breast cancer: a nested
substudy of the MAP.3 randomised controlled trial
SO LANCET ONCOLOGY
LA English
DT Article
ID X-RAY ABSORPTIOMETRY; MINERAL DENSITY; ADJUVANT TREATMENT; DISTAL
RADIUS; INTERGROUP EXEMESTANE; AROMATASE INHIBITORS; ATAC TRIAL;
TAMOXIFEN; ANASTROZOLE; OSTEOPOROSIS
AB Background Exemestane can prevent breast cancer in postmenopausal women. Because of potential widespread use, we examined the safety of exemestane on bone health.
Methods In this nested safety substudy of the MAP. 3 trial (a randomised, placebo-controlled, double-blind trial of exemestane 25 mg a day for the primary prevention of breast cancer), we included postmenopausal women from five centres who were eligible to participate in MAP. 3, not osteoporotic, not receiving drugs for bone-related disorders, with baseline lumbar spine, total hip, and femoral neck T-scores above -2.0. The primary endpoint was percent change from baseline to 2 years in total volumetric bone mineral density (BMD) at the distal radius by high-resolution peripheral quantitative CT. The primary analysis was per protocol using a non-inferiority margin. This analysis was done earlier than originally planned because of the impending announcement of MAP. 3 results and subsequent unmasking of patients to treatment assignment. This study is registered with ClinicalTrials.gov, number NCT01144468, and has been extended to 5 years of unmasked follow-up.
Findings 351 women (176 given exemestane, 175 given placebo; median age 61.3 years [IQR 59.2-64.9]) met our inclusion criteria and completed baseline assessment. At the time of clinical cutoff, 242 women had completed 2-year follow-up (124 given exemestane, 118 given placebo). From baseline to 2 years, the mean percent change in total volumetric BMD at the distal radius was -6.1% (95% CI -7.0 to -5.2) in the exemestane group and -1.8% (-2.4 to -1.2) in the placebo group (difference -4.3%, 95% CI -5.3 to -3.2; p<0.0001). The lower limit of the 95% CI was lower than our non-inferiority margin of negative 4% (one-sided test for non-inferiority p=0.70), meaning the hypothesis that exemestane was inferior could not be rejected. At the distal tibia, the mean percent change in total volumetric BMD from baseline to 2 years was -5.0% (95% CI -5.5 to -4.4) in the exemestane group and -1.3% (-1.7 to -1.0) in the placebo group (difference -3.7%, 95% CI -4.3 to -3.0; p<0.0001). The mean percent change in cortical thickness was -7.9% (SD 7.3) in the exemestane group and -1.1% (5.7) in the placebo group at the distal radius (difference -6.8%, 95% CI -8.5 to -5.0; p<0.0001) and -7.6% (SD 5.9) in the exemestane group and -0.7% (4.9) in the placebo group at the distal tibia (difference -6.9%, -8.4 to -5.5; p<0.0001). Decline in areal BMD, as measured by dual-energy x-ray absorptiometry, in the exemestane group compared with the placebo group occurred at the lumbar spine (-2.4% [95% CI -3.1 to -1.7] exemestane vs -0.5% [-1.1 to 0.2] placebo; difference -1.9%, 95% CI -2.9 to -1.0; p<0.0001), total hip (-1.8% [-2.3 to -1.2] exemestane vs -0.6% [-1.1 to -0.1] placebo; difference -1.2%, -1.9 to -0.4; p=0.004), and femoral neck (-2.4% [-3.2 to -1.7] exemestane vs -0.8% [-1.5 to 0.1] placebo; difference -1.6%, -2.7 to -0.6; p=0.002).
Interpretation 2 years of treatment with exemestane worsens age-related bone loss in postmenopausal women despite calcium and vitamin D supplementation. Women considering exemestane for the primary prevention of breast cancer should weigh their individual risks and benefits. For women taking exemestane, regular bone monitoring plus adequate calcium and vitamin D supplementation are important. To assess the effect of our findings on fracture risk, long-term follow-up is needed.
C1 [Cheung, Angela M.; Tile, Lianne; Cardew, Savannah; Tomlinson, George; Kapral, Moira K.; Erlandson, Marta; Scher, Judy; Hu, Hanxian; Demaras, Alice] Univ Hlth Network, Toronto, ON M5G 2C4, Canada.
[Elser, Christine] Univ Toronto, Mt Sinai Hosp, Marvelle Koffl er Breast Ctr, Toronto, ON M5G 1X5, Canada.
[Lickley, Lavina] Univ Toronto, Womens Coll Hosp, Toronto, ON, Canada.
[Khosla, Sundeep] Mayo Clin, Endocrine Res Unit, Rochester, MN USA.
[Majumdar, Sharmila] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA.
[Robbins, John] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA.
[Bordeleau, Louise] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON, Canada.
[Richardson, Harriet] Queens Univ, Canc Res Inst, Kingston, ON, Canada.
[Goss, Paul E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Cheung, AM (reprint author), Univ Hlth Network, 200 Elizabeth St,7 Eaton N,Room 221, Toronto, ON M5G 2C4, Canada.
EM angela.cheung@uhn.ca
RI Tomlinson, George/L-5432-2016
OI Khosla, Sundeep/0000-0002-2936-4372; Tomlinson,
George/0000-0002-9328-6399
FU Canadian Breast Cancer Research Alliance (Canadian Institutes of Health
Research/Canadian Cancer Society); Canadian Breast Cancer Research
Alliance, Canadian Institutes of Health Research [018518]; Canadian
Breast Cancer Research Alliance, Canadian Cancer Society [018518];
Canadian Cancer Society; Pfizer; Canadian Institutes of Health
Research/Institute of Gender and Health; Lillian Love Chair in Women's
Health at the University of Toronto/University Health Network; Avon
Foundation
FX Canadian Breast Cancer Research Alliance (Canadian Institutes of Health
Research/Canadian Cancer Society).; We thank the women who volunteered
their time to participate in this substudy; Cancer Care Ontario; David
McCready and Ruth Heisey for their assistance in identifying potential
participants; the clinical coordinators (Irene Ho, Suzanne Cohen,
Alexandra Tse, Jean Jensen, Denise Macias, Olivera Jugovic, Ilda
Carvalhana, Nicole Heffernan); those who contributed to data collection,
cleaning, analysis, and quality control (Queenie Wong, Gail Jefferson,
Farrah Ahmed, Diana Yau, and Karen Stratton); the central office staff
of the NCIC CTG who contributed to the conduct of the MAP. 3 trial as
well as this substudy; Jamieson Laboratories for their provision of
calcium and vitamin D supplements; and Pfizer Pharmaceuticals for their
provision of exemestane and placebo. This study (NCIC CTG MAP.3BSS) was
supported by the Canadian Breast Cancer Research Alliance, a joint
initiative between the Canadian Institutes of Health Research and the
Canadian Cancer Society [grant number 018518], and is a substudy of the
NCIC CTG MAP.3 study. The main study was supported the Canadian Cancer
Society and Pfizer. AMC is supported in part by a Canadian Institutes of
Health Research/Institute of Gender and Health Senior Investigator
Award, and the Lillian Love Chair in Women's Health at the University of
Toronto/University Health Network. PEG is supported in part by the Avon
Foundation.
NR 44
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U1 0
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD MAR
PY 2012
VL 13
IS 3
BP 275
EP 284
DI 10.1016/S1470-2045(11)70389-8
PG 10
WC Oncology
SC Oncology
GA 900IO
UT WOS:000300880600035
PM 22318095
ER
PT J
AU Lee, BL
Liedke, PER
Barrios, CH
Simon, SD
Finkelstein, DM
Goss, PE
AF Lee, Brittany L.
Liedke, Pedro E. R.
Barrios, Carlos H.
Simon, Sergio D.
Finkelstein, Dianne M.
Goss, Paul E.
TI Breast cancer in Brazil: present status and future goals
SO LANCET ONCOLOGY
LA English
DT Review
ID MIDDLE-INCOME COUNTRIES; GUIDELINE IMPLEMENTATION; COST-EFFECTIVENESS;
CHRONIC DISEASES; LATIN-AMERICA; HEALTH-CARE; RADIOTHERAPY; MANAGEMENT;
DIAGNOSIS; SURVIVAL
AB Breast cancer is the most common cancer in women worldwide and 70% of breast cancer deaths occur in women from low-income and middle-income countries. Latin America has about 115 000 new cases of disease every year, with about 50 000 arising in Brazil. We examined the present status of breast cancer in Brazil as an example of the health effects of geographical, ethnic, and socioeconomic diversities on delivery of care. Our goal was to identify deficiencies that could be responsible for disparities in survival from breast cancer. We searched the English and Portuguese published work and reviewed national databases and Brazilian publications. Although the availability of publications specific to Brazil is low in general, we identified several factors that could account for disparities: delays in diagnosis due to low cancer awareness and implementation of mammography screening, unknown quality of surgery, and restricted access to radiotherapy and modern systemic therapies.
C1 [Lee, Brittany L.; Liedke, Pedro E. R.; Finkelstein, Dianne M.; Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Int Breast Canc Res Program, Boston, MA 02114 USA.
[Lee, Brittany L.; Liedke, Pedro E. R.; Finkelstein, Dianne M.; Goss, Paul E.] Harvard Univ, Sch Med, Boston, MA USA.
[Barrios, Carlos H.] Pontificia Univ Rio Grande Sul PUCRS, Sch Med, Ctr Pesquisa Oncol, Porto Alegre, RS, Brazil.
[Liedke, Pedro E. R.; Barrios, Carlos H.; Simon, Sergio D.] Grp Brasileiro Estudos Canc Mama GBECAM, Sao Paulo, Brazil.
[Barrios, Carlos H.] Grp Latino Amer Invest Clin Oncol GLICO, Porto Alegre, RS, Brazil.
[Simon, Sergio D.] Univ Fed Sao Paulo UNIFESP, Sao Paulo, Brazil.
RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Int Breast Canc Res Program, 55 Fruit St,Lawrence House,LRH 302, Boston, MA 02114 USA.
EM pgoss@partners.org
RI Barrios, Carlos/G-8525-2015
FU Avon Foundation New York, NY, USA
FX PEG, DMF, and PERL are supported by The Avon Foundation New York, NY,
USA, which had no role in the planning or writing of this manuscript.
BLL would like to thank the Department of Medicine and Division of
Global Health for supporting her clinical rotation in Brazil, and the
Pontificia Universidade do Rio Grande do Sul.
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD MAR
PY 2012
VL 13
IS 3
BP E95
EP E102
PG 8
WC Oncology
SC Oncology
GA 900IO
UT WOS:000300880600010
PM 22381937
ER
PT J
AU Lee, SH
DeCandia, TR
Ripke, S
Yang, J
Sullivan, PF
Goddard, ME
Keller, MC
Visscher, PM
Wray, NR
AF Lee, S. Hong
DeCandia, Teresa R.
Ripke, Stephan
Yang, Jian
Sullivan, Patrick F.
Goddard, Michael E.
Keller, Matthew C.
Visscher, Peter M.
Wray, Naomi R.
CA Schizophrenia Psychiat Genome-Wide
Int Schizophrenia Consortium ISC
Mol Genetics Schizophrenia
TI Estimating the proportion of variation in susceptibility to
schizophrenia captured by common SNPs
SO NATURE GENETICS
LA English
DT Article
ID MULTIPLE RARE ALLELES; COMPLEX TRAIT; HUMAN HEIGHT; DISEASE;
ASSOCIATION; VARIANTS; TWIN
AB Schizophrenia is a complex disorder caused by both genetic and environmental factors. Using 9,087 affected individuals, 12,171 controls and 915,354 imputed SNPs from the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC-SCZ), we estimate that 23% (s.e. = 1%) of variation in liability to schizophrenia is captured by SNPs. We show that a substantial proportion of this variation must be the result of common causal variants, that the variance explained by each chromosome is linearly related to its length (r = 0.89, P = 2.6 x 10(-8)), that the genetic basis of schizophrenia is the same in males and females, and that a disproportionate proportion of variation is attributable to a set of 2,725 genes expressed in the central nervous system (CNS; P = 7.6 x 10(-8)). These results are consistent with a polygenic genetic architecture and imply more individual SNP associations will be detected for this disease as sample size increases.
C1 [Lee, S. Hong; Visscher, Peter M.; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
[Lee, S. Hong; Yang, Jian; Visscher, Peter M.; Wray, Naomi R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[DeCandia, Teresa R.; Keller, Matthew C.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.
[DeCandia, Teresa R.; Keller, Matthew C.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA.
[Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Ripke, Stephan] MIT, Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA.
[Ripke, Stephan] Harvard Univ, Cambridge, MA 02138 USA.
[Yang, Jian; Visscher, Peter M.] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld 4102, Australia.
[Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Goddard, Michael E.] Univ Melbourne, Dept Agr & Food Syst, Melbourne, Vic, Australia.
[Goddard, Michael E.] Dept Primary Ind, Biosci Res Div, Melbourne, Vic, Australia.
RP Wray, NR (reprint author), Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
EM naomi.wray@uq.edu.au
RI Lee, Sang Hong/A-2569-2011; Hansen, Thomas/O-5965-2014; Wray,
Naomi/C-8639-2015; Yang, Jian/A-5852-2010;
OI Lee, Sang Hong/0000-0001-9701-2718; Hansen, Thomas/0000-0001-6703-7762;
Wray, Naomi/0000-0001-7421-3357; Yang, Jian/0000-0003-2001-2474; KELLER,
MATTHEW/0000-0002-6075-9882; Goddard, Michael/0000-0001-9917-7946;
Visscher, Peter/0000-0002-2143-8760
FU Australian National Health and Medical Research Council [389892, 442915,
496688, 613672, 613601]; Australian Research Council [DP0770096,
DP1093502, FT0991360]; US National Institute of Mental Health
[MH085812]; Netherlands Scientific Organization (NWO) [480-05-003]
FX We thank S. D. Gordon for technical assistance. We acknowledge funding
from the Australian National Health and Medical Research Council
(389892, 442915, 496688, 613672 and 613601), the Australian Research
Council (DP0770096, DP1093502 and FT0991360) and the US National
Institute of Mental Health (MH085812). This research utilized the
Cluster Computer, which is funded by the Netherlands Scientific
Organization (NWO; 480-05-003). Acknowledgments for PGC-SCZ are listed
in the Supplementary Note.
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD MAR
PY 2012
VL 44
IS 3
BP 247
EP U35
DI 10.1038/ng.1108
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 899VC
UT WOS:000300843600006
PM 22344220
ER
PT J
AU Ghoussaini, M
Fletcher, O
Michailidou, K
Turnbull, C
Schmidt, MK
Dicks, E
Dennis, J
Wang, Q
Humphreys, MK
Luccarini, C
Baynes, C
Conroy, D
Maranian, M
Ahmed, S
Driver, K
Johnson, N
Orr, N
Silva, ID
Waisfisz, Q
Meijers-Heijboer, H
Uitterlinden, AG
Rivadeneira, F
Hall, P
Czene, K
Irwanto, A
Liu, JJ
Nevanlinna, H
Aittomaki, K
Blomqvist, C
Meindl, A
Schmutzler, RK
Muller-Myhsok, B
Lichtner, P
Chang-Claude, J
Hein, R
Nickels, S
Flesch-Janys, D
Tsimiklis, H
Makalic, E
Schmidt, D
Bui, M
Hopper, JL
Apicella, C
Park, DJ
Southey, M
Hunter, DJ
Chanock, SJ
Broeks, A
Verhoef, S
Hogervorst, FBL
Fasching, PA
Lux, MP
Beckmann, MW
Ekici, AB
Sawyer, E
Tomlinson, I
Kerin, M
Marme, F
Schneeweiss, A
Sohn, C
Burwinkel, B
Guenel, P
Truong, T
Cordina-Duverger, E
Menegaux, F
Bojesen, SE
Nordestgaard, BG
Nielsen, SF
Flyger, H
Milne, RL
Alonso, MR
Gonzalez-Neira, A
Benitez, J
Anton-Culver, H
Ziogas, A
Bernstein, L
Dur, CC
Brenner, H
Muller, H
Arndt, V
Stegmaier, C
Justenhoven, C
Brauch, H
Bruning, T
Wang-Gohrke, S
Eilber, U
Dork, T
Schurmann, P
Bremer, M
Hillemanns, P
Bogdanova, NV
Antonenkova, NN
Rogov, YI
Karstens, JH
Bermisheva, M
Prokofieva, D
Khusnutdinova, E
Lindblom, A
Margolin, S
Mannermaa, A
Kataja, V
Kosma, VM
Hartikainen, JM
Lambrechts, D
Yesilyurt, BT
Floris, G
Leunen, K
Manoukian, S
Bonanni, B
Fortuzzi, S
Peterlongo, P
Couch, FJ
Wang, XS
Stevens, K
Lee, A
Giles, GG
Baglietto, L
Severi, G
McLean, C
Alnaes, GG
Kristensen, V
Borrensen-Dale, AL
John, EM
Miron, A
Winqvist, R
Pylkas, K
Jukkola-Vuorinen, A
Kauppila, S
Andrulis, IL
Glendon, G
Mulligan, AM
Devilee, P
van Asperen, CJ
Tollenaar, RAEM
Seynaeve, C
Figueroa, JD
Garcia-Closas, M
Brinton, L
Lissowska, J
Hooning, MJ
Hollestelle, A
Oldenburg, RA
van den Ouweland, AMW
Cox, A
Reed, MWR
Shah, M
Jakubowska, A
Lubinski, J
Jaworska, K
Durda, K
Jones, M
Schoemaker, M
Ashworth, A
Swerdlow, A
Beesley, J
Chen, XQ
Muir, KR
Lophatananon, A
Rattanamongkongul, S
Chaiwerawattana, A
Kang, D
Yoo, KY
Noh, DY
Shen, CY
Yu, JC
Wu, PE
Hsiung, CN
Perkins, A
Swann, R
Velentzis, L
Eccles, DM
Tapper, WJ
Gerty, SM
Graham, NJ
Ponder, BAJ
Chenevix-Trench, G
Pharoah, PDP
Lathrop, M
Dunning, AM
Rahman, N
Peto, J
Easton, DF
AF Ghoussaini, Maya
Fletcher, Olivia
Michailidou, Kyriaki
Turnbull, Clare
Schmidt, Marjanka K.
Dicks, Ed
Dennis, Joe
Wang, Qin
Humphreys, Manjeet K.
Luccarini, Craig
Baynes, Caroline
Conroy, Don
Maranian, Melanie
Ahmed, Shahana
Driver, Kristy
Johnson, Nichola
Orr, Nicholas
Silva, Isabel dos Santos
Waisfisz, Quinten
Meijers-Heijboer, Hanne
Uitterlinden, Andre G.
Rivadeneira, Fernando
Hall, Per
Czene, Kamila
Irwanto, Astrid
Liu, Jianjun
Nevanlinna, Heli
Aittomaki, Kristiina
Blomqvist, Carl
Meindl, Alfons
Schmutzler, Rita K.
Mueller-Myhsok, Bertram
Lichtner, Peter
Chang-Claude, Jenny
Hein, Rebecca
Nickels, Stefan
Flesch-Janys, Dieter
Tsimiklis, Helen
Makalic, Enes
Schmidt, Daniel
Bui, Minh
Hopper, John L.
Apicella, Carmel
Park, Daniel J.
Southey, Melissa
Hunter, David J.
Chanock, Stephen J.
Broeks, Annegien
Verhoef, Senno
Hogervorst, Frans B. L.
Fasching, Peter A.
Lux, Michael P.
Beckmann, Matthias W.
Ekici, Arif B.
Sawyer, Elinor
Tomlinson, Ian
Kerin, Michael
Marme, Frederik
Schneeweiss, Andreas
Sohn, Christof
Burwinkel, Barbara
Guenel, Pascal
Truong, Therese
Cordina-Duverger, Emilie
Menegaux, Florence
Bojesen, Stig E.
Nordestgaard, Borge G.
Nielsen, Sune F.
Flyger, Henrik
Milne, Roger L.
Rosario Alonso, M.
Gonzalez-Neira, Anna
Benitez, Javier
Anton-Culver, Hoda
Ziogas, Argyrios
Bernstein, Leslie
Dur, Christina Clarke
Brenner, Hermann
Mueller, Heiko
Arndt, Volker
Stegmaier, Christa
Justenhoven, Christina
Brauch, Hiltrud
Bruening, Thomas
Wang-Gohrke, Shan
Eilber, Ursula
Doerk, Thilo
Schuermann, Peter
Bremer, Michael
Hillemanns, Peter
Bogdanova, Natalia V.
Antonenkova, Natalia N.
Rogov, Yuri I.
Karstens, Johann H.
Bermisheva, Marina
Prokofieva, Darya
Khusnutdinova, Elza
Lindblom, Annika
Margolin, Sara
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Lambrechts, Diether
Yesilyurt, Betul T.
Floris, Giuseppe
Leunen, Karin
Manoukian, Siranoush
Bonanni, Bernardo
Fortuzzi, Stefano
Peterlongo, Paolo
Couch, Fergus J.
Wang, Xianshu
Stevens, Kristen
Lee, Adam
Giles, Graham G.
Baglietto, Laura
Severi, Gianluca
McLean, Catriona
Alnaes, Grethe Grenaker
Kristensen, Vessela
Borrensen-Dale, Anne-Lise
John, Esther M.
Miron, Alexander
Winqvist, Robert
Pylkas, Katri
Jukkola-Vuorinen, Arja
Kauppila, Saila
Andrulis, Irene L.
Glendon, Gord
Mulligan, Anna Marie
Devilee, Peter
van Asperen, Christie J.
Tollenaar, Rob A. E. M.
Seynaeve, Caroline
Figueroa, Jonine D.
Garcia-Closas, Montserrat
Brinton, Louise
Lissowska, Jolanta
Hooning, Maartje J.
Hollestelle, Antoinette
Oldenburg, Rogier A.
van den Ouweland, Ans M. W.
Cox, Angela
Reed, Malcolm W. R.
Shah, Mitul
Jakubowska, Ania
Lubinski, Jan
Jaworska, Katarzyna
Durda, Katarzyna
Jones, Michael
Schoemaker, Minouk
Ashworth, Alan
Swerdlow, Anthony
Beesley, Jonathan
Chen, Xiaoqing
Muir, Kenneth R.
Lophatananon, Artitaya
Rattanamongkongul, Suthee
Chaiwerawattana, Arkom
Kang, Daehee
Yoo, Keun-Young
Noh, Dong-Young
Shen, Chen-Yang
Yu, Jyh-Cherng
Wu, Pei-Ei
Hsiung, Chia-Ni
Perkins, Annie
Swann, Ruth
Velentzis, Louiza
Eccles, Diana M.
Tapper, Will J.
Gerty, Susan M.
Graham, Nikki J.
Ponder, Bruce A. J.
Chenevix-Trench, Georgia
Pharoah, Paul D. P.
Lathrop, Mark
Dunning, Alison M.
Rahman, Nazneen
Peto, Julian
Easton, Douglas F.
CA Netherlands Collaborative Grp Here
FBCS
Gene Environm Interaction Breast C
kConFab Investigators
Australian Ovarian Canc Study Grp
TI Genome-wide association analysis identifies three new breast cancer
susceptibility loci
SO NATURE GENETICS
LA English
DT Article
ID HORMONE-RELATED PROTEIN; DEVELOPMENTAL REGULATORY MOLECULE;
ULNAR-MAMMARY SYNDROME; PARATHYROID-HORMONE; NEGATIVE-FEEDBACK; COMMON
VARIANTS; CONFER SUSCEPTIBILITY; GENE-EXPRESSION; CELL CARCINOMA;
RETINOIC ACID
AB Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for similar to 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in similar to 70,000 cases and similar to 68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 x 10(-35)), 12q24 (rs1292011; P = 4.3 x 10(-19)) and 21q21 (rs2823093; P = 1.1 x 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.
C1 [Ghoussaini, Maya; Dicks, Ed; Luccarini, Craig; Baynes, Caroline; Conroy, Don; Maranian, Melanie; Ahmed, Shahana; Driver, Kristy; Shah, Mitul; Pharoah, Paul D. P.; Dunning, Alison M.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
[Fletcher, Olivia; Johnson, Nichola; Orr, Nicholas; Ashworth, Alan] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Michailidou, Kyriaki; Dennis, Joe; Wang, Qin; Humphreys, Manjeet K.; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
[Turnbull, Clare; Garcia-Closas, Montserrat; Rahman, Nazneen; FBCS] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England.
[Schmidt, Marjanka K.; Broeks, Annegien] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Expt Therapy, Amsterdam, Netherlands.
[Schmidt, Marjanka K.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands.
[Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Dept, London WC1, England.
[Waisfisz, Quinten; Meijers-Heijboer, Hanne] Vrije Univ Amsterdam Med Ctr, Sect Oncogenet, Dept Clin Genet, Amsterdam, Netherlands.
[Uitterlinden, Andre G.; Rivadeneira, Fernando] Erasmus MC, Dept Internal Med & Epidemiol, Rotterdam, Netherlands.
[Hall, Per; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Irwanto, Astrid; Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland.
[Irwanto, Astrid; Nevanlinna, Heli; Aittomaki, Kristiina; Blomqvist, Carl] Univ Helsinki, Cent Hosp, Helsinki, Finland.
[Liu, Jianjun] Genome Inst Singapore, Human Genet Div, Singapore, Singapore.
[Aittomaki, Kristiina] Univ Helsinki, Dept Clin Genet, Helsinki, Finland.
[Blomqvist, Carl] Univ Helsinki, Dept Oncol, Helsinki, Finland.
[Meindl, Alfons] Tech Univ Munich, Div Gynaecol Tumor Genet, Clin Gynaecol & Obstet, Munich, Germany.
[Schmutzler, Rita K.] Univ Cologne, Dept Obstet & Gynaecol, Div Mol Gynaecooncol, D-50931 Cologne, Germany.
[Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Lichtner, Peter] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Chang-Claude, Jenny; Hein, Rebecca; Nickels, Stefan; Eilber, Ursula] Deutsch Krebsforschungszentrum, Div Canc Epidemiol, D-6900 Heidelberg, Germany.
[Hein, Rebecca] Univ Cologne, Dept Child & Adolescent Psychiat & Psychotherapy, Primar Med Versorgung PMV Res Grp, D-50931 Cologne, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, Hamburg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany.
[Tsimiklis, Helen; Park, Daniel J.; Southey, Melissa] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia.
[Makalic, Enes; Schmidt, Daniel; Bui, Minh; Hopper, John L.; Apicella, Carmel; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Chanock, Stephen J.; Figueroa, Jonine D.; Brinton, Louise] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Verhoef, Senno] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, Dept Clin Genet, Amsterdam, Netherlands.
[Hogervorst, Frans B. L.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, Dept Mol Pathol, Amsterdam, Netherlands.
[Fasching, Peter A.; Lux, Michael P.; Beckmann, Matthias W.] Univ Hosp Erlangen, Univ Breast Ctr, Dept Gynecol & Obstet, Erlangen, Germany.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany.
[Sawyer, Elinor] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Div Canc Studies, Natl Inst Hlth Res NIHR Comprehens Biomed Res Ctr, London, England.
[Sawyer, Elinor] Kings Coll London, Div Canc Studies, London WC2R 2LS, England.
[Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England.
[Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Kerin, Michael] Univ Hosp Galway, Inst Clin Sci, Galway, Ireland.
[Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
[Marme, Frederik; Schneeweiss, Andreas] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany.
[Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Unit, Heidelberg, Germany.
[Guenel, Pascal; Truong, Therese; Cordina-Duverger, Emilie; Menegaux, Florence] Ctr Rech Epidemiol & Populat Hlth CESP, INSERM, U1018, Villejuif, France.
[Guenel, Pascal; Truong, Therese; Cordina-Duverger, Emilie; Menegaux, Florence] Univ Paris 11, Unite Mixte Rech Sante UMRS 1018, Villejuif, France.
[Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark.
[Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark.
[Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Copenhagen, Denmark.
[Milne, Roger L.] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Genet & Mol Epidemiol Grp, Madrid, Spain.
[Rosario Alonso, M.; Gonzalez-Neira, Anna] CNIO, Human Canc Genet Programme, Human Genotyping Unit, Madrid, Spain.
[Benitez, Javier] CNIO, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Bernstein, Leslie] City Hope Canc Ctr, Duarte, CA USA.
[Dur, Christina Clarke; John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Brenner, Hermann; Mueller, Heiko; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany.
[Justenhoven, Christina; Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany.
[Justenhoven, Christina; Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
[Bruening, Thomas] German Social Accid Insurance IPA, Inst Prevent & Occupat Med, Bochum, Germany.
DKFZ, Heidelberg, Germany.
[Gene Environm Interaction Breast C] Johanniter Krankenhaus, Evangel Kliniken Bonn, Dept Internal Med, Bonn, Germany.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany.
[Doerk, Thilo; Schuermann, Peter; Bremer, Michael; Hillemanns, Peter] Hannover Med Sch, Dept Obstet & Gynaecol, D-3000 Hannover, Germany.
[Bogdanova, Natalia V.; Karstens, Johann H.] Hannover Med Sch, Dept Radiat Oncol, D-3000 Hannover, Germany.
[Antonenkova, Natalia N.; Rogov, Yuri I.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus.
[Bermisheva, Marina; Prokofieva, Darya; Khusnutdinova, Elza] Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, Ufa 450001, Russia.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Inst Clin Med, Sch Med, Dept Pathol & Forens Med, Kuopio, Finland.
[Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Lee, Adam] Univ Eastern Finland, Bioctr Kuopio, Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Dept Clin Pathol, SF-70210 Kuopio, Finland.
[Kataja, Vesa] Univ Eastern Finland, Inst Clin Med, Sch Med, Dept Oncol, Kuopio, Finland.
[Kataja, Vesa] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland.
[Lambrechts, Diether; Yesilyurt, Betul T.] VIB, VRC, Louvain, Belgium.
[Floris, Giuseppe; Leunen, Karin] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium.
[Manoukian, Siranoush] Ist Nazl Tumori, Unit Med Genet, Dept Prevent & Predict Med, Fdn Ist Ricovero & Cura Carattere Sci IRCCS, I-20133 Milan, Italy.
[Bonanni, Bernardo] IEO, Div Canc Prevent & Genet, Milan, Italy.
[Fortuzzi, Stefano; Peterlongo, Paolo] Ist FIRC Fdn Italiana Ric Canc Oncol Mol IFOM, Milan, Italy.
[Peterlongo, Paolo] Fdn IRCCS INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, Milan, Italy.
[Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Couch, Fergus J.; Stevens, Kristen] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Lee, Adam] Mayo Clin, Dept Pharmacol, Rochester, MN USA.
[Giles, Graham G.; Baglietto, Laura; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[McLean, Catriona] Alfred Hosp, Dept Anat Pathol, Melbourne, Vic, Australia.
[Alnaes, Grethe Grenaker; Kristensen, Vessela; Borrensen-Dale, Anne-Lise] Radiumhosp, Dept Genet, Inst Canc Res, Oslo Univ Hosp, Oslo, Norway.
[Kristensen, Vessela; Borrensen-Dale, Anne-Lise] Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway.
[John, Esther M.] Stanford Univ, Dept Hlth Res Policy, Div Epidemiol, Sch Med, Stanford, CA 94305 USA.
[Miron, Alexander] Dana Farber Canc Ctr, Boston, MA USA.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Oulu Univ Hosp, Dept Clin Genet, Lab Canc Genet, Oulu, Finland.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Oulu Univ Hosp, Bioctr Oulu, Oulu, Finland.
[Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland.
[Kauppila, Saila] Univ Oulu, Dept Pathol, Oulu Univ Hosp, Oulu, Finland.
[Andrulis, Irene L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Glendon, Gord] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada.
[Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Dept Lab Med, Toronto, ON M5B 1W8, Canada.
[Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands.
[van Asperen, Christie J.] Leiden Univ, Dept Clin Genet, Med Ctr, Leiden, Netherlands.
[Tollenaar, Rob A. E. M.] Leiden Univ, Dept Surg, Med Ctr, Leiden, Netherlands.
[Seynaeve, Caroline] Erasmus MC Daniel den Hoed Canc Ctr, Rotterdam Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands.
[Garcia-Closas, Montserrat; Jones, Michael; Schoemaker, Minouk; Swerdlow, Anthony] Inst Canc Res, Epidemiol Sect, Sutton, Surrey, England.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Hooning, Maartje J.] Erasmus Univ, Dept Med Oncol, Family Canc Clin, Med Ctr, Rotterdam, Netherlands.
[Hollestelle, Antoinette] Erasmus Univ, Dept Med Oncol, Josephine Nefkens Inst, Med Ctr, Rotterdam, Netherlands.
[Oldenburg, Rogier A.; van den Ouweland, Ans M. W.] Erasmus Univ, Dept Clin Genet, Family Canc Clin, Med Ctr, Rotterdam, Netherlands.
[Cox, Angela] Univ Sheffield, Dept Oncol, Inst Canc Studies, Sheffield, S Yorkshire, England.
[Reed, Malcolm W. R.] Univ Sheffield, Acad Unit Surg Oncol, Dept Oncol, Sheffield, S Yorkshire, England.
[Jakubowska, Ania; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland.
[Beesley, Jonathan; Chen, Xiaoqing; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Muir, Kenneth R.; Lophatananon, Artitaya] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
[Rattanamongkongul, Suthee] Srinakharainwirot Univ, Dept Prevent Med, Ongkharak, Thailand.
[Chaiwerawattana, Arkom] Minist Publ Hlth, Natl Canc Inst Thailand, Dept Acad Support, Bangkok, Thailand.
[Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Shen, Chen-Yang; Wu, Pei-Ei; Hsiung, Chia-Ni] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
[Yu, Jyh-Cherng] Triserv Gen Hosp, Dept Surg, Taipei, Taiwan.
[Perkins, Annie; Swann, Ruth; Velentzis, Louiza] Univ Westminster, Breast Canc Res Grp, Dept Mol & Appl Biosci, London W1R 8AL, England.
[Eccles, Diana M.; Tapper, Will J.; Gerty, Susan M.; Graham, Nikki J.] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England.
[Ponder, Bruce A. J.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Ponder, Bruce A. J.] Canc Res UK CRUK Cambridge Res Inst, Cambridge, England.
[Lathrop, Mark] Ctr Natl Genotypage, Evry, France.
[Lathrop, Mark] CEPH, Fdn Jean Dausset, Paris, France.
RP Easton, DF (reprint author), Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
EM douglas@srl.cam.ac.uk
RI Gonzalez-Neira, Anna/C-5791-2015; Garcia-Closas, Montserrat
/F-3871-2015; Brinton, Louise/G-7486-2015; Hartikainen,
Jaana/E-6256-2015; Bowtell, David/H-1007-2016; Bruning,
Thomas/G-8120-2015; Khusnutdinova, Elza/A-4810-2013; Brenner,
Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; Andrulis,
Irene/E-7267-2013; Dzhemileva, Lilya/K-8636-2013; Dork,
Thilo/J-8620-2012; Jakubowska, Anna/O-8050-2014; Shen, CY/F-6271-2010;
Verdrengh, Evelien/H-4571-2012; Noh, Dong-Young/G-5531-2011; Kang, Dae
Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; truong,
therese/A-2837-2013; Muller-Myhsok, Bertram/A-3289-2013; Kerin,
Michael/D-6748-2013; Ekici, Arif/C-3971-2013; Rahman,
Nazneen/D-2802-2013;
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562; Bowtell, David/0000-0001-9089-7525; Bruning,
Thomas/0000-0001-9560-5464; Brenner, Hermann/0000-0002-6129-1572;
manoukian, siranoush/0000-0002-6034-7562; Fortuzzi,
Stefano/0000-0002-5662-3800; Hollestelle,
Antoinette/0000-0003-1166-1966; Dennis, Joe/0000-0003-4591-1214; Czene,
Kamila/0000-0002-3233-5695; Dzhemileva, Lilya/0000-0003-3315-4746;
Giles, Graham/0000-0003-4946-9099; Arndt, Volker/0000-0001-9320-8684;
Rahman, Nazneen/0000-0003-4376-0440; Schoemaker,
Minouk/0000-0001-8403-2234; Lux, Michael Patrick/0000-0002-2781-2178;
Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison
Margaret/0000-0001-6651-7166; Rivadeneira, Fernando/0000-0001-9435-9441;
Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva,
Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Bui,
Minh/0000-0002-9099-6870; Park, Daniel/0000-0002-6354-0931
FU Cancer Research UK [10118, 10124, A10710]; Medical Research Council
[G0700491]; NCI NIH HHS [R25 CA092049]; Wellcome Trust [090532]
NR 67
TC 135
Z9 139
U1 4
U2 65
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 MAR
PY 2012
VL 44
IS 3
BP 312
EP U120
DI 10.1038/ng.1049
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 899VC
UT WOS:000300843600018
PM 22267197
ER
PT J
AU Bellenguez, C
Bevan, S
Gschwendtner, A
Spencer, CCA
Burgess, AI
Pirinen, M
Jackson, CA
Traylor, M
Strange, A
Su, Z
Band, G
Syme, PD
Malik, R
Pera, J
Norrving, B
Lemmens, R
Freeman, C
Schanz, R
James, T
Poole, D
Murphy, L
Segal, H
Cortellini, L
Cheng, YC
Woo, D
Nalls, MA
Muller-Myhsok, B
Meisinger, C
Seedorf, U
Ross-Adams, H
Boonen, S
Wloch-Kopec, D
Valant, V
Slark, J
Furie, K
Delavaran, H
Langford, C
Deloukas, P
Edkins, S
Hunt, S
Gray, E
Dronov, S
Peltonen, L
Gretarsdottir, S
Thorleifsson, G
Thorsteinsdottir, U
Stefansson, K
Boncoraglio, GB
Parati, EA
Attia, J
Holliday, E
Levi, C
Franzosi, MG
Goel, A
Helgadottir, A
Blackwell, JM
Bramon, E
Brown, MA
Casas, JP
Corvin, A
Duncanson, A
Jankowski, J
Mathew, CG
Palmer, CNA
Plomin, R
Rautanen, A
Sawcer, SJ
Trembath, RC
Viswanathan, AC
Wood, NW
Worrall, BB
Kittner, SJ
Mitchell, BD
Kissela, B
Meschia, JF
Thijs, V
Lindgren, A
Macleod, MJ
Slowik, A
Walters, M
Rosand, J
Sharma, P
Farrall, M
Sudlow, CLM
Rothwell, PM
Dichgans, M
Donnelly, P
Markus, HS
AF Bellenguez, Celine
Bevan, Steve
Gschwendtner, Andreas
Spencer, Chris C. A.
Burgess, Annette I.
Pirinen, Matti
Jackson, Caroline A.
Traylor, Matthew
Strange, Amy
Su, Zhan
Band, Gavin
Syme, Paul D.
Malik, Rainer
Pera, Joanna
Norrving, Bo
Lemmens, Robin
Freeman, Colin
Schanz, Renata
James, Tom
Poole, Deborah
Murphy, Lee
Segal, Helen
Cortellini, Lynelle
Cheng, Yu-Ching
Woo, Daniel
Nalls, Michael A.
Mueller-Myhsok, Bertram
Meisinger, Christa
Seedorf, Udo
Ross-Adams, Helen
Boonen, Steven
Wloch-Kopec, Dorota
Valant, Valerie
Slark, Julia
Furie, Karen
Delavaran, Hossein
Langford, Cordelia
Deloukas, Panos
Edkins, Sarah
Hunt, Sarah
Gray, Emma
Dronov, Serge
Peltonen, Leena
Gretarsdottir, Solveig
Thorleifsson, Gudmar
Thorsteinsdottir, Unnur
Stefansson, Kari
Boncoraglio, Giorgio B.
Parati, Eugenio A.
Attia, John
Holliday, Elizabeth
Levi, Chris
Franzosi, Maria-Grazia
Goel, Anuj
Helgadottir, Anna
Blackwell, Jenefer M.
Bramon, Elvira
Brown, Matthew A.
Casas, Juan P.
Corvin, Aiden
Duncanson, Audrey
Jankowski, Janusz
Mathew, Christopher G.
Palmer, Colin N. A.
Plomin, Robert
Rautanen, Anna
Sawcer, Stephen J.
Trembath, Richard C.
Viswanathan, Ananth C.
Wood, Nicholas W.
Worrall, Bradford B.
Kittner, Steven J.
Mitchell, Braxton D.
Kissela, Brett
Meschia, James F.
Thijs, Vincent
Lindgren, Arne
Macleod, Mary Joan
Slowik, Agnieszka
Walters, Matthew
Rosand, Jonathan
Sharma, Pankaj
Farrall, Martin
Sudlow, Cathie L. M.
Rothwell, Peter M.
Dichgans, Martin
Donnelly, Peter
Markus, Hugh S.
CA ISGC
WTCCC2
TI Genome-wide association study identifies a variant in HDAC9 associated
with large vessel ischemic stroke
SO NATURE GENETICS
LA English
DT Article
ID ATRIAL-FIBRILLATION; HISTONE DEACETYLASES; SUSCEPTIBILITY LOCI;
ALGORITHM; GENETICS; DISEASE; SIGNALS; ROLES; RISK
AB Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
C1 [Bellenguez, Celine; Spencer, Chris C. A.; Pirinen, Matti; Strange, Amy; Su, Zhan; Band, Gavin; Freeman, Colin; Goel, Anuj; Helgadottir, Anna; Rautanen, Anna; Farrall, Martin; Donnelly, Peter] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Bevan, Steve; Traylor, Matthew; James, Tom; Markus, Hugh S.] St Georges Univ London, Stroke & Dementia Res Grp, London, England.
[Gschwendtner, Andreas; Malik, Rainer; Dichgans, Martin] Univ Munich, Univ Munchen Klinikum, Inst Stroke & Dementia Res, Munich, Germany.
[Burgess, Annette I.; Poole, Deborah; Segal, Helen; Rothwell, Peter M.] Univ Oxford, Nuffield Dept Clin Neurosci, Stroke Prevent Res Unit, Oxford, England.
[Jackson, Caroline A.; Sudlow, Cathie L. M.] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland.
[Syme, Paul D.; Macleod, Mary Joan] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland.
[Pera, Joanna; Ross-Adams, Helen; Wloch-Kopec, Dorota; Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland.
[Norrving, Bo; Delavaran, Hossein; Lindgren, Arne] Lund Univ, Dept Clin Sci, Lund, Sweden.
[Norrving, Bo; Delavaran, Hossein; Lindgren, Arne] Skane Univ Hosp, Dept Neurol, Lund, Sweden.
[Lemmens, Robin; Thijs, Vincent] Univ Hosp Leuven, Dept Neurol, Louvain, Belgium.
[Lemmens, Robin; Thijs, Vincent] VIB, Vesalius Res Ctr, Louvain, Belgium.
[Schanz, Renata; Slark, Julia; Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, ICCRU, London, England.
[Murphy, Lee] Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil Genet Core Lab, Edinburgh, Midlothian, Scotland.
[Cortellini, Lynelle; Valant, Valerie; Furie, Karen; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA.
[Cortellini, Lynelle; Valant, Valerie; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Cheng, Yu-Ching; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Cheng, Yu-Ching; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Woo, Daniel; Kissela, Brett] Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH USA.
[Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Meisinger, Christa] German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Seedorf, Udo] Univ Munster, Leibniz Inst Arterioskleroseforsch, Munster, Germany.
[Boonen, Steven] Univ Hosp Leuven, Div Geriatr Med, Louvain, Belgium.
[Langford, Cordelia; Deloukas, Panos; Edkins, Sarah; Hunt, Sarah; Gray, Emma; Dronov, Serge; Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge, England.
[Gretarsdottir, Solveig; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari; Helgadottir, Anna] deCODE Genet, Reykjavik, Iceland.
[Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Boncoraglio, Giorgio B.; Parati, Eugenio A.] Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Ist Neurol Carlo Besta, Milan, Italy.
[Attia, John; Holliday, Elizabeth; Levi, Chris] Univ Newcastle, Hunter Med Res Inst, Ctr Brain & Mental Hlth Res, Newcastle, NSW 2300, Australia.
[Franzosi, Maria-Grazia] Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
[Goel, Anuj; Helgadottir, Anna; Farrall, Martin] Univ Oxford, Dept Cardiovasc Med, Oxford, England.
[Blackwell, Jenefer M.] Univ Western Australia, Ctr Child Hlth Res, Perth, WA, Australia.
[Blackwell, Jenefer M.] Univ Cambridge, Sch Clin Med, Cambridge Inst Med Res, Cambridge, England.
[Bramon, Elvira] Kings Coll London, Inst Psychiat, Biomed Res Ctr Mental Hlth, Div Psychol Med & Psychiat, London WC2R 2LS, England.
[Brown, Matthew A.] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld, Australia.
[Casas, Juan P.] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England.
[Casas, Juan P.] UCL, Dept Epidemiol & Publ Hlth, London, England.
[Corvin, Aiden] Trinity Coll Dublin, Inst Mol Med, Neuropsychiat Genet Res Grp, Dublin, Ireland.
[Duncanson, Audrey] Wellcome Trust Res Labs, London, England.
[Jankowski, Janusz] Barts & London Queen Marys Sch Med & Dent, Ctr Gastroenterol, London, England.
[Jankowski, Janusz] Univ Oxford, Div Clin Pharmacol, Oxford, England.
[Mathew, Christopher G.; Trembath, Richard C.] Kings Coll London, Guys Hosp, Sch Med, Dept Med & Mol Genet, London WC2R 2LS, England.
[Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Dundee DD1 9SY, Scotland.
[Plomin, Robert] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England.
[Sawcer, Stephen J.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England.
[Viswanathan, Ananth C.] Natl Hlth Serv NHS Fdn Trust, Moorfields Eye Hosp, Biomed Res Ctr Ophthalmol, Natl Inst Hlth Res NIHR, London, England.
[Viswanathan, Ananth C.] UCL, Inst Ophthalmol, London, England.
[Wood, Nicholas W.] UCL, Inst Neurol, Dept Mol Neuroscience, London, England.
[Worrall, Bradford B.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA.
[Worrall, Bradford B.] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
[Kittner, Steven J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
[Kittner, Steven J.] Baltimore Vet Affairs Med Ctr, Baltimore Geriatr Res Educ & Clin Ctr, Baltimore, MD USA.
[Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Walters, Matthew] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
RP Donnelly, P (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
EM peter.donnelly@well.ox.ac.uk; hmarkus@sgul.ac.uk
RI Jankowski, Janusz/H-2706-2012; Blackwell, Jenefer/H-3015-2015; Mathew,
Christopher/G-3434-2015; Study, GoDARTS/K-9448-2016; Boncoraglio,
Giorgio/B-8647-2011; Palmer, Colin/C-7053-2008; Thijs,
Vincent/C-3647-2009; Muller-Myhsok, Bertram/A-3289-2013; Deloukas,
Panos/B-2922-2013; Attia, John/F-5376-2013; Jackson,
Caroline/B-5954-2012; Meisinger, Christine/B-5358-2014; Wood,
Nicholas/C-2505-2009;
OI Seedorf, Udo/0000-0003-4652-5358; Murphy, Lee/0000-0001-6467-7449;
Corvin, Aiden/0000-0001-6717-4089; Norrving, Bo/0000-0002-8024-5096;
Hunt, Sarah/0000-0002-8350-1235; Brown, Matthew A/0000-0003-0538-8211;
Macleod, Mary Joan/0000-0003-2115-8184; Traylor,
Matthew/0000-0001-6624-8621; Jankowski, Janusz/0000-0003-2130-9181;
Mathew, Christopher/0000-0003-4178-1838; Palmer,
Colin/0000-0002-6415-6560; Thijs, Vincent/0000-0002-6614-8417; Deloukas,
Panos/0000-0001-9251-070X; Attia, John/0000-0001-9800-1308; Jackson,
Caroline/0000-0002-2067-2811; Wood, Nicholas/0000-0002-9500-3348;
Pirinen, Matti/0000-0002-1664-1350; Plomin, Robert/0000-0002-0756-3629;
Bevan, Steve/0000-0003-0490-6830; Trembath, Richard/0000-0003-0550-3400;
Meisinger, Christa/0000-0002-9026-6544; Mitchell,
Braxton/0000-0003-4920-4744; Kissela, Brett/0000-0002-9773-4013
FU Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02,
085475/B/08/Z, 085475/Z/08/Z, WT084724MA, WTCCC2]
FX We thank S. Bertrand, J. Bryant, S. L. Clark, J. S. Conquer, T. Dibling,
J. C. Eldred, S. Gamble, C. Hind, M. L. Perez, C. R. Stribling, S.
Taylor and A. Wilk of the Wellcome Trust Sanger Institute's Sample and
Genotyping Facilities for technical assistance. We acknowledge use of
the British 1958 Birth Cohort DNA collection, which is funded by the
Medical Research Council (G0000934) and the Wellcome Trust
(068545/Z/02), and of the UK National Blood Service controls funded by
the Wellcome Trust. We thank W. Bodmer and B. Winney for use of the
People of the British Isles DNA collection, which was funded by the
Wellcome Trust. We thank the following individuals who contributed to
collection, phenotyping, sample processing and data management for the
different cohorts: A. Burgess, A. Syed and N. Paul (Oxford Vascular
Study); M. Dennis, P. Sandercock, C. Warlow, S. Hart, S. Keir, J.
Wardlaw, A. Farrall, G. Potter, A. Hutchison and M. McDowall (Edinburgh
Stroke Study); A. Pasdar and H. Clinkscale (Aberdeen); P. Higgins
(Glasgow); T. G. Brott, R. D. Brown, S. Silliman, M. Frankel, D. Case,
S. Rich, J. Hardy, A. Singleton (ISGS); M. J. Sparks, K. Ryan, J. Cole,
M. Wozniak, B. Stern, R. Wityk, C. Johnson and D. Buchholz (GEOS); and
J. Maguire, S. Koblar, J. Golledge, J. Surm, G. Hankey, J. Jannes, M.
Lewis, R. Scott, L. Lincz; P. Moscato and R. Baker (Australian Stroke
Genetics Collaborative membership). The principal funding for this study
was provided by the Wellcome Trust as part of the WTCCC2 project
(085475/B/08/Z, 085475/Z/08/Z and WT084724MA). For details of other
funding support, see the Supplementary Note.
NR 30
TC 153
Z9 155
U1 2
U2 20
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 MAR
PY 2012
VL 44
IS 3
BP 328
EP U141
DI 10.1038/ng.1081
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 899VC
UT WOS:000300843600021
ER
PT J
AU Manning, AL
Dyson, NJ
AF Manning, Amity L.
Dyson, Nicholas J.
TI GENOMIC INSTABILITY IN CANCER - OPINION RB: mitotic implications of a
tumour suppressor
SO NATURE REVIEWS CANCER
LA English
DT Review
ID MEROTELIC KINETOCHORE ORIENTATION; CELL-CYCLE PROGRESSION; CHROMOSOMAL
INSTABILITY; DNA-DAMAGE; RETINOBLASTOMA PROTEIN; HISTONE DEACETYLASE;
CLONAL EVOLUTION; REPRESS TRANSCRIPTION; PROMOTES ANEUPLOIDY; MICROARRAY
ANALYSIS
AB RB, a well known tumour suppressor that functions in the control of cell cycle progression and proliferation, has recently been shown to have additional functions in the maintenance of genomic stability, such that inactivation of RB family proteins promotes chromosome instability (CIN) and aneuploidy. Several studies have provided potential explanations for these phenomena that occur following RB loss, and they suggest that this new function of RB may contribute to its role in tumour suppression.
C1 [Dyson, Nicholas J.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
EM dyson@helix.mgh.harvard.edu
FU American Cancer Society; Massachusetts General Hospital Cancer Center
Saltonstall Foundation; AstraZeneca; NIH [GM81607, CA64402]
FX We thank D. Compton and L. Kabeche for sharing their unpublished data,
N. Ganem for critical reading and suggestions on the manuscript, and the
reviewers for their helpful comments. This work was supported by an
American Cancer Society Fellowship to A. L. M., the Massachusetts
General Hospital Cancer Center Saltonstall Foundation Scholarship to
N.J.D., and funding from AstraZeneca and NIH grants GM81607 and CA64402
to N.J.D.
NR 70
TC 55
Z9 57
U1 2
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD MAR
PY 2012
VL 12
IS 3
BP 220
EP 226
DI 10.1038/nrc3216
PG 7
WC Oncology
SC Oncology
GA 899RK
UT WOS:000300833600014
PM 22318235
ER
PT J
AU Mahindra, A
Laubach, J
Raje, N
Munshi, N
Richardson, PG
Anderson, K
AF Mahindra, Anuj
Laubach, Jacob
Raje, Noopur
Munshi, Nikhil
Richardson, Paul G.
Anderson, Kenneth
TI Latest advances and current challenges in the treatment of multiple
myeloma
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Review
ID LENALIDOMIDE PLUS DEXAMETHASONE; RANDOMIZED CONTROLLED-TRIAL; STEM-CELL
TRANSPLANTATION; IN-VIVO CYTOTOXICITY; INHIBITS OSTEOCLASTOGENESIS;
EXTRAMEDULLARY DISEASE; COMBINATION THERAPY; ANTITUMOR-ACTIVITY; CLONAL
EVOLUTION; HEDGEHOG PATHWAY
AB Effectively treating patients with multiple myeloma is challenging. The development of therapeutic regimens over the past decade that incorporate the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide has been the cornerstone of improving the outcome of patients with myeloma. Although these treatment regimens have improved patient survival, nearly all patients eventually relapse. Our improved understanding of the biology of the disease and the importance of the microenvironment has translated into ongoing work to help overcome the challenge of relapse. Several classes of agents including next-generation proteasome inhibitors, immunomodulatory agents, selective histone-deacetylase inhibitors, antibody and antitumor immunotherapy approaches are currently undergoing preclinical and clinical evaluation. This Review provides an update on the latest advances in the treatment of multiple myeloma. In particular, we focus on novel therapies including modulating protein homeostasis, kinases inhibitors, targeting accessory cells and cytokines, and immunomodulatory agents. A discussion of the challenges associated with these therapeutic approaches is also presented.
C1 [Mahindra, Anuj; Raje, Noopur] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
[Laubach, Jacob; Munshi, Nikhil; Richardson, Paul G.; Anderson, Kenneth] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Mahindra, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol & Oncol, 55 Fruit St, Boston, MA 02114 USA.
EM amahindra@gmail.com
NR 102
TC 108
Z9 116
U1 5
U2 25
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD MAR
PY 2012
VL 9
IS 3
BP 135
EP 143
DI 10.1038/nrclinonc.2012.15
PG 9
WC Oncology
SC Oncology
GA 901DX
UT WOS:000300943000004
PM 22349016
ER
PT J
AU Bogdanova, Y
Verfaellie, M
AF Bogdanova, Yelena
Verfaellie, Mieke
TI Cognitive Sequelae of Blast-Induced Traumatic Brain Injury: Recovery and
Rehabilitation
SO NEUROPSYCHOLOGY REVIEW
LA English
DT Review
DE Neurorehabilitation; Executive function; Memory; OEF/OIF; TBI; PTSD
ID POSTTRAUMATIC-STRESS-DISORDER; TRANSCRANIAL MAGNETIC STIMULATION;
OF-THE-LITERATURE; MILD HEAD-INJURY; RANDOMIZED CONTROLLED-TRIAL;
SYMPTOM VALIDITY TEST; NEUROPSYCHOLOGICAL OUTCOMES; POSTCONCUSSIVE
SYMPTOMS; RECURRENT CONCUSSION; ABSTINENT ALCOHOLICS
AB Blast-related traumatic brain injury (bTBI) poses a significant concern for military personnel engaged in Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF). Given the highly stressful context in which such injury occurs, psychiatric comorbidities are common. This paper provides an overview of mild bTBI and discusses the cognitive sequelae and course of recovery typical of mild TBI (mTBI). Complicating factors that arise in the context of co-morbid posttraumatic stress disorder (PTSD) are considered with regard to diagnosis and treatment. Relatively few studies have evaluated the efficacy of cognitive rehabilitation in civilian mTBI, but we discuss cognitive training approaches that hold promise for addressing mild impairments in executive function and memory, akin to those seen in OEF/OIF veterans with bTBI and PTSD. Further research is needed to address the patient and environmental characteristics associated with optimal treatment outcome.
C1 [Verfaellie, Mieke] VA Boston Healthcare Syst, Psychol Res 151 A, Boston, MA 02130 USA.
[Bogdanova, Yelena; Verfaellie, Mieke] Boston Univ, Sch Med, Memory Disorders Res Ctr, VA Boston Healthcare Syst, Boston, MA 02118 USA.
RP Bogdanova, Y (reprint author), VA Boston Healthcare Syst, Psychol Res 151 A, 150 S Huntington Ave, Boston, MA 02130 USA.
EM bogdanov@bu.edu
RI Schueter, nicos/A-3625-2014;
OI Verfaellie, Mieke/0000-0001-5535-4584
FU Clinical Science Research and Development; Rehabilitation Research and
Development Services of the Department of Veterans Affairs; National
Institutes of Health; Boston University Clinical and Translational
Science Institute
FX This research was supported by the Clinical Science Research and
Development and the Rehabilitation Research and Development Services of
the Department of Veterans Affairs; the National Institutes of Health
and Boston University Clinical and Translational Science Institute. We
thank Dr. Jennifer J. Vasterling for her expert advice and helpful
discussion, and Sarah M. Kark, B.S., for assistance with manuscript
preparation. The authors have no conflicts of interest to disclose.
NR 188
TC 47
Z9 48
U1 7
U2 35
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1040-7308
EI 1573-6660
J9 NEUROPSYCHOL REV
JI Neuropsychol. Rev.
PD MAR
PY 2012
VL 22
IS 1
BP 4
EP 20
DI 10.1007/s11065-012-9192-3
PG 17
WC Psychology, Clinical; Neurosciences
SC Psychology; Neurosciences & Neurology
GA 900MU
UT WOS:000300892100003
PM 22350691
ER
PT J
AU Dolan, S
Martindale, S
Robinson, J
Kimbrel, NA
Meyer, EC
Kruse, MI
Morissette, SB
Young, KA
Gulliver, SB
AF Dolan, Sara
Martindale, Sarah
Robinson, Jennifer
Kimbrel, Nathan A.
Meyer, Eric C.
Kruse, Marc I.
Morissette, Sandra B.
Young, Keith A.
Gulliver, Suzy Bird
TI Neuropsychological Sequelae of PTSD and TBI Following War Deployment
among OEF/OIF Veterans
SO NEUROPSYCHOLOGY REVIEW
LA English
DT Review
DE PTSD; TBI; Veterans
ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; MEDIAL PREFRONTAL
CORTEX; VIETNAM COMBAT VETERANS; SYMPTOM VALIDITY TEST; HIPPOCAMPAL
VOLUME; IRAQ-WAR; TEST-PERFORMANCE; INTELLECTUAL RESOURCES;
COGNITIVE-ABILITY
AB Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are highly prevalent among Veterans of the conflicts in Iraq and Afghanistan. These conditions are associated with common and unique neuropsychological and neuroanatomical changes. This review synthesizes neuropsychological and neuroimaging studies for both of these disorders and studies examining their co-occurrence. Recommendations for future research, including use of combined neuropsychological and advanced neuroimaging techniques to study these disorders alone and in concert, are presented. It is clear from the dearth of literature that addiitonal studies are required to examine and understand the impact of specific factors on neurocognitive outcome. Of particular relevance are temporal relationships between PTSD and mTBI, risk and resilience factors associated with both disorders and their co-occurrence, and mTBI-specific factors such as time since injury and severity of injury, utilizing comprehensive, yet targeted cognitive tasks.
C1 [Dolan, Sara; Martindale, Sarah] Baylor Univ, Dept Psychol & Neurosci, Waco, TX 76798 USA.
[Dolan, Sara; Robinson, Jennifer; Kimbrel, Nathan A.; Meyer, Eric C.; Kruse, Marc I.; Morissette, Sandra B.; Young, Keith A.; Gulliver, Suzy Bird] US Dept Vet Affairs, Ctr Excellence Res Returning War Vet, Waco, TX USA.
[Dolan, Sara; Kimbrel, Nathan A.; Meyer, Eric C.; Kruse, Marc I.; Morissette, Sandra B.; Young, Keith A.; Gulliver, Suzy Bird] Texas A&M Hlth Sci Ctr, Coll Med, Dept Psychiat & Behav Sci, Temple, TX USA.
[Robinson, Jennifer] Scott & White Healthcare, Neurosci Inst, Temple, TX USA.
[Kruse, Marc I.] City Austin Travis Cty Emergency Med Serv Dept, Austin, TX USA.
[Kruse, Marc I.] Austin Fire Dept, Austin, TX USA.
RP Dolan, S (reprint author), Baylor Univ, Dept Psychol & Neurosci, Waco, TX 76798 USA.
EM sara_dolan@baylor.edu
RI Schueter, nicos/A-3625-2014; Kimbrel, Nathan/P-3109-2016;
OI Kimbrel, Nathan/0000-0001-7218-1005; Dolan, Sara/0000-0002-0156-8226;
Martindale, Sarah/0000-0002-0059-3454
FU Department of Veterans Affairs (VA) [I01RX000304]; Rehabilitation
Research and Development Service of the VA Office of Research and
Development
FX This research was supported by the Department of Veterans Affairs (VA)
VISN 17 Center of Excellence for Research on Returning War Veterans, a
Merit Award (I01RX000304) to Sandra B. Morissette, Ph.D. from the
Rehabilitation Research and Development Service of the VA Office of
Research and Development entitled, "Functional Outcomes in OEF/OIF
Veterans with PTSD and Alcohol Misuse," a DVA VISN 17 New Investigator
Award to Nathan A. Kimbrel, Ph.D. entitled, "Genetic and Environmental
Effects on PTSD, Depression, and Alcohol Misuse," and a DVA VISN 17 New
Investigator Award to Eric C. Meyer, Ph.D. entitled, "Experiential
Avoidance, Neurocognition, and Functional Outcomes in PTSD."
NR 116
TC 31
Z9 32
U1 4
U2 18
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1040-7308
J9 NEUROPSYCHOL REV
JI Neuropsychol. Rev.
PD MAR
PY 2012
VL 22
IS 1
BP 21
EP 34
DI 10.1007/s11065-012-9190-5
PG 14
WC Psychology, Clinical; Neurosciences
SC Psychology; Neurosciences & Neurology
GA 900MU
UT WOS:000300892100004
PM 22350690
ER
PT J
AU Betthauser, LM
Bahraini, N
Krengel, MH
Brenner, LA
AF Betthauser, Lisa M.
Bahraini, Nazanin
Krengel, Maxine H.
Brenner, Lisa A.
TI Self-Report Measures to Identify Post Traumatic Stress Disorder and/or
Mild Traumatic Brain Injury and Associated Symptoms in Military Veterans
of Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF)
SO NEUROPSYCHOLOGY REVIEW
LA English
DT Review
DE Operation Enduring Freedom; Operation Iraqi Freedom; Traumatic Brain
Injury; Post Traumatic Stress Disorder; Assessment; Self-report measures
ID AFGHANISTAN WAR VETERANS; VA HEALTH-CARE; POSTTRAUMATIC-STRESS;
POSTCONCUSSIVE SYMPTOMS; PSYCHOMETRIC PROPERTIES; OEF/OIF VETERANS; PTSD
CHECKLIST; MENTAL-HEALTH; BLAST INJURY; US VETERANS
AB Individuals serving in Iraq and Afghanistan sustain injuries associated with physical and psychological trauma. Among such injuries, mild traumatic brain injury (mTBI) and post traumatic stress disorder (PTSD) are common. Self-report measures are frequently used to identify mTBI and/or PTSD and symptoms associated with these conditions. In addition to providing information regarding mTBI and PTSD, the goal of this literature review was to identify and present information on the psychometric properties of measures used to obtain information regarding these common conditions among Veterans who have returned from Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF). A comprehensive review of studies in which self-report measures were used to evaluate mTBI, PTSD, and associated symptoms among OEF/OIF Veterans is presented. Findings suggest that additional work is needed to identify psychometrically sound and clinically useful self-report measures that assess mTBI and PTSD and associated symptoms among OEF/OIF Veterans.
C1 [Betthauser, Lisa M.; Bahraini, Nazanin; Brenner, Lisa A.] Mental Illness Res Educ & Clin Ctr, Vet Integrated Serv Network 19, Denver, CO 80220 USA.
[Betthauser, Lisa M.] Univ Colorado, Dept Psychol, Denver, CO 80202 USA.
[Bahraini, Nazanin; Brenner, Lisa A.] Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80262 USA.
[Krengel, Maxine H.] VA Boston Healthcare Syst, Boston, MA USA.
[Krengel, Maxine H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Brenner, Lisa A.] Univ Colorado Denver, Dept Neurol, Sch Med, Aurora, CO USA.
[Brenner, Lisa A.] Univ Colorado Denver, Sch Med, Dept Phys Med & Rehabil, Aurora, CO USA.
RP Betthauser, LM (reprint author), Mental Illness Res Educ & Clin Ctr, Vet Integrated Serv Network 19, 1055 Clermont St, Denver, CO 80220 USA.
EM Lisa.Betthauser@va.gov
RI Schueter, nicos/A-3625-2014;
OI Krengel, Maxine/0000-0001-7632-590X
NR 80
TC 12
Z9 13
U1 4
U2 18
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1040-7308
EI 1573-6660
J9 NEUROPSYCHOL REV
JI Neuropsychol. Rev.
PD MAR
PY 2012
VL 22
IS 1
BP 35
EP 53
DI 10.1007/s11065-012-9191-4
PG 19
WC Psychology, Clinical; Neurosciences
SC Psychology; Neurosciences & Neurology
GA 900MU
UT WOS:000300892100005
PM 22350740
ER
PT J
AU Passias, PG
Kozanek, M
Wood, KB
AF Passias, Peter G.
Kozanek, Michal
Wood, Kirkham B.
TI Surgical Treatment of Low-Grade Isthmic Spondylolisthesis With
Transsacral Fibular Strut Grafts
SO NEUROSURGERY
LA English
DT Article
DE Fibular allograft; Interbody; Isthmic spondylolisthesis; Low-grade;
Lumbar spine; Posterior arthrodesis
ID LUMBAR INTERBODY FUSION; POSTERIOR; DECOMPRESSION; FIXATION; SURGERY;
SPINE
AB BACKGROUND: The ideal surgical treatment for adult low-grade isthmic spondylolisthesis (ALIS) remains unknown. Isolated anterior and posterior procedures are popular but have resulted in equivocal outcomes, whereas combined anterior and posterior procedures are associated with higher complication rates despite improved outcome.
OBJECTIVE: To evaluate the clinical and radiographic outcomes following the treatment of ALIS using a 1-stage posterior approach with posterior decompression and posterolateral arthrodesis combined with an interbody fibular allograft strut.
METHODS: Fifteen patients underwent fusion by a single surgeon using our modified technique. Seven patients were female and 8 were male, with a mean age of 48 years. All patients were classified as Meyerding grade II slips and underwent a posterior approach only, a decompressive laminectomy, and a circumferential fusion with the use of a transsacral fibular allograft and a posterolateral instrumented fusion. Postoperative clinical and radiographic evaluations were performed at 3, 6, and 12 months, and then on an annual basis.
RESULTS: The average follow-up interval was 61 months. Three complications were seen: a single dural tear, an L5 radiculopathy secondary to a malpositioned pedicle screw, and one patient with urinary retention. The spines of all patients were determined to be fused by the 6-month postoperative visit. All patients returned to their normal activities of daily living. Significant improvements in the visual analog score were seen at all follow-up intervals.
CONCLUSION: Transsacral interbody fibular allograft can be used successfully to supplement a posterolateral instrumented fusion in selected patients with low-grade ALIS.
C1 [Passias, Peter G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Spine Surg,Dept Orthopaed Surg, Boston, MA 02114 USA.
RP Passias, PG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Spine Surg,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA.
EM panagmd@gmail.com
NR 18
TC 3
Z9 7
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD MAR
PY 2012
VL 70
IS 3
BP 758
EP 763
DI 10.1227/NEU.0b013e3182338b2b
PG 6
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 898ZU
UT WOS:000300781700034
PM 21866066
ER
PT J
AU Simon, MV
Chiappa, KH
Borges, LF
AF Simon, Mirela V.
Chiappa, Keith H.
Borges, Lawrence F.
TI Phase Reversal of Somatosensory Evoked Potentials Triggered by Gracilis
Tract Stimulation: Case Report of a New Technique for Neurophysiologic
Dorsal Column Mapping
SO NEUROSURGERY
LA English
DT Article
DE Dorsal column mapping; Phase reversal; Somatosensory evoked potentials
ID SURGERY; ADJUNCT
AB BACKGROUND AND IMPORTANCE: Reliable visual identification of the median raphae, essential for the preservation of function of the posterior dorsal columns during intramedullary spinal cord tumor resection, is not possible in many cases, because of distorted local anatomy. In such cases, intraoperative neurophysiologic mapping of the dorsal columns offers invaluable information to the surgeon, and guides the myelotomy. We hereby describe such a new technique.
CLINICAL PRESENTATION: A 41-year-old man with a C3-C4 intramedullary spinal cord tumor underwent successful myelotomy and tumor resection. Dorsal column mapping was performed by use of an 8-contact minielectrode strip placed on the dorsal spinal cord. Direct electrical stimulation was applied via 2 adjacent contacts of the strip at a time, in an attempt to stimulate in succession the left and right dorsal columns. Somatosensory evoked potentials (SSEPs) were recorded after each stimulation, via scalp electrodes. A sharp change in polarity of the recorded scalp SSEPs (phase reversal) indicated when the stimulation of the opposite dorsal column occurred. Myelotomy was performed in between the minielectrode contacts identified as being situated closest to the raphe. The posterior tibial SSEPs were continuously monitored during and after myelotomy and until the dura closure. No changes from premyelotomy SSEPs were present. Postoperatively, the patient had preservation of the posterior column function.
CONCLUSION: SSEP phase-reversal technique is a promising new method to identify the neurophysiologic midline in intramedullary tumor resection. Fast and easy to perform, its final role in neurophysiologic dorsal column mapping awaits confirmation in future applications.
C1 [Simon, Mirela V.; Chiappa, Keith H.] Massachusetts Gen Hosp, Neurophysiol Div, Dept Neurol, Boston, MA 02114 USA.
[Simon, Mirela V.; Chiappa, Keith H.; Borges, Lawrence F.] Harvard Univ, Sch Med, Boston, MA USA.
[Borges, Lawrence F.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
RP Simon, MV (reprint author), Massachusetts Gen Hosp, Neurophysiol Div, Dept Neurol, WACC 739-G,55 Fruit St, Boston, MA 02114 USA.
EM mvsimon@partners.org
NR 16
TC 4
Z9 4
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD MAR
PY 2012
VL 70
IS 3
BP E783
EP E788
DI 10.1227/NEU.0b013e31822e0a76
PG 6
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 898ZU
UT WOS:000300781700001
PM 21778916
ER
PT J
AU Tanna, AP
Budenz, DL
Bandi, J
Feuer, WJ
Feldman, RM
Herndon, LW
Rhee, DJ
Whiteside-de Vos, J
Huang, J
Anderson, DR
AF Tanna, Angelo P.
Budenz, Donald L.
Bandi, Jagadeesh
Feuer, William J.
Feldman, Robert M.
Herndon, Leon W.
Rhee, Douglas J.
Whiteside-de Vos, Julia
Huang, Joyce
Anderson, Douglas R.
TI Glaucoma Progression Analysis Software Compared with Expert Consensus
Opinion in the Detection of Visual Field Progression in Glaucoma
SO OPHTHALMOLOGY
LA English
DT Article
ID AUTOMATED PERIMETRY; CATARACT-EXTRACTION; TRIAL; VARIABILITY
AB Purpose: To compare the results of Glaucoma Progression Analysis (GPA, Carl Zeiss Meditec, Dublin, CA) to subjective expert consensus in the detection of glaucomatous visual field progression.
Design: Retrospective, observational case series.
Participants: We included 100 eyes of 83 glaucoma patients.
Methods: Five serial Humphrey visual fields from 100 eyes of 83 glaucoma patients were evaluated by 5 masked glaucoma subspecialists for determination of progression. Four months later, with a randomly reordered patient sequence, the same visual field series were reevaluated by the same graders, at which time they had access to the Glaucoma Progression Analysis (GPA) printout.
Main Outcome Measures: The level of agreement between majority expert consensus and GPA, both before and after access to GPA data, was assessed using kappa statistics.
Results: On initial review and on reevaluation with access to the GPA printout, the level of agreement between majority expert consensus and GPA was fair (kappa = 0.52, 95% confidence interval [CI], 0.35-0.69 and kappa = 0.62; 95% CI, 0.46-0.78, respectively). Expert consensus was more likely to classify a series of fields as showing progression than was GPA (P <= 0.002). There was good agreement between expert consensus on initial review and reevaluation 4 months later (kappa = 0.77; 95% CI, 0.65-0.90).
Conclusions: The level of agreement between majority expert consensus of subjective determination of visual field progression and GPA is fair. In cases of disagreement with GPA, the expert consensus classification was usually progression. Access to the results of GPA did not significantly change the level of agreement between expert consensus and the GPA result; however, expert consensus did change in 11 of 100 cases.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:468-473 (C) 2012 by the American Academy of Ophthalmology.
C1 [Tanna, Angelo P.; Huang, Joyce] Northwestern Univ, Feinberg Sch Med, Dept Ophthalmol, Chicago, IL 60611 USA.
[Budenz, Donald L.; Bandi, Jagadeesh; Feuer, William J.; Anderson, Douglas R.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
[Budenz, Donald L.; Bandi, Jagadeesh] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA.
[Feldman, Robert M.] Univ Texas Med Sch Houston, Dept Ophthalmol & Visual Sci, Houston, TX USA.
[Herndon, Leon W.] Duke Univ, Ctr Eye, Durham, NC USA.
[Rhee, Douglas J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Whiteside-de Vos, Julia] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Budenz, DL (reprint author), Univ N Carolina, Dept Ophthalmol, 5151 Bioinformat CB 7040, Chapel Hill, NC 27599 USA.
EM dbudenz@med.unc.edu
FU Research to Prevent Blindness; NEI [P30 EY-014801]; Carl Zeiss Meditec,
Inc; National Institutes of Health, National Eye Institute [EY 07127]
FX Supported by an unrestricted grant from Research to Prevent Blindness
(A.P.T., D.L.B., J.B., W.J.F., D.R.A.); NEI grant P30 EY-014801 (D.L.B.,
J.B., W.J.F., D.R.A.); an unrestricted grant from Carl Zeiss Meditec,
Inc; and National Institutes of Health, National Eye Institute Training
Grant EY 07127 Clinical Trials Training Program in Vision Research (Dr.
Whiteside).
NR 28
TC 10
Z9 10
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAR
PY 2012
VL 119
IS 3
BP 468
EP 473
DI 10.1016/j.ophtha.2011.08.041
PG 6
WC Ophthalmology
SC Ophthalmology
GA 901ID
UT WOS:000300957200006
PM 22137043
ER
PT J
AU Inamoto, Y
Chai, XY
Kurland, BF
Cutler, C
Flowers, MED
Palmer, JM
Carpenter, PA
Heffernan, MJ
Jacobsohn, D
Jagasia, MH
Pidala, J
Khera, N
Vogelsang, GB
Weisdorf, D
Martin, PJ
Pavletic, SZ
Lee, SJ
AF Inamoto, Yoshihiro
Chai, Xiaoyu
Kurland, Brenda F.
Cutler, Corey
Flowers, Mary E. D.
Palmer, Jeanne M.
Carpenter, Paul A.
Heffernan, Mary J.
Jacobsohn, David
Jagasia, Madan H.
Pidala, Joseph
Khera, Nandita
Vogelsang, Georgia B.
Weisdorf, Daniel
Martin, Paul J.
Pavletic, Steven Z.
Lee, Stephanie J.
CA Chronic GVHD Consortium
TI Validation of Measurement Scales in Ocular Graft-versus-Host Disease
SO OPHTHALMOLOGY
LA English
DT Article; Proceedings Paper
CT BMT Tandem Meeting
CY FEB, 2011
CL Honolulu, HI
ID QUALITY-OF-LIFE; CONSENSUS DEVELOPMENT PROJECT;
BONE-MARROW-TRANSPLANTATION; WORKING GROUP-REPORT; STEM-CELL
TRANSPLANTATION; DRY EYE SYNDROME; TERM-FOLLOW-UP; CLINICAL-TRIALS;
THERAPEUTIC RESPONSE; HEALTH-STATUS
AB Purpose: To validate measurement scales for rating ocular chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation. Candidate scales were recommended for use in clinical trials by the National Institutes of Health (NIH) Chronic GVHD Consensus Conference or have been previously validated in dry eye syndromes.
Design: Prospective follow-up study.
Participants: Between August 2007 and June 2010, the study enrolled 387 patients with chronic GVHD in a multicenter, prospective, observational cohort.
Methods: Using anchor-based methods, we compared clinician or patient-reported changes in eye symptoms (8-point scale) with calculated changes in 5 candidate scales: The NIH eye score, patient-reported global rating of eye symptoms, Lee eye subscale, Ocular Surface Disease Index, and Schirmer test. Change was examined for 333 follow-up visits where both clinician and patient reported eye involvement at the previous visit. Linear mixed models were used to account for within-patient correlation.
Main Outcome Measures: An 8-point scale of clinician or patient-reported symptom change was used as an anchor to measure symptom changes at the follow-up visits.
Results: In serial evaluations, agreement regarding improvement, stability, or worsening between the clinician and patient was fair (weighted kappa = 0.34). Despite only fair agreement between evaluators, all scales except the Schirmer test correlated with both clinician-reported and patient-reported changes in ocular GVHD activity. Among all scales, changes in the NIH eye scores showed the greatest sensitivity to symptom change reported by clinicians or patients.
Conclusions: Our results support the use of the NIH eye score as a sensitive measure of eye symptom changes in clinical trials assessing treatment of chronic GVHD.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:487-493 (C) 2012 by the American Academy of Ophthalmology.
C1 [Inamoto, Yoshihiro; Chai, Xiaoyu; Kurland, Brenda F.; Flowers, Mary E. D.; Carpenter, Paul A.; Heffernan, Mary J.; Khera, Nandita; Martin, Paul J.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Palmer, Jeanne M.] Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA.
[Jacobsohn, David] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC 20010 USA.
[Jagasia, Madan H.] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplant Program, Nashville, TN USA.
[Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Vogelsang, Georgia B.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Weisdorf, Daniel] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA.
[Pavletic, Steven Z.] NCI, Bethesda, MD 20892 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
OI Kurland, Brenda/0000-0002-5669-0595
FU NCI NIH HHS [P01 CA018029, CA118953, CA18029, P30 CA015704, R01
CA118953, U01 CA118953, U01 CA118953-05, U54 CA163438]
NR 37
TC 30
Z9 30
U1 2
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAR
PY 2012
VL 119
IS 3
BP 487
EP 493
DI 10.1016/j.ophtha.2011.08.040
PG 7
WC Ophthalmology
SC Ophthalmology
GA 901ID
UT WOS:000300957200009
PM 22153706
ER
PT J
AU Yonker, LM
Mark, EJ
Canapari, CA
AF Yonker, Lael M.
Mark, Eugene J.
Canapari, Craig A.
TI Aspergilloma in a Patient With an Occult Congenital Pulmonary Airway
Malformation
SO PEDIATRIC PULMONOLOGY
LA English
DT Article
ID BRONCHOGENIC CYST; HEMOPTYSIS; LUNG
AB We describe the case of a 14-year-old male who presented with a right upper lobe aspergilloma forming in a previously occult congenital pulmonary airway malformation. This is the first case describing an aspergilloma forming within a CPAM. Pediatr Pulmonol. 2012; 47:308-310. (c) 2011 Wiley Periodicals, Inc.
C1 [Yonker, Lael M.; Mark, Eugene J.; Canapari, Craig A.] Harvard Univ, Sch Med, Boston, MA USA.
[Yonker, Lael M.; Mark, Eugene J.; Canapari, Craig A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Yonker, LM (reprint author), 275 Cambridge St,5th Floor, Boston, MA 02114 USA.
EM lyonker@partners.org
NR 20
TC 3
Z9 3
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 8755-6863
J9 PEDIATR PULM
JI Pediatr. Pulmonol.
PD MAR
PY 2012
VL 47
IS 3
BP 308
EP 310
DI 10.1002/ppul.21538
PG 3
WC Pediatrics; Respiratory System
SC Pediatrics; Respiratory System
GA 897ZJ
UT WOS:000300702300013
PM 21905264
ER
PT J
AU Lee, ACW
Harada, N
AF Lee, Alan Chong W.
Harada, Nancy
TI Telehealth as a Means of Health Care Delivery for Physical Therapist
Practice
SO PHYSICAL THERAPY
LA English
DT Editorial Material
ID TELEREHABILITATION; OUTCOMES; REHABILITATION
C1 [Lee, Alan Chong W.] Mt St Marys Coll, Doctor Phys Therapy Program, Los Angeles, CA 90007 USA.
[Lee, Alan Chong W.] Scripps Mercy Hosp, San Diego, CA USA.
[Lee, Alan Chong W.] Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA.
[Harada, Nancy] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Harada, Nancy] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Lee, ACW (reprint author), Mt St Marys Coll, Doctor Phys Therapy Program, 10 Chester Pl, Los Angeles, CA 90007 USA.
EM allee@msmc.la.edu
NR 33
TC 4
Z9 5
U1 1
U2 3
PU AMER PHYSICAL THERAPY ASSOC
PI ALEXANDRIA
PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA
SN 0031-9023
J9 PHYS THER
JI Phys. Ther.
PD MAR
PY 2012
VL 92
IS 3
BP 463
EP 468
DI 10.2522/ptj.20110100
PG 6
WC Orthopedics; Rehabilitation
SC Orthopedics; Rehabilitation
GA 901CY
UT WOS:000300940500011
PM 22135703
ER
PT J
AU Reisman, JS
Weinberg, A
Ponte, C
Kradin, R
AF Reisman, Jonathan S.
Weinberg, Arnold
Ponte, Carlos
Kradin, Richard
TI Monomicrobial Pseudomonas necrotizing fasciitis: A case of infection by
two strains and a review of 37 cases in the literature
SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES
LA English
DT Review
DE Pseudomonas infection; necrotizing fasciitis; immunocompromise
ID AERUGINOSA INFECTIONS; CLINICAL PRESENTATION; EYELID NECROSIS; OCULAR
ADNEXA; GANGRENE; MICROBIOLOGY; CHILDREN; BITE; SKIN
AB Necrotizing fasciitis due to Pseudomonas aeruginosa is rare. We report a case of monomicrobial Pseudomonas necrotizing fasciitis and review 37 cases in the literature. The mortality rate was 30%, and most infections occurred in the immunocompromised. Clinicians should consider empiric pseudomonal antibiotic coverage in the severely immunocompromised with potentially necrotizing infections.
C1 [Reisman, Jonathan S.] Massachusetts Gen Hosp, Harvard Internal Med Pediat Program, Boston, MA 02114 USA.
[Weinberg, Arnold] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Ponte, Carlos; Kradin, Richard] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kradin, Richard] Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA.
RP Reisman, JS (reprint author), Harvard Massachusetts Gen Hosp, Med Pediat Program, 275 Cambridge St,5th Floor, Boston, MA 02114 USA.
EM Reisman.jonathan@gmail.com
NR 41
TC 0
Z9 0
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0036-5548
J9 SCAND J INFECT DIS
JI Scand. J. Infect. Dis.
PD MAR
PY 2012
VL 44
IS 3
BP 216
EP 221
DI 10.3109/00365548.2011.626441
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA 898UT
UT WOS:000300768500009
PM 22126406
ER
PT J
AU Horan, WP
Foti, D
Hajcak, G
Wynn, JK
Green, MF
AF Horan, William P.
Foti, Dan
Hajcak, Greg
Wynn, Jonathan K.
Green, Michael F.
TI Intact motivated attention in schizophrenia: Evidence from event-related
potentials
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia Event-Related Potentials (ERP); Late Positive Potential;
P300; Emotion
ID EMOTION
AB Emotionally significant stimuli typically capture attention (called motivated attention) even when they are irrelevant to tasks where attention is directed. Previous studies indicate that several components of emotional processing are intact in schizophrenia when subjects are instructed to attend to emotionally-evocative stimuli. However, few studies have examined whether emotional stimuli capture attention to a normal degree in people with schizophrenia when attention is directed elsewhere. The current event-related potential study examined motivated attention to task-irrelevant emotional stimuli in 35 stabilized outpatients and 26 healthy controls with a modified visual P300 oddball detection task. Participants viewed images of rare target and commonly occurring standard letter stimuli, as well as intermixed emotional (unpleasant, pleasant, neutral) pictures. Subjects were instructed to count the number of rare targets; the emotional valence of the picture stimuli was, therefore, task-irrelevant. We separately evaluated the Early Posterior Negativity (EPN) and Late Positive Potential (LPP) to emotional pictures and the P300 to target stimuli. Patients and controls showed similar patterns of EPN and LPP amplitude to the emotional stimuli, such that the EPN and LPP were larger for both pleasant and unpleasant versus neutral pictures. Although patients performed worse than controls on the target counting task, both groups showed comparable P300 differentiation between target versus non-target stimuli. Emotional stimuli captured attentional resources in people with schizophrenia even when the emotional stimuli were task-irrelevant, suggesting intact motivated attention at the level of early electrophysiological responding. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Horan, William P.; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, Los Angeles, CA 90073 USA.
[Horan, William P.; Wynn, Jonathan K.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Foti, Dan; Hajcak, Greg] SUNY Stony Brook, Stony Brook, NY USA.
RP Horan, WP (reprint author), Univ Calif Los Angeles, MIRECC 210A,Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM horan@ucla.edu
RI Wynn, Jonathan/H-3749-2014
OI Wynn, Jonathan/0000-0002-1763-8540
FU NARSAD; National Institute of Mental Health [MH082782, MH065707,
MH43292]
FX This work was supported by a NARSAD Young Investigator Award (to WPH)
and the National Institute of Mental Health (MH082782 to WPH; MH065707,
MH43292 to MFG). Funding sources had no role in study design or in the
collection, analysis and interpretation of data; or in the writing of
this report.
NR 20
TC 22
Z9 22
U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD MAR
PY 2012
VL 135
IS 1-3
BP 95
EP 99
DI 10.1016/j.schres.2011.11.005
PG 5
WC Psychiatry
SC Psychiatry
GA 901CT
UT WOS:000300940000017
PM 22126898
ER
PT J
AU Tucker, JD
Yang, LG
Yang, B
Young, D
Henderson, GE
Huang, SJ
Lu, HK
Chen, XS
Cohen, MS
AF Tucker, Joseph D.
Yang, Li-Gang
Yang, Bin
Young, Darwin
Henderson, Gail E.
Huang, Shu-Jie
Lu, He-Kun
Chen, Xiang-Sheng
Cohen, Myron S.
TI Prior HIV Testing Among STD Patients in Guangdong Province, China:
Opportunities for Expanding Detection of Sexually Transmitted HIV
Infection
SO SEXUALLY TRANSMITTED DISEASES
LA English
DT Article
ID SERVICE PROVIDERS; RURAL CHINA; ATTITUDES; STIGMA; WILLINGNESS;
PHYSICIANS; KNOWLEDGE; SYPHILIS; HEALTH
AB Background: Expanding HIV testing is important among individuals at increased risk for sexual HIV transmission in China, but little is known about prior HIV testing experiences among sexually transmitted disease (STD) patients.
Methods: This cross-sectional study of 1792 outpatients from 6 public STD clinics in Guangdong Province recorded detailed information about ever having been tested for HIV infection in addition to sociodemographic variables, health seeking, clinical STD history, and HIV stigma using a validated survey instrument.
Results: A total of 456 (25.4%) of the STD patients in this sample had ever been tested for HIV infection. STD patients who were male, had higher income, more education, were at City A and City C, received STD services at public facilities, had used intravenous drugs, and had a history of an STD were more likely to ever receive an HIV test in multivariate analysis. Low perceived HIV risk was the most common reason for not receiving an HIV test. Only 7.7% of the sample reported fear of discrimination or loss of face as influencing their lack of HIV testing.
Conclusion: Incomplete prior HIV screening among STD patients in China suggests the need for broadening HIV testing opportunities at STD clinics and similar clinical settings attended by those with increased sexual risk.
C1 [Tucker, Joseph D.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA.
[Tucker, Joseph D.; Yang, Li-Gang; Yang, Bin] Guangdong Prov Ctr Skin Dis & STD Control, STD Control Dept, Guangzhou, Guangdong, Peoples R China.
[Tucker, Joseph D.; Young, Darwin; Henderson, Gail E.; Cohen, Myron S.] Univ N Carolina, Dept Med, Chapel Hill Sch Med, Chapel Hill, NC USA.
[Huang, Shu-Jie; Lu, He-Kun] Jiangmen Municipal Skin Hosp, STD Control Dept, Jiangmen, Peoples R China.
[Chen, Xiang-Sheng] Chinese Acad Med Sci, Natl Ctr STD Control, Nanjing, Jiangsu, Peoples R China.
[Chen, Xiang-Sheng] Peking Union Med Coll, Inst Dermatol, Nanjing, Jiangsu, Peoples R China.
RP Tucker, JD (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med, 55 Fruit St,GRJ 504, Boston, MA 02114 USA.
EM jtucker4@partners.org
FU NIH (US NIH) [1K01TW008200-01A1]; UNC [NIH FIC D43 TW01039]; UNC Social
Science Research on HIV/AIDS in China [NIH NICHD R24 HD056670-01]; UNC
Center for AIDS Research; China-Australia Health and HIV/AIDS Facility
Project [HIV 04]; WHO [A70577]; Harvard Institute for Global Health;
American Society of Tropical Medicine and Hygiene
FX Supported by funds from an NIH Fogarty K01 Award (US NIH
1K01TW008200-01A1), the UNC Fogarty AIDS International Research and
Training Program (NIH FIC D43 TW01039), the UNC Social Science Research
on HIV/AIDS in China (NIH NICHD R24 HD056670-01), the UNC Center for
AIDS Research, the China-Australia Health and HIV/AIDS Facility Project
(HIV 04), the WHO Rapid Syphilis Test Project (UNICEF/UNDP/World Bank/
WHO A70577), the Harvard Institute for Global Health, and Burroughs
Wellcome Fund/American Society of Tropical Medicine and Hygiene Wellcome
Postdoctoral Fellowship in Tropical Infectious Diseases.
NR 33
TC 1
Z9 1
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-5717
J9 SEX TRANSM DIS
JI Sex. Transm. Dis.
PD MAR
PY 2012
VL 39
IS 3
BP 182
EP 187
DI 10.1097/OLQ.0b013e318237b3b4
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA 900VS
UT WOS:000300920400004
PM 22337103
ER
PT J
AU Schnelldorfer, T
AF Schnelldorfer, Thomas
TI Image-enhanced laparoscopy: A promising technology for detection of
peritoneal micrometastases
SO SURGERY
LA English
DT Article
ID GREEN FLUORESCENT PROTEIN; ACID-INDUCED FLUORESCENCE; 5-AMINOLEVULINIC
ACID; PHOTODYNAMIC DIAGNOSIS; ENDOMETRIOTIC LESIONS; CANCER METASTASES;
SERUM ALBUMIN; FLUOROPHORE; ANTIBODY; SURGERY
C1 [Schnelldorfer, Thomas] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA.
[Schnelldorfer, Thomas] Philadelphia Vet Affairs Med Ctr, Sect Gen Surg, Philadelphia, PA USA.
RP Schnelldorfer, T (reprint author), Univ Penn, Sch Med, Dept Surg, 3400 Spruce St, Philadelphia, PA 19104 USA.
EM thomas.schnelldorfer@va.gov
NR 38
TC 5
Z9 5
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD MAR
PY 2012
VL 151
IS 3
BP 345
EP 350
DI 10.1016/j.surg.2011.12.012
PG 6
WC Surgery
SC Surgery
GA 902CP
UT WOS:000301016500001
PM 22329962
ER
PT J
AU Wang, LH
Lin, F
Wang, J
Wu, JC
Han, R
Zhu, LJ
Zhang, GX
DiFiglia, M
Qin, ZH
AF Wang, Linhui
Lin, Fang
Wang, Jin
Wu, Junchao
Han, Rong
Zhu, Lujia
Zhang, Guoxing
DiFiglia, Marian
Qin, Zhenghong
TI Truncated N-terminal huntingtin fragment with expanded-polyglutamine
(htt552-100Q) suppresses brain-derived neurotrophic factor transcription
in astrocytes
SO ACTA BIOCHIMICA ET BIOPHYSICA SINICA
LA English
DT Article
DE Huntingtons disease; astrocytes; brain-derived neurotrophic factor;
huntingtin; transcription
ID MUTANT HUNTINGTIN; CELLULAR TOXICITY; CASPASE CLEAVAGE; MEDIATED
TRANSCRIPTION; ALZHEIMERS-DISEASE; REDUCES TOXICITY; BDNF-GENE; IN-VIVO;
EXPRESSION; PROTEIN
AB Although huntingtin (htt) can be cleaved at many sites by caspases, calpains, and aspartyl proteases, amino acid (aa) 552 was defined as a preferred site for cleavage in human Huntington disease (HD) brains in vivo. To date, the normal function of wild-type N-terminal htt fragment 1-552 aa (htt552) and its pathological roles of mutant htt552 are still unknown. Although mutant htt (mhtt) is also expressed in astrocytes, whether and how mhtt contributes to the neurodegeneration through astrocytes in HD remains largely unknown. In this study, a glia HD model, using an adenoviral vector to express wild-type htt552 (htt552-18Q) and its mutation (htt552-100Q) in rat primary cortical astrocytes, was generated to investigate the influence of htt552 on the transcription of brain-derived neurotrophic factor (BDNF). Results from enzyme linked immunosorbent assay showed that the level of BDNF in astrocyte-conditioned medium was decreased in the astrocytes expressing htt552-100Q. Quantitative real-time polymerase chain reaction demonstrated that htt552-100Q reduced the transcripts of the BDNF III and IV, hence, repressed the transcription of BDNF. Furthermore, immunofluorescence showed that aggregates formed by htt552-100Q entrapped transcription factors cAMP-response element-binding protein and stimulatory protein 1, which might account for the reduction of BDNF transcription. These findings suggest that mhtt552 reduces BDNF transcription in astrocytes, which might contribute to the neuronal dysfunction in HD.
C1 [Lin, Fang; Wang, Jin; Wu, Junchao; Han, Rong; Zhu, Lujia; Qin, Zhenghong] Soochow Univ, Sch Pharm, Dept Pharmacol, Suzhou 215123, Peoples R China.
[Lin, Fang; Wang, Jin; Wu, Junchao; Han, Rong; Zhu, Lujia; Qin, Zhenghong] Soochow Univ, Sch Pharm, Lab Aging & Nervous Dis, Suzhou 215123, Peoples R China.
[Wang, Linhui; Zhang, Guoxing] Soochow Univ, Sch Biol & Basic Med Sci, Dept Physiol, Suzhou 215123, Peoples R China.
[DiFiglia, Marian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurobiol Lab, Boston, MA 02129 USA.
RP Qin, ZH (reprint author), Soochow Univ, Sch Pharm, Dept Pharmacol, Suzhou 215123, Peoples R China.
EM qinzhenhong@suda.edu.cn
FU National Natural Science Foundation of China [30900464]; Jiangsu Higher
Education Institutions
FX This work was supported by grants from the National Natural Science
Foundation of China (No. 30900464) and PAPD (the Priority Academic
Program Development of Jiangsu Higher Education Institutions).
NR 52
TC 3
Z9 4
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1672-9145
J9 ACTA BIOCH BIOPH SIN
JI Acta Biochim. Biophys. Sin.
PD MAR
PY 2012
VL 44
IS 3
BP 249
EP 258
DI 10.1093/abbs/gmr125
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 898GM
UT WOS:000300727400008
PM 22234237
ER
PT J
AU Melendez, RI
McGinty, JF
Kalivas, PW
Becker, HC
AF Melendez, Roberto I.
McGinty, Jacqueline F.
Kalivas, Peter W.
Becker, Howard C.
TI Brain region-specific gene expression changes after chronic intermittent
ethanol exposure and early withdrawal in C57BL/6J mice
SO ADDICTION BIOLOGY
LA English
DT Article
DE Alcohol dependence; alcohol withdrawal; brain regional adaptations;
chronic intermittent alcohol exposure; gene expression profiling;
microarray analysis
ID FRONTAL-CORTEX; MICROARRAY ANALYSIS; ALCOHOL-DRINKING; SYNAPTIC
PLASTICITY; NEUROTROPHIC FACTOR; NONPREFERRING RATS; NUCLEUS-ACCUMBENS;
DENDRITIC SPINES; DRUG-ADDICTION; DEFICIENT MICE
AB Neuroadaptations that participate in the ontogeny of alcohol dependence are likely a result of altered gene expression in various brain regions. The present study investigated brain region-specific changes in the pattern and magnitude of gene expression immediately following chronic intermittent ethanol (CIE) exposure and 8 hours following final ethanol exposure [i.e. early withdrawal (EWD)]. High-density oligonucleotide microarrays (Affymetrix 430A 2.0, Affymetrix, Santa Clara, CA, USA) and bioinformatics analysis were used to characterize gene expression and function in the prefrontal cortex (PFC), hippocampus (HPC) and nucleus accumbens (NAc) of C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME, USA). Gene expression levels were determined using gene chip robust multi-array average followed by statistical analysis of microarrays and validated by quantitative real-time reverse transcription polymerase chain reaction and Western blot analysis. Results indicated that immediately following CIE exposure, changes in gene expression were strikingly greater in the PFC (284 genes) compared with the HPC (16 genes) and NAc (32 genes). Bioinformatics analysis revealed that most of the transcriptionally responsive genes in the PFC were involved in Ras/MAPK signaling, notch signaling or ubiquitination. In contrast, during EWD, changes in gene expression were greatest in the HPC (139 genes) compared with the PFC (four genes) and NAc (eight genes). The most transcriptionally responsive genes in the HPC were involved in mRNA processing or actin dynamics. Of the few genes detected in the NAc, the most representatives were involved in circadian rhythms. Overall, these findings indicate that brain region-specific and time-dependent neuroadaptive alterations in gene expression play an integral role in the development of alcohol dependence and withdrawal.
C1 [Becker, Howard C.] Med Univ S Carolina, Charleston Alcohol Res Ctr, Ctr Drug & Alcohol Programs, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
[Becker, Howard C.] Ralph H Johnson Dept Vet Affairs, Charleston, SC USA.
[Melendez, Roberto I.; McGinty, Jacqueline F.; Kalivas, Peter W.; Becker, Howard C.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
RP Becker, HC (reprint author), Med Univ S Carolina, Charleston Alcohol Res Ctr, Ctr Drug & Alcohol Programs, Dept Psychiat & Behav Sci, 67 President St,MSC-861, Charleston, SC 29425 USA.
EM beckerh@musc.edu
FU [R01 AA013885]; [P50 AA010761]; [P50 DA015369]
FX This study was supported by grants R01 AA013885 (H.C.B.), P50 AA010761
(H.C.B.) and P50 DA015369 (P.W.K.). The authors thank Rolf Fritz and Kay
Fernandez for excellent technical assistance and Saurin Jani for
assistance with bioinformatics analysis.
NR 83
TC 30
Z9 31
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1355-6215
J9 ADDICT BIOL
JI Addict. Biol.
PD MAR
PY 2012
VL 17
IS 2
BP 351
EP 364
DI 10.1111/j.1369-1600.2011.00357.x
PG 14
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 896LT
UT WOS:000300568500012
PM 21812870
ER
PT J
AU Wray, LO
Mavandadi, S
Klaus, JR
Tew, JD
Oslin, DW
Sweet, RA
AF Wray, Laura O.
Mavandadi, Shahrzad
Klaus, Johanna R.
Tew, James D., Jr.
Oslin, David W.
Sweet, Robert A.
TI The Association Between Mental Health and Cognitive Screening Scores in
Older Veterans
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE Cognitive impairment; mental health screening; older adults; primary
care
ID PRIMARY-CARE SETTINGS; LATE-LIFE DEPRESSION; ALZHEIMERS-DISEASE;
COMMUNITY POPULATION; RISK-FACTOR; DEMENTIA; IMPAIRMENT; METAANALYSIS;
RELIABILITY; VALIDATION
AB Objectives: To examine overall cognitive screening results and the relationship between cognitive screen score and sociodemographic characteristics, reason for referral, and clinical outcomes of older veterans referred by primary care for a behavioral health assessment. Design: Cross-sectional, naturalistic study. Setting: Primary care clinics affiliated with two VA Medical Centers. Participants: The sample included 4,325 older veterans referred to the Behavioral Health Laboratory who completed an initial mental health/substance abuse assessment. Veterans were categorized into the following three groups on the basis of cognitive status: within normal limits, possible cognitive impairment, and possible dementia. Measurements: Sociodemographic and clinical data on reason for referral, cognitive functioning (i.e., Blessed Orientation-Memory-Concentration test), and behavioral health assessment outcomes were extracted from patients' medical records. Data were analyzed using multiple linear and logistic regressions. Results: Results of cognitive screenings indicated that the majority of the sample was within normal limits (62.5%), with 25.8%, 8.1%, and 3.6% of patients evidencing possible cognitive impairment, possible dementia, and Blessed Orientation-Memory-Concentration scores of 17 or more, respectively. With regard to reason for referral, patients with greater cognitive impairment were more likely to be identified by the antidepressant case finder than patients with less impairment. Increased age, non-white ethnicity, self-perceived inadequate finances, major depressive disorder, and symptoms of psychosis were associated with greater cognitive impairment. Conclusions: Findings highlight the importance of evaluating cognitive status in older adults who are referred for a behavioral health assessment and/or receive a new mental health/substance abuse diagnosis. Doing so has the potential to improve recognition and treatment of cognitive impairment and dementia, thereby improving quality of care for many older adults. (Am J Geriatr Psychiatry 2012; 20:215-227)
C1 [Wray, Laura O.] Ctr Integrated Healthcare, Dept Vet Affairs, Buffalo, NY 14215 USA.
[Wray, Laura O.] SUNY Buffalo, Sch Med & Biomed Sci, Div Geriatr, Buffalo, NY 14260 USA.
[Mavandadi, Shahrzad; Klaus, Johanna R.; Oslin, David W.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA.
[Mavandadi, Shahrzad; Klaus, Johanna R.; Oslin, David W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Tew, James D., Jr.; Sweet, Robert A.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA.
[Tew, James D., Jr.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA.
[Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
RP Wray, LO (reprint author), Ctr Integrated Healthcare, Dept Vet Affairs, VAWNYHS 116N,3495 Bailey Ave, Buffalo, NY 14215 USA.
EM laura.wray@va.gov
FU USPHS [AG027224]
FX This study was supported in part by USPHS grant AG027224.
NR 51
TC 3
Z9 3
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
BP 215
EP 227
DI 10.1097/JGP.0b013e3182410cdb
PG 13
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 897IH
UT WOS:000300642300004
PM 22251868
ER
PT J
AU Shah, A
Fried, LF
Chen, SC
Qiu, Y
Li, SY
Cavanaugh, KL
Norris, KC
Whaley-Connell, AT
McCullough, PA
Mehrotra, R
AF Shah, Anuja
Fried, Linda F.
Chen, Shu-Cheng
Qiu, Yang
Li, Suying
Cavanaugh, Kerri L.
Norris, Keith C.
Whaley-Connell, Adam T.
McCullough, Peter A.
Mehrotra, Rajnish
CA KEEP Investigators
TI Associations Between Access to Care and Awareness of CKD
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Access to care; awareness; chronic kidney disease; health insurance
ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; HEALTH-CARE; US ADULTS;
POPULATION; PREVALENCE; PATIENT; TRENDS
AB Background: Most individuals with chronic kidney disease (CKD) in the United States are unaware of their condition, creating challenges in implementing early interventions to delay disease progression. Whether characteristics expected to enhance health care access are associated with greater CKD awareness has not been studied adequately.
Method: Data from volunteer participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP), 2000-2010, with presumed CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m(2) or albumin-creatinine ratio >30 mg/g) were analyzed. Given that the diagnosis of CKD was based on a single measurement of kidney function, the diagnosis is presumed, but not confirmed. Associations of CKD awareness with measures of access to care (health insurance coverage, type of health insurance, prescription drug coverage, and self-reported level of difficulty obtaining care) were examined using logistic regression.
Results: Of 29,144 participants with CKD, 6,751 (23%) reported CKD awareness. No significant association was found between availability of health insurance or prescription drug coverage and CKD awareness; results did not vary by diabetic status or in analyses restricted to participants with eGFR <60 mL/min/1.73 m(2). Participants reporting extreme or some difficulty obtaining medical care were more likely than those reporting no difficulty to be aware of CKD (adjusted OR, 1.25; 95% CI, 1.05-1.50).
Conclusions: Most KEEP participants with CKD are unaware of the condition, results that are not modified by the availability of health insurance or prescription drug coverage. The mechanisms underlying the association of perceived difficulty in access to care with greater CKD awareness require further study. Am J Kidney Dis. 59(3)(S2):S16-S23. 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 [Shah, Anuja; Mehrotra, Rajnish] Harbor UCLA, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA.
[Fried, Linda F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Chen, Shu-Cheng; Qiu, Yang; Li, Suying] Minneapolis Med Res Fdn Inc, Chron Kidney Dis Res Grp, Minneapolis, MN USA.
[Cavanaugh, Kerri L.] Vanderbilt Univ, Nashville, TN USA.
[Norris, Keith C.] Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA.
[Whaley-Connell, Adam T.] Univ Missouri, Columbia Sch Med, Harry S Truman VA Med Ctr, Columbia, MO USA.
[Whaley-Connell, Adam T.] Univ Missouri, Columbia Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Columbia, MO USA.
[McCullough, Peter A.] St John Providence Hlth Syst, Providence Pk Heart Inst, Novi, MI USA.
RP Mehrotra, R (reprint author), Harbor UCLA, Los Angeles Biomed Res Inst, 1124 W Carson St, Torrance, CA 90502 USA.
EM rmehrotra@labiomed.org
OI Whaley-Connell, Adam/0000-0001-8955-5560
FU Amgen; Abbott; Siemens; Astellas; Fresenius Medical Care; Genzyme;
LifeScan; Nephroceuticals; Pfizer; National Kidney Foundation of
Southern California; National Institutes of Health (NIH) [R21 DK077341,
RR026138, MD000182, R03AG040638-01]; DaVita Inc.; Department of
Veteran's Affairs [CDA-2]; American Society of Nephrology-Association of
Specialty Professors-National Institute on Aging; [DK K23080952]
FX The KEEP is a program of the National Kidney Foundation Inc and is
supported by Amgen, Abbott, Siemens, Astellas, Fresenius Medical Care,
Genzyme, LifeScan, Nephroceuticals, and Pfizer. Dr Shah is supported by
a research grant from the National Kidney Foundation of Southern
California and a Genzyme Fellowship Grant. Dr Mehrotra is supported by
National Institutes of Health (NIH) grant R21 DK077341 and a research
grant from DaVita Inc. Dr Cavanaugh is supported by DK K23080952. Dr
Norris receives support from NIH grants RR026138 and MD000182. Dr
Whaley-Connell is supported by the Department of Veteran's Affairs
CDA-2, the NIH grant R03AG040638-01, and the American Society of
Nephrology-Association of Specialty Professors-National Institute on
Aging Development Grant in Geriatric Nephrology.
NR 17
TC 10
Z9 10
U1 2
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 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD MAR
PY 2012
VL 59
IS 3
SU 2
BP S16
EP S23
DI 10.1053/j.ajkd.2011.10.042
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 896ZA
UT WOS:000300608900003
PM 22339898
ER
PT J
AU Viron, M
Baggett, T
Hill, M
Freudenreich, O
AF Viron, Mark
Baggett, Travis
Hill, Michele
Freudenreich, Oliver
TI Schizophrenia for Primary Care Providers: How to Contribute to the Care
of a Vulnerable Patient Population
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Review
DE Cardiovascular disease; Management; Medical morbidity; Primary care;
Schizophrenia; Treatment
ID SERIOUS MENTAL-ILLNESS; HEALTH-CARE; 1ST-EPISODE PSYCHOSIS;
GENERAL-PRACTITIONERS; ANTIPSYCHOTIC-DRUGS; BIPOLAR DISORDER;
MEDICAL-CARE; LIFE-STYLE; MORTALITY; PEOPLE
AB Patients with schizophrenia represent a vulnerable population with high medical needs that are often missed or undertreated. Primary care providers have the potential to reduce health disparities experienced by this population and make a substantial difference in the overall health of these patients. This review provides primary care providers with a general understanding of the psychiatric and medical issues specific to patients with schizophrenia and a clinically practical framework for engaging and assessing this vulnerable patient population and assisting them in achieving optimal health. Initial steps in this framework include conducting a focused medical evaluation of psychosis and connecting patients with untreated psychosis to psychiatric care as promptly as possible. Given the significant contribution of cardiovascular disease to morbidity and mortality in schizophrenia, a top priority of primary care for patients with schizophrenia should be cardiovascular disease prevention and treatment through regular risk factor screening, appropriate lifestyle interventions, and other indicated therapies. (C) 2012 Elsevier Inc. All rights reserved. . The American Journal of Medicine (2012) 125, 223-230
C1 [Viron, Mark; Hill, Michele; Freudenreich, Oliver] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA.
[Baggett, Travis] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
RP Viron, M (reprint author), Massachusetts Gen Hosp, Schizophrenia Program, 25 Staniford St, Boston, MA 02114 USA.
EM mviron@partners.org
FU Pfizer
FX Dr Freudenreich has received research grant support from Pfizer and
honoraria from Reed Medical Education for Continuing Medical Education
lectures, and has served as a consultant for Transcept and Beacon Health
Strategies. The remaining authors have no conflicts of interests to
disclose.
NR 59
TC 7
Z9 7
U1 3
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD MAR
PY 2012
VL 125
IS 3
BP 223
EP 230
DI 10.1016/j.amjmed.2011.05.002
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 897BI
UT WOS:000300615400010
PM 22340915
ER
PT J
AU O'Seaghdha, CM
Lyass, A
Massaro, JM
Meigs, JB
Coresh, J
D'Agostino, RB
Astor, BC
Fox, CS
AF O'Seaghdha, Conall M.
Lyass, Asya
Massaro, Joseph M.
Meigs, James B.
Coresh, Josef
D'Agostino, Ralph B., Sr.
Astor, Brad C.
Fox, Caroline S.
TI A Risk Score for Chronic Kidney Disease in the General Population
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Chronic kidney disease; CKD; Risk score
ID GLOMERULAR-FILTRATION-RATE; CORONARY-HEART-DISEASE; IMPROVING GLOBAL
OUTCOMES; ATHEROSCLEROSIS RISK; POSITION STATEMENT; SERUM CREATININE;
RENAL-DISEASE; PREDICTION; COMMUNITIES; PROGRESSION
AB BACKGROUND: Stratification of individuals at risk for chronic kidney disease may allow optimization of preventive measures to reduce disease incidence and complications. We sought to develop a risk score that estimates an individual's absolute risk of incident chronic kidney disease.
METHODS: Framingham Heart Study participants free of baseline chronic kidney disease, who attended a baseline examination in 1995-1998 and follow-up in 2005-2008, were included in the analysis (n = 2490). Chronic kidney disease was defined as an estimated glomerular filtration rate <60 mL/min/1.73m(2) using the Modification of Diet in Renal Disease equation. Participants were assessed for the development of chronic kidney disease at 10 years follow-up. Stepwise logistic regression was used to identify chronic kidney disease risk factors, and these were used to construct a risk score predicting 10-year chronic kidney disease risk. Performance characteristics were assessed using calibration and discrimination measures. The final model was externally validated in the bi-ethnic Atherosclerosis Risk in Communities Study (n = 1777).
RESULTS: There were 1171 men and 1319 women at baseline, and the mean age was 57.1 years. At follow-up, 9.2% (n = 229) had developed chronic kidney disease. Age, diabetes, hypertension, baseline estimated glomerular filtration rate, and albuminuria were independently associated with incident chronic kidney disease (P < .05), and these covariates were incorporated into a risk function (c-statistic 0.813). In external validation in the ARIC study, the c-statistic was 0.74 in whites (n = 1353) and 0.75 in blacks (n = 424).
CONCLUSION: Risk stratification for chronic kidney disease is achievable using a risk score derived from clinical factors that are readily accessible in primary care. The utility of this score in identifying individuals in the community at high risk of chronic kidney disease warrants further investigation. Published by Elsevier Inc. . The American Journal of Medicine (2012) 125, 270-277
C1 [O'Seaghdha, Conall M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Seaghdha, Conall M.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Brigham & Womens Hosp, Boston, MA 02114 USA.
[O'Seaghdha, Conall M.; Meigs, James B.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Lyass, Asya; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Massaro, Joseph M.] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Coresh, Josef; Astor, Brad C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Coresh, Josef; Astor, Brad C.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Coresh, Josef; Astor, Brad C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA.
[Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, 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, N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022]; National Institute of Diabetes and Digestive and Kidney
Diseases [1 R01 DK076770-01]; [U01HL075572-01]
FX The Framingham Heart Study is supported by the National Heart, Lung, and
Blood Institute (N01-HC-25195); urinary albumin excretion assay reagents
were donated by Roche Diagnostics Inc. The Atherosclerosis Risk in
Communities (ARIC) Study is carried out as a collaborative study
supported by National Heart, Lung, and Blood Institute contracts
N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021, and N01-HC-55022, with the ARIC Carotid MRI Study funded
by U01HL075572-01. Drs Astor and Coresh are supported by the National
Institute of Diabetes and Digestive and Kidney Diseases (1 R01
DK076770-01).
NR 39
TC 16
Z9 16
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD MAR
PY 2012
VL 125
IS 3
BP 270
EP 277
DI 10.1016/j.amjmed.2011.09.009
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 897BI
UT WOS:000300615400020
PM 22340925
ER
PT J
AU Miranda, A
Figoni, SF
Cha, T
Flanagan, T
Mandal, O
Silva, M
Scremin, AME
Scremin, OU
AF Miranda, Alberto
Figoni, Stephen F.
Cha, Tha
Flanagan, Terrance
Mandal, Oanh
Silva, Mariana
Scremin, A. M. Erika
Scremin, Oscar U.
TI Calf Tissue Oxygenation During Exercise in Men with and Without Risk
Factors for Developing Peripheral Arterial Disease
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE Rehabilitation; Exercise Test; Spectroscopy; Near-Infrared; Peripheral
Vascular Diseases
ID NEAR-INFRARED SPECTROSCOPY; INTERMITTENT CLAUDICATION; SHORT-TERM;
VASCULAR-DISEASE; LOWER-EXTREMITY; SMOKING; POPULATION; SATURATION;
REHABILITATION; DYSFUNCTION
AB Miranda A, Figoni SF, Cha T, Flanagan T, Mandal O, Silva M, Scremin AME, Scremin OU: Calf tissue oxygenation during exercise in men with and without risk factors for developing peripheral arterial disease. Am J Phys Med Rehabil 2012;91:200Y210.
Objective: This study aimed to compare calf tissue oxygenation responses to calf exercise in men without diagnosed peripheral arterial disease but with selected risk factors for peripheral arterial disease with those without risk factors.
Design: A cross-sectional quasi-experimental design was used. The no-risk group (n = 20) had none of the risk factors (diabetes, hypertension, hyperlipidemia, obesity, current or 10 pack-yr smoking history, or age >= 65 yrs). The at-risk group (n = 45) had one to six risk factors. Medial calf tissue oxygenation (percentage saturation) was determined using near-infrared spectroscopy during seven consecutive 5-min test stages: rest, O-W active plantar/dorsiflexion, rest, 4-W resistive plantar flexion, rest, 8-W resistive plantar flexion, and rest. Resistive exercise was performed on the Stresst'er calf ergometer.
Results: Compared with the no-risk group, decrements in calf tissue oxygenation induced by light-to-moderate resistive calf exercise in the at-risk group was significantly greater (by 9% saturation) (4-W: P < 0.001; 8-W: P = 0.002).
Conclusions: Men with risk factors for developing peripheral arterial disease but without such diagnosis demonstrated greater decrements in calf tissue oxygenation during calf exercise compared with men without risk factors. Further development of this test may lead to early diagnosis and intervention to modify risk factors and prevent co-morbidities.
C1 [Scremin, A. M. Erika] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, VA Greater Los Angeles Healthcare Syst,Phys Med &, Los Angeles, CA 90095 USA.
[Miranda, Alberto; Figoni, Stephen F.; Cha, Tha; Flanagan, Terrance; Mandal, Oanh; Silva, Mariana; Scremin, A. M. Erika] VA Greater Los Angeles Healthcare Syst, Rehabil Serv, Los Angeles, CA USA.
[Scremin, Oscar U.] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA.
[Scremin, Oscar U.] Univ Calif Los Angeles, Dept Physiol, Geffen Sch Med, VA Greater Los Angeles Healthcare Syst,Phys Med &, Los Angeles, CA 90024 USA.
RP Miranda, A (reprint author), VA W Los Angeles Healthcare Ctr, PM&RS 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
NR 35
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-9115
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD MAR
PY 2012
VL 91
IS 3
BP 200
EP 210
DI 10.1097/PHM.0b013e3182411df9
PG 11
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 898BA
UT WOS:000300708900003
PM 22257970
ER
PT J
AU Saladin, ME
Santa Ana, EJ
LaRowe, SD
Simpson, AN
Tolliver, BK
Price, KL
McRae-Clark, AL
Brady, KT
AF Saladin, Michael E.
Santa Ana, Elizabeth J.
LaRowe, Steven D.
Simpson, Annie N.
Tolliver, Bryan K.
Price, Kimber L.
McRae-Clark, Aimee L.
Brady, Kathleen T.
TI Does Alexithymia Explain Variation in Cue-Elicited Craving Reported by
Methamphetamine-Dependent Individuals?
SO AMERICAN JOURNAL ON ADDICTIONS
LA English
DT Article
ID PSYCHOACTIVE SUBSTANCE DEPENDENCE; MAINTAINING ABSTINENCE; SCALE;
ALCOHOL; ABUSERS; VALIDATION; DEPRESSION; REACTIVITY; DISORDERS; WOMEN
AB Drug craving is an important motivational phenomenon among addicted individuals, and successful management of craving is essential to both the initiation and maintenance of abstinence. Although craving in response to drug cues is common in drug-dependent individuals, it is not universal. At the present time, it is not known why approximately 2030% of all addicted persons fail to report appreciable craving in laboratory-based cue reactivity studies. This study examined the possibility that alexithymia, a personality attribute characterized by a difficulty identifying and describing emotions, may contribute to the impoverished cue-elicited craving experienced by some addicts. Specifically, we tested the hypothesis that alexithymia, as measured by the Toronto Alexithymia Scale (TAS), would be inversely related to the magnitude of cue-elicited craving obtained in a cue reactivity protocol. Forty methamphetamine-dependent individuals completed the TAS and provided craving ratings for methamphetamine after presentation of methamphetamine-associated cues. Thirteen participants (32%) reported no methamphetamine cue-elicited craving. Contrary to expectation, TAS factor 1 (a measure of difficulty identifying feelings) scores were positively associated with cue-elicited craving. Thus, the results suggest that increasing difficulty-identifying feelings may be associated with higher cue-elicited craving. Clinical implications for this finding are discussed. (Am J Addict 2012:21:130135)
C1 [Saladin, Michael E.] Med Univ S Carolina, Coll Hlth Profess, Dept Hlth Sci & Res, Charleston, SC 29425 USA.
[Saladin, Michael E.; Santa Ana, Elizabeth J.; Simpson, Annie N.; Tolliver, Bryan K.; Price, Kimber L.; McRae-Clark, Aimee L.; Brady, Kathleen T.] Med Univ S Carolina, Clin Neurosci Div, Charleston, SC 29425 USA.
[Santa Ana, Elizabeth J.; LaRowe, Steven D.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Subst Abuse Treatment Ctr, Charleston, SC USA.
[LaRowe, Steven D.] Med Univ S Carolina, Ctr Drug & Alcohol Programs, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
[Simpson, Annie N.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA.
RP Saladin, ME (reprint author), Med Univ S Carolina, Coll Hlth Profess, Dept Hlth Sci & Res, 77 President St,Room 222,MSC700, Charleston, SC 29425 USA.
EM saladinm@musc.edu
RI McRae-Clark, Aimee/I-3341-2013
OI McRae-Clark, Aimee/0000-0002-9774-318X
FU NCRR NIH HHS [KL2 RR029880, KL2 RR029880-01, KL2 RR029880-02, KL2
RR029880-03, TL1 RR029881, TL1 RR029881-01, TL1 RR029881-02, TL1
RR029881-03, UL1 RR029882, UL1 RR029882-01, UL1 RR029882-02, UL1
RR029882-03]; NIDA NIH HHS [R25 DA020537, P20 DA022658, P20 DA022658-01,
P20 DA022658-02, P20 DA022658-02S1, P20 DA022658-03, P20 DA022658-04,
U10 DA013727, U10 DA013727-10, U10 DA013727-10S1, U10 DA013727-10S2, U10
DA013727-10S3, U10 DA013727-11, U10 DA013727-11S1, U10 DA013727-12]
NR 47
TC 7
Z9 8
U1 2
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1055-0496
J9 AM J ADDICTION
JI Am. J. Addict.
PD MAR-APR
PY 2012
VL 21
IS 2
BP 130
EP 135
DI 10.1111/j.1521-0391.2011.00214.x
PG 6
WC Substance Abuse
SC Substance Abuse
GA 894SO
UT WOS:000300447300006
PM 22332856
ER
PT J
AU Cooper, ZR
Powers, CL
Cobb, JP
AF Cooper, Zara R.
Powers, Carol L.
Cobb, J. Perren
TI Putting the Patient First Honoring Advance Directives Prior to Surgery
SO ANNALS OF SURGERY
LA English
DT Editorial Material
ID QUALITY-OF-LIFE; CARE; END; DECISIONS; CANCER; ILL
C1 [Cooper, Zara R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Powers, Carol L.] Harvard Univ, Community Eth Comm, Boston, MA 02115 USA.
[Cobb, J. Perren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Crit Care Ctr,Dept Anaesthesia, Boston, MA 02115 USA.
[Cobb, J. Perren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Crit Care Ctr,Dept Surg, Boston, MA 02115 USA.
RP Cooper, ZR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, 75 Francis St, Boston, MA 02115 USA.
EM ZCOOPER@partners.org
NR 23
TC 9
Z9 9
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
J9 ANN SURG
JI Ann. Surg.
PD MAR
PY 2012
VL 255
IS 3
BP 424
EP 426
DI 10.1097/SLA.0b013e318246c1ad
PG 3
WC Surgery
SC Surgery
GA 897FI
UT WOS:000300631300004
PM 22281702
ER
PT J
AU Wang, JP
Dang, P
Raut, CP
Pandalai, PK
Maduekwe, UN
Rattner, DW
Lauwers, GY
Yoon, SS
AF Wang, Jiping
Dang, Ping
Raut, Chandrajit P.
Pandalai, Prakash K.
Maduekwe, Ugwuji N.
Rattner, David W.
Lauwers, Gregory Y.
Yoon, Sam S.
TI Comparison of a Lymph Node Ratio-Based Staging System With the 7th AJCC
System for Gastric Cancer Analysis of 18,043 Patients From the SEER
Database
SO ANNALS OF SURGERY
LA English
DT Article
ID INDEPENDENT PROGNOSTIC-FACTOR; N-RATIO; UNITED-STATES; SURVIVAL;
ADENOCARCINOMA; CARCINOMA; IMPACT; CHEMORADIOTHERAPY; LYMPHADENECTOMY;
GASTRECTOMY
AB Objectives: The American Joint Committee on Cancer (AJCC) staging system for gastric cancer bases N status on absolute number of metastatic nodes, regardless of the number of examined nodes. We examined a modified staging system utilizing node ratio (Nr), the ratio of metastatic to examined nodes.
Methods: A total of 18,043 gastric cancer patients who underwent gastrectomy were identified from the US Surveillance, Epidemiology, and End Results (SEER) database. A training set was divided into 5 Nr groups, and a TNrM staging system was constructed. Median survival and overall survival, based on 7th edition AJCC and TNrM staging systems, were compared, and the analysis was repeated in a validation set.
Results: Median examined nodes were 10 to 11. For the training set, overall survival for all 5 AJCC N categories was significantly different when sub-grouped into 15 or fewer versus more than 15 examined nodes, but overall survival was similar regardless of the number of examined nodes in 4 of 5 Nr categories. Seven AJCC stages had statistically different overall survival between subgroups, whereas only 1 TNrM stage had statistically different overall survival between subgroups. When misclassification was defined as any subgroup in which median survival fell outside the 95% confidence interval of the group's overall median survival, AJCC staging misclassified 57% of patients and TNrM staging misclassified only 12%. Similar results were found in the validation set.
Conclusions: The AJCC system classifies SEER gastric cancer patients into stages in which subgroups often have wide variations in survival. For patients undergoing limited lymph node analysis, the proposed TNrM system may predict survival more accurately.
C1 [Wang, Jiping; Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Wang, Jiping; Raut, Chandrajit P.] Harvard Univ, Sch Med, Boston, MA USA.
[Dang, Ping; Pandalai, Prakash K.; Maduekwe, Ugwuji N.; Rattner, David W.; Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Wang, JP (reprint author), Brigham & Womens Hosp, Dept Surg, 353 Carrie Hall,75 Francis St, Boston, MA 02115 USA.
EM jwang39@partners.org; syoon@partners.org
NR 32
TC 69
Z9 78
U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
J9 ANN SURG
JI Ann. Surg.
PD MAR
PY 2012
VL 255
IS 3
BP 478
EP 485
DI 10.1097/SLA.0b013e31824857e2
PG 8
WC Surgery
SC Surgery
GA 897FI
UT WOS:000300631300013
PM 22330040
ER
PT J
AU Derwall, M
Malhotra, R
Lai, CS
Beppu, Y
Aikawa, E
Seehra, JS
Zapol, WM
Bloch, KD
Yu, PB
AF Derwall, Matthias
Malhotra, Rajeev
Lai, Carol S.
Beppu, Yuko
Aikawa, Elena
Seehra, Jasbir S.
Zapol, Warren M.
Bloch, Kenneth D.
Yu, Paul B.
TI Inhibition of Bone Morphogenetic Protein Signaling Reduces Vascular
Calcification and Atherosclerosis
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE atherosclerosis; calcification; lipids; reactive oxygen species; signal
transduction
ID LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE-CELLS; MATRIX GLA PROTEIN; FATTY
LIVER-DISEASE; OXIDATIVE STRESS; ENDOTHELIAL-CELLS; REGULATORY
MECHANISMS; MURINE MODELS; NADPH OXIDASE; IN-VIVO
AB Objective-The expression of bone morphogenetic proteins (BMPs) is enhanced in human atherosclerotic and calcific vascular lesions. Although genetic gain-and loss-of-function experiments in mice have supported a causal role of BMP signaling in atherosclerosis and vascular calcification, it remains uncertain whether BMP signaling might be targeted pharmacologically to ameliorate both of these processes.
Methods and Results-We tested the impact of pharmacological BMP inhibition on atherosclerosis and calcification in LDL receptor-deficient (LDLR-/-) mice. LDLR-/- mice fed a high-fat diet developed abundant vascular calcification within 20 weeks. Prolonged treatment of LDLR-/- mice with the small molecule BMP inhibitor LDN-193189 was well-tolerated and potently inhibited development of atheroma, as well as associated vascular inflammation, osteogenic activity, and calcification. Administration of recombinant BMP antagonist ALK3-Fc replicated the antiatherosclerotic and anti-inflammatory effects of LDN-193189. Treatment of human aortic endothelial cells with LDN-193189 or ALK3-Fc abrogated the production of reactive oxygen species induced by oxidized LDL, a known early event in atherogenesis. Unexpectedly, treatment of mice with LDN-193189 lowered LDL serum cholesterol by 35% and markedly decreased hepatosteatosis without inhibiting HMG-CoA reductase activity. Treatment with BMP2 increased, whereas LDN-193189 or ALK3-Fc inhibited apolipoprotein B100 secretion in HepG2 cells, suggesting that BMP signaling contributes to the regulation of cholesterol biosynthesis.
Conclusion-These results definitively implicate BMP signaling in atherosclerosis and calcification, while uncovering a previously unidentified role for BMP signaling in LDL cholesterol metabolism. BMP inhibition may be helpful in the treatment of atherosclerosis and associated vascular calcification. (Arterioscler Thromb Vasc Biol. 2012;32:613-622.)
C1 [Derwall, Matthias] Rhein Westfal TH Aachen, Uniklin Aachen, Dept Anesthesia, D-52074 Aachen, Germany.
[Derwall, Matthias; Beppu, Yuko; Zapol, Warren M.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Malhotra, Rajeev; Lai, Carol S.; Bloch, Kenneth D.; Yu, Paul B.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Malhotra, Rajeev; Lai, Carol S.; Bloch, Kenneth D.; Yu, Paul B.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA.
[Aikawa, Elena] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Derwall, Matthias] Rhein Westfal TH Aachen, D-52074 Aachen, Germany.
[Seehra, Jasbir S.] Acceleron Pharma Inc, Cambridge, MA USA.
RP Derwall, M (reprint author), Rhein Westfal TH Aachen, Uniklin Aachen, Dept Anesthesia, Pauwelsstr 30, D-52074 Aachen, Germany.
EM mderwall@ukaachen.de; pbyu@partners.org
OI Yu, Paul/0000-0003-2145-4944; Malhotra, Rajeev/0000-0003-0120-4630
FU German Research Foundation (Deutsche Forschungsgemeinschaft)
[DE-1685-1/1]; US National Institutes of Health [T32HL007208, AR057374];
Leducq Foundation; Massachusetts Technology Transfer Center, Boston MA;
Howard Hughes Medical Institute; American Heart Association
[11FTF7290032]
FX This work was supported by a research fellowship award of the German
Research Foundation (Deutsche Forschungsgemeinschaft, DE-1685-1/1,
M.D.), the US National Institutes of Health (T32HL007208, R.M.;
AR057374, P.B.Y.), the Leducq Foundation (Multidisciplinary Program to
Elucidate the Role of Bone Morphogenetic Protein Signaling in the
Pathogenesis of Pulmonary and Systemic Vascular Diseases, K.D.B. and
P.B.Y.), the Massachusetts Technology Transfer Center, Boston MA
(P.B.Y.), the Howard Hughes Medical Institute (P.B.Y.), and the American
Heart Association (11FTF7290032, R.M.).
NR 53
TC 68
Z9 77
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD MAR
PY 2012
VL 32
IS 3
BP 613
EP U168
DI 10.1161/ATVBAHA.111.242594
PG 23
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 897HP
UT WOS:000300639300016
PM 22223731
ER
PT J
AU Noto, D
Cefalu, AB
Valenti, V
Fayer, F
Pinotti, E
Ditta, M
Spina, R
Vigna, G
Yue, P
Kathiresan, S
Tarugi, P
Averna, MR
AF Noto, Davide
Cefalu, Angelo B.
Valenti, Vincenza
Fayer, Francesca
Pinotti, Elisa
Ditta, Mariangela
Spina, Rossella
Vigna, Giovanni
Yue, Pin
Kathiresan, Sekar
Tarugi, Patrizia
Averna, Maurizio R.
TI Prevalence of ANGPTL3 and APOB Gene Mutations in Subjects With Combined
Hypolipidemia
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE epidemiology; lipoproteins; genetics; hypobetalipoproteinemia
ID FAMILIAL HYPOBETALIPOPROTEINEMIA; LIPOPROTEIN-LIPASE; TRIGLYCERIDE;
CHOLESTEROL; METABOLISM
AB Objective-Mutations of the ANGPTL3 gene have been associated with a novel form of primary hypobetalipoproteinemia, the combined hypolipidemia (cHLP), characterized by low total cholesterol and low HDL-cholesterol levels. The aim of this work is to define the role of ANGPTL3 gene as determinant of the combined hypolipidemia phenotype in 2 large cohorts of 913 among American and Italian subjects with primary hypobetalipoproteinemia (total cholesterol <5th percentile).
Methods and Results-The combined hypolipidemia cut-offs were chosen according to total cholesterol and HDL-cholesterol levels reported in the ANGPTL3 kindred described to date: total cholesterol levels, <2nd percentile and HDL-cholesterol, levels <2nd decile. Seventy-eight subjects with combined hypolipidemia were analyzed for ANGPTL3 and APOB genes. We identified nonsense and/or missense mutations in ANGPTL3 gene in 8 subjects; no mutations of the APOB gene were found. Mutated ANGPTL3 homozygous/compound heterozygous subjects showed a more severe biochemical phenotype compared to heterozygous or ANGPTL3 negative subjects, although ANGPTL3 heterozygotes did not differ from ANGPTL3 negative subjects.
Conclusion-These results demonstrated that in a cohort of subjects with severe primary hypobetalipoproteinemia the prevalence of ANGPTL3 gene mutations responsible for a combined hypolipidemia phenotype is about 10%, whereas mutations of APOB gene are absent. (Arterioscler Thromb Vasc Biol. 2012; 32:805-809.)
C1 [Noto, Davide; Cefalu, Angelo B.; Valenti, Vincenza; Fayer, Francesca; Ditta, Mariangela; Spina, Rossella; Averna, Maurizio R.] Univ Palermo, Dept Internal Med & Med Specialties, I-90127 Palermo, Italy.
[Pinotti, Elisa; Tarugi, Patrizia] Univ Modena & Reggio Emilia, Dept Biomed Sci, I-41100 Modena, Italy.
[Vigna, Giovanni] Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy.
[Yue, Pin] Washington Univ, Sch Med, St Louis, MO USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Averna, MR (reprint author), Univ Palermo, Dept Internal Med & Med Specialties, Via Vespro 141, I-90127 Palermo, Italy.
EM tarugi@unimore.it; maurizio.averna@unipa.it
RI Tarugi, Patrizia/D-2179-2015; Vigna, Giovanni/H-2826-2015;
OI Tarugi, Patrizia/0000-0001-6864-7853; Vigna,
Giovanni/0000-0001-8640-7052; Noto, Davide/0000-0002-5346-2829; Cefalu',
Angelo Baldassare/0000-0003-1259-8284; Averna,
Maurizio/0000-0003-3558-9209
FU University of Palermo; Italian Ministry of Education, University and
Research [2009-RLKXPF]; Fondazione Cassa di Risparmio di Modena
FX This work was supported by contract grants from the University of
Palermo (60% to M.R.A. and A.B.C.), Grant 2009-RLKXPF "PRIN 2009" from
the Italian Ministry of Education, University and Research (to M.R.A.),
and the "Fondazione Cassa di Risparmio di Modena" (to P.T.).
NR 18
TC 25
Z9 25
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD MAR
PY 2012
VL 32
IS 3
BP 805
EP U591
DI 10.1161/ATVBAHA.111.238766
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 897HP
UT WOS:000300639300037
PM 22247256
ER
PT J
AU Tian, L
Luo, NL
Zhu, XL
Chung, BH
Garvey, WT
Fu, YC
AF Tian, Ling
Luo, Nanlan
Zhu, Xiaolin
Chung, Byung-Hong
Garvey, W. Timothy
Fu, Yuchang
TI Adiponectin-AdipoR1/2-APPL1 signaling axis suppresses human foam cell
formation: Differential ability of AdipoR1 and AdipoR2 to regulate
inflammatory cytokine responses
SO ATHEROSCLEROSIS
LA English
DT Article
DE Adiponectin; Adiponectin receptor; APPL1; Macrophages; Foam cells;
Atherosclerosis; Inflammation
ID MONOCYTE-DERIVED MACROPHAGES; PLASMA-PROTEIN ADIPONECTIN;
LIPID-ACCUMULATION; METABOLIC SYNDROME; RECEPTORS; ATHEROSCLEROSIS;
DISEASE; OBESITY; PERSPECTIVE; ACTIVATION
AB Objective: Adiponectin is an adipokine that exerts anti-inflammatory and anti-atherogenic effects during macrophage transformation into foam cells. To further understand the signaling pathways of adiponectin involved in macrophage foam cell transformation, we investigated the roles of two adiponectin receptors (AdipoR1 and AdipoR2) and their downstream adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1 (APPL1) in mediating adiponectin action on foam cell transformation.
Methods and Results: Transfections were performed to overexpress or knockdown AdipoR1 or AdipoR2 genes in human THP-1 monocytes. Lentiviral-shRNAs were also used to knockdown APPL1 gene in these cells. Foam cell transformation was induced via exposure to oxidized low-density lipoprotein (oxLDL). Our results showed that both AdipoR1 and AdipoR2 were critical for transducing the adiponectin signal that suppresses lipid accumulation and inhibits transformation from macrophage to foam cell. However, AdipoR1 and AdipoR2 were found to have differential effects in diminishing proinflammatory responses. While AdipoR1 was required by adiponectin to suppress tumor necrosis factor alpha (TNF alpha) and monocyte chemotactic protein 1 (MCP-1) gene expression, AdipoR2 served as the dominant receptor for adiponectin suppression of scavenger receptor A type 1 (SR-AI) and upregulation of interleukin-1 receptor antagonist (IL-1Ra). Knockdown of APPL1 significantly abrogated the ability of adiponectin to inhibit lipid accumulation, SR-AI and nuclear factor-kappa B (NF-kappa B) gene expression, and Akt phosphorylation in macrophage foam cells.
Conclusions: In current studies, we have demonstrated that adiponectin's abilty to suppress macrophage lipid accumulation and foam cell formation is mediated through AdipoR1 and AdipoR2 and the APPL1 docking protein. However, AdipoR1 and AdipoR2 exhibited a differential ability to regulate inflammatory cytokines and SR-A1. These novel data support the idea that the adiponectin-AdipoR1/ 2-APPL1 axis may serve as a potential therapeutic target for preventing macrophage foam cell formation and atherosclerosis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Tian, Ling; Luo, Nanlan; Chung, Byung-Hong; Garvey, W. Timothy; Fu, Yuchang] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Zhu, Xiaolin] Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA.
[Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA.
RP Fu, YC (reprint author), Univ Alabama, Dept Nutr Sci, 1675 Univ Blvd, Birmingham, AL 35294 USA.
EM yfu@uab.edu
RI 王, 强/F-4212-2011
FU UAB Diabetes Research and Training Center [P60-DK079626]; American
Diabetes Association [1-07-RA-49]; National Institutes of Health
[DK-083562, DK-038764]; Department of Veterans Affairs; research core
facilities of the UAB Diabetes Research and Training Center
[P60-DK079626]
FX We are grateful to Dr. Feng Liu, and Dr. Lily Q. Dong (University of
Texas Health Science Center at San Antonio) for their generous provision
of reagents. We thank Drs. Stacey Cofield, Katherine Ingram, Nianjun
Liu, Guodong Wu and Rongbing Xie (University of Alabama at Birmingham)
for their help on statistical analysis. This work was supported by a
pilot & feasibility grant from the UAB Diabetes Research and Training
Center (P60-DK079626), a grant from American Diabetes Association
(1-07-RA-49) to YF, grants from the National Institutes of Health
(DK-083562 and DK-038764) to WTG, and a Merit Review grant from the
Department of Veterans Affairs to WTG. We also gratefully acknowledge
the support of the research core facilities of the UAB Diabetes Research
and Training Center (P60-DK079626).
NR 30
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Z9 36
U1 0
U2 10
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD MAR
PY 2012
VL 221
IS 1
BP 66
EP 75
DI 10.1016/j.atherosclerosis.2011.12.014
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 897EV
UT WOS:000300629500010
PM 22227293
ER
PT J
AU Huang, G
Wang, D
Zeb, I
Budoff, MJ
Harman, SM
Miller, V
Brinton, EA
El Khoudary, SR
Manson, JE
Sowers, MR
Hodis, HN
Merriam, GR
Cedars, MI
Taylor, HS
Naftolin, F
Lobo, RA
Santoro, N
Wildman, RP
AF Huang, Gary
Wang, Dan
Zeb, Irfan
Budoff, Matthew J.
Harman, S. Mitchell
Miller, Virginia
Brinton, Eliot A.
El Khoudary, Samar R.
Manson, JoAnn E.
Sowers, MaryFran R.
Hodis, Howard N.
Merriam, George R.
Cedars, Marcelle I.
Taylor, Hugh S.
Naftolin, Frederick
Lobo, Rogerio A.
Santoro, Nanette
Wildman, Rachel P.
TI Intra-thoracic fat, cardiometabolic risk factors, and subclinical
cardiovascular disease in healthy, recently menopausal women screened
for the Kronos Early Estrogen Prevention Study (KEEPS)
SO ATHEROSCLEROSIS
LA English
DT Article
DE Coronary calcification; Ectopic fat; Cardiac fat; Hepatic fat; Risk
factors; Women
ID EPICARDIAL ADIPOSE-TISSUE; CORONARY-ARTERY-DISEASE; VISCERAL ABDOMINAL
FAT; INTIMA-MEDIA THICKNESS; PERICARDIAL FAT; LIVER-DISEASE; METABOLIC
SYNDROME; INSULIN-RESISTANCE; ASSOCIATION; OBESITY
AB Objective: To examine the correlations between intra-hepatic and intra-thoracic (total, epicardial, and pericardial) fat deposition with cardiovascular disease (CVD) risk factors and subclinical atherosclerosis burden in healthy, recently postmenopausal women.
Methods: Women screened for the Kronos Early Estrogen Prevention Study (mean age 52.9 years) who underwent electron beam or multidetector computed tomography (CT) imaging for the quantification of intra-hepatic fat and thoracic adipose tissue, and coronary artery calcification (CAC) were included (n = 650).
Results: Higher levels of intra-hepatic and thoracic fat were each associated with CVD risk markers. After adjustment for BMI, the associations for intra-hepatic fat with hs-CRP and insulin persisted (r = 0.21 and 0.19, respectively; P < 0.001), while those between thoracic fat indices and lipids persisted (r for total thoracic fat with HDL, LDL, and triglycerides = -0.16, 0.11, and 0.11, respectively, P < 0.05). Total thoracic fat was associated with CAC after initial multivariable adjustment (odds ratio [OR] of 2nd, 3rd, and 4th vs. 1st quartile and [95% confidence intervals]: 0.8 [0.4-1.6], 1.5 [0.8-2.9], and 1.8 [1.0-3.4]; p for linear trend = 0.017) and was only slightly attenuated after additional adjustment for BMI. Associations between total thoracic fat and CVD risk markers and CAC appeared due slightly more to associations with epicardial than pericardial fat.
Conclusion: While hepatic fat is related to hs-CRP and insulin, cardiac fat is associated with subclinical atherosclerosis as demonstrated by CAC. Cardiac fat may represent a useful marker for increased CVD risk beyond the standard adiposity measures of BMI and WC. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Huang, Gary; Wang, Dan; Wildman, Rachel P.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Zeb, Irfan; Budoff, Matthew J.] Harbor UCLA, Los Angeles Biomed Res Inst, Div Cardiol, Torrance, CA USA.
[Harman, S. Mitchell] Kronos Longev Res Inst, Phoenix, AZ USA.
[Miller, Virginia] Mayo Clin, Dept Surg, Rochester, MN USA.
[Miller, Virginia] Mayo Clin, Dept Physiol, Rochester, MN USA.
[Brinton, Eliot A.] Univ Utah, Sch Med, Dept Cardiovasc Genet, Salt Lake City, UT USA.
[El Khoudary, Samar R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Sowers, MaryFran R.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Hodis, Howard N.] Univ So Calif, Keck Sch Med, Atherosclerosis Res Unit, Los Angeles, CA 90033 USA.
[Merriam, George R.] Univ Washing, Sch Med, Dept Med, Seattle, WA USA.
[Cedars, Marcelle I.] Univ Washing, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Cedars, Marcelle I.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA.
[Taylor, Hugh S.] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA.
[Naftolin, Frederick] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA.
[Lobo, Rogerio A.] Columbia Univ, Coll Med, Dept Obstet & Gynecol, New York, NY USA.
[Santoro, Nanette] Univ Colorado, Denver Sch Med, Dept Obstet & Gynecol & Womens Hlth, Aurora, CO USA.
RP Wildman, RP (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave,Belfer Bldg,Room 1309, Bronx, NY 10461 USA.
EM rachel.wildman@einstein.yu.edu
OI El Khoudary Abushaban, Samar/0000-0003-2913-0821
FU Aurora Foundation; National Institutes of Health (NIH) [HL90639]; Mayo
CTSA [1 UL1 RR024150]; Mayo Foundation; National Center for Research
Resources (NCRR), a component of at NIH [CTSA UL1 RR024139, UL1
RR024131]; NIH Roadmap for Medical Research
FX KEEPS is funded by grants from the Aurora Foundation to the Kronos
Longevity Research Institute, National Institutes of Health (NIH)
HL90639 to VMM, 1 UL1 RR024150, Mayo CTSA 1 UL1 RR024150, the Mayo
Foundation, CTSA UL1 RR024139 and UL1 RR024131 from the National Center
for Research Resources (NCRR), a component of at NIH and NIH Roadmap for
Medical Research. The manuscript's contents are solely the
responsibility of the authors and do not necessarily represent the
official view of NCRR or NIH. Information on NCRR is available at
http://www.ncrr.nih.gov. Study medications were supplied in part by
Bayer Health Care and by Abbott Pharmaceuticals.
NR 30
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Z9 18
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD MAR
PY 2012
VL 221
IS 1
BP 198
EP 205
DI 10.1016/j.atherosclerosis.2011.12.004
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 897EV
UT WOS:000300629500029
PM 22209479
ER
PT J
AU Doss, BD
Rowe, LS
Morrison, KR
Libet, J
Birchler, GR
Madsen, JW
McQuaid, JR
AF Doss, Brian D.
Rowe, Lorelei Simpson
Morrison, Kristen R.
Libet, Julian
Birchler, Gary R.
Madsen, Joshua W.
McQuaid, John R.
TI Couple Therapy for Military Veterans: Overall Effectiveness and
Predictors of Response
SO BEHAVIOR THERAPY
LA English
DT Article
DE couple therapy; marital therapy; effectiveness; veterans; military
ID RANDOMIZED CLINICAL-TRIAL; MARITAL-THERAPY; OUTCOME RESEARCH; COMMUNITY
SAMPLE; MARRIED-COUPLES; COMBAT VETERANS; CLIENT FEEDBACK;
PSYCHOTHERAPY; METAANALYSIS; DISSATISFACTION
AB Despite the numerous challenges facing U.S. veterans and their relationships, there have been no examinations of the effectiveness of couple therapy for relationship distress provided to veterans. In the present study, 177 couples presenting for couple therapy at two Veteran Administration Medical Centers completed assessments of relationship satisfaction prior to therapy and weekly during therapy. Results revealed that the average couple showed significant gains in relationship satisfaction during treatment (d=0.44 for men; d=0.47 for women); gains were larger for couples beginning therapy in the distressed range (d=0.61 for men; d=0.58 for women) than for couples in the nondistressed range (d=0.19 for men; d=0.22 for women). Rates of premature termination were high, with 19% of couples completing fewer than three sessions and 62% rated as not completing a "full course" of therapy. Benchmarking analyses demonstrated that the average gains were larger than would be expected from natural remission and similar to previous effectiveness trials; however, average gains were smaller than those observed in couple therapy efficacy trials. Relationship, psychological, and demographic characteristics were generally unrelated to the amount of change in therapy after controlling for initial satisfaction. However, African American couples showed significantly larger gains than Caucasian, non-Hispanic couples. Thus, though yielding smaller effects than those shown in efficacy trials, the impact of couple therapy for veterans' relationship problems appears to generalize across various demographic, psychological, and relationship characteristics.
C1 [Doss, Brian D.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA.
[Rowe, Lorelei Simpson] So Methodist Univ, Dallas, TX 75275 USA.
[Birchler, Gary R.; Madsen, Joshua W.] VA San Diego Healthcare Syst, San Diego, CA USA.
[Madsen, Joshua W.] Univ Calif San Diego, San Diego, CA 92103 USA.
[McQuaid, John R.] San Francisco VA Med Ctr, San Francisco, CA USA.
[McQuaid, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Doss, BD (reprint author), Univ Miami, Dept Psychol, POB 248185, Coral Gables, FL 33124 USA.
EM bdoss@miami.edu
NR 51
TC 14
Z9 14
U1 1
U2 6
PU ASSOC ADV BEHAVIOR THERAPY
PI NEW YORK
PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA
SN 0005-7894
J9 BEHAV THER
JI Behav. Therapy
PD MAR
PY 2012
VL 43
IS 1
BP 216
EP 227
PG 12
WC Psychology, Clinical
SC Psychology
GA 897JQ
UT WOS:000300647400019
PM 22304892
ER
PT J
AU Cholas, RH
Hsu, HP
Spector, M
AF Cholas, Rahmatullah H.
Hsu, Hu-Ping
Spector, Myron
TI The reparative response to cross-linked collagen-based scaffolds in a
rat spinal cord gap model
SO BIOMATERIALS
LA English
DT Article
DE Collagen; Scaffold; Nerve tissue engineering; Nerve guide; Stem cells;
Growth factors
ID NEUROTROPHIC FACTOR GDNF; AXONAL REGENERATION; FUNCTIONAL RECOVERY;
CORTICOSPINAL TRACT; NERVOUS-SYSTEM; SCAR FORMATION; GENE DELIVERY;
IN-VITRO; INJURY; TRANSECTION
AB Prior work demonstrated the improvement of peripheral nerve regeneration in gaps implanted with collagen scaffold-filled collagen tubes, compared with nerve autografts, and the promise of such implants for treating gaps in spinal cord injury (SCI) in rats. The objective of this study was to investigate collagen implants alone and incorporating select therapeutic agents in a 5-mm full-resection gap model in the rat spinal cord. Two studies were performed, one with a 6-week time point and one with a 2-week time point. For the 6-week study the groups included: (1) untreated control, (2) dehydrothermally (DHT)cross-linked collagen scaffold, (3) DHT-cross-linked collagen scaffold seeded with adult rat neural stem cells (NSCs), and (4) DHT-cross-linked collagen scaffold incorporating plasmid encoding glial cell linederived neurotropic factor (pGDNF). The 2-week study groups were: (1) nontreated control, (2) DHTcross-linked collagen scaffold; (3) DHT-cross-linked collagen scaffold containing laminin; and (4) carbodiimide-cross-linked collagen scaffold containing laminin. The tissue filling the defect of all groups at 6 weeks was largely composed of fibrous scar; however, the tissue was generally more favorably aligned with the long axis of the spinal cord in all of the treatment groups, but not in the control group. Quantification of the percentage of animals per group containing cystic cavities in the defect showed a trend toward fewer rats with cysts in the groups in which the scaffolds were implanted compared to control. All of the collagen implants were clearly visible and mostly intact after 2 weeks. A band of fibrous tissue filling the control gaps was not seen in the collagen implant groups. In all of the groups there was a narrowing of the spinal canal within the gap as a result of surrounding soft tissue collapse into the defect. The narrowing of the spinal canal occurred to a greater extent in the control and DHT scaffold alone groups compared to the DHT scaffold/laminin and EDAC scaffold/laminin groups. Collagen biomaterials can be useful in the treatment of SCI to: favorably align the reparative tissue with the long axis of the spinal cord; potentially reduce the formation of fluid-filled cysts; serve as a delivery vehicle for NSCs and the gene for GDNF; and impede the collapse of musculature and connective tissue into the defect. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Cholas, Rahmatullah H.; Hsu, Hu-Ping; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA 02130 USA.
[Cholas, Rahmatullah H.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Hsu, Hu-Ping; Spector, Myron] Harvard Univ, Sch Med, Dept Orthoped Surg, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Spector, M (reprint author), VA Boston Healthcare Syst, Tissue Engn Labs, Mail Stop 151,150 S Huntington Ave, Boston, MA 02130 USA.
EM mspector@rics.bwh.harvard.edu
FU U.S. Department of Veterans Affairs; Veterans Health Administration;
Rehabilitation Research and Development Service; Department of Defense;
VA; Gates Millennium Scholars Program
FX The research reported here was supported by the U.S. Department of
Veterans Affairs, Veterans Health Administration, Rehabilitation
Research and Development Service and the Department of Defense. MS was
supported by a VA Research Career Scientist Award, and RC received a
fellowship from the Gates Millennium Scholars Program. The authors are
grateful to Professor Martha C. Bohn, Ph.D., of Northwestern University
for the pGDNF, and to the University of California San Diego for
providing the HCN-A94-2 cells.
NR 41
TC 26
Z9 31
U1 2
U2 26
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 MAR
PY 2012
VL 33
IS 7
BP 2050
EP 2059
DI 10.1016/j.biomaterials.2011.11.028
PG 10
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 895CN
UT WOS:000300473900011
PM 22182744
ER
PT J
AU Zhang, JW
Deng, XM
Choi, HG
Alessi, DR
Gray, NS
AF Zhang, Jinwei
Deng, Xianming
Choi, Hwan Geun
Alessi, Dario R.
Gray, Nathanael S.
TI Characterization of TAE684 as a potent LRRK2 kinase inhibitor
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Parkinson's disease; LRRK2; TAE684
ID PARKINSONS-DISEASE; SELECTIVITY
AB Leucine-rich repeat kinase 2 (LRRK2) is linked to Parkinson's disease and may represent an attractive therapeutic target. Here we report a 2,4-dianilino-5-chloro-pyrimidine, TAE684, a previously reported inhibitor of anaplastic lymphoma kinase (ALK), is also a potent inhibitor of LRRK2 kinase activity (IC50 of 7.8 nM against wild-type LRRK2, 6.1 nM against the G2019S mutant). TAE684 substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.1-0.3 mu M in cells and in mouse spleen and kidney, but not in brain, following oral doses of 10 mg/kg. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Zhang, Jinwei; Alessi, Dario R.] Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland.
[Deng, Xianming; Choi, Hwan Geun; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Deng, Xianming; Choi, Hwan Geun; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Alessi, DR (reprint author), Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat Unit, Dow St, Dundee DD1 5EH, Scotland.
EM d.r.alessi@dundee.ac.uk; nathanael_gray@dfci.harvard.edu
OI Alessi, Dario/0000-0002-2140-9185; Zhang, Jinwei/0000-0001-8683-509X
FU NIH [P41 GM079575-03]; Medical Research Council; Michael J Fox
foundation; AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck
KgaA and Pfizer
FX We wish to thank staff at the National Centre for Protein Kinase
Profiling (www.kinase-screen.mrc.ac.uk) for undertaking Dundee kinase
specificity screening as well as Nicholas Dzamko for providing the LRRK2
rabbit monoclonal antibodies. We also thank Faycal Hentati Institut
National de Neurologie, Tunis, Tunisia as well as Alastair D. Reith
GlaxoSmithKline Stevenage U.K. for providing the human lymphoblastoid
cells, SAI Advantium for performing pharmacokinetic studies, and the
antibody purification teams [Division of Signal Transduction Therapy
(DSTT), University of Dundee] coordinated by Hilary McLauchlan and James
Hastie for generation of antibodies. This work was supported by NIH
grant P41 GM079575-03 (N. Gray) the Medical Research Council (D.
Alessi), the Michael J Fox foundation for Parkinson's disease research
(N. Gray & D. Alessi), the pharmaceutical companies supporting the DSTT
(AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KgaA and
Pfizer) (D. Alessi)
NR 15
TC 40
Z9 41
U1 0
U2 12
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 MAR 1
PY 2012
VL 22
IS 5
BP 1864
EP 1869
DI 10.1016/j.bmcl.2012.01.084
PG 6
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 894UA
UT WOS:000300451200005
PM 22335897
ER
PT J
AU Wang, JQ
Zhang, ZD
Kuruppu, D
Brownell, AL
AF Wang, Ji-Quan
Zhang, Zhaoda
Kuruppu, Darshini
Brownell, Anna-Liisa
TI Radiosynthesis of PET radiotracer as a prodrug for imaging group II
metabotropic glutamate receptors in vivo
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Group II mGluRs; mGluR2; mGluR3; PET; Prodrug
ID PHARMACOLOGICAL CHARACTERIZATION; ACID LY354740; POTENT; ANTAGONIST;
LIGANDS; LY341495; AGONISTS; EPILEPSY; TARGETS
AB Group II metabotropic glutamate receptors (mGluRs) have been implicated in a variety of neurological and psychiatric disorders in recent studies. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers the possibility to visualize and study group II mGluRs in vivo under physiologic and pathologic conditions. We synthesized a PET tracer, (S,S,S)-2-(2-carboxycyclopropyl)-2-(3-[C-11]methoxyphenethyl) glycine dimethyl ester ([C-11]CMGDE), as a prodrug for group II mGluRs, and studied its preliminary biological properties in Sprague-Dawley rats to visualize group II mGluRs. The microPET studies demonstrated that [C-11]CMGDE readily penetrated into the brain and the radiotracer generated from [C-11]CMGDE had fast reversible binding in the group II mGluRs rich regions including striatum, hippocampus and different cortical areas. Blocking studies with LY341495 showed 20-30% decrease of binding of the radiotracer generated from [C-11]CMGDE in all brain areas with the highest decrease in the striatum 31.5 +/- 3.2%. The results show [C-11]CMGDE is the first PET tracer that is brain penetrating and can be used to image group II mGluRs in vivo. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Wang, Ji-Quan; Zhang, Zhaoda; Kuruppu, Darshini; Brownell, Anna-Liisa] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Biomed Imaging Ctr, Charlestown, MA USA.
RP Brownell, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Biomed Imaging Ctr, 149 13th St, Charlestown, MA USA.
EM abrownell@partners.org
FU NIH-NIBIB [R01EB-012864]; NIH-NIMH [R01MH-091684]
FX This work was supported by the NIH-NIBIB R01EB-012864 and NIH-NIMH
R01MH-091684 to A-LB.
NR 21
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Z9 7
U1 0
U2 5
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 MAR 1
PY 2012
VL 22
IS 5
BP 1958
EP 1962
DI 10.1016/j.bmcl.2012.01.039
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 894UA
UT WOS:000300451200025
PM 22318160
ER
PT J
AU Hicks, JW
Wilson, AA
Rubie, EA
Woodgett, JR
Houle, S
Vasdev, N
AF Hicks, Justin W.
Wilson, Alan A.
Rubie, Elizabeth A.
Woodgett, James R.
Houle, Sylvain
Vasdev, Neil
TI Towards the preparation of radiolabeled 1-aryl-3-benzyl ureas:
Radiosynthesis of [C-11-carbonyl] AR-A014418 by [C-11]CO2 fixation
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Glycogen synthase kinase; AR-A014418; Carbon-11; CO2 fixation; In vitro;
PET
ID PET; INHIBITORS; VERSATILE; MONOXIDE; CARRIER; AGENT; GSK3
AB The highly selective glycogen synthase kinase-3 (GSK-3) inhibitor N-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl) urea (AR-A014418) was radiolabeled with carbon-11 (C-11; half-life = 20.4 min) at the urea moiety via [C-11]CO2 fixation. Reaction of [C-11]CO2 with 4-methoxybenzylamine in the presence of a CO2 fixating base was followed by dehydration with POCl3 and addition of 2-amino-5-nitrothiazole to prepare [C-11-carbonyl] AR-A014418. This reaction resulted in an 8% uncorrected radiochemical yield, based on [C-11]CO2, with high specific activity (4 Ci/mu mol) within 30 min. An in vitro GSK-3 beta enzyme activity assay revealed that AR-A014418 (K-i = 770 nM) is not as potent as previously claimed. The [C-11]CO2 fixation methodology described herein should prove generally applicable to preparing 1-aryl-3-benzyl-[C-11-carbonyl] ureas as radiotracers for positron emission tomography. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Hicks, Justin W.; Wilson, Alan A.; Houle, Sylvain; Vasdev, Neil] Univ Toronto, Inst Med Sci, Dept Psychiat, PET Ctr,Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada.
[Rubie, Elizabeth A.; Woodgett, James R.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
RP Vasdev, N (reprint author), Massachusetts Gen Hosp, Dept Nucl Med & Mol Imaging, 55 Fruit St, Boston, MA 02114 USA.
EM vasdev.neil@mgh.harvard.edu
RI Wilson, Alan/A-1788-2011; Woodgett, Jim/F-1087-2010
OI Woodgett, Jim/0000-0003-3731-5797
FU Ontario Ministry of Research and Innovation
FX The Ontario Ministry of Research and Innovation is acknowledged for
financial support for this work in the form of an Early Researcher Award
(N.V.). The authors thank Armando Garcia, Winston Stableford, and Min
Wong for their expertise with the radiochemistry.
NR 27
TC 13
Z9 13
U1 1
U2 12
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 MAR 1
PY 2012
VL 22
IS 5
BP 2099
EP 2101
DI 10.1016/j.bmcl.2011.12.139
PG 3
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 894UA
UT WOS:000300451200051
PM 22321216
ER
PT J
AU Goodwin, JM
Schmitt, AD
McGinn, CM
Fuchs, BC
Kuruppu, D
Tanabe, KK
Lanuti, M
AF Goodwin, Jonathan M.
Schmitt, Anthony D.
McGinn, Christopher M.
Fuchs, Bryan C.
Kuruppu, Darshini
Tanabe, Kenneth K.
Lanuti, Michael
TI Angiogenesis Inhibition Using an Oncolytic Herpes Simplex Virus
Expressing Endostatin in a Murine Lung Cancer Model
SO CANCER INVESTIGATION
LA English
DT Article
DE Herpes simplex virus; Viral oncolysis; Endostatin; Angiogenesis; Lung
cancer
ID MOUSE ENDOSTATIN; VIRAL ONCOLYSIS; TUMOR-GROWTH; PHASE-I; EFFICACY;
THERAPY; MUTANT; CELLS; REPLICATION; COMBINATION
AB Herpes-mediated viral oncolysis alone is not sufficient to completely eradicate tumors. In this study we used a replication conditional, endostatin-expressing herpes simplex virus-1 mutant (HSV-Endo) in a murine lung cancer model. We hypothesized that the anti-angiogenic action of endostatin would improve upon the oncolytic effect of HSV-1. HSV-Endo was evaluated in a pulmonary metastases and orthotopic flank model, where there was significantly less tumor burden and reduced microvessel density compared to a control virus. Endostatin expression appears to improve the anti-tumor effect of HSV-1 in a lung cancer model.
C1 [Goodwin, Jonathan M.; Schmitt, Anthony D.; McGinn, Christopher M.; Lanuti, Michael] Massachusetts Gen Hosp, Ctr Canc, Div Thorac Surg, Boston, MA 02114 USA.
[Fuchs, Bryan C.; Kuruppu, Darshini; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Lanuti, M (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA.
EM Mlanuti@partners.org
FU Department of Surgery, Division of Thoracic Surgery, Massachusetts
General Hospital, Boston, MA
FX This work was supported by departmental funds from the Department of
Surgery, Division of Thoracic Surgery, Massachusetts General Hospital,
Boston, MA.
NR 32
TC 6
Z9 7
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0735-7907
J9 CANCER INVEST
JI Cancer Invest.
PD MAR
PY 2012
VL 30
IS 3
BP 243
EP 250
DI 10.3109/07357907.2012.654870
PG 8
WC Oncology
SC Oncology
GA 897NI
UT WOS:000300657200007
PM 22360364
ER
PT J
AU LeTourneau, JL
Pinney, J
Phillips, CR
AF LeTourneau, Jennifer L.
Pinney, Jamie
Phillips, Charles R.
TI Extravascular lung water predicts progression to acute lung injury in
patients with increased risk
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE acute lung injury; extravascular lung water; physiologic dead-space
fraction; pulmonary edema; pulmonary permeability index; thermodilution;
transpulmonary
ID RESPIRATORY-DISTRESS-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; CRITICALLY
ILL PATIENTS; INTENSIVE-CARE-UNIT; LOWER TIDAL VOLUMES; TRANSPULMONARY
THERMODILUTION; BODY-WEIGHT; CLINICAL-TRIAL; VENTILATION; SEVERITY
AB Objectives: To compare the extravascular lung water index and other markers of disease severity in patients with acute lung injury vs. patients at risk for development of acute lung injury and to determine their ability to predict progression to acute lung injury in patients at risk.
Design: Extravascular lung water index, dead space fraction, Pao(2)/Fio(2), and other markers of disease severity were measured prospectively in 29 patients daily for 5 days after admission to the intensive care unit. Patients had acute lung injury as defined by the American European Consensus Committee criteria or had risk factors for development of it.
Setting: The intensive care units of an academic tertiary referral hospital.
Measurements and Main Results: The mean extravascular lung water index on day 1 for patients who progressed to acute lung injury was higher than for those who did not (15.5 +/- 7.4 mL/kg vs. 8.7 +/- 2.3 mL/kg; p = .04). None of the other physiologic parameters tested discriminated progression to acute lung injury to include the mean physiologic dead space (0.61 +/- 0.06] vs. 0.59 +/- 0.10; p = .67), Pao(2)/Fio(2) ratio (322 +/- 35 vs. 267 +/- 98; p = .15), and static lung compliance (30.9 +/- 13.5 vs. 38.5 +/- 11.7; p = .24). An extravascular lung water index cutoff value on day 1 of 10 mL/kg had a 63% sensitivity, 88% specificity, positive predictive value of 83%, and negative predictive value of 70% to predict progression to acute lung injury. There was no difference in extravascular lung water index between those who progressed to acute lung injury vs. those who had acute lung injury (14.3 +/- 4.7 vs. 15.5 +/- 7.4; P = .97).
Conclusions: Elevated extravascular lung water index is a feature of early acute lung injury and discriminates between those with acute lung injury and those without. Furthermore, extravascular lung water index predicts progression to acute lung injury in patients with risk factors for development of acute lung injury 2.6 +/- 0.3 days before the patients meet American European Consensus Committee criteria for it. These 2.6 +/- 0.3 days may then represent missed opportunity for therapeutic intervention and improved outcome. (Crit Care Med 2012; 40:847-854)
C1 [LeTourneau, Jennifer L.] Portland VA Med Ctr, Pulm Dis Sect, Portland, OR 97239 USA.
[LeTourneau, Jennifer L.; Pinney, Jamie; Phillips, Charles R.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA.
Oregon Hlth & Sci Univ, Ctr Intens Care Res, Portland, OR 97201 USA.
RP LeTourneau, JL (reprint author), Portland VA Med Ctr, Pulm Dis Sect, 3710 SW US Vet Hosp Rd,P3PULM, Portland, OR 97239 USA.
EM Jennifer.Letourneau@va.gov
FU Medical Research Foundation, Oregon Health & Science University,
Portland, Oregon; Center of Excellence in Human Research, Oregon Health
& Science University, Portland, Oregon; Oregon Clinical and
Translational Research Institute (OCTRI); National Center for Research
Resources (NCRR), a component of the National Institutes of Health (NIH)
[UL1 RR024140]; NIH Roadmap for Medical Research; MAB
FX Supported, in part, by Medical Research Foundation, Oregon Health &
Science University, Portland, Oregon; Center of Excellence in Human
Research, Oregon Opportunity Funds, Oregon Health & Science University,
Portland, Oregon; the Oregon Clinical and Translational Research
Institute (OCTRI); grant number UL1 RR024140 from the National Center
for Research Resources (NCRR), a component of the National Institutes of
Health (NIH); and NIH Roadmap for Medical Research.; Dr. Phillips
consulted for and received honoraria/speaking fees from MAB. The
remaining authors have not disclosed any potential conflicts of
interest.
NR 43
TC 41
Z9 48
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAR
PY 2012
VL 40
IS 3
BP 847
EP 854
DI 10.1097/CCM.0b013e318236f60e
PG 8
WC Critical Care Medicine
SC General & Internal Medicine
GA 895YO
UT WOS:000300532800019
PM 22036857
ER
PT J
AU Ackerman, HC
Carroll, RW
Casals-Pascual, C
AF Ackerman, Hans C.
Carroll, Ryan W.
Casals-Pascual, Climent
TI A better biomarker for cerebral malaria: In the eye of the beheld?
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE angiopoietin; biomarker; cerebral malaria; endothelium; malaria; nitric
oxide; retinopathy; sensitivity; specificity
ID FALCIPARUM-MALARIA; AFRICAN CHILDREN; NITRIC-OXIDE; ANGIOPOIETIN-2;
INDICATORS; LIGAND; TIE2
C1 [Ackerman, Hans C.] NIAID, Lab Malaria & Vector Res, Rockville, MD 20892 USA.
[Carroll, Ryan W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Crit Care Med, Boston, MA USA.
[Carroll, Ryan W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesiol Ctr Crit Care Res, Boston, MA USA.
[Casals-Pascual, Climent] Wellcome Trust Ctr Human Genet, Oxford, England.
RP Ackerman, HC (reprint author), NIAID, Lab Malaria & Vector Res, Rockville, MD 20892 USA.
FU Intramural NIH HHS [ZIA AI001150-02]; Medical Research Council
[G0701885]
NR 18
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAR
PY 2012
VL 40
IS 3
BP 1018
EP 1020
DI 10.1097/CCM.0b013e31823d7810
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA 895YO
UT WOS:000300532800063
PM 22343865
ER
PT J
AU Kacmarek, RM
Villar, J
AF Kacmarek, Robert M.
Villar, Jesus
TI Noisy ventilation. When is it normal? Reply
SO CRITICAL CARE MEDICINE
LA English
DT Letter
C1 [Kacmarek, Robert M.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Kacmarek, Robert M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Spain.
[Villar, Jesus] Inst Salud Carlos III, CIBER Enfermedades Resp, Las Palmas Gran Canaria, Spain.
RP Kacmarek, RM (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
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 MAR
PY 2012
VL 40
IS 3
BP 1036
EP 1036
DI 10.1097/CCM.0b013e31824102f6
PG 1
WC Critical Care Medicine
SC General & Internal Medicine
GA 895YO
UT WOS:000300532800078
ER
PT J
AU Dudzinski, DM
Mak, GS
Hung, JW
AF Dudzinski, David M.
Mak, Gary S.
Hung, Judy W.
TI Pericardial Diseases
SO CURRENT PROBLEMS IN CARDIOLOGY
LA English
DT Review
ID EXPERIMENTAL CARDIAC-TAMPONADE; RECURRENT ACUTE PERICARDITIS;
CONSTRICTIVE PERICARDITIS; CONSECUTIVE PATIENTS; ETIOLOGIC DIAGNOSIS;
CONGENITAL ABSENCE; MEDICAL PATIENTS; PR-SEGMENT; MODERN-ERA; EFFUSION
AB The pericardium provides an enclosed lubricated space for the beating heart and functions to fix the heart in the chest cavity relative to adjacent organs. Pericardial pathophysiology is often manifested in a spectrum of distinct cardiac and systemic disease states. The pericardial response to injury typically involves a spectrum of inflammation with both acute and chronic features and/or fluid accumulation. Recent advances in imaging methods have refined the diagnosis and therapy of pericardial disease. This article presents the anatomy and physiology of pericardial disease and the clinical approach for diagnosis and treatment. (Curr Probl Cardiol 2012;37:75-118.)
C1 [Dudzinski, David M.; Mak, Gary S.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Hung, Judy W.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA.
[Hung, Judy W.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Dudzinski, DM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
FU Lippincott Williams and Wilkins
FX David M. Dudzinski has received payment from Lippincott Williams and
Wilkins for authorship of a medical review manual unrelated to this
topic and has nothing else to disclose. Gary Mak and Judy Hung have no
conflicts of interest to disclose.
NR 82
TC 24
Z9 25
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0146-2806
J9 CURR PROB CARDIOLOGY
JI Curr. Probl. Cardiol.
PD MAR
PY 2012
VL 37
IS 3
BP 75
EP 118
DI 10.1016/j.cpcardiol.2011.10.002
PG 44
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 895CZ
UT WOS:000300475100002
PM 22289657
ER
PT J
AU Hansen, P
Barry, D
Restell, A
Sylvia, D
Magnin, O
Dombkowski, D
Preffer, F
AF Hansen, P.
Barry, D.
Restell, A.
Sylvia, D.
Magnin, O.
Dombkowski, D.
Preffer, F.
TI Physics of a rapid CD4 lymphocyte count with colloidal gold
SO CYTOMETRY PART A
LA English
DT Article
DE CD4 lymphocytes; nanoparticles; point of care; light scatter; cytometry
AB The inherent surface charges and small diameters that confer colloidal stability to gold particle conjugates (immunogold) are detrimental to rapid cell surface labeling and distinct cluster definition in flow cytometric light scatter assays. Although the inherent immunogold surface charge prevents self aggregation when stored in liquid suspension, it also slows binding to cells to timeframes of hours and inhibits cell surface coverage. Although the small diameter of immunogold particles prevents settling when in liquid suspension, small particles have small light scattering cross sections and weak light scatter signals. We report a new, small particle lyophilized immunogold reagent that maintains activity after 42 degrees C storage for a year and can be rapidly dissolved into stable liquid suspension for use in labelling cells with larger particle aggregates that have enhanced scattering cross section. Labeling requires less than 1 min at 20 degrees C, which is similar to 30 times faster than customary fluorescent antibody labeling. The labeling step involves neutralizing the surface charge of immunogold and creating specifically bound aggregates of gold on the cell surface. This process provides distinct side-scatter cluster separation with blue laser light at 488 nm, which is further improved by using red laser light at 640 nm. Similar comparisons using LED light sources showed less improvement with red light, thereby indicating that coherent light scatter is of significance in enhancing side-scatter cluster separation. The physical principles elucidated here for this technique are compatible with most flow cytometers; however, future studies of its clinical efficacy should be of primary interest in point-of-care applications where robust reagents and rapid results are important. (C) 2011 International Society for Advancement of Cytometry
C1 [Hansen, P.] Union Biometr Technol Inc, Canaan, NY 12029 USA.
[Barry, D.; Restell, A.; Sylvia, D.] PointCare Technol Inc, Marlborough, MA USA.
[Magnin, O.] C2 Diagnost, Montpellier, France.
[Dombkowski, D.; Preffer, F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Hansen, P (reprint author), Union Biometr Technol Inc, 121 Top Dean Hill Rd,PO 315, Canaan, NY 12029 USA.
EM phansen5488@gmail.com
NR 12
TC 1
Z9 1
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD MAR
PY 2012
VL 81A
IS 3
BP 222
EP 231
DI 10.1002/cyto.a.21139
PG 10
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 897SQ
UT WOS:000300677100007
PM 21990088
ER
PT J
AU Wang, LM
Lovejoy, NF
Faustman, DL
AF Wang, Limei
Lovejoy, Nicholas Fraser
Faustman, Denise L.
TI Persistence of Prolonged C-peptide Production in Type 1 Diabetes as
Measured With an Ultrasensitive C-peptide Assay
SO DIABETES CARE
LA English
DT Article
ID BETA-CELL FUNCTION; RESIDUAL INSULIN PRODUCTION; GLYCEMIC CONTROL;
SECRETION; ONSET; AUTOANTIBODIES; PREVALENCE; DIAGNOSIS; CHILDREN;
MELLITUS
AB OBJECTIVE-To examine persistence of C-peptide production by ultrasensitive assay years after onset of type 1 diabetes and factors associated with preserving beta-cell function.
RESEARCH DESIGN AND METHODS-Serum C-peptide levels, a marker of insulin production and surviving beta-cells, were measured in human subjects (n = 182) by ultrasensitive assay, as was beta-cell functioning. Twenty-two times more sensitive than standard assays, this assay's lower detection limit is 1.5 pmol/L. Disease duration, age at onset, age, sex, and autoantibody titers were analyzed by regression analysis to determine their relationship to C-peptide production. Another group of four patients was serially studied for up to 20 weeks to examine C-peptide levels and functioning.
RESULTS-The ultrasensitive assay detected C-peptide in 10% of individuals 31-40 years after disease onset and with percentages higher at shorter duration. Levels as low as 2.8 +/- 1.1 pmol/L responded to hyperglycemia with increased C-peptide production, indicating residual beta-cell functioning. Several other analyses showed that beta-cells, whose C-peptide production was formerly undetectable, were capable of functioning. Multivariate analysis found disease duration (beta = -2.721; P = 0.005) and level of zinc transporter 8 autoantibodies (beta = 0.127; P = 0.015) significantly associated with C-peptide production. Unexpectedly, onset at >40 years of age was associated with low C-peptide production, despite short disease duration.
CONCLUSIONS-The ultrasensitive assay revealed that C-peptide production persists for decades after disease onset and remains functionally responsive. These findings suggest that patients with advanced disease, whose beta-cell function was thought to have long ceased, may benefit from interventions to preserve beta-cell function or to prevent complications.
C1 [Wang, Limei; Lovejoy, Nicholas Fraser; Faustman, Denise L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunobiol Labs, Boston, MA 02114 USA.
RP Faustman, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunobiol Labs, Boston, MA 02114 USA.
EM faustman@helix.mgh.harvard.edu
FU Iacocca Foundation
FX This study was supported by the Iacocca Foundation.
NR 23
TC 51
Z9 51
U1 2
U2 6
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 MAR
PY 2012
VL 35
IS 3
BP 465
EP 470
DI 10.2337/dc11-1236
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 899FI
UT WOS:000300801400004
PM 22355018
ER
PT J
AU Cavallerano, JD
Silva, PS
Tolson, AM
Francis, T
Tolls, D
Patel, B
Eagan, S
Aiello, LM
Aiello, LP
AF Cavallerano, Jerry D.
Silva, Paolo S.
Tolson, Ann M.
Francis, Taniya
Tolls, Dorothy
Patel, Bina
Eagan, Sharon
Aiello, Lloyd M.
Aiello, Lloyd P.
TI Imager Evaluation of Diabetic Retinopathy at the Time of Imaging in a
Telemedicine Program
SO DIABETES CARE
LA English
DT Article
AB OBJECTIVE-To evaluate the ability of certified retinal imagers to identify presence versus absence of sight-threatening diabetic retinopathy (stDR) (moderate nonproliferative diabetic retinopathy or worse or diabetic macular edema) at the time of retinal imaging in a telemedicine program.
RESEARCH DESIGN AND METHODS-Diabetic patients in a primary care setting or specialty diabetes clinic received Joslin Vision Network protocol retinal imaging as part of their care. Trained nonphysician imagers graded the presence versus absence of stDR at the time of imaging. These gradings were compared with masked gradings of certified readers.
RESULTS-Of 158 patients (316 eyes) imaged, all cases of stDR (42 eyes [13%]) were identified by the imagers at the time of imaging. Six eyes with mild nonproliferative diabetic retinopathy were graded by the imagers to have stDR (sensitivity 1.00, 95% CI 0.90-1.00; specificity 0.97, 0.94-0.99).
CONCLUSIONS-Appropriately trained imagers can accurately identify stDR at the time of imaging.
C1 [Cavallerano, Jerry D.; Silva, Paolo S.; Tolson, Ann M.; Francis, Taniya; Tolls, Dorothy; Patel, Bina; Eagan, Sharon; Aiello, Lloyd M.; Aiello, Lloyd P.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA.
[Cavallerano, Jerry D.; Silva, Paolo S.; Aiello, Lloyd M.; Aiello, Lloyd P.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Patel, Bina] New England Coll Optometry, Boston, MA USA.
RP Silva, PS (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA.
EM paoloantonio.silva@joslin.havard.edu
NR 13
TC 8
Z9 8
U1 1
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2012
VL 35
IS 3
BP 482
EP 484
DI 10.2337/dc11-1317
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 899FI
UT WOS:000300801400007
PM 22238278
ER
PT J
AU Benedict, C
Brooks, SJ
Kullberg, J
Burgos, J
Kempton, MJ
Nordenskjold, R
Nylander, R
Kilander, L
Craft, S
Larsson, EM
Johansson, L
Ahlstrom, H
Lind, L
Schioth, HB
AF Benedict, Christian
Brooks, Samantha J.
Kullberg, Joel
Burgos, Jonathan
Kempton, Matthew J.
Nordenskjold, Richard
Nylander, Ruta
Kilander, Lena
Craft, Suzanne
Larsson, Elna-Marie
Johansson, Lars
Ahlstrom, Hakan
Lind, Lars
Schioth, Helgi B.
TI Impaired Insulin Sensitivity as Indexed by the HOMA Score Is Associated
With Deficits in Verbal Fluency and Temporal Lobe Gray Matter Volume in
the Elderly
SO DIABETES CARE
LA English
DT Article
ID MIDDLE-AGED ADULTS; ALZHEIMERS-DISEASE; BRAIN; MEMORY; HUMANS;
SEGMENTATION; PATHOGENESIS; RESISTANCE; LANGUAGE; ANATOMY
AB OBJECTIVE-Impaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.
RESEARCH DESIGN AND METHODS-Insulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants. also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume).
RESULTS-The HOMA-IR was negatively correlated with verbal fluency performance, brain size, and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses.
CONCLUSIONS-These cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies.
C1 [Benedict, Christian; Brooks, Samantha J.; Burgos, Jonathan; Schioth, Helgi B.] Uppsala Univ, Dept Neurosci, Uppsala, Sweden.
[Kullberg, Joel; Nordenskjold, Richard; Nylander, Ruta; Larsson, Elna-Marie; Johansson, Lars; Ahlstrom, Hakan] Uppsala Univ, Dept Radiol, Uppsala, Sweden.
[Kempton, Matthew J.] Kings Coll London, Dept Neuroimaging, London WC2R 2LS, England.
[Kilander, Lena] Uppsala Univ, Dept Publ Hlth & Caring Sci Geriatr, Uppsala, Sweden.
[Craft, Suzanne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Vet Affairs Puget Sound Hlth Care Syst,Geriatr Re, Seattle, WA 98195 USA.
[Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
RP Benedict, C (reprint author), Uppsala Univ, Dept Neurosci, Uppsala, Sweden.
EM christian.benedict@neuro.uu.se
RI Kempton, Matthew/F-8683-2011;
OI Kempton, Matthew/0000-0003-3541-9947; Benedict,
Christian/0000-0002-8911-4068
FU Swedish Research Council; Brain Research Foundation (Sweden); Olle
Engkvist Byggmastare Foundation (Sweden); Tore Nilsons Foundation
(Sweden); Gunvor och Josef Aners Foundation (Sweden); Ake Wibergs
Foundation (Sweden); Ahlens Foundation (Sweden); Uppsala University
(Sweden); Novo Nordisk (Denmark); AstraZeneca (Sweden)
FX This study was funded by the Swedish Research Council, the Brain
Research Foundation (Sweden), the Olle Engkvist Byggmastare Foundation
(Sweden), the Tore Nilsons Foundation (Sweden), the Gunvor och Josef
Aners Foundation (Sweden), the Ake Wibergs Foundation (Sweden), the
Ahlens Foundation (Sweden), and Uppsala University (Sweden).; Funding
for the study also was provided by Novo Nordisk (Denmark) and
AstraZeneca (Sweden). The funding sources had no role in the design and
conduct of the study; collection, management, analysis, and
interpretation of data; and preparation, review, or approval of the
manuscript. No other potential conflicts of interest relevant to this
article were reported.
NR 41
TC 43
Z9 45
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 MAR
PY 2012
VL 35
IS 3
BP 488
EP 494
DI 10.2337/dc11-2075
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 899FI
UT WOS:000300801400009
PM 22301128
ER
PT J
AU Pittas, AG
Nelson, J
Mitri, J
Hillmann, W
Garganta, C
Nathan, DM
Hu, FB
Dawson-Hughes, B
AF Pittas, Anastassios G.
Nelson, Jason
Mitri, Joanna
Hillmann, William
Garganta, Cheryl
Nathan, David M.
Hu, Frank B.
Dawson-Hughes, Bess
CA Diabet Prevention Program Res Grp
TI Plasma 25-Hydroxyvitamin D and Progression to Diabetes in Patients at
Risk for Diabetes An ancillary analysis in the Diabetes Prevention
Program
SO DIABETES CARE
LA English
DT Article
ID VITAMIN-D SUPPLEMENTATION; RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE;
BASE-LINE; METABOLIC SYNDROME; CALCIUM INTAKE; BLOOD-GLUCOSE; SERUM;
WOMEN; MELLITUS
AB OBJECTIVE-To investigate the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes.
RESEARCH DESIGN AND METHODS-Prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multicenter trial comparing different strategies for prevention of diabetes in patients with prediabetes. We assessed the association between plasma 25-hydroxyvitamin D, measured repeatedly during follow-up, and incident diabetes in the combined placebo (n = 1,022) and intensive lifestyle (n = 1,017) randomized arms of the DPP. Variables measured at multiple study time points (25-hydroxyvitamin D, BMI, and physical activity) entered the analyses as time-varying "lagged" covariates, as the mean of the previous and current visits at which diabetes status was assessed.
RESULTS-After multivariate adjustment, including for the DPP intervention, participants in the highest tertile of 25-hydroxyvitamin D (median concentration, 30.1 ng/mL) had a hazard ratio of 0.72 (95% CI 0.56-0.90) for developing diabetes compared with participants in the lowest tertile (median concentration, 12.8 ng/mL). The association was in the same direction in placebo (0.70; 0.52-0.94) versus lifestyle arm (0.80; 0.54-1.17).
CONCLUSIONS-Higher plasma 25-hydroxyvitamin D, assessed repeatedly, was associated with lower risk of incident diabetes in high-risk patients, after adjusting for lifestyle interventions (dietary changes, increased physical activity, and weight loss) known to decrease diabetes risk. Because of the observational nature of the study, the potential association between vitamin D and diabetes needs to be confirmed in intervention studies.
C1 [Pittas, Anastassios G.; Mitri, Joanna; Dawson-Hughes, Bess] Tufts Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA USA.
[Nelson, Jason] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA.
[Hillmann, William] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Garganta, Cheryl] Tufts Med Ctr, Floating Hosp Children, Boston, MA USA.
[Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
[Nathan, David M.] Harvard Univ, Sch Med, Boston, MA USA.
[Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Hu, Frank B.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Dawson-Hughes, Bess] Tufts Univ, Bone Metab Lab, Jean Mayer US Dept Agr Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
RP Pittas, AG (reprint author), Tufts Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA USA.
EM apittas@tuftsmedicalcenter.org
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[R01-DK-76092, R01-DK-79003]; National Institutes of Health; National
Institutes of Health Office of Dietary Supplements [UL1RR025752];
National Center for Research Resources; U.S. Department of Agriculture
[58-1950-9001]; Endocrine Fellows Foundation; NIDDK [UO1-DK-48489];
Indian Health Service; National Institute of Child Health and Human
Development; National Institute on Aging; National Eye Institute;
National Heart, Lung, and Blood Institute; Office of Research on Women's
Health; National Center for Minority Health and Human Disease; Centers
for Disease Control and Prevention; American Diabetes Association
FX This work was supported by grants R01-DK-76092 and R01-DK-79003 (to
A.G.P.) from the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK), the National Institutes of Health, and the National
Institutes of Health Office of Dietary Supplements; Grant UL1RR025752
(to Tufts University) from the National Center for Research Resources;
the U.S. Department of Agriculture Agreement 58-1950-9001 (to B.D.-H.);
the Marilyn Fishman Grant for Diabetes Research (to J.M.) from the
Endocrine Fellows Foundation; and Grant UO1-DK-48489 from the NIDDK to
the DPP clinical centers and the Coordinating Center for the design and
conduct of the DPP study. The Southwestern American Indian Centers were
supported directly by the NIDDK, including its Intramural Research
Program, and the Indian Health Service. The General Clinical Research
Center Program, National Center for Research Resources, supported data
collection at many of the clinical centers. Funding was also provided by
the National Institute of Child Health and Human Development; the
National Institute on Aging; the National Eye Institute; the National
Heart, Lung, and Blood Institute; the Office of Research on Women's
Health; the National Center for Minority Health and Human Disease; the
Centers for Disease Control and Prevention; the Indian Health Service;
and the American Diabetes Association.
NR 40
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U1 0
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2012
VL 35
IS 3
BP 565
EP 573
DI 10.2337/dc11-1795
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 899FI
UT WOS:000300801400022
PM 22323410
ER
PT J
AU Taylor, RM
Tujios, S
Jinjuvadia, K
Davern, T
Shaikh, OS
Han, S
Chung, RT
Lee, WM
Fontana, RJ
AF Taylor, Ryan M.
Tujios, Shannan
Jinjuvadia, Kartik
Davern, Timothy
Shaikh, Obaid S.
Han, Steve
Chung, Raymond T.
Lee, William M.
Fontana, Robert J.
TI Short and Long-Term Outcomes in Patients with Acute Liver Failure Due to
Ischemic Hepatitis
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE Liver transplantation; Hypoxic hepatitis; Aminotransferase levels;
Coagulopathy; Encephalopathy
ID HYPOXIC HEPATITIS; TRANSPLANTATION; PROGNOSIS; DISEASE; INJURY
AB The purpose of this study is to describe the incidence and presenting features of patients with acute liver failure (ALF) due to ischemic hepatitis and the prognostic factors associated with short (three-week) and long-term outcomes.
Retrospective cohort analysis of adult patients enrolled in the Acute Liver Failure Study Group between 1998 and 2008 with ALF due to ischemic hepatitis. Predictors of adverse outcomes three weeks after presentation were identified by univariate and multivariate analysis.
Ischemic hepatitis accounted for 51 (4.4%) of the 1147 ALF patients enrolled. Mean age was 50 years, 63% were female, and only 31% had known heart disease before presentation. However, a cardiopulmonary precipitant of hepatic ischemia was identified in 69%. Three-week spontaneous survival was 71%, two patients (4%) underwent liver transplantation, and the remaining 13 patients (25%) died of multi-organ failure. Adverse outcomes were more frequent in subjects with higher admission phosphate levels (HR 1.3, 95% CI 1.1-1.6, P = 0.008) and in subjects with grade 3/4 encephalopathy at presentation (HR: 8.4, 95% CI 1.1-66.5, P = 0.04). Nineteen of the 28 short-term survivors (68%) were still alive at a median follow-up of 3.7 years whereas nine (32%) others had died at a median follow-up of 2 months.
A higher admission serum phosphate level and more advanced encephalopathy are associated with a lower likelihood of short-term survival of hospitalized patients with ALF due to ischemic hepatitis. Long-term outcomes are largely determined by underlying cardiovascular morbidity and mortality.
C1 [Tujios, Shannan; Jinjuvadia, Kartik; Fontana, Robert J.] Univ Michigan, Sch Med, Dept Internal Med, Med Ctr,Taubman Ctr 3912, Ann Arbor, MI 48109 USA.
[Taylor, Ryan M.] Univ Kansas, Dept Internal Med, Kansas City, KS USA.
[Davern, Timothy] Calif Pacific Med Ctr, San Francisco, CA USA.
[Shaikh, Obaid S.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Han, Steve] Univ Calif Los Angeles, Los Angeles, CA USA.
[Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lee, William M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
RP Fontana, RJ (reprint author), Univ Michigan, Sch Med, Dept Internal Med, Med Ctr,Taubman Ctr 3912, Ann Arbor, MI 48109 USA.
EM rtaylor2@kumc.edu; Shannan.Tujios@UTSouthwestern.edu;
kartik.jinjuvadia@gmail.com; davernt@sutterhealth.org; obiad@pitt.edu;
steven.han@ucla.edu; rtchung@partners.org;
william.lee@utsouthwestern.edu; rfontana@med.umich.edu
FU NIH [DK U-01 58369]; National Institute of Diabetes, Digestive, and
Kidney Disease; Northwestern Medical Foundation; Southwestern Medical
Foundation [T-32 DK007745-12]
FX We gratefully acknowledge the support provided by the members of The
Acute Liver Failure Study Group 1998-2008. This study was funded by NIH
grant DK U-01 58369 for the Acute Liver Failure Study Group provided by
the National Institute of Diabetes, Digestive, and Kidney Disease.
Additional funding was provided by the Tips Fund of the Northwestern
Medical Foundation and the Jeanne Roberts and Rollin and Mary Ella King
Funds of the Southwestern Medical Foundation, and T-32 DK007745-12 to
DD.
NR 23
TC 11
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U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD MAR
PY 2012
VL 57
IS 3
BP 777
EP 785
DI 10.1007/s10620-011-1918-1
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 896OQ
UT WOS:000300578200026
PM 21948394
ER
PT J
AU Taborsky, GJ
Mundinger, TO
AF Taborsky, Gerald J., Jr.
Mundinger, Thomas O.
TI Minireview: The Role of the Autonomic Nervous System in Mediating the
Glucagon Response to Hypoglycemia
SO ENDOCRINOLOGY
LA English
DT Review
ID PANCREATIC SYMPATHETIC-NERVES; INSULIN-INDUCED HYPOGLYCEMIA;
DIABETIC-RATS; VENTROMEDIAL HYPOTHALAMUS; SECRETION; DOG; HORMONE;
HUMANS; ISLETS; COUNTERREGULATION
AB In type 1 diabetes, the impairment of the glucagon response to hypoglycemia increases both its severity and duration. In nondiabetic individuals, hypoglycemia activates the autonomic nervous system, which in turn mediates the majority of the glucagon response to moderate and marked hypoglycemia. The first goal of this minireview is therefore to illustrate and document these autonomic mechanisms. Specifically we describe the hypoglycemic thresholds for activating the three autonomic inputs to the islet (parasympathetic nerves, sympathetic nerves, and adrenal medullary epinephrine) and their magnitudes of activation as glucose falls from euglycemia to near fatal levels. The implication is that their relative contributions to this glucagon response depend on the severity of hypoglycemia. The second goal of this minireview is to discuss known and suspected down-regulation or damage to these mechanisms in diabetes. We address defects in the central nervous system, the peripheral nervous system, and in the islet itself. They are categorized as either functional defects caused by glucose dysregulation or structural defects caused by the autoimmune attack of the islet. In the last section of the minireview, we outline approaches for reversing these defects. Such reversal has both scientific and clinical benefit. Scientifically, one could determine the contribution of these defects to the impairment of glucagon response seen early in type 1 diabetes. Clinically, restoring this glucagon response would allow more aggressive treatment of the chronic hyperglycemia that is linked to the debilitating long-term complications of this disease. (Endocrinology 153: 1055-1062, 2012)
C1 [Taborsky, Gerald J., Jr.; Mundinger, Thomas O.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
RP Taborsky, GJ (reprint author), Div Endocrinol & Metab 151, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM taborsky@u.washington.edu
FU NIDDK NIH HHS [P30 DK017047, R01 DK050154]
NR 35
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Z9 38
U1 1
U2 12
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAR
PY 2012
VL 153
IS 3
BP 1055
EP 1062
DI 10.1210/en.2011-2040
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 897JG
UT WOS:000300645600012
PM 22315452
ER
PT J
AU Yang, JJ
Caligioni, CS
Chan, YM
Seminara, SB
AF Yang, Jasmine J.
Caligioni, Claudia S.
Chan, Yee-Ming
Seminara, Stephanie B.
TI Uncovering Novel Reproductive Defects in Neurokinin B Receptor Null
Mice: Closing the Gap Between Mice and Men
SO ENDOCRINOLOGY
LA English
DT Article
ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; MONKEY MACACA-MULATTA;
KALLMANN-SYNDROME; ARCUATE NUCLEUS; PREOPTIC AREA; GNRH NEURONS;
GONADOTROPIN-SECRETION; TACHYKININ RECEPTORS; HORMONE RELEASE; TACR3
MUTATIONS
AB Patients bearing mutations in TAC3 and TACR3 (which encode neurokinin B and its receptor, respectively) have sexual infantilism and infertility due to GnRH deficiency. In contrast, Tacr3(-/-) mice have previously been reported to be fertile. Because of this apparent phenotypic discordance between mice and men bearing disabling mutations in Tacr3/TACR3, Tacr3 null mice were phenotyped with close attention to pubertal development, estrous cyclicity, andfertility. Tacr3(-/-) mice demonstrated normal timing of preputial separation and day of first estrus, markers of sexual maturation. However, at postnatal d 60, Tacr3(-/-) males had significantly smaller testes and lower FSH levels than their wild-type littermates. Tacr3(-/-) females had lower uterine weights and abnormal estrous cyclicity. Approximately half of Tacr3(-/-) females had no detectable corpora lutea on ovarian histology at postnatal d 60. Despite this apparent ovulatory defect, all Tacr3(-/-) females achieved fertility when mated. However, Tacr3(-/-) females were subfertile, having both reduced numbers of litters and pups per litter. The subfertility of these animals was not due to a primary ovarian defect, because they demonstrated a robust response to exogenous gonadotropins. Thus, although capable of fertility, Tacr3-deficient mice have central reproductive defects. The remarkable ability of acyclic female Tacr3 null mice to achieve fertility is reminiscent of the reversal of hypogonadotropic hypogonadism seen in a high proportion of human patients bearing mutations in TACR3. Tacr3 mice are a useful model to examine the mechanisms by which neurokinin B signaling modulates GnRH release. (Endocrinology 153: 1498-1508, 2012)
C1 [Yang, Jasmine J.; Caligioni, Claudia S.; Chan, Yee-Ming; Seminara, Stephanie B.] Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, Reprod Endocrine Unit, Boston, MA 02114 USA.
[Chan, Yee-Ming] Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA.
RP Seminara, SB (reprint author), 55 Fruit St,Bartlett Hall Extens 5, Boston, MA 02114 USA.
EM seminara.stephanie@mgh.harvard.edu
FU National Institutes of Health (NIH) [U54 HD028138, T32 HD07396]; Charles
A. King Trust; Children's Hospital Boston
FX This work was supported by National Institutes of Health (NIH) Grant U54
HD028138, NIH Grant T32 HD07396 (to J.Y.Y. and C. S. C.), and a Charles
A. King Trust Postdoctoral Fellowship and a Children's Hospital Boston
Career Development Award (Y.-M.C.).
NR 60
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Z9 51
U1 0
U2 2
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAR
PY 2012
VL 153
IS 3
BP 1498
EP 1508
DI 10.1210/en.2011-1949
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 897JG
UT WOS:000300645600052
PM 22253416
ER
PT J
AU Demetri, GD
Le Cesne, A
Chawla, SP
Brodowicz, T
Maki, RG
Bach, BA
Smethurst, DP
Bray, S
Hei, YJ
Blay, JY
AF Demetri, George D.
Le Cesne, Axel
Chawla, Sant P.
Brodowicz, Thomas
Maki, Robert G.
Bach, Bruce A.
Smethurst, Dominic P.
Bray, Sarah
Hei, Yong-jiang
Blay, Jean-Yves
TI First-line treatment of metastatic or locally advanced unresectable soft
tissue sarcomas with conatumumab in combination with doxorubicin or
doxorubicin alone: A Phase I/II open-label and double-blind study
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Conatumumab; Doxorubicin; Soft tissue sarcomas; Death receptor 5; TRAIL
ID IFOSFAMIDE PLUS DOXORUBICIN; STANDARD-DOSE DOXORUBICIN; DEATH RECEPTOR
5; EUROPEAN ORGANIZATION; SOLID TUMORS; II TRIAL; BONE; APOPTOSIS;
CANCER; CHEMOTHERAPY
AB Background: Conatumumab is a fully human monoclonal agonist antibody that binds to death receptor 5 and induces apoptosis in sensitive cells. This study evaluated the safety and efficacy of doxorubicin +/- conatumumab as first-line systemic therapy for metastatic or locally advanced/unresectable soft-tissue sarcoma.
Methods: In Phase I, six patients received doxorubicin (75 mg/m(2)) with conatumumab (15 mg/kg) every 3 weeks. In Phase II, patients were randomised (2:1) to receive doxorubicin with either double-blind conatumumab 15 mg/kg (conatumumab-doxorubicin; n = 86) or placebo (placebo-doxorubicin; n = 42). Patients who progressed on placebo-doxorubicin could receive open-label conatumumab monotherapy post-chemotherapy (n = 21).
Findings: The expected histopathologic subtypes (e.g. leiomyosarcoma, liposarcoma, others) were represented in this trial. No unexpected adverse events were noted in either Phase I or II. Median progression-free survival in Phase II was 5.6 and 6.4 months in the conatumumab-doxorubicin and placebo-doxorubicin arms, respectively (stratified HR: 1.00; p = 0.973), with more early progressions noted in the first 3.5 months in the conatumumab-doxorubicin arm. Median overall survival was not reached after 8.6 months median follow-up in either arm. Common adverse events were nausea (conatumumab-doxorubicin: 66%; placebo-doxorubicin: 80%), alopecia (55%; 63%), fatigue (60%; 38%) and neutropenia (32%; 50%). Post-chemotherapy results were not notably improved by conatumumab dosing.
Interpretation: Addition of conatumumab to doxorubicin appeared to be safe but did not improve disease control in a heterogeneous unselected group of patients with soft tissue sarcomas. The results of this trial are very useful for estimating the outcomes of first-line therapy of sarcoma patients treated with standard doxorubicin.
Funding: This study was supported by Amgen Inc. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Demetri, George D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA.
[Le Cesne, Axel] Inst Gustave Roussy, Villejuif, France.
[Chawla, Sant P.] Sarcoma Oncol Ctr, Santa Monica, CA USA.
[Brodowicz, Thomas] Med Univ Vienna, Gen Hosp, Vienna, Austria.
[Maki, Robert G.] Mt Sinai Sch Med, New York, NY USA.
[Bach, Bruce A.; Hei, Yong-jiang] Amgen Inc, Thousand Oaks, CA 91320 USA.
[Smethurst, Dominic P.; Bray, Sarah] Amgen Ltd, Uxbridge, Middx, England.
[Blay, Jean-Yves] Ctr Leon Berard, F-69373 Lyon, France.
RP Demetri, GD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 1212, Boston, MA 02215 USA.
EM gdemetri@partners.org
RI Blay, Jean-Yves/N-3966-2016;
OI Blay, Jean-Yves/0000-0001-7190-120X; Bach, Bruce
Allen/0000-0003-3535-9518
FU Amgen Inc.
FX This study was supported by Amgen Inc.
NR 29
TC 28
Z9 29
U1 0
U2 8
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 MAR
PY 2012
VL 48
IS 4
BP 547
EP 563
DI 10.1016/j.ejca.2011.12.008
PG 17
WC Oncology
SC Oncology
GA 898HD
UT WOS:000300730300017
PM 22240283
ER
PT J
AU Refaat, MM
Lubitz, SA
Makino, S
Islam, Z
Frangiskakis, JM
Mehdi, H
Gutmann, R
Zhang, ML
Bloom, HL
MacRae, CA
Dudley, SC
Shalaby, AA
Weiss, R
McNamara, DM
London, B
Ellinor, PT
AF Refaat, Marwan M.
Lubitz, Steven A.
Makino, Seiko
Islam, Zahid
Frangiskakis, J. Michael
Mehdi, Haider
Gutmann, Rebecca
Zhang, Michael L.
Bloom, Heather L.
MacRae, Calum A.
Dudley, Samuel C.
Shalaby, Alaa A.
Weiss, Raul
McNamara, Dennis M.
London, Barry
Ellinor, Patrick T.
TI Genetic variation in the alternative splicing regulator RBM20 is
associated with dilated cardiomyopathy
SO HEART RHYTHM
LA English
DT Article
DE Dilated cardiomyopathy; Genetics; Mutation; Single nucleotide
polymorphism; RBM20
ID HEART-FAILURE; MUTATIONS; FREQUENCY; DISEASE; RELATIVES
AB BACKGROUND Dilated cardiomyopathy (DCM) is a leading cause of heart failure and death. The etiology of DCM is genetically heterogeneous.
OBJECTIVES We sought to define the prevalence of mutations in the RNA splicing protein RBM20 in a large cohort with DCM and to determine whether genetic variation in RBM20 is associated with clinical outcomes.
METHODS Subjects included in the Genetic Risk Assessment of Defibrillator Events (GRADE) study were aged at least 18 years, had an ejection fraction of <= 30%, and an implantable cardioverter-defibrillator (ICD). The coding region and splice junctions of RBM20 were screened in subjects with DCM; 2 common polymorphisms in RBM20, rs942077 and rs35141404, were genotyped in all GRADE subjects.
RESULTS A total of 1465 subjects were enrolled in the GRADE study, and 283 with DCM were screened for RBM20 mutations. The mean age of subjects with DCM was 58 +/- 13 years, 64% were males, and the mean follow-up time was 24.2 +/- 17.1 months after ICD placement. RBM20 mutations were identified in 8 subjects with DCM (2.8%). Mutation carriers had a similar survival, transplantation rate, and frequency of ICD therapy compared with nonmutation carriers. Three of 8 subjects with RBM20 mutations (37.5%) had atrial fibrillation (AF), whereas 19 subjects without mutations (7.4%) had AF (P = .02). Among all GRADE subjects, rs35141404 was associated with AF (minor allele odds ratio = 0.62; 95% confidence interval = 0.44-0.86; P = .006). In the subset of GRADE subjects with DCM, rs35141404 was associated with AF (minor allele odds ratio = 0.58; P = .047).
CONCLUSIONS: Mutations in RBM20 were observed in approximately 3% of subjects with DCM. There were no differences in survival, transplantation rate, and frequency of ICD therapy in mutation carriers.
C1 [Lubitz, Steven A.; Makino, Seiko; Zhang, Michael L.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
[Refaat, Marwan M.; Islam, Zahid; Frangiskakis, J. Michael; Mehdi, Haider; Gutmann, Rebecca; Shalaby, Alaa A.; McNamara, Dennis M.; London, Barry] Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15213 USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Bloom, Heather L.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA.
[MacRae, Calum A.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA.
[Dudley, Samuel C.] Univ Illinois, Cardiol Sect, Chicago, IL USA.
[Weiss, Raul] Ohio State Univ, Med Ctr, Div Cardiovasc Med, Columbus, OH 43210 USA.
RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA.
EM londonb@upmc.edu; pellinor@partners.org
FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [UL1 RR024153]; NHLBI NIH HHS
[R01 HL104156, R01 HL075431, K24 HL105780, R01 HL092577, R01
HL092577-04, R01 HL104156-03, K24 HL105780-03, R01 HL109264]; NIDA NIH
HHS [R21 DA027021-02, R21 DA027021]
NR 35
TC 35
Z9 36
U1 2
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
J9 HEART RHYTHM
JI Heart Rhythm
PD MAR
PY 2012
VL 9
IS 3
BP 390
EP 396
DI 10.1016/j.hrthm.2011.10.016
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 898CJ
UT WOS:000300712700019
PM 22004663
ER
PT J
AU Milan, DJ
Acha, MR
AF Milan, David J.
Acha, Moshe Rav
TI Recovery of myocardial tissue from extracted leads
SO HEART RHYTHM
LA English
DT Editorial Material
ID QT INTERVAL DURATION; COMMON VARIANTS; REPOLARIZATION; BIOMARKERS
C1 [Milan, David J.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
RP Milan, DJ (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
EM dmilan@partners.org
NR 13
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 1547-5271
J9 HEART RHYTHM
JI Heart Rhythm
PD MAR
PY 2012
VL 9
IS 3
BP 405
EP 406
DI 10.1016/j.hrthm.2011.11.002
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 898CJ
UT WOS:000300712700022
PM 22063082
ER
PT J
AU Armoundas, AA
Mela, T
Merchant, FM
AF Armoundas, Antonis A.
Mela, Theofanie
Merchant, Faisal M.
TI On the estimation of T-wave alternans using the spectral fast fourier
transform method
SO HEART RHYTHM
LA English
DT Article
DE Arrhythmias; Alternans; Phase resetting; Random and colored noise
ID SUDDEN CARDIAC DEATH; RISK STRATIFICATION; ISCHEMIC CARDIOMYOPATHY;
ELECTRICAL ALTERNANS; HEART-FAILURE; VULNERABILITY; TRIAL; INFARCTION;
PHASE
AB BACKGROUND T-wave alternans (TWA) has been associated with increased vulnerability to ventricular tachyarrhythmias and sudden cardiac death. However, both random (white) noise and (patho)physiologic processes (ie, premature ventricular contractions and heart and respiration rates) may hamper TWA estimation and therefore lessen its clinical utility for risk stratification.
OBJECTIVE To investigate the effect of random noise and certain (patho) physiologic processes on the estimation of TWA by using the fast Fourier transform method and to develop methods to overcome these potential sources of error.
METHODS We used a combination of human electrocardiogram data and computer simulations to assess the effects of a premature ventricular contraction and random and colored noise on the accuracy of TWA estimation.
RESULTS We quantitatively demonstrate that replacing a "bad" beat with an odd/even median beat is a more accurate approach than replacing it with the overall average or the overall median beat. We also show that phase resetting may have a significant effect on alternans estimation and that estimation of alternans by using frequencies >0.4922 cycles/beat in a 128-point fast Fourier transform provides the most accurate approach for estimating the alternans when phase resetting is likely to occur. In addition, our data demonstrate that the number of indeterminate TWA tests due to high levels of noise can be reduced when the alternans voltage exceeds a new higher threshold. Furthermore, the amplitude of random noise has a significant effect on alternans estimation and the alternans voltage threshold should be adjusted for noise levels >1.8 mu V. Finally, we quantitatively demonstrate that colored noise may lead to a false-positive or a false-negative result. We propose methods to estimate the effect of these (patho)physiologic processes on the alternans estimation in order to determine whether a TWA test is likely to be a true positive or a true negative.
CONCLUSION This study introduces novel methods to overcome potential sources of error in the estimation of TWA. These methods may improve the utility of TWA either for ambulatory monitoring or for clinical risk stratification for ventricular arrhythmias and sudden cardiac death.
C1 [Armoundas, Antonis A.; Mela, Theofanie; Merchant, Faisal M.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Div Cardiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
RP Armoundas, AA (reprint author), Harvard Univ, Sch Med, Cardiovasc Res Ctr, Div Cardiol,Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA.
EM aarmoundas@partners.org
FU American Heart Association [0635127N]; NIA [1R21 AG035128]; NIH
[1RO1HL103961]; Center for Integration of Medicine and Innovative
Technology (CIMIT); Deane Institute for Integrative Research in Atrial
Fibrillation and Stroke; Cardiovascular Research Society
FX This work was supported by a Scientist Development Grant (0635127N) from
the American Heart Association, NIA grant 1R21 AG035128, and NIH grant
1RO1HL103961. This work was also supported by a Fellowship and a Science
Award from the Center for Integration of Medicine and Innovative
Technology (CIMIT), the Deane Institute for Integrative Research in
Atrial Fibrillation and Stroke, and the Cardiovascular Research Society.
T. Mela is involved with Medtronic, Boston Scientific, and St Jude.
NR 21
TC 3
Z9 5
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
J9 HEART RHYTHM
JI Heart Rhythm
PD MAR
PY 2012
VL 9
IS 3
BP 449
EP 456
DI 10.1016/j.hrthm.2011.10.013
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 898CJ
UT WOS:000300712700029
PM 22001706
ER
PT J
AU Faghih, RT
Savla, K
Dahleh, MA
Brown, EN
AF Faghih, Rose T.
Savla, Ketan
Dahleh, Munther A.
Brown, Emery N.
TI Broad Range of Neural Dynamics From a Time-Varying FitzHugh-Nagumo Model
and its Spiking Threshold Estimation
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Algorithms; biological system modeling; biomedical signal processing;
parameter estimation
ID CANONIC MODELS; OSCILLATORS; NEURONS; NERVE
AB We study the use of the FitzHugh-Nagumo (FHN) model for capturing neural spiking. The FHN model is a widely used approximation of the Hodgkin-Huxley model that has significant limitations. In particular, it cannot produce the key spiking behavior of bursting. We illustrate that by allowing time-varying parameters for the FHN model, these limitations can be overcome while retaining its low-order complexity. This extension has applications in modeling neural spiking behaviors in the thalamus and the respiratory center. We demonstrate the use of the FHN model from an estimation perspective by presenting a novel parameter estimation method that exploits its multiple time-scale properties, and compare the performance of this method with the extended Kalman filter in several illustrative examples. We demonstrate that the dynamics of the spiking threshold can be recovered even in the absence of complete specifications for the system.
C1 [Faghih, Rose T.; Dahleh, Munther A.] MIT, Lab Informat & Decis Syst, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Brown, Emery N.] MIT, Harvard Massachusetts Div Hlth Sci & Technol, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Brown, Emery N.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Faghih, Rose T.] MIT, Neurosci Stat Res Lab, Cambridge, MA 02139 USA.
RP Faghih, RT (reprint author), MIT, Lab Informat & Decis Syst, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM rfaghih@mit.edu; ksavla@mit.edu; dahleh@mit.edu; enbrown1@mit.edu
FU National Institutes of Health [DP1 OD003646]; National Science
Foundation (NSF) [0836720]; Massachusetts Institute of Technology
FX This work was supported in part by National Institutes of Health under
Grant DP1 OD003646 and by the National Science Foundation (NSF) under
Grant 0836720. The work of R. T. Faghih was supported in part by the
Massachusetts Institute of Technology Fellowship in Control and NSF
Graduate Fellowship. This paper was presented in part at the proceedings
of the IEEE Engineering in Medicine and Biology Society Conference [5]
and R. T. Faghih's Master's Thesis [6].
NR 23
TC 4
Z9 4
U1 2
U2 4
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 MAR
PY 2012
VL 59
IS 3
BP 816
EP 823
DI 10.1109/TBME.2011.2180020
PG 8
WC Engineering, Biomedical
SC Engineering
GA 895PK
UT WOS:000300508400024
PM 22186931
ER
PT J
AU Growdon, WB
Rauh-Hain, JJA
Cordon, A
Garrett, L
Schorge, JO
Goodman, A
Boruta, DM
Horowitz, NS
del Carmen, MG
AF Growdon, Whitfield B.
Rauh-Hain, J. Jose A.
Cordon, Adriana
Garrett, Leslie
Schorge, John O.
Goodman, Annekathryn
Boruta, David M.
Horowitz, Neil S.
del Carmen, Marcela G.
TI Prognostic Determinants in Patients With Stage I Uterine Papillary
Serous Carcinoma A 15-Year Multi-Institutional Review
SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
LA English
DT Article
DE Uterine papillary serous cancer; Stage; Endometrial cancer; Surgery
ID PLATINUM-BASED CHEMOTHERAPY; CLEAR-CELL CARCINOMA; PHASE-II; ENDOMETRIAL
CARCINOMA; RADIATION-THERAPY; SURVIVAL OUTCOMES; ADJUVANT THERAPY;
ONCOLOGY-GROUP; CANCER; UPSC
AB Objective: The aim of this retrospective, multi-institutional study was to evaluate the importance of surgical staging for stage I uterine papillary serous carcinomas (UPSCs) to determine optimal management of this rare tumor.
Methods: With institutional review board approval from both participating institutions, all patients with 2009 International Federation of Gynecology and Obstetrics stage I mixed serous and UPSC diagnosed between January 1, 1992, and December 31, 2007, were identified at the 2 institutions. Clinical factors were correlated using Spearman correlation coefficients, Kaplan-Meier survival estimates and a Cox proportional hazards model.
Results: Of the 204 UPSC patients treated during this period, 84 were classified as stage I, with substages as follows: stage IA, n = 71; stage IB, n = 13. Thirty-seven patients (44%) had a history of a second cancer (22 breast tumors, 9 synchronous mullerian cancers). Surgical staging with at least hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and bilateral pelvic lymph node dissection was performed in 60 (71%) of 84 patients. The median survival for all patients was 10 years. Univariate analysis revealed surgical staging (P < 0.001), normal preoperative CA-125 (P < 0.001), and absence of additional cancers (P < 0.01) to be associated with improved survival. Age-adjusted multivariate analysis incorporating these factors revealed that advancing substage (hazard ratio, 4.59; P < 0.05), a second malignancy (hazard ratio, 2.75; P < 0.04), and surgical staging (hazard ratio, 0.18; P G 0.001) were independent factors associated with overall survival. In a subset analysis excluding patients with a second malignancy, substage (hazard ratio, 3.52; P < 0.05), and surgical staging (hazard ratio, 0.16; P < 0.001) were independent factors affecting overall survival.
Conclusions: Independent of adjuvant chemotherapy or radiation, stage of disease, comprehensive surgical staging, and the presence of a second malignancy were predictors of overall survival.
C1 [Growdon, Whitfield B.; Rauh-Hain, J. Jose A.; Cordon, Adriana; Garrett, Leslie; Schorge, John O.; Goodman, Annekathryn; Boruta, David M.; del Carmen, Marcela G.] Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02114 USA.
[Rauh-Hain, J. Jose A.; Horowitz, Neil S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02115 USA.
RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA.
EM mdelcarmen@partners.org
NR 30
TC 17
Z9 18
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1048-891X
J9 INT J GYNECOL CANCER
JI Int. J. Gynecol. Cancer
PD MAR
PY 2012
VL 22
IS 3
BP 417
EP 424
DI 10.1097/IGC.0b013e31823c6e36
PG 8
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 898IN
UT WOS:000300735900013
PM 22237383
ER
PT J
AU Rombi, B
Delaney, TF
Macdonald, SM
Huang, MS
Ebb, DH
Liebsch, NJ
Raskin, KA
Yeap, BY
Marcus, KJ
Tarbell, NJ
Yock, TI
AF Rombi, Barbara
Delaney, Thomas F.
Macdonald, Shannon M.
Huang, Mary S.
Ebb, David H.
Liebsch, Norbert J.
Raskin, Kevin A.
Yeap, Beow Y.
Marcus, Karen J.
Tarbell, Nancy J.
Yock, Torunn I.
TI PROTON RADIOTHERAPY FOR PEDIATRIC EWING'S SARCOMA: INITIAL CLINICAL
OUTCOMES
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Proton radiation; Ewing's sarcoma
ID ACUTE MYELOID-LEUKEMIA; PRIMITIVE NEUROECTODERMAL TUMOR;
CHILDRENS-ONCOLOGY-GROUP; LONG-TERM SURVIVORS; RADIATION-THERAPY;
NEOADJUVANT CHEMOTHERAPY; STANDARD CHEMOTHERAPY; 2ND MALIGNANCIES;
CHILDHOOD-CANCER; LOCAL THERAPY
AB Purpose: Proton radiotherapy (PT) has been prescribed similarly to photon radiotherapy to achieve comparable disease control rates at comparable doses. The chief advantage of protons in this setting is to reduce acute and late toxicities by decreasing the amount of normal tissue irradiated. We report the preliminary clinical outcomes including late effects on our pediatric Ewing's sarcoma patients treated with PT at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (Boston, MA).
Methods and Materials: This was a retrospective review of the medical records of 30 children with Ewing's sarcoma who were treated with PT between April 2003 and April 2009.
Results: A total of 14 male and 16 female patients with tumors in several anatomic sites were treated with PT at a median age of 10 years. The median dose was 54 Gy (relative biological effectiveness) with a median follow-up of 38.4 months. The 3-year actuarial rates of event-free survival, local control, and overall survival were 60%, 86%, and 89%, respectively. PT was acutely well tolerated, with mostly mild-to-moderate skin reactions. At the time of writing, the only serious late effects have been four hematologic malignancies, which are known risks of topoisomerase and anthracyline exposure.
Conclusions: Proton radiotherapy was well tolerated, with few adverse events. Longer follow-up is needed to more fully assess tumor control and late effects, but the preliminary results are encouraging. (C) 2012 Elsevier Inc.
C1 [Delaney, Thomas F.; Macdonald, Shannon M.; Liebsch, Norbert J.; Tarbell, Nancy J.; Yock, Torunn I.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Sch Med, Boston, MA 02114 USA.
[Huang, Mary S.; Ebb, David H.] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Hematol & Oncol, Sch Med, Boston, MA 02114 USA.
[Yeap, Beow Y.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, Boston, MA 02114 USA.
[Marcus, Karen J.] Childrens Hosp Boston, Div Radiat Oncol, Boston, MA USA.
[Raskin, Kevin A.] Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Sch Med, Boston, MA 02114 USA.
[Rombi, Barbara] ATreP Prov Agcy Proton Therapy, Trento, Italy.
RP Yock, TI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Sch Med, 100 Blossom St,Cox Bldg 341, Boston, MA 02114 USA.
EM tyock@partners.org
FU Massachusetts General Hospital on National Institutes of Health [C06
CA059267]
FX Supported in part by the Federal Share of program income earned by
Massachusetts General Hospital on National Institutes of Health Grant
#C06 CA059267, Proton Therapy Research and Treatment Center.
NR 44
TC 21
Z9 21
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 1
PY 2012
VL 82
IS 3
BP 1142
EP 1148
DI 10.1016/j.ijrobp.2011.03.038
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 894JR
UT WOS:000300423500050
PM 21856094
ER
PT J
AU Hattangadi-Gluth, JA
Wo, JY
Nguyen, PL
Raad, RFA
Sreedhara, M
Niemierko, A
Freer, PE
Georgian-Smith, D
Bellon, JR
Wong, JS
Smith, BL
Harris, JR
Taghian, AG
AF Hattangadi-Gluth, Jona A.
Wo, Jennifer Y.
Nguyen, Paul L.
Raad, Rita F. Abi
Sreedhara, Meera
Niemierko, Andrzej
Freer, Phoebe E.
Georgian-Smith, Dianne
Bellon, Jennifer R.
Wong, Julia S.
Smith, Barbara L.
Harris, Jay R.
Taghian, Alphonse G.
TI BASAL SUBTYPE OF INVASIVE BREAST CANCER IS ASSOCIATED WITH A HIGHER RISK
OF TRUE RECURRENCE AFTER CONVENTIONAL BREAST-CONSERVING THERAPY
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article; Proceedings Paper
CT 51st Annual Meeting of the
American-Society-for-Therapeutic-Radiology-and Oncology (ASTRO)
CY OCT 31-NOV 05, 2009
CL Chicago, IL
SP Amer Soc Therapeut Radiol & Oncol (ASTRO)
DE Basal; Biologic subtype; Breast cancer; Local recurrence; Elsewhere
local recurrence; Triple negative; True recurrence
ID 20-YEAR FOLLOW-UP; LOCAL RECURRENCE; CONSERVATIVE SURGERY;
RADIATION-THERAPY; STAGE-I; ADJUVANT CHEMOTHERAPY;
PROGESTERONE-RECEPTOR; DISTANT RECURRENCE; ESTROGEN-RECEPTOR; TUMOR
RECURRENCE
AB Purpose: To determine whether breast cancer subtype is associated with patterns of ipsilateral breast tumor recurrence (IBTR), either true recurrence (TR) or elsewhere local recurrence (ELR), among women with pT1-T2 invasive breast cancer (IBC) who receive breast-conserving therapy (BCT).
Methods and Materials: From Jan 1998 to Dec 2003, 1,223 women with pT1-T2N0-3 IBC were treated with BCT (lumpectomy plus whole-breast radiation). Ninety percent of patients received adjuvant systemic therapy, but none received trastuzumab. Biologic cancer subtypes were approximated by determining estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), and human epidermal growth factor receptor-2-positive (HER-2+) expression, classified as luminal A (ER+ or PR+ and HER-2 negative [HER-2-]), luminal B (ER+ or PR+ and HER-2+), HER-2 (ER- and PR- and HER-2+), and basal (ER- and PR- and HER-2-) subtypes. Imaging, pathology, and operative reports were reviewed by two physicians independently, including an attending breast radiologist. Readers were blinded to subtype and outcome. TR was defined as IBTR within the same quadrant and within 3 cm of the primary tumor. All others were defined as ELR.
Results: At a median follow-up of 70 months, 24 patients developed IBTR (5-year cumulative incidence of 1.6%), including 15 TR and 9 ELR patients. At 5 years, basal (4.4%) and HER-2 (9%) subtypes had a significantly higher incidence of TR than luminal B (1.2%) and luminal A (0.2%) subtypes (p < 0.0001). On multivariate analysis, basal subtype (hazard ratio [HR], 4.8,p = 0.01), younger age at diagnosis (HR, 0.97;p = 0.05), and increasing tumor size (HR, 2.1;p = 0.04) were independent predictors of TR. Only younger age (HR, 0.95;p = 0.01) significantly predicted for ELR.
Conclusions: Basal and HER-2 subtypes are significantly associated with higher rates of TR among women with pT1-T2 IBC after BCT. Younger age predicts for both TR and ELR. Strategies to reduce TR in basal breast cancers, such as increased boost doses, concomitant radiation and chemotherapy, or targeted therapy agents, should be explored. (C) 2012 Elsevier Inc.
C1 [Wo, Jennifer Y.; Raad, Rita F. Abi; Niemierko, Andrzej; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Hattangadi-Gluth, Jona A.] Harvard Radiat Oncol Program, Boston, MA USA.
[Nguyen, Paul L.; Sreedhara, Meera; Bellon, Jennifer R.; Wong, Julia S.; Harris, Jay R.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Freer, Phoebe E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Georgian-Smith, Dianne] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA.
EM ataghian@partners.org
OI Freer, Phoebe/0000-0001-6886-7100
FU NCI NIH HHS [CA50628, P50 CA089393, P50CA089393, R01CA139118, R01
CA050628, R01 CA139118, R01 CA139118-01]
NR 43
TC 27
Z9 28
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 1
PY 2012
VL 82
IS 3
BP 1185
EP 1191
DI 10.1016/j.ijrobp.2011.02.061
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 894JR
UT WOS:000300423500056
PM 21601377
ER
PT J
AU Park, JJ
Chen, MH
Loffredo, M
D'Amico, AV
AF Park, Jessica J.
Chen, Ming-Hui
Loffredo, Marian
D'Amico, Anthony V.
TI PROSTATE-SPECIFIC ANTIGEN VELOCITY BEFORE AND AFTER ELIMINATION OF
FACTORS THAT CAN CONFOUND THE PROSTATE-SPECIFIC ANTIGEN LEVEL
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Prostate cancer; PSA velocity; Prostate cancer-specific mortality;
Prostate cancer management; High risk
ID PREOPERATIVE PSA VELOCITY; BEAM RADIATION-THERAPY; RADICAL
PROSTATECTOMY; HIGH-RISK; BIOLOGICAL VARIATION; CANCER; SERUM; DEATH;
MEN; FLUCTUATIONS
AB Purpose: Prostate-specific antigen (PSA) velocity, like PSA level, can be confounded. In this study, we estimated the impact that confounding factors could have on correctly identifying a patient with a PSA velocity >2 ng/ml/y.
Methods and Materials: Between 2006 and 2010, a total of 50 men with newly diagnosed PC comprised the study cohort. We calculated and compared the false-positive and false-negative PSA velocity >2 ng/ml/y rates for all men and those with low-risk disease using two approaches to calculate PSA velocity. First, we used PSA values obtained within 18 months of diagnosis; second, we used values within 18 months of diagnosis, substituting the prebiopsy PSA for a repeat, nonconfounded PSA that was obtained using the same assay and without confounders.
Results: Using PSA levels pre-biopsy, 46% of all men had a PSA velocity >2 ng/ml/y; whereas this value declined to 32% when substituting the last prebiopsy PSA for a repeat, nonconfounded PSA using the same assay and without confounders. The false-positive rate for PSA velocity >2 ng/ml/y was 43% as compared with a false-negative rate of PSA velocity >2 ng/ml/y of 11% (p = 0.0008) in the overall cohort. These respective values in the low-risk subgroup were 60% and 16.7% (p = 0.09).
Conclusion: This study provides evidence to explain the discordance in cancer-specific outcomes among groups investigating the prognostic significance of PSA velocity >2 ng/ml/y, and highlights the importance of patient education on potential confounders of the PSA test before obtaining PSA levels. (C) 2012 Elsevier Inc.
C1 [Park, Jessica J.; Loffredo, Marian; D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
[Park, Jessica J.; Loffredo, Marian; D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA.
RP Park, JJ (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA.
EM park16@fas.harvard.edu
NR 21
TC 2
Z9 2
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 1
PY 2012
VL 82
IS 3
BP 1217
EP 1221
DI 10.1016/j.ijrobp.2011.04.019
PG 5
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 894JR
UT WOS:000300423500060
PM 21640512
ER
PT J
AU Kang, J
Chen, MH
Zhang, YY
Moran, BJ
Dosoretz, DE
Katin, MJ
Braccioforte, MH
Salenius, SA
D'Amico, AV
AF Kang, Josephine
Chen, Ming-Hui
Zhang, Yuanye
Moran, Brian J.
Dosoretz, Daniel E.
Katin, Michael J.
Braccioforte, Michelle H.
Salenius, Sharon A.
D'Amico, Anthony V.
TI Type of Diabetes Mellitus and the Odds of Gleason Score 8 to 10 Prostate
Cancer
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Prostate cancer; Gleason score; Type II diabetes; Type I diabetes; PSA
ID RISK; TESTOSTERONE; METAANALYSIS; MORTALITY; THERAPY
AB Purpose: It has been recently shown that diabetes mellitus (DM) is significantly associated with the likelihood of presenting with high-grade prostate cancer (PCa) or Gleason score (GS) 8 to 10; however, whether this association holds for both Type 1 and 2 DM is unknown. In this study we evaluated whether DM Type 1, 2, or both are associated with high-grade PCa after adjusting for known predictors of high-grade disease.
Methods and Materials: Between 1991 and 2010, a total of 15,330 men diagnosed with PCa and treated with radiation therapy were analyzed. A polychotomous logistic regression analysis was performed to evaluate whether Type 1 or 2 DM was associated with odds of GS 7 or GS 8 to 10 compared with 6 or lower PCa, adjusting for African American race, age, prostate-specific antigen (PSA) level, and digital rectal examination findings.
Results: Men with Type 1 DM (adjusted odds ratio [AOR], 2.05; 95% confidence interval [CI], 1.28-3.27; p = 0.003) or Type 2 DM (AOR, 1.58; 95% CI, 1.26-1.99; p < 0.001) were significantly more likely to be diagnosed with GS 8 to 10 PCa compared with nondiabetic men. However this was not true for GS 7, for which these respective results were AOR, 1.30; 95% CI, 0.93-1.82; p = 0.12 and AOR, 1.13; 95% CI, 0.98-1.32; p = 0.10.
Conclusion: Type 1 and 2 DM were associated with a higher odds of being diagnosed with Gleason score 8 to 10 but not 7 PCa. Pending validation, men who are diagnosed with Type I DM with GS 7 or lower should be considered for additional workup to rule out occult high-grade disease. (C) 2012 Elsevier Inc.
C1 [Kang, Josephine; D'Amico, Anthony V.] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dept Radiat Oncol, Boston, MA 02115 USA.
[D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Chen, Ming-Hui; Zhang, Yuanye] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA.
[Moran, Brian J.; Braccioforte, Michelle H.] Prostate Canc Fdn Chicago, Westmont, IL USA.
[Dosoretz, Daniel E.; Katin, Michael J.; Salenius, Sharon A.] 21 Century Oncol Inc, Dept Radiat Oncol, Ft Myers, FL USA.
RP Kang, J (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA.
EM jkang3@partners.org
RI zhang, yuanye/H-6315-2013
NR 22
TC 12
Z9 12
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 1
PY 2012
VL 82
IS 3
BP E463
EP E467
DI 10.1016/j.ijrobp.2011.07.003
PG 5
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 894JR
UT WOS:000300423500017
PM 21944463
ER
PT J
AU Merrick, GS
Wallner, KE
Butler, WM
Galbreath, RW
Taira, AV
Orio, P
Adamovich, E
AF Merrick, Gregory S.
Wallner, Kent E.
Butler, Wayne M.
Galbreath, Robert W.
Taira, Al V.
Orio, Peter
Adamovich, Edward
TI 20 GY VERSUS 44 GY OF SUPPLEMENTAL EXTERNAL BEAM RADIOTHERAPY WITH
PALLADIUM-103 FOR PATIENTS WITH GREATER RISK DISEASE: RESULTS OF A
PROSPECTIVE RANDOMIZED TRIAL
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Prostate cancer; Brachytherapy; Higher risk; Prospective randomized
trial
ID PERMANENT PROSTATE BRACHYTHERAPY; BIOCHEMICAL OUTCOMES;
RADIATION-THERAPY; PARTIN TABLES; TARGET VOLUME; CANCER; EXTENSION
AB Purpose: The necessity of external beam radiotherapy (EBRT) as a supplement to prostate brachytherapy remains unknown. We report brachytherapy outcomes for patients with higher risk features randomized to substantially different supplemental EBRT regimens.
Methods and Materials: Between December 1999 and June 2004, 247 patients were randomized to 20 Gy vs. 44 Gy EBRT followed by a palladium-103 boost (115 Gy vs. 90 Gy). The eligibility criteria included clinically organ-confined disease with Gleason score 7-10 and/or pretreatment prostate-specific antigen (PSA) level 10-20 ng/mL. The median follow-up period was 9.0 years. Biochemical progression-free survival (bPFS) was defined as a PSA level of <= 0.40 ng/mL after nadir. The median day 0 prescribed dose covering 90% of the target volume was 125.7%; 80 men received androgen deprivation therapy (median, 4 months). Multiple parameters were evaluated for their effect on bPFS.
Results: For the entire cohort, the cause-specific survival, bPFS, and overall survival rates were 97.7%, 93.2%, and 80.8% at 8 years and 96.9%, 93.2%, and 75.4% at 10 years, respectively. The bPFS rate was 93.1% and 93.4% for the 20-Gy and 44-Gy arms, respectively (p = .994). However, no statistically significant differences were found in cause-specific survival or overall survival were identified. When stratified by PSA level of <= 10 ng/mL vs. >10 ng/mL, Gleason score, or androgen deprivation therapy, no statistically significant differences in bPFS were discerned between the two EBRT regimens. On multivariate analysis, bPFS was most closely related to the preimplant PSA and clinical stage. For patients with biochemically controlled disease, the median PSA level was <0.02 ng/mL.
Conclusion: The results of the present trial strongly suggest that two markedly different supplemental EBRT regimens result in equivalent cause-specific survival, bPFS, and overall survival. It is probable that the lack of benefit for a higher supplemental EBRT dose is the result of the high-quality brachytherapy dose distributions. (C) 2012 Elsevier Inc.
C1 [Merrick, Gregory S.; Butler, Wayne M.; Galbreath, Robert W.] Wheeling Jesuit Univ, Schiffler Canc Ctr, Wheeling, WV USA.
[Wallner, Kent E.] Univ Washington, Puget Sound Healthcare Corp, Seattle, WA 98195 USA.
[Taira, Al V.] Western Radiat Oncol Inc, Mountain View, CA USA.
[Orio, Peter] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA.
[Adamovich, Edward] Wheeling Hosp, Dept Pathol, Wheeling, WV 26003 USA.
RP Merrick, GS (reprint author), Wheeling Hosp, Schiffler Canc Ctr, 1 Med Pk, Wheeling, WV 26003 USA.
EM gmerrick@urologicresearchinstitute.org
NR 23
TC 7
Z9 7
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 1
PY 2012
VL 82
IS 3
BP E449
EP E455
DI 10.1016/j.ijrobp.2011.07.016
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 894JR
UT WOS:000300423500015
PM 22196131
ER
PT J
AU Nordenstedt, H
Younes, M
El-Serag, HB
AF Nordenstedt, Helena
Younes, Mamoun
El-Serag, Hashem B.
TI Expression of Androgen Receptors in Barrett Esophagus
SO JOURNAL OF CLINICAL GASTROENTEROLOGY
LA English
DT Letter
ID ADENOCARCINOMA; SEX; HORMONES; CANCER
C1 [Nordenstedt, Helena; El-Serag, Hashem B.] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA.
[Nordenstedt, Helena; El-Serag, Hashem B.] Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA.
[Nordenstedt, Helena] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Younes, Mamoun] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
RP Nordenstedt, H (reprint author), Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA.
OI Younes, Mamoun/0000-0001-9618-3451
FU NCI NIH HHS [P30 CA125123, R01 CA116845]; NIDDK NIH HHS [K24 DK078154,
T32 DK083266]; PHS HHS [R01 116845, NIDDK K24-04-107]
NR 8
TC 4
Z9 4
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0192-0790
J9 J CLIN GASTROENTEROL
JI J. Clin. Gastroenterol.
PD MAR
PY 2012
VL 46
IS 3
BP 251
EP 252
DI 10.1097/MCG.0b013e318238353e
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 895TG
UT WOS:000300518700014
PM 22327304
ER
PT J
AU Sonnenberg, A
Boardman, CR
AF Sonnenberg, Amnon
Boardman, Charles R.
TI Is it Justifiable to Withhold Endoscopic Information?
SO JOURNAL OF CLINICAL GASTROENTEROLOGY
LA English
DT Letter
ID BARRETTS-ESOPHAGUS; DIAGNOSIS
C1 [Sonnenberg, Amnon; Boardman, Charles R.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR 97201 USA.
RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR 97201 USA.
NR 7
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0192-0790
J9 J CLIN GASTROENTEROL
JI J. Clin. Gastroenterol.
PD MAR
PY 2012
VL 46
IS 3
BP 252
EP 253
DI 10.1097/MCG.0b013e318238e7d1
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 895TG
UT WOS:000300518700015
PM 22186741
ER
PT J
AU Erickson, JI
AF Erickson, Jeanette Ives
TI Leading a Highly Visible Hospital Through a Serious Reportable Event
SO JOURNAL OF NURSING ADMINISTRATION
LA English
DT Article
AB Most preventable adverse events result from systemic causes, not human error. The senior vice president for patient care/chief nurse at a leading hospital recounts the unnecessary death of a patient and the investigation that followed. Citing the critical importance of a "just culture,'' this case study offers a blueprint for managing a serious reportable event.
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Erickson, JI (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 230, Boston, MA 02114 USA.
EM jiveserickson@partners.org
NR 7
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-0443
J9 J NURS ADMIN
JI J. Nurs. Adm.
PD MAR
PY 2012
VL 42
IS 3
BP 131
EP 133
DI 10.1097/NNA.0b013e31824808b6
PG 3
WC Nursing
SC Nursing
GA 898HM
UT WOS:000300731600003
PM 22361868
ER
PT J
AU Banister, G
Winfrey, ME
AF Banister, Gaurdia
Winfrey, Marion E.
TI Enhancing Diversity in Nursing A Partnership Approach
SO JOURNAL OF NURSING ADMINISTRATION
LA English
DT Article
ID EDUCATION
AB Recent census data highlight the ongoing shift toward greater levels of racial and ethnic diversity in the US population. In 2000, non-Hispanic whites accounted for 69% of the population. By 2010, this decreased to 64%. The Census Bureau predicts that minorities will become the majority over the upcoming decades. In nursing and other healthcare professions, however, a different picture emerges, with minorities consistently underrepresented. The authors describe the development, outcomes, and benefits of the clinical leadership collaborative for diversity in nursing. Strategies for overcoming barriers to increasing diversity in the nursing profession are addressed.
C1 [Banister, Gaurdia] Massachusetts Gen Hosp, Inst Patient Care, Patient Care Serv, Boston, MA 02114 USA.
[Winfrey, Marion E.] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA.
RP Banister, G (reprint author), Massachusetts Gen Hosp, Inst Patient Care, Patient Care Serv, 55 Fruit St,FND 316, Boston, MA 02114 USA.
EM gbanister@partners.org
FU Partners HealthCare Chief Nurse Council
FX The authors thank Jariza Rodriguez for her invaluable support of program
operations; the members of the CLCDN steering committee for challenging
us to make the program the best it can be; the Partners HealthCare Chief
Nurse Council for their ongoing guidance and support; and Beth Kantz,
MS, RN, of Corrigan Kantz Consulting for writing and editing support.
NR 17
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-0443
J9 J NURS ADMIN
JI J. Nurs. Adm.
PD MAR
PY 2012
VL 42
IS 3
BP 176
EP 181
DI 10.1097/NNA.0b013e3182480a97
PG 6
WC Nursing
SC Nursing
GA 898HM
UT WOS:000300731600011
PM 22361876
ER
PT J
AU Gardiner, S
Hartzell, TL
AF Gardiner, Sonya
Hartzell, Tristan L.
TI Telemedicine and plastic surgery: A review of its applications,
limitations and legal pitfalls
SO JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY
LA English
DT Review
DE Telemedicine; Plastic surgery; Medico-legal; Limitations
ID MOBILE CAMERA-PHONE; RURAL TRAUMA CARE; MAXILLOFACIAL TRAUMA; DIGITAL
PHOTOGRAPHY; CLINICAL-EXPERIENCE; SURGICAL TRAUMA; FOLLOW-UP;
TELECONSULTATION; BURNS; MANAGEMENT
AB Background: Telemedicine is a rapidly expanding technology involving the exchange of medical information to assist diagnosis and treatment at a distance. Within the field of plastic surgery, where visual examination contributes heavily to patient management decision-making, telemedicine has great potential. However, privacy and medico-legal issues must be considered when using electronic communication to assist our clinical practice.
Methods: A comprehensive literature review of manuscripts published on telemedicine was performed. Articles were selected for relevance to plastic and reconstructive surgery and reviewed for applications, benefits and complications of telemedicine. In addition, the manuscripts were reviewed for conforming to current legal guidelines for the electronic transfer of patient information.
Results: Twenty-nine articles met the inclusion criteria (11 trauma and burns, 4 hand, 5 wound-care, 5 maxillofacial, 1 digital replantation, 2 free-flap monitoring, and 1 technical application). Twenty-eight (96%) manuscripts reported a benefit of telemedicine (commonly including increased access to expertise and costs saved through reduction of unnecessary transfers). However only five (17%) reported a statistical benefit compared to a standard treatment cohort (face-to-face interactions). Fifteen (51%) reported on adverse effects, which included misdiagnosis, time consumption, training, technical and cost issues. Only four manuscripts (14%) discussed conforming to legal guidelines within their institution.
Conclusions: Telemedicine can improve access to the specialty of plastic surgery by facilitating the provision of expertise at remote sites. Its application can be used in many situations and between a variety of healthcare professionals. However, there is little critical analysis on the benefits and risks of telemedicine. In addition, its legal implications need to be carefully considered if it is to be safely integrated into our daily practice. (C) 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
C1 [Gardiner, Sonya] Addenbrookes Hosp, Cambridge, England.
[Hartzell, Tristan L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Gardiner, S (reprint author), Addenbrookes Hosp, Cambridge, England.
EM sg410@cam.ac.uk
NR 42
TC 21
Z9 23
U1 1
U2 12
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1748-6815
EI 1878-0539
J9 J PLAST RECONSTR AES
JI J. Plast. Reconstr. Aesthet. Surg.
PD MAR
PY 2012
VL 65
IS 3
BP E47
EP E53
DI 10.1016/j.bjps.2011.11.048
PG 7
WC Surgery
SC Surgery
GA 895VM
UT WOS:000300524800001
PM 22178033
ER
PT J
AU King, G
Wood, MJ
AF King, Gerard
Wood, Malissa J.
TI The Right Ventricle of the Elite High End Endurance Athlete Cannot Be
Underestimated
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Editorial Material
ID MYOCARDIAL ADAPTATION; ARRHYTHMIAS; EXERCISE
C1 [Wood, Malissa J.] Massachusetts Gen Hosp, Boston, MA 02214 USA.
[King, Gerard] Eagle Lodge Cardiol, Limerick, Ireland.
RP Wood, MJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Blake 256, Boston, MA 02214 USA.
EM mjwood@partners.org
NR 14
TC 1
Z9 1
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD MAR
PY 2012
VL 25
IS 3
BP 272
EP 273
DI 10.1016/j.echo.2012.01.018
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 897FW
UT WOS:000300633200007
PM 22353337
ER
PT J
AU Bettmann, MA
White, RD
Woodard, PK
Abbara, S
Atalay, MK
Dorbala, S
Haramati, LB
Hendel, RC
Martin, ET
Ryan, T
Steiner, RM
AF Bettmann, Michael A.
White, Richard D.
Woodard, Pamela K.
Abbara, Suhny
Atalay, Michael K.
Dorbala, Sharmila
Haramati, Linda B.
Hendel, Robert C.
Martin, Edward T.
Ryan, Thomas
Steiner, Robert M.
TI ACR Appropriateness Criteria (R) Acute Chest Pain-Suspected Pulmonary
Embolism
SO JOURNAL OF THORACIC IMAGING
LA English
DT Review
DE Appropriateness Criteria; diagnosis of pulmonary embolism and DVT;
CTPAgrams; ventilation and perfusion (V/Q) scan
ID VENTILATION-PERFUSION SCINTIGRAPHY; RIGHT-VENTRICULAR DYSFUNCTION;
COMPUTED-TOMOGRAPHY; SPIRAL CT; HELICAL CT; DIAGNOSIS; ANGIOGRAPHY;
PREGNANCY; US
AB Pulmonary embolism (PE) remains a common and important clinical condition that cannot be accurately diagnosed on the basis of signs, symptoms, and history alone. In the absence of high pretest probability and with a negative high-sensitivity D-dimer test, PE can be effectively excluded; in other situations, diagnostic imaging is necessary. The diagnosis of PE has been facilitated by technical advancements and multidetector computed tomography pulmonary angiography, which is the major diagnostic modality currently used. Ventilation and perfusion (V/Q) scans remain largely accurate and useful in certain settings. Lower-extremity ultrasound can substitute by demonstrating deep vein thrombosis; however, if negative, further studies to exclude PE are indicated. In all cases, correlation with the clinical status, particularly with risk factors, improves not only the accuracy of diagnostic imaging but also overall utilization. Other diagnostic tests have limited roles. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multi-disciplinary expert panel. The development and review of the guidelines 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 [Bettmann, Michael A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC USA.
[White, Richard D.] Ohio State Univ, Med Ctr, Dept Radiol, Columbus, OH 43210 USA.
[Woodard, Pamela K.] Washington Univ, Mallinckrodt Inst Radiol, Sch Med, St Louis, MS USA.
[Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Atalay, Michael K.] Brown Univ, Dept Diagnost Imaging, Warren Alpert Sch Med, Providence, RI 02912 USA.
[Dorbala, Sharmila] Brigham & Womens Hosp, Dept Radiol, Soc Nucl Med, Boston, MA 02115 USA.
[Haramati, Linda B.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10467 USA.
[Hendel, Robert C.] Univ Miami, Miller Sch Med, Amer Coll Cardiol, Outpatient Serv Cardiovasc Div, Miami, FL 33136 USA.
[Martin, Edward T.] Oklahoma Heart Inst, Amer Coll Cardiol, Tulsa, OK USA.
[Ryan, Thomas] Ohio State Univ, Amer Coll Cardiol, Heart & Vasc Ctr, Columbus, OH 43210 USA.
[Steiner, Robert M.] Temple Univ Hlth Syst, Dept Radiol, Philadelphia, PA USA.
RP Bettmann, MA (reprint author), Amer Coll Radiol, Dept Qual & Safety, 1891 Preston White Dr, Reston, VA 20191 USA.
EM bettmann@wfubmc.edu
OI White, Richard D./0000-0002-1133-7819
FU Astellas Pharma US Inc.; NIH
FX Robert M. Steiner, is an consultant and course director Educational
Symposium Inc. and also consultant to Johnson and Johnson Co. Sharmila
Dorbala, has a research grant from Astellas Pharma US Inc. and funded by
NIH, a K23 grant. The other authors declare no conflicts of interest.
NR 28
TC 34
Z9 34
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0883-5993
J9 J THORAC IMAG
JI J. Thorac. Imaging
PD MAR
PY 2012
VL 27
IS 2
BP W28
EP W31
DI 10.1097/RTI.0b013e31823efeb6
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 897EP
UT WOS:000300628400002
PM 22343403
ER
PT J
AU Ochsenbauer, C
Edmonds, TG
Ding, HT
Keele, BF
Decker, J
Salazar, MG
Salazar-Gonzalez, JF
Shattock, R
Haynes, BF
Shaw, GM
Hahn, BH
Kappes, JC
AF Ochsenbauer, Christina
Edmonds, Tara G.
Ding, Haitao
Keele, Brandon F.
Decker, Julie
Salazar, Maria G.
Salazar-Gonzalez, Jesus F.
Shattock, Robin
Haynes, Barton F.
Shaw, George M.
Hahn, Beatrice H.
Kappes, John C.
TI Generation of Transmitted/Founder HIV-1 Infectious Molecular Clones and
Characterization of Their Replication Capacity in CD4 T Lymphocytes and
Monocyte-Derived Macrophages
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 R5 ENVELOPES;
CENTRAL-NERVOUS-SYSTEM; ANTIBODY NEUTRALIZATION; BIOLOGICAL PHENOTYPE;
SEXUAL TRANSMISSION; VIRAL DETERMINANTS; LYMPHOID-TISSUES; FUSION
INHIBITOR; TROPISM
AB Genome sequences of transmitted/founder (T/F) HIV-1 have been inferred by analyzing single genome amplicons of acute infection plasma viral RNA in the context of a mathematical model of random virus evolution; however, few of these T/F sequences have been molecularly cloned and biologically characterized. Here, we describe the derivation and biological analysis of ten infectious molecular clones, each representing a T/F genome responsible for productive HIV-1 clade B clinical infection. Each of the T/F viruses primarily utilized the CCR5 coreceptor for entry and replicated efficiently in primary human CD4(+) T lymphocytes. This result supports the conclusion that single genome amplification-derived sequences from acute infection allow for the inference of T/F viral genomes that are consistently replication competent. Studies with monocyte-derived macrophages (MDM) demonstrated various levels of replication among the T/F viruses. Although all T/F viruses replicated in MDM, the overall replication efficiency was significantly lower compared to prototypic "highly macrophage-tropic" virus strains. This phenotype was transferable by expressing the env genes in an isogenic proviral DNA backbone, indicating that T/F virus macrophage tropism mapped to Env. Furthermore, significantly higher concentrations of soluble CD4 were required to inhibit T/F virus infection compared to prototypic macrophage-tropic virus strains. Our findings suggest that the acquisition of clinical HIV-1 subtype B infection occurs by mucosal exposure to virus that is not highly macrophage tropic and that the generation and initial biological characterization of 10 clade B T/F infectious molecular clones provides new opportunities to probe virus-host interactions involved in HIV-1 transmission.
C1 [Ochsenbauer, Christina; Ding, Haitao; Decker, Julie; Salazar, Maria G.; Salazar-Gonzalez, Jesus F.; Kappes, John C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Edmonds, Tara G.; Kappes, John C.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL USA.
[Kappes, John C.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL USA.
[Keele, Brandon F.] NCI Frederick, SAIC Frederick Inc, Frederick, MD USA.
[Shattock, Robin] Univ London Imperial Coll Sci Technol & Med, London, England.
[Haynes, Barton F.] Duke Univ, Sch Med, Dept Med, Duke Human Vaccine Inst, Durham, NC 27706 USA.
[Haynes, Barton F.] Duke Univ, Sch Med, Dept Immunol, Duke Human Vaccine Inst, Durham, NC USA.
[Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
[Kappes, John C.] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA.
RP Kappes, JC (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
EM kappesjc@uab.edu
RI Ghartouchent, malek/B-9088-2012
FU NIH Center for HIV/AIDS Vaccine Immunology (CHAVI) [UO1-AI067854]; Bill
and Melinda Gates Foundation's Collaboration for AIDS Vaccine
Discovery/Comprehensive Antibody Vaccine Immune Monitoring Consortium
[38619]; Bill and Melinda Gates Foundation [37874]; facilities of the
Virology, Biostatistics, and Genetic Sequencing cores of the UAB Center
for AIDS Research [P30-AI-27767]; Genetically Defined Microbe and
Expression Core of the UAB Mucosal HIV and Immunobiology Center [R24
DK-64400]; Department of Veterans Affairs Medical Center, Research
Services; NIH [AI007439]
FX This study was supported by the NIH Center for HIV/AIDS Vaccine
Immunology (CHAVI; UO1-AI067854); the Bill and Melinda Gates
Foundation's Collaboration for AIDS Vaccine Discovery/Comprehensive
Antibody Vaccine Immune Monitoring Consortium (grant 38619); a Bill and
Melinda Gates Foundation Grand Challenges grant (grant 37874); the
facilities of the Virology, Biostatistics, and Genetic Sequencing cores
of the UAB Center for AIDS Research (P30-AI-27767); and the Genetically
Defined Microbe and Expression Core of the UAB Mucosal HIV and
Immunobiology Center (R24 DK-64400). Research was also supported by a
Merit Review Award (J.C.K.) and a Research Career Scientist Award
(J.C.K.) from the Department of Veterans Affairs Medical Center,
Research Services. T.G.E. is supported by NIH training grant AI007439.
NR 71
TC 123
Z9 123
U1 2
U2 13
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 MAR
PY 2012
VL 86
IS 5
BP 2715
EP 2728
DI 10.1128/JVI.06157-11
PG 14
WC Virology
SC Virology
GA 896AC
UT WOS:000300536800029
PM 22190722
ER
PT J
AU Wright, JK
Naidoo, VL
Brumme, ZL
Prince, JL
Claiborne, DT
Goulder, PJR
Brockman, MA
Hunter, E
Ndung'u, T
AF Wright, Jaclyn K.
Naidoo, Vanessa L.
Brumme, Zabrina L.
Prince, Jessica L.
Claiborne, Daniel T.
Goulder, Philip J. R.
Brockman, Mark A.
Hunter, Eric
Ndung'u, Thumbi
TI Impact of HLA-B(star)81-Associated Mutations in HIV-1 Gag on Viral
Replication Capacity
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE RESPONSE; CAPSID PROTEIN;
COMPENSATORY MUTATION; CHRONIC INFECTION; ESCAPE MUTATIONS; CELL
RESPONSES; HLA; EPITOPE; IMMUNE
AB HIV-1 attenuation resulting from immune escape mutations selected in Gag may contribute to slower disease progression in HIV-1-infected individuals expressing certain HLA class I alleles. We previously showed that the protective allele HLA-B(star)81 and the HLA-B(star)81-selected Gag T186S mutation are strongly associated with a lower viral replication capacity of recombinant viruses encoding Gag-protease derived from individuals chronically infected with HIV-1 subtype C. In the present study, we directly tested the effect of this mutation on viral replication capacity. In addition, we investigated potential compensatory effects of various polymorphisms, including other HLA-B(star)81-associated mutations that significantly covary with the T186S mutation. Mutations were introduced into a reference subtype B backbone and into patient-derived subtype C sequences in subtype B and C backbones by site-directed mutagenesis. The exponential-phase growth of mutant and wild-type viruses was assayed by flow cytometry of a green fluorescent protein reporter T cell line or by measurement of HIV-1 reverse transcriptase activity in culture supernatants. Engineering of the T186S mutation alone into all patient-derived subtype C sequences failed to yield replication-competent viruses, while in the subtype B sequence, the T186S mutation resulted in impaired replication capacity. Only the T186S mutation in combination with the T190I mutation yielded replication-competent viruses for all virus backbones tested; however, these constructs replicated slower than the wild type, suggesting that only partial compensation is mediated by the T190I mutation. Constructs encoding the T186S mutation in combination with other putative compensatory mutations were attenuated or defective. These results suggest that the T186S mutation is deleterious to HIV-1 subtype C replication and likely requires complex compensatory pathways, which may contribute to the clinical benefit associated with HLA-B(star)81.
C1 [Wright, Jaclyn K.; Naidoo, Vanessa L.; Goulder, Philip J. R.; Ndung'u, Thumbi] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, Durban, South Africa.
[Brumme, Zabrina L.; Brockman, Mark A.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada.
[Brumme, Zabrina L.; Brockman, Mark A.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
[Prince, Jessica L.; Claiborne, Daniel T.; Hunter, Eric] Emory Univ, Dept Pathol & Lab Med, Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Goulder, Philip J. R.; Ndung'u, Thumbi] MIT, Ragon Inst, Massachusetts Gen Hosp, Boston, MA USA.
[Goulder, Philip J. R.; Ndung'u, Thumbi] Harvard Univ, Boston, MA 02115 USA.
[Goulder, Philip J. R.] Univ Oxford, Nuffield Dept Med, Dept Paediat, Oxford, England.
RP Ndung'u, T (reprint author), Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, Durban, South Africa.
EM ndungu@ukzn.ac.za
RI Ghartouchent, malek/B-9088-2012;
OI Ndung'u, Thumbi/0000-0003-2962-3992; Brockman, Mark/0000-0001-6432-1426
FU South African Department of Science and Technology through the National
Research Foundation; Ragon Institute Fund for Innovation and New
International Initiatives; Mark and Lisa Schwartz Foundation; NIH
[ROI-AI 64060, 3 D43 TW000231 16S2]; National Research Foundation; Ragon
Institute of Massachusetts General Hospital, Massachusetts Institute of
Technology; Harvard University; Columbia University-Southern African
Fogarty through the Fogarty International Center; Canadian Institutes
for Health Research (CIHR)
FX This research was funded by the South African Department of Science and
Technology through the National Research Foundation, the Ragon Institute
Fund for Innovation and New International Initiatives, and the Mark and
Lisa Schwartz Foundation. Additional funding came from the NIH (ROI-AI
64060) (E.H.). J.K.W. was funded by the National Research Foundation and
the Ragon Institute of Massachusetts General Hospital, Massachusetts
Institute of Technology, and Harvard University. V.L.N. was supported by
the Columbia University-Southern African Fogarty AIDS International
Training and Research Program (AITRP) through the Fogarty International
Center, National Institutes of Health (grant 3 D43 TW000231 16S2).
Z.L.B. was supported by a New Investigator Award from the Canadian
Institutes for Health Research (CIHR). M.A.B. holds a Canada Research
Chair, Tier 2, in Viral Pathogenesis and Immunity. T.N. holds the South
African Department of Science and Technology/National Research
Foundation Research Chair in Systems Biology of HIV/AIDS.
NR 37
TC 27
Z9 27
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 MAR
PY 2012
VL 86
IS 6
BP 3193
EP 3199
DI 10.1128/JVI.06682-11
PG 7
WC Virology
SC Virology
GA 897GC
UT WOS:000300634100027
PM 22238317
ER
PT J
AU Mohr, DC
Young, GJ
AF Mohr, David C.
Young, Gary J.
TI Slack Resources and Quality of Primary Care
SO MEDICAL CARE
LA English
DT Article
DE veterans health; personnel staffing and scheduling; workload; patient;
satisfaction; vaccination; primary health care
ID HEALTH-CARE; OF-CARE; ORGANIZATIONS; INTERVENTIONS; IMMUNIZATION;
SATISFACTION; METAANALYSIS; PERFORMANCE; MANAGEMENT; INNOVATION
AB Background: Research generally shows that greater resource utilization fails to translate into higher-quality healthcare. Organizational slack is defined as extra organizational resources needed to meet demand. Divergent views exist on organizational slack in healthcare. Some investigators view slack negatively because it is wasteful, inefficient, and costly, whereas others view slack positively because it allows flexibility in work practices, expanding available services, and protecting against environmental changes.
Objective: We tested a curvilinear relationship between organizational slack and care quality.
Methods: The study setting was primary care clinics (n = 568) in the Veterans Health Administration. We examined organizational slack using the patient panel size per clinic capacity ratio and support staff per provider ratio staffing guidelines developed by the Veterans Health Administration. Patient-level measures were influenza vaccinations, continuity of care, and overall quality of care ratings. We obtained 2 independent patient samples with approximately 28,000 and 62,000 observations for the analysis. We used multilevel modeling and examined the linear and quadratic terms for both organizational slack measures.
Results: We found a significant curvilinear effect for panel size per clinic capacity for influenza vaccinations and overall quality of care. We also found support staff per provider exhibited a curvilinear effect for continuity of care and influenza vaccinations. Greater available resources led to better care, but at a certain point, additional resources provided minimal quality gains.
Conclusions: Our findings highlight the importance of primary care clinic managers monitoring staffing levels. Healthcare systems managing a balanced provider workload and staff-mix may realize better patient care delivery and cost management.
C1 [Mohr, David C.; Young, Gary J.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Dept Vet Affairs, Boston, MA USA.
[Mohr, David C.] Boston Univ, Sch Med, Dept Hlth Policy & Management, Boston, MA 02118 USA.
[Young, Gary J.] Northwestern Univ, Ctr Hlth Policy & Healthcare Res, Boston, MA USA.
RP Mohr, DC (reprint author), VA Boston Healthcare Syst 152M, 150 S Huntington Ave, Boston, MA 02130 USA.
EM david.mohr2@va.gov
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development, Health Services Research and Development
[IIR 05-221]
FX Supported by the Department of Veterans Affairs, Veterans Health
Administration, Office of Research and Development, Health Services
Research and Development for IIR 05-221.
NR 53
TC 3
Z9 4
U1 2
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
J9 MED CARE
JI Med. Care
PD MAR
PY 2012
VL 50
IS 3
BP 203
EP 209
DI 10.1097/MLR.0b013e318241e3e6
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 896YF
UT WOS:000300606600004
PM 22193414
ER
PT J
AU Curran, GM
Bauer, M
Mittman, B
Pyne, JM
Stetler, C
AF Curran, Geoffrey M.
Bauer, Mark
Mittman, Brian
Pyne, Jeffrey M.
Stetler, Cheryl
TI Effectiveness-implementation Hybrid Designs Combining Elements of
Clinical Effectiveness and Implementation Research to Enhance Public
Health Impact
SO MEDICAL CARE
LA English
DT Article
DE diffusion of innovation; implementation science; clinical trials;
pragmatic designs
ID HEALTH-SERVICES RESEARCH; QUERI SERIES; COLLABORATIVE CARE; BIPOLAR
DISORDER; FORMATIVE EVALUATION; TRIALS; EFFICACY; INTERVENTION;
PRINCIPLES; FRAMEWORK
AB Objectives: This study proposes methods for blending design components of clinical effectiveness and implementation research. Such blending can provide benefits over pursuing these lines of research independently; for example, more rapid translational gains, more effective implementation strategies, and more useful information for decision makers. This study proposes a "hybrid effectiveness-implementation" typology, describes a rationale for their use, outlines the design decisions that must be faced, and provides several real-world examples.
Results: An effectiveness-implementation hybrid design is one that takes a dual focus a priori in assessing clinical effectiveness and implementation. We propose 3 hybrid types: (1) testing effects of a clinical intervention on relevant outcomes while observing and gathering information on implementation; (2) dual testing of clinical and implementation interventions/strategies; and (3) testing of an implementation strategy while observing and gathering information on the clinical intervention's impact on relevant outcomes.
Conclusions: The hybrid typology proposed herein must be considered a construct still in evolution. Although traditional clinical effectiveness and implementation trials are likely to remain the most common approach to moving a clinical intervention through from efficacy research to public health impact, judicious use of the proposed hybrid designs could speed the translation of research findings into routine practice.
C1 [Curran, Geoffrey M.] Univ Arkansas Med Sci, Dept Psychiat, Div Hlth Serv Res, Little Rock, AR 72205 USA.
[Curran, Geoffrey M.; Pyne, Jeffrey M.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA.
[Bauer, Mark] Harvard Univ, VA Boston Healthcare Syst, Sch Med, Boston, MA USA.
[Mittman, Brian; Stetler, Cheryl] VA Greater Angeles Healthcare Syst, CIPRS, Los Angeles, CA USA.
RP Curran, GM (reprint author), Univ Arkansas Med Sci, Dept Psychiat, Div Hlth Serv Res, 4301 W Markham St 755, Little Rock, AR 72205 USA.
EM currangeoffreym@uams.edu
FU Department of Veterans Affairs, Health Services Research and Development
Service [MNT-05-152]; National Institute on Drug Abuse [K01 DA15102]
FX Supported by a research grant for the Department of Veterans Affairs,
Health Services Research and Development Service: MNT-05-152 (Pyne, PI)
and also funded by a research grant from the National Institute on Drug
Abuse: K01 DA15102 (Curran, PI).
NR 39
TC 184
Z9 185
U1 4
U2 31
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
J9 MED CARE
JI Med. Care
PD MAR
PY 2012
VL 50
IS 3
BP 217
EP 226
DI 10.1097/MLR.0b013e3182408812
PG 10
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 896YF
UT WOS:000300606600006
PM 22310560
ER
PT J
AU Keyhani, S
Falk, R
Bishop, T
Howell, E
Korenstein, D
AF Keyhani, Salomeh
Falk, Raphael
Bishop, Tara
Howell, Elizabeth
Korenstein, Deborah
TI The Relationship Between Geographic Variations and Overuse of Healthcare
Services A Systematic Review
SO MEDICAL CARE
LA English
DT Review
DE quality of health care; small-area analysis; physicians practice
pattern; Delphi Technique; Guidelines and topic; guideline adeherence;
health services misuse
ID ACUTE MYOCARDIAL-INFARCTION; SMALL-AREA VARIATIONS; REGIONAL-VARIATIONS;
OUTCOMES; QUALITY
AB Objective: To examine the relationship between overuse of healthcare services and geographic variations in medical care.
Design: Systematic Review.
Data Sources: Articles published in Medline between 1978, the year of publication of the first framework to measure quality, and January 1, 2009.
Study Selection: Four investigators screened 114,830 titles and 2 investigators screened all selected abstracts and articles for possible inclusion and extracted all data.
Data Extraction: We extracted data on rates of overuse in different geographic areas. We also extracted data on underuse, if available, for the same population in which overuse was measured.
Results: Five papers examined the relationship between geographic variations and overuse of healthcare services. One study in 2008 compared the appropriateness of coronary angiography (CA) for acute myocardial infarction in high-cost areas versus low cost areas in the Medicare population and found largely similar rates of inappropriateness (12.2% vs. 16.2%). A study in 2000 using national data concluded that overuse of CA explained little of the geographic variations in the use of this procedure in the Medicare program. An older study of Medicare patients found similar rates of inappropriate use of CA (15% to 17% vs. 18%), endoscopy (15% vs. 18% 19%), and carotid endarterectomy (29% vs. 30%) in low-use and high-use regions. A small area reanalysis of data from this study of 3 procedures found no evidence of a relationship between inappropriate use of procedures and volume in 23 adjacent counties of California. Another 2008 study found that inappropriate chemotherapy for stage I cancer was less common in low-cost areas compared with high-cost areas (3.1% vs. 6.3%).
Conclusions: The limited available evidence does not lend support to the hypothesis that inappropriate use of procedures is a major source of geographic variations in intensity and/or costs of care. More research is needed to improve our understanding of the relationship between geographic variations and the quality of care.
C1 [Keyhani, Salomeh] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94121 USA.
[Keyhani, Salomeh] San Francisco VA Med Ctr, WHSR & D Res Enhancement Award Program, San Francisco, CA USA.
[Falk, Raphael] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94121 USA.
[Howell, Elizabeth] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY USA.
[Korenstein, Deborah] Mt Sinai Sch Med, Div Gen Internal Med, Dept Med, New York, NY USA.
[Bishop, Tara] Weill Cornell Med Coll, Dept Publ Hlth & Med, New York, NY USA.
RP Keyhani, S (reprint author), Univ Calif San Francisco, Div Gen Internal Med, San Francisco VA Med Ctr 4150,Clement 111A1, San Francisco, CA 94121 USA.
EM salomeh.keyhani@ucsf.edu
FU Commonwealth Fund; VA HSR&D Career Development Award
FX Supported by the Commonwealth Fund. Dr Keyhani is also supported by a VA
HSR&D Career Development Award.
NR 14
TC 20
Z9 20
U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
J9 MED CARE
JI Med. Care
PD MAR
PY 2012
VL 50
IS 3
BP 257
EP 261
DI 10.1097/MLR.0b013e3182422b0f
PG 5
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 896YF
UT WOS:000300606600011
PM 22329997
ER
PT J
AU Burks, DJ
Kobus, AM
AF Burks, Derek J.
Kobus, Amy M.
TI The legacy of altruism in health care: the promotion of empathy,
prosociality and humanism
SO MEDICAL EDUCATION
LA English
DT Article
ID US MEDICAL-STUDENTS; PATIENT-CENTEREDNESS; ACADEMIC MEDICINE; TEACH
EMPATHY; BURNOUT; EDUCATION; PHYSICIANS; COMMUNICATION; VIEWPOINT;
ATTITUDES
AB OBJECTIVES This study aimed to examine concepts of altruism and empathy among medical students and professionals in conjunction with health care initiatives designed to support the maintenance of these qualities.
METHODS We searched for the terms ` altruism', ` altruistic', ` helping', ` prosocial behaviour' and ` empathy' in the Englishlanguage literature published from 1980 to the present within the Ovid MEDLINE, PsycInfo and PubMed databases. We used conceptual analysis to examine the relationships among altruism, empathy and related prosocial concepts in health care in order to understand how such factors may relate to emotional and career burnout, cynicism, decreased helping and decreased patient- centredness in care.
RESULTS Altruistic ideals and qualities of empathy appear to decrease among some medical students as they progress through their education. During this process, students face increasingly heavy workloads, deal with strenuous demands and become more acquainted with non- humanistic informal practices inherent in the culture of medicine. In combination, these factors increase the likelihood that emotional suppression, detachment from patients, burnout and other negative consequences may result, perhaps as a means of self-preservation. Alternatively, by making a mindful and intentional choice to endeavour for self-care and a healthy work-life balance, medical students can uphold humanistic and prosocial attitudes and behaviours.
CONCLUSIONS Promoting altruism in the context of a compensated health care career is contradictory and misguided. Instead, an approach to clinical care that is prosocial and empathic is recommended. Training in mindfulness, self-reflection and emotion skills may help medical students and professionals to recognise, regulate and behaviourally demonstrate empathy within clinical and professional encounters. However, health care initiatives to increase empathy and other humanistic qualities will be limited unless more practical and feasible emotion skills training is offered to and accepted by medical students. Success will be further moderated by the culture of medicine's full acceptance of empathy and humanism into its customs, beliefs, values, interactions and daily practices.
C1 [Burks, Derek J.] Portland VA Med Ctr, Dept Mental Hlth & Neurosci, Portland, OR USA.
[Burks, Derek J.] VISN 20 Mental Illness Res Educ & Clin Ctr, Portland, OR USA.
[Burks, Derek J.] Oregon Hlth & Sci Univ, Sch Med, Dept Clin Res, Portland, OR 97201 USA.
[Kobus, Amy M.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA.
RP Burks, DJ (reprint author), Natl Ctr Telehlth & Technol, 9933 W Hayes St, Tacoma, WA 98431 USA.
EM derekjburks@gmail.com
NR 74
TC 23
Z9 24
U1 8
U2 50
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0308-0110
J9 MED EDUC
JI Med. Educ.
PD MAR
PY 2012
VL 46
IS 3
BP 317
EP 325
DI 10.1111/j.1365-2923.2011.04159.x
PG 9
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 895NW
UT WOS:000300504100011
PM 22324531
ER
PT J
AU Conway, KE
Cotten, JF
AF Conway, Kevin E.
Cotten, Joseph F.
TI Covalent Modification of a Volatile Anesthetic Regulatory Site Activates
TASK-3 (KCNK9) Tandem-Pore Potassium Channels
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID TRANSMEMBRANE CONDUCTANCE REGULATOR; DOMAIN K+ CHANNELS;
GENERAL-ANESTHETICS; ISOFLURANE ANESTHESIA; INHIBITION;
NEUROTRANSMITTERS; OSCILLATIONS; MODULATION; MECHANISMS; RECEPTORS
AB TASK-3 (KCNK9) tandem-pore potassium channels provide a volatile anesthetic-activated and G alpha(q) protein-and acidic pHinhibited potassium conductance important in neuronal excitability. Met-159 of TASK-3 is essential for anesthetic activation and may contribute to the TASK-3 anesthetic binding site(s). We hypothesized that covalent occupancy of an anesthetic binding site would irreversibly activate TASK-3. We introduced a cysteine at residue 159 (M159C) and studied the rate and effect of Cys-159 modification by N-ethylmaleimide (NEM), a cysteine-selective alkylating agent. TASK-3 channels were transiently expressed in Fischer rat thyroid cells, and their function was studied in an Ussing chamber. NEM irreversibly activated M159C TASK-3, with minimal effects on wild-type TASK-3. NEM-modified M159C channels were resistant to inhibition by both acidic pH and active G alpha(q) protein. M159C channels that were first inhibited by G alpha(q) protein were more-slowly activated by NEM, which suggests protection of Cys159, and similar results were observed with isoflurane activation of wild-type TASK-3. M159W and M159F TASK-3 mutants behaved like NEM-modified M159C channels, with increased basal currents and resistance to inhibition by active G alpha(q) protein or acidic pH. TASK-3 wild-type/M159C dimers expressed as a single polypeptide demonstrated that modification of a single Cys-159 was sufficient for TASK-3 activation, and M159F/ M159C and M159W/M159C dimers provided evidence for cross-talk between subunits. The data are consistent with residue 159 contributing to an anesthetic regulatory site or sites, and they suggest that volatile anesthetics, through perturbations at a single site, increase TASK-3 channel activity and disrupt its regulation by active G alpha(q) protein, a determinant of central nervous system arousal and consciousness.
C1 [Conway, Kevin E.; Cotten, Joseph F.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
RP Cotten, JF (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRB 444, Boston, MA 02114 USA.
EM jcotten@partners.org
FU Foundation for Anesthesia Education and Research; National Institutes of
Health National Institute of General Medical Sciences [GM083216]
FX This research was supported by grants from the Foundation for Anesthesia
Education and Research and the National Institutes of Health National
Institute of General Medical Sciences [Grant GM083216].
NR 24
TC 7
Z9 7
U1 1
U2 3
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD MAR
PY 2012
VL 81
IS 3
BP 393
EP 400
DI 10.1124/mol.111.076281
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 897CK
UT WOS:000300618800013
PM 22147752
ER
PT J
AU Chang, SC
Xie, P
Anton, RF
De Vivo, I
Farrer, LA
Kranzler, HR
Oslin, D
Purcell, SM
Roberts, AL
Smoller, JW
Uddin, M
Gelernter, J
Koenen, KC
AF Chang, S-C
Xie, P.
Anton, R. F.
De Vivo, I.
Farrer, L. A.
Kranzler, H. R.
Oslin, D.
Purcell, S. M.
Roberts, A. L.
Smoller, J. W.
Uddin, M.
Gelernter, J.
Koenen, K. C.
TI No association between ADCYAP1R1 and post-traumatic stress disorder in
two independent samples
SO MOLECULAR PSYCHIATRY
LA English
DT Letter
ID GENOMEWIDE LINKAGE SCAN; SEMISTRUCTURED ASSESSMENT; ALCOHOLISM SSADDA;
DRUG-DEPENDENCE; ENVIRONMENT; RELIABILITY
C1 [Chang, S-C; Roberts, A. L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Xie, P.; Gelernter, J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Xie, P.; Gelernter, J.] VA CT Healthcare Ctr, West Haven, CT USA.
[Anton, R. F.] Med Univ S Carolina, Dept Psychiat, Ctr Alcohol & Drug Programs, Charleston, SC 29425 USA.
[De Vivo, I.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[De Vivo, I.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Farrer, L. A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Farrer, L. A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Farrer, L. A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA.
[Farrer, L. A.] Boston Univ, Sch Med, Dept Genet, Boston, MA 02118 USA.
[Farrer, L. A.] Boston Univ, Sch Med, Dept Genom Epidemiol & Biostat, Boston, MA 02118 USA.
[Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Genom Epidemiol & Biostat, Boston, MA 02118 USA.
[Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Genet, Boston, MA 02118 USA.
[Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Ophthalmol, Boston, MA 02118 USA.
[Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA 02118 USA.
[Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Med, Boston, MA 02118 USA.
[Kranzler, H. R.; Oslin, D.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Kranzler, H. R.; Oslin, D.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Purcell, S. M.; Smoller, J. W.] Massachusetts Gen Hosp, Ctr Genet Res, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Purcell, S. M.; Smoller, J. W.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Purcell, S. M.] Broad Inst, Cambridge, MA USA.
[Uddin, M.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA.
[Uddin, M.] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA.
[Gelernter, J.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Koenen, K. C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
RP Chang, SC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM joel.gelernter@yale.edu; kck5@columbia.edu
OI Farrer, Lindsay/0000-0001-5533-4225; Roberts, Andrea/0000-0001-5023-4399
NR 11
TC 25
Z9 25
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD MAR
PY 2012
VL 17
IS 3
BP 239
EP 241
DI 10.1038/mp.2011.118
PG 4
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 898BC
UT WOS:000300709300004
PM 21912390
ER
PT J
AU Solit, DB
Janne, PA
AF Solit, David B.
Jaenne, Pasi A.
TI TRANSLATIONAL MEDICINE Primed for resistance
SO NATURE
LA English
DT Editorial Material
ID WILD-TYPE BRAF; INHIBITORS
C1 [Solit, David B.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Solit, David B.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA.
RP Solit, DB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
EM solitd@mskcc.org; pjanne@partners.org
NR 12
TC 8
Z9 8
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAR 1
PY 2012
VL 483
IS 7387
BP 44
EP 45
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900040
PM 22382978
ER
PT J
AU Keller, TL
Zocco, D
Sundrud, MS
Hendrick, M
Edenius, M
Yum, J
Kim, YJ
Lee, HK
Cortese, JF
Wirth, DF
Dignam, JD
Rao, A
Yeo, CY
Mazitschek, R
Whitman, M
AF Keller, Tracy L.
Zocco, Davide
Sundrud, Mark S.
Hendrick, Margaret
Edenius, Maja
Yum, Jinah
Kim, Yeon-Jin
Lee, Hak-Kyo
Cortese, Joseph F.
Wirth, Dyann F.
Dignam, John David
Rao, Anjana
Yeo, Chang-Yeol
Mazitschek, Ralph
Whitman, Malcolm
TI Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA
synthetase
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID AMINO-ACID-METABOLISM; GENE-EXPRESSION; CELL-DIFFERENTIATION;
MAMMALIAN-CELLS; DENDRITIC CELLS; STRESS-RESPONSE; INFLAMMATION;
SPECIFICITY; DEPRIVATION; LIMITATION
AB Febrifugine, the bioactive constituent of one of the SO fundamental herbs of traditional Chinese medicine, has been characterized for its therapeutic activity, though its molecular target has remained unknown. Febrifugine derivatives have been used to treat malaria, cancer, fibrosis and inflammatory disease. We recently demonstrated that halofuginone (HF), a widely studied derivative of febrifugine, inhibits the development of T(H)17-driven autoimmunity in a mouse model of multiple sclerosis by activating the amino acid response (AAR) pathway. Here we show that HF binds glutamyl-prolyl-tRNA synthetase (EPRS), inhibiting prolyl-tRNA synthetase activity; this inhibition is reversed by the addition of exogenous proline or EPRS. We further show that inhibition of EPRS underlies the broad bioactivities of this family of natural product derivatives. This work both explains the molecular mechanism of a promising family of therapeutics and highlights the AAR pathway as an important drug target for promoting inflammatory resolution.
C1 [Keller, Tracy L.; Zocco, Davide; Hendrick, Margaret; Edenius, Maja; Yeo, Chang-Yeol; Whitman, Malcolm] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
[Sundrud, Mark S.; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Sundrud, Mark S.; Rao, Anjana] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
[Yum, Jinah; Kim, Yeon-Jin; Yeo, Chang-Yeol] Ewha Womans Univ, Div Life & Pharmaceut Sci, Dept Life Sci, Seoul, South Korea.
[Lee, Hak-Kyo] Hankyong Natl Univ, Genom Informat Ctr, Ansung, Kyongi Do, South Korea.
[Cortese, Joseph F.; Wirth, Dyann F.; Mazitschek, Ralph] Broad Inst Harvard & MIT, Infect Dis Initiat, Cambridge, MA USA.
[Wirth, Dyann F.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Dignam, John David] Univ Toledo, Coll Med, Dept Biochem & Canc Biol, Toledo, OH 43606 USA.
[Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
RP Keller, TL (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA.
EM tkeller@hms.harvard.edu; cyeo@ewha.ac.kr; rmazitschek@mgh.harvard.edu;
mwhitman@hms.harvard.edu
RI Mazitschek, Ralph/E-3741-2013;
OI Mazitschek, Ralph/0000-0002-1105-689X; Yeo,
Chang-Yeol/0000-0002-4440-1215
FU US National Institutes of Health (NIH) [GM089885]; Harvard Technology
Accelerator Award; Rural Development Administration, Republic of Korea
[PJ00812701, PJ008196]; NIH [AI40127, AI48213]; Juvenile Diabetes
Research Foundation [17-2010-421]
FX The authors would like to thank R. Copeland (Epizyme) for advice on the
execution of tight-binding analysis, W Kilo Harvard Catalyst Laboratory
for Innovative Translational Technologies for assistance with the
establishment of qPCR assays, and C. Walsh (Harvard), T. Roberts
(Dana-Farber Cancer Institute) anti S. Thomas (National Institute of
Environmental Health Science, USA) for their valuable comments on the
manuscript. This work was supported by US National Institutes of Health
(NIH) grant GM089885 and a Harvard Technology Accelerator Award (to MW);
by grants PJ00812701 and PJ008196 from The Next Generation BioGreen 21
Program, Rural Development Administration, Republic of Korea (to C.Y.Y.
and H.K.L.); and by NIH grants AI40127 and AI48213 and Juvenile Diabetes
Research Foundation 17-2010-421 (to A.R.).
NR 50
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U1 1
U2 24
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD MAR
PY 2012
VL 8
IS 3
BP 311
EP 317
DI 10.1038/NCHEMBIO.790
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 896VR
UT WOS:000300600000017
PM 22327401
ER
PT J
AU Gordon, DJ
Resio, B
Pellman, D
AF Gordon, David J.
Resio, Benjamin
Pellman, David
TI Causes and consequences of aneuploidy in cancer
SO NATURE REVIEWS GENETICS
LA English
DT Review
ID ACUTE MYELOID-LEUKEMIA; MEROTELIC KINETOCHORE ORIENTATION;
RETINOBLASTOMA TUMOR-SUPPRESSOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; MEDIATED
CHROMOSOME TRANSFER; DOSAGE LETHAL SCREENS; GENETIC INSTABILITY;
COLORECTAL CANCERS; DOWN-SYNDROME; HUMAN-CELLS
AB Genetic instability, which includes both numerical and structural chromosomal abnormalities, is a hallmark of cancer. Whereas the structural chromosome rearrangements have received substantial attention, the role of whole-chromosome aneuploidy in cancer is much less well-understood. Here we review recent progress in understanding the roles of whole-chromosome aneuploidy in cancer, including the mechanistic causes of aneuploidy, the cellular responses to chromosome gains or losses and how cells might adapt to tolerate these usually detrimental alterations. We also explore the role of aneuploidy in cellular transformation and discuss the possibility of developing aneuploidy-specific therapies.
C1 [Gordon, David J.; Resio, Benjamin; Pellman, David] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM david_pellman@dfci.harvard.edu
FU NCI NIH HHS [K08 CA160346]; NIGMS NIH HHS [R01 GM083299]
NR 123
TC 246
Z9 251
U1 7
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0056
J9 NAT REV GENET
JI Nat. Rev. Genet.
PD MAR
PY 2012
VL 13
IS 3
BP 189
EP 203
DI 10.1038/nrg3123
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 896ZI
UT WOS:000300609900004
PM 22269907
ER
PT J
AU Goldberg, NRS
Fields, V
Pflibsen, L
Salvatore, MF
Meshul, CK
AF Goldberg, Natalie R. S.
Fields, Victoria
Pflibsen, Lacey
Salvatore, Michael F.
Meshul, Charles K.
TI Social enrichment attenuates nigrostriatal lesioning and reverses motor
impairment in a progressive 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) mouse model of Parkinson's disease
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Dopamine; Striatum; MPTP; Social enrichment; Tyrosine hydroxylase
ID VESICULAR MONOAMINE TRANSPORTER; SLEEP BEHAVIOR DISORDER; POTENTIAL
EARLY MARKERS; ADULT SUBSTANTIA-NIGRA; DOPAMINE TRANSPORTER;
TYROSINE-HYDROXYLASE; STRIATAL DOPAMINE; NEURONAL DEATH; BASAL GANGLIA;
MICE LACKING
AB Environmental enrichment has been shown to be both neuroprotective and neurorestorative in 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of Parkinson's disease (PD). However, whether social interaction or novel physical stimulation is responsible for this recovery is controversial. in the current study, we have investigated the effects of only social enrichment (SocE) in progressively MPTP-lesioned mice. After mice were lesioned using a progressively increased dose (4 mg/kg, 8 mg/kg, 16 mg/kg and 32 mg/kg; each dose daily for 5 days), the MPTP-induced behavioral deficits, after the 32 mg/kg dose, were reversed with acute l-DOPA. This acute behavioral recovery suggests that this progressive MPTP-induced neurodegeneration is an appropriate murine model of PD. Mice were housed four per cage for the first 2 weeks of progressive lesioning or vehicle treatment. After the 8 mg/kg MPTP dose (prior to SocE intervention) mice showed a significant decrease in rearing and foot fault behaviors (FF/BB) compared to the vehicle group. Additionally, there was a 38% decrease in mean number of tyrosine hydroxylase immunoreactive (TH-ir) substantia nigra pars compacta (SNpc) neurons/section, and a 50% decrease in the optical density of TH-ir dorsolateral caudate putamen (CPu) terminals compared to the vehicle group. Mice were then housed either two (socially limited environment; SLE) or twelve (SocE) mice per cage during continued MPTP lesioning for the next 2 weeks at 16 mg/kg and 32 mg/kg MPTP. MPTP treatment was then discontinued, while mice remained in the SLE or SocE cages for an additional week. Rearing behavior was further impaired in SLE-MPTP mice following progressive MPTP, accompanied by additional decreases in the mean number of TH-ir SNpc neurons/section and CPu TH-ir terminals. CPu TH and dopamine transporter (DAT) protein expression, as well as dopamine tissue and TH protein levels was significantly decreased compared to either vehicle group. However, the deficit in rearing behavior in SLE-MPTP mice was reversed with acute I-DOPA following the intervention period. SocE-MPTP mice showed rearing and FF/BB behaviors similar to vehicle levels, although FF/BB was not significantly different from pre-intervention levels. The reversal from pre-intervention rearing deficits was correlated with an attenuated decrease in the mean number of SNpc TH-ir neurons/section and CPu TH and DAT protein, and with a blocked decrease in CPu TH-ir terminals compared to pre-intervention levels. Our findings show that SocE mice not only resist further nigrostriatal lesioning and FF/BB deficit, but rearing behavior is recovered to the level of the vehicle group despite continued MPTP treatment. In contrast, SLE mice showed continued loss of nigrostriatal TH-ir and decline of motor behaviors with progressive MPTP. The data suggest that non-pharmacological intervention that started at an early stage of dopamine loss is effective at slowing or blocking further nigrostriatal degeneration. Published by Elsevier Inc.
C1 [Goldberg, Natalie R. S.; Pflibsen, Lacey; Meshul, Charles K.] Portland VA Med Ctr, Portland, OR USA.
[Fields, Victoria; Salvatore, Michael F.] Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol Toxicol & Neurosci, Shreveport, LA 71105 USA.
[Meshul, Charles K.] Oregon Hlth & Sci Univ, Dept Behav Neurosci & Pathol, Portland, OR 97201 USA.
RP Meshul, CK (reprint author), VA Med Ctr RD 29, 3710 SW Vet Hosp Rd, Portland, OR 97239 USA.
EM meshulc@ohsu.edu
FU Department of Veterans Affairs; Edward P Stiles Trust - LSUHSC -
Shreveport; Biomedical Research Foundation of NW Louisiana
FX Support was from the Department of Veterans Affairs Merit Review Program
to CKM, and the Edward P Stiles Trust Fund - LSUHSC - Shreveport and
Biomedical Research Foundation of NW Louisiana to MFS. We also thank
Deborah Finn for consultation regarding statistical analyses.
NR 122
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U1 1
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD MAR
PY 2012
VL 45
IS 3
BP 1051
EP 1067
DI 10.1016/j.nbd.2011.12.024
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA 895TP
UT WOS:000300519600023
PM 22198503
ER
PT J
AU Undurraga, J
Baldessarini, RJ
AF Undurraga, Juan
Baldessarini, Ross J.
TI Randomized, Placebo-Controlled Trials of Antidepressants for Acute Major
Depression: Thirty-Year Meta-Analytic Review
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Review
DE antidepressants; evidence-based medicine; depression; meta-analysis;
controlled trials; secular changes
ID DOUBLE-BLIND TRIAL; EXTENDED-RELEASE XR; SEROTONIN REUPTAKE INHIBITORS;
SELEGILINE TRANSDERMAL SYSTEM; PAROXETINE-CONTROLLED TRIAL; DOSE
FLUOXETINE THERAPY; TO-MODERATE DEPRESSION; ST-JOHNS-WORT; HYPERICUM
EXTRACT; SUSTAINED-RELEASE
AB Antidepressant-placebo response-differences (RDs) in controlled trials have been declining, potentially confounding comparisons among older and newer drugs. For clinically employed antidepressants, we carried out a meta-analytic review of placebo-controlled trials in acute, unipolar, major depressive episodes reported over the past three decades to compare efficacy (drug-placebo RDs) of individual antidepressants and classes, and to consider factors associated with year-of-reporting by bivariate and multivariate regression modeling. Observed drug-placebo differences were moderate and generally similar among specific drugs, but larger among older antidepressants, notably tricyclics, than most newer agents. This outcome parallels selective increases in placebo-associated responses as trial-size has increased in recent years. Study findings generally support moderate efficacy of clinically employed antidepressants for acute major depression, but underscore limitations of meta-analyses of controlled trials for ranking drugs by efficacy. We suggest that efficiency and drug-placebo differences may be improved with fewer sites and subjects, and better quality-control of diagnostic and clinical assessments. Neuropsychopharmacology (2012) 37, 851-864; doi: 10.1038/npp.2011.306; published online 14 December 2011
C1 [Undurraga, Juan; Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Psychopharmacol Program, Boston, MA 02115 USA.
[Undurraga, Juan; Baldessarini, Ross J.] Massachusetts Gen Hosp, Int Consortium Psychot & Mood Disorders Res, Mailman Res Ctr, McLean Div, Boston, MA 02114 USA.
[Undurraga, Juan] Univ Barcelona, Bipolar Disorders Program, Dept Psychiat, Hosp Clin,IDIBAPS,CIBERSAM, Barcelona, Spain.
RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 312, 115 Mill St, Belmont, MA 02478 USA.
EM rbaldessarini@mclean.harvard.edu
RI Undurraga, Juan/F-3438-2012
OI Undurraga, Juan/0000-0001-6958-2369
FU Bruce J Anderson Foundation; McLean Private Donors Psychopharmacology
Research Fund; University of Barcelona; Fundacion Espanola de
Psiquiatria y Salud Mental
FX This work was supported by a grant from the Bruce J Anderson Foundation
and by the McLean Private Donors Psychopharmacology Research Fund (to
RJB), and by a Traveling Research Fellowship from the University of
Barcelona and the Fundacion Espanola de Psiquiatria y Salud Mental (to
JU). Leonardo Tondo, MD provided helpful technical advice.
NR 135
TC 74
Z9 75
U1 2
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAR
PY 2012
VL 37
IS 4
BP 851
EP 864
DI 10.1038/npp.2011.306
PG 14
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 896PB
UT WOS:000300580100001
PM 22169941
ER
PT J
AU Barry, MJ
Edgman-Levitan, S
AF Barry, Michael J.
Edgman-Levitan, Susan
TI Shared Decision Making - The Pinnacle of Patient-Centered Care
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Barry, Michael J.] Massachusetts Gen Hosp, Fdn Informed Med Decis Making, Boston, MA 02114 USA.
Massachusetts Gen Hosp, John D Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA.
RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Fdn Informed Med Decis Making, Boston, MA 02114 USA.
NR 5
TC 461
Z9 467
U1 8
U2 58
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 MAR 1
PY 2012
VL 366
IS 9
BP 780
EP 781
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 900GI
UT WOS:000300874300002
PM 22375967
ER
PT J
AU Kahn, R
Gorgon, L
Jones, K
McSherry, F
Glover, ED
Anthenelli, RM
Jackson, T
Williams, J
Murtaugh, C
Montoya, I
Yu, E
Elkashef, A
AF Kahn, Roberta
Gorgon, Liza
Jones, Karen
McSherry, Frances
Glover, Elbert D.
Anthenelli, Robert M.
Jackson, Thomas
Williams, Jill
Murtaugh, Cristin
Montoya, Ivan
Yu, Elmer
Elkashef, Ahmed
TI Selegiline Transdermal System (STS) as an Aid for Smoking Cessation
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID PLACEBO-CONTROLLED TRIAL; MONOAMINE-OXIDASE; CIGARETTE SMOKERS;
DOUBLE-BLIND; ABSTINENCE; HYDROCHLORIDE; INHIBITION; DEPRESSION
AB Introduction: This study examined the efficacy and safety of selegiline transdermal system (STS) and brief repeated behavioral intervention (BRBI) for smoking cessation in heavy smokers. We hypothesized that the quit rate of subjects who received STS and BRBI would be significantly greater than that of those who received placebo patch and BRBI.
Methods: This was a double-blind, placebo-controlled parallel-group study in which 246 men and women were randomized to receive either STS (n = 121) or placebo patch (n = 125) for 9 weeks. Recruitment targeted heavy smokers, defined as individuals with self-reported use of = 15 cigarettes/day in the 30 days prior to enrollment, who had smoked cigarettes for the past 5 years, and had an expired CO level >= 9 ppm during screening.
Results: Although STS was well tolerated, the overall results indicated that STS with BRBI was not more effective than placebo plus BRBI for smoking cessation (p = .58).
Conclusions: The results are discussed in relation to interventions for heavy smokers. Although 2 trials using oral selegiline both showed trends toward improved abstinence, these results indicate that STS with BRBI was not an effective aid for smoking cessation at the end of treatment (10 weeks), 14, or 26 weeks.
C1 [Kahn, Roberta; Gorgon, Liza; Montoya, Ivan; Elkashef, Ahmed] Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD 20892 USA.
[Jones, Karen; McSherry, Frances; Murtaugh, Cristin] Cooperat Studies Program Coordinating Ctr, Dept Vet Affairs, Perry Point, MD USA.
[Glover, Elbert D.] Univ Maryland, Ctr Hlth Behav Res, Dept Publ & Community Hlth, College Pk, MD 20742 USA.
[Anthenelli, Robert M.] Univ Cincinnati, Tri State Tobacco & Alcohol Res Ctr, Cincinnati, OH USA.
[Anthenelli, Robert M.] Cincinnati VA Med Ctr, Cincinnati, OH USA.
[Jackson, Thomas] Univ Wisconsin, UW Ctr Tobacco Res & Intervent, Sch Med & Publ Hlth, Madison, WI USA.
[Williams, Jill] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA.
[Yu, Elmer] Philadelphia VA Med Ctr, Philadelphia, PA USA.
RP Kahn, R (reprint author), Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, 6001 Execut Blvd Room 4123,MSC 9551, Bethesda, MD 20892 USA.
EM rkan@nida.nih.gov
FU National Institutes of Health, National Institute on Drug Abuse through
the Department of Veterans Affairs [Y1-DA4006]
FX This study was supported by the National Institutes of Health, National
Institute on Drug Abuse through the Department of Veterans Affairs
Cooperative Studies Program (Interagency Agreement No. Y1-DA4006).
NR 21
TC 9
Z9 9
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD MAR
PY 2012
VL 14
IS 3
BP 377
EP 382
DI 10.1093/ntr/ntr143
PG 6
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 898DB
UT WOS:000300714500018
PM 21846661
ER
PT J
AU Reed, SD
Guthrie, KA
Joffe, H
Shifren, JL
Seguin, RA
Freeman, EW
AF Reed, Susan D.
Guthrie, Katherine A.
Joffe, Hadine
Shifren, Jan L.
Seguin, Rebecca A.
Freeman, Ellen W.
TI Sexual Function in Nondepressed Women Using Escitalopram for Vasomotor
Symptoms A Randomized Controlled Trial
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT 22nd Annual Meeting of the North-American-Menopause-Society (NAMS)
CY SEP 21-24, 2011
CL Washington, DC
SP N Amer Menopause Soc (NAMS)
ID POSTMENOPAUSAL WOMEN; HOT FLASHES; DOUBLE-BLIND; INDEX FSFI;
DYSFUNCTION; ANTIDEPRESSANTS; MENOPAUSE; EFFICACY; HEALTH; POPULATION
AB OBJECTIVE: To evaluate sexual function in midlife women using selective serotonin reuptake inhibitors for vasomotor symptoms. Selective serotonin reuptake inhibitors effectively treat vasomotor symptoms but adversely affect sexual function in depressed populations. Information on sexual function in nondepressed midlife women using selective serotonin reuptake inhibitors for vasomotor symptoms is lacking; any treatments that might impair function are of concern.
METHODS: This was a randomized controlled trial comparing 8 weeks of escitalopram with placebo in women ages 40-62 years with 28 or more bothersome vasomotor symptoms per week. Change in Female Sexual Function Index composite score (ranges from 2 [not sexually active, no desire] to 36) and six sexual domains (desire, arousal, lubrication, orgasm, satisfaction, pain) and the Female Sexual Distress Scale, and a single-question of sexually-related personal distress from the Female Sexual Distress Scale, were compared between groups.
RESULTS: Among all women, median composite baseline Female Sexual Function Index score was 18.1 (interquartile range 2.4-26.5, n=200) and among sexually active women was 22.8 (interquartile range 17.4-27.0, n=75) in the escitalopram group and 23.6 (interquartile range 14.9-31.0, n=70) in the placebo group. Treatment with escitalopram did not affect composite Female Sexual Function Index score at follow-up compared with placebo (P=.18 all women; P=.47 sexually active at baseline). Composite mean Female Sexual Function Index change from baseline to week 8 was 0.1 (95% confidence interval [CI] -1.5 to 1.7) for escitalopram and 2.0 (95% CI 0.2-3.8) for placebo. The Female Sexual Distress Scale results did not differ between groups (P=.73) nor did adverse reports of sexual function. At week 8, among those women sexually active at baseline, there was a small difference between groups in Female Sexual Function Index domain mean score change in lubrication (P=.02) and a marginal nonsignificant difference in orgasm (P=.07).
CONCLUSION: Escitalopram, when used in the treatment of vasomotor symptoms, did not worsen overall sexual function among nondepressed midlife women.
C1 Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA 98195 USA.
Fred Hutchinson Canc Res Ctr, Data Coordinating Ctr, Seattle, WA 98104 USA.
Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA.
Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
RP Reed, SD (reprint author), Epidemiol Univ Washington, Dept Obstet & Gynecol, 325 9th Ave,Box 359865, Seattle, WA 98104 USA.
EM reeds@u.washington.edu
FU NCRR NIH HHS [UL1 RR025761]; NHLBI NIH HHS [K01 HL108807]; NIA NIH HHS
[U01 AG032669, U01AG032682, U01 AG032699-03, U01 AG032700, U01 AG032682,
U01 AG032699, U01 AG032656-04, U01AG032669, U01AG032700, U01 AG032656,
U01 AG032659, U01 AG032682-03, U01AG032699, U01AG032659]
NR 33
TC 7
Z9 8
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD MAR
PY 2012
VL 119
IS 3
BP 527
EP 538
DI 10.1097/AOG.0b013e3182475fa4
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 897GY
UT WOS:000300637400007
PM 22353950
ER
PT J
AU Katon, J
Reiber, G
Williams, MA
Yanez, D
Miller, E
AF Katon, Jodie
Reiber, Gayle
Williams, Michelle A.
Yanez, David
Miller, Edith
TI Hemoglobin A(1c) and Postpartum Abnormal Glucose Tolerance Among Women
With Gestational Diabetes Mellitus
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID GLYCATED HEMOGLOBIN; DCA 2000; A1C; MULTICENTER; INTOLERANCE;
POPULATION; PREDICTORS; ANTEPARTUM; PREVENTION; ANALYZER
AB OBJECTIVE: To analyze the association of hemoglobin A(1c) (HbA(1c)) at gestational diabetes mellitus (GDM) diagnosis with postpartum abnormal glucose in a cohort of women with GDM.
METHODS: Women with singleton pregnancies treated for GDM at a large diabetes and pregnancy program located in Charlotte, North Carolina, who completed a postpartum 2-hour oral glucose tolerance test were eligible for inclusion in this retrospective cohort study. Clinical information, including maternal HbA(1c) at diagnosis, was abstracted from medical records. A parametric survival model was used to assess the association of HbA(1c) at GDM diagnosis with postpartum maternal abnormal glucose including impaired fasting glucose, impaired glucose tolerance, and any postpartum abnormal glucose.
RESULTS: Of the 277 postpartum women with GDM, 75 (32%) had impaired fasting glucose, 61 (28%) had impaired glucose tolerance, and 15 (9%) were diagnosed with type 2 diabetes mellitus after delivery. After adjustment for clinic, maternal age, parity, prepregnancy body mass index 25 or higher, nonwhite race or ethnicity, and gestational week at first HbA(1c), we detected a trend of increased risk for impaired fasting glucose (P=.01), impaired glucose tolerance (P=.002), and any glucose abnormality (P<.001) associated with increased quartile of HbA1c at GDM diagnosis.
CONCLUSION: Hemoglobin A1c measured at GDM diagnosis may be a useful tool for identifying patients with GDM at highest risk of developing postpartum abnormal glucose. LEVEL OF EVIDENCE: II (Obstet Gynecol 2012;119:566-74) DOI: 10.1097/AOG.0b013e3182475ac2
C1 [Katon, Jodie] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
VA Puget Sound Hlth Care Syst, Seattle, WA USA.
Carolinas Med Ctr, Diabet & Pregnancy Program, Charlotte, NC 28203 USA.
RP Katon, J (reprint author), Univ Washington, Dept Epidemiol, Box 357236, Seattle, WA 98195 USA.
EM jkaton@u.washington.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health [T32 HD052462]; Seattle
chapter of Achievement Rewards for College Scientists; Samuel and Althea
Stroum Foundation; University of Washington Department of Epidemiology
FX Dr. Katon was supported by grant number T32 HD052462 from the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health; the Seattle chapter of
Achievement Rewards for College Scientists; and the Samuel and Althea
Stroum Foundation. This study was also funded by a grant from the
University of Washington Department of Epidemiology.
NR 35
TC 6
Z9 7
U1 0
U2 6
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 MAR
PY 2012
VL 119
IS 3
BP 566
EP 574
DI 10.1097/AOG.0b013e3182475ac2
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 897GY
UT WOS:000300637400012
PM 22353955
ER
PT J
AU Ter-Minassian, M
Chan, JA
Hooshmand, SM
Brais, LK
Daskalova, A
Heafield, R
Lin, XH
Christiani, DC
Kulke, MH
AF Ter-Minassian, Monica
Chan, Jennifer A.
Hooshmand, Susanne M.
Brais, Lauren K.
Daskalova, Anastassia
Heafield, Rachel
Lin, Xihong
Christiani, David C.
Kulke, Matthew H.
TI Prognostic Value of Chromogranin A and Alkaline Phosphatase in Patients
with Advanced Neuroendocrine Tumor
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Ter-Minassian, Monica; Chan, Jennifer A.; Hooshmand, Susanne M.; Brais, Lauren K.; Daskalova, Anastassia; Heafield, Rachel; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD MAR
PY 2012
VL 41
IS 2
BP 341
EP 342
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 897ID
UT WOS:000300641500050
ER
PT J
AU Chan, JA
Ryan, DP
Fuchs, CS
Zhu, AX
Abrams, TA
Wolpin, BM
Malinowski, P
Regan, E
Kulke, MH
AF Chan, Jennifer A.
Ryan, David P.
Fuchs, Charles S.
Zhu, Andrew X.
Abrams, Thomas A.
Wolpin, Brian M.
Malinowski, Paige
Regan, Eileen
Kulke, Matthew H.
TI Updated Results of a Phase I Study of Pasireotide (SOM230) in
Combination with Everolimus in Patients (pts) with Advanced
Neuroendocrine Tumors (NET)
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Chan, Jennifer A.; Fuchs, Charles S.; Abrams, Thomas A.; Wolpin, Brian M.; Malinowski, Paige; Regan, Eileen; Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Chan, Jennifer A.; Fuchs, Charles S.; Abrams, Thomas A.; Wolpin, Brian M.; Kulke, Matthew H.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Ryan, David P.; Zhu, Andrew X.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD MAR
PY 2012
VL 41
IS 2
BP 344
EP 344
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 897ID
UT WOS:000300641500057
ER
PT J
AU Kulke, MH
O'Dorisio, T
Phan, A
Langdon, R
Marek, B
Ikhlaque, N
Bergsland, E
Freiman, J
Law, L
Banks, P
Frazier, K
Jackson, J
Zambrowicz, B
AF Kulke, Matthew H.
O'Dorisio, Thomas
Alexandria Phan
Langdon, Robert, Jr.
Marek, Billie
Ikhlaque, Nadeem
Bergsland, Emily
Freiman, Joel
Law, Linda
Banks, Phillip
Frazier, Kenny
Jackson, Jessica
Zambrowicz, Brian
TI Efficacy of Telotristat Etiprate in Refractory Carcinoid Syndrome:
Preliminary Results of a Randomized, Placebo-Controlled, Multicenter
Study
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[O'Dorisio, Thomas] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA.
[Alexandria Phan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Langdon, Robert, Jr.] Nebraska Methodist Hosp Syst, Omaha, NE USA.
[Marek, Billie] Texas Oncol PA, McAllen, TX USA.
[Ikhlaque, Nadeem] St Francis Mem Hosp, Grove Beach, IN USA.
[Bergsland, Emily] Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA.
[Freiman, Joel; Law, Linda; Banks, Phillip; Frazier, Kenny; Jackson, Jessica; Zambrowicz, Brian] Lexicon Pharmaceut Inc, The Woodlands, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD MAR
PY 2012
VL 41
IS 2
BP 346
EP 346
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 897ID
UT WOS:000300641500064
ER
PT J
AU Townsend, E
Pallotta, S
AF Townsend, Elise
Pallotta, Sheila
TI Commentary on "Volumetric MRI and MRS and Early Motor Development of
Infants Born Preterm"
SO PEDIATRIC PHYSICAL THERAPY
LA English
DT Editorial Material
ID BIRTH-WEIGHT INFANTS
C1 [Townsend, Elise] MGH Inst Hlth Profess, Boston, MA USA.
[Townsend, Elise; Pallotta, Sheila] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Townsend, E (reprint author), MGH Inst Hlth Profess, Boston, MA USA.
NR 9
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0898-5669
EI 1538-005X
J9 PEDIATR PHYS THER
JI Pediatr. Phys. Ther.
PD SPR
PY 2012
VL 24
IS 1
BP 44
EP 45
DI 10.1097/PEP.0b013e31823e0abb
PG 3
WC Pediatrics; Rehabilitation
SC Pediatrics; Rehabilitation
GA 896IL
UT WOS:000300558800007
ER
PT J
AU Tucker, JD
Wong, FY
Nehl, EJ
Zhang, FJ
AF Tucker, Joseph D.
Wong, Frank Y.
Nehl, Eric J.
Zhang, Fujie
TI HIV testing and care systems focused on sexually transmitted HIV in
China
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Article
ID ANTIRETROVIRAL TREATMENT PROGRAM; HUMAN-IMMUNODEFICIENCY-VIRUS; FEMALE
SEX WORKERS; COST-EFFECTIVENESS; INFECTION; PREVENTION; HEALTH;
SERVICES; SYPHILIS; PROVINCE
AB Background Over three-quarters of new HIV infections in China during 2009 were estimated to be from sexual transmission. Over half of those living with HIV do not know their serostatus and identifying and treating individuals with sexually transmitted HIV infection has been challenging.
Objective This global assessment explores Chinese systems for detecting and treating those with HIV infection with a particular focus on groups at increased risk of sexually transmitted HIV.
Methods Published literature, grey sources and non-governmental reports were reviewed to describe HIV testing and care systems in China.
Results HIV testing and care in China involve several parallel health systems and have been largely successful in reaching large numbers of vulnerable individuals. Provider-initiated testing and counselling has been more effective than voluntary counselling and testing programmes for expanding HIV testing efforts in China. Individuals with sexually transmitted HIV infection are underrepresented in the antiretroviral care system compared with other high-risk groups.
Conclusions Comprehensive HIV testing and care bring together a number of Chinese health systems, but there are still gaps and challenges. Research and programmes focused on HIV testing and care for those with increased sexual risk are needed.
C1 [Tucker, Joseph D.] UNC Chapel Hill Sch Med, Dept Med, Div Infect Dis, Chapel Hill, NC USA.
[Tucker, Joseph D.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02139 USA.
[Wong, Frank Y.; Nehl, Eric J.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Zhang, Fujie] Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, Beijing, Peoples R China.
[Zhang, Fujie] Capital Med Med Univ, Ditan Hosp, Beijing, Peoples R China.
RP Tucker, JD (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02139 USA.
EM jtucker4@partners.org
RI Ghartouchent, malek/B-9088-2012
FU NIH (US NIH) [1K01TW008200-01A1]; UNC [NIH FIC D43 TW01039]; UNC Social
Science Research on HIV/AIDS in China (NIH NICHD) [R24 HD056670-01]; UNC
Center for AIDS Research; Emory Center for AIDS Research [P30 AI050409]
FX Financial support for this research came from an NIH Fogarty K01 award
(US NIH 1K01TW008200-01A1), the UNC Fogarty AIDS International Research
and Training Program (NIH FIC D43 TW01039), the UNC Social Science
Research on HIV/AIDS in China (NIH NICHD R24 HD056670-01), the UNC
Center for AIDS Research and the Emory Center for AIDS Research (P30
AI050409).
NR 52
TC 12
Z9 12
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD MAR
PY 2012
VL 88
IS 2
BP 116
EP 119
DI 10.1136/sextrans-2011-050135
PG 4
WC Infectious Diseases
SC Infectious Diseases
GA 897HH
UT WOS:000300638300008
PM 22345024
ER
PT J
AU Narva, E
Rahkonen, N
Emani, MR
Lund, R
Pursiheimo, JP
Nasti, J
Autio, R
Rasool, O
Denessiouk, K
Lahdesmaki, H
Rao, A
Lahesmaa, R
AF Narva, Elisa
Rahkonen, Nelly
Emani, Maheswara Reddy
Lund, Riikka
Pursiheimo, Juha-Pekka
Nasti, Juuso
Autio, Reija
Rasool, Omid
Denessiouk, Konstantin
Lahdesmaki, Harri
Rao, Anjana
Lahesmaa, Riitta
TI RNA-Binding Protein L1TD1 Interacts with LIN28 via RNA and is Required
for Human Embryonic Stem Cell Self-Renewal and Cancer Cell Proliferation
SO STEM CELLS
LA English
DT Article
DE L1TD1; Pluripotent stem cells; Embryonic stem cells; Embryonal
carcinoma; Proliferation
ID PROCESSING BODIES; CARCINOMA-CELLS; MESSENGER-RNAS; ES CELLS; P-BODIES;
EXPRESSION; OCT4; REGULATOR; SITES; DIFFERENTIATION
AB Human embryonic stem cells (hESC) have a unique capacity to self-renew and differentiate into all the cell types found in human body. Although the transcriptional regulators of pluripotency are well studied, the role of cytoplasmic regulators is still poorly characterized. Here, we report a new stem cell-specific RNA-binding protein L1TD1 (ECAT11, FLJ10884) required for hESC self-renewal and cancer cell proliferation. Depletion of L1TD1 results in immediate downregulation of OCT4 and NANOG. Furthermore, we demonstrate that OCT4, SOX2, and NANOG all bind to the promoter of L1TD1. Moreover, L1TD1 is highly expressed in seminomas, and depletion of L1TD1 in these cancer cells influences self-renewal and proliferation. We show that L1TD1 colocalizes and interacts with LIN28 via RNA and directly with RNA helicase A (RHA). LIN28 has been reported to regulate translation of OCT4 in complex with RHA. Thus, we hypothesize that L1TD1 is part of the L1TD1-RHA-LIN28 complex that could influence levels of OCT4. Our results strongly suggest that L1TD1 has an important role in the regulation of stemness. STEM CELLS 2012;30:452-460
C1 [Narva, Elisa; Rahkonen, Nelly; Emani, Maheswara Reddy; Lund, Riikka; Pursiheimo, Juha-Pekka; Nasti, Juuso; Autio, Reija; Rasool, Omid; Denessiouk, Konstantin; Lahesmaa, Riitta] Univ Turku, Turku Ctr Biotechnol, FIN-20521 Turku, Finland.
[Narva, Elisa; Rahkonen, Nelly; Emani, Maheswara Reddy; Lund, Riikka; Pursiheimo, Juha-Pekka; Nasti, Juuso; Autio, Reija; Rasool, Omid; Denessiouk, Konstantin; Lahesmaa, Riitta] Abo Akad Univ, FIN-20521 Turku, Finland.
[Autio, Reija; Lahdesmaki, Harri] Tampere Univ Technol, Dept Signal Proc, FIN-33101 Tampere, Finland.
[Lahdesmaki, Harri] Aalto Univ, Dept Informat & Comp Sci, Espoo, Finland.
[Rao, Anjana] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
[Rao, Anjana] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Rao, Anjana] La Jolla Inst Allergy & Immunol, La Jolla, CA USA.
RP Lahesmaa, R (reprint author), Univ Turku, Turku Ctr Biotechnol, POB 123, FIN-20521 Turku, Finland.
EM riitta.lahesmaa@btk.fi
RI Autio, Reija/D-2037-2014;
OI Lund, Riikka/0000-0002-1068-5918
FU European Union; JDRF; Academy of Finland; Finnish Cancer Organizations;
Turku Graduate School of Biomedical Sciences; Ida Montin Foundation;
Finnish Cultural Foundation
FX We thank Outi Hovatta (Karolinska Institute, Sweden) for the hESC lines;
Peter Andrews (University of Sheffield, U. K.) for the EC cell lines,
antibodies and plasmids; Jianliang Li (University of Sheffield, U. K.)
for the NT2D1-TetR3 cell line; Anne-Mari Tveit, Joel Nystrom, Subhanjan
Bhowmik, Kirsi Rautajoki, and technicians Marjo Hakkarainen, Paivi
Junni, Arja Reinikainen, and Sarita Heinonen for the assistance with the
experiments and data mining; Cell Imaging Core and The Finnish
Microarray and Sequencing Centre. This study was supported by funding
for the ESTOOLS consortium under the Sixth Research Framework Programme
of the European Union, JDRF, The Academy of Finland, the Finnish Cancer
Organizations, Turku Graduate School of Biomedical Sciences, Ida Montin
Foundation, and Finnish Cultural Foundation. A. R. is currently
affiliated with La Jolla Institute for Allergy and Immunology, La Jolla,
CA.
NR 46
TC 27
Z9 30
U1 0
U2 9
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 MAR
PY 2012
VL 30
IS 3
BP 452
EP 460
DI 10.1002/stem.1013
PG 9
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 896ZW
UT WOS:000300611400013
PM 22162396
ER
PT J
AU Remer, EM
Casalino, DD
Arellano, RS
Bishoff, JT
Coursey, CA
Dighe, M
Fulgham, P
Israel, GM
Lazarus, E
Leyendecker, JR
Majd, M
Nikolaidis, P
Papanicolaou, N
Prasad, S
Ramchandani, P
Sheth, S
Vikram, R
Karmazyn, B
AF Remer, Erick M.
Casalino, David D.
Arellano, Ronald S.
Bishoff, Jay T.
Coursey, Courtney A.
Dighe, Manjiri
Fulgham, Pat
Israel, Gary M.
Lazarus, Elizabeth
Leyendecker, John R.
Majd, Massoud
Nikolaidis, Paul
Papanicolaou, Nicholas
Prasad, Srinivasa
Ramchandani, Parvati
Sheth, Sheila
Vikram, Raghunandan
Karmazyn, Boaz
TI ACR Appropriateness Criteria (R) Acute Onset of Scrotal Pain - Without
Trauma, Without Antecedent Mass
SO ULTRASOUND QUARTERLY
LA English
DT Article
DE appropriateness criteria; acute scrotum/acute scrotal pain; testicular
torsion; epididymoorchitis; ultrasound; MRI
ID COLOR DOPPLER SONOGRAPHY; SEGMENTAL TESTICULAR INFARCTION; SPERMATIC
CORD TORSION; EMERGENCY-DEPARTMENT; PEDIATRIC-PATIENTS;
CLINICAL-OUTCOMES; CHILDREN; ULTRASOUND; US; ULTRASONOGRAPHY
AB Men or boys, who present with acute scrotal pain without prior trauma or a known mass, most commonly suffer from torsion of the spermatic cord; epididymitis or epididymoorchitis; or torsion of the testicular appendages. Less common causes of pain include a strangulated hernia, segmental testicular infarction, or a previously undiagnosed testicular tumor. Ultrasound is the study of choice to distinguish these disorders; it has supplanted Tc-99 m scrotal scintigraphy for the diagnosis of spermatic cord torsion. MRI should be used in a problem solving role if the ultrasound examination is inconclusive. The ACR Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every two 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 where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
C1 [Remer, Erick M.] Cleveland Clin, Cleveland, OH 44106 USA.
[Casalino, David D.; Nikolaidis, Paul] Northwestern Univ, Chicago, IL 60611 USA.
[Arellano, Ronald S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bishoff, Jay T.] Intermt Urol Inst, Murray, UT USA.
[Bishoff, Jay T.; Fulgham, Pat] Amer Urol Assoc, Linthicum, MD 21090 USA.
[Coursey, Courtney A.] Emory Univ Hosp, Atlanta, GA 30322 USA.
[Dighe, Manjiri] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Fulgham, Pat] Presbyterian Med Ctr, Dallas, TX USA.
[Israel, Gary M.] Yale Univ, Sch Med, New Haven, CT USA.
[Lazarus, Elizabeth] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Leyendecker, John R.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Majd, Massoud] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Majd, Massoud] Soc Nucl Med, Reston, VA USA.
[Papanicolaou, Nicholas; Ramchandani, Parvati] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Prasad, Srinivasa] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Sheth, Sheila] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Vikram, Raghunandan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Karmazyn, Boaz] Indiana Univ, James Whitcomb Riley Hosp Children, Indianapolis, IN USA.
RP Remer, EM (reprint author), Cleveland Clin Fdn, Dept Radiol A21, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM remere1@ccf.org
NR 63
TC 5
Z9 5
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-8771
J9 ULTRASOUND Q
JI Ultrasound Q.
PD MAR
PY 2012
VL 28
IS 1
BP 47
EP 51
DI 10.1097/RUQ.0b013e3182493c97
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 898GB
UT WOS:000300725600007
PM 22357246
ER
PT J
AU O'Donovan, DJ
Stokes-Rees, I
Nam, Y
Blacklow, SC
Schroder, GF
Brunger, AT
Sliz, P
AF O'Donovan, Daniel J.
Stokes-Rees, Ian
Nam, Yunsun
Blacklow, Stephen C.
Schroeder, Gunnar F.
Brunger, Axel T.
Sliz, Piotr
TI A grid-enabled web service for low-resolution crystal structure
refinement
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID PROTEIN DATA-BANK; CRYSTALLOGRAPHY; COMPLEX
AB Deformable elastic network (DEN) restraints have proved to be a powerful tool for refining structures from low-resolution X-ray crystallographic data sets. Unfortunately, optimal refinement using DEN restraints requires extensive calculations and is often hindered by a lack of access to sufficient computational resources. The DEN web service presented here intends to provide structural biologists with access to resources for running computationally intensive DEN refinements in parallel on the Open Science Grid, the US cyberinfrastructure. Access to the grid is provided through a simple and intuitive web interface integrated into the SBGrid Science Portal. Using this portal, refinements combined with full parameter optimization that would take many thousands of hours on standard computational resources can now be completed in several hours. An example of the successful application of DEN restraints to the human Notch1 transcriptional complex using the grid resource, and summaries of all submitted refinements, are presented as justification.
C1 [O'Donovan, Daniel J.; Stokes-Rees, Ian; Nam, Yunsun; Blacklow, Stephen C.; Sliz, Piotr] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Blacklow, Stephen C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Blacklow, Stephen C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Schroeder, Gunnar F.] Forschungszentrum Julich, Inst Complex Syst ICS 6, D-52425 Julich, Germany.
[Brunger, Axel T.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Brunger, Axel T.] Stanford Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
[Brunger, Axel T.] Stanford Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
[Brunger, Axel T.] Stanford Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
[Brunger, Axel T.] Stanford Sch Med, Dept Photon Sci, Stanford, CA 94305 USA.
[Sliz, Piotr] Childrens Hosp, Mol Med Lab, Boston, MA 02115 USA.
RP Sliz, P (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM sliz@hkl.hms.harvard.edu
RI Schroder, Gunnar/H-5261-2013;
OI Schroder, Gunnar/0000-0003-1803-5431; Brunger, Axel/0000-0001-5121-2036;
Stokes-Rees, Ian/0000-0002-6832-6168; Sliz, Piotr/0000-0002-6522-0835
FU National Science Foundation [0639193]; US Department of Energy's Office
of Science
FX This research was performed using resources provided by the Open Science
Grid, which is supported by the National Science Foundation and the US
Department of Energy's Office of Science. This work was supported by the
National Science Foundation grant 0639193 (PS).
NR 17
TC 12
Z9 12
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0907-4449
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD MAR
PY 2012
VL 68
BP 261
EP 267
DI 10.1107/S0907444912001163
PN 3
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 894RM
UT WOS:000300444300008
PM 22349228
ER
PT J
AU Adeseun, GA
Bonney, CC
Rosas, SE
AF Adeseun, Gbemisola A.
Bonney, Christine C.
Rosas, Sylvia E.
TI Health Literacy Associated With Blood Pressre but not Other
Cardiovascular Disease Risk Factors Among Dialysis Patients
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure; cardiovascular disease; end-stage renal disease; health
literacy; hemodialysis; hypertension; peritoneal dialysis
ID BODY-MASS INDEX; HEMODIALYSIS-PATIENTS; ALL-CAUSE; MORTALITY;
HYPERTENSION; KNOWLEDGE; CKD; PREVALENCE; CHOLESTEROL; SURVIVAL
AB BACKGROUND
Limited health literacy is prevalent and has been linked to adverse patient outcomes. We examined the relationship between health literacy and cardiovascular disease (CVD) risk factors, including blood pressure (BP) parameters, lipids, waist-to-hip ratio (WHR), body mass index (BMI), and tobacco utilization among dialysis patients.
METHODS
We conducted a cross-sectional study of 72 participants in a prospective cohort study of vascular calcification in newly initiated dialysis patients. Health literacy was assessed using the Short Test of Functional Health Literacy (S-TOFHLA) in Adults. The study population was dichotomized into those with and without adequate literacy. Linear and logistic regression analyses were used to predict continuous and dichotomous cardiovascular risk factor variables, respectively.
RESULTS
Twenty-one percent had limited health literacy. Compared to limited health literacy, adequate health literacy was associated with lower BP parameters in multivariable analyses (systolic blood pressure (SBP): beta-16.8, s.e. 6.7, P = 0.01; diastolic blood pressure (DBP):beta-13.8, s.e. 4.1, P = 0.001; mean arterial pressure (MAP):beta-14.8, s.e. 4.6, P = 0.002). Health literacy was not a statistically significant predictor of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, WHR, BMI, or tobacco utilization.
CONCLUSIONS
Limited health literacy is common in individuals on dialysis. Individuals with adequate health literacy skills had DBP readings that were on average 13.8 mm Hg lower and MAP that was 14.8 mm Hg lower than those with inadequate health literacy. Prospective studies to elucidate if improvements in health literacy skills will lead to improvement in BP control are needed.
C1 [Adeseun, Gbemisola A.; Bonney, Christine C.; Rosas, Sylvia E.] Univ Penn, Dept Med, Div Renal Electrolyte & Hypertens, Philadelphia, PA 19104 USA.
[Rosas, Sylvia E.] Philadelphia Vet Adm Med Ctr, Dept Med, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
RP Rosas, SE (reprint author), Univ Penn, Dept Med, Div Renal Electrolyte & Hypertens, Philadelphia, PA 19104 USA.
EM sylvia.rosas@uphs.upenn.edu
RI Rosas, Sylvia/D-1106-2009
FU NIH [R21 HL 086971]; Veterans Health Administration; National Center for
Research Resources [UL1RR024134]; [R01 DK 080033]
FX This work was supported by NIH grants R21 HL 086971. Salary support was
provided by the Veterans Health Administration and R01 DK 080033 (Dr
Rosas). The project described was supported by Grant Number UL1RR024134
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. Funding sources had no involvement in
study design, data collection, analysis, and interpretation, writing of
the report, or decision to submit the paper for publication.
NR 38
TC 14
Z9 14
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0895-7061
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD MAR
PY 2012
VL 25
IS 3
BP 348
EP 353
DI 10.1038/ajh.2011.252
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 893VN
UT WOS:000300385900013
PM 22237154
ER
PT J
AU Yang, X
Cao, W
Zhang, L
Zhang, W
Zhang, X
Lin, H
AF Yang, X.
Cao, W.
Zhang, L.
Zhang, W.
Zhang, X.
Lin, H.
TI Targeting 14-3-3zeta in cancer therapy
SO CANCER GENE THERAPY
LA English
DT Review
DE 14-3-3zeta; apoptosis; cancer therapy; cell cycle; invasion
ID SQUAMOUS-CELL CARCINOMA; MULTIDIMENSIONAL LIQUID-CHROMATOGRAPHY;
ISOFORM-SPECIFIC EXPRESSION; TANDEM MASS-SPECTROMETRY; LUNG-CANCER;
PROTEOMIC ANALYSIS; INDUCED APOPTOSIS; HUMAN ASTROCYTOMA;
DOWN-REGULATION; BREAST-CANCER
AB An effective therapeutic target is imperative for cancer treatment, including gene therapy. 14-3-3zeta, a member of the 14-3-3 protein family, acts as a suppressor of apoptosis and has a central role in tumor genesis and progression. Owing to its wide upregulation in human tumors and its involvement in cancer progression and treatment resistance, 14-3-3zeta is currently undergoing extensive investigation as a novel therapeutic target. In this review, we widely investigate the role of 14-3-3zeta in cancer and suggest a potential therapeutic target for new anticancer interventions. Cancer Gene Therapy (2012) 19, 153-159; doi:10.1038/cgt.2011.85; published online 23 December 2011
C1 [Yang, X.; Cao, W.; Zhang, L.; Zhang, W.; Zhang, X.; Lin, H.] Fourth Mil Med Univ, Inst Neurosurg, Xijing Hosp, Xian 710032, Shaanxi Provinc, Peoples R China.
[Zhang, W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg,Mol Neurosurg Lab,Brain Tumor Res, Boston, MA USA.
RP Zhang, X (reprint author), Fourth Mil Med Univ, Inst Neurosurg, Xijing Hosp, Changle Western Rd 127, Xian 710032, Shaanxi Provinc, Peoples R China.
EM xzhang@fmmu.edu.cn
FU Scientific and Technological Project of ShaanXi Province [2008K09-09];
National Natural Science Foundation of China [81072083]
FX Supported by Scientific and Technological Project of ShaanXi Province
(No: 2008K09-09) and National Natural Science Foundation of China (No:
81072083).
NR 77
TC 20
Z9 23
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0929-1903
J9 CANCER GENE THER
JI Cancer Gene Ther.
PD MAR
PY 2012
VL 19
IS 3
BP 153
EP 159
DI 10.1038/cgt.2011.85
PG 7
WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Research & Experimental Medicine
GA 893VK
UT WOS:000300385600001
PM 22193627
ER
PT J
AU Yamada, S
Kuroda, T
Fuchs, BC
He, X
Supko, JG
Schmitt, A
McGinn, CM
Lanuti, M
Tanabe, KK
AF Yamada, S.
Kuroda, T.
Fuchs, B. C.
He, X.
Supko, J. G.
Schmitt, A.
McGinn, C. M.
Lanuti, M.
Tanabe, K. K.
TI Oncolytic Herpes simplex virus expressing yeast cytosine deaminase:
relationship between viral replication, transgene expression, prodrug
bioactivation
SO CANCER GENE THERAPY
LA English
DT Article
DE cytosine deaminase; HSV-1; pharmacokinetics; viral oncolysis
ID POSITRON-EMISSION-TOMOGRAPHY; ADENOVIRUS-MEDIATED TRANSFER; IN-VIVO;
GENE-THERAPY; URACIL PHOSPHORIBOSYLTRANSFERASE; CHEMOTHERAPEUTIC-AGENTS;
COLORECTAL-CANCER; CYP2B1 TRANSGENE; TUMOR-REGRESSION; SUICIDE GENE
AB Yeast cytosine deaminase (yCD) is a well-characterized prodrug/enzyme system that converts 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU), and has been combined with oncolytic viruses. However, in vivo studies of the interactions between 5-FC bioactivation and viral replication have not been previously reported, nor have the kinetics of transgene expression and the pharmacokinetics of 5-FC and 5-FU. We constructed a replication-conditional Herpes simplex virus 1 (HSV-1) expressing yCD and examined cytotoxicity when 5-FC was initiated at different times after viral infection, and observed that earlier 5-EC administration led to greater cytotoxicity than later 5-EC administration in vitro and in vivo. In animal models, 12 days of 5-FC administration was superior to 6 days, but dosing beyond 12 days did not further enhance efficacy. Consistent with the dosing-schedule results, both viral genomic DNA copy number and viral titers were observed to peak on Day 3 after viral injection and gradually decrease thereafter. The virus is replication-conditional and was detected in tumors for as long as 2 weeks after viral injection. The maximum relative extent of yCD conversion of 5-EC to 5-FU in tumors was observed on Day 6 after viral injection and it decreased progressively thereafter. The observation that 5-FU generation within tumors did not lead to appreciable levels of systemic 5-FU (<10 ng ml(-1)) is important and has not been previously reported. The approaches used in these studies of the relationship between the viral replication kinetics, transgene expression, prodrug administration and anti-tumor efficacy are useful in the design of clinical trials of armed, oncolytic viruses. Cancer Gene Therapy (2012) 19, 160-170; doi:10.1038/cgt.2011.70; published online 11 November 2011
C1 [Yamada, S.; Kuroda, T.; Fuchs, B. C.; Tanabe, K. K.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA 02114 USA.
[Yamada, S.; Kuroda, T.; Fuchs, B. C.; He, X.; Supko, J. G.; Schmitt, A.; McGinn, C. M.; Lanuti, M.; Tanabe, K. K.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[He, X.; Supko, J. G.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA.
[Schmitt, A.; McGinn, C. M.; Lanuti, M.] Massachusetts Gen Hosp, Ctr Canc, Div Thorac Surg, Boston, MA 02114 USA.
RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Yawkey 7-924,55 Fruit St, Boston, MA 02114 USA.
EM ktanabe@partners.org
OI Kuroda, Toshihiko/0000-0001-6660-8930
FU NIH [R01CA76183, 5K01CA140861]
FX This work was supported by NIH grants R01CA76183 (KKT) and 5K01CA140861
(BCF).
NR 46
TC 8
Z9 9
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0929-1903
J9 CANCER GENE THER
JI Cancer Gene Ther.
PD MAR
PY 2012
VL 19
IS 3
BP 160
EP 170
DI 10.1038/cgt.2011.70
PG 11
WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Research & Experimental Medicine
GA 893VK
UT WOS:000300385600002
PM 22076044
ER
PT J
AU Heddleston, JM
Wu, Q
Rivera, M
Minhas, S
Lathia, JD
Sloan, AE
Iliopoulos, O
Hjelmeland, AB
Rich, JN
AF Heddleston, J. M.
Wu, Q.
Rivera, M.
Minhas, S.
Lathia, J. D.
Sloan, A. E.
Iliopoulos, O.
Hjelmeland, A. B.
Rich, J. N.
TI Hypoxia-induced mixed-lineage leukemia 1 regulates glioma stem cell
tumorigenic potential
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
DE hypoxia; MLL1; cancer stem cell; HIF2 alpha; epigenetics
ID MYELOID-LEUKEMIA; GENE-EXPRESSION; GLIOBLASTOMA; MLL; IDENTIFICATION;
NEUROGENESIS; ACTIVATION; SUBCLASSES; PATHWAYS; SURVIVAL
AB Normal stem cells reside in functional niches critical for self-renewal and maintenance. Neural and hematopoietic stem cell niches, in particular, are characterized by restricted availability of oxygen and the resulting regulation by hypoxia-inducible factors (HIFs). Glioblastoma multiforme (GBM) is the most common malignant brain tumor and also contains high degrees of hypoxia. Heterogeneity within the neoplastic compartment has been well characterized in GBM and may be derived from genetic and epigenetic sources that co-evolve during malignant progression. Recent experimental evidence has supported the importance of hypoxia in glioma stem cell (GSC) niches. We hypothesized that HIFs require epigenetic-modifying proteins to promote tumor malignancy in GBM. Here we demonstrate that in GBM the histone methyltransferase mixed-lineage leukemia 1 (MLL1) is induced by hypoxia and enhances hypoxic responses. Loss of MLL1 reduces the expression of HIF transcripts and HIF2 alpha protein. Targeting MLL1 by RNA interference inhibited the expression of HIF2 alpha and target genes, including vascular endothelial growth factor (VEGF). GSCs expressed higher levels of MLL1 than matched non-stem tumor cells and depletion of MLL1 reduced GSC self-renewal, growth, and tumorigenicity. These studies have uncovered a novel mechanism mediating tumor hypoxic responses linking microenvironmental regulation of epigenetic-modifying proteins to cellular heterogeneity and provide rationale for the design of more sophisticated clinical approaches targeting epigenetic regulation. Cell Death and Differentiation (2012) 19, 428-439; doi: 10.1038/cdd.2011.109; published online 12 August 2011
C1 [Heddleston, J. M.; Wu, Q.; Rivera, M.; Minhas, S.; Lathia, J. D.; Hjelmeland, A. B.; Rich, J. N.] Cleveland Clin, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44106 USA.
[Sloan, A. E.] Case Comprehens Canc Ctr, Univ Hosp Case Med Ctr, Dept Neurol Surg, Cleveland, OH USA.
[Sloan, A. E.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Iliopoulos, O.] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA USA.
RP Rich, JN (reprint author), Cleveland Clin, Dept Stem Cell Biol & Regenerat Med, 9500 Euclid Ave,Mailstop NE30, Cleveland, OH 44106 USA.
EM richj@ccf.org
FU McDonnell Foundation; NIH [NS054276, CA129958, CA116659, CA154130,
CA151522]; National Brain Tumor Society; American Brain Tumor
Association; Joelle Syverson Fund; NCI [F32 CA142159]; CWRU; Cleveland
Clinic Foundation Tissue Procurement Service; Tissue Procurement and
Biorepository Cores at University Hospitals; Case Comprehensive Cancer
Center; [RO1 CA122591]; [CA137443]; [CA116257]; [HHS N2612010]
FX We thank Cathy Shemo, Moneen Morgan, and Sage O'Bryant for flow
cytometry assistance; Linda Vargo for histology assistance; and the
members of the Rich laboratory for technical assistance and critical
review of the manuscript. Work in the Rich laboratory is supported by
the McDonnell Foundation and NIH Grants NS054276, CA129958, CA116659,
and CA154130. AH is supported by the National Brain Tumor Society and
the NIH Grant CA151522. JDL is supported by an American Brain Tumor
Association Basic Research Fellowship (sponsored by the Joelle Syverson
Fund) and a National Service Research Award (NCI F32 CA142159). OI is
supported by RO1 CA122591. AS is supported by CA137443, CA116257, HHS
N2612010, the Kimble Fund and Cristal Chair at CWRU. Studies were also
supported by the Cleveland Clinic Foundation Tissue Procurement Service
and the Tissue Procurement and Biorepository Cores at University
Hospitals and the Case Comprehensive Cancer Center, and we also thank S
Staugatis, R Weil, and M McGraw for their assistance.
NR 40
TC 43
Z9 45
U1 1
U2 9
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 MAR
PY 2012
VL 19
IS 3
BP 428
EP 439
DI 10.1038/cdd.2011.109
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 892SF
UT WOS:000300305200007
PM 21836617
ER
PT J
AU Anglaret, X
Minga, A
Gabillard, D
Ouassa, T
Messou, E
Morris, B
Traore, M
Coulibaly, A
Freedberg, KA
Lewden, C
Menan, H
Abo, Y
Dakoury-Dogbo, N
Toure, S
Seyler, C
AF Anglaret, Xavier
Minga, Albert
Gabillard, Delphine
Ouassa, Timothee
Messou, Eugene
Morris, Brandon
Traore, Moussa
Coulibaly, Ali
Freedberg, Kenneth A.
Lewden, Charlotte
Menan, Herve
Abo, Yao
Dakoury-Dogbo, Nicole
Toure, Siaka
Seyler, Catherine
CA ANRS 12222 Morbidity Mortality Stu
TI AIDS and Non-AIDS Morbidity and Mortality Across the Spectrum of CD4
Cell Counts in HIV-Infected Adults Before Starting Antiretroviral
Therapy in Cote d'Ivoire
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; AFRICAN GOLD MINERS; SHORT-TERM RISK;
TRIMETHOPRIM-SULFAMETHOXAZOLE; SOUTH-AFRICA; COTRIMOXAZOLE PROPHYLAXIS;
OPPORTUNISTIC INFECTIONS; HIV-1-INFECTED PATIENTS; NAIVE INDIVIDUALS;
VIRAL LOAD
AB Background. In WesternEurope, NorthAmerica, andAustralia, large cohort collaborations have been able to estimate the short-term CD4 cell count-specific risk of AIDS or death in untreated human immunodeficiency virus (HIV)infected adults with high CD4 cell counts. In sub-Saharan Africa, these CD4 cell count-specific estimates are scarce.
Methods. From 1996 through 2006, we followed up 2 research cohorts of HIV-infected adults in Cote d'Ivoire. This included follow-up off antiretroviral therapy (ART) across the entire spectrum of CD4 cell counts before the ART era, and only in patients with CD4 cell counts > 200 cells/mu L once ART became available. Data were censored at ART initiation. We modeled the CD4 cell count decrease using an adjusted linear mixed model. CD4 cell count-specific rates of events were obtained by dividing the number of first events occurring in a given CD4 cell count stratum by the time spent in that stratum.
Results. Eight hundred sixty patients were followed off ART over 2789 person-years (PY). In the >= 650, 500-649, 350-499, 200-349, 100-199, 50-99, and 0-49 cells/mu L CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, 10.4, 30.9, 60.8, and 99.9 events per 100 PY, respectively. In patients with CD4 cell counts >= 200 CD4 cells/mu L, the most frequent AIDS-defining disease was tuberculosis (decreasing from 4.0 to 0.6 events per 100 PY for 200-349 and >= 650 cells/mu L, respectively), and the most frequent HIV non-AIDS severe diseases were visceral bacterial diseases (decreasing from 9.1 to 3.6 events per 100 PY).
Conclusions. Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts >= 200 cells/mu L. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in sub-Saharan Africa.
C1 [Anglaret, Xavier; Minga, Albert; Gabillard, Delphine; Ouassa, Timothee; Messou, Eugene; Traore, Moussa; Coulibaly, Ali; Lewden, Charlotte; Menan, Herve; Abo, Yao; Dakoury-Dogbo, Nicole; Toure, Siaka; Seyler, Catherine] CHU Treichville, Programme PAC CI, Abidjan, Cote Ivoire.
[Ouassa, Timothee] CHU Treichville, Ctr Diagnost & Rech SIDA CeDReS, Abidjan, Cote Ivoire.
[Anglaret, Xavier; Minga, Albert; Gabillard, Delphine; Messou, Eugene; Lewden, Charlotte] INSERM U897, Bordeaux, France.
[Anglaret, Xavier; Minga, Albert; Gabillard, Delphine; Messou, Eugene; Lewden, Charlotte] Univ Bordeaux Segalen, Bordeaux, France.
[Seyler, Catherine] Hop La Timone, Serv Sante Publ & Informat Med, Marseille, France.
[Freedberg, Kenneth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Univ Ctr AIDS Res,Div Infect Dis, Boston, MA USA.
[Freedberg, Kenneth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Univ Ctr AIDS Res,Div Gen Med, Boston, MA USA.
[Freedberg, Kenneth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Univ Ctr AIDS Res,Med Practice Evaluat Ct, Boston, MA USA.
[Morris, Brandon; Freedberg, Kenneth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Univ Ctr AIDS Res,Dept Med, Boston, MA USA.
[Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Anglaret, X (reprint author), CHU Treichville, Programme PAC CI, 18 BP 1954, Abidjan, Cote Ivoire.
EM xavier.anglaret@pacci.ci
RI Ghartouchent, malek/B-9088-2012; Van de Perre, Philippe/B-9692-2008;
Nagot, Nicolas/I-9467-2014; Anglaret, Xavier/F-7333-2013;
OI Van de Perre, Philippe/0000-0002-3912-0427; DENOEUD-NDAM,
Lise/0000-0002-9482-1461
FU French Agence Nationale de Recherche sur le SIDA et les hepatites
virales, Paris, France) [ANRS 1203, ANRS 1220, ANRS 12222]; US National
Institute of Allergy and Infectious Diseases [NIAID AI058736]
FX This work was supported by the French Agence Nationale de Recherche sur
le SIDA et les hepatites virales, Paris, France (grants ANRS 1203, ANRS
1220, and ANRS 12222) and the US National Institute of Allergy and
Infectious Diseases (grant NIAID AI058736).
NR 29
TC 45
Z9 45
U1 1
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAR 1
PY 2012
VL 54
IS 5
BP 714
EP 723
DI 10.1093/cid/cir898
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 891PE
UT WOS:000300228300022
PM 22173233
ER
PT J
AU Gandhi, RT
Deeks, SG
AF Gandhi, Rajesh T.
Deeks, Steven G.
TI Plasma HIV-1 RNA Levels During Antiretroviral Therapy: How Low Is Low
Enough?
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID RALTEGRAVIR INTENSIFICATION; VIREMIA; SUPPRESSION; ADHERENCE; DURATION;
HAART; RISK
C1 [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Gandhi, Rajesh T.] Massachusetts Gen Hosp, Ragon Inst, Massachusetts Inst Technol & Harvard, Charlestown, MA USA.
[Deeks, Steven G.] Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA USA.
RP Deeks, SG (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Posit Hlth Program, San Francisco, CA 94110 USA.
EM sdeeks@php.ucsf.edu
RI Ghartouchent, malek/B-9088-2012
FU NIAID NIH HHS [2P30 AI060354-06, K24 AI069994, K24AI069994, P0 AI27763,
P30 AI027763, P30 AI060354, R01 AI066992, R01 AI066992-04A1, R01
AI087145, U01 AI 694722, U19 AI096109]; NLM NIH HHS [G08 LM008830,
G08LM008830-01]
NR 16
TC 11
Z9 11
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAR 1
PY 2012
VL 54
IS 5
BP 733
EP 735
DI 10.1093/cid/cir933
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 891PE
UT WOS:000300228300024
PM 22238162
ER
PT J
AU Pfab, F
Nowak-Machen, M
Napadow, V
Fleckenstein, J
AF Pfab, Florian
Nowak-Machen, Martina
Napadow, Vitaly
Fleckenstein, Johannes
TI Alternatives to prokinetics to move the pylorus and colon
SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
LA English
DT Review
DE critically ill; motility; mu-opioid receptor antagonists; prokinetics;
therapies
ID CRITICALLY-ILL PATIENTS; OPIOID-INDUCED CONSTIPATION; INDUCED BOWEL
DYSFUNCTION; FUNCTIONAL GASTROINTESTINAL DISORDERS; ACUPUNCTURE-POINT
STIMULATION; RANDOMIZED CONTROLLED-TRIAL; INTENSIVE-CARE UNITS; ENTERAL
NUTRITION; CRITICAL ILLNESS; ELECTRICAL-STIMULATION
AB Purpose of review Gastrointestinal motility disorders (GMDs) are common in the ICU. When encountering these problems, one typically thinks of prokinetics. This review summarizes current evidence of treatments.
Recent findings
Prokinetics are not the first-line therapy for GMDs. In fact, the clinical implications of using prokinetic agents are rather controversial. Current evidence on alternative treatment modalities such as fluid and electrolyte management, laxatives, opioid antagonists, purgative enemas, acupuncture, physical therapies and probiotics is growing.
Summary
Current state of the art to treat GMDs is primarily focused at the elimination of underlying trigger factors. Fluid and electrolyte management as well as laxatives and peripherally acting m-opioid receptor antagonists are the recommended first-line therapies that can be complemented with prokinetics. Acupuncture as well as physical modalities, such as massage or warming of the abdomen, is promising with few side-effects and should be considered as well.
C1 [Pfab, Florian] Tech Univ Munich, Dept Prevent & Rehabil Sports Med, D-80809 Munich, Germany.
[Pfab, Florian; Napadow, Vitaly] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA.
[Pfab, Florian] Tech Univ Munich, Dept Dermatol & Allergy, D-80809 Munich, Germany.
[Pfab, Florian] Harvard Univ, Brigham & Womens Hosp, Sch Med, CK CARE, Boston, MA 02115 USA.
[Nowak-Machen, Martina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA.
[Fleckenstein, Johannes] Univ Munich, Klinikum Grosshadern, Dept Anesthesiol, D-8000 Munich, Germany.
RP Pfab, F (reprint author), Tech Univ Munich, Dept Prevent & Sports Med, Conollystr 32, D-80809 Munich, Germany.
EM pfab@sport.med.tum.de
OI Fleckenstein, Johannes/0000-0003-3442-0380
NR 80
TC 3
Z9 3
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1363-1950
J9 CURR OPIN CLIN NUTR
JI Curr. Opin. Clin. Nutr. Metab. Care
PD MAR
PY 2012
VL 15
IS 2
BP 166
EP 173
DI 10.1097/MCO.0b013e32834f3000
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 894FD
UT WOS:000300411600013
PM 22234164
ER
PT J
AU Dummer, R
Flaherty, KT
AF Dummer, Reinhard
Flaherty, Keith T.
TI Resistance patterns with tyrosine kinase inhibitors in melanoma: new
insights
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE molecular classification of melanoma; resistance; targeted therapy;
tyrosine kinase inhibitor
ID METASTATIC MELANOMA; SOMATIC MUTATIONS; IMATINIB MESYLATE; UVEAL
MELANOMA; BRAF; RAF; KIT; PATHWAY; CANCER; CELLS
AB Purpose of review
After years of therapeutic approaches with limited effects in metastatic melanoma, new inhibitors of serine-threonine and tyrosine kinases have demonstrated impressive clinical efficacy and improved survival.
Recent findings
This review explains the molecular background for the development of specific kinase inhibitors and briefly summarizes their clinical impact on advanced melanoma.
Summary
Despite robust early clinical efficacy, the antiproliferative effect of these kinase inhibitors is limited. The resistance mechanisms are explored currently and will help to identify new targets for melanoma therapy.
C1 [Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland.
[Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Dummer, R (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland.
EM reinhard.dummer@usz.ch
FU Gottfried und Julia Bangerter-Rhyner-Stiftung; G+B Schwyzer Stiftung
FX This work was supported in part by the Gottfried und Julia
Bangerter-Rhyner-Stiftung and by G+B Schwyzer Stiftung.
NR 41
TC 36
Z9 36
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8746
EI 1531-703X
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD MAR
PY 2012
VL 24
IS 2
BP 150
EP 154
DI 10.1097/CCO.0b013e32834fca92
PG 5
WC Oncology
SC Oncology
GA 894DG
UT WOS:000300406600007
PM 22316627
ER
PT J
AU Kuijk, EW
van Tol, LTA
Van de Velde, H
Wubbolts, R
Welling, M
Geijsen, N
Roelen, BAJ
AF Kuijk, Ewart W.
van Tol, Leni T. A.
Van de Velde, Hilde
Wubbolts, Richard
Welling, Maaike
Geijsen, Niels
Roelen, Bernard A. J.
TI The roles of FGF and MAP kinase signaling in the segregation of the
epiblast and hypoblast cell lineages in bovine and human embryos
SO DEVELOPMENT
LA English
DT Article
DE FGF; Lineage segregation; MAP kinase; Epiblast; Hypoblast; Bovine; Human
ID PLURIPOTENT STEM-CELLS; PRIMITIVE ENDODERM; DEVELOPMENTAL BIOLOGY; MOUSE
BLASTOCYST; RAT BLASTOCYSTS; GROUND-STATE; SELF-RENEWAL; NANOG;
DIFFERENTIATION; MAMMALS
AB At the blastocyst stage of mammalian pre-implantation development, three distinct cell lineages have formed: trophectoderm, hypoblast (primitive endoderm) and epiblast. The inability to derive embryonic stem (ES) cell lines in a variety of species suggests divergence between species in the cell signaling pathways involved in early lineage specification. In mouse, segregation of the primitive endoderm lineage from the pluripotent epiblast lineage depends on FGF/MAP kinase signaling, but it is unknown whether this is conserved between species. Here we examined segregation of the hypoblast and epiblast lineages in bovine and human embryos through modulation of FGF/MAP kinase signaling pathways in cultured embryos. Bovine embryos stimulated with FGF4 and heparin form inner cell masses (ICMs) composed entirely of hypoblast cells and no epiblast cells. Inhibition of MEK in bovine embryos results in ICMs with increased epiblast precursors and decreased hypoblast precursors. The hypoblast precursor population was not fully ablated upon MEK inhibition, indicating that other factors are involved in hypoblast differentiation. Surprisingly, inhibition of FGF signaling upstream of MEK had no effects on epiblast and hypoblast precursor numbers in bovine development, suggesting that GATA6 expression is not dependent on FGF signaling. By contrast, in human embryos, inhibition of MEK did not significantly alter epiblast or hypoblast precursor numbers despite the ability of the MEK inhibitor to potently inhibit ERK phosphorylation in human ES cells. These findings demonstrate intrinsic differences in early mammalian development in the role of the FGF/MAP kinase signaling pathways in governing hypoblast versus epiblast lineage choices.
C1 [van Tol, Leni T. A.; Roelen, Bernard A. J.] Univ Utrecht, Fac Vet Med, Dept Farm Anim Hlth, NL-3584 CM Utrecht, Netherlands.
[Kuijk, Ewart W.; Welling, Maaike; Geijsen, Niels] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.
[Kuijk, Ewart W.; Welling, Maaike; Geijsen, Niels] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
[Van de Velde, Hilde] Vrije Univ Brussel, Dept Embryol & Genet, B-1090 Brussels, Belgium.
[Van de Velde, Hilde] UZ Brussel, Ctr Reprod Med, B-1090 Brussels, Belgium.
[Wubbolts, Richard] Univ Utrecht, Fac Vet Med, Ctr Cellular Imaging, Dept Biochem & Cell Biol, NL-3584 CM Utrecht, Netherlands.
[Geijsen, Niels] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA.
[Geijsen, Niels] Univ Utrecht, Fac Vet Med, Dept Clin Sci Compan Anim, NL-3584 CM Utrecht, Netherlands.
[Roelen, Bernard A. J.] Univ Utrecht, Fac Vet Med, Dept Equine Sci, NL-3584 CM Utrecht, Netherlands.
RP Roelen, BAJ (reprint author), Univ Utrecht, Fac Vet Med, Dept Farm Anim Hlth, Yalelaan 104, NL-3584 CM Utrecht, Netherlands.
EM b.a.j.roelen@uu.nl
OI Kuijk, Ewart/0000-0002-1385-6516
FU Hubrecht Imaging Center; Netherlands Organization for Scientific
Research (NWO); National Institutes of Health (NIH)
FX We are very grateful to the support of Ir. Anko de Graaff of the
Hubrecht Imaging Center.; N.G. was supported by funding from the
Netherlands Organization for Scientific Research (NWO) and by the
National Institutes of Health (NIH). Deposited in PMC for release after
12 months.
NR 49
TC 82
Z9 82
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 MAR 1
PY 2012
VL 139
IS 5
BP 871
EP 882
DI 10.1242/dev.071688
PG 12
WC Developmental Biology
SC Developmental Biology
GA 894BQ
UT WOS:000300402400004
PM 22278923
ER
PT J
AU Ricks, J
Molnar, MZ
Kovesdy, CP
Shah, A
Nissenson, AR
Williams, M
Kalantar-Zadeh, K
AF Ricks, Joni
Molnar, Mildos Z.
Kovesdy, Csaba P.
Shah, Anuja
Nissenson, Allen R.
Williams, Mark
Kalantar-Zadeh, Kamyar
TI Glycemic Control and Cardiovascular Mortality in Hemodialysis Patients
With Diabetes A 6-Year Cohort Study
SO DIABETES
LA English
DT Article
ID MAINTENANCE HEMODIALYSIS; GLYCOSYLATED HEMOGLOBIN; GLUCOSE CONTROL;
SURVIVAL; MELLITUS; INSULIN; DISEASE; ASSOCIATION; RISK; COMPLICATIONS
AB Previous observational studies using differing methodologies have yielded inconsistent results regarding the association between glycemic control and outcomes in diabetic patients receiving maintenance hemodialysis (MHD). We examined mortality predictability of A1C and random serum glucose over time in a contemporary cohort of 54,757 diabetic MHD patients (age 63 +/- 13 years, 51% men, 30% African Americans, 19% Hispanics). Adjusted all-cause death hazard ratio (HR) for baseline A1C increments of 8.0-8.9, 9.0-9.9, and >= 10%, compared with 7.0-7.9% (reference), was 1.06 (95% CI 1.01-1.12), 1.05 (0.99-1.12), and 1.19 (1.12-1.28), respectively, and for time-averaged A1C was 1.11 (1.05-1.16), 1.36 (1.27-1.45), and 1.59 (1.46-1.72). A symmetric increase in mortality also occurred with time-averaged A1C levels in the low range (6.0-6.9%, HR 1.05 [95% CI 1.01-1.08]; 5.0-5.9%, 1.08 [1.04-1.11], and <= 5%, 1.35 [1.29-1.42]) compared with 7.0-7.9% in fully adjusted models. Adjusted all-cause death HR for time-averaged blood glucose 175-199, 200-249, 250-299, and >= 300 mg/dL, compared with 150-175 mg/dL (reference), was 1.03 (95% CI 0.99-1.07), 1.14 (1.10-1.19), 1.30 (1.23-1.37), and 1.66 (1.56-1.76), respectively. Hence, poor glycemic control (A1C >= 8% or serum glucose >= 200 mg/dL) appears to be associated with high all-cause and cardiovascular death in MHD patients. Very low glycemic levels are also associated with high mortality risk. Diabetes 61:708-715, 2012
C1 [Ricks, Joni; Molnar, Mildos Z.; Kalantar-Zadeh, Kamyar] Harbor UCLA Med Ctr, Harold Simmons Ctr Chron Dis Res & Epidemiol, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.
[Molnar, Mildos Z.] Semmelweis Univ, Inst Pathophysiol, Budapest, Hungary.
[Kovesdy, Csaba P.] Salem VA Med Ctr, Div Nephrol, Salem, VA USA.
[Kovesdy, Csaba P.] Univ Virginia, Div Nephrol, Charlottesville, VA USA.
[Shah, Anuja; Kalantar-Zadeh, Kamyar] Harbor UCLA Med Ctr, Div Nephrol & Hypertens, Torrance, CA 90509 USA.
[Nissenson, Allen R.] DaVita Inc, Denver, CO USA.
[Nissenson, Allen R.; Kalantar-Zadeh, Kamyar] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Williams, Mark] Harvard Univ, Sch Med, Joslin Diabet Ctr, Renal Unit, Boston, MA 02115 USA.
[Kalantar-Zadeh, Kamyar] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
RP Kalantar-Zadeh, K (reprint author), Harbor UCLA Med Ctr, Harold Simmons Ctr Chron Dis Res & Epidemiol, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.
EM kamkal@ucla.edu
OI Molnar, Miklos Z/0000-0002-9665-330X; Kalantar-Zadeh,
Kamyar/0000-0002-8666-0725
FU National Institutes of Health [DK077341]; National Institute of Diabetes
and Digestive and Kidney Diseases of the National Institutes of Health
[R01 DK078106]; National Developmental Agency [KTIA-OTKA-EU
7KP-HUMAN-MB08-A-81231]; Hungarian Kidney Foundation; DaVita Inc.
FX This study was partly supported by a research grant from the National
Institutes of Health (DK077341) to K.K.-Z. K.K-Z. also receives funding
from the National Institute of Diabetes and Digestive and Kidney
Diseases of the National Institutes of Health (R01 DK078106) and a
philanthropic grant from Mr. Harold Simmons. M.Z.M. received grants from
the National Developmental Agency (KTIA-OTKA-EU 7KP-HUMAN-MB08-A-81231)
from the Research and Technological Innovation Fund and was also
supported by the Hungarian Kidney Foundation.; This study was also
supported by a research grant from DaVita Inc. (to K.K.-Z.). No other
potential conflicts of interest relevant to this article were reported.
NR 38
TC 56
Z9 57
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD MAR
PY 2012
VL 61
IS 3
BP 708
EP 715
DI 10.2337/db11-1015
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 899FA
UT WOS:000300800600022
PM 22315308
ER
PT J
AU Qi, QB
Liang, LM
Doria, A
Hu, FB
Qi, L
AF Qi, Qibin
Liang, Liming
Doria, Alessandro
Hu, Frank B.
Qi, Lu
TI Genetic Predisposition to Dyslipidemia and Type 2 Diabetes Risk in Two
Prospective Cohorts
SO DIABETES
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE; PHYSICAL-ACTIVITY;
MELLITUS; BEZAFIBRATE; WOMEN; LOCI; MEN; ATHEROSCLEROSIS; CLASSIFICATION
AB Dyslipidemia has been associated with type 2 diabetes, but it remains unclear whether dyslipidemia plays a causal role in type 2 diabetes. We aimed to examine the association between the genetic predisposition to dyslipdemia and type 2 diabetes risk. The current study included 2,447 patients with type 2 diabetes and 3,052 control participants of European ancestry from the Nurses' Health Study and the Health Professionals Follow-up Study. Genetic predisposition to dyslipidemia was estimated by three genotype scores of lipids (LDL cholesterol, HDL cholesterol, and triglycerides) on the basis of the established loci for blood lipids. Linear relation analysis indicated that the HDL cholesterol and triglyceride genotype scores, but not the LDL cholesterol genotype score, were linearly related to elevated type 2 diabetes risk. Each point of the HDL cholesterol and triglyceride genotype scores was associated with a 3% (odds ratio [OR] 1.03 [95% CI 1.01-1.04]) and a 2% (1.02 [1.00-1.04]) increased risk of developing type 2 diabetes, respectively. The ORs were 1.39 (1.17-1.65) and 1.19 (1.01-1.41) for type 2 diabetes by comparing extreme quartiles of the HDL cholesterol genotype score and triglyceride genotype score, respectively. In conclusion, genetic predisposition to low HDL cholesterol or high triglycerides is related to elevated type 2 diabetes risk. Diabetes 61:745-752, 2012
C1 [Qi, Qibin; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Liang, Liming; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Doria, Alessandro] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA.
[Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Hu, Frank B.; Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
EM nhlqi@channing.harvard.edu
RI Qi, Qibin/H-9055-2012
FU National Institutes of Health [HL-71981, HL-073168, U01-HG-004399,
DK-58845, DK-46200]; American Heart Association [0730094N]
FX This study was supported by grants HL-71981, HL-073168, U01-HG-004399,
DK-58845, and DK-46200 from the National Institutes of Health. L.Q. is a
recipient of the American Heart Association Scientist Development Award
(0730094N).
NR 30
TC 25
Z9 25
U1 0
U2 0
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD MAR
PY 2012
VL 61
IS 3
BP 745
EP 752
DI 10.2337/db11-1254
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 899FA
UT WOS:000300800600026
PM 22315312
ER
PT J
AU Bind, MA
Baccarelli, A
Zanobetti, A
Tarantini, L
Suh, H
Vokonas, P
Schwartz, J
AF Bind, Marie-Abele
Baccarelli, Andrea
Zanobetti, Antonella
Tarantini, Letizia
Suh, Helen
Vokonas, Pantel
Schwartz, Joel
TI Air Pollution and Markers of Coagulation, Inflammation, and Endothelial
Function Associations and Epigene-environment Interactions in an Elderly
Cohort
SO EPIDEMIOLOGY
LA English
DT Article
ID CORONARY-HEART-DISEASE; DNA METHYLATION; CARDIOVASCULAR-DISEASE;
ADHESION MOLECULES; PARTICULATE MATTER; RESPONSES; EXPOSURE; RISK;
ACTIVATION; EXPRESSION
AB Background: Previous studies suggest that air pollution is related to thrombosis, inflammation, and endothelial dysfunction. Mechanisms and sources of susceptibility are still unclear. One possibility is that these associations can be modified by DNA methylation states.
Methods: We conducted a cohort study with repeated measurements of fibrinogen, C-reactive protein, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in 704 elderly men participating in the Veterans Administration Normative Aging Study (2000-2009). We investigated short-and intermediateterm air pollution effects on these blood markers, and epigene-environment interactions by DNA methylation of Alu, LINE-1, tissue factor (F3), Toll-like receptor 2 (TLR-2), and ICAM-1.
Results: We found effects of particle number, black carbon, nitrogen dioxide (NO2), and carbon monoxide (CO) on fibrinogen. Ozone was a predictor of C-reactive protein and ICAM-1. Particle number, black carbon, NO2, CO, PM2.5, and sulfates were associated with ICAM-1 and VCAM-1. An interquartile range increase in 24-hour exposure for NO2 was associated with a 1.7% (95% confidence interval = 0.2%-3.3%) increase in fibrinogen for ozone; a 10.8% (2.2%-20.0%) increase in C-reactive protein for particle number; a 5.9% (3.6%-8.3%) increase in ICAM-1; and for PM2.5, a 3.7% (1.7%-5.8%) increase in VCAM-1. The air pollution effect was stronger among subjects having higher Alu, lower LINE-1, tissue factor, or TLR-2 methylation status.
Conclusion: We observed associations of traffic-related pollutants on fibrinogen, and both traffic and secondary particles on C-reactive protein, ICAM-1, and VCAM-1. There was effect modification by DNA methylation status, indicating that epigenetic states can convey susceptibility to air pollution.
C1 [Bind, Marie-Abele] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program,Landmark Ctr, Boston, MA 02115 USA.
[Tarantini, Letizia] Univ Milan, IRCCS Ca Granda Osped Maggiore Policlin Fdn, Ctr Mol & Genet Epidemiol, Milan, Italy.
[Tarantini, Letizia] Univ Milan, Dept Environm & Occupat Hlth, Milan, Italy.
[Vokonas, Pantel] Boston Univ, Sch Med, VA Normat Aging Study, VA Boston Healthcare Syst, Boston, MA 02118 USA.
[Vokonas, Pantel] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
RP Bind, MA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program,Landmark Ctr, 401 Pk Dr,Suite 415, Boston, MA 02115 USA.
EM mbind@hsph.harvard.edu
OI Baccarelli, Andrea/0000-0002-3436-0640
FU U.S. Environmental Protection Agency [EPA R827353, R832416]; National
Institute of Environmental Health Sciences (NIEHS) [RO1-ES015172,
2RO1-ES015172, ES014663, ES00002, PO1_ES008925, RD-83479701];
Epidemiology Research and Information Center of the U.S. Department of
Veterans Affairs
FX Supported by the U.S. Environmental Protection Agency grants EPA R827353
and R832416; National Institute of Environmental Health Sciences (NIEHS)
grants RO1-ES015172, 2RO1-ES015172, ES014663, ES00002, PO1_ES008925 and
Clean Air Act (CLARC) grant RD-83479701. The VA Normative Aging Study is
supported by the Cooperative Studies Program/Epidemiology Research and
Information Center of the U.S. Department of Veterans Affairs and is a
component of the Massachusetts Veterans Epidemiology Research and
Information Center, Boston, Massachusetts. The authors reported no other
financial interests related to this research.
NR 41
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U1 7
U2 25
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAR
PY 2012
VL 23
IS 2
BP 332
EP 340
DI 10.1097/EDE.0b013e31824523f0
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 894VX
UT WOS:000300456500024
PM 22237295
ER
PT J
AU Scheffel, H
Stolzmann, P
Schlett, CL
Engel, LC
Major, GP
Karolyi, M
Do, S
Maurovich-Horvat, P
Hoffmann, U
AF Scheffel, Hans
Stolzmann, Paul
Schlett, Christopher L.
Engel, Leif-Christopher
Major, Gyoengi Petra
Karolyi, Mihaly
Do, Synho
Maurovich-Horvat, Pal
Hoffmann, Udo
TI Coronary artery plaques: Cardiac CT with model-based and
adaptive-statistical iterative reconstruction technique
SO EUROPEAN JOURNAL OF RADIOLOGY
LA English
DT Article
DE Adaptive statistical iterative reconstruction; Model-based iterative
reconstruction; CT angiography; Plaque visualization; Image quality
ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; IMPROVED IMAGE QUALITY; INTRAVASCULAR
ULTRASOUND; INTRACORONARY ULTRASOUND; ANGIOGRAPHY; ACCURACY; EXPERIENCE;
CHEST; CALCIUM; DISEASE
AB Objectives: To compare image quality of coronary artery plaque visualization at CT angiography with images reconstructed with filtered back projection (FBP), adaptive statistical iterative reconstruction (ASIR), and model based iterative reconstruction (MBIR) techniques.
Methods: The coronary arteries of three ex vivo human hearts were imaged by CT and reconstructed with FBP, ASIR and MBIR. Coronary cross-sectional images were co-registered between the different reconstruction techniques and assessed for qualitative and quantitative image quality parameters. Readers were blinded to the reconstruction algorithm.
Results: A total of 375 triplets of coronary cross-sectional images were co-registered. Using MBIR, 26% of the images were rated as having excellent overall image quality, which was significantly better as compared to ASIR and FBP (4% and 13%, respectively, all p < 0.001). Qualitative assessment of image noise demonstrated a noise reduction by using ASIR as compared to FBP (p < 0.01) and further noise reduction by using MBIR (p < 0.001). The contrast-to-noise-ratio (CNR) using MBIR was better as compared to ASIR and FBP (44 +/- 19, 29 +/- 15, 26 +/- 9, respectively; all p < 0.001).
Conclusions: Using MBIR improved image quality, reduced image noise and increased CNR as compared to the other available reconstruction techniques. This may further improve the visualization of coronary artery plaque and allow radiation reduction. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02144 USA.
[Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02144 USA.
RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02144 USA.
EM uhoffmann@partners.org
OI Maurovich-Horvat, Pal/0000-0003-0885-736X
FU GE Healthcare
FX This study was partially funded by an unrestricted research grant of GE
Healthcare.
NR 20
TC 59
Z9 62
U1 1
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0720-048X
J9 EUR J RADIOL
JI Eur. J. Radiol.
PD MAR
PY 2012
VL 81
IS 3
BP E363
EP E369
DI 10.1016/j.ejrad.2011.11.051
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 894DV
UT WOS:000300408100033
PM 22197733
ER
PT J
AU Stephenson, AJ
Bolla, M
Briganti, A
Cozzarini, C
Moul, JW
Roach, M
van Poppel, H
Zietman, A
AF Stephenson, Andrew J.
Bolla, Michel
Briganti, Alberto
Cozzarini, Cesare
Moul, Judd W.
Roach, Mack, III
van Poppel, Hein
Zietman, Anthony
TI Postoperative Radiation Therapy for Pathologically Advanced Prostate
Cancer After Radical Prostatectomy
SO EUROPEAN UROLOGY
LA English
DT Article
DE Prostatic neoplasms; Prostate-specific antigen; Radiotherapy;
Radiotherapy, adjuvant; Salvage therapy; Neoplasm recurrence, local;
Prostatectomy; Radiotherapy; Treatment outcome
ID RANDOMIZED CONTROLLED-TRIAL; BICALUTAMIDE 150 MG; TERM-FOLLOW-UP;
ADJUVANT RADIOTHERAPY; SALVAGE RADIOTHERAPY; ANDROGEN SUPPRESSION; LOCAL
RECURRENCE; RETROPUBIC PROSTATECTOMY; 10-YEAR PROBABILITY;
CLINICAL-TRIAL
AB Context: Approximately 15-25% of men who undergo radical prostatectomy for localized prostate cancer (PCa) will experience recurrence of their cancer; men with poorly differentiated cancer, non-organ-confined disease, and positive surgical margins are at the highest risk.
Objective: Review accumulating evidence indicating that postoperative radiotherapy (RT) to the prostate bed favorably influences the course of disease in men with adverse pathologic features.
Evidence acquisition: Three phase 3 randomized trials of adjuvant RT versus observation have reported improved freedom from biochemical recurrence (BCR) and local control: Southwest Oncology Group (SWOG) 8794, European Organization for Research and Treatment of Cancer (EORTC) 22911, and the German Cancer Society (ARO 96-02). Evidence synthesis: Conflicting evidence from these trials suggests that adjuvant RT can have a favorable impact on systemic progression, PCa-specific mortality, or overall survival. Observational studies have reported durable responses to salvage RT in a substantial proportion of high-risk patients (provided that it is administered at the earliest evidence of BCR) and reduced PCa-specific mortality. There is consensus that the outcome of patients receiving postoperative RT is best when the prostate-specific antigen (PSA) level is the lowest. However, it is unclear if better outcomes will be achieved administering adjuvant RT to all patients at increased risk for recurrent PCa who have an undetectable postoperative PSA level compared to close observation and timely salvage RT at the earliest indications of BCR.
Conclusions: Given the absence of data from randomized trials demonstrating superiority of one approach over the other in terms of quantity and quality of life, we advocate multidisciplinary input and shared and informed decision making among patients, urologists, and radiation oncologists based on the relative advantages and disadvantages of each approach. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
C1 [Stephenson, Andrew J.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44195 USA.
[Bolla, Michel] Univ Grenoble, Ctr Hosp Reg, Grenoble, France.
[Briganti, Alberto] Univ Vita Salute San Raffaele, Dept Urol, Milan, Italy.
[Cozzarini, Cesare] Ist Sci San Raffaele, Dept Radiotherapy, I-20132 Milan, Italy.
[Moul, Judd W.] Duke Univ, Div Urol, Durham, NC USA.
[Roach, Mack, III] Univ Calif San Francisco, Dept Radiat Oncol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
[van Poppel, Hein] Katholieke Univ Leuven, Dept Urol, Univ Hosp Gasthuisberg, Louvain, Belgium.
[Zietman, Anthony] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Stephenson, AJ (reprint author), Cleveland Clin, Glickman Urol & Kidney Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM stephea2@ccf.org
OI Cozzarini, Cesare/0000-0002-7006-8196
NR 60
TC 69
Z9 69
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD MAR
PY 2012
VL 61
IS 3
BP 443
EP 451
DI 10.1016/j.eururo.2011.10.010
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 891CM
UT WOS:000300194000013
PM 22036777
ER
PT J
AU Bachmann, A
Muir, GH
Collins, EJ
Choi, BB
Tabatabaei, S
Reich, OM
Gomez-Sancha, F
Woo, HH
AF Bachmann, Alexander
Muir, Gordon H.
Collins, Edward J.
Choi, Benjamin B.
Tabatabaei, Shahin
Reich, Oliver M.
Gomez-Sancha, Fernando
Woo, Henry H.
TI 180-W XPS GreenLight Laser Therapy for Benign Prostate Hyperplasia:
Early Safety, Efficacy, and Perioperative Outcome After 201 Procedures
SO EUROPEAN UROLOGY
LA English
DT Article
DE BPH; BPE; Laser therapy; GreenLight; Photoselective vaporisation; XPS;
HPS; KTP; TURP; Laser prostatectomy
ID HPS 120-W LASER; PHOTOSELECTIVE VAPORIZATION PROSTATECTOMY; RANDOMIZED
CLINICAL-TRIAL; URINARY-TRACT SYMPTOMS; TRANSURETHRAL RESECTION;
FOLLOW-UP; COMPLICATIONS; EXPERIENCE; MULTICENTER; RETENTION
AB Background: Photoselective vaporisation of the prostate has evolved from the GreenLight 80-W KTP powered laser to the latest 180-W XPS laser involving a MoXy fibre.
Objective: Evaluate the prevalence of perioperative complications and short-term outcome for the first time with the XPS laser in men with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE).
Design, setting, and participants: Prospective data were collected from consecutive patients at seven centres worldwide during June 2010 and March 2011. Indication for surgery was based on the European Association of Urology and the American Urological Association guidelines. Patients receiving anticoagulants or those with retention were included and analysed separately.
Intervention: 180-W XPS GreenLight laser prostatectomy using the MoXy fibre.
Measurements: Standard parameters associated with transurethral prostate surgery and perioperative prevalence of surgery-associated problems or complications were documented.
Results and limitations: A total of 201 patients were included in the study. Mean follow-up was 5.8 mo (standard deviation [SD]: 2.8; range: 1-12 mo). A quarter of the patients had a prostate volume >= 80 ml. For prostates between 51 and 60 ml, a mean of 300 kJ (SD: 112) of energy was applied (lasing time: 35.0 min; SD: 15). Statistically significant improvements were noted in all key parameters postoperatively. The prevalence of perioperative complications was low. Limitations of the study are short duration of follow-up and limited number of available patients for the functional follow-up.
Conclusions: The 180-W GreenLight XPS laser is a new effective treatment option with a low prevalence of perioperative complications for patients suffering from LUTS due to BPE. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.
C1 [Bachmann, Alexander] Univ Basel, Univ Basel Hosp, Dept Urol, CH-4031 Basel, Switzerland.
[Muir, Gordon H.] Kings Coll Hosp London, Dept Urol, London, England.
[Collins, Edward J.] Calif Urol Serv, San Francisco, CA USA.
[Choi, Benjamin B.] Cornell Univ, Weill Med Coll, Dept Urol, New York, NY 10021 USA.
[Tabatabaei, Shahin] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[Reich, Oliver M.] Univ Munich, Harlaching Hosp, Dept Urol, Munich, Germany.
[Gomez-Sancha, Fernando] Inst Adv Urol Surg, Madrid, Spain.
[Woo, Henry H.] Univ Sydney, Sydney Adventist Hosp Clin Sch, Sydney, NSW 2006, Australia.
RP Bachmann, A (reprint author), Univ Basel, Univ Basel Hosp, Dept Urol, Spitalstr 21, CH-4031 Basel, Switzerland.
EM bachmanna@uhbs.ch
NR 28
TC 74
Z9 75
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD MAR
PY 2012
VL 61
IS 3
BP 600
EP 607
DI 10.1016/j.eururo.2011.11.041
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 891CM
UT WOS:000300194000041
PM 22153927
ER
PT J
AU LaVela, SL
Gering, J
Schectman, G
Weaver, FM
AF LaVela, Sherri L.
Gering, Jeffrey
Schectman, Gordon
Weaver, Frances M.
TI Optimizing Primary Care Telephone Access and Patient Satisfaction
SO EVALUATION & THE HEALTH PROFESSIONS
LA English
DT Article
DE access to care; patient satisfaction; patient-centered care; quality
improvement; telephone medicine
ID CONSULTATION; SERVICES; TRIAGE
AB Telephone medicine is often preferred by patients to meet primary care needs and may be associated with high patient satisfaction. This article presents findings about incoming patient calls to primary care for medically based reasons during office hours and reports factors independently associated with telephone encounter satisfaction, considering patient characteristics, call reasons, and staff responsiveness, for a national cohort of primary care users. Interviews were conducted with patients from 18 nationwide primary care clinics during the fall of 2009. Calling for an urgent medical issue was associated with dissatisfaction. Odds of call satisfaction were greater when patients thought staff was friendly (10x), call answer was timely (5x), and needed medical information was provided (7x). These findings can be used for interventions to optimize telephone access and patient satisfaction which is beneficial because satisfactory telephone encounters reduce primary care use and satisfied patients are more likely to be engaged in their health care.
C1 [LaVela, Sherri L.; Weaver, Frances M.] US Dept Vet Affairs, Ctr Management Complex Chron Care, Edward Hines Jr VA Hosp, Hines, IL 60141 USA.
[LaVela, Sherri L.] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA.
[Gering, Jeffrey] Chillicothe Vet Affairs Med Ctr, Chillicothe, OH 45601 USA.
[Gering, Jeffrey] Ohio Univ, Chillicothe, OH USA.
[Schectman, Gordon] Vet Affairs Cent Off, Off Patient Care Serv, Washington, DC USA.
[Schectman, Gordon] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA.
[Weaver, Frances M.] Loyola Univ, Stritch Sch Med, Program Hlth Serv Res, Maywood, IL 60153 USA.
RP LaVela, SL (reprint author), US Dept Vet Affairs, Ctr Management Complex Chron Care, Edward Hines Jr VA Hosp, 5000 S 5th Ave,151-H, Hines, IL 60141 USA.
EM sherri.lavela@va.gov
FU Office of Systems Redesign of the Department of Veterans Affairs
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This material
is based upon work supported by the Office of Systems Redesign of the
Department of Veterans Affairs. This paper reflects only the authors'
opinions and does not necessarily reflect the official position of the
Department of Veterans Affairs.
NR 19
TC 8
Z9 8
U1 0
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0163-2787
J9 EVAL HEALTH PROF
JI Eval. Health Prof.
PD MAR
PY 2012
VL 35
IS 1
BP 77
EP 86
DI 10.1177/0163278711411479
PG 10
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 894HJ
UT WOS:000300417400005
PM 21685222
ER
PT J
AU Konstantinidis, IT
Bajpai, S
Kambadakone, AR
Tanabe, KK
Berger, DL
Zheng, H
Sahani, DV
Lauwers, GY
Fernandez-del Castillo, C
Warshaw, AL
Ferrone, CR
AF Konstantinidis, Ioannis T.
Bajpai, Surabhi
Kambadakone, Avinash R.
Tanabe, Kenneth K.
Berger, David L.
Zheng, Hui
Sahani, Dushyant V.
Lauwers, Gregory Y.
Fernandez-del Castillo, Carlos
Warshaw, Andrew L.
Ferrone, Cristina R.
TI Gallbladder Lesions Identified on Ultrasound. Lessons from the Last 10
Years
SO JOURNAL OF GASTROINTESTINAL SURGERY
LA English
DT Article
DE Gallbladder mass; Gallbladder polyp; Gallbladder adenocarcinoma;
Ultrasonographic characteristics
ID POLYPOID LESIONS; FOLLOW-UP; NATURAL-HISTORY; CLINICOPATHOLOGICAL
FEATURES; OPERATIVE INDICATIONS; GALL-BLADDER; DIAGNOSIS; PREVALENCE
AB Possible mass lesions identified on ultrasound (US) of the gallbladder may prompt an aggressive surgical intervention due to the possibility of a malignant neoplasm.
This study aims to utilize a large modern series of patients with gallbladder lesions identified on US to evaluate imaging characteristics consistent with malignancy.
A retrospective review was conducted of gallbladder ultrasound reports and clinicopathologic data of patients with a mass identified on US.
Approximately 59,271 abdominal ultrasounds and 9,117 cholecystectomies were performed between February 2000 and February 2010. We identified 213 patients with a questionable gallbladder neoplasm on ultrasonography who underwent surgical exploration. Median age was 52 years (range = 11-87 years) and 147 (69%) were females. Final pathology demonstrated no neoplasm in 130 patients (61%), while 32 patients (15%) had a wall adenomyoma, 36 (17%) had a polyp (five of which were malignant), 14 (7%) had an adenocarcinoma not arising from a polyp, and one patient had a cystic papillary neoplasm. The smaller the lesion, the more likely it was to be a pseudo-mass. For lesions measuring < 5 mm on US, 83% had no lesion found on final pathology. Significant predictors of malignancy were age > 52 years (p < 0.001), presence of gallstones on US (p = 0.004), size > 9 mm (p < 0.001), evidence of invasion at the liver interface (p < 0.001), and wall thickening > 5 mm (p < 0.001). Shape (sessile or penduculated), echogenicity (echogenic or isoechoic), or presence of flow on Doppler were not predictors of malignancy. An US size of a parts per thousand currency sign9 mm had a negative predictive value of 100% for malignancy.
Despite improvements in imaging, most apparent lesions measuring < 5 mm on US are not identified in the surgical specimen. US size > 9 mm, age > 52 years, US suggestion of invasion at the liver interface, and wall thickening > 5 mm, especially in the presence of gallstones, should raise the suspicion of malignancy.
C1 [Konstantinidis, Ioannis T.; Tanabe, Kenneth K.; Berger, David L.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Konstantinidis, Ioannis T.; Bajpai, Surabhi; Kambadakone, Avinash R.; Tanabe, Kenneth K.; Berger, David L.; Zheng, Hui; Sahani, Dushyant V.; Lauwers, Gregory Y.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Ferrone, Cristina R.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Bajpai, Surabhi; Kambadakone, Avinash R.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Zheng, Hui] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA.
RP Ferrone, CR (reprint author), Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr 460,15 Parkman St, Boston, MA 02114 USA.
EM cferrone@partners.org
NR 24
TC 15
Z9 16
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1091-255X
J9 J GASTROINTEST SURG
JI J. Gastrointest. Surg.
PD MAR
PY 2012
VL 16
IS 3
BP 549
EP 553
DI 10.1007/s11605-011-1696-2
PG 5
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 892NU
UT WOS:000300293700014
PM 22108768
ER
PT J
AU Al Natour, RH
Saund, MS
Sanchez, VM
Whang, EE
Sharma, AM
Huang, Q
Boosalis, VA
Gold, JS
AF Al Natour, Riad H.
Saund, Mandeep S.
Sanchez, Vivian M.
Whang, Edward E.
Sharma, Ashish M.
Huang, Qin
Boosalis, Valia A.
Gold, Jason S.
TI Tumor Size and Depth Predict Rate of Lymph Node Metastasis in Colon
Carcinoids and Can Be Used to Select Patients for Endoscopic Resection
SO JOURNAL OF GASTROINTESTINAL SURGERY
LA English
DT Article
DE Colon carcinoid; Neuroendocrine tumors; Lymph node metastasis
ID NEUROENDOCRINE TUMORS; GUIDELINES; SYSTEM; RECTUM
AB Regional lymphadenectomy is recommended for all colon carcinoids, whereas resection without lymphadenectomy is accepted for selected appendiceal and rectal carcinoids. We examined the relation of tumor size and depth to lymph node metastasis in order to determine whether colon carcinoids could be selected for endoscopic resection.
Patients were identified from the Surveillance Epidemiology and End Results Registry. The Pearson chi-square and the log rank tests were used. P < 0.05 was considered significant.
We identified 929 patients who underwent resection of localized colon carcinoids without distant metastasis diagnosed from 1973 to 2006. The diagnosis of small and superficial tumors increased over time (p < 0.001). The presence of lymph node metastasis was adversely associated with survival (p < 0.001); however, there was only a trend toward independence on multivariate analysis (p = 0.054). Tumor size and depth were associated with lymph node metastasis (p < 0.001, p < 0.001). Tumors were subgrouped by size and depth to find cases with a low risk of lymph node metastasis. Intramucosal tumors < 1 cm had a 4% rate of lymph node metastasis, while all other subgroups had rates a parts per thousand yen14%.
Tumor size and depth predict lymph node metastasis for colon carcinoids. Endoscopic resection may be appropriate for intramucosal tumors < 1 cm.
C1 [Al Natour, Riad H.; Saund, Mandeep S.; Whang, Edward E.; Huang, Qin; Gold, Jason S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Al Natour, Riad H.; Saund, Mandeep S.; Sanchez, Vivian M.; Whang, Edward E.; Gold, Jason S.] VA Boston Healthcare Syst, Surg Serv, W Roxbury, MA 02132 USA.
[Huang, Qin] VA Boston Healthcare Syst, Pathol Serv, W Roxbury, MA 02132 USA.
[Huang, Qin] Harvard Univ, Sch Med, W Roxbury, MA 02132 USA.
[Sharma, Ashish M.; Boosalis, Valia A.] VA Boston Healthcare Syst, Med Serv, W Roxbury, MA 02132 USA.
[Sanchez, Vivian M.; Sharma, Ashish M.; Boosalis, Valia A.] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Gold, JS (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM jgold4@partners.org
RI Gold, Jason/O-5112-2014;
OI Gold, Jason/0000-0002-2925-4755; Sanchez, Vivian/0000-0001-5565-9687
FU Department of Veterans Affairs Office of Research and Development
FX This work was supported by the Department of Veterans Affairs Office of
Research and Development through a Career Development Award-2 (JSG).
NR 18
TC 12
Z9 12
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1091-255X
J9 J GASTROINTEST SURG
JI J. Gastrointest. Surg.
PD MAR
PY 2012
VL 16
IS 3
BP 595
EP 602
DI 10.1007/s11605-011-1786-1
PG 8
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 892NU
UT WOS:000300293700020
PM 22143420
ER
PT J
AU Bogoch, II
Robbins, GK
AF Bogoch, Isaac I.
Robbins, Gregory K.
TI Varicella zoster mimicking infectious tenosynovitis
SO JOURNAL OF INFECTION
LA English
DT Letter
C1 [Bogoch, Isaac I.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Bogoch, II (reprint author), Massachusetts Gen Hosp, Div Infect Dis, COX 5,55 Fruit St, Boston, MA 02114 USA.
EM ibogoch@partners.org
NR 2
TC 0
Z9 0
U1 0
U2 1
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0163-4453
J9 J INFECTION
JI J. Infect.
PD MAR
PY 2012
VL 64
IS 3
BP 341
EP 342
DI 10.1016/j.jinf.2011.12.001
PG 2
WC Infectious Diseases
SC Infectious Diseases
GA 892BA
UT WOS:000300260300014
PM 22178586
ER
PT J
AU Waisbren, SE
Potter, NL
Gordon, CM
Green, RC
Greenstein, P
Gubbels, CS
Rubio-Gozalbo, E
Schomer, D
Welt, C
Anastasoaie, V
D'Anna, K
Gentile, J
Guo, CY
Hecht, L
Jackson, R
Jansma, BM
Li, YJ
Lip, V
Miller, DT
Murray, M
Power, L
Quinn, N
Rohr, F
Shen, YP
Skinder-Meredith, A
Timmers, I
Tunick, R
Wessel, A
Wu, BL
Levy, H
Elsas, L
Berry, GT
AF Waisbren, Susan E.
Potter, Nancy L.
Gordon, Catherine M.
Green, Robert C.
Greenstein, Patricia
Gubbels, Cynthia S.
Rubio-Gozalbo, Estela
Schomer, Donald
Welt, Corrine
Anastasoaie, Vera
D'Anna, Kali
Gentile, Jennifer
Guo, Chao-Yu
Hecht, Leah
Jackson, Roberta
Jansma, Bernadette M.
Li, Yijun
Lip, Va
Miller, David T.
Murray, Michael
Power, Leslie
Quinn, Nicolle
Rohr, Frances
Shen, Yiping
Skinder-Meredith, Amy
Timmers, Inge
Tunick, Rachel
Wessel, Ann
Wu, Bai-Lin
Levy, Harvey
Elsas, Louis
Berry, Gerard T.
TI The adult galactosemic phenotype
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Article
ID CLASSICAL GALACTOSEMIA; FEMALE-PATIENTS; CHILDREN; ADOLESCENTS
AB Classic galactosemia is an autosomal recessive disorder due to galactose-1-phosphate uridyltransferase (GALT) deficiency. Newborn screening and early treatment do not completely prevent tremor, speech deficits, and diminished IQ in both sexes and premature ovarian insufficiency (POI) in women. Data on how individuals with galactosemia fare as adults will improve our ability to predict disease progression.
Thirty-three adults (mean age = 32.6 +/- 11.7 years; range = 18-59) with classic galactosemia, confirmed by genotype and undetectable GALT enzyme activity, were evaluated. Analyses assessed associations among age, genotype, clinical features and laboratory measures.
The sample included 17 men and 16 women. Subjects exhibited cataracts (21%), low bone density (24%), tremor (46%), ataxia (15%), dysarthria (24%), and apraxia of speech (9%). Subjects reported depression (39%) and anxiety (67%). Mean full scale IQ was 88 +/- 20, (range = 55-122). All subjects followed a dairy-free diet and 75-80% reported low intake of calcium and vitamin D. Mean height, weight and body mass were within established norms. All female subjects had been diagnosed with POI. One woman and two men had had children. Logistic regression analyses revealed no associations between age, genotype or gender with IQ, tremor, ataxia, dysarthria, apraxia of speech or anxiety. Each 10- year increment of age was associated with a twofold increase in odds of depression.
Taken together, these data do not support the hypothesis that galactosemia is a progressive neurodegenerative disease. However, greater attention to depression, anxiety, and social relationships may relieve the impact of this disorder in adults.
C1 [Waisbren, Susan E.; Gordon, Catherine M.; Anastasoaie, Vera; D'Anna, Kali; Gentile, Jennifer; Guo, Chao-Yu; Hecht, Leah; Li, Yijun; Lip, Va; Miller, David T.; Quinn, Nicolle; Rohr, Frances; Shen, Yiping; Tunick, Rachel; Wessel, Ann; Wu, Bai-Lin; Levy, Harvey] Childrens Hosp, Boston, MA 02115 USA.
[Potter, Nancy L.; Power, Leslie; Skinder-Meredith, Amy] Washington State Univ, Pullman, WA 99164 USA.
[Green, Robert C.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Greenstein, Patricia; Schomer, Donald] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Gubbels, Cynthia S.; Rubio-Gozalbo, Estela; Timmers, Inge] Maastricht Univ Med Ctr, Maastricht, Netherlands.
[Welt, Corrine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jackson, Roberta] Eastern Washington Univ, Seattle, WA USA.
[Jansma, Bernadette M.] Maastricht Univ, Maastricht, Netherlands.
[Murray, Michael] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Elsas, Louis] Univ Miami, Coral Gables, FL 33124 USA.
[Berry, Gerard T.] Harvard Univ, Sch Med, Manton Ctr Orphan Dis Res, Childrens Hosp Boston, Boston, MA USA.
RP Waisbren, SE (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA.
EM Susan.Waisbren@childrens.harvard.edu
RI Timmers, Inge/H-1887-2011; rubio, estela/H-1833-2011;
OI Berry, Gerard/0000-0001-5299-3313; Welt, Corrine/0000-0002-8219-5504
FU Parents of Galactosemic Children, USA; National Center for Research
Resources, National Institutes of Health [UL1 RR025758-01]
FX This project was funded in part by a research grant from the Parents of
Galactosemic Children, USA, and in part by the grant UL1 RR025758-01
from the National Center for Research Resources, National Institutes of
Health, to the Harvard Catalyst Clinical & Translational Science Center
(Harvard Catalyst). The authors thank the CTSU staff of Children's
Hospital Boston for their superb assistance and the patients with
galactosemia and their families who traveled to Boston from around the
U.S.A. and participated in this study. We thank the Parents of
Galactosemic Children, USA for their support. We also thank Al Ozonoff,
Linda Manis, Michelle Fowler, Judith Muir, Catherine Arnold, Brian
Deutsch, Stephanie Kon, Anya Kwasnik, and Rebecca Owen for their
invaluable help.
NR 38
TC 45
Z9 47
U1 0
U2 12
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 MAR
PY 2012
VL 35
IS 2
BP 279
EP 286
DI 10.1007/s10545-011-9372-y
PG 8
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 893FT
UT WOS:000300342300008
PM 21779791
ER
PT J
AU Ng, K
Kim, R
Kesari, S
Carter, B
Chen, CC
AF Ng, Kimberly
Kim, Ryan
Kesari, Santosh
Carter, Bob
Chen, Clark C.
TI Genomic profiling of glioblastoma: convergence of fundamental biologic
tenets and novel insights
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Review
DE Glioblastoma; TCGA; Genomics; RTK; RB; p53; IDH1; Telomerase;
Angiogenesis; Invasion; Subtype; Cancer
ID RECEPTOR TYROSINE KINASES; ENDOTHELIAL GROWTH-FACTOR; GENE-EXPRESSION;
MALIGNANT GLIOMAS; CLINICALLY-RELEVANT; TUMOR-SUPPRESSOR; DIFFUSE
GLIOMAS; IDH2 MUTATIONS; CANCER-THERAPY; CELLS
AB With advances in genomic profiling and sequencing technology, we are beginning to understand the landscape of the genetic events that accumulated during the neoplastic process. The insights gleamed from these genomic profiling studies with regards to glioblastoma etiology has been particularly satisfying because it cemented the clinical pertinence of major concepts in cancer biology-concepts developed over the past three decades. This article will review how the glioblastoma genomic data set serves as an illustrative platform for the concepts put forward by Hanahan and Weinberg on the cancer phenotype. The picture emerging suggests that most glioblastomas evolve along a multitude of pathways rather than a single defined pathway. In this context, the article will further provide a discussion of the subtypes of glioblastoma as they relate to key principles of developmental neurobiology.
C1 [Chen, Clark C.] Univ Calif San Diego, Div Neurosurg, La Jolla, CA 92093 USA.
[Ng, Kimberly; Chen, Clark C.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Kim, Ryan; Kesari, Santosh] Univ Calif San Diego, Moores UCSD Canc Ctr, Dept Neurol, La Jolla, CA 92093 USA.
[Carter, Bob; Chen, Clark C.] Univ Calif San Diego, Ctr Theoret & Appl Neurooncol, La Jolla, CA 92093 USA.
RP Chen, CC (reprint author), Univ Calif San Diego, Div Neurosurg, 3855 Hlth Sci Dr 0987, La Jolla, CA 92093 USA.
EM clarkchen@ucsd.edu
RI Kesari, Santosh/E-8461-2013
NR 78
TC 19
Z9 19
U1 0
U2 2
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 MAR
PY 2012
VL 107
IS 1
BP 1
EP 12
DI 10.1007/s11060-011-0714-2
PG 12
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 892VG
UT WOS:000300313100001
PM 22002595
ER
PT J
AU Drappatz, J
Lee, EQ
Hammond, S
Grimm, SA
Norden, AD
Beroukhim, R
Gerard, M
Schiff, D
Chi, AS
Batchelor, TT
Doherty, LM
Ciampa, AS
LaFrankie, DC
Ruland, S
Snodgrass, SM
Raizer, JJ
Wen, PY
AF Drappatz, J.
Lee, E. Q.
Hammond, S.
Grimm, S. A.
Norden, A. D.
Beroukhim, R.
Gerard, M.
Schiff, D.
Chi, A. S.
Batchelor, T. T.
Doherty, L. M.
Ciampa, A. S.
LaFrankie, D. C.
Ruland, S.
Snodgrass, S. M.
Raizer, J. J.
Wen, P. Y.
TI Phase I study of panobinostat in combination with bevacizumab for
recurrent high-grade glioma
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Panobinostat; Bevacizumab; High-grade glioma; Vascular endothelial
growth factor; Histone deacetylase inhibitor
ID HISTONE DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; TYROSINE
KINASE INHIBITOR; MALIGNANT GLIOMAS; PLUS IRINOTECAN; GLIOBLASTOMA;
GROWTH; VITRO; ANGIOGENESIS; APOPTOSIS
AB Bevacizumab is frequently used to treat patients with recurrent high-grade glioma (HGG), but responses are generally not durable. Panobinostat is a histone deacetylase inhibitor with anti-neoplastic and anti-angiogenic effects and may work synergistically with VEGF inhibitors. We performed a phase I study to evaluate the safety and tolerability of the combination of orally administered panobinostat with bevacizumab in patients with recurrent HGG. Patients with recurrent HGG were treated on a 3 + 3 trial design. Patients received bevacizumab 10 mg/kg every other week in combination with oral panobinostat. The starting dose of panobinostat was 20 mg three times per week, weekly (cohort 1). Due to concerns for thrombocytopenia with the weekly dosing regimen, the protocol was amended to examine an every other week regimen. Cohort 2 received panobinostat 20 mg three times per week, every other week, and cohort 3 received 30 mg three times per week, every other week. Dose-limiting toxicity during the first 30 days was used to determine the maximum-tolerated dose. Twelve patients (median age 50, median KPS 90) with recurrent HGG were enrolled. One dose-limiting toxicity (DLT) (Grade 3 thrombocytopenia) was observed in cohort 1. No DLTs were observed in cohorts 2 and 3. The following grade 3 toxicities were seen in one patient each: thrombocytopenia, hypophosphatemia, esophageal hemorrhage, and deep venous thrombosis. There were no grade 4 or 5 toxicities. There were three patients with partial responses and seven with stable disease. The recommended doses for further study are oral panobinostat 30 mg three times per week, every other week, in combination with bevacizumab 10 mg/kg every other week. A phase II clinical trial in recurrent HGG is underway.
C1 [Drappatz, J.; Lee, E. Q.; Hammond, S.; Norden, A. D.; Beroukhim, R.; Gerard, M.; Doherty, L. M.; Ciampa, A. S.; LaFrankie, D. C.; Ruland, S.; Wen, P. Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA.
[Grimm, S. A.; Raizer, J. J.] Northwestern Univ, Chicago, IL 60611 USA.
[Schiff, D.] Univ Virginia, Charlottesville, VA USA.
[Chi, A. S.; Batchelor, T. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Snodgrass, S. M.] Novartis Pharmaceut, E Hanover, NJ USA.
RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave,SW 430, Boston, MA 02215 USA.
EM pwen@partners.org
FU Novartis; Genentech/Roche
FX E.Q. Lee has served on the advisory board of Novartis and
Genentech/Roche. T. T. Batchelor has served on the advisory board for
Genentech/Roche. R. Beroukhim has received research support from
Novartis. S. M. Snodgrass is an employee of Novartis. J.J. Raizer has
received research support from Novartis and Genentech/Roche, served on
the advisory boards of both Novartis and Genentech/Roche and is on the
speaker's bureau of Genentech/Roche. P.Y. Wen has received research
support from Novartis and Genentech/Roche and served on the advisory
boards of both Novartis and Genentech/Roche.
NR 29
TC 34
Z9 34
U1 0
U2 4
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 MAR
PY 2012
VL 107
IS 1
BP 133
EP 138
DI 10.1007/s11060-011-0717-z
PG 6
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 892VG
UT WOS:000300313100014
PM 21984064
ER
PT J
AU Reardon, DA
Herndon, JE
Peters, K
Desjardins, A
Coan, A
Lou, E
Sumrall, A
Turner, S
Sathornsumetee, S
Rich, JN
Boulton, S
Lipp, ES
Friedman, HS
Vredenburgh, JJ
AF Reardon, David A.
Herndon, James E., II
Peters, Katherine
Desjardins, Annick
Coan, April
Lou, Emil
Sumrall, Ashley
Turner, Scott
Sathornsumetee, Sith
Rich, Jeremy N.
Boulton, Susan
Lipp, Eric S.
Friedman, Henry S.
Vredenburgh, James J.
TI Outcome after bevacizumab clinical trial therapy among recurrent grade
III malignant glioma patients
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Malignant glioma; Angiogenesis; Bevacizumab; Vascular endothelial growth
factor; Anaplastic astrocytoma
ID PHASE-II; METRONOMIC CHEMOTHERAPY; PLUS IRINOTECAN; ANAPLASTIC
ASTROCYTOMA; GLIOBLASTOMA; PROGRESSION; ERLOTINIB; PROGNOSIS; PATTERNS;
OLIGODENDROGLIOMA
AB Although outcome following bevacizumab among recurrent grade IV malignant glioma patients is documented as poor by several analyses, outcome for recurrent grade III patients following bevacizumab therapy has not been specifically evaluated. We performed a pooled analysis of 96 recurrent grade III malignant glioma patients enrolled on three consecutive phase II bevacizumab salvage trials to evaluate overall outcome following bevacizumab trial discontinuation. Outcome on the three bevacizumab trials, which included similar eligibility, treatment and assessment criteria, was comparable. Forty-nine patients who progressed on bevacizumab trial therapy and remained alive for at least 30 days elected to receive additional therapy. These patients achieved a median PFS-6 and OS of 30.6% (95% CI: 18.4, 43.6) and 10.3 months (95% CI: 5.2, 11.7), respectively. Among patients who continued bevacizumab therapy (n = 23) after study progression, PFS-6 and median OS were 39.1% (95% CI: 19.9, 58.0) and 9.2 months (95% CI: 5.2, 13.6), respectively, compared to 23.1% (95% CI: 9.4, 40.3; P = 0.51) and 10.3 months (95% CI: 2.5, 14.4; P = 0.91) for patients who initiated non-bevacizumab containing therapy (n = 26). Outcome after discontinuation of bevacizumab therapy for recurrent grade III malignant glioma patients is associated with improved outcome compared to historical data for recurrent grade IV malignant glioma patients. Salvage therapies following bevacizumab failure have modest activity for grade III malignant glioma patients that is independent of further bevacizumab continuation.
C1 [Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA.
[Herndon, James E., II] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Dept Canc Ctr Biostat, Durham, NC USA.
[Peters, Katherine; Desjardins, Annick; Vredenburgh, James J.] Duke Univ, Med Ctr, Dept Med, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
[Coan, April] Duke Univ, Med Ctr, Dept Pathol, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
[Lou, Emil; Sumrall, Ashley; Turner, Scott; Boulton, Susan; Lipp, Eric S.] Duke Univ, Med Ctr, Dept Surg, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
[Sathornsumetee, Sith] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Med Neurol, Bangkok 10700, Thailand.
[Rich, Jeremy N.] Cleveland Clin, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44106 USA.
Duke Univ, Med Ctr, Dept Pediat, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
RP Reardon, DA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave,SW 460F, Boston, MA 02215 USA.
EM david_reardon@dfci.harvard.edu
OI Sykes, April/0000-0002-7667-8155
FU NIH [P50-NS20023-29, R37- CA11898-42]; Genentech Pharmaceuticals
FX This work was supported by NIH Grants P50-NS20023-29 and R37-
CA11898-42; and a grant from Genentech Pharmaceuticals.
NR 35
TC 15
Z9 15
U1 0
U2 4
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 MAR
PY 2012
VL 107
IS 1
BP 213
EP 221
DI 10.1007/s11060-011-0740-0
PG 9
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 892VG
UT WOS:000300313100024
PM 21997879
ER
PT J
AU Blackham, KA
Meyers, PM
Abruzzo, TA
Alberquerque, FC
Fiorella, D
Fraser, J
Frei, D
Gandhi, CD
Heck, DV
Hirsch, JA
Hsu, DP
Jayaraman, M
Narayanan, S
Prestigiacomo, C
Sunshine, JL
AF Blackham, K. A.
Meyers, P. M.
Abruzzo, T. A.
Alberquerque, F. C.
Fiorella, D.
Fraser, J.
Frei, D.
Gandhi, C. D.
Heck, D. V.
Hirsch, J. A.
Hsu, D. P.
Jayaraman, M.
Narayanan, S.
Prestigiacomo, C.
Sunshine, J. L.
CA Soc NeuroInterventional Surg
TI Endovascular therapy of acute ischemic stroke: report of the Standards
of Practice Committee of the Society of NeuroInterventional Surgery
SO JOURNAL OF NEUROINTERVENTIONAL SURGERY
LA English
DT Article
ID INTRAARTERIAL THROMBOLYTIC THERAPY; TISSUE-PLASMINOGEN ACTIVATOR;
CEREBRAL-ARTERY OCCLUSION; RANDOMIZED CONTROLLED-TRIALS;
CLINICAL-PRACTICE GUIDELINES; PERIPHERAL-VASCULAR-DISEASE; BRAIN ATTACK
COALITION; QUALITY-OF-CARE; INTRAVENOUS THROMBOLYSIS;
COMPUTED-TOMOGRAPHY
AB Objective To summarize and classify the evidence for the use of endovascular techniques in the treatment of patients with acute ischemic stroke.
Methods Recommendations previously published by the American Heart Association (AHA) (Guidelines for the early management of adults with ischemic stroke (Circulation 2007) and Scientific statement indications for the performance of intracranial endovascular neurointerventional procedures (Circulation 2009)) were vetted and used as a foundation for the current process. Building on this foundation, a critical review of the literature was performed to evaluate evidence supporting the endovascular treatment of acute ischemic stroke. The assessment was based on guidelines for evidence based medicine proposed by the Stroke Council of the AHA and the University of Oxford, Centre for Evidence Based Medicine (CEBM). Procedural safety, technical efficacy and impact on patient outcomes were specifically examined.
C1 [Blackham, K. A.; Hirsch, J. A.; Sunshine, J. L.] Case Western Reserve Univ, Dept Radiol, Univ Hosp Cleveland, Cleveland, OH 44106 USA.
[Meyers, P. M.] Columbia Univ, Coll Phys & Surg, Neuroendovasc Serv New York Presbyterian Columbia, Dept Radiol & Neurol Surg,Neurol Inst New York, New York, NY USA.
[Abruzzo, T. A.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA.
[Alberquerque, F. C.] Barrow Neurosurg Associates LTD, Div Neurol Surg, Phoenix, AZ USA.
[Fiorella, D.] SUNY Stony Brook, Med Ctr, Dept Neurol Surg, Stony Brook, NY 11794 USA.
[Fraser, J.] Univ Kentucky, Dept Neurol Surg, Lexington, KY USA.
[Frei, D.] Radiol Imaging Associates, Intervent Neuroradiol, Englewood, CO USA.
[Gandhi, C. D.] UMDNJ New Jersey Med Sch, Dept Neurol Surg, Newark, NJ USA.
[Heck, D. V.] Forsyth Radiol Associates, Dept Radiol, Winston Salem, NC USA.
[Hirsch, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jayaraman, M.] Brown Univ, Warren Alpert Sch Med, Rhode Isl Hosp, Providence, RI 02912 USA.
[Narayanan, S.] Wayne State Univ, Detroit Med Ctr, Dept Neurosurg, Detroit, MI USA.
[Narayanan, S.] Wayne State Univ, Detroit Med Ctr, Dept Neurol, Detroit, MI USA.
[Prestigiacomo, C.] Univ Med & Dent New Jersey, Dept Neurol Surg, Newark, NJ 07103 USA.
RP Blackham, KA (reprint author), Case Western Reserve Univ, Dept Radiol, Univ Hosp Cleveland, 11100 Euclid Ave, Cleveland, OH 44106 USA.
EM kristine.blackham@uhhospitals.org
OI Fraser, Justin/0000-0002-5980-3989
NR 83
TC 25
Z9 28
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1759-8478
J9 J NEUROINTERV SURG
JI J. NeuroInterventional Surg.
PD MAR
PY 2012
VL 4
IS 2
BP 87
EP 93
DI 10.1136/neurintsurg-2011-010243
PG 7
WC Neuroimaging; Surgery
SC Neurosciences & Neurology; Surgery
GA 891KU
UT WOS:000300216600006
PM 22278933
ER
PT J
AU Gupta, AC
Hirsch, JA
Chaudhry, ZA
Chandra, RV
Pulli, B
Galinsky, JG
Hirsch, AE
Yoo, AJ
AF Gupta, Amar C.
Hirsch, Joshua A.
Chaudhry, Zeshan A.
Chandra, Ronil V.
Pulli, Benjamin
Galinsky, Janice G.
Hirsch, Ariel E.
Yoo, Albert J.
TI Evaluating the safety and effectiveness of percutaneous acetabuloplasty
SO JOURNAL OF NEUROINTERVENTIONAL SURGERY
LA English
DT Article
ID BONE METASTASIS; RECONSTRUCTION; CEMENTOPLASTY; ACETABULUM; ABLATION;
SCALE; PAIN
AB Purpose To evaluate the safety and effectiveness of percutaneous acetabuloplasty in treating the pain and disability related to metastatic lesions of the acetabulum.
Materials and methods This institutional review board approved retrospective study examined 11 patients who underwent percutaneous acetabuloplasty in our hospital from April 2007 to June 2010. All patients gave informed consent prior to the procedure, and all records were HIPAA compliant. Chart review was performed to collect patient demographics and to assess pre- and post-treatment patient performance on the Visual Analog Scale, Functional Mobility Scale and Analgesic Scale. Paired testing comparing the pre-and post-treatment scores for each patient was performed using the Wilcoxon signed rank test.
Results There were 11 procedures: 10 performed under CT guidance and one using fluoroscopic guidance. There was a statistically significant decrease in patient Visual Analog Scale score (p=0.001) and Functional Mobility Scale score (p=0.03) after treatment. There was no change in median Analgesic Scale scores pre-and post-treatment although paired testing revealed a trend towards reduced analgesic use postoperatively (p=0.06). There were no clinically significant complications in this series.
Conclusion Percutaneous acetabuloplasty appears to be safe and effective for improving the pain and decreased mobility secondary to metastatic lesions of the acetabulum.
C1 [Gupta, Amar C.; Hirsch, Joshua A.; Chaudhry, Zeshan A.; Chandra, Ronil V.; Pulli, Benjamin; Galinsky, Janice G.; Hirsch, Ariel E.; Yoo, Albert J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Yoo, AJ (reprint author), Massachusetts Gen Hosp, Gray 241,55 Fruit St, Boston, MA 02114 USA.
EM ajyoo@partners.org
NR 22
TC 7
Z9 7
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1759-8478
J9 J NEUROINTERV SURG
JI J. NeuroInterventional Surg.
PD MAR
PY 2012
VL 4
IS 2
BP 134
EP 138
DI 10.1136/jnis.2011.004879
PG 5
WC Neuroimaging; Surgery
SC Neurosciences & Neurology; Surgery
GA 891KU
UT WOS:000300216600018
PM 21990476
ER
PT J
AU Manchikanti, L
Hirsch, JA
AF Manchikanti, Laxmaiah
Hirsch, Joshua A.
TI Patient Protection and Affordable Care Act of 2010: a primer for
NeuroInterventionalists
SO JOURNAL OF NEUROINTERVENTIONAL SURGERY
LA English
DT Review
ID INTERVENTIONAL PAIN MANAGEMENT; HEALTH-CARE; REFORM; INSURANCE; DECADE
AB The Patient Protection and Affordable Care Act (the ACA, for short) became law on 23 March 2010. It represents the most significant transformation of the American healthcare system since Medicare and Medicaid. Essentials of ACA include: (1) a mandate for individuals and businesses requiring as a matter of law that nearly every American has an approved level of health insurance or pay a penalty; (2) a system of federal subsidies to completely or partially pay for the now required health insurance for similar to 34 million Americans who are currently uninsured-subsidized through Medicaid and Exchanges; (3) extensive new requirements on the health insurance industry and (4) changes in the practice of medicine. The Act is divided into 10 titles. It contains provisions that went into effect starting on 21 June 2010 with many of the provisions going into effect in 2014 and later. The ACA goes well beyond insurance and payment reform. Practicing physicians will potentially be impacted by the Independent Payment Advisory Board and the Patient Centered Outcomes Research Institute.
C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA.
[Manchikanti, Laxmaiah] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA.
[Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept NeuroIntervent Radiol, Boston, MA USA.
RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA.
EM drlm@thepainmd.com
NR 31
TC 26
Z9 26
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1759-8478
J9 J NEUROINTERV SURG
JI J. NeuroInterventional Surg.
PD MAR
PY 2012
VL 4
IS 2
BP 141
EP 146
DI 10.1136/neurintsurg-2011-010036
PG 6
WC Neuroimaging; Surgery
SC Neurosciences & Neurology; Surgery
GA 891KU
UT WOS:000300216600020
PM 21990501
ER
PT J
AU Morgans, AK
Hancock, ML
Barnette, KG
Steiner, MS
Morton, RA
Smith, MR
AF Morgans, Alicia K.
Hancock, Michael L.
Barnette, K. Gary
Steiner, Mitchell S.
Morton, Ronald A.
Smith, Matthew R.
TI Racial Differences in Bone Mineral Density and Fractures in Men
Receiving Androgen Deprivation Therapy for Prostate Cancer
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostatic neoplasms; androgens; bone density; fractures, bone; survival
rate
ID OLDER MEN; VERTEBRAL FRACTURES; HORMONE AGONISTS; WHITE MEN;
OSTEOPOROSIS; BLACK; RISK; PREVENTION; CARCINOMA; HEALTH
AB Purpose: Whether race influences bone loss and fracture risk during androgen deprivation therapy for prostate cancer is unknown. Using data from a prospective clinical trial we compared bone mineral density and fracture between African-American and Caucasian men receiving androgen deprivation therapy.
Materials and Methods: A total of 516 subjects were in the placebo group of a 2-year randomized placebo controlled fracture prevention trial, and were African-American (68) or Caucasian (448). We compared baseline characteristics, changes in bone mineral density and rates of new fractures between races.
Results: Compared to Caucasian men, African-American men had higher baseline hip bone mineral density (mean +/- SD 0.98 +/- 0.15 vs 0.91 +/- 0.15 gm/m(2), p = 0.001) and similar spine bone mineral density (1.09 +/- 0.22 vs 1.11 +/- 0.22, p = 0.51). There was no difference in prevalent vertebral fractures between African-American and Caucasian men (7.4% vs 15.0%, p = 0.13). The percentage change in hip bone mineral density at 2 years was similar between African-American and Caucasian men (mean +/- SE -2.21% +/- 0.59% vs -2.54% +/- 0.26%, p = 0.65). Changes in bone mineral density of the lumbar spine were also similar between African-American and Caucasian men (-1.74% +/- 0.69% vs -1.30% +/- 0.33%, p = 0.64). No new vertebral fractures were reported in African-American men but 2 fractures were reported in Caucasian men.
Conclusions: In a clinical trial African-American men receiving androgen deprivation therapy for prostate cancer have a greater hip bone mineral density and tended to have fewer prevalent vertebral fractures than Caucasian men. Despite a lower baseline risk of osteoporosis and fracture, African-American men experience a decrease in bone mineral density similar to that of Caucasian men.
C1 [Morgans, Alicia K.; Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Hancock, Michael L.; Barnette, K. Gary; Steiner, Mitchell S.; Morton, Ronald A.] GTx Inc, Memphis, TN USA.
RP Morgans, AK (reprint author), Massachusetts Gen Hosp, Ctr Canc, POB 221, Boston, MA 02114 USA.
EM amorgans@partners.org
FU NCI NIH HHS [K24 CA121990]
NR 24
TC 5
Z9 5
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD MAR
PY 2012
VL 187
IS 3
BP 889
EP 893
DI 10.1016/j.juro.2011.10.136
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 892CY
UT WOS:000300265500038
PM 22245322
ER
PT J
AU Palevsky, PM
AF Palevsky, Paul M.
TI Chronic-on-acute kidney injury
SO KIDNEY INTERNATIONAL
LA English
DT Editorial Material
ID ACUTE-RENAL-FAILURE; DIALYSIS; DISEASE
AB Although older teaching suggested that patients who survived an episode of acute kidney injury (AKI) had a benign course, recent studies have demonstrated that AKI is strongly associated with increased risk for development of progressive chronic kidney disease (CKD) and longer-term mortality. Much as we understand that CKD predisposes to the development of AKI, we must recognize that the relationship is bidirectional and that our patients with AKI are at risk for chronic-on-acute kidney disease. Kidney International (2012) 81, 430-431. doi:10.1038/ki.2011.435
C1 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA.
[Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA.
RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Room 7E123 111F-U,Univ Dr, Pittsburgh, PA 15240 USA.
EM palevsky@pitt.edu
OI Palevsky, Paul/0000-0002-7334-5400
NR 10
TC 14
Z9 15
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD MAR
PY 2012
VL 81
IS 5
BP 430
EP 431
DI 10.1038/ki.2011.435
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 893SY
UT WOS:000300377000002
PM 22333743
ER
PT J
AU Barnard, ZR
Walcott, BP
Kahle, KT
Nahed, BV
Coumans, JV
AF Barnard, Zachary R.
Walcott, Brian P.
Kahle, Kristopher T.
Nahed, Brian V.
Coumans, Jean Valery
TI Hyponatremia associated with Ipilimumab-induced hypophysitis
SO MEDICAL ONCOLOGY
LA English
DT Article
DE Pituitary gland; Melanoma; Antibodies; Monoclonal; Inappropriate ADH
syndrome
ID ANTIGEN-4 BLOCKADE; TUMOR-REGRESSION; AUTOIMMUNITY; CTLA-4
AB A 75-year-old woman with a history of stage IV metastatic melanoma underwent treatment with the CTLA-4 blocking agent Ipilimumab. She presented 2 months after initiating treatment with a severe headache. Laboratories were consistent with severe hyponatremia. MRI of the brain revealed enlargement of the pituitary gland, enhancement of the infundibulum, and an enhancing, centrally necrotic foci in the anterior pituitary. Based on the clinical and radiographic findings, she was diagnosed with treatment-related syndrome of inappropriate antidiuretic hormone secretion (SIADH). Effective treatment consisted of fluid restriction, hyperosmolar therapy, and steroids.
C1 [Barnard, Zachary R.; Walcott, Brian P.; Kahle, Kristopher T.; Nahed, Brian V.; Coumans, Jean Valery] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Barnard, Zachary R.; Walcott, Brian P.; Kahle, Kristopher T.; Nahed, Brian V.; Coumans, Jean Valery] 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 19
TC 17
Z9 18
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1357-0560
J9 MED ONCOL
JI Med. Oncol.
PD MAR
PY 2012
VL 29
IS 1
BP 374
EP 377
DI 10.1007/s12032-010-9794-7
PG 4
WC Oncology
SC Oncology
GA 892WV
UT WOS:000300317200056
PM 21264545
ER
PT J
AU Tombini, M
Rigosa, J
Zappasodi, F
Porcaro, C
Citi, L
Carpaneto, J
Rossini, PM
Micera, S
AF Tombini, Mario
Rigosa, Jacopo
Zappasodi, Filippo
Porcaro, Camillo
Citi, Luca
Carpaneto, Jacopo
Rossini, Paolo Maria
Micera, Silvestro
TI Combined Analysis of Cortical (EEG) and Nerve Stump Signals Improves
Robotic Hand Control
SO NEUROREHABILITATION AND NEURAL REPAIR
LA English
DT Article
DE robotic hand prosthesis; LIFE; ERS/ERD analysis
ID PHANTOM LIMB PAIN; INTRANEURAL ELECTRODES; AMPUTEES; MOTOR;
SYNCHRONIZATION; CLASSIFICATION; FEEDBACK
AB Background. Interfacing an amputee's upper-extremity stump nerves to control a robotic hand requires training of the individual and algorithms to process interactions between cortical and peripheral signals. Objective. To evaluate for the first time whether EEG-driven analysis of peripheral neural signals as an amputee practices could improve the classification of motor commands. Methods. Four thin-film longitudinal intrafascicular electrodes (tf-LIFEs-4) were implanted in the median and ulnar nerves of the stump in the distal upper arm for 4 weeks. Artificial intelligence classifiers were implemented to analyze LIFE signals recorded while the participant tried to perform 3 different hand and finger movements as pictures representing these tasks were randomly presented on a screen. In the final week, the participant was trained to perform the same movements with a robotic hand prosthesis through modulation of tf-LIFE-4 signals. To improve the classification performance, an event-related desynchronization/synchronization (ERD/ERS) procedure was applied to EEG data to identify the exact timing of each motor command. Results. Real-time control of neural (motor) output was achieved by the participant. By focusing electroneurographic (ENG) signal analysis in an EEG-driven time window, movement classification performance improved. After training, the participant regained normal modulation of background rhythms for movement preparation (alpha/beta band desynchronization) in the sensorimotor area contralateral to the missing limb. Moreover, coherence analysis found a restored alpha band synchronization of Rolandic area with frontal and parietal ipsilateral regions, similar to that observed in the opposite hemisphere for movement of the intact hand. Of note, phantom limb pain (PLP) resolved for several months. Conclusions Combining information from both cortical (EEG) and stump nerve (ENG) signals improved the classification performance compared with tf-LIFE signals processing alone; training led to cortical reorganization and mitigation of PLP.
C1 [Tombini, Mario] Univ Campus Biomed, Neurol Clin, I-00128 Rome, Italy.
[Rigosa, Jacopo; Citi, Luca; Carpaneto, Jacopo; Micera, Silvestro] Scuola Super Sant Anna, BioRobot Inst, Pisa, Italy.
[Zappasodi, Filippo] Univ G DAnnunzio, Chieti, Italy.
[Porcaro, Camillo] Osped Fatebenefratelli, ISTC CNR, Rome, Italy.
[Porcaro, Camillo] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Citi, Luca] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Rossini, Paolo Maria] IRCCS S Raffaele Pisana, Rome, Italy.
[Rossini, Paolo Maria] Casa Cura S Raffaele, Cassino, Italy.
[Rossini, Paolo Maria] Catholic Univ, Rome, Italy.
[Micera, Silvestro] Swiss Fed Inst Technol, Zurich, Switzerland.
RP Tombini, M (reprint author), Univ Campus Biomed, Neurol Clin, Via Alvaro Portillo 200, I-00128 Rome, Italy.
EM m.tombini@unicampus.it
RI Citi, Luca/G-2270-2011; Rossini, Paolo /D-4994-2013;
OI Citi, Luca/0000-0001-8702-5654; Rossini, Paolo /0000-0003-2665-534X;
Tombini, Mario/0000-0002-0328-7815; Porcaro, Camillo/0000-0003-4847-163X
FU Commission of the European Community [FP6-IST-001917]; TIME
[FP7-ICT-224012]
FX This study was partially supported by the Commission of the European
Community within the projects NEUROBOTICS (Contract No. FP6-IST-001917)
and TIME (Contract No. FP7-ICT-224012). None of these funding sources
had a role in the study design, data collection, data analysis, data
interpretation, or writing.
NR 21
TC 15
Z9 15
U1 2
U2 13
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1545-9683
J9 NEUROREHAB NEURAL RE
JI Neurorehabil. Neural Repair
PD MAR-APR
PY 2012
VL 26
IS 3
BP 275
EP 281
DI 10.1177/1545968311408919
PG 7
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 894OD
UT WOS:000300435300008
PM 21730360
ER
PT J
AU Huang, SP
Bao, BY
Wu, MT
Choueiri, TK
Goggins, WB
Liu, CC
Huang, CY
Pu, YS
Yu, CC
Wu, TT
Huang, CN
Huang, CH
Wu, WJ
AF Huang, Shu-Pin
Bao, Bo-Ying
Wu, Ming-Tsang
Choueiri, Toni K.
Goggins, William B.
Liu, Chia-Chu
Huang, Chao-Yuan
Pu, Yeong-Shiau
Yu, Chia-Cheng
Wu, Tony T.
Huang, Chun-Nung
Huang, Chun-Hsiung
Wu, Wen-Jeng
TI Significant associations of prostate-specific antigen nadir and time to
prostate-specific antigen nadir with survival in prostate cancer
patients treated with androgen-deprivation therapy
SO AGING MALE
LA English
DT Article
DE Prostate cancer; androgen-deprivation therapy; metastatic prostate
cancer; prostate-specific antigen kinetics; time to prostate-specific
antigen nadir; prostate-specific antigen nadir
ID BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; PROGNOSTIC-SIGNIFICANCE;
POSTRADICAL PROSTATECTOMY; ANTIANDROGEN WITHDRAWAL; HORMONAL-THERAPY;
PSA VELOCITY; RECEPTOR; RISK; POLYMORPHISMS
AB Objective. The influence of prostate-specific antigen (PSA) kinetics on the outcome of metastatic prostate cancer (PCa) after androgen-deprivation therapy (ADT) remains poorly characterised. We evaluated the prognostic significance of PSA nadir and time to PSA nadir as well as their interactive effect on prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT.
Methods. A total of 650 men with advanced or metastatic PCa treated with ADT were studied. The prognostic significance of PSA nadir and time to PSA nadir on PCSM and ACM were analysed using Kaplan-Meier analysis and the Cox regression model.
Results. On multivariate analysis, clinical M1 stage, Gleason Score 8-10, PSA nadir >= 0.2 ng/ml and time to PSA nadir 5 10 months were independent predictors of PCSM and ACM. The combined analysis showed that patient with higher PSA nadir and shorter time to PSA nadir had significantly higher risk of PCSM and ACM compared to those with lower PSA nadir and longer time to PSA nadir (hazard ratios = 6.30 and 4.79, respectively, all P < 0.001).
Conclusions. Our results suggest that higher PSA nadir level and faster time to reach PSA nadir after ADT were associated with shorter survival for PCa.
C1 [Huang, Shu-Pin; Huang, Chun-Hsiung; Wu, Wen-Jeng] Kaohsiung Med Univ, Dept Urol, Fac Med, Coll Med, Kaohsiung 807, Taiwan.
[Huang, Shu-Pin; Liu, Chia-Chu; Huang, Chun-Nung; Huang, Chun-Hsiung; Wu, Wen-Jeng] Kaohsiung Med Univ Hosp, Dept Urol, Kaohsiung, Taiwan.
[Huang, Shu-Pin] Kaohsiung Med Univ Hosp, Ctr Canc, Kaohsiung, Taiwan.
[Bao, Bo-Ying] China Med Univ, Dept Pharm, Taichung, Taiwan.
[Wu, Ming-Tsang] Kaohsiung Med Univ Hosp, Dept Family Med, Kaohsiung, Taiwan.
[Wu, Ming-Tsang] Kaohsiung Med Univ, Grad Inst Occupat Safety & Hlth, Kaohsiung 807, Taiwan.
[Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Goggins, William B.] Chinese Univ Hong Kong, Div Biostat, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
[Huang, Chao-Yuan; Pu, Yeong-Shiau] Natl Taiwan Univ, Dept Urol, Taipei 10764, Taiwan.
[Yu, Chia-Cheng; Wu, Tony T.] Kaohsiung Vet Gen Hosp, Div Urol, Dept Surg, Kaohsiung, Taiwan.
RP Huang, SP (reprint author), Kaohsiung Med Univ, Dept Urol, Fac Med, Coll Med, 100 Shih Chuan 1st Rd, Kaohsiung 807, Taiwan.
EM shpihu@yahoo.com.tw
RI Wu, Ming-Tsang/G-5637-2012; Bao, Bo-Ying/D-1789-2012;
OI Bao, Bo-Ying/0000-0001-5510-6513; HUANG, CHAO-YUAN/0000-0002-9322-6062;
PU, YEONG-SHIAU/0000-0002-2859-3966
FU Taiwan National Science Council [NSC 95-2314-B-037-053-MY2, NSC
96-2314-B-037-012-MY3, NSC 99-2314-B-037-018-MY3]; Kaohsiung Medical
University Hospital [KMUH96-6G27, KMUH96-6G28]; Kaohsiung Municipal
Hsiao-Kang Hospital [kmhk-96-009, kmhk-97-008]
FX This study was supported by grants from the Taiwan National Science
Council (NSC 95-2314-B-037-053-MY2, NSC 96-2314-B-037-012-MY3 and NSC
99-2314-B-037-018-MY3), Kaohsiung Medical University Hospital
(KMUH96-6G27 and KMUH96-6G28) and Kaohsiung Municipal Hsiao-Kang
Hospital (kmhk-96-009 and kmhk-97-008). The authors thank Ms. Chao-Shih
Chen and Professor Hung-Yi Chuang for their help on data analyses.
NR 38
TC 8
Z9 10
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1368-5538
J9 AGING MALE
JI Aging Male
PD MAR
PY 2012
VL 15
IS 1
BP 34
EP 41
DI 10.3109/13685538.2011.580398
PG 8
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 886GB
UT WOS:000299840800006
PM 21615239
ER
PT J
AU Anderson, RM
Weindruch, R
AF Anderson, Rozalyn M.
Weindruch, Richard
TI The caloric restriction paradigm: Implications for healthy human aging
SO AMERICAN JOURNAL OF HUMAN BIOLOGY
LA English
DT Article
ID GENE-EXPRESSION PROFILE; RANDOMIZED CONTROLLED-TRIAL; TERM DIETARY
RESTRICTION; RHESUS-MONKEYS; LIFE-SPAN; ADIPOSE-TISSUE;
METABOLIC-DISORDERS; ENERGY-INTAKE; MITOCHONDRIAL BIOGENESIS;
SKELETAL-MUSCLE
AB Underlying the importance of research on the biology of aging is the fact that many nations face the demographic reality of a rapidly aging populace and the looming healthcare challenges that it brings. This reality is a result of aging itself being the most significant risk factor for a range of the most prevalent diseases, including many cancers, cardiovascular disease, and diabetes. Accordingly, interventions are sorely needed that would be able to delay or prevent diseases and disorders associated with the aging process and thereby increase the period of time that aging individuals are in good health (the health-span). Caloric restriction (CR) has emerged as a model of major interest as it is widely agreed that CR is the most potent environmental intervention that delays the onset of aging and extends life span in diverse experimental organisms. A better understanding of the mechanisms by which CR delays aging will reveal new insights into the aging process and the underlying causes of disease vulnerability with age. These novel insights will allow the development of novel treatments and preventive measures for age-associated diseases and disorders. Am. J. Hum. Biol. 2012. (C) 2012 Wiley Periodicals, Inc.
C1 [Anderson, Rozalyn M.; Weindruch, Richard] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Anderson, Rozalyn M.; Weindruch, Richard] William S Middleton Mem Vet Adm Med Ctr, Geriatr Educ Res & Clin Ctr, Madison, WI USA.
RP Anderson, RM (reprint author), Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA.
EM rmanderson@medicine.wisc.edu
FU NIH [NIA P01AG11915, R01AG037000]; NCRR/CTSA [UL1RR025011]
FX Contract grant sponsor: NIH; Contract grant numbers: NIA P01AG11915,
R01AG037000, and NCRR/CTSA UL1RR025011.
NR 66
TC 57
Z9 59
U1 2
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1042-0533
J9 AM J HUM BIOL
JI Am. J. Hum. Biol.
PD MAR-APR
PY 2012
VL 24
IS 2
BP 101
EP 106
DI 10.1002/ajhb.22243
PG 6
WC Anthropology; Biology
SC Anthropology; Life Sciences & Biomedicine - Other Topics
GA 888IQ
UT WOS:000299997500001
PM 22290875
ER
PT J
AU Ackerman, KE
Skrinar, GS
Medvedova, E
Misra, M
Miller, KK
AF Ackerman, Kathryn E.
Skrinar, Gary S.
Medvedova, Eva
Misra, Madhusmita
Miller, Karen K.
TI Estradiol levels predict bone mineral density in male collegiate
athletes: a pilot study
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID ANOREXIA-NERVOSA; SERUM TESTOSTERONE; PHYSICAL-ACTIVITY; DISTANCE
RUNNERS; ADOLESCENT GIRLS; YOUNG-ADULTS; MEN; WOMEN; MASS; ESTROGEN
AB Objective Strenuous training commonly results in amenorrhoea, which contributes to bone loss in some female collegiate athletes. However, the impact of athletic training on endocrine function and bone mineral density (BMD) in male collegiate athletes is less well understood. The objective of the study was to investigate the specific endocrine determinants of BMD in male collegiate runners and wrestlers, including the potential impact of gonadal steroid levels.
Design Cross-sectional study.
Patients Twenty-six division I collegiate male athletes (wrestlers, runners and golfers).
Measurements Main outcome measures included (i) BMD endpoints measured by dual energy x-ray absorptiometry (DXA); (ii) endocrine end-points: total and free oestradiol, total and free testosterone; (iii) body composition end-points: lean and fat mass, measured by DXA; and (iv) exercise end-points: maximal oxygen uptake (VO2 max), number of miles run weekly and grip strength.
Results Free and total oestradiol levels were important positive determinants of BMD. In contrast, total and free testosterone levels were not significant predictors of BMD at any skeletal site (except for free testosterone at the radius). In addition, lean body mass, % ideal body weight, total body weight, body mass index (BMI) and hours per week of resistance training were positive predictors of BMD. VO2 max was a negative predictor of BMD. Mean BMD was higher at all skeletal sites in the wrestlers compared with the runners and a comparison group (golfers).
Conclusions Our data suggest that oestradiol levels, BMI, and resistance training are more important determinants of BMD in male collegiate athletes than testosterone.
C1 [Ackerman, Kathryn E.; Medvedova, Eva; Misra, Madhusmita; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Ackerman, Kathryn E.; Medvedova, Eva; Misra, Madhusmita; Miller, Karen K.] Harvard Univ, Sch Med, Boston, MA USA.
[Ackerman, Kathryn E.] Childrens Hosp Boston, Div Sports Med, Boston, MA USA.
[Skrinar, Gary S.] Boston Univ, Dept Hlth Sci GSS, Boston, MA 02215 USA.
[Misra, Madhusmita] MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA USA.
MIT, Gen Clin Res Ctr, Cambridge, MA 02139 USA.
RP Ackerman, KE (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA.
EM KEAckerman@partners.org
FU [MO1 RR01066]
FX We thank the nurses and bionutritionists of the Massachusetts Institute
of Technology General Clinical Research Center, and we thank the
athletes for their participation in this study. The authors have no
conflicts of interest. This work was supported in part by the following
grant: MO1 RR01066. The authors have nothing else to declare.
NR 38
TC 5
Z9 6
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
EI 1365-2265
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD MAR
PY 2012
VL 76
IS 3
BP 339
EP 345
DI 10.1111/j.1365-2265.2011.04212.x
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 887RF
UT WOS:000299946000005
PM 21942923
ER
PT J
AU Gill, TJ
Van de Velde, SK
Carroll, KM
Robertson, WJ
Heyworth, BE
AF Gill, Thomas J.
Van de Velde, Samuel K.
Carroll, Kaitlin M.
Robertson, William J.
Heyworth, Benton E.
TI Surgical Technique: Aperture Fixation in PCL Reconstruction: Applying
Biomechanics to Surgery
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID POSTERIOR CRUCIATE LIGAMENT; TIBIAL INLAY TECHNIQUES; FOLLOW-UP;
SINGLE-BUNDLE; TRANSTIBIAL TECHNIQUES; DEFICIENT KNEE; TENDON GRAFT;
INJURIES; TRANSLATION; KINEMATICS
AB Biomechanical studies suggest reducing the effective graft length during transtibial posterior cruciate ligament (PCL) reconstruction by augmenting the distal tibial fixation with a proximal screw near the tibial tunnel aperture could increase graft stiffness and provide a more stable reconstruction. However, it remains unknown to what extent this mechanical theory influences in vivo graft performance over time.
We developed a technique to augment tibial distal fixation with a proximal screw near the tibial tunnel aperture to shorten the effective graft length and increase graft stiffness.
We retrospectively reviewed all 10 patients who had isolated PCL reconstructions with combined distal and proximal tibial fixation from 2003 to 2007. Mean age of the patients was 36.5 years. We measured ROM and obtained Tegner, International Knee Documentation Committee (IKDC), and Lysholm scores. Anteroposterior stability was evaluated with a KT-2000 arthrometer. Minimum followup was 1 year (mean, 2.5 years; range, 1-4.8 years).
Mean Tegner scores before injury and at last followup were 7.3 and 6.5, respectively. Mean postoperative IKDC score was 87 versus a preoperative IKDC score of 43. Mean Lysholm score was 89 at last followup. All patients achieved full terminal extension. No patient had greater than a 5-mm difference in anterior or posterior displacement from the contralateral knee as measured by a KT-2000 arthrometer postoperatively (0.93 +/- A 0.79 mm).
In this small series, augmentation of tibial distal fixation with a proximal screw near the tibial tunnel aperture during reconstruction of the isolated PCL rupture restored function, motion, and stability.
Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
C1 [Gill, Thomas J.; Van de Velde, Samuel K.; Carroll, Kaitlin M.; Robertson, William J.; Heyworth, Benton E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sports Med Serv, Boston, MA 02114 USA.
RP Gill, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sports Med Serv, 175 Cambridge St,4th Floor, Boston, MA 02114 USA.
EM tgill@partners.org
FU National Institutes of Health [NIH F32AR056451]
FX One or more of the authors (SKV) received financial support from the
National Institutes of Health: NIH F32AR056451.
NR 35
TC 1
Z9 1
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD MAR
PY 2012
VL 470
IS 3
BP 853
EP 860
DI 10.1007/s11999-011-2100-y
PG 8
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 889EF
UT WOS:000300055600028
PM 21997781
ER
PT J
AU Steele, SR
Stein, SL
Bordeianou, LG
Johnson, E
Herzig, DO
Champagne, BJ
AF Steele, Scott R.
Stein, Sharon L.
Bordeianou, Liliana G.
Johnson, Eric
Herzig, Dan O.
Champagne, Bradley J.
CA Amer Soc Colon & Rectal Surg Young
TI The impact of practice environment on laparoscopic colectomy utilization
following colorectal residency: a survey of the ASCRS Young Surgeons
SO COLORECTAL DISEASE
LA English
DT Article
DE Laparoscopy; colectomy; fellowship; university; private practice
ID COLON-CANCER; RANDOMIZED-TRIAL; POSTOPERATIVE COMPLICATIONS; EXPERIENCE;
OUTCOMES; RESECTION; VOLUME
AB Aim It is often thought that practice patterns are different in private (PP) vs university hospital (UH) settings. We aimed to describe the impact of practice environment on the type of laparoscopic colectomy procedures performed by graduating colorectal surgeons.
Method A review was carried out of prospectively gathered self-reported questionnaire data. Graduates of American Society of Colon and Rectal Surgeons' (ASCRS)-approved colorectal residencies from 2004 to 2008 underwent an on-line survey, developed by the ASCRS Young Surgeons' Committee.
Results About 177 (52%) of 342 graduates surveyed responded. Practice setting data were available for 157 (89%) surgeons. Gender, geographical location and age were similar in both cohorts. PP surgeons utilized a laparoscopic approach more often for rectal cancer (37% vs 19%; P = 0.003). There was no significant difference in the rate of laparoscopic surgery in colon cancer, diverticular disease, inflammatory bowel disease, Clostridium difficile or emergency surgery. PP surgeons operated more often with a partner (43% vs 8%) or surgical assistant (13% vs 4%; both P < 0.001), while UH surgeons had a colorectal resident (10% vs 21%) or general surgery resident (15% vs 55%; both P < 0.001). Impediments to performing laparoscopic surgery for PP surgeons included a perceived lack of hospital equipment (33% vs 20%) and support (29% vs 17%; both P < 0.05). Perception of personal experience, access to trained assistants, financial reimbursement, length of surgery and patient availability were equivalent in both groups.
Conclusion While differences such as type of assistant and impediments to laparoscopic utilization exist between PP-and UH-based practices, early laparoscopic practice patterns remain similar. PP surgeons more frequently perform laparoscopic resection for rectal cancer and with hand-assistance. Despite differences, newly trained colorectal surgeons in both settings utilize and require laparoscopic skills.
C1 [Steele, Scott R.] Madigan Army Med Ctr, Dept Surg, Tacoma, WA 98431 USA.
[Stein, Sharon L.; Champagne, Bradley J.] Case Western Reserve Univ, Dept Surg, Div Colorectal Surg, Cleveland, OH 44106 USA.
[Bordeianou, Liliana G.] Massachusetts Gen Hosp, Dept Surg, Colorectal Surg Program, Boston, MA 02114 USA.
[Johnson, Eric] Dwight D Eisenhower Army Med Ctr, Dept Surg, Div Colorectal Surg, Augusta, GA USA.
[Herzig, Dan O.] Oregon Hlth & Sci Univ, Dept Surg, Div Colorectal Surg, Portland, OR 97201 USA.
RP Steele, SR (reprint author), 9606 Piperhill Dr SE, Olympia, WA 98513 USA.
EM harkersteele@mac.com
NR 31
TC 6
Z9 6
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1462-8910
J9 COLORECTAL DIS
JI Colorectal Dis.
PD MAR
PY 2012
VL 14
IS 3
BP 374
EP 381
DI 10.1111/j.1463-1318.2011.02614.x
PG 8
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 887SE
UT WOS:000299949100029
PM 21689306
ER
PT J
AU Bergen, SE
Petryshen, TL
AF Bergen, Sarah E.
Petryshen, Tracey L.
TI Genome-wide association studies of schizophrenia: does bigger lead to
better results?
SO CURRENT OPINION IN PSYCHIATRY
LA English
DT Review
DE association; genetic; genome-wide association studies; risk gene;
schizophrenia
ID COMMON VARIANTS; MACULAR DEGENERATION; CONFERRING RISK; STEM-CELLS;
GENETICS; SUSCEPTIBILITY; LOCI; PSYCHOSIS; DISEASE; TCF4
AB Purpose of review
Numerous genome-wide association studies (GWAS) of schizophrenia have been published in the past 6 years, with a number of key reports published in the last year. The studies have evolved in scale from small individual samples to large collaborative endeavors. This review aims to critically assess whether the results have improved as the sample size and scale of genetic association studies have grown.
Recent findings
Genomic genotyping and increasing sample sizes for schizophrenia association studies have led to parallel increases in the number of risk genes discovered with high statistical confidence. Nearly 20 genes or loci have surpassed the genome-wide significance threshold (P = 5 x 10(-8)) in a single study, and several have been replicated in more than one GWAS.
Summary
Identifying the genetic underpinnings of complex diseases offers insight into the etiological mechanisms leading to manifestation of the disease. New and more effective treatments for schizophrenia are desperately needed, and the ability to target the relevant biological processes grows with our understanding of the genes involved. As the size of GWAS samples has increased, more genes have been identified with high confidence that have begun to provide insight into the etiological and pathophysiological foundations of this disorder.
C1 [Bergen, Sarah E.; Petryshen, Tracey L.] Harvard Univ, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA.
[Bergen, Sarah E.; Petryshen, Tracey L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA.
[Bergen, Sarah E.; Petryshen, Tracey L.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA.
RP Petryshen, TL (reprint author), Harvard Univ, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Massachusetts Gen Hosp,Med Sch, 185 Cambridge St,6th Floor, Boston, MA 02114 USA.
EM petryshen@chgr.mgh.harvard.edu
RI Bergen, Sarah/I-8313-2012;
OI Bergen, Sarah/0000-0002-5888-0034
FU US National Institutes of Health [MH080272]; Stanley Medical Research
Institute
FX This work was supported by the US National Institutes of Health (grant
MH080272) and the Stanley Medical Research Institute.
NR 52
TC 30
Z9 30
U1 0
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0951-7367
J9 CURR OPIN PSYCHIATR
JI Curr. Opin. Psychiatr.
PD MAR
PY 2012
VL 25
IS 2
BP 76
EP 82
DI 10.1097/YCO.0b013e32835035dd
PG 7
WC Psychiatry
SC Psychiatry
GA 888ZG
UT WOS:000300042700002
PM 22277805
ER
PT J
AU AhnAllen, CG
AF AhnAllen, Christopher G.
TI The role of the alpha 7 nicotinic receptor in cognitive processing of
persons with schizophrenia
SO CURRENT OPINION IN PSYCHIATRY
LA English
DT Review
DE alpha7; cognition; nicotinic agonists; positive allosteric modulators;
schizophrenia
ID ACETYLCHOLINE-RECEPTORS; ENHANCEMENT THERAPY; CIGARETTE-SMOKING; DEFAULT
NETWORK; AGONIST; TROPISETRON; DISEASE; TRIAL; ENDOPHENOTYPES;
ASSOCIATION
AB Purpose of review
Cognitive abilities are established as major deficits in those with schizophrenia and represent significant impediments toward successful psychosocial functioning within the community. Pharmacological treatments have historically focused on reducing the positive and negative symptoms of schizophrenia, with recent increased attention to developing agents to improve cognition as a treatment outcome. This review will highlight the recent advances in developing agents that act at neuronal alpha 7 nicotinic acetylcholine receptors (nAChRs).
Recent findings
A number of agents have demonstrated improvements in cognitive deficits in studies using both preclinical and clinical models. Evidence suggests that alpha 7 nAChR activation impacts rule acquisition and initial learning in preclinical models. Preclinical studies indicate improved spatial working memory and reversal of phencyclidine-induced learning and memory deficits. Clinical studies indicate normalization of neuronal default network activity using functional magnetic resonance imaging methods. In addition, research on new agents developed to improve cognition suggests improved cognitive functioning in multiple domains (e. g., attention, memory, executive functioning, sensory gating and overall cognition) and promising safety profiles of additional agents.
Summary
Improvements in cognitive functioning within preclinical and clinical studies of schizophrenia are evident through the use of alpha 7 nAChR agonists, while positive allosteric modulators may gain increased attention in the future.
C1 [AhnAllen, Christopher G.] VA Boston Healthcare Syst, Inpatient Mental Hlth Serv, Brockton Div, Ward 23B, Brockton, MA 02301 USA.
[AhnAllen, Christopher G.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP AhnAllen, CG (reprint author), VA Boston Healthcare Syst, Inpatient Mental Hlth Serv, Brockton Div, Ward 23B, 940 Belmont St, Brockton, MA 02301 USA.
EM Christopher.AhnAllen@va.gov
NR 49
TC 18
Z9 20
U1 2
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0951-7367
J9 CURR OPIN PSYCHIATR
JI Curr. Opin. Psychiatr.
PD MAR
PY 2012
VL 25
IS 2
BP 103
EP 108
DI 10.1097/YCO.0b013e3283503637
PG 6
WC Psychiatry
SC Psychiatry
GA 888ZG
UT WOS:000300042700006
PM 22262029
ER
PT J
AU Igoillo-Esteve, M
Marselli, L
Cunha, DA
Ladriere, L
Ortis, F
Grieco, FA
Dotta, F
Weir, GC
Marchetti, P
Eizirik, DL
Cnop, M
AF Igoillo-Esteve, M.
Marselli, L.
Cunha, D. A.
Ladriere, L.
Ortis, F.
Grieco, F. A.
Dotta, F.
Weir, G. C.
Marchetti, P.
Eizirik, D. L.
Cnop, M.
TI Palmitate induces a pro-inflammatory response in human pancreatic islets
that mimics CCL2 expression by beta cells in type 2 diabetes (vol 53, pg
1395, 2010)
SO DIABETOLOGIA
LA English
DT Correction
C1 [Igoillo-Esteve, M.; Cunha, D. A.; Ladriere, L.; Ortis, F.; Eizirik, D. L.; Cnop, M.] Univ Libre Bruxelles, Expt Med Lab, B-1070 Brussels, Belgium.
[Marselli, L.; Marchetti, P.] Univ Pisa, Dept Endocrinol & Metab, Metab Unit, Pisa, Italy.
[Grieco, F. A.; Dotta, F.] Univ Siena, Dept Internal Med, I-53100 Siena, Italy.
[Grieco, F. A.; Dotta, F.] Umberto Di Mario Fdn, Siena, Italy.
[Weir, G. C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Cnop, M.] Univ Libre Bruxelles, Erasmus Hosp, Div Endocrinol, B-1070 Brussels, Belgium.
RP Cnop, M (reprint author), Univ Libre Bruxelles, Expt Med Lab, CP-618,Route Lennik 808, B-1070 Brussels, Belgium.
EM mcnop@ulb.ac.be
RI Dotta, Francesco/H-3788-2012; Ortis, Fernanda/K-7917-2014; Marchetti,
Piero/J-7439-2013
OI Marchetti, Piero/0000-0003-4907-0635
NR 1
TC 0
Z9 0
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD MAR
PY 2012
VL 55
IS 3
BP 863
EP 863
DI 10.1007/s00125-011-2389-9
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 887IX
UT WOS:000299921200041
ER
PT J
AU Cullen, G
Bader, C
Korzenik, JR
Sands, BE
AF Cullen, Garret
Bader, Caroline
Korzenik, Joshua R.
Sands, Bruce E.
TI Serological response to the 2009 H1N1 influenza vaccination in patients
with inflammatory bowel disease
SO GUT
LA English
DT Article
ID CROHNS-DISEASE; IMMUNE-RESPONSE; ANTIBODY-RESPONSE; CONTROLLED-TRIAL;
DOUBLE-BLIND; EFFICACY; SAFETY; VIRUS; IMMUNOGENICITY; IMMUNIZATION
AB Background Influenza vaccination is recommended for patients with inflammatory bowel disease (IBD). The 2009 H1N1 influenza vaccine produced seroprotection rates of >85% in the general population but there are no data on the immunogenicity of the vaccine in patients with IBD.
Methods An observational prospective open-label study was conducted to examine the immunogenicity of the 2009 H1N1 influenza vaccine in 108 patients with IBD. Patient details, medications and disease activity were recorded. Pre- and post-vaccination haemagglutinin inhibition titres and geometric mean titres were measured. A functional assay of T lymphocyte activity was measured at vaccination in a subset of patients as an alternative measure of immunosuppression. Subjects were followed for 6 months post-vaccination.
Results Of 108 patients enrolled, 105 completed the study. The post-vaccination seroprotection rate was 50%. Immunosuppressed subjects had a lower rate of seroprotection than non-immunosuppressed subjects (44% vs 64%, p=0.06). The proportion with seroprotection was significantly lower in subjects on combination immunosuppression than in those receiving no immunosuppression (36% vs 64%, p=0.02). Patients receiving combined immunosuppression had a significantly lower fold increase in geometric mean titres than those on monotherapy immunosuppression (3.5 vs 11.5, p=0.03). An assay of T lymphocyte activity was performed in a subgroup of 48 subjects. Those with intermediate activity had lower seroprotection than those with high activity (28% vs 61%, p=0.02). The vaccine was well tolerated.
Conclusions Patients with IBD vaccinated with the 2009 H1N1 influenza vaccine had a low rate of seroprotection, particularly among those who were immunosuppressed. Although there is a need for studies of the clinical benefit of vaccines in this population, patients with IBD need to be aware of this reduced immunogenicity.
C1 [Cullen, Garret; Bader, Caroline; Korzenik, Joshua R.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA.
[Cullen, Garret; Bader, Caroline; Korzenik, Joshua R.] Harvard Univ, Sch Med, Boston, MA USA.
[Sands, Bruce E.] Mt Sinai Sch Med, Dr Henry D Janowitz Div Gastroenterol, New York, NY USA.
RP Cullen, G (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA.
EM gcullen@bidmc.harvard.edu
FU Sanofi Pasteur, USA; Crohn's and Colitis Center; Massachusetts General
Hospital, Boston
FX Sanofi Pasteur, USA provided an educational grant to the Crohn's and
Colitis Center, Massachusetts General Hospital, Boston to part-fund the
cost of the haemagglutinin inhibition assays that were performed at the
Laboratory for Specialized Clinical Studies at Cincinnati Children's
Hospital Medical Center. BES
NR 26
TC 30
Z9 31
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
J9 GUT
JI Gut
PD MAR
PY 2012
VL 61
IS 3
BP 385
EP 391
DI 10.1136/gutjnl-2011-300256
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 889FH
UT WOS:000300058500009
PM 21757451
ER
PT J
AU Lu, XM
Tompkins, RG
Fischman, AJ
AF Lu, X. -M.
Tompkins, R. G.
Fischman, A. J.
TI SILAM for quantitative proteomics of liver Akt1/PKB alpha after burn
injury
SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
LA English
DT Article
DE Akt1/PKB alpha; SILAM; MS/MS; burn injury
ID PROTEIN-KINASE-B/AKT; SKELETAL-MUSCLE DIFFERENTIATION; INSULIN-RECEPTOR
SUBSTRATE-1; S-NITROSYLATED PROTEINS; NITRIC-OXIDE PRODUCTION;
CAPLC-Q-TOFMICRO; MASS-SPECTROMETRY; CRYSTAL-STRUCTURE; THERMAL-INJURY;
STABLE-ISOTOPES
AB Akt1/protein kinase B alpha (Akt1/PKB alpha) is a downstream mediator of the insulin signaling system. In this study we explored mechanism(s) for its role in burn injury. Akt1/PKB alpha in liver extracts from mice with burn injury fed with (H-2(7))-L-Leu was immunoprecipitated and isolated with SDS-PAGE. Two tryptic peptides, one in the kinase loop and a control peptide just outside of the loop were sequenced via nano-LC interfaced with quadruple time-of-flight tandem mass spectrometry (Q-TOF tandem MS). Their relative isotopologue abundances were determined by stable isotope labeling by amino acids in mammalians (SILAM). Relative quantifications based on paired heavy/light peptides were obtained in 3 steps. The first step included homogenization of mixtures of equal amounts of tissue from burned and sham-treated animals (i.e., isotope dilution) and acquisition of uncorrected data based on parent monoisotopic MS ion ratios. The second step included determination of isotopic enrichment of the kinase from burned mice on Day 7 and the third step enrichment correction of partially labeled heavy and light monoisotopic MS ion ratios for relative quantification of bioactivity (loop peptide) and expression level (control peptide). Protein synthesis and enrichment after injury were found to be dependent on tissue and turnover of individual proteins. Three heavy and light monoisotopic ion ratios for albumin peptides from burned mice indicated similar to 55% enrichment and similar to 16.7-fold downregulation. In contract, serum amyloid P had similar to 66% enrichment and was significantly upregulated. Akt1/PKB alpha had similar to 56% enrichment and kinase level in response to the burn injury was upregulated compared with the control peptide. However, kinase bioactivity, represented by the Cys(296) peptide, was significantly reduced. Overall, we demonstrated that i) quantitative proteomics can be performed without completely labeled mice; ii) measurement of enrichment of acyl-tRNAs is unnecessary and iii) Cys(296) plays an important role in kinase activity after burn injury.
C1 [Lu, X. -M.; Tompkins, R. G.; Fischman, A. J.] Shriners Hosp Children, Boston, MA 02114 USA.
[Lu, X. -M.; Tompkins, R. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lu, X. -M.; Tompkins, R. G.; Fischman, A. J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Fischman, AJ (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA.
EM aajjff@gmail.com
FU National Institutes of Health [NIGMS P50 GM21000]; Shriners Hospitals
for Children
FX This study was supported in part by grants from the National Institutes
of Health (NIGMS P50 GM21000) and Shriners Hospitals for Children. We
would like to thank Dr E.A. Carter and Ms. F. Lin for their assistance
with these studies.
NR 63
TC 3
Z9 3
U1 0
U2 5
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1107-3756
J9 INT J MOL MED
JI Int. J. Mol. Med.
PD MAR
PY 2012
VL 29
IS 3
BP 461
EP 471
DI 10.3892/ijmm.2011.861
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 889ZV
UT WOS:000300115800019
PM 22179310
ER
PT J
AU Wang, JI
Hui, P
Zeng, MS
Rabkin, SD
Liu, RB
AF Wang, Jiani
Hui, Pan
Zeng, Musheng
Rabkin, Samuel D.
Liu, Renbin
TI Oncolytic herpes simplex virus treatment of metastatic breast cancer
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE breast cancer; pulmonary metastatic breast cancer; oncolytic herpes
simplex virus; immortalized breast cells; pulmonary metastatic model
ID TERM-FOLLOW-UP; NODE METASTASES; THERAPY; GENE; CARCINOMA; VECTORS;
CELLS; GAMMA-134.5; PROGRESSION; MUTANT
AB The high prevalence and poor prognosis of breast cancer provides a strong rationale for developing new treatment strategies and preventive and therapeutic agents. Oncolytic replication-competent herpes simplex virus (HSV) can infect tumor cells, replicating and killing the cells by direct cytopathic effect and then spreading within the tumor. Replication of oncolytic HSV leads to the destruction of the infected tumor cell and release of new virions, which are able to infect adjacent cells until potentially all tumor cells are destroyed. In this study, the cytotoxicity of a third-generation oncolytic HSV vector, designated G47 Delta, was examined in human breast cancer cell lines, as well as in immortalized and normal breast cells. A pulmonary metastatic model of breast cancer established in Balb/c nude mice was used to evaluate the efficacy of G47 Delta treatment. Systemic treatment by intravenous administration of G47 Delta for metastatic lung tumors was initiated 14 days after injection of tumor cells. On Day 56, the mice were sacrificed and tumor nodules on the surface of the lung were counted. G47 Delta was highly cytotoxic to breast cancer and immortalized breast cells in vitro at low multiplicities of infection (MOI), while normal breast cells remained viable 5 days after infection. In the pulmonary metastatic model, the average number ;of surface lung tumor nodules in the G47 Delta-treated group was approximately 9-fold less than in the control-treated group. X-gal staining illustrated viral replication and spread in the tumor cells in vitro and in vivo. In conclusion, G47 Delta effectively killed human breast cancer cells and immortalized breast cells but not normal breast cells. Systemic administration of G47 Delta by tail vein injection was effective in inhibiting the growth of established breast cancer lung metastases.
C1 [Wang, Jiani; Hui, Pan; Liu, Renbin] Sun Yat Sen Univ, Breast Canc Ctr, Affiliated Hosp 3, Guangzhou 510630, Guangdong, Peoples R China.
[Zeng, Musheng] Sun Yat Sen Univ, Dept Lab Med, Tumor Hosp, Guangzhou 510630, Guangdong, Peoples R China.
[Rabkin, Samuel D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurosurg Lab, Boston, MA USA.
RP Liu, RB (reprint author), Sun Yat Sen Univ, Breast Canc Ctr, Affiliated Hosp 3, 600 Tianhe Rd, Guangzhou 510630, Guangdong, Peoples R China.
EM liur@vip.163.com
RI rabkin, samuel/C-2443-2012
OI rabkin, samuel/0000-0003-2344-2795
FU NSF of China [30672410]; Guangdong Natural Science Foundation [06104599]
FX This study was supported by the NSF of China (30672410) and the
Guangdong Natural Science Foundation (06104599).
NR 27
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U1 0
U2 15
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
J9 INT J ONCOL
JI Int. J. Oncol.
PD MAR
PY 2012
VL 40
IS 3
BP 757
EP 763
DI 10.3892/ijo.2011.1266
PG 7
WC Oncology
SC Oncology
GA 890AT
UT WOS:000300118200017
PM 22108767
ER
PT J
AU Roach, NT
Lieberman, DE
Gill, TJ
Palmer, WE
Gill, TJ
AF Roach, Neil Thomas
Lieberman, Daniel E.
Gill, Thomas J.
Palmer, William E.
Gill, Thomas J., III
TI The effect of humeral torsion on rotational range of motion in the
shoulder and throwing performance
SO JOURNAL OF ANATOMY
LA English
DT Review
DE glenohumeral joint; humeral retroversion; humeral rotation; humeral
torsion; throwing
ID PROFESSIONAL BASEBALL PITCHERS; GLENOHUMERAL INTERNAL-ROTATION; TENNIS
PLAYERS; PITCHING MECHANICS; HEAD RETROVERSION; INJURIES; ATHLETE;
BIOMECHANICS; JOINT; ELBOW
AB Several recent studies have found that throwing athletes typically have lower humeral torsion (retroversion) and a greater range of external rotation at the shoulder than non-athletes. How these two parameters are related is debated. This study uses data from a sample of both throwers and non-throwers to test a new model that predicts torsion values from a range of motion data. The model proposes a series of predicted regressions which can help provide new insight into the factors affecting rotational range of motion at the shoulder. Humeral torsion angles were measured from computed tomography scans collected from 25 male subjects. These values are compared to predicted torsion values for the same subjects calculated from both kinematic and goniometric range-of-motion data. Results show that humeral torsion is negatively correlated (goniometric: r = -0.409, P = 0.047; kinematic: r = -0.442, P = 0.035) with external rotational range of motion and positively correlated (goniometric: r = 0.741, P < 0.001; kinematic: r = 0.559, P = 0.006) with internal rotational range of motion. The predicted torsion values are highly correlated (goniometric: r = 0.815, P < 0.001; kinematic: r = 0.617, P = 0.006) with actual torsion values. Deviations in the data away from predicted equations highlight significant differences between high torsion and low torsion individuals that may have significant functional consequences. The method described here may be useful for non-invasively assessing the degree of torsion in studies of the evolution and biomechanics of the shoulder and arm, and for testing hypotheses about the etiology of repetitive stress injuries among athletes and others who throw frequently.
C1 [Roach, Neil Thomas; Lieberman, Daniel E.] Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA.
[Gill, Thomas J.; Gill, Thomas J., III] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Gill, Thomas J.; Palmer, William E.; Gill, Thomas J., III] Harvard Univ, Sch Med, Boston, MA USA.
[Palmer, William E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Roach, NT (reprint author), Harvard Univ, Dept Human Evolutionary Biol, 11 Div Ave, Cambridge, MA 02138 USA.
EM ntroach@fas.harvard.edu
FU Hintze Family Charitable Trust; American School for Prehistoric
Research; National Science Foundation [BCS 0961943]
FX The authors would like to thank the subjects who volunteered their time,
the staff at the MGH Imaging Service, Michelle Cardillo, Louise Borda
and Isabella Suzarte for their help making this study possible. The
authors would also like to thank the two reviewers for their helpful
comments and criticisms. Generous funding for the Qualisys Oqus camera
system was provided by the Hintze Family Charitable Trust and the
American School for Prehistoric Research. External funding was provided
by the National Science Foundation (BCS 0961943).
NR 60
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U1 0
U2 17
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-8782
J9 J ANAT
JI J. Anat.
PD MAR
PY 2012
VL 220
IS 3
BP 293
EP 301
DI 10.1111/j.1469-7580.2011.01464.x
PG 9
WC Anatomy & Morphology
SC Anatomy & Morphology
GA 889BJ
UT WOS:000300048200008
PM 22257273
ER
PT J
AU Smith, DJ
AF Smith, D. J.
TI Prospects in Caries Vaccine Development
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Editorial Material
DE mucosal immunity; Streptococcus mutans; vaccine(s); adjuvants; dental
caries; DNA vaccines
ID STREPTOCOCCUS-MUTANS; ESCHERICHIA-COLI; IMMUNIZATION; INFECTION
C1 Forsyth Inst, Cambridge, MA 02146 USA.
RP Smith, DJ (reprint author), Forsyth Inst, 245 1st St, Cambridge, MA 02146 USA.
EM dsmith@forsyth.org
NR 12
TC 5
Z9 7
U1 2
U2 16
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 MAR
PY 2012
VL 91
IS 3
BP 225
EP 226
DI 10.1177/0022034511425928
PG 2
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 888HF
UT WOS:000299993800001
PM 22027715
ER
PT J
AU Bleier, BS
Mulligan, RM
Schlosser, RJ
AF Bleier, Benjamin S.
Mulligan, Ryan M.
Schlosser, Rodney J.
TI Primary human sinonasal epithelial cell culture model for topical drug
delivery in patients with chronic rhinosinusitis with nasal polyposis
SO JOURNAL OF PHARMACY AND PHARMACOLOGY
LA English
DT Article
DE chronic rhinosinusitis; in-vitro model; nasal polyposis; primary human
sinonasal epithelial cell culture; topical drug delivery
ID CILIARY BEAT FREQUENCY; IN-VITRO; CHRONIC SINUSITIS; INTERLEUKIN-8;
EXPRESSION; TRANSPORT; BETA
AB Objectives The primary human sinonasal epithelial cell culture (HSNEC) allows for in-vitro modelling of mucosal responses to topical therapy. Cultures grown from healthy donors may underestimate changes in individuals with chronic sinonasal disease thereby yielding inaccurate results with respect to this large patient population. The purpose of this study was to analyse HSNECs derived from patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) to determine whether expected disease dependent variables salient to topical drug delivery persist in culture.
Methods Cultures were grown from patients with CRSwNP. Ciliary beat frequency (CBF) (basal and stimulated), permeability (trans and paracellular), inflammatory response, and glucocorticoid dose response were measured and compared with healthy controls.
Key findings Methylcholine stimulated CBF was greater in CRSwNP versus controls (Delta CBF60min 7.25 +/- 1.02 vs 0.89 +/- 1.04 Hz, respectively). Paracellular permeability was greater in CRSwNP versus controls (basolateral dextran(120min) 18.97 +/- 3.90 vs 11.31 +/- 4.35 mu g/ml, respectively). Lipopolysaccharide (0.1 mg/ml) stimulated interleukin-6 (IL-6) and IL-8 secretion was increased in CRSwNP versus controls (IL-6 Delta baseline 1738.72 +/- 654.82 vs 1461.61 +/- 533.51%, respectively; IL-8 Delta baseline 137.11 +/- 0.83 vs 111.27 +/- 0.67%, respectively). CRSwNP cultures were more sensitive than controls to dexamethasone (1 mu g/ml) dependent IL-6 and IL-8 suppression.
Conclusions HSNECs derived from patients with CRSwNP retained their primary phenotype with respect to ciliary function, epithelial permeability, irritant induced inflammatory cytokine secretion, and glucocorticoid dose response.
C1 [Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Mulligan, Ryan M.; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA.
RP Bleier, BS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA.
EM bleierb@gmail.com
FU Flight Attendant Medical Research Institute
FX These studies were supported by grants to Rodney J. Schlosser from the
Flight Attendant Medical Research Institute.
NR 19
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Z9 8
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3573
J9 J PHARM PHARMACOL
JI J. Pharm. Pharmacol.
PD MAR
PY 2012
VL 64
IS 3
BP 449
EP 456
DI 10.1111/j.2042-7158.2011.01409.x
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 886XW
UT WOS:000299889100016
PM 22309277
ER
PT J
AU Psaros, C
Kagan, L
Auba, E
Alert, M
Park, ER
AF Psaros, Christina
Kagan, Leslee
Auba, Enrique
Alert, Marissa
Park, Elyse R.
TI A brief report of depressive symptoms and health promoting behaviors
among women with infertility attending a clinical mind-body program
SO JOURNAL OF PSYCHOSOMATIC OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE Mind-body influences; consequences of infertility; depression;
infertility; mental health
ID IN-VITRO FERTILIZATION; PSYCHOLOGICAL INTERVENTIONS; GENERAL-POPULATION;
MENTAL-HEALTH; COUPLES; DISORDERS; ANXIETY; STYLE; CARE; PREVALENCE
AB Diagnosis of infertility or treatment for infertility can result in distress, including for some women, depressive symptoms. Integrative infertility treatment programs are gaining recognition and popularity, and many women may seek this kind of care. However, depressive symptoms may be a barrier to fully engaging in and benefiting from mind-body infertility programs. The aim of this retrospective, cross-sectional chart review, was to describe the baseline level of depressive symptoms and differences in baseline health promoting behaviors by level of depressive symptoms among women (n = 104) presenting to a mind-body infertility program in the clinical setting. Depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II), and health promoting behaviors were assessed using the Health Promoting Lifestyle Profile-II (HPLP-II). The mean BDI-II score for the sample was 16.3 (+/- 8.5). Participants scoring in the moderate-severe range on the BDI-II had significantly lower scores on Spiritual Growth, Interpersonal Relations, Stress Management and Nutrition subscales of the HPLP-II. There were no significant differences on the Physical Activity or Health Responsibility subscales. These findings may have implications for the treatment of women with infertility, particularly those who seek an integrative approach to treatment.
C1 [Psaros, Christina; Park, Elyse R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Kagan, Leslee; Alert, Marissa] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA.
[Auba, Enrique] Univ Navarra, Sch Med, Dept Psychiat & Med Psychol, E-31080 Pamplona, Spain.
[Park, Elyse R.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
RP Psaros, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM cpsaros@partners.org
FU Centers for Disease Control, Atlanta, GA [5R01DP00039]
FX This publication resulted (in part) from Centers for Disease Control,
Atlanta, GA [Grant #5R01DP00039].
NR 31
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U1 1
U2 8
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0167-482X
J9 J PSYCHOSOM OBST GYN
JI J. Psychosomat. Obstet. Gynecol.
PD MAR
PY 2012
VL 33
IS 1
BP 32
EP 36
DI 10.3109/0167482X.2011.643933
PG 5
WC Psychology, Clinical; Obstetrics & Gynecology; Psychiatry
SC Psychology; Obstetrics & Gynecology; Psychiatry
GA 887AM
UT WOS:000299897500005
PM 22214290
ER
PT J
AU Larauche, M
AF Larauche, M.
TI Novel insights in the role of peripheral corticotropin-releasing factor
and mast cells in stress-induced visceral hypersensitivity
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Article
DE mast cells; peripheral corticotropin releasing factor; stress-induced
visceral hypersensitivity
ID IRRITABLE-BOWEL-SYNDROME; COLONIC EPITHELIAL BARRIER; FACTOR SIGNALING
PATHWAYS; LIGHT-CHAIN KINASE; PSYCHOLOGICAL STRESS;
MATERNAL-DEPRIVATION; IBS PATIENTS; GASTROINTESTINAL-TRACT; RECTAL
DISTENSION; PROTEASE ACTIVITY
AB Visceral hypersensitivity is one of the hallmarks in irritable bowel syndrome (IBS) pathophysiology. Stress is well known to affect visceral sensitivity in humans and rodents, an effect which is associated in part with alterations of intestinal epithelial permeability in rodents. Although the pathophysiology of visceral hypersensitivity is still unclear, two key factors have been identified as playing a major role in its modulation, namely peripheral corticotropin-releasing factor (CRF) and mast cells. In a recent study in Neurogastroenterology and Motility, van den Wijngaard etal. demonstrate that the mast-cell dependent visceral hypersensitivity observed in maternally separated rats after an acute exposure to a psychological stress can be prevented but not reversed by the peripherally restricted CRF receptor antagonist, a-helical CRF941. They further show that the preventive effect of the CRF receptor antagonist is linked to a stabilization of mast cells and maintenance of the epithelial barrier at the colonic level. These data suggest that post stress mast cell activation and subsequent visceral hypersensitivity are not targeted by peripheral CRF receptor antagonists. These novel insights in the role of peripheral CRF in the modulation of stress-induced visceral hypersensitivity add to our growing understanding of the mechanisms that may lie at the origin of visceral pain disturbances following stress and will contribute to enhance the development of drugs that may have potential therapeutic benefits for IBS patients.
C1 [Larauche, M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Oppenheimer Family Ctr Neurobiol Stress,Dept Med, Los Angeles, CA 90073 USA.
[Larauche, M.] VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA USA.
RP Larauche, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Oppenheimer Family Ctr Neurobiol Stress,Dept Med, Los Angeles, CA 90073 USA.
EM mlarauche@mednet.ucla.edu
OI Larauche, Muriel/0000-0003-3320-3675
NR 53
TC 15
Z9 17
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1350-1925
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD MAR
PY 2012
VL 24
IS 3
BP 201
EP 205
DI 10.1111/j.1365-2982.2011.01867.x
PG 5
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 888JX
UT WOS:000300000900006
PM 22316289
ER
PT J
AU Giuliari, GP
Sadaka, A
AF Paolo Giuliari, Gian
Sadaka, Ama
TI Uveal metastatic disease: Current and new treatment options (Review)
SO ONCOLOGY REPORTS
LA English
DT Article
DE ocular malignancy; uveal metastasis; choroidal metastasis; ocular
masquerade syndrome; vascular endothelial growth factor; bevacizumab
ID CHOROIDAL METASTASIS; BREAST-CARCINOMA; INTRAVITREAL BEVACIZUMAB;
COMPLETE REGRESSION; TUMOR METASTASIS; LUNG-CANCER; FOLLOW-UP; EYE;
RADIOTHERAPY; SECONDARY
AB Choroidal metastasis represents the most common form of intraocular malignancies. It may occur in up to 10% of patients with systemic metastasis with almost half of the patients developing central nervous system disease. The most common primary sites of ocular metastasis are breast cancer in women and lung cancer in men. In most cases, these lesions tend to be asymptomatic and are not evaluated by an ophthalmologist. The diagnosis is generally made by the history of present or prior malignancies and an ophthalmological examination with slit-lamp biomicroscopy and indirect ophthalmoscopy. As with other malignancies, management may vary with each patient. Small tumors, that do not compromise the vision and that have responded previously to systemic treatment, may be closely observed. For larger lesions and for symptomatic ones, external beam radiation offers an excellent alternative to save the eye and stabilize vision. Bevacizumab (Avastin), a potent monoclonal antibody that has also been employed for the treatment of ocular vaso-proliferative diseases, has been used in the treatment of choroidal metastasis and has shown promising results.
C1 [Paolo Giuliari, Gian] Ctr Cirugia Oftalmol CECOF, Caracas, Venezuela.
[Paolo Giuliari, Gian] Domingo Luciani Hosp, Dept Ophthalmol, Caracas, Venezuela.
[Sadaka, Ama] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
RP Giuliari, GP (reprint author), Ctr Cirugia Oftalmol CECOF, Av Francisco de Miranda,Torre Cavendes,Piso 6,Ofi, Caracas, Venezuela.
EM gpgiuliari@gmail.com
NR 58
TC 5
Z9 5
U1 0
U2 2
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1021-335X
J9 ONCOL REP
JI Oncol. Rep.
PD MAR
PY 2012
VL 27
IS 3
BP 603
EP 607
DI 10.3892/or.2011.1563
PG 5
WC Oncology
SC Oncology
GA 890AY
UT WOS:000300118700001
PM 22134585
ER
PT J
AU Biederman, J
Spencer, T
Lomedico, A
Day, H
Petty, CR
Faraone, SV
AF Biederman, J.
Spencer, T.
Lomedico, A.
Day, H.
Petty, C. R.
Faraone, S. V.
TI Deficient emotional self-regulation and pediatric attention deficit
hyperactivity disorder: a family risk analysis
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE ADHD; deficient emotional self-regulation; pediatric
ID CHILD-BEHAVIOR CHECKLIST; BIPOLAR DISORDER; ADHD; CBCL; DIAGNOSES;
PREDICTS; ADULTS
AB Background. Although deficient emotional self-regulation (DESR) is associated with attention deficit hyperactivity disorder (ADHD), little research investigates this association and little is known about its etiology. Family studies provide a method of clarifying the co-occurrence of clinical features, but no family studies have yet addressed ADHD and DESR in children.
Method. Subjects were 242 children with ADHD and 224 children without ADHD. DESR was operationalized using an aggregate score >= 180 and <210 in the anxious/depressed, attention and aggression scales (AAA profile) of the Child Behavior Checklist (CBCL), termed the CBCL-DESR profile. The CBCL-bipolar (CBCL-BP) profile was defined as >= 210 on the CBCL-AAA scale. We examined the familial transmission of ADHD and the CBCL-AAA scale in families selected through probands with and without these conditions.
Results. We found a linear increase in the prevalence of CBCL-DESR in siblings as indexed by the Control, ADHD, ADHD + CBCL-DESR and ADHD + CBCL-BP proband groups. While the ADHD siblings were at elevated risk for both the CBCL-DESR and CBCL-BP compared with non-ADHD siblings, a significantly higher rate of CBCL-BP in the siblings of ADHD + CBCL-BP probands was found compared with siblings of the Control probands.
Conclusions. ADHD shows the same degree of familial transmission in the presence or absence of DESR. CBCL-DESR and CBCL-BP are familial, but further work is needed to determine if these definitions are distinctly familial or represent a continuum of the same psychopathology.
C1 [Biederman, J.; Spencer, T.; Lomedico, A.; Day, H.; Petty, C. R.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA.
[Biederman, J.; Spencer, T.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA.
[Faraone, S. V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
[Faraone, S. V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA.
RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, YAW-6A-6900,32 Fruit St, Boston, MA 02114 USA.
EM jbiederman@partners.org
OI Faraone, Stephen/0000-0002-9217-3982
FU Shire Pharmaceuticals; Elminda; Janssen; McNeil; Next Wave
Pharmaceuticals; Shire; Fundacion Dr Manuel; Cipher Pharmaceuticals
Inc.; Fundacion Areces; Medice Pharmaceuticals; Spanish Child Psychiatry
Association; Abbott; Alza; Bristol-Myers Squibb; Celltech; Cephalon; Eli
Lilly and Co.; Esai; Forest; Glaxo; Gliatech; Merck; NARSAD; NIDA; New
River; NICHD; NIMH; Novartis; Noven; Neurosearch; Organon; Otsuka;
Pfizer; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma,
Inc.; Wyeth; Shire Laboratories, Inc; Eli Lilly Company;
GlaxoSmithKline; Janssen Pharmaceutical; McNeil Pharmaceutical; Novartis
Pharmaceuticals; National Institute of Mental Health; National
Institutes of Health (NIH); Guilford Press
FX Shire Pharmaceuticals provided support for this analysis.; Dr J.
Biederman is currently receiving research support from the following
sources: Elminda, Janssen, McNeil, Next Wave Pharmaceuticals and Shire.
In 2011, Dr Biederman gave a single unpaid talk for Juste Pharmaceutical
Spain, and received honoraria from the MGH Psychiatry Academy for a
tuition-funded CME course. He also received an honorarium from Cambridge
University Press for a chapter publication. In 2010, Dr Biederman
received a speaker's fee from Fundacion Dr Manuel Camelo A. C., provided
single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals
Inc. and received honoraria from the MGH Psychiatry Academy for a
tuition-funded CME course. In 2009, Dr Biederman received a speaker's
fee from the following sources: Fundacion Areces, Medice Pharmaceuticals
and the Spanish Child Psychiatry Association. In previous years, Dr
Biederman received research support, consultation fees or speaker's fees
for/from the following additional sources: Abbott, Alza, AstraZeneca,
Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai,
Forest, Glaxo, Gliatech, Janssen, McNeil, Merck, NARSAD, NIDA, New
River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka,
Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley
Foundation, UCB Pharma, Inc. and Wyeth.; Dr T. Spencer has received
research support from, has been a speaker for or on a speaker's bureau
or has been an Advisor or on an Advisory Board of the following sources:
Shire Laboratories, Inc, Eli Lilly & Company, GlaxoSmithKline, Janssen
Pharmaceutical, McNeil Pharmaceutical, Novartis Pharmaceuticals,
Cephalon, Pfizer, the National Institute of Mental Health and royalties
on adult ADHD scales (research support).; In the past year, Dr Faraone
received consulting fees and was on Advisory Boards for Shire
Development and received research support from Shire and the National
Institutes of Health (NIH). In previous years, he received consulting
fees or was on Advisory Boards or participated in continuing medical
education programs sponsored by: Shire, McNeil, Janssen, Novartis,
Pfizer and Eli Lilly. In previous years he received research support
from Eli Lilly, Shire, Pfizer and the NIH. Dr Faraone receives royalties
from a book published by Guilford Press: Straight Talk about Your
Child's Mental Health.
NR 26
TC 22
Z9 24
U1 1
U2 16
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 MAR
PY 2012
VL 42
IS 3
BP 639
EP 646
DI 10.1017/S0033291711001644
PG 8
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 886XC
UT WOS:000299886500017
PM 21861953
ER
PT J
AU Seker, E
Berdichevsky, Y
Staley, KJ
Yarmush, ML
AF Seker, Erkin
Berdichevsky, Yevgeny
Staley, Kevin J.
Yarmush, Martin L.
TI Microfabrication-Compatible Nanoporous Gold Foams as Biomaterials for
Drug Delivery
SO ADVANCED HEALTHCARE MATERIALS
LA English
DT Article
ID MECHANICAL-PROPERTIES; SIGNALS; ARRAYS
C1 [Seker, Erkin] Univ Calif Davis, Dept Elect & Comp Engn, Livermore, CA 95616 USA.
[Seker, Erkin; Yarmush, Martin L.] Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA 02114 USA.
[Seker, Erkin; Yarmush, Martin L.] Massachusetts Gen Hosp, Shriners Hosp Children, Boston, MA 02114 USA.
[Berdichevsky, Yevgeny; Staley, Kevin J.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA.
[Berdichevsky, Yevgeny; Staley, Kevin J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA.
RP Seker, E (reprint author), Univ Calif Davis, Dept Elect & Comp Engn, Livermore, CA 95616 USA.
EM eseker@ucdavis.edu
OI Seker, Erkin/0000-0003-2401-3562
FU Massachusetts General Hospital (MGH) Fund for Medical Discovery award
[217035]; University of California, Davis-College of Engineering;
National Institutes of Health (NIH) [AI063795, EB002503]
FX ES acknowledges support by Massachusetts General Hospital (MGH) Fund for
Medical Discovery award 217035, facilities at Harvard University-Center
for Nanoscale Systems, and start-up funds from University of California,
Davis-College of Engineering. MLY acknowledges support by National
Institutes of Health (NIH) awards AI063795 and EB002503. We acknowledge
the help of Dr. Gavrielle Price (MGH) with endothelial cell culture, Dr.
Hansang Cho (MGH) with microglia culture, and Dr. Eloise Hudry (MGH)
with cortical neuron culture.
NR 22
TC 15
Z9 15
U1 0
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2192-2640
J9 ADV HEALTHC MATER
JI Adv. Healthc. Mater.
PD MAR
PY 2012
VL 1
IS 2
BP 172
EP 176
DI 10.1002/adhm.201200002
PG 5
WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials
Science, Biomaterials
SC Engineering; Science & Technology - Other Topics; Materials Science
GA 092HN
UT WOS:000315111100006
PM 23184720
ER
PT J
AU Benson, A
Maust, DT
Tanh, D
Mavandadi, S
Streim, JE
DiFilippo, S
Oslin, D
AF Benson, Amy
Maust, Donovan T.
Tanh, Daniel
Mavandadi, Shahrzad
Streim, Joel E.
DiFilippo, Suzanne
Oslin, David
TI Self-reported Reasons for New Psychotropic Medications in Asymptomatic
Older Adults
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Benson, Amy; Maust, Donovan T.; Tanh, Daniel; Mavandadi, Shahrzad; Streim, Joel E.; DiFilippo, Suzanne; Oslin, David] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Mavandadi, Shahrzad; Streim, Joel E.; DiFilippo, Suzanne; Oslin, David] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN4, Philadelphia, PA USA.
FU Pennsylvania Department of Aging, PACE Program
FX This research was funded by: Funded by the Pennsylvania Department of
Aging, PACE Program.
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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA EI 48
BP S95
EP S95
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500098
ER
PT J
AU Cohen, CI
Kasckow, J
Vahia, I
Jeste, DV
AF Cohen, Carl I.
Kasckow, John
Vahia, Ipsit
Jeste, Dilip V.
TI NEW RESEARCH ADVANCES IN LATE LIFE SCHIZOPHRENIA
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Kasckow, John] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA.
[Kasckow, John] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Cohen, Carl I.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Vahia, Ipsit; Jeste, Dilip V.] Univ Calif San Diego, San Diego, CA USA.
FU Astra Zeneca
FX John Kasckow, MD, PhD; Research Support: Astra Zeneca
NR 0
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U1 0
U2 0
PU ELSEVIER SCIENCE INC
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PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA 307
BP S31
EP S31
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500031
ER
PT J
AU Kasckow, J
Golshan, S
Zisook, S
AF Kasckow, John
Golshan, Shahrokh
Zisook, Sidney
TI Subsyndromal Depressive Symptoms in Middle Aged and Older Patients with
Schizophrenia: Relationship to Suicidal Ideation
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Kasckow, John] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA.
[Kasckow, John] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Golshan, Shahrokh; Zisook, Sidney] Univ Calif San Diego, San Diego, CA 92103 USA.
FU VISN 4; 22 MIRECC; [MH6398]
FX This research was funded by: Supported by MH6398 (SZ, JWK), the VISN 4
and 22 MIRECC. The contents do not represent the views of the Dept of
Veterans Affairs of the US government.
NR 0
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PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA NR 1
BP S121
EP S121
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500126
ER
PT J
AU Maust, DT
Benson, A
Mavandadi, S
Streim, JE
Glasenberg, J
DiFilippo, S
Oslin, D
AF Maust, Donovan T.
Benson, Amy
Mavandadi, Shahrzad
Streim, Joel E.
Glasenberg, Jenna
DiFilippo, Suzanne
Oslin, David
TI Who Gets Prescribed Antipsychotic Monotherapy versus Combination Therapy
with an Antidepressant in a Community Sample of Older Persons?
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Maust, Donovan T.; Benson, Amy; Mavandadi, Shahrzad; Streim, Joel E.; Glasenberg, Jenna; DiFilippo, Suzanne; Oslin, David] Univ Penn, Philadelphia, PA 19104 USA.
[Mavandadi, Shahrzad; Streim, Joel E.; DiFilippo, Suzanne; Oslin, David] Philadelphia VA Med Ctr, Philadelphia, PA USA.
FU PACE Program, Pennsylvania Department of Aging, Harrisburg, PA
FX This research was funded by: PACE Program, Pennsylvania Department of
Aging, Harrisburg, PA.
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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA EI 49
BP S96
EP S97
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500099
ER
PT J
AU Mavandadi, S
Benson, A
Tanh, D
DiFilippo, S
Streim, JE
Oslin, D
AF Mavandadi, Shahrzad
Benson, Amy
Tanh, Daniel
DiFilippo, Suzanne
Streim, Joel E.
Oslin, David
TI The Association between Caregiver Burden and Neuropsychiatric Symptom
Severity among Community-Dwelling Older Adults with Dementia
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
C1 [Mavandadi, Shahrzad; DiFilippo, Suzanne; Streim, Joel E.; Oslin, David] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Mavandadi, Shahrzad; Benson, Amy; Tanh, Daniel; DiFilippo, Suzanne; Streim, Joel E.; Oslin, David] Univ Penn, Philadelphia, PA 19104 USA.
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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA NR 27
BP S142
EP S143
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500152
ER
PT J
AU Melrose, RJ
Harwood, DG
Khoo, T
Mandelkern, MA
Sultzer, D
AF Melrose, Rebecca J.
Harwood, Dylan G.
Khoo, Theresa
Mandelkern, Mark A.
Sultzer, David
TI The association between regional cerebral metabolism and
visuoconstructive skills in probable Alzheimer's Disease
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Melrose, Rebecca J.; Harwood, Dylan G.; Khoo, Theresa; Sultzer, David] VA Greater Los Angeles Healthcare Syst, Brain Behav & Aging Res Ctr, Los Angeles, CA USA.
[Melrose, Rebecca J.; Harwood, Dylan G.; Sultzer, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Mandelkern, Mark A.] VA Greater Los Angeles Healthcare Syst, Nucl Med Serv, Los Angeles, CA USA.
[Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA.
FU Dept. of Veterans Affairs
FX This research was funded by: Supported by the Dept. of Veterans Affairs
(Career Development Award to R. Melrose; Office of R&D Merit Review)
NR 0
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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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA EI 39
BP S88
EP S89
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500089
ER
PT J
AU Metti, AL
Cauley, JA
Newman, AB
Ayonayon, H
Barry, LC
Kuller, LM
Satterfield, S
Simonsick, EM
Yaffe, K
AF Metti, Andrea L.
Cauley, Jane A.
Newman, Anne B.
Ayonayon, Hilsa
Barry, Lisa C.
Kuller, Lewis M.
Satterfield, Suzanne
Simonsick, Eleanor M.
Yaffe, Kristine
TI Plasma Beta Amyloid Level and Depression in Older Adults
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Metti, Andrea L.; Cauley, Jane A.; Newman, Anne B.; Kuller, Lewis M.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Ayonayon, Hilsa; Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Barry, Lisa C.] Yale Univ, Sch Med, New Haven, CT USA.
[Satterfield, Suzanne] Univ Tennessee Memphis, Memphis, TN USA.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
FU National Institute of Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; NIA [R01-AG028050, 2T32AG000181]; NINR [R01-NR012459];
Intramural Research Program on the NIH, National Institute of Aging
FX This research was funded by: This research was supported by National
Institute of Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103;
N01-AG-6-2106; NIA grant R01-AG028050, and NINR grant R01-NR012459. This
research was supported in part by the Intramural Research Program on the
NIH, National Institute of Aging. Andrea Metti is supported by NIA
Training Grant 2T32AG000181.
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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA EI 66
BP S109
EP S110
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500114
ER
PT J
AU Murray, PS
Kirkwood, CM
Gray, MC
Ikonomovic, MD
Paljug, WR
Abrahamson, EE
Hamilton, RL
Kofler, JK
Klunk, WE
Lopez, OL
Penzes, P
Sweet, RA
AF Murray, Patrick S.
Kirkwood, Caitlin M.
Gray, Megan C.
Ikonomovic, Milos D.
Paljug, William R.
Abrahamson, Eric E.
Hamilton, Ronald L.
Kofler, Julia K.
Klunk, William E.
Lopez, Oscar L.
Penzes, Peter
Sweet, Robert A.
TI Increased ratio of beta-amyloid 42/40 and reduced Kalirin expression in
prefrontal cortex in Alzheimer disease with psychosis
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Murray, Patrick S.; Ikonomovic, Milos D.; Paljug, William R.; Abrahamson, Eric E.; Hamilton, Ronald L.; Kofler, Julia K.; Klunk, William E.; Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Kirkwood, Caitlin M.; Gray, Megan C.] Univ Pittsburgh, Pittsburgh, PA USA.
[Murray, Patrick S.; Sweet, Robert A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Penzes, Peter] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
FU Veterans Health Administration [5I01BX000452]; National Institute on
Aging [5P50AG005133, 5R01AG027224]; National Institute of Mental Health
[5T32MH019986]
FX This research was funded by: Supported by Grants 5I01BX000452 from the
Veterans Health Administration and by 5P50AG005133 and 5R01AG027224 from
the National Institute on Aging. Patrick Murray is supported by
5T32MH019986 from the National Institute of Mental Health.
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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA EI 40
BP S89
EP S90
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500090
ER
PT J
AU Okereke, O
Hoang, T
Qiu, W
Byers, AL
AF Okereke, Olivia
Hoang, Tina
Qiu, Wendy (Wei Qiao)
Byers, Amy L.
TI LIFESTYLE FACTORS AND TRAJECTORIES OF LATE-LIFE MENTAL HEALTH
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Okereke, Olivia] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA.
[Byers, Amy L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hoang, Tina; Byers, Amy L.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Qiu, Wendy (Wei Qiao)] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Okereke, Olivia] Harvard Sch Publ Hlth, Boston, MA USA.
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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA 320
BP S39
EP S39
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500042
ER
PT J
AU Park, M
Huang, DL
AF Park, Mijung
Huang, Deborah L.
TI More Variety In Sources of Social Support is Better for Late-Life
Depression Outcome
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Park, Mijung; Huang, Deborah L.] Univ Washington, Seattle, WA 98195 USA.
[Huang, Deborah L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
FU Geriatric Mental Health Research Fellowship [NIMH 2 T32 MH 73553-6]; VA
Advanced Fellowship in Geriatrics, VA Puget Sound Health Care System,
Seattle, Washington
FX This research was funded by: Dr. Park is supported by Geriatric Mental
Health Research Fellowship (NIMH 2 T32 MH 73553-6). Dr. Huang is
supported by VA Advanced Fellowship in Geriatrics, VA Puget Sound Health
Care System, Seattle, Washington.
NR 0
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U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA EI 13
BP S68
EP S69
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500063
ER
PT J
AU Ravven, S
Bader, C
Azar, AR
Rudolph, JL
AF Ravven, Simha
Bader, Caroline
Azar, Armin R.
Rudolph, James L.
TI Depression after CABG Surgery: A Meta-analysis
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Ravven, Simha] Harvard Med Sch, Cambridge Hlth Alliance, Cambridge, MA USA.
[Bader, Caroline] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Azar, Armin R.] Povidence VA Med Ctr, Geriatr & Extended Care, Providence, RI USA.
[Rudolph, James L.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA.
FU VA Rehabilitation Career Development Award; American Federation for
Aging Research; Boston MSTAR; NIH [AG038027-01]; Harvard Medical School
Kaplan Depression Fellowship
FX This research was funded by: Dr. Rudolph is funded by a VA
Rehabilitation Career Development Award. Ms Bader and Dr. Rudolph
received support provided by the American Federation for Aging Research,
the Boston MSTAR, and NIH grants (AG038027-01). Dr Azara(sic)(TM) S
effort was supported by a Harvard Medical School Kaplan Depression
Fellowship. The authors retained full independence in the conduct of
this work.
NR 0
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U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA EI 32
BP S84
EP S84
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500082
ER
PT J
AU Streim, JE
DiFilippo, S
TenHave, T
Mavandadi, S
Weintraub, D
Oslin, D
AF Streim, Joel E.
DiFilippo, Suzanne
TenHave, Thomas
Mavandadi, Shahrzad
Weintraub, Daniel
Oslin, David
TI Antidepressant Discontinuation Associated with Cognitive Decline in
Older Adult Residents of Long-term Care Facilities
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
C1 [Streim, Joel E.; DiFilippo, Suzanne; Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA.
[TenHave, Thomas] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Streim, Joel E.; DiFilippo, Suzanne; Mavandadi, Shahrzad; Weintraub, Daniel; Oslin, David] Dept Vet Affairs Med Ctr, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Philadelphia, PA 19104 USA.
[Oslin, David] Univ Penn, Dept Psychiat, Perelman Sch Med, Treatment Res Ctr, Philadelphia, PA 19104 USA.
FU National Institute for Mental Health [R01 MH051247-13]; Department of
Veterans Affairs (VA) VISN 4 Mental Illness Research Education and
Clinical Center (MIRECC)
FX This research was funded by: This work was supported by the National
Institute for Mental Health (grant no. R01 MH051247-13) and partially
supported by the Department of Veterans Affairs (VA) VISN 4 Mental
Illness Research Education and Clinical Center (MIRECC)
NR 0
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PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
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PD MAR
PY 2012
VL 20
IS 3
SU 1
MA NR 34
BP S147
EP S148
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500159
ER
PT J
AU Sultzer, D
Leskin, LS
Melrose, RJ
Harwood, DG
Narvaez, T
Ando, T
Walston, A
Bussel, N
Mandelkern, MA
AF Sultzer, David
Leskin, Lorraine S.
Melrose, Rebecca J.
Harwood, Dylan G.
Narvaez, Theresa
Ando, Timothy
Walston, Amy
Bussel, Natalya
Mandelkern, Mark A.
TI Delusions, memory, and insight in Alzheimer's disease: clinical
associations and relationships with FDG-PET cortical metabolic activity
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
C1 [Sultzer, David; Leskin, Lorraine S.; Melrose, Rebecca J.; Harwood, Dylan G.; Narvaez, Theresa; Ando, Timothy; Walston, Amy; Bussel, Natalya; Mandelkern, Mark A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Sultzer, David; Melrose, Rebecca J.; Harwood, Dylan G.; Walston, Amy] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA USA.
[Mandelkern, Mark A.] UC Irvine, Dept Phys, Irvine, CA USA.
FU NIMH; Department of Veterans Affairs
FX This research was funded by: Supported in part by the NIMH and the
Department of Veterans Affairs
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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA NR 25
BP S140
EP S141
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500150
ER
PT J
AU Valdez, K
Brown, GK
Johnson, JC
Oslin, D
AF Valdez, Karen
Brown, Gregory K.
Johnson, Jerry C.
Oslin, David
TI Comparison of Two Screening Instruments in the Detection of Suicidal
Ideation in Older Primary Care Veterans: Paykel Questionnaire and
Patient Health Questionnaire-9
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Valdez, Karen; Brown, Gregory K.; Oslin, David] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Johnson, Jerry C.] Univ Penn, Dept Geriatr Med, Philadelphia, PA 19104 USA.
[Oslin, David] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Oslin, David] VISN 4 Mental Illness Res Educ & Clin Ctr MIRECC, Philadelphia, PA USA.
FU Philadelphia Veterans Affairs Medical Center; VISN 4 Mental Illness
Research, Education, and Clinical Center (MIRECC)
FX This research was funded by: Poster funding by Philadelphia Veterans
Affairs Medical Center and the VISN 4 Mental Illness Research,
Education, and Clinical Center (MIRECC)
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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA EI 16
BP S70
EP S71
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500066
ER
PT J
AU Wang, S
Luo, XD
Barnes, D
Sano, M
Yaffe, K
AF Wang, Sophia
Luo, Xiaodong
Barnes, Deborah
Sano, Mary
Yaffe, Kristine
TI The Effects of Late Life Physical Activity on Cognition over 20 Years in
Oldest Old Women
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Wang, Sophia; Sano, Mary] James J Peters VA, Bronx, NY USA.
[Wang, Sophia; Luo, Xiaodong; Sano, Mary] Mt Sinai Sch Med, New York, NY USA.
[Barnes, Deborah; Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Barnes, Deborah; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
FU NIA; Alzheimer's Association; University of California, San Francisco,
School of Medicine; NIA [K24 AG 031155]; National Institutes of Health
[AG05407, AR35582, AG05394, AR35584, AR35583, R01 AG005407, R01
AG027576-22, 2 R01 AG005394-22A1, 2 R01 AG027574-22A1, 5 R01AG026720-04]
FX This research was funded by: SW is a VA Neurosciences Research Fellow.
XL is supported by a NIA funded ADRC grant. DB is supported by the
Alzheimer's Association and the University of California, San Francisco,
School of Medicine. MS is supported by a NIA funded ADRC grant and CTSA
grant. KY is supported by a NIA grant K24 AG 031155 and an Independent
Investigator Award from the Alzheimer's Association. The Study of
Osteoporotic Fractures (SOF) and the SOF-WISE are supported by grants
AG05407, AR35582, AG05394, AR35584, AR35583, R01 AG005407, R01
AG027576-22, 2 R01 AG005394-22A1, 2 R01 AG027574-22A1, and 5
R01AG026720-04 from the National Institutes of Health.
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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA EI 69
BP S112
EP S112
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500117
ER
PT J
AU Wu, P
Read, S
Biscow, M
AF Wu, Pauline
Read, Stephen
Biscow, Mark
TI Sustained Cognitive Benefit in Mild Alzheimer's Disease with
Pioglitazone - Case Report of a 4.5 Year Treatment Trial
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of American-Association-for-Geriatric-Psychiatry
CY MAR 16-19, 2012
CL Washington, DC
C1 [Wu, Pauline; Read, Stephen] Univ Calif Los Angeles, Los Angeles, CA USA.
[Wu, Pauline; Read, Stephen] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Biscow, Mark] St Johns Hlth Ctr, Santa Monica, CA USA.
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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2012
VL 20
IS 3
SU 1
MA EI 41
BP S90
EP S90
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA V45WK
UT WOS:000209846500091
ER
PT J
AU Serrano, NA
Trenite, GN
Yueh, B
Farwell, G
Futran, ND
Mendez, E
AF Serrano, Nicholas A.
Trenite, Gilean N.
Yueh, Bevan
Farwell, Gregory
Futran, Neal D.
Mendez, Eduardo
TI Risk Factors Associated With Repair of Orbital and Lateral Skull Defects
SO ARCHIVES OF FACIAL PLASTIC SURGERY
LA English
DT Article
ID FREE-FLAP RECONSTRUCTION; MYOCUTANEOUS FREE-FLAP; FREE-TISSUE TRANSFER;
MICROVASCULAR RECONSTRUCTION; CLASSIFICATION-SYSTEM; BASE
RECONSTRUCTION; MIDFACIAL DEFECTS; EXENTERATION; NECK; HEAD
AB Objective: To explore the complications and associated risks factors after orbital exenteration and lateral skull base defect repair.
Methods: Patients who had undergone a reconstruction of their orbital cavity and lateral skull base defects were selected from our departmental database. The outcome of interest was postoperative complications. The risks factors were defined as age, sex, history of radiation therapy, and intracranial involvement (with and without dural involvement). Information was collected on the type of reconstruction used after the orbital cavity repair. The chi(2) test and logistic regression were used to analyze associations between postoperative complications and the various risks factors.
Results: Of the 32 identified patients, 19 had intracranial involvement (9 with dural involvement). Twenty-four patients underwent reconstruction with free tissue transfer in the same setting. Reconstruction with free tissue transfer was significantly associated with fewer major postoperative complications (P < .053). There was a trend toward more complications with a history of radiation therapy or intracranial involvement.
Conclusions: Reconstruction of the orbital cavity and lateral skull base can be challenging, especially if there is a history of radiation therapy and intracranial involvement. Free tissue transfer is a safe and effective method for reconstruction of such defects.
C1 [Mendez, Eduardo] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA.
[Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
[Mendez, Eduardo] Vet Affairs Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA.
[Serrano, Nicholas A.] Univ Washington, Sch Med, Seattle, WA USA.
[Trenite, Gilean N.] Onze Lieve Vrouw Hosp, Dept Surg, Amsterdam, Netherlands.
[Yueh, Bevan] Univ Minnesota, Dept Otolaryngol Head & Neck Surg, Minneapolis, MN USA.
[Farwell, Gregory] Univ Calif Davis, Sacramento, CA 95817 USA.
RP Mendez, E (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Dept Otolaryngol Head & Neck Surg, 1959 NE Pacific St,Mailbox 356515, Seattle, WA 98195 USA.
EM edmendez@u.washington.edu
OI Yueh, Bevan/0000-0003-1380-1053
NR 25
TC 3
Z9 3
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 1521-2491
J9 ARCH FACIAL PLAST S
JI Arch. Facial Plast. Surg.
PD MAR-APR
PY 2012
VL 14
IS 2
BP 97
EP 103
DI 10.1001/archfacial.2011.1301
PG 7
WC Surgery
SC Surgery
GA 914LI
UT WOS:000301951100005
PM 22183060
ER
PT J
AU Abbott, AL
Adelman, MAA
Alexandrov, AV
Barnett, HJM
Beard, J
Bell, P
Bjorck, M
Blacker, D
Buckley, CJ
Cambria, RP
Comerota, AJ
Connolly, S
Davies, AH
Eckstein, HH
Faruqi, R
Fraedrich, G
Gloviczki, P
Hankey, GJ
Harbaugh, RE
Heldenberg, E
Kittner, SJ
Kleinig, TJ
Mikhailidis, DP
Moore, WS
Naylor, R
Nicolaides, A
Paraskevas, KI
Pelz, DM
Prichard, JW
Purdie, G
Ricco, JB
Riles, T
Rothwell, P
Sandercock, P
Sillesen, H
Spence, JD
Spinelli, F
Tan, A
Thapar, A
Veith, FJ
Zhou, W
AF Abbott, Anne L.
Adelman, Mark A. A.
Alexandrov, Andrei V.
Barnett, Henry J. M.
Beard, Jonathan
Bell, Peter
Bjorck, Martin
Blacker, David
Buckley, Clifford J.
Cambria, Richard P.
Comerota, Anthony J.
Connolly, Sander, Jr.
Davies, Alun H.
Eckstein, Hans-Henning
Faruqi, R.
Fraedrich, Gustav
Gloviczki, Peter
Hankey, Graeme J.
Harbaugh, Robert E.
Heldenberg, E.
Kittner, Steven J.
Kleinig, Timothy J.
Mikhailidis, Dimitri P.
Moore, Wesley S.
Naylor, R.
Nicolaides, Andrew
Paraskevas, Kosmas I.
Pelz, David M.
Prichard, James W.
Purdie, Grant
Ricco, Jean-Baptiste
Riles, Thomas
Rothwell, Peter
Sandercock, Peter
Sillesen, Henrik
Spence, J. David
Spinelli, Francesco
Tan, Aron
Thapar, Ankur
Veith, Frank J.
Zhou, Wei
TI Why the United States Center for Medicare and Medicaid Services (CMS)
should not extend reimbursement indications for carotid artery
angioplasty/stenting
SO BRAIN AND BEHAVIOR
LA English
DT Review
DE Carotid angioplasty; carotid endarterectomy; carotid stenting; carotid
surgery; health economics; public health; vascular disease medical
intervention
AB In recent years, many important discoveries have been made to challenge current policy, guidelines, and practice regarding how best to prevent stroke associated with atherosclerotic stenosis of the origin of the internal carotid artery. The United States Center for Medicare and Medicaid Services (CMS), for instance, is calling for expert advice as to whether its current policies should be modified. Using a thorough review of literature, 41 leading academic stroke-prevention clinicians from the United States and other countries, have united to advise CMS not to extend current reimbursement indications for carotid angioplasty/stenting (CAS) to patients with asymptomatic carotid stenosis or to patients with symptomatic carotid stenosis considered to be at "low or standard risk from carotid endarterectomy (CEA)." It was concluded that such expansion of reimbursement indications would have disastrous health and economic consequences for the United States and any other country that may follow such inappropriate action. This was an international effort because the experts to best advise CMS are relatively few and scattered around the world. In addition, US health policy, practice, and research have tended to have strong influences on other countries.
C1 [Abbott, Anne L.] Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004, Australia.
[Abbott, Anne L.] Florey Neurosci Inst, Melbourne, Vic, Australia.
[Adelman, Mark A. A.] NYU, Langone Med Ctr, New York, NY 10003 USA.
[Alexandrov, Andrei V.] Univ Alabama Hosp & Clin, South Birmingham, AL USA.
[Barnett, Henry J. M.] Univ Western Ontario, Robarts Res Inst, Toronto, ON, Canada.
[Beard, Jonathan] No Gen Hosp, Sheffield Vasc Inst, Sheffield S5 7AU, S Yorkshire, England.
[Bell, Peter] Univ Leicester, Leicester, Leics, England.
[Bell, Peter] Univ Leicester Hosp, Leicester, Leics, England.
[Bjorck, Martin] Uppsala Univ, Uppsala, Sweden.
[Blacker, David] Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia.
[Buckley, Clifford J.] Texas A&M Hlth Sci Ctr, Coll Med, Scott & White Hlth Care Syst, Bryan, TX USA.
[Buckley, Clifford J.] Cent Texas Vet Hlth Care Syst, Arlington, TX USA.
[Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Cambria, Richard P.] Harvard Univ, Sch Med, Boston, MA USA.
[Comerota, Anthony J.] Toledo Hosp, Jobst Vasc Inst, Toledo, OH USA.
[Connolly, Sander, Jr.] Columbia Univ, New York, NY 10027 USA.
[Davies, Alun H.] Charing Cross Hosp, Imperial Coll Sch Med, London, England.
[Eckstein, Hans-Henning] Tech Univ Munich, D-80290 Munich, Germany.
[Eckstein, Hans-Henning] Tech Univ Munich, Klinikum Rechts Isar, D-80290 Munich, Germany.
[Faruqi, R.] Stanford Univ, Univ Calif, Stanford, CA 94305 USA.
[Faruqi, R.] Kaiser Permanente Med Ctr, Los Angeles, CA USA.
[Fraedrich, Gustav] Med Univ Innsbruck, A-6020 Innsbruck, Austria.
[Gloviczki, Peter] Mayo Clin, Rochester, MN USA.
[Hankey, Graeme J.] Royal Perth Hosp, Perth, WA, Australia.
[Harbaugh, Robert E.] Penn State Univ, Penn State Inst Neurosci, Hershey, PA USA.
[Heldenberg, E.] Assaf Harofeh Med Ctr, IL-70300 Zerifin, Israel.
[Kittner, Steven J.] Univ Maryland, Sch Med, Baltimore, MD USA.
[Kleinig, Timothy J.] Univ Adelaide, Royal Adelaide & Lyell McEwin Hosp, Adelaide, SA, Australia.
[Mikhailidis, Dimitri P.] UCL, Sch Med, London W1N 8AA, England.
[Moore, Wesley S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Naylor, R.] Leicester Royal Infirm, Leicester, Leics, England.
[Nicolaides, Andrew] Univ London Imperial Coll Sci Technol & Med, Vasc Diagnost Ctr, London, England.
[Paraskevas, Kosmas I.] Klinikum Nurnberg Sud, Nurnberg, Germany.
[Pelz, David M.; Spence, J. David] Univ Western Ontario, London, ON, Canada.
[Prichard, James W.] Yale Univ, Sch Med, New Haven, CT USA.
[Purdie, Grant] Queen Elizabeth Hosp, Adelaide, SA, Australia.
[Ricco, Jean-Baptiste] Univ Poitiers, Poitiers, France.
[Riles, Thomas] NYU, Sch Med, New York, NY 10003 USA.
[Rothwell, Peter] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford OX1 2JD, England.
[Sandercock, Peter] Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland.
[Sillesen, Henrik] Univ Copenhagen, DK-1168 Copenhagen, Denmark.
[Spence, J. David] Robarts Res Inst, London, ON N6A 5C1, Canada.
[Spinelli, Francesco] Univ Messina, Messina, Italy.
[Tan, Aron] Queen Elizabeth & Lyell McEwin Hosp, Adelaide, SA, Australia.
[Thapar, Ankur] Charing Cross Hosp, Royal Coll Surg, London, England.
[Veith, Frank J.] NYU, Case Western Reserve Univ, Univ Hlth Sci, Sch Med,Cleveland Clin,Edward Hebert Sch Med, New York, NY 10003 USA.
[Zhou, Wei] Stanford Univ, Stanford, CA 94305 USA.
[Zhou, Wei] Palo Alto VA Hlth Care Syst, Stanford, CA USA.
RP Abbott, AL (reprint author), Baker IDI Heart & Diabet Inst, 75 Commercial Rd, Melbourne, Vic 3004, Australia.
EM Anne.L.Abbott@gmail.com; Mark.Adelman@nyumc.org; avalexandrov@att.net;
hjmb@bell.net; j.d.beard@btinternet.com; peterrfbell@googlemail.com;
martin@bjorck.pp.se; David.Blacker@health.wa.gov.au;
Clifford.Buckley@VA.GOV; RCAMBRIA@PARTNERS.ORG;
anthony.comerotamd@promedica.org; esc5@columbia.edu;
a.h.davies@imperial.ac.uk; HHEckstein@web.de; Rishad.Faruqi@kp.org;
gustav.fraedrich@i-med.ac.at; gloviczki.peter@mayo.edu;
gjhankey@cyllene.uwa.edu.au; rharbaugh@psu.edu;
eitanh@asaf.health.gov.il; skittner@umaryland.edu; tkleinig@hotmail.com;
MIKHAILIDIS@aol.com; WMoore@mednet.ucla.edu; ross.naylor@uhl-tr.nhs.uk;
anicolaides1@gmail.com; paraskevask@hotmail.com; Pelz@uwo.ca;
james.prichard@yale.edu; Grant.Purdie@health.sa.gov.au;
jeanbaptistericco@gmail.com; Thomas.Riles@nyumc.org;
peter.rothwell@clneuro.ox.ac.uk; Peter.sandercock@ed.ac.uk;
sillesen@mac.com; dspence@robarts.ca; f.spinelli@mac.com;
Aaron.Tan@health.sa.gov.au; a.thapar09@imperial.ac.uk; fjvmd@msn.com;
weizhou@stanford.edu
RI Spence, J. David/K-6396-2013; Hankey, Graeme /H-4968-2014;
OI Spence, J. David/0000-0001-7478-1098; Hankey, Graeme
/0000-0002-6044-7328; Alexandrov, Andrei V/0000-0001-8871-1023;
Eckstein, Hans-Henning/0000-0002-0743-1642
FU Australian National Health and Medical Research Council (NHMRC)
Fellowship [472700]
FX Anne Abbott's time on this project has been supported by an Australian
National Health and Medical Research Council (NHMRC) Fellowship (ID:
472700).
NR 57
TC 0
Z9 0
U1 1
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 MAR
PY 2012
VL 2
IS 2
BP 200
EP 207
DI 10.1002/brb3.32
PG 8
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA V35UQ
UT WOS:000209173900009
ER
PT J
AU Au, DH
Udris, EM
Engelberg, RA
Diehr, PH
Bryson, CL
Reinke, LE
Curtis, JR
AF Au, David H.
Udris, Edmunds M.
Engelberg, Ruth A.
Diehr, Paula H.
Bryson, Christopher L.
Reinke, Lynn E.
Curtis, J. Randall
TI A Randomized Trial to Improve Communication About End-of-Life Care Among
Patients With COPD
SO CHEST
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; ADVANCE DIRECTIVE EDUCATION; LUNG-CANCER;
PALLIATIVE CARE; HEALTH; REHABILITATION; EFFICACY; QUALITY; DEATH;
QUESTIONNAIRE
AB Objective: Patients with COPD consistently express a desire to discuss end-of-life care with clinicians, but these discussions rarely occur. We assessed whether an intervention using patient-specific feedback about preferences for discussing end-of-life care would improve the occurrence and quality of communication between patients with COPD and their clinicians.
Methods: We performed a cluster-randomized trial of clinicians and patients from the outpatient clinics at the Veterans Affairs Puget Sound Health Care System. Using self-reported questionnaires, we assessed patients' preferences for communication, life-sustaining therapy, and experiences at the end of life. The intervention clinicians and patients received a one-page patient-specific feedback form, based on questionnaire responses, to stimulate conversations. The control group completed questionnaires but did not receive feedback. Patient-reported occurrence and quality of end-of-life communication (QOC) were assessed within 2 weeks of a targeted visit. Intention-to-treat regression analyses were performed with generalized estimating equations to account for clustering of patients within clinicians.
Results: Ninety-two clinicians contributed 376 patients. Patients in the intervention arm reported nearly a threefold higher rate of discussions about end-of-life care (unadjusted, 30% vs 11%; P<.001). Baseline end-of-life communication was poor (intervention group QOC score, 23.3; 95% CI, 19.9-26.8; control QOC score, 19.2; 95% CI, 15.9-22.4). Patients in the intervention arm reported higher-quality end-of-life communication that was statistically significant, although the overall improvement was small (Cohen effect size, 0.21).
Conclusions: A one-page patient-specific feedback form about preferences for end-of-life care and communication improved the occurrence and quality of communication from patients' perspectives. Trial Registry: ClinicalTrials.gov; No.: NCT00106080; URL: www.clinicaltrials.gov CHEST 2012; 141(3):726-735
C1 [Au, David H.; Udris, Edmunds M.; Bryson, Christopher L.; Reinke, Lynn E.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA.
[Au, David H.; Engelberg, Ruth A.; Bryson, Christopher L.; Curtis, J. Randall] Univ Washington, Dept Med, Seattle, WA USA.
[Diehr, Paula H.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA.
[Diehr, Paula H.] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA.
RP Au, DH (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA.
EM David.Au@VA.gov
FU Department of Veterans Affairs [IIR-02-292]; Veterans Affairs Health
Services Research and Development Career Development Award; National
Heart Lung and Blood Institute [K24 HL068593]
FX This study was funded by the Department of Veterans Affairs [Grant
IIR-02-292]. Dr Au was funded during the trial period by a Veterans
Affairs Health Services Research and Development Career Development
Award. Dr Curtis was funded by a K24 Award from that National Heart Lung
and Blood Institute [Grant K24 HL068593].
NR 29
TC 38
Z9 38
U1 1
U2 7
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD MAR
PY 2012
VL 141
IS 3
BP 726
EP 735
DI 10.1378/chest.11-0362
PG 10
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 120KO
UT WOS:000317169400025
PM 21940765
ER
PT J
AU Muzaffar, SAF
Christiani, DC
AF Muzaffar, Saeher A. F.
Christiani, David C.
TI Frontiers in Occupational and Environmental Lung Disease Research
SO CHEST
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; NECROSIS-FACTOR-ALPHA; CHRONIC BERYLLIUM
DISEASE; IDIOPATHIC PULMONARY-FIBROSIS; EXHALED BREATH CONDENSATE;
TOBACCO-SMOKE EXPOSURE; CHILDHOOD ASTHMA; GENETIC SUSCEPTIBILITY;
DIISOCYANATE EXPOSURE; POLYMORPHISMS MODIFY
AB Two central challenges in the field of occupational and environmental epidemiology include accurately measuring biologic responses to exposure and preventing subsequent disease. As exposure-related lung diseases continue to be identified, advances in exposure biology have introduced toxicogenomic approaches that detect biomarkers of exposure at the gene, protein, and metabolite levels. Moreover, genetic epidemiology research has focused more recently on common, low-penetrant (ie, low-relative-risk) genetic variants that may interact with commonly encountered exposures. A number of such gene by environment interactions have been identified for airways and interstitial lung diseases, with the goal of preventing disease among susceptible populations that may not otherwise have been identified. Exhaled breath condensate analysis has provided another noninvasive means of assessing toxicant exposures and systemic effects. As these technologies become more refined, clinicians and public health practitioners will need to appreciate the social implications of the individual- and population-level risks conferred by certain genetic polymorphisms or by biomarker evidence of exposure. At present, the primary approach to occupational and environmental lung disease prevention remains elimination or reduction of known hazardous exposures and requires continued application of local and international resources toward exposure control. CHEST 2012; 141(3):772-781
C1 [Muzaffar, Saeher A. F.] Hosp Univ Penn, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA.
[Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Christiani, David C.] Harvard Univ, Sch Med, Boston, MA USA.
[Christiani, David C.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
RP Christiani, DC (reprint author), Massachusetts Gen Hosp, Div Pulm & Crit Care Med, 665 Huntington Ave,SPH I-1407, Boston, MA 02115 USA.
EM dchris@hsph.harvard.edu
NR 84
TC 1
Z9 1
U1 0
U2 2
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD MAR
PY 2012
VL 141
IS 3
BP 772
EP 781
DI 10.1378/chest.11-0156
PG 10
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 120KO
UT WOS:000317169400030
PM 22396562
ER
PT J
AU Goel, S
Wong, AHK
Jain, RK
AF Goel, Shom
Wong, Andus Hon-Kit
Jain, Rakesh K.
TI Vascular Normalization as a Therapeutic Strategy for Malignant and
Nonmalignant Disease
SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; HEREDITARY
HEMORRHAGIC TELANGIECTASIA; METASTATIC COLORECTAL-CANCER; CELL
LUNG-CANCER; INTERSTITIAL FLUID PRESSURE; FACTOR RECEPTOR-2 BLOCKADE;
INDUCIBLE-FACTOR 1-ALPHA; SUPPRESSES TUMOR-GROWTH; ANTI-VEGF TREATMENT
AB Pathological angiogenesis-driven byan imbalance of pro-and antiangiogenic signaling-is a hallmark of many diseases, both malignant and benign. Unlike in the healthy adult in which angiogenesis is tightly regulated, such diseases are characterized by uncontrolled new vessel formation, resulting in a microvascular network characterized by vessel immaturity, with profound structural and functional abnormalities. The consequence of these abnormalities is further modification of the microenvironment, often serving to fuel disease progression and attenuate response to conventional therapies. In this article, we present the "vascular normalization" hypothesis, which states that antiangiogenic therapy, by restoring the balance between pro-and antiangiogenic signaling, can induce a more structurally and functionally normal vasculature in a variety of diseases. We present the preclinical and clinical evidence supporting this concept and discuss how it has contributed to successful treatment of both solid tumors and several benign conditions.
C1 [Goel, Shom; Wong, Andus Hon-Kit; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin Steele Lab Tumor Biol, Boston, MA 02114 USA.
RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin Steele Lab Tumor Biol, Boston, MA 02114 USA.
EM jain@steele.mgh.harvard.edu
RI Wong, Hon-Kit/G-3944-2014
OI Wong, Hon-Kit/0000-0003-0049-8454
FU Australian-American Fulbright Commission; American Society for Clinical
Oncology; U.S. National Institutes of Health (NIH) [P01-CA80124,
R01-CA85140, R01-CA115767, R01-CA126642]; Federal Share/NCI Proton Beam
Program Income; National Foundation for Cancer Research; Department of
Defense [W81XWH-10-1-0016]; AstraZeneca; Dyax; MedImmune; Roche
FX S.G. is supported by the Australian-American Fulbright Commission and an
American Society for Clinical Oncology Young Investigator Award. The
research of R.K.J. is supported by the U.S. National Institutes of
Health (NIH) grants P01-CA80124, R01-CA85140, R01-CA115767, and
R01-CA126642, Federal Share/NCI Proton Beam Program Income, National
Foundation for Cancer Research, and Department of Defense Breast Cancer
Research Innovator Award (W81XWH-10-1-0016).; R.K.J. has served in a
consultant or advisory role to Astellas, AstraZeneca, Dyax, Genzyme,
Noxxon Pharma, Regeneron, and SynDevRx, has equity in SynDevRx, has
received honoraria from Genzyme, and has received research funding from
AstraZeneca, Dyax, MedImmune, and Roche.
NR 189
TC 70
Z9 72
U1 6
U2 14
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 2157-1422
J9 CSH PERSPECT MED
JI Cold Spring Harb. Perspect. Med.
PD MAR
PY 2012
VL 2
IS 3
AR a006486
DI 10.1101/cshperspect.a006486
PG 24
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 080WL
UT WOS:000314274700005
PM 22393532
ER
PT J
AU Porichis, F
Kaufmann, DE
AF Porichis, Filippos
Kaufmann, Daniel E.
TI Role of PD-1 in HIV Pathogenesis and as Target for Therapy
SO CURRENT HIV/AIDS REPORTS
LA English
DT Article
DE HIV; AIDS; Chronic viral infection; T-cell exhaustion; Programmed-death
1 (PD-1); Programmed death-ligand 1 (PD-L1); Programmed death-ligand 2
AB Major advances in Antiretroviral Therapy (ART) have resulted in a dramatic decline in HIV-related deaths. However, no current treatment regimen leads to viral eradication or restoration of HIV-specific immune responses capable of durable viral control after cessation of ART. Thus, there is a need for novel interventions that could complement ART in order to eliminate virus or reach a state of " functional cure." It has been shown in murine models and humans that the negative co-signaling molecule programmed-death 1 (PD-1) plays an active and reversible role in mediating T-cell exhaustion in chronic infections. This review summarizes recent advances in our understanding of the PD-1 pathway in HIV infection, and the lessons learned from studies in the SIV model and cancer. We discuss the potential of immunotherapeutic interventions targeting PD-1 in order to augment immune responses or facilitate viral eradication. We also present the challenges to therapies targeting immunoregulatory networks.
C1 [Porichis, Filippos; Kaufmann, Daniel E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA.
[Kaufmann, Daniel E.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Kaufmann, Daniel E.] Massachusetts Gen Hosp E, Ragon Inst MGH MIT & Harvard, Charlestown, MA 02129 USA.
RP Kaufmann, DE (reprint author), Massachusetts Gen Hosp E, Ragon Inst MGH MIT & Harvard, Room 5239,149 13th St, Charlestown, MA 02129 USA.
EM dkaufmann@partners.org
FU National Institutes of Health [NIH RO1 HL 092565, P01AI-080192];
Executive Committee on Research of the Massachusetts General Hospital
(ECOR)
FX D.E.K. is supported by grants from the National Institutes of Health
(NIH RO1 HL 092565 and P01AI-080192). F.P. is supported by a fellowship
grant from Executive Committee on Research of the Massachusetts General
Hospital (ECOR).
NR 77
TC 35
Z9 36
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1548-3568
EI 1548-3576
J9 CURR HIV-AIDS REP
JI Curr. Hiv/Aids Rep.
PD MAR
PY 2012
VL 9
IS 1
BP 81
EP 90
DI 10.1007/s11904-011-0106
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA V32TS
UT WOS:000208974100010
PM 22198819
ER
PT J
AU Ham, M
Moss, AC
AF Ham, Maggie
Moss, Alan C.
TI Mesalamine in the treatment and maintenance of remission of ulcerative
colitis
SO EXPERT REVIEW OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE 5-ASA; inflammatory bowel disease; mesalamine; ulcerative colitis
AB Ulcerative colitis (UC) is a chronic disease of the GI tract that is characterized by mucosal inflammation in the colon. Mesalamine (mesalazine) is a 5-aminosalicylic acid compound that is the first-line treatment for patients with mild-to-moderate UC. There are multiple formulations of mesalamine available, primarily differentiated by their means of delivering active mesalamine to the colon. Mesalamine has been demonstrated in randomized controlled trials to induce both clinical response and remission, and maintain clinical remission, in these patients. It has few serious adverse effects and is generally well tolerated by patients. The main areas of uncertainty with use of mesalamine in patients with UC center on the optimal dose for induction of response, how to maintain patient adherence and the role of mesalamine in cancer chemoprophylaxis. Generic forms of mesalamine have yet to be approved by regulatory bodies in the USA.
C1 [Ham, Maggie; Moss, Alan C.] Harvard Univ, Sch Med, BIDMC, Ctr Inflammatory Bowel Dis, Boston, MA 02215 USA.
RP Moss, AC (reprint author), Harvard Univ, Sch Med, BIDMC, Ctr Inflammatory Bowel Dis, 330 Brookline Ave, Boston, MA 02215 USA.
EM amoss@bidmc.harvard.edu
FU Salix; Shire; Procter Gamble; NIH [K23DK084338]
FX AC Moss has received research funding from Salix, Shire and Procter &
Gamble, and is supported by NIH grant K23DK084338. The authors have no
other relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 85
TC 18
Z9 22
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1751-2433
EI 1751-2441
J9 EXPERT REV CLIN PHAR
JI Expert Rev. Clin. Pharmacol.
PD MAR
PY 2012
VL 5
IS 2
BP 113
EP 123
DI 10.1586/ECP.12.2
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA V37PO
UT WOS:000209287900007
PM 22390554
ER
PT J
AU Pulliam, SJ
Weinstein, MM
Wakamatsu, MM
AF Pulliam, Samantha J.
Weinstein, Milena M.
Wakamatsu, May M.
TI Minimally Invasive Apical Sacropexy: A Retrospective Review of
Laparoscopic and Robotic Operating Room Experiences
SO FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY
LA English
DT Article
DE minimally invasive surgery; sacral colpopexy; learning curve; robotic
colpopexy; laparoscopic colpopexy
AB Objectives: Minimally invasive apical sacropexies (MI-APSC) can be performed using robotics or laparoscopy. We hypothesized that operative characteristics of MI-APSC, laparoscopic (LSC) and robotic (RSC), were similar. The objective of our study was to compare operative characteristics, objective prolapse outcomes, and robotic learning curve.
Methods: Ninety-two women planning MI-APSC for treatment of apical pelvic organ prolapse from 2006 to 2010 were included in the study. The primary outcome was operative time. The secondary outcomes included estimated blood loss, rate of conversion, intraoperative complications, hospital stay, and objective prolapse outcome. We also analyzed the robotic learning curve. Statistical analysis included independent samples t test, Wilcoxon rank sum test, chi(2), and multiple logistic regressions; significance was set at P < 0.05. Learning curve was graphed with moving average and analyzed with moving block technique.
Results: Forty-eight RSCs and 43 LSCs were analyzed. Mean operative times were LSC, 238 +/- 59 minutes; and RSC, 242 +/- 54 minutes. Robotic MI-APSC setup was longer (P = 0.02). Complications, conversions, estimated blood loss and hospital stay were low and similar between groups. Patients' characteristics were similar. Concomitant procedures produced longer operative times.
Conclusions: Operating room experiences with laparoscopic- and robotic-assisted approaches to MI-APSC were similar, but setup time is longer for the robotic-assisted approach. The robotic learning curve is short for surgeons who have experience with LSC.
C1 [Pulliam, Samantha J.; Weinstein, Milena M.; Wakamatsu, May M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Urogynecol & Reconstruct Pelv Surg,Dept Vince, Boston, MA USA.
RP Weinstein, MM (reprint author), 55 Fruit St,Founders 5, Boston, MA 02114 USA.
EM mweinstein2@partners.org
FU Vincent Memorial Obstetrics and Gynecology Service, Massachusetts
General Hospital, Boston, MA
FX Departmental funding was received from Vincent Memorial Obstetrics and
Gynecology Service, Massachusetts General Hospital, Boston, MA.
NR 27
TC 5
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2151-8378
J9 FEMALE PELVIC MED RE
JI Female Pelvic Med. Reconstr. Surg.
PD MAR-APR
PY 2012
VL 18
IS 2
BP 122
EP 126
DI 10.1097/SPV.0b013e31824a3995
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA V35XH
UT WOS:000209178000012
PM 22453324
ER
PT J
AU Roberts, SR
Crigler, J
Lafferty, WE
Bonham, AJ
Hunter, JL
Smith, AJ
Banderas, JW
Early, GL
King, RK
AF Roberts, Shauna R.
Crigler, Jane
Lafferty, William E.
Bonham, Aaron J.
Hunter, Jennifer L.
Smith, Andrew J.
Banderas, Julie W.
Early, Gerald L.
King, Roderick K.
TI Addressing Social Determinants to Improve HealthCare Quality and Reduce
Cost
SO JOURNAL FOR HEALTHCARE QUALITY
LA English
DT Article
DE Care/Disease; Management; Continuum of Care; Delivery Models; Social
Work; Urban
AB Most healthcare quality improvement and cost reduction efforts currently focus on care processes, or transitions-for example, the hospital discharge process. While identification and adoption of best practices to address these aspects of healthcare are essential, more is needed for systems that serve vulnerable populations: to account for social factors that often inhibit patients' ability to take full advantage of available healthcare. Our urban safety net healthcare system developed and implemented an innovative quality improvement approach. The programs, Guided Chronic Care (TM), and Passport to Wellness, use Assertive Care and provide social support for patients between medical encounters, enabling patients to make better use of the healthcare system and empowering them to better manage their conditions. Results: The majority of patients reported problems with mobility and nearly half reported anxiety or depression. Early indications show improved quality of care and significant reduction in costs. Challenges encountered and lessons learned in implementing the programs are described, to assist others developing similar interventions.
C1 [Roberts, Shauna R.] Qual Truman Med Ctr, Kansas City, MO 64108 USA.
[Roberts, Shauna R.] Univ Missouri Kansas City, Dept Med, Sch Med, Kansas City, MO USA.
[Lafferty, William E.] Univ Missouri Kansas City, Off Hlth Serv & Publ Hlth Outcomes Res, Sch Med, Kansas City, MO USA.
[Bonham, Aaron J.] Univ Missouri Kansas City, Sch Med, Hicklin Off Hlth Serv & Publ Hlth Outcomes Res, Kansas City, MO USA.
[Hunter, Jennifer L.] Univ Missouri Kansas City, Sch Nursing, Kansas City, MO USA.
[Smith, Andrew J.] Univ Missouri Kansas City, Sch Pharm, Kansas City, MO USA.
[Smith, Andrew J.; Early, Gerald L.] Truman Med Ctr, Kansas City, MO USA.
[Banderas, Julie W.; Early, Gerald L.] Univ Missouri Kansas City, Sch Med, Kansas City, MO USA.
[King, Roderick K.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA.
[King, Roderick K.] Next Generat Consulting Grp, Boston, MA USA.
[King, Roderick K.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA.
RP Roberts, SR (reprint author), Qual Truman Med Ctr, Kansas City, MO 64108 USA.
EM shauna.roberts@tmcmed.org
NR 25
TC 4
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1062-2551
EI 1945-1474
J9 J HEALTHC QUAL
JI J. Healthc. Qual.
PD MAR-APR
PY 2012
VL 34
IS 2
BP 12
EP 20
DI 10.1111/j.1945-1474.2011.00179.x
PG 9
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA V36OM
UT WOS:000209221000003
PM 23552199
ER
PT J
AU Dillon, AR
Dell'Italia, LJ
Tillson, M
Killingsworth, C
Denney, T
Hathcock, J
Botzman, L
AF Dillon, A. Ray
Dell'Italia, Louis J.
Tillson, Michael
Killingsworth, Cheryl
Denney, Thomas
Hathcock, John
Botzman, Logan
TI Left ventricular remodeling in preclinical experimental mitral
regurgitation of dogs
SO JOURNAL OF VETERINARY CARDIOLOGY
LA English
DT Review
DE Cardiac remodeling; Volume overload; Extracellular matrix
AB Dogs with experimental mitral regurgitation (MR) provide insights into the left ventricular remodeling in preclinical MR. The early preclinical left ventricular (LV) changes after mitral regurgitation represent progressive dysfunctional remodeling, in that no compensatory response returns the functional stroke volume (SV) to normal even as total SV increases. The gradual disease progression leads to mitral annulus stretch and enlargement of the regurgitant orifice, further increasing the regurgitant volume. Remodeling with loss of collagen weave and extracellular matrix (ECM) is accompanied by stretching and hypertrophy of the cross-sectional area and length of the cardiomyocyte. Isolated ventricular cardiomyocytes demonstrate dysfunction based on decreased cell shortening and reduced intracellular calcium transients before chamber enlargement or decreases in contractility in the whole heart can be clinically appreciated. The genetic response to increased end-diastolic pressure is down-regulation of genes associated with support of the collagen and ECM and up-regulation of genes associated with matrix remodeling. Experiments have not demonstrated any beneficial effects on remodeling from treatments that decrease afterload via blocking the renin-angiotensin system (RAS). Beta-1 receptor blockade and chymase inhibition have altered the progression of the LV remodeling and have supported cardiomyocyte function. The geometry of the LV during the remodeling provides insight into the importance of regional differences in responses to wall stress. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Dillon, A. Ray; Tillson, Michael; Hathcock, John; Botzman, Logan] Auburn Univ, Coll Vet Med, Auburn, AL 36849 USA.
[Dell'Italia, Louis J.; Killingsworth, Cheryl] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA.
[Dell'Italia, Louis J.] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA.
[Denney, Thomas] Auburn Univ, Coll Engn, Auburn, AL 36849 USA.
[Denney, Thomas] Auburn Univ, MRI Ctr, Auburn, AL 36849 USA.
RP Dillon, AR (reprint author), Auburn Univ, Coll Vet Med, Auburn, AL 36849 USA.
EM dilloar@auburn.edu
NR 43
TC 9
Z9 11
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1760-2734
EI 1875-0834
J9 J VET CARDIOL
JI J. Vet. Cardiol.
PD MAR
PY 2012
VL 14
IS 1
BP 73
EP 92
DI 10.1016/j.jvc.2012.01.012
PG 20
WC Veterinary Sciences
SC Veterinary Sciences
GA V31VG
UT WOS:000208910500008
PM 22386719
ER
PT J
AU Morone, NE
Lynch, CP
Losasso, VJ
Liebe, K
Greco, CM
AF Morone, Natalia E.
Lynch, Cheryl P.
Losasso, Vincent J., III
Liebe, Karl
Greco, Carol M.
TI Mindfulness to Reduce Psychosocial Stress
SO MINDFULNESS
LA English
DT Article
DE Psychosocial stress; Mindfulness; Meditation; Qualitative
AB While the adverse impact of stress on health states has been established, effective stress reduction programs are largely underused in clinical settings. In an area with little published information, this study identifies themes that describe the process of applying mindfulness methods to cope with psychosocial stressors in participants of the Mindfulness-Based Stress Reduction (MBSR) program. The study design is a qualitative investigation with a phenomenological approach using participant feedback from 11 MBSR 8-week programs. Participants were 74 adults from the greater Pittsburgh area. Content analysis was used to inductively generate thematic categories. Four themes were identified that described the process and results of learning mindfulness to adapt to psychosocial stressors. We categorized participants' feedback into interrelated themes of awareness (subdivided into self-discovery-" step back from my thoughts in order to view them more clearly", and being in the present), coping-" pause, take a breath", serenity-" increased feeling of calm, centeredness", and change in perspective-" different understanding interpersonally and intrapersonally." In addition, a brief section describes specific health benefits identified by participants. Participants found the mindfulness-based approach effective for stress reduction. The learning process allowed them to routinely apply mindfulness strategies that provided multiple benefits.
C1 [Morone, Natalia E.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA.
[Morone, Natalia E.] Univ Pittsburgh, Translat Sci Inst, Pittsburgh, PA 15213 USA.
[Morone, Natalia E.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
[Lynch, Cheryl P.] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Div Populat, Charleston, SC USA.
[Lynch, Cheryl P.] Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA.
[Losasso, Vincent J., III] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA.
[Liebe, Karl] HealthSouth Harmarville Rehabil Hosp, Dept Med Phys & Rehabil, Pittsburgh, PA USA.
[Greco, Carol M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
RP Morone, NE (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA.
EM moronene@upmc.edu
NR 21
TC 4
Z9 5
U1 0
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1868-8527
EI 1868-8535
J9 MINDFULNESS
JI Mindfulness
PD MAR
PY 2012
VL 3
IS 1
BP 22
EP 29
DI 10.1007/s12671-011-0076-z
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA V33HM
UT WOS:000209009900004
ER
PT J
AU Dastani, Z
Hivert, MF
Timpson, N
Perry, JRB
Yuan, X
Scott, RA
Henneman, P
Heid, IM
Kizer, JR
Lyytikainen, LP
Fuchsberger, C
Tanaka, T
Morris, AP
Small, K
Isaacs, A
Beekman, M
Coassin, S
Lohman, K
Qi, L
Kanoni, S
Pankow, JS
Uh, HW
Wu, Y
Bidulescu, A
Rasmussen-Torvik, LJ
Greenwood, CMT
Ladouceur, M
Grimsby, J
Manning, AK
Liu, CT
Kooner, J
Mooser, VE
Vollenweider, P
Kapur, KA
Chambers, J
Wareham, NJ
Langenberg, C
Frants, R
Willems-vanDijk, K
Oostra, BA
Willems, SM
Lamina, C
Winkler, TW
Psaty, BM
Tracy, RP
Brody, J
Chen, I
Viikari, J
Kahonen, M
Pramstaller, PP
Evans, DM
St Pourcain, B
Sattar, N
Wood, AR
Bandinelli, S
Carlson, OD
Egan, JM
Bohringer, S
van Heemst, D
Kedenko, L
Kristiansson, K
Nuotio, ML
Loo, BM
Harris, T
Garcia, M
Kanaya, A
Haun, M
Klopp, N
Wichmann, HE
Deloukas, P
Katsareli, E
Couper, DJ
Duncan, BB
Kloppenburg, M
Adair, LS
Borja, JB
Wilson, JG
Musani, S
Guo, XQ
Johnson, T
Semple, R
Teslovich, TM
Allison, MA
Redline, S
Buxbaum, SG
Mohlke, KL
Meulenbelt, I
Ballantyne, CM
Dedoussis, GV
Hu, FB
Liu, YM
Paulweber, B
Spector, TD
Slagboom, PE
Ferrucci, L
Jula, A
Perola, M
Raitakari, O
Florez, JC
Salomaa, V
Eriksson, JG
Frayling, TM
Hicks, AA
Lehtimaki, T
Smith, GD
Siscovick, DS
Kronenberg, F
van Duijn, C
Loos, RJF
Waterworth, DM
Meigs, JB
Dupuis, J
Richards, JB
AF Dastani, Zari
Hivert, Marie-France
Timpson, Nicholas
Perry, John R. B.
Yuan, Xin
Scott, Robert A.
Henneman, Peter
Heid, Iris M.
Kizer, Jorge R.
Lyytikainen, Leo-Pekka
Fuchsberger, Christian
Tanaka, Toshiko
Morris, Andrew P.
Small, Kerrin
Isaacs, Aaron
Beekman, Marian
Coassin, Stefan
Lohman, Kurt
Qi, Lu
Kanoni, Stavroula
Pankow, James S.
Uh, Hae-Won
Wu, Ying
Bidulescu, Aurelian
Rasmussen-Torvik, Laura J.
Greenwood, Celia M. T.
Ladouceur, Martin
Grimsby, Jonna
Manning, Alisa K.
Liu, Ching-Ti
Kooner, Jaspal
Mooser, Vincent E.
Vollenweider, Peter
Kapur, Karen A.
Chambers, John
Wareham, Nicholas J.
Langenberg, Claudia
Frants, Rune
Willems-vanDijk, Ko
Oostra, Ben A.
Willems, Sara M.
Lamina, Claudia
Winkler, Thomas W.
Psaty, Bruce M.
Tracy, Russell P.
Brody, Jennifer
Chen, Ida
Viikari, Jorma
Kahonen, Mika
Pramstaller, Peter P.
Evans, David M.
St Pourcain, Beate
Sattar, Naveed
Wood, Andrew R.
Bandinelli, Stefania
Carlson, Olga D.
Egan, Josephine M.
Bohringer, Stefan
van Heemst, Diana
Kedenko, Lyudmyla
Kristiansson, Kati
Nuotio, Marja-Liisa
Loo, Britt-Marie
Harris, Tamara
Garcia, Melissa
Kanaya, Alka
Haun, Margot
Klopp, Norman
Wichmann, H. -Erich
Deloukas, Panos
Katsareli, Efi
Couper, David J.
Duncan, Bruce B.
Kloppenburg, Margreet
Adair, Linda S.
Borja, Judith B.
Wilson, James G.
Musani, Solomon
Guo, Xiuqing
Johnson, Toby
Semple, Robert
Teslovich, Tanya M.
Allison, Matthew A.
Redline, Susan
Buxbaum, Sarah G.
Mohlke, Karen L.
Meulenbelt, Ingrid
Ballantyne, Christie M.
Dedoussis, George V.
Hu, Frank B.
Liu, Yongmei
Paulweber, Bernhard
Spector, Timothy D.
Slagboom, P. Eline
Ferrucci, Luigi
Jula, Antti
Perola, Markus
Raitakari, Olli
Florez, Jose C.
Salomaa, Veikko
Eriksson, Johan G.
Frayling, Timothy M.
Hicks, Andrew A.
Lehtimaki, Terho
Smith, George Davey
Siscovick, David S.
Kronenberg, Florian
van Duijn, Cornelia
Loos, Ruth J. F.
Waterworth, Dawn M.
Meigs, James B.
Dupuis, Josee
Richards, J. Brent
CA DIAGRAM Consortium
MAGIC Consortium
GLGC Investigators
MuTHER Consortium
TI Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes
and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE;
LIPID CONCENTRATIONS; ADIPOSE-TISSUE; GENETIC-BASIS; RISK; POPULATION;
RECEPTOR; VARIANTS
AB Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P=4.5 x 10(-8)-1.2 x 10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3 x 10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p=4.3 x 10(-3), n = 22,044), increased triglycerides (p=2.6 x 10(-14), n = 93,440), increased waist-to-hip ratio (p=1.8 x 10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p=4.4 x 10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p=4.5x10(-13), n = 96,748) and decreased BMI (p= 1.4 x 10(-14), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
C1 [Dastani, Zari] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3T 1E2, Canada.
[Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada.
[Hivert, Marie-France; Grimsby, Jonna; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Timpson, Nicholas; Evans, David M.; Smith, George Davey] Univ Bristol, MRC CAiTE Ctr, Bristol, Avon, England.
[Timpson, Nicholas; Evans, David M.; St Pourcain, Beate; Smith, George Davey] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Perry, John R. B.; Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Perry, John R. B.; Wood, Andrew R.; Frayling, Timothy M.] Univ Exeter, Peninsula Med Sch, Exeter, Devon, England.
[Yuan, Xin; Mooser, Vincent E.; Waterworth, Dawn M.] GlaxoSmithKline, King Of Prussia, PA USA.
[Scott, Robert A.; Wareham, Nicholas J.; Langenberg, Claudia; Loos, Ruth J. F.] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
[Henneman, Peter; Frants, Rune; Willems-vanDijk, Ko] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
[Heid, Iris M.; Winkler, Thomas W.] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany.
[Kizer, Jorge R.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Kizer, Jorge R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Lyytikainen, Leo-Pekka; Kahonen, Mika; Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland.
[Fuchsberger, Christian; Teslovich, Tanya M.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Small, Kerrin; Spector, Timothy D.; Richards, J. Brent] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Small, Kerrin; Kanoni, Stavroula; Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, England.
[Isaacs, Aaron; Willems, Sara M.; van Duijn, Cornelia] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands.
[Isaacs, Aaron; Oostra, Ben A.; van Duijn, Cornelia] Ctr Med Syst Biol, Leiden, Netherlands.
[Beekman, Marian; van Heemst, Diana; Meulenbelt, Ingrid] Leiden Univ, Med Ctr, Sect Mol Epidemiol, Leiden, Netherlands.
[Beekman, Marian; Meulenbelt, Ingrid] Netherlands Consortium Healthy Aging, Netherlands Genom Initiat, Leiden, Netherlands.
[Coassin, Stefan; Lamina, Claudia; Haun, Margot; Kronenberg, Florian] Innsbruck Med Univ, Div Genet Epidemiol, Innsbruck, Austria.
[Lohman, Kurt; Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Qi, Lu; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Wu, Ying; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Bidulescu, Aurelian] Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA.
[Rasmussen-Torvik, Laura J.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Greenwood, Celia M. T.] McGill Univ, Dept Oncol, Lady Davis Inst Med Res, Montreal, PQ, Canada.
[Grimsby, Jonna; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Manning, Alisa K.; Liu, Ching-Ti; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Kooner, Jaspal] Ealing Gen Hosp, Natl Hlth Serv NHS Trust, London, England.
[Vollenweider, Peter] Univ Lausanne, Dept Internal Med, Lausanne, Switzerland.
[Kapur, Karen A.; Johnson, Toby] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Chambers, John] Univ London Imperial Coll Sci Technol & Med, London, England.
[Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Psaty, Bruce M.; Brody, Jennifer] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98195 USA.
[Tracy, Russell P.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA.
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[Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland.
[Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland.
[Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Pramstaller, Peter P.; Hicks, Andrew A.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.
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[Pramstaller, Peter P.] Univ Lubeck, Dept Neurol, Lubeck, Germany.
[Sattar, Naveed] Univ Glasgow, Glasgow Cardiovasc Res Ctr, British Heart Fdn, Glasgow, Lanark, Scotland.
[Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy.
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[Harris, Tamara; Garcia, Melissa] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Kanaya, Alka] Univ Calif San Francisco, Womens Hlth Clin Res Ctr, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Klopp, Norman; Wichmann, H. -Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Munich, Germany.
[Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H. -Erich] Klinikum Grosshadern, Munich, Germany.
[Katsareli, Efi; Dedoussis, George V.] Harokopio Univ, Athens, Greece.
[Couper, David J.] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA.
[Duncan, Bruce B.] Univ Fed Rio Grande do Sul, Sch Med, Porto Alegre, RS, Brazil.
[Duncan, Bruce B.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Kloppenburg, Margreet] Dept Rheumatol, Leiden, Netherlands.
[Kloppenburg, Margreet] Leiden Univ Hosp, Dept Clin Epidemiol, Leiden, Netherlands.
[Adair, Linda S.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Borja, Judith B.] Univ San Carlos, Off Populat Studies Fdn, Cebu, Philippines.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Musani, Solomon] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Guo, Xiuqing] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Johnson, Toby] CHU Vaudois, Univ Inst Social & Preventat Med, Lausanne, Switzerland.
[Johnson, Toby] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Semple, Robert] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England.
[Allison, Matthew A.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Redline, Susan] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Buxbaum, Sarah G.] Jackson State Univ, Jackson Heart Study Coordinating Ctr, Jackson, MS USA.
[Ballantyne, Christie M.] Baylor Coll Med, Houston, TX 77030 USA.
[Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland.
[Eriksson, Johan G.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Diabet Prevent Unit, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Ctr Hosp, Unit Gen Practice, Helsinki, Finland.
[Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland.
[Eriksson, Johan G.] Vaasa Cent Hosp, Vaasa, Finland.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Dupuis, Josee] Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA.
[Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Med, Montreal, PQ H3T 1E2, Canada.
[Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Human Genet, Montreal, PQ H3T 1E2, Canada.
[Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Epidemiol, Montreal, PQ H3T 1E2, Canada.
[Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Biostat, Montreal, PQ H3T 1E2, Canada.
[Oostra, Ben A.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Psaty, Bruce M.; Brody, Jennifer] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
RP Dastani, Z (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3T 1E2, Canada.
EM brent.richards@mcgill.ca
RI Erdmann, Jeanette/P-7513-2014; Buxbaum, Sarah/E-1970-2013; Slagboom, P.
Eline/R-4790-2016; Davey Smith, George/A-7407-2013; Naitza,
Silvia/D-5620-2017; Feitosa, Mary/K-8044-2012; Hicks,
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Smith, Albert/K-5150-2015; Kyvik, Kirsten /K-5680-2016; Visvikis-Siest,
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Peter/B-5127-2013; Fox, Laura /C-6249-2016; Johansson, Asa/G-5270-2011;
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Sigrid/A-8310-2011; Kronenberg, Florian/B-1736-2008; SIMPSON,
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Ozren/B-6002-2011; Meitinger, Thomas/O-1318-2015; Prokopenko,
Inga/H-3241-2014; Singleton, Andrew/C-3010-2009; Fuchsberger,
Christian/C-9646-2010; Deloukas, Panos/B-2922-2013; Evans,
David/H-6325-2013; Hide, Winston Hide/C-7217-2009; Pramstaller,
Peter/C-2357-2008; Thorand, Barbara/B-5349-2014; Elliott,
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FU NIH, National Institute on Aging; MedStar Research Institute;
Netherlands Organisation for Scientific Research, Erasmus MC; Centre for
Medical Systems Biology (CMSB); European Network for Genetic and Genomic
Epidemiology (ENGAGE) consortium; National Heart, Lung, and Blood
Institute [N01-HC-25195, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01
HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01
HL087652, HL105756, HL094555]; Affymetrix, Inc [N02-HL-6-4278]; Robert
Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine; Boston Medical Center; "Tiroler
Wissenschaftsfonds" [UNI-0407/29]; Helmholtz Zentrum Munchen; NIH
subcontract from the Children's Hospital, Boston, US [1 R01
DK075787-01A1]; German National Genome Research Net NGFN2 and NGFNplus
[01GS0823]; Wellcome Trust; European Commission [FP7/2007-2013,
HEALTH-F4-2007-201413, QLG2-CT-2002-01254]; Arthritis Research Campaign,
Chronic Disease Research Foundation; National Institute for Health
Research (NIHR) comprehensive Biomedical Research Centre; St Thomas' NHS
Foundation Trust in partnership with King's College London;
Biotechnology and Biological Sciences Research Council [G20234];
National Institute of Neurological Disorders and Stroke; National Center
for Research Resources [M01-RR00425]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK063491, R01DK056918]; NHLBI
[R01-HL085251]; Academy of Finland [114382, 126775, 127437, 129255,
129306, 130326, 209072, 210595, 213225, 216374, 126925, 121584, 124282,
129378, 117787, 41071, 125973, 129322, 129494, 139635, 129907, 135072];
Finnish Diabetes Research Society; Finnish Foundation for Pediatric
Research; Samfundet Folkhalsan; Juho Vainio Foundation; Novo Nordisk
Foundation; Finska Lakaresallskapet; Paivikki; Sakari Sohlberg
Foundation; Signe and Ane Gyllenberg Foundation; Yrjo Jahnsson
Foundation; Finnish Academy [118065]; Social Insurance Institution of
Finland, Kuopio; Tampere; Turku University Hospital; Paavo Nurmi
Foundation; Finnish Foundation of Cardiovascular Research; Tampere
Tuberculosis Foundation; Emil Aaltonen Foundation; Finnish Cultural
Foundation; Orion-Farmos Research Foundation; Finnish Foundation for
Cardiovascular Research; Sigrid Juselius Foundation; Medical Research
Council; Support for Science Funding programme; CamStrad; National
Heart, Lung, and Blood Institute (NHLBI) [N01-HC-65226, N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, RC2 HL102419];
National Heart, Lung, and Blood Institute, through contracts with
Jackson State University [N01-HC-95170]; University of Mississippi
Medical Center [N01-HC-95171]; Tougaloo College [N01-HC-95172]; National
Institutes of Health, National Center for Research Resources (NCRR) [UL1
RR025008]; NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1];
National Institutes of Health [HHSN268200782096C, DK078150, TW05596,
HL085144, RR20649, ES10126, DK56350]; NIH, National Institute on Aging.
Genetics, Arthrosis, and Progression; Leiden University Medical Centre;
Dutch Arthritis Association; Pfizer; Groton; CT; USA; Netherlands
Organization of Scientific Research [MW 904-61-095, 911-03-016, 917
66344, 911-03-012]; Centre of Medical System Biology; Netherlands
Consortium for Healthy Aging; TI-Pharma; National Human Genome Research
Institute [U01HG004402]; a component of the National Institutes of
Health and NIH Roadmap for Medical Research [UL1RR025005]; "Austrian
Genome Research Programme" (GEN-AU); Medizinische Forschungsgesellschaft
Salzburg; "Kamillo Eisner Stiftung" (Switzerland); General Secretary of
Research and Technology [PENED 03, EPSILON, DELTA. 474]; Canadian
Foundation for Innovation; Canadian Institutes of Health Research
(CIHR); Fonds de la recherche en sante du Quebec; Lady Davis Institute;
Ministere du Developpement economique; de l'Innovation et de
l'Exportation du Quebec; Jewish General Hospital; [092447/Z/10/Z];
[N01 HC-95159]; [N01-HC-95160]; [N01-HC-95161]; [N01-HC-95162];
[N01-HC-95163]; [N01-HC-95164]; [N01-HC-95165]; [N01-HC-95166];
[N01-HC-95167]; [N01-HC-95168]; [N01-HC-95169]; [RR-024156]
FX Baltimore Longitudinal Study of Aging (BLSA): The BLSA was supported in
part by the Intramural Research Program of the NIH, National Institute
on Aging. A portion of that support was through an R&D contract with
MedStar Research Institute. Erasmus Rucphen Family (ERF). The ERF study
was supported by grants from The Netherlands Organisation for Scientific
Research, Erasmus MC and the Centre for Medical Systems Biology (CMSB),
and the European Network for Genetic and Genomic Epidemiology (ENGAGE)
consortium. Invecchaire in Chianti (InCHIANTI). JRB Perry is a Sir Henry
Wellcome Postdoctoral Research Fellow (092447/Z/10/Z). Framingham Heart
Study (FHS): This research was conducted in part using data and
resources from the Framingham Heart Study of the National Heart Lung and
Blood Institute of the National Institutes of Health and Boston
University School of Medicine. The analyses reflect intellectual input
and resource development from the Framingham Heart Study investigators
participating in the SNP Health Association Resource (SHARe) project.
This work was partially supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its
contract with Affymetrix, Inc for genotyping services (Contract No.
N02-HL-6-4278). A portion of this research utilized the Linux Cluster
for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans
Endowment of the Department of Medicine at Boston University School of
Medicine and Boston Medical Center. The Collaborative Health Research in
the Region of Augsburg (KORA F3): This study was partially funded by the
"Tiroler Wissenschaftsfonds" (Project UNI-0407/29) and by the "Genomics
of Lipid-associated Disorders - GOLD" of the "Austrian Genome Research
Programme GEN-AU" to F Kronenberg. The MONICA/KORA Augsburg cohort study
was financed by the Helmholtz Zentrum Munchen. It was further funded by
the NIH subcontract from the Children's Hospital, Boston, US, (H-E
Wichmann and IM Heid, prime grant 1 R01 DK075787-01A1 to JN Hirschhorn)
and the German National Genome Research Net NGFN2 and NGFNplus (H-E
Wichmann 01GS0823). TwinsUK: Study was funded by the Wellcome Trust,
European Commission Framework (FP7/2007-2013), ENGAGE project
HEALTH-F4-2007-201413, and the FP5 GenomEUtwin Project
(QLG2-CT-2002-01254). It also receives support from the Arthritis
Research Campaign, Chronic Disease Research Foundation, the National
Institute for Health Research (NIHR) comprehensive Biomedical Research
Centre award to Guy's and St Thomas' NHS Foundation Trust in partnership
with King's College London, and a Biotechnology and Biological Sciences
Research Council project grant (G20234). Cardiovascular Health Study
(CHS): The CHS research reported in this article was supported by
contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01
HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01
HL080295 and R01 HL087652, HL105756, and HL094555 from the National
Heart, Lung, and Blood Institute, with additional contribution from the
National Institute of Neurological Disorders and Stroke. A full list of
principal CHS investigators and institutions can be found at
http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was
supported in part by National Center for Research Resources grant
M01-RR00425 to the Cedars-Sinai General Clinical Research Center
Genotyping core and National Institute of Diabetes and Digestive and
Kidney Diseases grant DK063491 to the Southern California Diabetes
Endocrinology Research Center, NHLBI R01-HL085251.; Helsinki Birth
Cohort Study (HBCS): HBCS has been supported by grants from Academy of
Finland (project numbers 114382, 126775, 127437, 129255, 129306, 130326,
209072, 210595, 213225, 216374), Finnish Diabetes Research Society,
Finnish Foundation for Pediatric Research, Samfundet Folkhalsan, Juho
Vainio Foundation, Novo Nordisk Foundation, Finska Lakaresallskapet,
Paivikki and Sakari Sohlberg Foundation, Signe and Ane Gyllenberg
Foundation, and Yrjo Jahnsson Foundation. DILGOM survey was funded by
the Finnish Academy, grant number 118065. Cardiovascular Risk in Young
Finns (YFS): The Young Finns Study has been financially supported by the
Academy of Finland: grants 126925, 121584, 124282, 129378 (Salve),
117787 (Gendi), and 41071 (Skidi), the Social Insurance Institution of
Finland, Kuopio, Tampere and Turku University Hospital Medical Funds,
Juho Vainio Foundation, Paavo Nurmi Foundation, Finnish Foundation of
Cardiovascular Research (T. L., OT.R), Tampere Tuberculosis Foundation
(Te.Le., Mik, Ka), the Emil Aaltonen Foundation (T. L.) and Finnish
Cultural Foundation. The expert technical assistance in the statistical
analyses by Irina Lisinen and Ville Aalto are gratefully acknowledged.
Dietary, Lifestyle, and Genetic determinants of Obesity and Metabolic
syndrome (DILGOM): K Kristiansson was supported by the Orion-Farmos
Research Foundation and the Academy of Finland (grant no. 125973). M
Perola and V Salomaa were supported by the Finnish Foundation for
Cardiovascular Research, the Sigrid Juselius Foundation, and the Academy
of Finland (grants 129322, 129494 and 139635). JG Eriksson was supported
by the Academy of Finland (grants 126775, 129255, 129907, and 135072).
Fenland study: The Fenland Study is funded by the Wellcome Trust and the
Medical Research Council, as well as by the Support for Science Funding
programme and CamStrad. We are grateful to all the volunteers for their
time and help, and to the General Practitioners and practice staff for
help with recruitment. We thank the Fenland Study co-ordination team and
the Field Epidemiology team of the MRC Epidemiology Unit for recruitment
and clinical testing. Multiethnic Study of Atherosclerosis (MESA): The
MESA project is conducted and supported by the National Heart, Lung, and
Blood Institute (NHLBI) in collaboration with MESA investigators.
Support is provided by grants and contracts N01 HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, and RR-024156.
Funding for CARe genotyping was provided by NHLBI Contract N01-HC-65226.
Jackson Heart Study (JHS): The Jackson Heart Study is supported by the
National Heart, Lung, and Blood Institute, through contracts with
Jackson State University (N01-HC-95170), the University of Mississippi
Medical Center (N01-HC-95171), and Tougaloo College (N01-HC-95172).
Adiponectin measurements used in the current study were funded by PHS
Award UL1 RR025008 from the Clinical and Translational Science Award
program, National Institutes of Health, National Center for Research
Resources (NCRR). Health ABC: This research was supported by NIA
contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide
association study was funded by NIA grant 1R01AG032098-01A1 to Wake
Forest University Health Sciences and genotyping services were provided
by the Center for Inherited Disease Research (CIDR). CIDR is fully
funded through a federal contract from the National Institutes of Health
to The Johns Hopkins University, contract number HHSN268200782096C.;
This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging. Genetics, Arthrosis, and
Progression) study (GARP): This study was supported the Leiden
University Medical Centre and the Dutch Arthritis Association. Pfizer,
Groton, CT, USA supported the inclusion of the GARP study. The genotypic
work was supported by the Netherlands Organization of Scientific
Research (MW 904-61-095, 911-03-016, 917 66344 and 911-03-012), Leiden
University Medical Centre and the Centre of Medical System Biology and
Netherlands Consortium for Healthy Aging both in the framework of the
Netherlands Genomics Initiative (NGI). The adiponectin measurements were
supported by TI-Pharma. Atherosclerosis Risk in Communities (ARIC): The
Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by National Heart, Lung, and Blood
Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018,
N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641,
R01HL59367, R01HL086694, and RC2 HL102419; National Human Genome
Research Institute contract U01HG004402; National Institutes of Health
contract HHSN268200625226C; and National Institute of Diabetes and
Digestive and Kidney Diseases R01DK056918. Infrastructure was partly
supported by Grant Number UL1RR025005,a component of the National
Institutes of Health and NIH Roadmap for Medical Research. Salzburg
Atherosclerosis Prevention Program in subjects at High Individual Risk
(SHAPIR): Part of this work was funded by the "Genomics of
Lipid-associated Disorders" (GOLD) of the "Austrian Genome Research
Programme" (GEN-AU) to Florian Kronenberg, and grants from the
"Medizinische Forschungsgesellschaft Salzburg" and the "Kamillo Eisner
Stiftung" (Switzerland) to Bernhard Paulweber. THISEAS: The genotyping
of the THISEAS study was funded by the Wellcome Trust. The recruitment
was partially supported by the General Secretary of Research and
Technology (PENED 03, EPSILON., DELTA. 474). We are grateful to all the
volunteers for their time and help, the medical staff of the hospitals
and the field investigators, Eirini Theodoraki, Maria Dimitriou and
Kathy Stirrups for her assistance in the genotyping. Cebu Longitudinal
Health and Nutrition Survey (CLHNS): We thank the Office of Population
Studies Foundation research and data collection teams and the study
participants who generously provided their time for this study. This
work was supported by National Institutes of Health grants DK078150,
TW05596, HL085144, RR20649, ES10126, and DK56350. Coordinating Centre:
McGill University. This work was supported by grants from the Canadian
Foundation for Innovation, the Canadian Institutes of Health Research
(CIHR), Fonds de la recherche en sante du Quebec, the Lady Davis
Institute, the Ministere du Developpement economique, de l'Innovation et
de l'Exportation du Quebec and the Jewish General Hospital. JB Richards
and Z Dastani are supported by the CIHR. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 56
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2012
VL 8
IS 3
AR e1002607
DI 10.1371/journal.pgen.1002607
PG 23
WC Genetics & Heredity
SC Genetics & Heredity
GA 918MV
UT WOS:000302254800080
PM 22479202
ER
PT J
AU White, YAR
Woods, DC
Takai, Y
Ishihara, O
Seki, H
Tilly, JL
AF White, Yvonne A. R.
Woods, Dori C.
Takai, Yasushi
Ishihara, Osamu
Seki, Hiroyuki
Tilly, Jonathan L.
TI Oogonial Stem Cells Isolated from Adult Human Ovaries Generate Oocytes
In Vitro and In Vivo
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [White, Yvonne A. R.; Woods, Dori C.; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA.
[Takai, Yasushi; Ishihara, Osamu; Seki, Hiroyuki] Saitama Med Sch, Saitama Med Ctr, Dept Obstet & Gynecol, Saitama, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 73A
EP 73A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543601003
ER
PT J
AU Wang, N
White, YA
Woods, DC
Tilly, JL
AF Wang, Ning
White, Yvonne Ar
Woods, Dori C.
Tilly, Jonathan L.
TI Steroid Hormone Regulation of Ovarian Germline Stem Cell Differentiation
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Wang, Ning; White, Yvonne Ar; Woods, Dori C.; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 79A
EP 80A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543601024
ER
PT J
AU Woods, DC
White, YAR
Rueda, BR
Tilly, JL
AF Woods, Dori C.
White, Yvonne A. R.
Rueda, Bo R.
Tilly, Jonathan L.
TI Tumorigenic Potential of Oogonial Stem Cells Is Actively Suppressed by
the Intraovarian Microenvironment.
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Woods, Dori C.; White, Yvonne A. R.; Rueda, Bo R.; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 93A
EP 93A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543601071
ER
PT J
AU Wang, N
Satirapod, C
Tilly, JL
AF Wang, Ning
Satirapod, Chonthicha
Tilly, Jonathan L.
TI Progressive Decline of Oogonial Stem Cell Activity Contributes to
Ovarian Aging.
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Wang, Ning; Satirapod, Chonthicha; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 110A
EP 110A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543601129
ER
PT J
AU Stanic, AK
Attaman, JA
Kim, M
Styer, AK
Rueda, BR
AF Stanic, Aleksandar K.
Attaman, Jill A.
Kim, Minji
Styer, Aaron K.
Rueda, Bo R.
TI Characterization of Immune Cell Populations in Murine Endometriosis-Like
Lesions
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Stanic, Aleksandar K.; Attaman, Jill A.; Kim, Minji; Styer, Aaron K.; Rueda, Bo R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Dept Obstet & Gyn, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 142A
EP 143A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543601240
ER
PT J
AU Faustino, LR
Woods, DC
White, YAR
Tilly, JL
AF Faustino, Luciana R.
Woods, Dori C.
White, Yvonne A. R.
Tilly, Jonathan L.
TI Oogonial Stem Cells Increase in Numbers in Aged Mouse Ovaries
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Faustino, Luciana R.; Woods, Dori C.; White, Yvonne A. R.; Tilly, Jonathan L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Bosotn, MA USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 224A
EP 224A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543602123
ER
PT J
AU Groeneweg, JW
Woods, DC
White, YAR
Takai, Y
Tilly, JL
AF Groeneweg, Jolijn W.
Woods, Dori C.
White, Yvonne A. R.
Takai, Yasushi
Tilly, Jonathan L.
TI Characterization of Meiosis in Ovarian Germ Cells of Reproductive-Age
Women
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Groeneweg, Jolijn W.; Woods, Dori C.; White, Yvonne A. R.; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA.
[Takai, Yasushi] Saitama Med Ctr, Dept Obstet & Gynecol, Saitama, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 225A
EP 225A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543602125
ER
PT J
AU Shalowitz, DI
Unger, C
Saadi, A
Shelton, K
Leffert, L
Albrecht, M
Wylie, B
AF Shalowitz, David I.
Unger, Cecile
Saadi, Altaf
Shelton, Kenneth
Leffert, Lisa
Albrecht, Meredith
Wylie, Blair
TI Intrapartum Pulse Pressure, Volume Status and Response to Epidural
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Shalowitz, David I.; Unger, Cecile; Saadi, Altaf; Shelton, Kenneth; Leffert, Lisa; Albrecht, Meredith; Wylie, Blair] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
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PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 233A
EP 233A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543602153
ER
PT J
AU Chattergoon, NN
Louey, S
Giraud, GD
Thornburg, KL
AF Chattergoon, Natasha N.
Louey, Samantha
Giraud, George D.
Thornburg, Kent L.
TI Myocardial Thyroid Hormone Deiodinases Are Regulated by Fetal T-3.
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Chattergoon, Natasha N.; Louey, Samantha; Giraud, George D.; Thornburg, Kent L.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97201 USA.
[Louey, Samantha; Giraud, George D.; Thornburg, Kent L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Giraud, George D.] Portland VA Med Ctr, Portland, OR USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 252A
EP 252A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543602219
ER
PT J
AU Edlow, A
Kaimal, A
Lee, H
Felsenstein, D
Riley, L
AF Edlow, Andrea
Kaimal, Anjali
Lee, Hang
Felsenstein, Donna
Riley, Laura
TI Screening for Herpes Simplex Virus in Pregnancy Does Not Impact Quality
of Life.
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Edlow, Andrea; Kaimal, Anjali; Riley, Laura] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Lee, Hang; Felsenstein, Donna] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 279A
EP 279A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543602309
ER
PT J
AU Doyle, J
Lee, HJ
Selesniemi, K
Ghazal, S
Rueda, B
Tilly, J
AF Doyle, Joseph
Lee, Ho Joon
Selesniemi, Kaisa
Ghazal, Sanaz
Rueda, Bo
Tilly, Jonathan
TI Effect of Vitrification on Aurora Kinase A Expression and Germinal
Vesicle Breakdown in Isolated Mouse Oocytes
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Doyle, Joseph; Lee, Ho Joon; Selesniemi, Kaisa; Ghazal, Sanaz; Rueda, Bo; Tilly, Jonathan] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA.
NR 0
TC 0
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U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 336A
EP 336A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543603123
ER
PT J
AU Young, BC
Panda, B
Madden, E
Bryant, A
AF Young, Brett C.
Panda, Britta
Madden, Erin
Bryant, Allison
TI What Happens after the Puerperium? The Impact of Pregnancy on the
Duration of Future Hospitalization
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 59th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 21-24, 2012
CL San Diego, CA
SP Soc Gynecol Invest
C1 [Young, Brett C.; Panda, Britta; Bryant, Allison] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Madden, Erin] VCIRE, Vet Res Inst, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 374A
EP 374A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543603253
ER
PT J
AU Young, BC
Panda, B
Madden, E
Bryant, A
AF Young, Brett C.
Panda, Britta
Madden, Erin
Bryant, Allison
TI To Bleed or Not To Bleed: What Are Risk Factors for Early Delivery with
Placenta Previa?
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 59th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 21-24, 2012
CL San Diego, CA
SP Soc Gynecol Invest
C1 [Young, Brett C.; Panda, Britta; Bryant, Allison] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Madden, Erin] VCIRE, Vet Res Inst, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2012
VL 19
IS S3
SU 3
BP 374A
EP 375A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LP
UT WOS:000329543603254
ER
PT J
AU Guanci, MM
AF Guanci, Mary McKenna
TI Can nurses place esophageal temperature probes? What is the procedure to
place an esophageal probe?
SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT
LA English
DT Letter
C1 Massachusetts Gen Hosp, Neurosci ICU, Boston, MA 02114 USA.
RP Guanci, MM (reprint author), Massachusetts Gen Hosp, Neurosci ICU, Boston, MA 02114 USA.
NR 4
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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 MAR 1
PY 2012
VL 2
IS 1
BP 45
EP 45
PG 1
WC Critical Care Medicine
SC General & Internal Medicine
GA V38PJ
UT WOS:000209355000012
ER
PT J
AU Borba, CPC
DePadilla, L
McCarty, FA
von Esenwein, SA
Druss, BG
Sterk, CE
AF Borba, Christina P. C.
DePadilla, Lara
McCarty, Frances A.
von Esenwein, Silke A.
Druss, Benjamin G.
Sterk, Claire E.
TI A Qualitative Study Examining the Perceived Barriers and Facilitators to
Medical Healthcare Services among Women with a Serious Mental Illness
SO WOMENS HEALTH ISSUES
LA English
DT Article
AB Objective: This qualitative study investigates the barriers and facilitators to accessing and utilizing healthcare services among women with a serious mental illness (SMI).
Methods: A purposive sample of 30 poor, urban, predominantly African-American women with a diagnosis of an SMI was recruited. Interviews were audio-taped and transcribed verbatim. Data analysis was guided by a modified constant comparison approach.
Results: The findings highlight a variety of nonmedical factors that serve as both barriers and facilitators to accessing and utilizing medical healthcare services, such as a trusting relationship with a mental health provider and a women's social network.
Conclusion: Nonmedical factors and personal circumstances seem to be important factors influencing pathways to healthcare services among women with an SMI. Efforts to better engage and retain women with an SMI into healthcare will need to better acknowledge and incorporate the larger social context of the women's lives. Copyright (C) 2012 by the Jacobs Institute of Women's Health. Published by Elsevier Inc.
C1 [Borba, Christina P. C.; DePadilla, Lara; Druss, Benjamin G.; Sterk, Claire E.] Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA.
[Borba, Christina P. C.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[McCarty, Frances A.] Georgia State Univ, Coll Hlth & Human Sci, Inst Publ Hlth, Atlanta, GA 30303 USA.
[von Esenwein, Silke A.; Druss, Benjamin G.] Emory Univ, Rollins Sch Publ Hlth, Dept Hlth Policy & Management, Atlanta, GA 30322 USA.
RP Borba, CPC (reprint author), 25 Staniford St, Boston, MA 02114 USA.
EM cborba@partners.org
NR 51
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
EI 1878-4321
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD MAR-APR
PY 2012
VL 22
IS 2
BP E217
EP E224
DI 10.1016/j.whi.2011.10.001
PG 8
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA V33SQ
UT WOS:000209038900015
PM 22172651
ER
PT J
AU Oshima, M
Deitiker, PR
Smith, RG
Mosier, D
Atassi, MZ
AF Oshima, Minako
Deitiker, Philip R.
Smith, R. Glenn
Mosier, Dennis
Atassi, M. Zouhair
TI T-cell recognition of acetylcholine receptor provides a reliable means
for monitoring autoimmunity to acetylcholine receptor in
antibody-negative myasthenia gravis patients
SO AUTOIMMUNITY
LA English
DT Article
DE Myasthenia gravis; acetylcholine receptor; seronegative; T cells;
synthetic peptides
ID PERIPHERAL-BLOOD LYMPHOCYTES; HIGH-RESOLUTION; ALPHA-SUBUNIT; IN-VITRO;
HLA-DQ; EXTRACELLULAR PART; CHAIN PEPTIDES; UNITED-STATES; ASSOCIATION;
DQB1-ASTERISK-0502
AB Myasthenia gravis (MG) is an autoimmune disease usually associated with autoantibodies (auto-Abs) against nicotinic acetylcholine receptor (AChR). Some MG patients appear negative for anti-AChR Abs (seronegative), and a fraction of these have auto-Abs against muscle-specific kinase. The remaining patients, although displaying MG symptoms, show no detectable auto-Abs. We describe here a possible association of a rare human leukocyte antigen (HLA)-DQ type and AChR Ab-negative MG. We also found that the majority of seronegative patients exhibit an anti-AChR autoimmune T lymphocyte response. We investigated the existence of AChR-reactive T cells in peripheral blood lymphocytes from seronegative patients by their proliferative responses against a mixture of 18 overlapping synthetic peptides encompassing the extracellular part of human AChR a-chain. Of the 10 samples, eight exhibited positive T-cell proliferative responses against the peptide mixtures. The proliferative assay was equally efficient using a mixture of eight peptides frequently recognized by MG T cells. This T-cell proliferative assay should provide a reliable method for monitoring seronegative MG patients.
C1 [Oshima, Minako; Deitiker, Philip R.; Atassi, M. Zouhair] Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
[Smith, R. Glenn] Univ Texas Med Branch, Dept Neurol, Galveston, TX 77555 USA.
[Mosier, Dennis] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Atassi, M. Zouhair] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.
[Mosier, Dennis] ME DeBakey VA Med Ctr, Neurol Serv, Houston, TX 77030 USA.
[Mosier, Dennis] ME DeBakey VA Med Ctr, Med Res Serv, Houston, TX 77030 USA.
RP Atassi, MZ (reprint author), Baylor Coll Med, Dept Biochem & Mol Biol, 1 Baylor Plaza,BCM125, Houston, TX 77030 USA.
EM matassi@bcm.edu
FU Muscular Dystrophy Association; Welch Foundation [Q-0007]
FX This study was partly supported by grants from the Muscular Dystrophy
Association. The support of the Welch Foundation (Grant Q-0007), due to
the award to M.Z. Atassi of the Robert A. Welch Chair of Chemistry, is
also gratefully acknowledged.
NR 31
TC 6
Z9 9
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0891-6934
J9 AUTOIMMUNITY
JI Autoimmunity
PD MAR
PY 2012
VL 45
IS 2
BP 153
EP 160
DI 10.3109/08916934.2011.611550
PG 8
WC Immunology
SC Immunology
GA 885AA
UT WOS:000299748800005
PM 21985279
ER
PT J
AU Yu, HE
Hawash, K
Picker, J
Stoler, J
Urion, D
Wu, BL
Shen, Y
AF Yu, H. E.
Hawash, K.
Picker, J.
Stoler, J.
Urion, D.
Wu, B-L
Shen, Y.
TI A recurrent 1.71 Mb genomic imbalance at 2q13 increases the risk of
developmental delay and dysmorphism
SO CLINICAL GENETICS
LA English
DT Article
DE 2q13-autism spectrum disorders; developmental delay; DNA copy number
variant; dysmorphism
ID COPY NUMBER; MICRODELETION SYNDROMES; REARRANGEMENTS; DIAGNOSIS; AUTISM;
BCL-2
AB Whole genome profiling such as array comparative genomic hybridization has identified novel genomic imbalances. Many of these genomic imbalances have since been shown to associate with developmental delay, intellectual disability and congenital malformation. Here we identified five unrelated individuals who have a recurrent 1.71 Mb deletion/ duplication at 2q13 (Human Genome Build 19: 111,392,197-113,102,594). Four of these individuals have developmental issues, four have cranial dysmorphism. Literature review revealed 14 more cases that had similar genomic imbalances at 2q13. Many of them had developmental delay and dysmorphism. Taken together, 93% and 63% of individuals with this genomic imbalance displayed impaired developmental skills and/ or abnormal facial features respectively. This copy number variant (CNV) has not been reported in normal control databases. We, therefore, propose that CNV in this region is a risk factor for developmental delay and dysmorphism.
C1 [Yu, H. E.; Wu, B-L; Shen, Y.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA.
[Hawash, K.; Urion, D.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Hawash, K.; Picker, J.; Stoler, J.; Urion, D.; Wu, B-L; Shen, Y.] Harvard Univ, Sch Med, Boston, MA USA.
[Picker, J.; Stoler, J.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Wu, B-L] Fudan Univ, Shanghai 200433, Peoples R China.
[Shen, Y.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Shen, Y (reprint author), Geisinger Hlth Syst, Dept Lab Med, Danville, PA 17822 USA.
EM yiping.shen@childrens.harvard.edu
FU Genetic Diagnostic Laboratory at Children's Hospital Boston; 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]
FX The authors thank the members of the Genetic Diagnostic Laboratory at
Children's Hospital Boston for support. Y. S. holds a Young Investigator
Award from the Children's Tumor Foundation and Catalyst Award from
Harvard Medical School. B. L. W. holds a Fudan Scholar Research Award
from Fudan University and a grant from Chinese National "973" project on
Population and Health (Grant Number: 2010CB529601) and a grant from
Science and Technology Council of Shanghai (Grant Number: 09JC1402400.)
NR 21
TC 17
Z9 18
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD MAR
PY 2012
VL 81
IS 3
BP 257
EP 264
DI 10.1111/j.1399-0004.2011.01637.x
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 884HB
UT WOS:000299694400008
PM 21255006
ER
PT J
AU Cayabyab, MJ
Kashino, SS
Campos-Neto, A
AF Cayabyab, Mark J.
Kashino, Suely S.
Campos-Neto, Antonio
TI Robust immune response elicited by a novel and unique Mycobacterium
tuberculosis protein using an optimized DNA/protein heterologous
prime/boost protocol
SO IMMUNOLOGY
LA English
DT Article
DE Mycobacterium tuberculosis; prime; boost; vaccine
ID BACILLE CALMETTE-GUERIN; VACCINIA VIRUS ANKARA; T-CELL RESPONSES; ACTIVE
PULMONARY TUBERCULOSIS; CROSS-PRESENTATION; ENHANCED IMMUNOGENICITY;
PROTECTIVE EFFICACY; EXOGENOUS ANTIGENS; DENDRITIC CELLS; LEUKEMIA-VIRUS
AB An efficacious tuberculosis (TB) vaccine will probably need to induce both CD4 and CD8 T-cell responses specific to a protective Mycobacterium tuberculosis antigen(s). To achieve this broad cellular immune response we tested a heterologous DNA/protein combination vaccine strategy. We used a purified recombinant protein preparation of a unique M. tuberculosis antigen (rMT1721) found in the urine of TB patients, an optimized plasmid DNA expressing this protein (DNA-MT1721), and a Toll-like receptor 4 agonist adjuvant. We found that priming mice with DNA-MT1721 and subsequently boosting with rMT1721 elicited high titres of specific IgG1 and IgG2a antibodies as well as high magnitude and polyfunctional CD4+ T-cell responses. However, no detectable CD8+ T-cell response was observed using this regimen of immunization. In contrast, both CD4+ and CD8+ T-cell responses were detected after a prime/boost vaccination regimen using rMT1721 as the priming antigen and DNA-MT1721 as the boosting immunogen. These findings support the exploration of heterologous DNA/protein immunization strategies in vaccine development against TB and possibly other infectious diseases.
C1 [Cayabyab, Mark J.; Kashino, Suely S.; Campos-Neto, Antonio] Forsyth Inst, Global Infect Dis Res Ctr, Cambridge, MA 02142 USA.
[Cayabyab, Mark J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
RP Campos-Neto, A (reprint author), Forsyth Inst, Global Infect Dis Res Ctr, 245 1st St, Cambridge, MA 02142 USA.
EM acampos@forsyth.org
RI Kashino, Suely/F-4171-2012
FU Colorado State University (NIAID/NIH) [1-A125174]; National Institutes
of Health [R01 AI076425]
FX We thank Dr John Beslile, Dr Angelo Izzo and Dr Karen Dobos, Colorado
State University (NIAID/NIH Tuberculosis Research Materials contract no.
1-A125174), for kindly supplying M. tuberculosis culture filtrate
proteins and Dr Lizeng Qin for his expert help with the intracellular
cytokine staining assay and analysis.; This work was supported by the
following grant from the National Institutes of Health: R01 AI076425 to
A. Campos-Neto.
NR 42
TC 7
Z9 7
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD MAR
PY 2012
VL 135
IS 3
BP 216
EP 225
DI 10.1111/j.1365-2567.2011.03525.x
PG 10
WC Immunology
SC Immunology
GA 880PC
UT WOS:000299418400005
PM 22043824
ER
PT J
AU Hardy, DC
Ross, JH
Schuyler, CA
Leite, RS
Slate, EH
Huang, Y
AF Hardy, Douglas C.
Ross, Jonathan H.
Schuyler, Corinne A.
Leite, Renata S.
Slate, Elizabeth H.
Huang, Yan
TI Matrix metalloproteinase-8 expression in periodontal tissues surgically
removed from diabetic and non-diabetic patients with periodontal disease
SO JOURNAL OF CLINICAL PERIODONTOLOGY
LA English
DT Article
DE diabetes mellitus; gene expression; metalloproteinase-8; periodontal
diseases
ID GINGIVAL CREVICULAR FLUID; NEUTROPHIL COLLAGENASE ACTIVITY; CHAIR-SIDE
TEST; IN-VIVO; MMP-8; INTERLEUKIN-6; LIPOPOLYSACCHARIDE; MELLITUS;
OBESITY; CELLS
AB Background: Although it is known that periodontal matrix metalloproteinase-8 (MMP-8) expression is associated with periodontal disease, the information concerning the periodontal MMP-8 expression in diabetic patients with periodontal disease is insufficient.
Materials and Methods: Periodontal tissue specimens were collected from seven patients without periodontal disease and diabetes (Group 1), 15 patients with periodontal disease alone (Group 2) and 10 patients with both periodontal disease and diabetes (Group 3). The frozen sections were prepared and MMP-8 protein expression was detected using immunohistochemistry and quantified. For in vitro study, human U937 mononuclear cells were pre-exposed to normal or high glucose and then treated with lipopolysaccharide (LPS).
Results: The nonparametric Kruskal-Wallis test showed that the difference in MMP-8 protein levels among the three groups were statistically significant (p = 0.003). Nonparametric analysis using Jonckheere-Terpstra test showed a tendency of increase in periodontal MMP-8 levels across Group 1 to Group 2 to Group 3 (p = 0.0002). In vitro studies showed that high glucose and LPS had a synergistic effect on MMP-8 expression.
Conclusion: Our current study showed an increasing trend in MMP-8 protein expression levels across patients without both periodontal disease and diabetes, patients with periodontal disease alone and patients with both diseases.
C1 [Huang, Yan] Med Univ S Carolina, Dept Med, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA.
[Hardy, Douglas C.; Ross, Jonathan H.] Med Univ S Carolina, Coll Dent Med, Dept Stomatol, Div Periodont, Charleston, SC 29403 USA.
[Leite, Renata S.; Slate, Elizabeth H.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29403 USA.
[Huang, Yan] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA.
RP Huang, Y (reprint author), Med Univ S Carolina, Dept Med, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA.
EM huangyan@musc.edu
FU NIH [DE016353]; Department of Veterans Affairs
FX There is no conflict of interest to declare. This study was supported by
NIH grant DE016353 and Merit Review Grant from Department of Veterans
Affairs (to Y. H.).
NR 40
TC 10
Z9 13
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0303-6979
J9 J CLIN PERIODONTOL
JI J. Clin. Periodontol.
PD MAR
PY 2012
VL 39
IS 3
BP 249
EP 255
DI 10.1111/j.1600-051X.2011.01788.x
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 883LM
UT WOS:000299635500005
PM 22092744
ER
PT J
AU Oliveira, APD
de Faveri, M
Gursky, LC
Mestnik, MJ
Feres, M
Haffajee, AD
Socransky, SS
Teles, RP
AF de Lima Oliveira, Ana Paula
de Faveri, Marcelo
Gursky, Lauren Christine
Mestnik, Maria Josefa
Feres, Magda
Haffajee, Anne D.
Socransky, Sigmund S.
Teles, Ricardo Palmier
TI Effects of periodontal therapy on GCF cytokines in generalized
aggressive periodontitis subjects
SO JOURNAL OF CLINICAL PERIODONTOLOGY
LA English
DT Article
DE cytokines; gingival crevicular fluid; periodontal disease; periodontal
therapy
ID GINGIVAL CREVICULAR FLUID; TUMOR-NECROSIS-FACTOR;
PORPHYROMONAS-GINGIVALIS; CLINICAL-PARAMETERS; PROGRESSIVE
PERIODONTITIS; NONSURGICAL TREATMENT; ADULT PERIODONTITIS;
BONE-RESORPTION; INTERLEUKIN-1-BETA; METRONIDAZOLE
AB Aim: To examine changes in levels of gingival crevicular fluid (GCF) cytokines, after periodontal therapy of generalized aggressive periodontitis (GAgP).
Materials and Methods: Twenty-five periodontally healthy and 24 GAgP subjects had periodontal clinical parameters measured and gingival crevicular fluid (GCF) samples collected from up to 14 sites/subject. GCF samples were analysed using multiplex bead immunoassay for: GM-CSF, IFN-gamma, IL-10, IL-1 beta, IL-2, IL-6 and TNF-alpha. Aggressive periodontitis subjects were randomly assigned to either scaling and root planing (SRP) alone or SRP plus systemic amoxicillin (500 mg) and metronidazole (400 mg) 3 times a day for 14 days. Clinical parameters and GCF cytokines were re-measured 6 months after treatment. Differences over time were analysed using the Wilcoxon test and between groups using the Mann-Whitney test.
Results: Significant reductions in GCF GM-CSF, IL-1 beta and the ratio IL-1 beta/IL-10 and increases in GCF IL-6 were detected after therapy. The mean change in GCF cytokines did not differ significantly between groups.
Conclusions: Periodontal therapy improved GCF cytokine profiles by lowering IL-1 beta and increasing IL-10 levels. The reduction in GCF GM-CSF after therapy implicates this cytokine in the pathogenesis of GAgP. There was no difference between therapies in changes of GCF cytokines.
C1 [Teles, Ricardo Palmier] Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA.
[de Lima Oliveira, Ana Paula] Univ Fed Minas Gerais, Sch Dent, Dept Periodontol, Belo Horizonte, MG, Brazil.
[de Faveri, Marcelo; Mestnik, Maria Josefa; Feres, Magda] Univ Guarulhos, Dept Periodontol, Dent Res Div, Guarulhos, SP, Brazil.
[Gursky, Lauren Christine] Pontificia Univ Catolica Parana, Sch Dent, Curitiba, PR, Brazil.
[Teles, Ricardo Palmier] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
RP Teles, RP (reprint author), Forsyth Inst, Dept Periodontol, 245 1st St, Cambridge, MA 02142 USA.
EM rteles@forsyth.org
RI Faveri, Marcelo/C-4738-2012; Oliveira, Ana Paula/M-6700-2013; Feres,
Magda/H-7964-2012
OI Oliveira, Ana Paula/0000-0001-6532-1700;
FU NIDCR [U01 DE021127]; Fundacao de Amparo a Pesquisa do Estado de Sao
Paulo (FAPESP, Brazil) [2007/56413-0]
FX This study was supported in part by NIDCR grant U01 DE021127 and by
grant 2007/56413-0 from Fundacao de Amparo a Pesquisa do Estado de Sao
Paulo (FAPESP, Brazil).
NR 41
TC 29
Z9 32
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0303-6979
J9 J CLIN PERIODONTOL
JI J. Clin. Periodontol.
PD MAR
PY 2012
VL 39
IS 3
BP 295
EP 302
DI 10.1111/j.1600-051X.2011.01817.x
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 883LM
UT WOS:000299635500010
PM 22126282
ER
PT J
AU Poynter, JN
Hooten, AJ
Frazier, AL
Ross, JA
AF Poynter, Jenny N.
Hooten, Anthony J.
Frazier, A. Lindsay
Ross, Julie A.
TI Associations between variants in KITLG, SPRY4, BAK1, and DMRT1 and
pediatric germ cell tumors
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID TESTIS DIFFERENTIATION; MAMMALIAN TESTIS; UNITED-STATES; CANCER; MOUSE;
FETAL; SUSCEPTIBILITY; PROLIFERATION; MIGRATION; MIDLINE
AB Recent genome wide association studies have identified susceptibility loci for adult testicular germ cell tumors (GCT) near KITLG, SPRY4, BAK1, and DMRT1. We evaluated variants in these four genes to determine whether these are also susceptibility loci for pediatric GCTs. DNA was isolated from 52 pediatric GCTs (ages 021 years) obtained from the Cooperative Human Tissue Network. Control DNA was isolated from de-identified dried blood spots from 141 white newborns. Genotyping was conducted using TaqMan assays (rs4474514) or by PCR and sequencing (rs4324715, rs210138, and rs755383). Associations between variants and GCT were evaluated using logistic regression with adjustment for sex. We also evaluated whether the associations differed by age at GCT diagnosis (09 years, 1021 years), sex, and tumor location (gonadal, non-gonadal). We observed a significant association for rs210138 (BAK1) and pediatric GCT overall (odds ratio (OR) = 1.80, 95% confidence interval (CI) 1.102.95, P = 0.02) with non-significant associations similar in magnitude in both the pediatric (P = 0.09) and adolescent (P = 0.06) age groups. The KITLG (rs4474514) and SPRY4 (rs4324715) variants were significantly associated with GCT only in the adolescent age group (rs4474514: OR = 2.28, 95% CI 1.094.79, P = 0.03 and rs4324715: OR = 2.40, 95% CI 1.194.83, P = 0.01). Associations were mostly similar when stratified by sex. This is the first study to suggest that these loci may also be important in susceptibility to GCTs in the adolescent (KITLG, SPRY4, and BAK1) and pediatric (BAK1) age groups. (c) 2011 Wiley Periodicals, Inc.
C1 [Poynter, Jenny N.; Ross, Julie A.] Univ Minnesota, Div Pediat Epidemiol & Clin Res, Dept Pediat, Minneapolis, MN 55455 USA.
[Poynter, Jenny N.; Hooten, Anthony J.; Ross, Julie A.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA.
[Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Poynter, JN (reprint author), Univ Minnesota, Div Pediat Epidemiol & Clin Res, Dept Pediat, 420 Delaware St SE,MMC 715, Minneapolis, MN 55455 USA.
EM poynt006@umn.edu
FU Children's Cancer Research Fund
FX Supported by: Children's Cancer Research Fund.
NR 28
TC 17
Z9 17
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1045-2257
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD MAR
PY 2012
VL 51
IS 3
BP 266
EP 271
DI 10.1002/gcc.20951
PG 6
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 873JU
UT WOS:000298880000007
PM 22072546
ER
PT J
AU Cianchetti, M
Varvares, MA
Deschler, DG
Liebsch, NJ
Wang, JJ
Chan, ANW
AF Cianchetti, Marco
Varvares, Mark A.
Deschler, Daniel G.
Liebsch, Nobert J.
Wang, Jing J.
Chan, Annie W.
TI Risk of sinonasal-cutaneous fistula after treatment for advanced
sinonasal cancer
SO JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 52nd Annual Meeting of the
American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO)
CY OCT 31-NOV 04, 2010
CL San Diego, CA
SP Amer Soc Therapeut Radiol & Oncol (ASTRO)
DE fistula; sinonasal malignancy; paranasal sinus cancer; craniofacial
resection; radiation
ID PARANASAL SINUSES; RADIATION-THERAPY; NECK-CANCER; CARCINOMA; HEAD;
RECONSTRUCTION; RADIOTHERAPY; TUMORS; FLAP
AB Background and Objectives To determine the rate and the risk factors for sinonasal-cutaneous fistula formation after treatment for sinonasal malignancy.
Methods: Between 1991 and 2002, 99 patients with advanced sinonasal malignancy received radiation therapy +/- surgery. Primary site was maxillary sinus in 30, ethmoid sinus in 19, nasal cavity in 32, nasopharynx in 3, and sphenoid sinus in 15 patients. Eighty-two percent of patients had T4 disease. Sixty-eight percent of patients had undergone surgical resection. Median follow-up was 70.6 months.
Results: Eight patients developed >= grade 3 sinonasal-cutaneous fistulas at a median time of 3.8 months after radiation. The overall rates of developing >= grade 3 fistulas in the entire group at 2 and 5 years were 6% and 10%, respectively. The fistulas were in the medial canthus in seven patients and in the infraorbital region in one patient. Fistulas developed exclusively along the transfacial incision scar and in patients whose tumors extended to the subcutaneous tissues. In univariate analysis, squamous cell carcinoma histology (P = 0.008), <= T4a primary tumor category (P = 0.02), and transfacial incision (P = 0.02) were associated with increased risk of fistula formation.
Conclusions: Histologic subtype, T category, and quality of the skin and the underlying supporting tissues after transfacial incision are risk factors for sinonasal-cutaneous fistula formation. J. Surg. Oncol. 2012;105:261-265. (C) 2011 Wiley Periodicals, Inc.
C1 [Cianchetti, Marco; Liebsch, Nobert J.; Wang, Jing J.; Chan, Annie W.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Varvares, Mark A.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Varvares, Mark A.; Deschler, Daniel G.; Liebsch, Nobert J.; Chan, Annie W.] Harvard Univ, Sch Med, Boston, MA USA.
RP Chan, ANW (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St,Cox 337, Boston, MA 02114 USA.
EM awchan@partners.org
NR 14
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-4790
J9 J SURG ONCOL
JI J. Surg. Oncol.
PD MAR
PY 2012
VL 105
IS 3
BP 261
EP 265
DI 10.1002/jso.22062
PG 5
WC Oncology; Surgery
SC Oncology; Surgery
GA 879ZV
UT WOS:000299374300009
PM 22375288
ER
PT J
AU Ryu, KY
Park, H
Rossi, DJ
Weissman, IL
Kopito, RR
AF Ryu, Kwon-Yul
Park, Hyejin
Rossi, Derrick J.
Weissman, Irving L.
Kopito, Ron R.
TI Perturbation of the Hematopoietic System during Embryonic Liver
Development Due to Disruption of Polyubiquitin Gene Ubc in Mice
SO PLOS ONE
LA English
DT Article
ID UBIQUITIN-PROTEASOME SYSTEM; STEM-CELLS; DEFICIENCIES; DEGRADATION;
PROGRESSION; LACKING
AB Disruption of the polyubiquitin gene Ubc leads to a defect in fetal liver development, which can be partially rescued by increasing the amount of ubiquitin. However, it is still not known why Ubc is required for fetal liver development and the nature of the defective cell types responsible for embryonic lethality have not been characterized. In this study, we assessed the cause of embryonic lethality with respect to the fetal liver hematopoietic system. We found that Ubc was highly expressed in the embryonic liver, and the proliferation capacity of fetal liver cells was reduced in Ubc(-/-) embryos. Specifically, Ubc was most highly expressed in hematopoietic cells, and the proliferation capacity of hematopoietic cells was significantly impaired in Ubc(-/-) embryos. While hematopoietic cell and hematopoietic stem cell (HSC) frequency was maintained in Ubc(-/-) embryos, the absolute number of these cells was diminished because of reduced total liver cell number in Ubc(-/-) embryos. Transplantations of fetal liver cells into lethally irradiated recipient mice by non-competitive and competitive reconstitution methods indicated that disruption of Ubc does not significantly impair the intrinsic function of fetal liver HSCs. These findings suggest that disruption of Ubc reduces the absolute number of HSCs in embryonic livers, but has no significant effect on the autonomous function of HSCs. Thus, the lethality of Ubc(-/-) embryos is not the result of intrinsic HSC failure.
C1 [Ryu, Kwon-Yul; Park, Hyejin] Univ Seoul, Dept Life Sci, Seoul, South Korea.
[Rossi, Derrick J.] Harvard Univ, Sch Med, Immune Dis Inst, Harvard Stem Cell Inst, Boston, MA USA.
[Rossi, Derrick J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Weissman, Irving L.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Kopito, Ron R.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
RP Ryu, KY (reprint author), Univ Seoul, Dept Life Sci, Seoul, South Korea.
EM kyryu@uos.ac.kr
FU National Research Foundation of Korea; Ministry of Education, Science
and Technology [20100009065, 20110004618]
FX This research was supported by Basic Science Research Program through
the National Research Foundation of Korea funded by the Ministry of
Education, Science and Technology (20100009065 & 20110004618,
http://www.nrf.re.kr/html/en/). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 24
TC 5
Z9 5
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 FEB 29
PY 2012
VL 7
IS 2
AR e32956
DI 10.1371/journal.pone.0032956
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 928SI
UT WOS:000303003500114
PM 22393459
ER
PT J
AU Sinha, AU
Armstrong, SA
AF Sinha, Amit U.
Armstrong, Scott A.
TI iCanPlot: Visual Exploration of High-Throughput Omics Data Using
Interactive Canvas Plotting
SO PLOS ONE
LA English
DT Article
AB Increasing use of high throughput genomic scale assays requires effective visualization and analysis techniques to facilitate data interpretation. Moreover, existing tools often require programming skills, which discourages bench scientists from examining their own data. We have created iCanPlot, a compelling platform for visual data exploration based on the latest technologies. Using the recently adopted HTML5 Canvas element, we have developed a highly interactive tool to visualize tabular data and identify interesting patterns in an intuitive fashion without the need of any specialized computing skills. A module for geneset overlap analysis has been implemented on the Google App Engine platform: when the user selects a region of interest in the plot, the genes in the region are analyzed on the fly. The visualization and analysis are amalgamated for a seamless experience. Further, users can easily upload their data for analysis-which also makes it simple to share the analysis with collaborators. We illustrate the power of iCanPlot by showing an example of how it can be used to interpret histone modifications in the context of gene expression.
C1 [Sinha, Amit U.; Armstrong, Scott A.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Div Hematol Oncol, Boston, MA 02115 USA.
[Sinha, Amit U.; Armstrong, Scott A.] Harvard Univ, Sch Med, Boston, MA USA.
[Armstrong, Scott A.] Harvard Stem Cell Inst, Boston, MA USA.
RP Sinha, AU (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Div Hematol Oncol, Boston, MA 02115 USA.
EM amit.sinha@childrens.harvard.edu; scott.armstrong@childrens.harvard.edu
FU Charles H. Hood Foundation; Leukemia and Lymphoma Society
FX This work was supported in part by the Charles H. Hood Foundation and
the Leukemia and Lymphoma Society. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript. No additional external funding was
received for this study.
NR 10
TC 7
Z9 7
U1 0
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 FEB 29
PY 2012
VL 7
IS 2
AR e31690
DI 10.1371/journal.pone.0031690
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 928SI
UT WOS:000303003500020
PM 22393367
ER
PT J
AU Zhang, N
Zhang, SL
Szostak, JW
AF Zhang, Na
Zhang, Shenglong
Szostak, Jack W.
TI Activated Ribonucleotides Undergo a Sugar Pucker Switch upon Binding to
a Single-Stranded RNA Template
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PROTON-MAGNETIC-RESONANCE; DIRECTED SYNTHESIS; HAIRPIN OLIGONUCLEOTIDES;
DNA; OLIGOMERIZATION; CONFORMATION; NUCLEOTIDES; GUANOSINE; RESIDUES;
LIGANDS
AB Template-directed polymerization of chemically activated ribonucleotide monomers, such as nucleotide 5'-phosphorimidazolides, has been studied as a model for nonenzymatic RNA replication during the origin of life. Kinetic studies of the polymerization of various nucleotide monomers on oligonucleotide templates have suggested that the A-form (C3'-endo sugar pucker) conformation is optimal for both monomers and templates for efficient copying. However, RNA monomers are predominantly in the C2'-endo conformation when free in solution, except for cytidine, which is approximately equally distributed between the C2'-endo and C3'-endo conformations. We hypothesized that ribonucleotides undergo a switch in sugar pucker upon binding to an A-type template and that this conformational switch allows or enhances subsequent polymerization. We used transferred nuclear Overhauser effect spectroscopy (TrNO-ESY), which can be used for specific detection of the bound conformation of small-molecule ligands with relatively weak affinity to receptors, to study the interactions between nucleotide 5'-phosphorimidazolides and single-stranded oligonucleotide templates. We found that the sugar pucker of activated ribonucleotides switches from C2'-endo in the free state to C3'-endo upon binding to an RNA template. This switch occurs only on RNA and not on DNA templates. Furthermore, activated 2'-deoxyribonucleotides maintain a C2'-endo sugar pucker in both the free and template-bound states. Our results provide a structural explanation for the observations that activated ribonucleotides are superior to activated deoxyribonucleotides and that RNA templates are superior to DNA templates in template-directed nonenzymatic primer-extension reactions.
C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA.
EM szostak@molbio.mgh.harvard.edu
FU F [CHE-0809413]
FX We are grateful to Itay Budin, Ting Zhu, and Aaron Engelhart for helpful
discussions and comments on the manuscript. This research was funded in
part by Grant CHE-0809413 from the NSF. J.W.S. is an Investigator of the
Howard Hughes Medical Institute.
NR 29
TC 20
Z9 20
U1 1
U2 28
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 FEB 29
PY 2012
VL 134
IS 8
BP 3691
EP 3694
DI 10.1021/ja212027q
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 903ZE
UT WOS:000301161600020
PM 22296305
ER
PT J
AU Sabolek, HR
Swiercz, WB
Lillis, KP
Cash, SS
Huberfeld, G
Zhao, G
Ste Marie, L
Clemenceau, S
Barsh, G
Miles, R
Staley, KJ
AF Sabolek, Helen R.
Swiercz, Waldemar B.
Lillis, Kyle P.
Cash, Sydney S.
Huberfeld, Gilles
Zhao, Grace
Ste Marie, Linda
Clemenceau, Stephane
Barsh, Greg
Miles, Richard
Staley, Kevin J.
TI A Candidate Mechanism Underlying the Variance of Interictal Spike
Propagation
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID TEMPORAL-LOBE EPILEPSY; SYNCHRONIZED HIPPOCAMPAL BURSTS; RECURRENT
COLLATERAL SYNAPSES; CA3 NETWORK ACTIVITY; EPILEPTIFORM ACTIVITY; RAT
HIPPOCAMPUS; IN-VITRO; GABAERGIC INHIBITION; SURROUND INHIBITION;
ORGANOTYPIC CULTURE
AB Synchronous activation of neural networks is an important physiological mechanism, and dysregulation of synchrony forms the basis of epilepsy. We analyzed the propagation of synchronous activity through chronically epileptic neural networks. Electrocorticographic recordings from epileptic patients demonstrate remarkable variance in the pathways of propagation between sequential interictal spikes (IISs). Calcium imaging in chronically epileptic slice cultures demonstrates that pathway variance depends on the presence of GABAergic inhibition and that spike propagation becomes stereotyped following GABA receptor blockade. Computer modeling suggests that GABAergic quenching of local network activations leaves behind regions of refractory neurons, whose late recruitment forms the anatomical basis of variability during subsequent network activation. Targeted path scanning of slice cultures confirmed local activations, while ex vivo recordings of human epileptic tissue confirmed the dependence of interspike variance on GABA-mediated inhibition. These data support the hypothesis that the paths by which synchronous activity spreads through an epileptic network change with each activation, based on the recent history of localized activity that has been successfully inhibited.
C1 [Sabolek, Helen R.; Swiercz, Waldemar B.; Lillis, Kyle P.; Cash, Sydney S.; Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Sabolek, Helen R.; Swiercz, Waldemar B.; Lillis, Kyle P.; Cash, Sydney S.; Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Huberfeld, Gilles; Clemenceau, Stephane; Miles, Richard] Univ Paris 06, Inst Cerveau Moelle, Cortex & Epilepsy Lab,CNRS,UMR7225, Inst Natl Sante & Rech Med,Ctr Rech,UMRS975, F-75654 Paris, France.
[Huberfeld, Gilles; Clemenceau, Stephane; Miles, Richard] Hop La Pitie Salpetriere, AP HP, Epilepsy Unit, F-75013 Paris, France.
[Huberfeld, Gilles; Clemenceau, Stephane; Miles, Richard] UPMC, F-75005 Paris, France.
[Zhao, Grace] Stanford Univ, Dept Neurobiol, Palo Alto, CA 94304 USA.
[Ste Marie, Linda; Barsh, Greg] Stanford Univ, Dept Genet, Palo Alto, CA 94304 USA.
RP Staley, KJ (reprint author), Massachusetts Gen Hosp, 114 16th St,Room 2600, Boston, MA 02129 USA.
EM kstaley@partners.org
FU NIH [5R01NS034700, 1R01NS074772]
FX This work was supported by NIH Grants 5R01NS034700 and 1R01NS074772.
NR 75
TC 24
Z9 24
U1 1
U2 8
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 29
PY 2012
VL 32
IS 9
BP 3009
EP 3021
DI 10.1523/JNEUROSCI.5853-11.2012
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 901CA
UT WOS:000300938100009
PM 22378874
ER
PT J
AU Hudry, E
Wu, HY
Arbel-Ornath, M
Hashimoto, T
Matsouaka, R
Fan, ZY
Spires-Jones, TL
Betensky, RA
Bacskai, BJ
Hyman, BT
AF Hudry, Eloise
Wu, Hai-Yan
Arbel-Ornath, Michal
Hashimoto, Tadafumi
Matsouaka, Roland
Fan, Zhanyun
Spires-Jones, Tara L.
Betensky, Rebecca A.
Bacskai, Brian J.
Hyman, Bradley T.
TI Inhibition of the NFAT Pathway Alleviates Amyloid Beta Neurotoxicity in
a Mouse Model of Alzheimer's Disease
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID LONG-TERM DEPRESSION; IN-VIVO; DENDRITIC SPINES; TRANSGENIC MICE;
SYNAPSE LOSS; MULTIPHOTON MICROSCOPY; NERVOUS-SYSTEM; AD BRAIN;
CALCINEURIN; PROTEIN
AB Amyloid beta (A beta) peptides, the main pathological species associated with Alzheimer's disease (AD), disturb intracellular calcium homeostasis, which in turn activates the calcium-dependent phosphatase calcineurin (CaN). CaN activation induced by A beta leads to pathological morphological changes in neurons, and overexpression of constitutively active calcineurin is sufficient to generate a similar phenotype, even without A beta. Here, we tested the hypothesis that calcineurin mediates neurodegenerative effects via activation of the nuclear transcription factor of activated T-cells (NFAT). We found that both spine loss and dendritic branching simplification induced by A beta exposure were mimicked by constitutively active NFAT, and abolished when NFAT activation was blocked using the genetically encoded inhibitor VIVIT. When VIVIT was specifically addressed to the nucleus, identical beneficial effects were observed, thus enforcing the role of NFAT transcriptional activity in A beta-related neurotoxicity. In vivo, when VIVIT or its nuclear counterpart were overexpressed in a transgenic model of Alzheimer's disease via a gene therapy approach, the spine loss and neuritic abnormalities observed in the vicinity of amyloid plaques were blocked. Overall, these results suggest that NFAT/calcineurin transcriptional cascades contribute to A beta synaptotoxicity, and may provide a new specific set of pathways for neuroprotective strategies.
C1 [Hudry, Eloise; Wu, Hai-Yan; Arbel-Ornath, Michal; Hashimoto, Tadafumi; Fan, Zhanyun; Spires-Jones, Tara L.; Bacskai, Brian J.; Hyman, Bradley T.] Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Dept Neurol, Charlestown, MA 02129 USA.
[Matsouaka, Roland; Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Hyman, BT (reprint author), Massachusetts Gen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA.
EM bhyman@partners.org
RI Hashimoto, Tadafumi/A-7723-2013;
OI Spires-Jones, Tara/0000-0003-2530-0598
FU National Institutes of Health [AG08487, EB000768, EY13399]; Harvard
Medical School; French Bettencourt-Schueller award
FX This work was supported by National Institutes of Health Grants AG08487,
EB000768, and EY13399, the Lefler fellowship (Harvard Medical School),
and the French Bettencourt-Schueller award for young scientists. We
thank Dr. Norris (Sanders-Brown Center on Aging, Lexington, KY) for
providing the VIVIT-GFP constructs and Dr. Ruthazer (Montreal
Neurological Institute, McGill University, Montreal, QC, Canada) for
providing the NLS-VIVIT-GFP plasmid. We thank Dr. Alberto Serrano-Pozo
for helpful comments during manuscript preparation and Daniel Joyner for
primary neuron preparation.
NR 63
TC 32
Z9 33
U1 1
U2 10
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 29
PY 2012
VL 32
IS 9
BP 3176
EP 3192
DI 10.1523/JNEUROSCI.6439-11.2012
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA 901CA
UT WOS:000300938100025
PM 22378890
ER
PT J
AU Soghoian, DZ
Jessen, H
Flanders, M
Sierra-Davidson, K
Cutler, S
Pertel, T
Ranasinghe, S
Lindqvist, M
Davis, I
Lane, K
Rychert, J
Rosenberg, ES
Piechocka-Trocha, A
Brass, AL
Brenchley, JM
Walker, BD
Streeck, H
AF Soghoian, Damien Z.
Jessen, Heiko
Flanders, Michael
Sierra-Davidson, Kailan
Cutler, Sam
Pertel, Thomas
Ranasinghe, Srinika
Lindqvist, Madelene
Davis, Isaiah
Lane, Kimberly
Rychert, Jenna
Rosenberg, Eric S.
Piechocka-Trocha, Alicja
Brass, Abraham L.
Brenchley, Jason M.
Walker, Bruce D.
Streeck, Hendrik
TI HIV-Specific Cytolytic CD4 T Cell Responses During Acute HIV Infection
Predict Disease Outcome
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID VIRUS TYPE-1 INFECTION; IMMUNODEFICIENCY-VIRUS; EFFECTOR FUNCTIONS;
VIREMIA; REPLICATION; MACROPHAGES; MACAQUES; NEF; GAG; ASSOCIATION
AB Early immunological events during acute HIV infection are thought to fundamentally influence long-term disease outcome. Whereas the contribution of HIV-specific CD8 T cell responses to early viral control is well established, the role of HIV-specific CD4 T cell responses in the control of viral replication after acute infection is unknown. A growing body of evidence suggests that CD4 T cells-besides their helper function-have the capacity to directly recognize and kill virally infected cells. In a longitudinal study of a cohort of individuals acutely infected with HIV, we observed that subjects able to spontaneously control HIV replication in the absence of antiretroviral therapy showed a significant expansion of HIV-specific CD4 T cell responses-but not CD8 T cell responses-compared to subjects who progressed to a high viral set point (P = 0.038). Markedly, this expansion occurred before differences in viral load or CD4 T cell count and was characterized by robust cytolytic activity and expression of a distinct profile of perforin and granzymes at the earliest time point. Kaplan-Meier analysis revealed that the emergence of granzyme A(+) HIV-specific CD4 T cell responses at baseline was highly predictive of slower disease progression and clinical outcome (average days to CD4 T cell count <350/mu l was 575 versus 306, P = 0.001). These data demonstrate that HIV-specific CD4 T cell responses can be used during the earliest phase of HIV infection as an immunological predictor of subsequent viral set point and disease outcome. Moreover, these data suggest that expansion of granzyme A(+) HIV-specific cytolytic CD4 T cell responses early during acute HIV infection contributes substantially to the control of viral replication.
C1 [Soghoian, Damien Z.; Flanders, Michael; Sierra-Davidson, Kailan; Cutler, Sam; Pertel, Thomas; Ranasinghe, Srinika; Lindqvist, Madelene; Davis, Isaiah; Lane, Kimberly; Piechocka-Trocha, Alicja; Brass, Abraham L.; Walker, Bruce D.; Streeck, Hendrik] Massachusetts Gen Hosp, MIT, Ragon Inst, Charlestown, MA 02129 USA.
[Soghoian, Damien Z.; Flanders, Michael; Sierra-Davidson, Kailan; Cutler, Sam; Pertel, Thomas; Ranasinghe, Srinika; Lindqvist, Madelene; Davis, Isaiah; Lane, Kimberly; Piechocka-Trocha, Alicja; Brass, Abraham L.; Walker, Bruce D.; Streeck, Hendrik] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Jessen, Heiko] Practice Jessen Jessen Stein, D-10777 Berlin, Germany.
[Rychert, Jenna; Rosenberg, Eric S.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
[Brenchley, Jason M.] NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Streeck, H (reprint author), Massachusetts Gen Hosp, MIT, Ragon Inst, Charlestown, MA 02129 USA.
EM hstreeck@partners.org
OI Pertel, Thomas/0000-0002-2286-6011
FU Charles H. Hood Foundation; Howard Hughes Medical Institute; intramural
National Institute of Allergy and Infectious Diseases/NIH;
[5P01AI074415-03]; [1R01AI091450-01]; [1R01AI094602-01]
FX This study was funded by a supplement to 5P01AI074415-03. H. S. is
funded by 1R01AI091450-01 and 1R01AI094602-01. A. L. B. and T. P. are
funded by the Charles H. Hood Foundation. B. D. W. and A.P.-T. are
supported by the Howard Hughes Medical Institute. J.M.B. is funded by
the intramural National Institute of Allergy and Infectious Diseases/NIH
program.
NR 48
TC 79
Z9 81
U1 3
U2 16
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 29
PY 2012
VL 4
IS 123
AR 123ra25
DI 10.1126/scitranslmed.3003165
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 901GT
UT WOS:000300952600004
PM 22378925
ER
PT J
AU Wood, DK
Soriano, A
Mahadevan, L
Higgins, JM
Bhatia, SN
AF Wood, David K.
Soriano, Alicia
Mahadevan, L.
Higgins, John M.
Bhatia, Sangeeta N.
TI A Biophysical Indicator of Vaso-occlusive Risk in Sickle Cell Disease
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID BIOMARKER QUALIFICATION; HEMOGLOBIN; ANEMIA; SEVERITY; MEDICINE; STROKE;
ULTRASONOGRAPHY; DEOXYGENATION; BIOMECHANICS; TRANSFUSIONS
AB The search for predictive indicators of disease has largely focused on molecular markers. However, biophysical markers, which can integrate multiple pathways, may provide a more global picture of pathophysiology. Sickle cell disease affects millions of people worldwide and has been studied intensely at the molecular, cellular, tissue, and organismal level for a century, but there are still few, if any, markers quantifying the severity of this disease. Because the complications of sickle cell disease are largely due to vaso-occlusive events, we hypothesized that a physical metric characterizing the vaso-occlusive process could serve as an indicator of disease severity. Here, we use a microfluidic device to characterize the dynamics of "jamming," or vaso-occlusion, in physiologically relevant conditions, by measuring a biophysical parameter that quantifies the rate of change of the resistance to flow after a sudden deoxygenation event. Our studies show that this single biophysical parameter could be used to distinguish patients with poor outcomes from those with good outcomes, unlike existing laboratory tests. This biophysical indicator could therefore be used to guide the timing of clinical interventions, to monitor the progression of the disease, and to measure the efficacy of drugs, transfusion, and novel small molecules in an ex vivo setting.
C1 [Mahadevan, L.] Harvard Univ, Dept Organism & Evolutionary Biol, Wyss Inst Biol Inspired Engn, Sch Engn & Appl Sci,Dept Phys, Cambridge, MA 02138 USA.
[Mahadevan, L.] Harvard Univ, Kavli Inst Nanobio Sci & Technol, Cambridge, MA 02138 USA.
[Wood, David K.; Bhatia, Sangeeta N.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Soriano, Alicia] Brigham & Womens Hosp, Special Hematol Lab, Boston, MA 02115 USA.
[Mahadevan, L.; Higgins, John M.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Higgins, John M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Higgins, John M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Bhatia, Sangeeta N.] MIT, Howard Hughes Med Inst, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Bhatia, Sangeeta N.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Bhatia, Sangeeta N.] Brigham & Womens Hosp, Div Med, Boston, MA 02115 USA.
RP Mahadevan, L (reprint author), Harvard Univ, Dept Organism & Evolutionary Biol, Wyss Inst Biol Inspired Engn, Sch Engn & Appl Sci,Dept Phys, Cambridge, MA 02138 USA.
EM lm@seas.harvard.edu; john_higgins@hms.harvard.edu
RI Wood, David/P-1998-2015
OI Wood, David/0000-0001-5225-2144
FU Stanford Microfluidics foundry; Massachusetts Institute of Technology
Microtechnology Laboratory; National Institute of Biomedical Imaging and
Bioengineering National Research Service; Kavli Institute for Nanobio
Science and Technology at Harvard; MacArthur Foundation; National
Institute of Diabetes and Digestive and Kidney Diseases [DK083242];
Howard Hughes Investigator
FX We thank the many patients who donated blood for this study. We thank E.
Mandell, R. Jaromin, H. Patel, S. Patel, M. Hames, P. Guglietta, M.
Huang, D. Ebb, L. Lampert, C. Markopoulos, and A. Griffin for help in
acquiring and testing blood samples. We thank F. Bunn, C. Brugnara, and
M. Okam for helpful discussions. All video processing was performed on
the Harvard Medical School Orchestra Computing Cluster. We thank the
Stanford Microfluidics foundry and the Massachusetts Institute of
Technology Microtechnology Laboratory for fabrication support.; Funding:
National Institute of Biomedical Imaging and Bioengineering National
Research Service Award fellowship (D. K. W.); Kavli Institute for
Nanobio Science and Technology at Harvard and MacArthur Foundation (L.
M.); and National Institute of Diabetes and Digestive and Kidney
Diseases grant DK083242 (J.M.H.). S.N.B. is a Howard Hughes
Investigator.
NR 58
TC 23
Z9 23
U1 2
U2 19
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 29
PY 2012
VL 4
IS 123
AR 123ra26
DI 10.1126/scitranslmed.3002738
PG 8
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 901GT
UT WOS:000300952600005
PM 22378926
ER
PT J
AU Rice, WL
Zhang, Y
Chen, Y
Matsuzaki, T
Brown, D
Lu, HAJ
AF Rice, William L.
Zhang, Yan
Chen, Ying
Matsuzaki, Toshiyuki
Brown, Dennis
Lu, Hua A. Jenny
TI Differential, Phosphorylation Dependent Trafficking of AQP2 in LLC-PK1
Cells
SO PLOS ONE
LA English
DT Article
ID WATER CHANNEL AQUAPORIN-2; RENAL EPITHELIAL-CELLS; NEPHROGENIC
DIABETES-INSIPIDUS; COLLECTING DUCT CELLS; PLASMA-MEMBRANE; PRINCIPAL
CELLS; ENDOPLASMIC-RETICULUM; SURFACE EXPRESSION; APICAL MEMBRANE;
IN-VIVO
AB The kidney maintains water homeostasis by modulating aquaporin 2 (AQP2) on the plasma membrane of collecting duct principal cells in response to vasopressin (VP). VP mediated phosphorylation of AQP2 at serine 256 is critical for this effect. However, the role of phosphorylation of other serine residues in the AQP2 C-terminus is less well understood. Here, we examined the effect of phosphorylation of S256, S261 and S269 on AQP2 trafficking and association with recycling pathway markers. We used LLC-PK1 cells expressing AQP2(S-D) or (S-A) phospho mutants and a 20 degrees C cold block, which allows endocytosis to continue, but prevents protein exit from the trans Golgi network (TGN), inducing formation of a perinuclear AQP2 patch. AQP2-S256D persists on the plasma membrane during cold block, while wild type AQP2, AQP2-S256A, S261A, S269A and S269D are internalized and accumulate in the patch. Development of this patch, a measure of AQP2 internalization, was most rapid with AQP2-S256A, and slowest with S261A and S269D. AQP2-S269D exhibited a biphasic internalization profile with a significant amount not internalized until 150 minutes of cold block. After rewarming to 37 degrees C, wt AQP2, AQP2-S261A and AQP2-S269D rapidly redistributed throughout the cytoplasm within 20 minutes, whereas AQP2-S256A dissipated more slowly. Colocalization of AQP2 mutants with several key vesicular markers including clathrin, HSP70/HSC70, EEA, GM130 and Rab11 revealed no major differences. Overall, our data provide evidence supporting the role of S256 and S269 in the maintenance of AQP2 at the cell surface and reveal the dynamics of internalization and recycling of differentially phosphorylated AQP2 in cell culture.
C1 [Rice, William L.] Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, Ctr Syst Biol,Div Nephrol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Rice, WL (reprint author), Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, Ctr Syst Biol,Div Nephrol, Boston, MA 02114 USA.
EM Halu@partners.org
FU National Institutes of Health (NIH) [DK075940, DK38452, 5T32
DK007540-24]; American Society of Nephrology (ASN); Boston Area Diabetes
and Endocrinology Research Center (NIH) [DK-57521]; Center for the Study
of Inflammatory Bowel Disease (NIH) [DK-43351]
FX Funding was provided by the National Institutes of Health (NIH),
www.nih.gov. H. J. Lu is supported by an NIH KO8 grant DK075940 and a
Gottschalk research grant from the American Society of Nephrology (ASN
http://www.asn-online.org/grants_and_funding/career-development-details.
aspx). Additional support was from NIH grant DK38452 (D. Brown). W. Rice
is supported by an NIH training grant (NIH 5T32 DK007540-24). The
Microscopy Core Facility of the Program in Membrane Biology receives
additional support from the Boston Area Diabetes and Endocrinology
Research Center (NIH DK-57521) and from the Center for the Study of
Inflammatory Bowel Disease (NIH DK-43351). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 42
TC 19
Z9 20
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 FEB 28
PY 2012
VL 7
IS 2
AR e32843
DI 10.1371/journal.pone.0032843
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 928RC
UT WOS:000302999600065
PM 22403603
ER
PT J
AU Cullen, KR
Wallace, S
Magnotta, VA
Bockholt, J
Ehrlich, S
Gollub, RL
Manoach, DS
Ho, BC
Clark, VP
Lauriello, J
Bustillo, JR
Schulz, SC
Andreasen, NC
Calhoun, VD
Lim, KO
White, T
AF Cullen, Kathryn R.
Wallace, Stuart
Magnotta, Vincent A.
Bockholt, Jeremy
Ehrlich, Stefan
Gollub, Randy L.
Manoach, Dara S.
Ho, Beng C.
Clark, Vincent P.
Lauriello, John
Bustillo, Juan R.
Schulz, S. Charles
Andreasen, Nancy C.
Calhoun, Vince D.
Lim, Kelvin O.
White, Tonya
TI Cigarette smoking and white matter microstructure in schizophrenia
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Diffusion tensor imaging; Nicotine; Fractional anisotropy
ID DIFFUSION-TENSOR MRI; TRANSDERMAL NICOTINE; GRAY-MATTER; ARCHITECTURE;
NONSMOKERS; DEPENDENCE; CORTEX; ADULTS; VOLUME; TRACTOGRAPHY
AB The majority of patients with schizophrenia smoke cigarettes. Both nicotine use and schizophrenia have been associated with alterations in brain white matter microstructure as measured by diffusion tensor imaging (DTI). The purpose of this study was to examine fractional anisotropy (FA) in smoking and non-smoking patients with schizophrenia and in healthy volunteers. A total of 43 patients (28 smoking and 15 nonsmoking) with schizophrenia and 40 healthy, non-smoking participants underwent DTI. Mean FA was calculated in four global regions of interest (ROIs) (whole brain, cerebellum, brainstem, and total cortical) as well as in four regional ROIs (frontal, temporal, parietal and occipital lobes). The non-smoking patient group had a significantly higher intellectual quotient (IQ) compared with the patients who smoked, and our results varied according to whether IQ was included as a covariate. Without IQ correction, significant between-group effects for FA were found in four ROIs: total brain, total cortical, frontal lobe and the occipital lobe. In all cases the FA was lower among the smoking patient group, and highest in the control group. Smoking patients differed significantly from non-smoking patients in the frontal lobe ROI. However, these differences were no longer significant after IQ correction. FA differences between non-smoking patients and controls were not significant. Among smoking and non-smoking patients with schizophrenia but not healthy controls, FA was correlated with IQ. In conclusion, group effects of smoking on FA in schizophrenia might be mediated by IQ. Further, low FA in specific brain areas may be a neural marker for complex pathophysiology and risk for diverse problems such as schizophrenia, low IQ and nicotine addiction. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Cullen, Kathryn R.] Univ Minnesota, Div Child & Adolescent Psychiat F256 28, Fairview Univ Med Ctr, Dept Psychiat,Med Sch, Minneapolis, MN 55454 USA.
[Cullen, Kathryn R.; Lim, Kelvin O.] Univ Minnesota, Ctr Neurobehav Dev, Minneapolis, MN 55454 USA.
[Wallace, Stuart; Ehrlich, Stefan; Gollub, Randy L.; Manoach, Dara S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Magnotta, Vincent A.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA.
[Bockholt, Jeremy; Clark, Vincent P.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA.
[Clark, Vincent P.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA.
[Ehrlich, Stefan; Gollub, Randy L.; Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Ho, Beng C.; Andreasen, Nancy C.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Bustillo, Juan R.; Calhoun, Vince D.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA.
[Lauriello, John] Univ Missouri, Missouri Psychiat Ctr, Columbia, MO USA.
[White, Tonya] Erasmus MC, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands.
RP Cullen, KR (reprint author), Univ Minnesota, Div Child & Adolescent Psychiat F256 28, Fairview Univ Med Ctr, Dept Psychiat,Med Sch, 2450 Riverside Ave, Minneapolis, MN 55454 USA.
EM rega0026@umn.edu
RI Ho, Beng-Choon/D-6959-2011; bustillo, juan/J-7067-2013; Cullen,
Kathryn/G-9654-2013; Clark, Vincent/B-3343-2010;
OI Ho, Beng-Choon/0000-0003-3976-1555; Gollub, Randy
L./0000-0002-9434-4044; Cullen, Kathryn/0000-0001-9631-3770; Clark,
Vincent/0000-0002-9151-2102; Ehrlich, Stefan/0000-0003-2132-4445
FU NIBIB NIH HHS [R01 EB006841-01A1, R01 EB006841, R01 EB006841-01A1S1, R01
EB006841-02, R01 EB006841-03, R01 EB006841-04, R01 EB006841-05, R01
EB006841-06]
NR 49
TC 19
Z9 19
U1 2
U2 8
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 FEB 28
PY 2012
VL 201
IS 2
BP 152
EP 158
DI 10.1016/j.pscychresns.2011.08.010
PG 7
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 929UA
UT WOS:000303090000009
PM 22386966
ER
PT J
AU van de Ven, AL
Kim, P
Haley, O
Fakhoury, JR
Adriani, G
Schmulen, J
Moloney, P
Hussain, F
Ferrari, M
Liu, XW
Yun, SH
Decuzzi, P
AF van de Ven, Anne L.
Kim, Pilhan
Haley, O'Hara
Fakhoury, Jean R.
Adriani, Giulia
Schmulen, Jeffrey
Moloney, Padraig
Hussain, Fazle
Ferrari, Mauro
Liu, Xuewu
Yun, Seok-Hyun
Decuzzi, Paolo
TI Rapid tumoritropic accumulation of systemically injected plateloid
particles and their biodistribution
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Nanoparticles; Size and shape; Biodistribution; Tumor accumulation;
Rational design; Intravital microscopy
ID POROUS SILICON MICROPARTICLES; HUMAN TUMOR XENOGRAFT; IN-VIVO;
MACROMOLECULAR THERAPEUTICS; VASCULAR-PERMEABILITY; DELIVERY-SYSTEM;
CANCER-THERAPY; DRUG-DELIVERY; SOLID TUMORS; BLOOD-FLOW
AB Nanoparticles for cancer therapy and imaging are designed to accumulate in the diseased tissue by exploiting the Enhanced Permeability and Retention (EPR) effect. This limits their size to about 100 nm. Here, using intravital microscopy and elemental analysis, we compare the in vivo localization of particles with different geometries and demonstrate that plateloid particles preferentially accumulate within the tumor vasculature at unprecedented levels, independent of the EPR effect. In melanoma-bearing mice, 1000 x 400 nm plateloid particles adhered to the tumor vasculature at about 5% and 10% of the injected dose per gram organ (ID/g) for untargeted and RGD-targeted particles respectively, and exhibited the highest tumor-to-liver accumulation ratios (0.22 and 0.35). Smaller and larger plateloid particles, as well as cylindroid particles, were more extensively sequestered by the liver, spleen, and lungs. Plateloid particles appeared well-suited for taking advantage of hydrodynamic forces and interfacial interactions required for efficient tumoritropic accumulation, even without using specific targeting ligands. (c) 2011 Elsevier B.V. All rights reserved.
C1 [van de Ven, Anne L.; Fakhoury, Jean R.; Adriani, Giulia; Schmulen, Jeffrey; Ferrari, Mauro; Liu, Xuewu; Decuzzi, Paolo] Methodist Hosp, Res Inst, Dept Translat Imaging, Houston, TX 77030 USA.
[van de Ven, Anne L.; Fakhoury, Jean R.; Adriani, Giulia; Schmulen, Jeffrey; Ferrari, Mauro; Liu, Xuewu; Decuzzi, Paolo] Methodist Hosp, Res Inst, Dept Nanomed, Houston, TX 77030 USA.
[Kim, Pilhan; Haley, O'Hara; Yun, Seok-Hyun] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kim, Pilhan; Haley, O'Hara; Yun, Seok-Hyun] Wellman Ctr Photomed, Boston, MA 02114 USA.
[Adriani, Giulia] Politecn Bari, Dept Mech & Management Engn, I-70125 Bari, Italy.
[Moloney, Padraig] Rice Univ, Dept Mech Engn & Mat Sci, Houston, TX 77005 USA.
[Hussain, Fazle] Univ Houston, Dept Mech Engn, Houston, TX 77204 USA.
[Decuzzi, Paolo] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy.
[Yun, Seok-Hyun] Korea Adv Inst Sci & Technol, Grad Sch Nano Sci & Technol, Taejon, South Korea.
RP van de Ven, AL (reprint author), Methodist Hosp, Res Inst, Dept Translat Imaging, 6670 Bertner Ave, Houston, TX 77030 USA.
EM avandeven@tmhs.org; pdecuzzi@tmhs.org
RI Kim, Pilhan/C-1836-2011; Decuzzi, Paolo/F-1899-2016
OI Kim, Pilhan/0000-0001-8388-1840; Decuzzi, Paolo/0000-0001-6050-4188
FU Telemedicine and Advanced Technology Research Center (TATRC)-United
States Army Medical Research Acquisition Activity (USAMRAA) through
Alliance for Nano Health [W81XWH09-2-0139]; National Institutes of
Health (USA) (NIH) [U54CA143837, U54CA151668]; Department of Defense
(DoD) [W81XWH-09-1-0212]; University of Magna Graecia-Italy
FX This work was supported by Telemedicine and Advanced Technology Research
Center (TATRC)-United States Army Medical Research Acquisition Activity
(USAMRAA) through the pre-centre grant W81XWH09-2-0139 of the Alliance
for Nano Health. This work was also partially supported through grants
from the National Institutes of Health (USA) (NIH)U54CA143837 and
U54CA151668, and the Department of Defense (DoD) grant W81XWH-09-1-0212.
The authors would like to thank Mr. Matthew Landry for helping with the
graphical work, Mr. Aaron Mack for advice on particle conjugation and
ICP-AES protocols, as well as Dr. W.M. Steve Lee and Dr. Jinwoo Choi for
helping with animal preparations. PD would like to thank the President
and staff at the University of Magna Graecia-Italy for their support.
NR 53
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U1 2
U2 39
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 FEB 28
PY 2012
VL 158
IS 1
BP 148
EP 155
DI 10.1016/j.jconrel.2011.10.021
PG 8
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 923FW
UT WOS:000302605900018
PM 22062689
ER
PT J
AU Nordenstedt, H
Mattsson, F
El-Serag, H
Lagergren, J
AF Nordenstedt, H.
Mattsson, F.
El-Serag, H.
Lagergren, J.
TI Gallstones and cholecystectomy in relation to risk of intra- and
extrahepatic cholangiocarcinoma
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE bile duct cancer; biliary tumour; cohort study; gallstones;
population-based
ID PRIMARY SCLEROSING CHOLANGITIS; UNITED-STATES; BILE-DUCT; INTRAHEPATIC
CHOLANGIOCARCINOMA; EPIDEMIOLOGY; CANCER; POPULATION; PANCREAS
AB BACKGROUND: Cholangiocarcinomas are highly lethal tumours of the intrahepatic or extrahepatic biliary tract. The aetiology is largely unknown, and the potential roles of gallstones and gall bladder removal (cholecystectomy) need to be addressed in a large study with a long follow-up.
METHODS: A population-based nationwide Swedish cohort study was carried out, in which patients hospitalised for gallstone diagnosis with or without gallbladder removal (cholecystectomy) between 1965 and 2008 were identified in the Swedish Patient Registry. The cohort was followed up for cancer in the Swedish Cancer Registry. The observed numbers of intra- and extrahepatic cholangiocarcinomas that developed after one year of follow-up were compared with the expected numbers, calculated from the corresponding background population, and the relative risks were estimated by standardised incidence ratios (SIRs) and 95% confidence intervals (CIs).
RESULTS: Among the 192 960 non-cholecystectomised individuals with gallstones, there was a more than two-fold overall increased risk of both intra- and extra-hepatic cholangiocarcinomas, which remained stable over the follow-up period (SIR 2.77, 95% CI 2.17-3.49, and SIR 2.58, 95% CI 2.21-3.00, respectively). In the cholecystectomy cohort, including 345 251 people and 4 854 969 person-years, 325 incident cholangiocarcinomas were identified, of which 98 (30%) were intrahepatic and 227 (70%) were extrahepatic. Initially (1-4 years after surgery), the risk was increased for both intrahepatic cholangiocarcinoma (SIR 1.80, 95% CI 1.19-2.62) and extrahepatic cholangiocarcinoma (SIR 2.29, 95% CI 1.83-2.82), but no increase remained after 10 years of follow-up or more (SIR 1.10, 95% CI 0.79-1.48, and SIR 0.87, 95% CI 0.70-1.07, respectively).
INTERPRETATION: Gallstones seem to increase the risk of both intra-and extrahepatic cholangiocarcinoma. However, this risk seems to decline to the level of the background population with time after cholecystectomy. British Journal of Cancer (2012) 106, 1011-1015. doi:10.1038/bjc.2011.607 www.bjcancer.com Published online 12 January 2012 (C) 2012 Cancer Research UK
C1 [Nordenstedt, H.; Mattsson, F.; Lagergren, J.] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[El-Serag, H.] Houston Ctr Qual Care & Utilizat Studies, Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA.
[El-Serag, H.] Houston Ctr Qual Care & Utilizat Studies, Baylor Coll Med, Houston, TX USA.
[Lagergren, J.] Kings Coll London, Div Canc Studies, London WC2R 2LS, England.
RP Nordenstedt, H (reprint author), Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
EM helena.nordenstedt@ki.se
OI Lagergren, Jesper/0000-0002-5143-5448
FU Swedish Research Council; Swedish Cancer Society
FX The study was supported by project grants from the Swedish Research
Council and the Swedish Cancer Society.
NR 21
TC 24
Z9 25
U1 6
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD FEB 28
PY 2012
VL 106
IS 5
BP 1011
EP 1015
DI 10.1038/bjc.2011.607
PG 5
WC Oncology
SC Oncology
GA 900NO
UT WOS:000300894300031
PM 22240785
ER
PT J
AU Alemani, D
Pappalardo, F
Pennisi, M
Motta, S
Brusic, V
AF Alemani, Davide
Pappalardo, Francesco
Pennisi, Marzio
Motta, Santo
Brusic, Vladimir
TI Combining cellular automata and lattice Boltzmann method to model
multiscale avascular tumor growth coupled with nutrient diffusion and
immune competition
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Immune system; Dosage optimization; Computational models; Cellular
automata; Hybrid models; Lattice Boltzmann
ID MATHEMATICAL-MODELS; SOLID TUMOR; INDUCED ANGIOGENESIS;
OXYGEN-CONSUMPTION; CANCER; INVASION; SYSTEM; CHEMOTHERAPY; ENVIRONMENT;
SIMULATION
AB In the last decades the Lattice Boltzmann method (LB) has been successfully used to simulate a variety of processes. The LB model describes the microscopic processes occurring at the cellular level and the macroscopic processes occurring at the continuum level with a unique function, the probability distribution function. Recently, it has been tried to couple deterministic approaches with probabilistic cellular automata (probabilistic CA) methods with the aim to model temporal evolution of tumor growths and three dimensional spatial evolution, obtaining hybrid methodologies. Despite the good results attained by CA-PDE methods, there is one important issue which has not been completely solved: the intrinsic stochastic nature of the interactions at the interface between cellular (microscopic) and continuum (macroscopic) level. CA methods are able to cope with the stochastic phenomena because of their probabilistic nature, while PDE methods are fully deterministic. Even if the coupling is mathematically correct, there could be important statistical effects that could be missed by the PDE approach. For such a reason, to be able to develop and manage a model that takes into account all these three level of complexity (cellular, molecular and continuum), we believe that PDE should be replaced with a statistic and stochastic model based on the numerical discretization of the Boltzmann equation: The Lattice Boltzmann (LB) method. In this work we introduce a new hybrid method to simulate tumor growth and immune system, by applying Cellular Automata Lattice Boltzmann (CA-LB) approach. (c) 2011 Elsevier B.V. All rights reserved.
C1 [Pappalardo, Francesco; Pennisi, Marzio; Motta, Santo] Univ Catania, Catania, Italy.
[Alemani, Davide] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
[Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr Bioinformat Core, Boston, MA 02115 USA.
RP Pappalardo, F (reprint author), Univ Catania, Catania, Italy.
EM davide.alemani@epfl.ch; fp@francescopappalardo.net;
mpennisi@dmi.unict.it; motta@dmi.unict.it;
Vladimir_Brusic@DFCI.HARVARD.EDU
RI Motta, Santo/I-5177-2012; Pappalardo, Francesco/C-5832-2011; Pennisi,
Marzio/G-4618-2015;
OI Pappalardo, Francesco/0000-0003-1668-3320; Pennisi,
Marzio/0000-0003-0231-7653; Motta, Santo/0000-0003-3533-2972
FU Swiss National Science Foundation
FX DA thanks financial support from the Swiss National Science Foundation
through the 'Bourse pour chercheur debutant' program fund.
NR 60
TC 21
Z9 21
U1 3
U2 21
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD FEB 28
PY 2012
VL 376
IS 1-2
BP 55
EP 68
DI 10.1016/j.jim.2011.11.009
PG 14
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 904OC
UT WOS:000301206800006
PM 22154892
ER
PT J
AU Ackerman, ME
Moldt, B
Wyatt, RT
Dugast, AS
McAndrew, E
Tsoukas, S
Jost, S
Berger, CT
Sciaranghella, G
Liu, QQ
Irvine, DJ
Burton, DR
Alter, G
AF Ackerman, Margaret E.
Moldt, Brian
Wyatt, Richard T.
Dugast, Anne-Sophie
McAndrew, Elizabeth
Tsoukas, Stephen
Jost, Stephanie
Berger, Christoph T.
Sciaranghella, Gaia
Liu, Qingquan
Irvine, Darrell J.
Burton, Dennis R.
Alter, Galit
TI A robust, high-throughput assay to determine the phagocytic activity of
clinical antibody samples (vol 376, pg 156, 2012)
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Correction
C1 [Ackerman, Margaret E.; Dugast, Anne-Sophie; McAndrew, Elizabeth; Tsoukas, Stephen; Jost, Stephanie; Berger, Christoph T.; Sciaranghella, Gaia; Liu, Qingquan; Irvine, Darrell J.; Burton, Dennis R.; Alter, Galit] MIT & Harvard Univ, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Moldt, Brian; Wyatt, Richard T.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Moldt, Brian; Wyatt, Richard T.; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Consortium, La Jolla, CA 92037 USA.
[Irvine, Darrell J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
RP Ackerman, ME (reprint author), 149 13th St,Room 6616, Charlestown, MA 02129 USA.
EM meackerman@partners.org
RI Dugast, AnneSophie/L-9541-2015
NR 1
TC 1
Z9 1
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD FEB 28
PY 2012
VL 376
IS 1-2
BP 156
EP 156
DI 10.1016/j.jim.2011.12.006
PG 1
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 904OC
UT WOS:000301206800018
ER
PT J
AU Cornier, MA
Melanson, EL
Salzberg, AK
Bechtell, JL
Tregellas, JR
AF Cornier, Marc-Andre
Melanson, Edward L.
Salzberg, Andrea K.
Bechtell, Jamie L.
Tregellas, Jason R.
TI The effects of exercise on the neuronal response to food cues
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE fMRI; Neuroimaging; Physical activity; Food intake; Appetite
ID POSITRON-EMISSION-TOMOGRAPHY; MODULATES BRAIN ACTIVITY;
PHYSICAL-ACTIVITY; WEIGHT-LOSS; ENERGY-BALANCE; BODY-WEIGHT; INDUCED
SUPPRESSION; NEURAL RESPONSES; FUNCTIONAL MRI; APPETITE
AB Increased physical activity is associated with successful long-term weight loss maintenance due to mechanisms likely more complex than simply increased energy expenditure. The impact of physical activity on the central regulation of food intake may be an important mechanism of this effect. The objective of this study was to examine the effects of exercise training and acute exercise on the neuronal response to food cues as well as eating behaviors. fMRI was performed in the fasted state at baseline and again after a 6 month progressive exercise intervention (supervised, 5 days/wk) both with and without an acute exercise bout in 12 overweight/obese (5 women, 7 men; BMI 33 +/- 4 kg/m(2)) healthy adults. fMRI data were acquired while subjects were presented with visual stimuli of foods of high hedonic value as compared to neutral control objects. Questionnaires on eating behaviors, ratings of appeal and desire for foods, and ratings of appetite (hunger, satiety, prospective intake) using visual analog scales were also performed at baseline and again after the 6-month exercise intervention. While only a trend was observed for a reduction in body weight (102 +/- 5 to 99 +/- 6 kg, p=0.09), a significant reduction in fat mass was observed (36.4 +/- 2.8 to 33.7 +/- 3.2 kg, p = 0.04), although as expected changes in fat mass were variable (-10.0 to +3.7 kg). Chronic exercise was associated with a reduction in the neuronal response to food, primarily in the posterior attention network and insula. A significant positive correlation between the change in fat/body mass and the change in insula response to food cues with chronic exercise was observed. An acute exercise bout attenuated the effects of chronic exercise. The exercise intervention, however, did not impact any of the measures of appetitive behavior. In summary, despite no effects on behavioral measures of appetite, chronic exercise training was associated with attenuation in the response to visual food cues in brain regions known to be important in food intake regulation. The insula, in particular, appears to play an important role in the potential exercise-induced weight loss and weight loss maintenance. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Cornier, Marc-Andre; Melanson, Edward L.; Salzberg, Andrea K.; Bechtell, Jamie L.] Univ Colorado, Div Endocrinol Metab & Diabet, Sch Med, Dept Med, Aurora, CO 80045 USA.
[Tregellas, Jason R.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO 80045 USA.
[Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA.
RP Cornier, MA (reprint author), Univ Colorado, Div Endocrinol Metab & Diabet, Sch Med, Dept Med, Anschutz Med Campus,Mail Stop 8106,12801 E 17th A, Aurora, CO 80045 USA.
EM marc.cornier@ucdenver.edu
RI Tregellas, Jason/J-3637-2015
FU NIH/NCRR Colorado CTSI [UL1 RR025780]; NIH/NIDDK Clinical Nutrition
Research Unit [DK48520]; NIH/NIDDK [R01DK07708, R01DK089095,
R01DK072174]
FX We acknowledge and thank Debra Singel and Yiping Du for their assistance
with the fMRI studies. We also thank the dietary services and metabolic
kitchen of the University of Colorado Denver CTRC. This publication was
supported by NIH/NCRR Colorado CTSI Grant Number UL1 RR025780, NIH/NIDDK
Clinical Nutrition Research Unit Grant Number DK48520, and NIH/NIDDK
Grant Numbers R01DK07708, R01DK089095 and R01DK072174. Its contents are
the authors' sole responsibility and do not necessarily represent
official NIH views.
NR 58
TC 41
Z9 42
U1 4
U2 22
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 FEB 28
PY 2012
VL 105
IS 4
BP 1028
EP 1034
DI 10.1016/j.physbeh.2011.11.023
PG 7
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA 898MW
UT WOS:000300747500017
PM 22155218
ER
PT J
AU Sampson, JH
Schmittling, RJ
Archer, GE
Congdon, KL
Nair, SK
Reap, EA
Desjardins, A
Friedman, AH
Friedman, HS
Herndon, JE
Coan, A
McLendon, RE
Reardon, DA
Vredenburgh, JJ
Bigner, DD
Mitchell, DA
AF Sampson, John H.
Schmittling, Robert J.
Archer, Gary E.
Congdon, Kendra L.
Nair, Smita K.
Reap, Elizabeth A.
Desjardins, Annick
Friedman, Allan H.
Friedman, Henry S.
Herndon, James E., II
Coan, April
McLendon, Roger E.
Reardon, David A.
Vredenburgh, James J.
Bigner, Darell D.
Mitchell, Duane A.
TI A Pilot Study of IL-2R alpha Blockade during Lymphopenia Depletes
Regulatory T-cells and Correlates with Enhanced Immunity in Patients
with Glioblastoma
SO PLOS ONE
LA English
DT Article
ID TUMOR-INFILTRATING LYMPHOCYTES; GROWTH-FACTOR-BETA; MONOCLONAL-ANTIBODY;
METASTATIC MELANOMA; PERIPHERAL-BLOOD; AUTOIMMUNE-DISEASE; HUMAN
CYTOMEGALOVIRUS; CANCER-PATIENTS; SELF-TOLERANCE; IN-VIVO
AB Background: Preclinical studies in mice have demonstrated that the prophylactic depletion of immunosuppressive regulatory T-cells (T-Regs) through targeting the high affinity interleukin-2 (IL-2) receptor (IL-2R alpha/CD25) can enhance antitumor immunotherapy. However, therapeutic approaches are complicated by the inadvertent inhibition of IL-2R alpha expressing anti-tumor effector T-cells.
Objective: To determine if changes in the cytokine milieu during lymphopenia may engender differential signaling requirements that would enable unarmed anti-IL-2R alpha monoclonal antibody (MAbs) to selectively deplete T-Regs while permitting vaccine-stimulated immune responses.
Methodology: A randomized placebo-controlled pilot study was undertaken to examine the ability of the anti-IL-2R alpha MAb daclizumab, given at the time of epidermal growth factor receptor variant III (EGFRvIII) targeted peptide vaccination, to safely and selectively deplete T-Regs in patients with glioblastoma (GBM) treated with lymphodepleting temozolomide (TMZ).
Results and Conclusions: Daclizumab treatment (n = 3) was well-tolerated with no symptoms of autoimmune toxicity and resulted in a significant reduction in the frequency of circulating CD4+Foxp3+ TRegs in comparison to saline controls (n = 3)( p = 0.0464). A significant (p < 0.0001) inverse correlation between the frequency of TRegs and the level of EGFRvIII specific humoral responses suggests the depletion of TRegs may be linked to increased vaccine-stimulated humoral immunity. These data suggest this approach deserves further study. Trial Registration:
C1 [Sampson, John H.; Schmittling, Robert J.; Archer, Gary E.; Congdon, Kendra L.; Reap, Elizabeth A.; Desjardins, Annick; Friedman, Allan H.; Friedman, Henry S.; Vredenburgh, James J.; Bigner, Darell D.; Mitchell, Duane A.] Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA.
[Sampson, John H.; Friedman, Henry S.; McLendon, Roger E.; Bigner, Darell D.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Nair, Smita K.] Duke Univ, Med Ctr, Dept Surg, Div Surg Sci, Durham, NC 27710 USA.
[Herndon, James E., II; Coan, April] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
[Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA.
EM john.sampson@duke.edu
OI Sykes, April/0000-0002-7667-8155
FU National Institutes of Health (NIH) [RO1-CA097222, R21-NS067980,
R21-CA132891]; NIH/National Institute of Neurological Disorders and
Stroke SRC on Primary and Metastatic Tumors of the Central Nervous
System [P50-NS020023]; Specialized Program of Research Excellence in
Brain Cancer [P50-CA108786]; Duke University from National Center for
Research Resources/NIH [1UL2-RR024128]
FX This work was supported in part by National Institutes of Health (NIH)
grants RO1-CA097222 (JHS), R21-NS067980 (JHS) and R21-CA132891 (JHS),
grants from the NIH/National Institute of Neurological Disorders and
Stroke SRC on Primary and Metastatic Tumors of the Central Nervous
System P50-NS020023 (DAR, JHS and DDB) and Specialized Program of
Research Excellence in Brain Cancer P50-CA108786 (DDB and JHS) and by
Duke University's CTSA grant 1UL2-RR024128 from National Center for
Research Resources/NIH. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.; Consultant or Advisory Role: JHS, Celldex Therapeutics (C);
DDB, Celldex Therapeutics (C) Honoraria: JHS, Celldex Therapeutics; DDB,
Celldex Therapeutics Research Funding: JHS. The designation (C)
indicates a compensated position. This does not alter the authors'
adherence to all the PLoS ONE policies on sharing data and materials.
CDX-110 is a Celldex product. There are no patents, products in
development or other marketed products to declare.
NR 76
TC 41
Z9 43
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 27
PY 2012
VL 7
IS 2
AR e31046
DI 10.1371/journal.pone.0031046
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927OV
UT WOS:000302918500017
PM 22383993
ER
PT J
AU Studenshi, SA
AF Studenshi, Stephanie A.
TI Gait Speed in Hospitalized Older People
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID ELDERLY-PATIENTS; DISABILITY; PREDICTOR; OUTCOMES; MOBILITY
C1 [Studenshi, Stephanie A.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Dept Internal Med, Pittsburgh, PA 15090 USA.
[Studenshi, Stephanie A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15090 USA.
RP Studenshi, SA (reprint author), Univ Pittsburgh, Sch Med, Div Geriatr Med, Dept Internal Med, 3471 5th Ave,Ste 500, Pittsburgh, PA 15090 USA.
EM studenskiS@dom.pitt.edu
FU NIA NIH HHS [AG024827, P30 AG024827]
NR 10
TC 6
Z9 6
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 FEB 27
PY 2012
VL 172
IS 4
BP 358
EP 359
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 898JU
UT WOS:000300739500012
PM 22371923
ER
PT J
AU Raldow, AC
Presley, CJ
Yu, JB
Sharma, R
Cramer, LD
Soulos, PR
Long, JB
Makarov, DV
Gross, CP
AF Raldow, Ann C.
Presley, Carolyn J.
Yu, James B.
Sharma, Richa
Cramer, Laura D.
Soulos, Pamela R.
Long, Jessica B.
Makarov, Danil V.
Gross, Cary P.
TI The Relationship Between Clinical Benefit and Receipt of Curative
Therapy for Prostate Cancer
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
ID RADIATION; OUTCOMES; QUALITY
C1 [Presley, Carolyn J.; Soulos, Pamela R.; Long, Jessica B.; Gross, Cary P.] Yale Univ, Sch Med, Gen Internal Med Sect, New Haven, CT 06510 USA.
[Raldow, Ann C.; Presley, Carolyn J.; Yu, James B.; Sharma, Richa; Cramer, Laura D.; Soulos, Pamela R.; Long, Jessica B.; Makarov, Danil V.; Gross, Cary P.] Yale Univ, Sch Med, Canc Outcomes Publ Policy & Effectiveness Res COP, Yale Comprehens Canc Ctr, New Haven, CT 06510 USA.
[Presley, Carolyn J.; Soulos, Pamela R.; Long, Jessica B.; Gross, Cary P.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
[Yu, James B.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA.
[Raldow, Ann C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Makarov, Danil V.] NYU, Sch Med, Dept Urol, New York, NY 10003 USA.
[Makarov, Danil V.] US Dept Vet Affairs, Washington, DC USA.
RP Gross, CP (reprint author), Yale Univ, Sch Med, Gen Internal Med Sect, 333 Cedar St,POB 208025, New Haven, CT 06510 USA.
EM cary.gross@yale.edu
FU NCI NIH HHS [5R01CA149045, R01 CA149045]
NR 8
TC 6
Z9 6
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD FEB 27
PY 2012
VL 172
IS 4
BP 362
EP 363
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 898JU
UT WOS:000300739500015
PM 22371925
ER
PT J
AU Myaskovsky, L
Doebler, DA
Posluszny, DM
Dew, MA
Unruh, M
Fried, LF
Switzer, GE
Kim, S
Chang, CCH
Ramkumar, M
Shapiro, R
AF Myaskovsky, Larissa
Doebler, Donna Almario
Posluszny, Donna M.
Dew, Mary Amanda
Unruh, Mark
Fried, Linda F.
Switzer, Galen E.
Kim, Sunghee
Chang, Chung-Chou H.
Ramkumar, Mohan
Shapiro, Ron
TI Perceived Discrimination Predicts Longer Time to Be Accepted for Kidney
Transplant
SO TRANSPLANTATION
LA English
DT Article
DE Kidney transplantation; Disparities; Discrimination
ID RENAL-TRANSPLANTATION; AFRICAN-AMERICANS; RACIAL-DIFFERENCES; ORGAN
DONATION; DONOR; DISPARITIES; HEALTH; SURVIVAL; ACCESS; RACE
AB Background. Although end-stage kidney disease in African Americans (AAs) is four times greater than in whites, AAs are less than one half as likely to undergo kidney transplantation (KT). This racial disparity has been found even after controlling for clinical factors such as comorbid conditions, dialysis vintage and type, and availability of potential living donors. Therefore, studying nonmedical factors is critical to understanding disparities in KT.
Methods. We conducted a longitudinal cohort study with 127 AA and white patients with end-stage kidney disease undergoing evaluation for KT (December 2006 to July 2007) to determine whether, after controlling for medical factors, differences in time to acceptance for transplant is explained by patients' cultural factors (e. g., perceived racism and discrimination, medical mistrust, religious objections to living donor KT), psychosocial characteristics (e. g., social support, anxiety, depression), or transplant knowledge. Participants completed two telephone interviews (shortly after initiation of transplant evaluation and after being accepted or found ineligible for transplant).
Results. Results indicated that AA patients reported higher levels of the cultural factors than did whites. We found no differences in comorbidity or availability of potential living donors. AAs took significantly longer to get accepted for transplant than did whites (hazard ratio = 1.49, P = 0.005). After adjustment for demographic, psychosocial, and cultural factors, the association of race with longer time for listing was no longer significant.
Conclusions. We suggest that interventions to address racial disparities in KT incorporate key nonmedical risk factors in patients.
C1 [Myaskovsky, Larissa; Fried, Linda F.; Switzer, Galen E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA.
[Myaskovsky, Larissa; Posluszny, Donna M.; Unruh, Mark; Fried, Linda F.; Switzer, Galen E.; Chang, Chung-Chou H.; Ramkumar, Mohan] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA.
[Myaskovsky, Larissa; Dew, Mary Amanda; Switzer, Galen E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Doebler, Donna Almario; Dew, Mary Amanda; Chang, Chung-Chou H.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA.
[Dew, Mary Amanda] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.
[Dew, Mary Amanda] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Fried, Linda F.; Ramkumar, Mohan] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15206 USA.
[Kim, Sunghee] Duke Univ, Med Ctr, Duke Clin Res Inst, Pittsburgh, PA USA.
[Shapiro, Ron] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA.
RP Myaskovsky, L (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA.
EM larissa.myaskovsky@va.gov
FU Veterans Administration (VA) Health Services Research and Development
Department (HSRD) [04-409]; VA HSRD Merit Award [IIR 06-220]; VA Center
for Health Equity Research and Promotion (CHERP) [LIP 72-023]; VA
Veterans Integrated Service Network (VISN) [XVA 72-034]; National
Institutes of Diabetes, Digestive, and Kidney Diseases (NIDDK)
[R01DK081325]; University of Pittsburgh Center for Social and Urban
Research [XNV 72-085]
FX This work was supported by the Veterans Administration (VA) Health
Services Research and Development Department (HSR&D) Merit Review Entry
Program 04-409, VA HSR&D Merit Award IIR 06-220, VA Center for Health
Equity Research and Promotion (CHERP) Pilot Fund LIP 72-023, VA Veterans
Integrated Service Network (VISN) 4 Competitive Pilot Project Funds XVA
72-034, National Institutes of Diabetes, Digestive, and Kidney Diseases
(NIDDK) R01DK081325, and the University of Pittsburgh Center for Social
and Urban Research Manners Faculty Development Award XNV 72-085.
NR 55
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Z9 8
U1 1
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD FEB 27
PY 2012
VL 93
IS 4
BP 423
EP 429
DI 10.1097/TP.0b013e318241d0cd
PG 7
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 894GT
UT WOS:000300415800018
PM 22228417
ER
PT J
AU Roberts, DJ
Wilson, ML
Nelson, AM
Adesina, AM
Fleming, KA
Milner, D
Guarner, J
Rebbeck, TR
Castle, P
Lucas, S
AF Roberts, Drucilla Jane
Wilson, Michael L.
Nelson, Ann Marie
Adesina, Adekunle M.
Fleming, Kenneth A.
Milner, Dan
Guarner, Jeannette
Rebbeck, Timothy R.
Castle, Philip
Lucas, Sebastian
TI The good news about cancer in developing countries-pathology answers the
call
SO LANCET
LA English
DT Letter
C1 [Roberts, Drucilla Jane] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Wilson, Michael L.] Univ Colorado, Sch Med, Denver, CO USA.
[Nelson, Ann Marie] Int Pathol & Lab Med Initiat, Denver, CO USA.
[Adesina, Adekunle M.] Texas Childrens Hosp, Hoston, TX USA.
[Fleming, Kenneth A.] Univ Oxford, Clin Acad, Grad Sch, Oxford, England.
[Milner, Dan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Guarner, Jeannette] Emory Univ, Atlanta, GA 30322 USA.
[Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Castle, Philip] Amer Soc Clin Pathologists, Amer Soc Clin Pathol Inst, Chicago, IL USA.
[Lucas, Sebastian] Kings Coll London, Sch Med, London WC2R 2LS, England.
RP Roberts, DJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM djroberts@partners.org
RI Guarner, Jeannette/B-8273-2013
NR 4
TC 5
Z9 5
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD FEB 25
PY 2012
VL 379
IS 9817
BP 712
EP 712
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 899CU
UT WOS:000300792600024
PM 22364759
ER
PT J
AU Meissner, TB
Li, A
Liu, YJ
Gagnon, E
Kobayashi, KS
AF Meissner, Torsten B.
Li, Amy
Liu, Yuen-Joyce
Gagnon, Etienne
Kobayashi, Koichi S.
TI The nucleotide-binding domain of NLRC5 is critical for nuclear import
and transactivation activity
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE MHC class I; NLR proteins; CITA
ID CLASS-II TRANSACTIVATOR; MHC CLASS-I; BARE LYMPHOCYTE SYNDROME; MICE
LACKING; GTP-BINDING; CIITA; EXPRESSION; COMPLEX; GENES; TRANSCRIPTION
AB Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. A member of the NLR (nucleotide-binding domain, leucine-rich repeat) protein family, NLRC5, has recently been identified as a transcriptional regulator of MHC class land related genes. While a 'master regulator' of MHC class II genes, CIITA, has long been known, NLRC5 specifically associates with and transactivates the proximal promoters of MHC class I genes. In this study, we analyzed the molecular requirements of NLRC5 nuclear import and transactivation activity. We show that NLRC5-mediated MHC class I gene induction requires an intact nuclear localization signal and nuclear distribution of NLRC5. In addition, we find that the nucleotide-binding domain (NBD) of NLRC5 is critical not only for nuclear translocation but also for the transactivation of MHC class I genes. Changing the cellular localization of NLRC5 is likely to immediately impact MHC class I expression as well as MHC class I-mediated antigen presentation. NLRC5 may thus provide a promising target for the modulation of MHC class I antigen presentation, especially in the setting of transplant medicine. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Meissner, Torsten B.; Li, Amy; Liu, Yuen-Joyce; Gagnon, Etienne; Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
[Meissner, Torsten B.; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA.
[Gagnon, Etienne] Univ Montreal, Dept Microbiol & Immunol, Inst Rech Immunol & Cancerol, Montreal, PQ H3T 1J4, Canada.
RP Kobayashi, KS (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Dana 1420A,450 Brookline Ave, Boston, MA 02215 USA.
EM Koichi_Kobayashi@dfci.harvard.edu
FU NIH [R01DK074738]; Crohn's and Colitis Foundation of America; Cancer
Research Institute; Claudia Adams Barr Award; EMBO
FX The authors thank Peter Cresswell, Peter van den Eisen, and Marja C.J.A.
van Eggermond for providing reagents: Lisa Cameron for assistance with
confocal microscopy. This work was supported by Grants from the NIH
(R01DK074738) and the Crohn's and Colitis Foundation of America. K.S.K.
is a recipient of the Investigator Award from the Cancer Research
Institute and the Claudia Adams Barr Award and T.B.M. is a recipient of
the EMBO Long Term fellowship. The authors have no conflicting financial
interests.
NR 27
TC 19
Z9 19
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD FEB 24
PY 2012
VL 418
IS 4
BP 786
EP 791
DI 10.1016/j.bbrc.2012.01.104
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 906GE
UT WOS:000301332100035
PM 22310711
ER
PT J
AU Vijayanand, P
Seumois, G
Simpson, LJ
Abdul-Wajid, S
Baumjohann, D
Panduro, M
Huang, XZ
Interlandi, J
Djuretic, VM
Brown, DR
Sharpe, AH
Rao, A
Ansel, KM
AF Vijayanand, Pandurangan
Seumois, Gregory
Simpson, Laura J.
Abdul-Wajid, Sarah
Baumjohann, Dirk
Panduro, Marisella
Huang, Xiaozhu
Interlandi, Jeneen
Djuretic, Vane M.
Brown, Daniel R.
Sharpe, Arlene H.
Rao, Anjana
Ansel, K. Mark
TI Interleukin-4 Production by Follicular Helper T Cells Requires the
Conserved Il4 Enhancer Hypersensitivity Site V
SO IMMUNITY
LA English
DT Article
ID TYPE-2 IMMUNITY; GENE-EXPRESSION; IL-4 PRODUCTION; COORDINATE REGULATOR;
CYTOKINE PRODUCTION; HELMINTH INFECTION; ALLERGIC DISEASES; GATA3
EXPRESSION; MAST-CELLS; TH2 CELLS
AB Follicular helper T cells (Tfh cells) are the major producers of interleukin-4 (IL-4) in secondary lymphoid organs where humoral immune responses develop. Il4 regulation in Tfh cells appears distinct from the classical T helper 2 (Th2) cell pathway, but the underlying molecular mechanisms remain largely unknown. We found that hypersensitivity site V (HS V; also known as CNS2), a 3' enhancer in the Il4 locus, is essential for IL-4 production by Tfh cells. Mice lacking HS V display marked defects in type 2 humoral immune responses, as evidenced by abrogated IgE and sharply reduced IgG1 production in vivo. In contrast, effector Th2 cells that are involved in tissue responses were far less dependent on HS V. HS V facilitated removal of repressive chromatin marks during Th2 and Tfh cell differentiation and increased accessibility of the Il4 promoter. Thus, Tfh and Th2 cells utilize distinct but overlapping molecular mechanisms to regulate Il4, a finding with important implications for understanding the molecular basis of allergic diseases.
C1 [Simpson, Laura J.; Abdul-Wajid, Sarah; Baumjohann, Dirk; Panduro, Marisella; Ansel, K. Mark] Univ Calif San Francisco, Dept Microbiol & Immunol, Sandler Asthma Basic Res Ctr, San Francisco, CA 94143 USA.
Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care, San Francisco, CA 94143 USA.
[Vijayanand, Pandurangan; Seumois, Gregory; Rao, Anjana] La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA 92037 USA.
[Vijayanand, Pandurangan; Seumois, Gregory] Southampton Gen Hosp, Sir Henry Wellcome Labs, Southampton NIHR Resp Biomed Res Unit, Div Infect Inflammat & Immun,Sch Med, Southampton SO16 6YD, Hants, England.
[Vijayanand, Pandurangan; Seumois, Gregory] Univ Southampton, Southampton SO16 6YD, Hants, England.
[Interlandi, Jeneen; Djuretic, Vane M.; Rao, Anjana] Harvard Univ, Sch Med, Immune Dis Inst, Dept Pathol, Boston, MA 02115 USA.
[Interlandi, Jeneen; Djuretic, Vane M.; Rao, Anjana] Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Brown, Daniel R.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Brown, Daniel R.; Sharpe, Arlene H.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Ansel, KM (reprint author), Univ Calif San Francisco, Dept Microbiol & Immunol, Sandler Asthma Basic Res Ctr, San Francisco, CA 94143 USA.
EM mark.ansel@ucsf.edu
RI Baumjohann, Dirk/C-9047-2009;
OI Baumjohann, Dirk/0000-0001-8385-8288; Abdul-Wajid,
Sarah/0000-0002-6000-7226
FU Burroughs Wellcome Fund; GSK National Clinician Scientist Fellowship
Award; Peel Travel Fellowship Award in United Kingdom; NIH [AI40127,
AI44432]; American Asthma Foundation; National Science Foundation; Swiss
National Science Foundation
FX The authors thank L. Du, L. Smith, E. Yanni, Z. Yang, Y. Soo Choi, and
J. Yang for expert technical assistance and M. Kubo and S. Crotty for
advice and critical reading of the manuscript. This project was funded
by the Burroughs Wellcome Fund (to K.M.A.), GSK National Clinician
Scientist Fellowship Award and Peel Travel Fellowship Award in United
Kingdom (to P.V.), NIH grants AI40127 and AI44432, and an award from the
American Asthma Foundation (to A.R.). L.J.S. is a National Science
Foundation Graduate Research Fellow. D.B. is the recipient of a Swiss
National Science Foundation Postdoctoral Fellowship. P.V., G.S., K.M.A.,
and A.R. conceived the work, designed, performed and analyzed
experiments, and wrote the paper; L.J.S., S.A.-W., J.I., I.M.D., and
D.R.B. assisted in some of the experiments under the supervision of
P.V., G.S., K.M.A., A.R., and A.H.S.; and X.H. performed some of the
experiments with the model of allergic airway disease.
NR 56
TC 51
Z9 51
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD FEB 24
PY 2012
VL 36
IS 2
BP 175
EP 187
DI 10.1016/j.immuni.2011.12.014
PG 13
WC Immunology
SC Immunology
GA 899JO
UT WOS:000300812400007
PM 22326582
ER
PT J
AU Yang, XH
Qiao, DH
Meyer, K
Pier, T
Keles, S
Friedl, A
AF Yang, Xinhai
Qiao, Dianhua
Meyer, Kristy
Pier, Thomas
Keles, Sunduz
Friedl, Andreas
TI Angiogenesis Induced by Signal Transducer and Activator of Transcription
5A (STAT5A) Is Dependent on Autocrine Activity of Proliferin
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MAMMARY EPITHELIAL-CELLS; GENE-EXPRESSION; ENDOTHELIAL-CELLS;
MESSENGER-RNA; GROWTH; PROLACTIN; RECEPTOR; PROTEIN; FAMILY;
FIBROSARCOMA
AB Multiple secreted factors induce the formation of new blood vessels (angiogenesis). The signal transduction events that orchestrate the numerous cellular activities required for angiogenesis remain incompletely understood. We have shown previously that STAT5 plays a pivotal role in angiogenesis induced by FGF2 and FGF8b. To delineate the signaling pathway downstream of STAT5, we expressed constitutively active (CA) or dominant-negative (DN) mutant STAT5A in mouse brain endothelial cells (EC). We found that the conditioned medium from CA-STAT5A but not from dominant-negative STAT5A overexpressing EC is sufficient to induce EC invasion and tube formation, indicating that STAT5A regulates the secretion of autocrine proangiogenic factors. Conversely, CA-STAT5A-induced conditioned medium had no effect on EC proliferation. Using a comparative genome-wide transcription array screen, we identified the prolactin family member proliferin (PLF1 and PLF4) as a candidate autocrine factor. The CA-STAT5A-dependent transcription and secretion of PLF by EC was confirmed by quantitative RT-PCR and Western blotting, respectively. CA-STAT5A binds to the PLF1 promoter region, suggesting a direct transcriptional regulation. Knockdown of PLF expression by shRNA or by blocking of PLF activity with neutralizing antibodies removed the CA-STAT5A-dependent proangiogenic activity from the conditioned medium of EC. Similarly, the ability of concentrated conditioned medium from CA-STAT5A transfected EC to induce angiogenesis in Matrigel plugs in vivo was abolished when PLF was depleted from the medium. These observations demonstrate a FGF/STAT5/PLF signaling cascade in EC and implicate PLF as autocrine regulator of EC invasion and tube formation.
C1 [Yang, Xinhai; Qiao, Dianhua; Meyer, Kristy; Pier, Thomas; Friedl, Andreas] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53792 USA.
[Keles, Sunduz] Univ Wisconsin, Dept Stat & Biostat & Med Informat, Madison, WI 53792 USA.
[Friedl, Andreas] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Dept Vet Affairs Med Ctr, Madison, WI 53705 USA.
RP Friedl, A (reprint author), WIMR Rm 6051,1111 Highland Ave, Madison, WI 53705 USA.
EM afriedl@wisc.edu
FU National Institutes of Health [RO1NS048921-01]; Biomedical Laboratory
Research and Development Service of the VA Office of Research and
Development [I01BX000137]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant RO1NS048921-01. This work was also based upon work
supported in part by Award I01BX000137 from the Biomedical Laboratory
Research and Development Service of the VA Office of Research and
Development.
NR 33
TC 7
Z9 7
U1 1
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 24
PY 2012
VL 287
IS 9
BP 6490
EP 6502
DI 10.1074/jbc.M111.254631
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 899CQ
UT WOS:000300791800038
PM 22199350
ER
PT J
AU Kakkar, R
Hei, H
Dobner, S
Lee, RT
AF Kakkar, Rahul
Hei, Hillary
Dobner, Stephan
Lee, Richard T.
TI Interleukin 33 as a Mechanically Responsive Cytokine Secreted by Living
Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PRESSURE-OVERLOAD; IN-VIVO; CARDIAC-HYPERTROPHY; IL-33; RECEPTOR; ST2;
TRANSPORT; ALARMIN
AB Interleukin 33 (IL-33), a member of the Interleukin 1 cytokine family, is implicated in numerous human inflammatory diseases such as asthma, atherosclerosis, and rheumatoid arthritis. Despite its pathophysiologic importance, fundamental questions regarding the basic biology of IL-33 remain. Nuclear localization and lack of an export signal sequence are consistent with the view of IL-33 as a nuclear factor with the ability to repress RNA transcription. However, signaling via the transmembrane receptor ST2 and documented caspase-dependent inactivation have suggested IL-33 is liberated during cellular necrosis to effect paracrine signaling. We determined the subcellular localization of IL-33 and tracked its intracellular mobility and extracellular release. In contrast to published data, IL-33 localized simultaneously to nuclear euchromatin and membrane-bound cytoplasmic vesicles. Fluorescent pulse-chase fate-tracking documented dynamic nucleo-cytoplasmic flux, which was dependent on nuclear pore complex function. In murine fibroblasts in vitro and in vivo, mechanical strain induced IL-33 secretion in the absence of cellular necrosis. These data document IL-33 dynamic inter-organelle trafficking and release during biomechanical overload. As such we recharacterize IL-33 as both an inflammatory as well as mechanically responsive cytokine secreted by living cells.
C1 [Kakkar, Rahul; Hei, Hillary; Dobner, Stephan; Lee, Richard T.] Brigham & Womens Hosp, Harvard Stem Cell Inst, Dept Med, Cambridge, MA 02139 USA.
[Kakkar, Rahul; Hei, Hillary; Dobner, Stephan; Lee, Richard T.] Brigham & Womens Hosp, Div Cardiovasc, Cambridge, MA 02139 USA.
Harvard Univ, Sch Med, Cambridge, MA 02139 USA.
[Kakkar, Rahul] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Lee, RT (reprint author), Partners Res Facil, 65 Landsdowne St, Cambridge, MA 02139 USA.
EM RLee@partners.org
FU NHLBI, National Institutes of Health [HL092930, T32HL007208];
Massachusetts General Hospital Division of Cardiology; Austrian Science
Fund (FWF) [J3004-B18]
FX This work was supported, in whole or in part, by Grants HL092930 (to
R.T.L.) and T32HL007208 (to R.K.) from the NHLBI, National Institutes of
Health. This work was also supported by the Massachusetts General
Hospital Division of Cardiology (to R.K.) and the Austrian Science Fund
(FWF Grant J3004-B18) (to S.D.).
NR 20
TC 114
Z9 122
U1 2
U2 15
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 24
PY 2012
VL 287
IS 9
BP 6941
EP 6948
DI 10.1074/jbc.M111.298703
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 899CQ
UT WOS:000300791800078
PM 22215666
ER
PT J
AU Paraskar, A
Soni, S
Roy, B
Papa, AL
Sengupta, S
AF Paraskar, Abhimanyu
Soni, Shivani
Roy, Bhaskar
Papa, Anne-Laure
Sengupta, Shiladitya
TI Rationally designed oxaliplatin-nanoparticle for enhanced antitumor
efficacy
SO NANOTECHNOLOGY
LA English
DT Article
ID DRUG-DELIVERY; LIPOSOMAL OXALIPLATIN; TUMOR-XENOGRAFT; CELLULAR-DNA;
IN-VIVO; CISPLATIN; CANCER; CHEMOTHERAPY; PHARMACOKINETICS; DERIVATIVES
AB Nanoscale drug delivery vehicles have been extensively studied as carriers for cancer chemotherapeutics. However, the formulation of platinum chemotherapeutics in nanoparticles has been a challenge arising from their physicochemical properties. There are only a few reports describing oxaliplatin nanoparticles. In this study, we derivatized the monomeric units of a polyisobutylene maleic acid copolymer with glucosamine, which chelates trans-1,2-diaminocyclohexane (DACH) platinum (II) through a novel monocarboxylato and O -> Pt coordination linkage. At a specific polymer to platinum ratio, the complex self-assembled into a nanoparticle, where the polymeric units act as the leaving group, releasing DACH-platinum in a sustained pH-dependent manner. Sizing was done using dynamic light scatter and electron microscopy. The nanoparticles were evaluated for efficacy in vitro and in vivo. Biodistribution was quantified using inductively coupled plasma atomic absorption spectroscopy (ICP-AAS). The PIMA-GA-DACH-platinum nanoparticle was found to be more active than free oxaliplatin in vitro. In vivo, the nanoparticles resulted in greater tumor inhibition than oxaliplatin (equivalent to 5 mg kg(-1) platinum dose) with minimal nephrotoxicity or body weight loss. ICP-AAS revealed significant preferential tumor accumulation of platinum with reduced biodistribution to the kidney or liver following PIMA-GA-DACH-platinum nanoparticle administration as compared with free oxaliplatin. These results indicate that the rational engineering of a novel polymeric nanoparticle inspired by the bioactivation of oxaliplatin results in increased antitumor potency with reduced systemic toxicity compared with the parent cytotoxic. Rational design can emerge as an exciting strategy in the synthesis of nanomedicines for cancer chemotherapy.
C1 [Paraskar, Abhimanyu; Soni, Shivani; Roy, Bhaskar; Papa, Anne-Laure; Sengupta, Shiladitya] Brigham & Womens Hosp, Div Biomed Engn, Dept Med, Cambridge, MA 02139 USA.
[Paraskar, Abhimanyu; Soni, Shivani; Roy, Bhaskar; Papa, Anne-Laure; Sengupta, Shiladitya] Brigham & Womens Hosp, Ctr Regenerat Therapeut, Cambridge, MA 02139 USA.
[Sengupta, Shiladitya] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA.
[Sengupta, Shiladitya] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Paraskar, A (reprint author), Brigham & Womens Hosp, Div Biomed Engn, Dept Med, Cambridge, MA 02139 USA.
EM ssengupta2@partners.org
FU Department of Defense BCRP [W81XWH-07-1-0482, W81XWH-09-1-0728]; BCRP;
NIH [1R01CA135242-01A2]
FX This work is funded by a Department of Defense BCRP Era of Hope Scholar
Award (W81XWH-07-1-0482), a BCRP Innovator Collaborative Award and an
NIH RO1 (1R01CA135242-01A2) to SS. AP is supported by a DOD BCRP
postdoctoral fellowship award (W81XWH-09-1-0728).
NR 36
TC 10
Z9 10
U1 3
U2 30
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0957-4484
EI 1361-6528
J9 NANOTECHNOLOGY
JI Nanotechnology
PD FEB 24
PY 2012
VL 23
IS 7
AR 075103
DI 10.1088/0957-4484/23/7/075103
PG 9
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
Physics, Applied
SC Science & Technology - Other Topics; Materials Science; Physics
GA 888MF
UT WOS:000300007000003
PM 22275055
ER
PT J
AU Demidova-Rice, TN
Wolf, L
Deckenback, J
Hamblin, MR
Herman, IM
AF Demidova-Rice, Tatiana N.
Wolf, Lindsey
Deckenback, Jeffry
Hamblin, Michael R.
Herman, Ira M.
TI Human Platelet-Rich Plasma- and Extracellular Matrix-Derived Peptides
Promote Impaired Cutaneous Wound Healing In Vivo
SO PLOS ONE
LA English
DT Article
ID GROWTH-FACTORS; CELLS; MICE; ANGIOGENESIS; CYTOKINES; INJURY; VITRO
AB Previous work in our laboratory has described several pro-angiogenic short peptides derived from endothelial extracellular matrices degraded by bacterial collagenase. Here we tested whether these peptides could stimulate wound healing in vivo. Our experiments demonstrated that a peptide created as combination of fragments of tenascin X and fibrillin 1 (comb1) applied into cranial dermal wounds created in mice treated with cyclophosphamide to impair wound healing, can improve the rate of wound closure. Furthermore, we identify and characterize a novel peptide (UN3) created and modified from two naturally-occurring peptides, which are present in human platelet-rich plasma. In vitro testing of UN3 demonstrates that it causes a 50% increase in endothelial proliferation, 250% increase in angiogenic response and a tripling of epithelial cell migration in response to injury. Results of in vivo experiments where comb1 and UN3 peptides were added together to cranial wounds in cyclophosphamide-treated mice leads to improvement of wound vascularization as shown by an increase of the number of blood vessels present in the wound beds. Application of the peptides markedly promotes cellular responses to injury and essentially restores wound healing dynamics to those of normal, acute wounds in the absence of cyclophosphamide impairment. Our current work is aimed at understanding the mechanisms underlying the stimulatory effects of these peptides as well as identification of the cellular receptors mediating these effects.
C1 [Demidova-Rice, Tatiana N.; Wolf, Lindsey; Deckenback, Jeffry; Herman, Ira M.] Tufts Univ, Sch Med, Ctr Innovat Wound Healing Res, Grad Program Cellular & Mol Physiol,Sackler Sch G, Boston, MA 02111 USA.
[Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Demidova-Rice, TN (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA.
EM ira.herman@tufts.edu
OI Hamblin, Michael/0000-0001-6431-4605
FU National Institutes of Heatlh [EY15125, EY19533]; Wound Care Partners,
LLC
FX This work was supported in part by National Institutes of Heatlh
EY15125, EY19533, and Wound Care Partners, LLC. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 25
TC 25
Z9 26
U1 1
U2 19
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 23
PY 2012
VL 7
IS 2
AR e32146
DI 10.1371/journal.pone.0032146
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927NZ
UT WOS:000302916100054
PM 22384158
ER
PT J
AU Ramanadhan, S
Salhi, C
Achille, E
Baril, N
D'Entremont, K
Grullon, M
Judge, C
Oppenheimer, S
Reeves, C
Savage, C
Viswanath, K
AF Ramanadhan, Shoba
Salhi, Carmel
Achille, Erline
Baril, Nashira
D'Entremont, Kerrie
Grullon, Milagro
Judge, Christine
Oppenheimer, Sarah
Reeves, Chrasandra
Savage, Clara
Viswanath, Kasisomayajula
TI Addressing Cancer Disparities via Community Network Mobilization and
Intersectoral Partnerships: A Social Network Analysis
SO PLOS ONE
LA English
DT Article
ID HEALTH-PROMOTION PROGRAMS; COLLABORATIVE ADVANTAGE; CAPACITY; STRATEGY;
PREVENTION; COALITIONS; FRAMEWORK
AB Community mobilization and collaboration among diverse partners are vital components of the effort to reduce and eliminate cancer disparities in the United States. We studied the development and impact of intersectoral connections among the members of the Massachusetts Community Network for Cancer Education, Research, and Training (MassCONECT). As one of the Community Network Program sites funded by the National Cancer Institute, this infrastructure-building initiative utilized principles of Community-based Participatory Research (CBPR) to unite community coalitions, researchers, policymakers, and other important stakeholders to address cancer disparities in three Massachusetts communities: Boston, Lawrence, and Worcester. We conducted a cross-sectional, sociometric network analysis four years after the network was formed. A total of 38 of 55 members participated in the study (69% response rate). Over four years of collaboration, the number of intersectoral connections reported by members (intersectoral out-degree) increased, as did the extent to which such connections were reported reciprocally (intersectoral reciprocity). We assessed relationships between these markers of intersectoral collaboration and three intermediate outcomes in the effort to reduce and eliminate cancer disparities: delivery of community activities, policy engagement, and grants/publications. We found a positive and statistically significant relationship between intersectoral out-degree and community activities and policy engagement (the relationship was borderline significant for grants/publications). We found a positive and statistically significant relationship between intersectoral reciprocity and community activities and grants/publications (the relationship was borderline significant for policy engagement). The study suggests that intersectoral connections may be important drivers of diverse intermediate outcomes in the effort to reduce and eliminate cancer disparities. The findings support investment in infrastructure-building and intersectoral mobilization in addressing disparities and highlight the benefits of using CBPR approaches for such work.
C1 [Ramanadhan, Shoba; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Salhi, Carmel] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA.
[Achille, Erline; Baril, Nashira] Boston Publ Hlth Commiss, New England Ctr Excellence Eliminat Dispar, Boston, MA USA.
[D'Entremont, Kerrie; Grullon, Milagro] City Lawrence, Mayors Hlth Task Force, Lawrence, MA USA.
[Judge, Christine; Oppenheimer, Sarah] Harvard Univ, Sch Publ Hlth, Div Publ Hlth Practice, Boston, MA 02115 USA.
[Reeves, Chrasandra] Boston Alliance Community Hlth, Boston, MA USA.
[Savage, Clara] Common Pathways, Worcester, MA USA.
[Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
RP Ramanadhan, S (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
EM shoba_ramanadhan@dfci.harvard.edu
FU National Cancer Institute [5 U01 CA114644]
FX This work was funded by the National Cancer Institute (Grant#: 5 U01
CA114644, Viswanath, PI). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. One co-author, Milagro Grullon, currently works for a
commercial enterprise, but was employed by the City of Lawrence Mayor's
Health Task Force at the time this work was conducted and the work was
not funded or impacted by Lawrence Community Connections.
NR 55
TC 7
Z9 7
U1 2
U2 19
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 23
PY 2012
VL 7
IS 2
AR e32130
DI 10.1371/journal.pone.0032130
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927NZ
UT WOS:000302916100053
PM 22384156
ER
PT J
AU de Calignon, A
Polydoro, M
Suarez-Calvet, M
William, C
Adamowicz, DH
Kopeikina, KJ
Pitstick, R
Sahara, N
Ashe, KH
Carlson, GA
Spires-Jones, TL
Hyman, BT
AF de Calignon, Alix
Polydoro, Manuela
Suarez-Calvet, Marc
William, Christopher
Adamowicz, David H.
Kopeikina, Kathy J.
Pitstick, Rose
Sahara, Naruhiko
Ashe, Karen H.
Carlson, George A.
Spires-Jones, Tara L.
Hyman, Bradley T.
TI Propagation of Tau Pathology in a Model of Early Alzheimer's Disease
SO NEURON
LA English
DT Article
ID ENTORHINAL CORTEX; DENTATE GYRUS; SYNAPSE LOSS; PATHOGENETIC
IMPLICATIONS; PROTEIN IMMUNOREACTIVITY; HIPPOCAMPAL-FORMATION;
ELECTRON-MICROSCOPY; CEREBROSPINAL-FLUID; PERFORANT PATH; NEURONAL LOSS
AB Neurofibrillary tangles advance from layer II of the entorhinal cortex (EC-II) toward limbic and association cortices as Alzheimer's disease evolves. However, the mechanism involved in this hierarchical pattern of disease progression is unknown. We describe a transgenic mouse model in which overexpression of human tau P301L is restricted to EC-II. Tau pathology progresses from EC transgene-expressing neurons to neurons without detectable transgene expression, first to EC neighboring cells, followed by propagation to neurons downstream in the synaptic circuit such as the dentate gyrus, CA fields of the hippocampus, and cingulate cortex. Human tau protein spreads to these regions and coaggregates with endogenous mouse tau. With age, synaptic degeneration occurs in the entorhinal target zone and EC neurons are lost. These data suggest that a sequence of progressive misfolding of tau proteins, circuit-based transfer to new cell populations, and deafferentation induced degeneration are part of a process of tau-induced neurodegeneration.
C1 [de Calignon, Alix; Polydoro, Manuela; Suarez-Calvet, Marc; William, Christopher; Adamowicz, David H.; Kopeikina, Kathy J.; Spires-Jones, Tara L.; Hyman, Bradley T.] Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis,Dept Neurol, Massachusetts Gen Hosp,Alzheimers Dis Res Lab, Charlestown, MA 02129 USA.
[de Calignon, Alix] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
[Suarez-Calvet, Marc] Univ Autonoma Barcelona, Dept Neurol, Hosp Santa Creu & St Pau, Barcelona 08025, Spain.
[Kopeikina, Kathy J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA.
[Pitstick, Rose; Carlson, George A.] McLaughlin Res Inst, Great Falls, MT 59405 USA.
[Sahara, Naruhiko] Univ Florida, Dept Neurosci, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA.
[Carlson, George A.] Univ Minnesota, Dept Neurol, Sch Med, Minneapolis, MN 55455 USA.
RP Hyman, BT (reprint author), Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis,Dept Neurol, Massachusetts Gen Hosp,Alzheimers Dis Res Lab, Charlestown, MA 02129 USA.
EM bhyman@partners.org
OI Suarez-Calvet, Marc/0000-0002-2993-569X; Spires-Jones,
Tara/0000-0003-2530-0598
FU Alzheimer's Association; National Institutes of Health [AG08487,
AG026249, K08NS069811, K99AG33670, R21AG038835-01A1, R21 NS067127];
American Health Assistance Foundation [A2011086]
FX This work was supported by an Alzheimer's Association Zenith award;
National Institutes of Health grants AG08487, AG026249, K08NS069811,
K99AG33670, R21AG038835-01A1, and R21 NS067127; and American Health
Assistance Foundation grant A2011086. We thank Mark Mayford for
providing neuropsin-tTA mice, Peter Davies for providing tau antibodies,
and Zhanyun Fan, Taylor Friedman, Charles Vanderburg, Ozge
Cagsal-Getkin, and Meredith Banigan for technical assistance.
NR 50
TC 448
Z9 451
U1 8
U2 119
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD FEB 23
PY 2012
VL 73
IS 4
BP 685
EP 697
DI 10.1016/j.neuron.2011.11.033
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 899KS
UT WOS:000300815400009
PM 22365544
ER
PT J
AU Sosman, JA
Kim, KB
Schuchter, L
Gonzalez, R
Pavlick, AC
Weber, JS
McArthur, GA
Hutson, TE
Moschos, SJ
Flaherty, KT
Hersey, P
Kefford, R
Lawrence, D
Puzanov, I
Lewis, KD
Amaravadi, RK
Chmielowski, B
Lawrence, HJ
Shyr, Y
Ye, F
Li, J
Nolop, KB
Lee, RJ
Joe, AK
Ribas, A
AF Sosman, Jeffrey A.
Kim, Kevin B.
Schuchter, Lynn
Gonzalez, Rene
Pavlick, Anna C.
Weber, Jeffrey S.
McArthur, Grant A.
Hutson, Thomas E.
Moschos, Stergios J.
Flaherty, Keith T.
Hersey, Peter
Kefford, Richard
Lawrence, Donald
Puzanov, Igor
Lewis, Karl D.
Amaravadi, Ravi K.
Chmielowski, Bartosz
Lawrence, H. Jeffrey
Shyr, Yu
Ye, Fei
Li, Jiang
Nolop, Keith B.
Lee, Richard J.
Joe, Andrew K.
Ribas, Antoni
TI Survival in BRAF V600-Mutant Advanced Melanoma Treated with Vemurafenib
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID METASTATIC MALIGNANT-MELANOMA; COOPERATIVE-ONCOLOGY-GROUP; RAF INHIBITOR
PLX4032; PHASE-III TRIAL; DACARBAZINE; RESISTANCE; KINASE; BRAF(V600E);
MUTATION; INTERFERON-ALPHA-2B
AB BACKGROUND
Approximately 50% of melanomas harbor activating (V600) mutations in the serinethreonine protein kinase B-RAF (BRAF). The oral BRAF inhibitor vemurafenib (PLX4032) frequently produced tumor regressions in patients with BRAF V600-mutant metastatic melanoma in a phase 1 trial and improved overall survival in a phase 3 trial.
METHODS
We designed a multicenter phase 2 trial of vemurafenib in patients with previously treated BRAF V600-mutant metastatic melanoma to investigate the efficacy of vemurafenib with respect to overall response rate (percentage of treated patients with a tumor response), duration of response, and overall survival. The primary end point was the overall response rate as ascertained by the independent review committee; overall survival was a secondary end point.
RESULTS
A total of 132 patients had a median follow-up of 12.9 months (range, 0.6 to 20.1). The confirmed overall response rate was 53% (95% confidence interval [CI], 44 to 62; 6% with a complete response and 47% with a partial response), the median duration of response was 6.7 months (95% CI, 5.6 to 8.6), and the median progression-free survival was 6.8 months (95% CI, 5.6 to 8.1). Primary progression was observed in only 14% of patients. Some patients had a response after receiving vemurafenib for more than 6 months. The median overall survival was 15.9 months (95% CI, 11.6 to 18.3). The most common adverse events were grade 1 or 2 arthralgia, rash, photosensitivity, fatigue, and alopecia. Cutaneous squamous-cell carcinomas (the majority, keratoacanthoma type) were diagnosed in 26% of patients.
CONCLUSIONS
Vemurafenib induces clinical responses in more than half of patients with previously treated BRAF V600-mutant metastatic melanoma. In this study with a long follow-up, the median overall survival was approximately 16 months. (Funded by Hoffmann-La Roche; ClinicalTrials.gov number, NCT00949702.)
C1 [Sosman, Jeffrey A.; Puzanov, Igor] Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
[Shyr, Yu; Ye, Fei] Vanderbilt Univ, Med Ctr, Ctr Quantitat Sci, Nashville, TN USA.
[Kim, Kevin B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Schuchter, Lynn; Amaravadi, Ravi K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Gonzalez, Rene; Lewis, Karl D.] Univ Colorado, Denver, CO 80202 USA.
[Pavlick, Anna C.] NYU, Med Ctr, New York, NY 10016 USA.
[Weber, Jeffrey S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[McArthur, Grant A.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Hersey, Peter] Univ Newcastle, Newcastle, NSW 2300, Australia.
[Kefford, Richard] Westmead Inst Canc Res, Westmead, NSW, Australia.
[Kefford, Richard] Melanoma Inst Australia, Westmead, NSW, Australia.
[Hutson, Thomas E.] Texas Oncol Baylor Sammons Canc Ctr, Dallas, TX USA.
[Moschos, Stergios J.] Univ Pittsburgh, Pittsburgh, PA USA.
[Flaherty, Keith T.; Lawrence, Donald] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Chmielowski, Bartosz; Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
[Lawrence, H. Jeffrey] Roche Mol Syst, Pleasanton, CA USA.
[Nolop, Keith B.] Plexxikon, Berkeley, CA USA.
[Li, Jiang; Lee, Richard J.; Joe, Andrew K.] Hoffmann La Roche, Nutley, NJ USA.
RP Sosman, JA (reprint author), Vanderbilt Ingram Canc Ctr, 777 Preston Res Bldg, Nashville, TN 37232 USA.
EM jeff.sosman@vanderbilt.edu
FU Hoffmann-La Roche
FX Supported by Hoffmann-La Roche.
NR 39
TC 1015
Z9 1037
U1 7
U2 92
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 23
PY 2012
VL 366
IS 8
BP 707
EP 714
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 896FS
UT WOS:000300551500008
PM 22356324
ER
PT J
AU Cho, TA
Larvie, M
Tian, D
Mino-Kenudson, M
AF Cho, Tracey A.
Larvie, Mykol
Tian, Di
Mino-Kenudson, Mari
TI Case 6-2012: A 45-Year-Old Man with a History of Alcohol Abuse and Rapid
Cognitive Decline Alcoholic liver disease with fibrosis. Brain abscess
due to toxoplasma. Advanced HIV infection
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ANTIRETROVIRAL THERAPY; COST-EFFECTIVENESS; AIDS; ENCEPHALITIS;
DIAGNOSIS; HEPATITIS; CRITERIA
C1 [Cho, Tracey A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Larvie, Mykol] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Tian, Di; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Cho, Tracey A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Larvie, Mykol] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Tian, Di; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Cho, TA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
NR 19
TC 1
Z9 1
U1 0
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 23
PY 2012
VL 366
IS 8
BP 745
EP 755
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 896FS
UT WOS:000300551500013
PM 22356328
ER
PT J
AU Cash, SS
Batchelor, TT
Dalmau, J
AF Cash, Sydney S.
Batchelor, Tracy T.
Dalmau, Josep
TI Case 34-2011: A Man with Memory Loss and Partial Seizures REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID ENCEPHALITIS
C1 [Cash, Sydney S.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Dalmau, Josep] Univ Penn, Philadelphia, PA 19104 USA.
RP Cash, SS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
OI Dalmau, Josep/0000-0001-5856-2813
NR 3
TC 0
Z9 0
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 23
PY 2012
VL 366
IS 8
BP 769
EP 769
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 896FS
UT WOS:000300551500027
ER
PT J
AU Blood, AJ
Kuster, JK
Woodman, SC
Kirlic, N
Makhlouf, ML
Multhaupt-Buell, TJ
Makris, N
Parent, M
Sudarsky, LR
Sjalander, G
Breiter, H
Breiter, HC
Sharma, N
AF Blood, Anne J.
Kuster, John K.
Woodman, Sandra C.
Kirlic, Namik
Makhlouf, Miriam L.
Multhaupt-Buell, Trisha J.
Makris, Nikos
Parent, Martin
Sudarsky, Lewis R.
Sjalander, Greta
Breiter, Henry
Breiter, Hans C.
Sharma, Nutan
TI Evidence for Altered Basal Ganglia-Brainstem Connections in Cervical
Dystonia
SO PLOS ONE
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; TOXIN TYPE-A; FOCAL DYSTONIA; DYT1 DYSTONIA;
PSYCHIATRIC COMORBIDITY; SPASMODIC TORTICOLLIS; ABNORMAL PLASTICITY;
CEREBELLUM; CARRIERS; LESIONS
AB Background: There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia.
Methodology/Principal Findings: In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients.
Conclusions/Significance: These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.
C1 [Blood, Anne J.; Kuster, John K.; Woodman, Sandra C.; Kirlic, Namik; Makhlouf, Miriam L.; Sjalander, Greta; Breiter, Henry; Breiter, Hans C.] Massachusetts Gen Hosp, Mood & Motor Control Lab, Charlestown, MA 02129 USA.
[Blood, Anne J.; Kuster, John K.; Kirlic, Namik; Breiter, Hans C.] Massachusetts Gen Hosp, Lab Neuroimaging & Genet, Charlestown, MA USA.
[Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA USA.
[Blood, Anne J.; Kuster, John K.; Woodman, Sandra C.; Kirlic, Namik; Makhlouf, Miriam L.; Makris, Nikos; Sjalander, Greta; Breiter, Henry; Breiter, Hans C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Blood, Anne J.; Kuster, John K.; Woodman, Sandra C.; Kirlic, Namik; Makris, Nikos; Breiter, Henry; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA.
[Blood, Anne J.; Kuster, John K.; Multhaupt-Buell, Trisha J.; Sjalander, Greta; Sharma, Nutan] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
[Breiter, Hans C.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA.
[Sudarsky, Lewis R.; Sharma, Nutan] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Blood, Anne J.; Makris, Nikos; Sudarsky, Lewis R.; Breiter, Hans C.; Sharma, Nutan] Harvard Univ, Sch Med, Boston, MA USA.
[Kuster, John K.] Boston Univ, Sch Med, Div Grad Med Sci, Boston, MA 02118 USA.
[Makhlouf, Miriam L.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Parent, Martin] Univ Laval, Fac Med, Ctr Rech Univ Laval Robert Giffard, Dept Psychiat & Neurosci, Quebec City, PQ G1K 7P4, Canada.
[Breiter, Hans C.] NW Univ Feinberg, Warren Wright Adolescent Ctr, Sch Med, Dept Psychiat & Behav Sci, Chicago, IL USA.
[Breiter, Hans C.] NW Univ Feinberg, Ctr Self Regulat, Chicago, IL USA.
RP Blood, AJ (reprint author), Massachusetts Gen Hosp, Mood & Motor Control Lab, Charlestown, MA 02129 USA.
EM ablood@nmr.mgh.harvard.edu
FU National Institute of Neurological Disorders and Stroke [R01NS052368,
NINP50NS037409]; Dystonia Medical Research Foundation; National Center
for Research Resources [P41 RR14075, UL1 RR025758-01]; Mental Illness
and Neuroscience Discovery (MIND) Institute
FX This work was supported by grants from the National Institute of
Neurological Disorders and Stroke (grant number R01NS052368 to Dr.
Blood, and grant number NINP50NS037409 to Dr. Breakefield with Dr.
Sharma as PI of the clinical core), and a grant from the Dystonia
Medical Research Foundation to Dr. Blood. The general infrastructure of
the Martinos Center for Biomedical Imaging in which research on these
grants was conducted, was supported by National Center for Research
Resources (grant number P41 RR14075 to Dr. Rosen), and the Mental
Illness and Neuroscience Discovery (MIND) Institute (Dr. Rosen).
Prescreening and exams were conducted in the General Clinical Research
Center, funded by National Center for Research Resources (grant number
UL1 RR025758-01). 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 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 22
PY 2012
VL 7
IS 2
AR e31654
DI 10.1371/journal.pone.0031654
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 926ZZ
UT WOS:000302875500028
PM 22384048
ER
PT J
AU Shapiro, RL
Souda, S
Parekh, N
Binda, K
Kayembe, M
Lockman, S
Svab, P
Babitseng, O
Powis, K
Jimbo, W
Creek, T
Makhema, J
Essex, M
Roberts, DJ
AF Shapiro, Roger L.
Souda, Sajini
Parekh, Natasha
Binda, Kelebogile
Kayembe, Mukendi
Lockman, Shahin
Svab, Petr
Babitseng, Orphinah
Powis, Kathleen
Jimbo, William
Creek, Tracy
Makhema, Joseph
Essex, Max
Roberts, Drucilla J.
TI High Prevalence of Hypertension and Placental Insufficiency, but No In
Utero HIV Transmission, among Women on HAART with Stillbirths in
Botswana
SO PLOS ONE
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; GESTATIONAL HYPERTENSION; PREGNANCY
OUTCOMES; INCREASED RISK; INFECTION; PREECLAMPSIA; DELIVERY
AB Background: Increased stillbirth rates occur among HIV-infected women, but no studies have evaluated the pathological basis for this increase, or whether highly active antiretroviral therapy (HAART) influences the etiology of stillbirths. It is also unknown whether HIV infection of the fetus is associated with stillbirth.
Methods: HIV-infected women and a comparator group of HIV-uninfected women who delivered stillbirths were enrolled at the largest referral hospital in Botswana between January and November 2010. Obstetrical records, including antiretroviral use in pregnancy, were extracted at enrollment. Verbal autopsies; maternal HIV, CD4 and HIV RNA testing; stillbirth HIV PCR testing; and placental pathology (blinded to HIV and treatment status) were performed.
Results: Ninety-nine stillbirths were evaluated, including 62 from HIV-infected women (34% on HAART from conception, 8% on HAART started in pregnancy, 23% on zidovudine started in pregnancy, and 35% on no antiretrovirals) and 37 from a comparator group of HIV-uninfected women. Only 2 (3.7%) of 53 tested stillbirths from HIV-infected women were HIV PCR positive, and both were born to women not receiving HAART. Placental insufficiency associated with hypertension accounted for most stillbirths. Placental findings consistent with chronic hypertension were common among HIV-infected women who received HAART and among HIV-uninfected women (65% vs. 54%, p = 0.37), but less common among HIV-infected women not receiving HAART (28%, p = 0.003 vs. women on HAART).
Conclusions: In utero HIV infection was rarely associated with stillbirths, and did not occur among women receiving HAART. Hypertension and placental insufficiency were associated with most stillbirths in this tertiary care setting.
C1 [Shapiro, Roger L.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
[Shapiro, Roger L.; Lockman, Shahin; Powis, Kathleen; Makhema, Joseph; Essex, Max] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Shapiro, Roger L.; Souda, Sajini; Parekh, Natasha; Binda, Kelebogile; Lockman, Shahin; Powis, Kathleen; Makhema, Joseph; Essex, Max] Botswana Harvard Sch Publ Hlth, AIDS Inst Partnership HIV Res & Educ, Boston, MA 02115 USA.
[Kayembe, Mukendi] Minist Hlth, Botswana Natl Hlth Lab, Gaborone, Botswana.
[Lockman, Shahin] Brigham & Womens Hosp, Infect Dis Unit, Boston, MA 02115 USA.
[Svab, Petr; Babitseng, Orphinah] Princess Marina Hosp, Minist Hlth, Gaborone, Botswana.
[Powis, Kathleen] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Powis, Kathleen] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Jimbo, William; Creek, Tracy] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Roberts, Drucilla J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Shapiro, RL (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
EM rshapiro@hsph.harvard.edu
FU Centers for Disease Control and Prevention [U2GPS000941]; Doris Duke
Charitable Research Foundation
FX This work was supported by a grant from the Centers for Disease Control
and Prevention (U2GPS000941), and by a Research Fellowship from the
Doris Duke Charitable Research Foundation (N.P.). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 23
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U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 22
PY 2012
VL 7
IS 2
AR e31580
DI 10.1371/journal.pone.0031580
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 926ZZ
UT WOS:000302875500026
PM 22384039
ER
PT J
AU Wey, MCY
Fernandez, E
Martinez, PA
Sullivan, P
Goldstein, DS
Strong, R
AF Wey, Margaret Chia-Ying
Fernandez, Elizabeth
Martinez, Paul Anthony
Sullivan, Patricia
Goldstein, David S.
Strong, Randy
TI Neurodegeneration and Motor Dysfunction in Mice Lacking Cytosolic and
Mitochondrial Aldehyde Dehydrogenases: Implications for Parkinson's
Disease
SO PLOS ONE
LA English
DT Article
ID HUMAN ALPHA-SYNUCLEIN; ENDOGENOUS DOPAMINERGIC NEUROTOXIN;
AMYOTROPHIC-LATERAL-SCLEROSIS; ONSET ALZHEIMERS-DISEASE; STRIDE LENGTH
REGULATION; TREADMILL GAIT ANALYSIS; L-DOPA; HYDROGEN-PEROXIDE;
3,4-DIHYDROXYPHENYLACETALDEHYDE; SEROTONIN
AB Previous studies have reported elevated levels of biogenic aldehydes in the brains of patients with Parkinson's disease (PD). In the brain, aldehydes are primarily detoxified by aldehyde dehydrogenases (ALDH). Reduced ALDH1 expression in surviving midbrain dopamine neurons has been reported in brains of patients who died with PD. In addition, impaired complex I activity, which is well documented in PD, reduces the availability of the NAD(+) co-factor required by multiple ALDH isoforms to catalyze the removal of biogenic aldehydes. We hypothesized that chronically decreased function of multiple aldehyde dehydrogenases consequent to exposure to environmental toxins and/or reduced ALDH expression, plays an important role in the pathophysiology of PD. To address this hypothesis, we generated mice null for Aldh1a1 and Aldh2, the two isoforms known to be expressed in substantia nigra dopamine neurons. Aldh1a1(-/-) xAldh2(-/-) mice exhibited age-dependent deficits in motor performance assessed by gait analysis and by performance on an accelerating rotarod. Intraperitoneal administration of L-DOPA plus benserazide alleviated the deficits in motor performance. We observed a significant loss of neurons immunoreactive for tyrosine hydroxylase (TH) in the substantia nigra and a reduction of dopamine and metabolites in the striatum of Aldh1a1(-/-) xAldh2(-/-) mice. We also observed significant increases in biogenic aldehydes reported to be neurotoxic, including 4-hydroxynonenal (4-HNE) and the aldehyde intermediate of dopamine metabolism, 3,4-dihydroxyphenylacetaldehyde (DOPAL). These results support the hypothesis that impaired detoxification of biogenic aldehydes may be important in the pathophysiology of PD and suggest that Aldh1a1(-/-) xAldh2(-/-) mice may be a useful animal model of PD.
C1 [Wey, Margaret Chia-Ying; Fernandez, Elizabeth; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Wey, Margaret Chia-Ying; Fernandez, Elizabeth; Martinez, Paul Anthony; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Fernandez, Elizabeth; Strong, Randy] S Texas Vet Hlth Care Network, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA.
[Sullivan, Patricia; Goldstein, David S.] Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res, Bethesda, MD USA.
RP Wey, MCY (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
EM FernandezE@uthscsa.edu; Strong@uthscsa.edu
FU Veteran Affairs Office of Research Development; National Institute of
Aging [T32 AG021890-08]
FX This work was supported by grants from the Veteran Affairs Office of
Research & Development (to E.F. and R.S.) and the National Institute of
Aging predoctoral training grant T32 AG021890-08 (to M.C.W.). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 22
PY 2012
VL 7
IS 2
AR e31522
DI 10.1371/journal.pone.0031522
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 926ZZ
UT WOS:000302875500023
PM 22384032
ER
PT J
AU Rice, TW
Wheeler, AP
Thompson, BT
Steingrub, J
Hite, RD
Moss, M
Morris, A
Dong, N
Rock, P
AF Rice, Todd W.
Wheeler, Arthur P.
Thompson, B. Taylor
Steingrub, Jay
Hite, R. Duncan
Moss, Marc
Morris, Alan
Dong, Ning
Rock, Peter
CA National Heart Lung & Blood Inst A
TI ONLINE FIRST Initial Trophic vs Full Enteral Feeding in Patients With
Acute Lung Injury The EDEN Randomized Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID MECHANICALLY VENTILATED PATIENTS; CRITICALLY-ILL PATIENTS;
CLINICAL-PRACTICE GUIDELINES; INTENSIVE-CARE-UNIT; NUTRITION SUPPORT;
PARENTERAL-NUTRITION; CALORIC-INTAKE; ADULT PATIENTS; OUTCOMES;
MORTALITY
AB Context The amount of enteral nutrition patients with acute lung injury need is unknown.
Objective To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days and decrease gastrointestinal intolerances compared with initial full enteral feeding.
Design, Setting, and Participants The EDEN study, a randomized, open-label, multicenter trial conducted from January 2, 2008, through April 12, 2011. Participants were 1000 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.
Interventions Participants were randomized to receive either trophic or full enteral feeding for the first 6 days. After day 6, the care of all patients who were still receiving mechanical ventilation was managed according to the full feeding protocol.
Main Outcome Measures Ventilator-free days to study day 28.
Results Baseline characteristics were similar between the trophic-feeding (n=508) and full-feeding (n=492) groups. The full-feeding group received more enteral calories for the first 6 days, about 1300 kcal/d compared with 400 kcal/d (P<.001). Initial trophic feeding did not increase the number of ventilator-free days (14.9 [95% CI, 13.9 to 15.8] vs 15.0 [95% CI, 14.1 to 15.9]; difference, -0.1 [95% CI, -1.4 to 1.2]; P=.89) or reduce 60-day mortality (23.2% [95% CI, 19.6% to 26.9%] vs 22.2% [95% CI, 18.5% to 25.8%]; difference, 1.0% [95% CI, -4.1% to 6.3%]; P=.77) compared with full feeding. There were no differences in infectious complications between the groups. Despite receiving more prokinetic agents, the full-feeding group experienced more vomiting (2.2% vs 1.7% of patient feeding days; P=.05), elevated gastric residual volumes (4.9% vs 2.2% of feeding days; P<.001), and constipation (3.1% vs 2.1% of feeding days; P=.003). Mean plasma glucose values and average hourly insulin administration were both higher in the full-feeding group over the first 6 days.
Conclusion In patients with acute lung injury, compared with full enteral feeding, a strategy of initial trophic enteral feeding for up to 6 days did not improve ventilator-free days, 60-day mortality, or infectious complications but was associated with less gastrointestinal intolerance.
C1 [Rice, Todd W.; Wheeler, Arthur P.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Thompson, B. Taylor; Dong, Ning] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Steingrub, Jay] Baystate Med Ctr, Springfield, MA USA.
[Hite, R. Duncan] Wake Forest Sch Med, Winston Salem, NC USA.
[Moss, Marc] Univ Colorado, Sch Med, Denver, CO USA.
[Morris, Alan] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Rock, Peter] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
RP Rice, TW (reprint author), Vanderbilt Univ Sch Med, T-1218 MCN, Nashville, TN 37232 USA.
EM todd.rice@vanderbilt.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268200536165C,
HHSN268200536179C]
FX This study was funded by National Heart, Lung, and Blood Institute
(NHLBI) contracts HHSN268200536165C and HHSN268200536179C.
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U2 16
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD FEB 22
PY 2012
VL 307
IS 8
BP 795
EP 803
DI 10.1001/jama.2012.137
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 896FQ
UT WOS:000300551300022
ER
PT J
AU Udell, JA
Wang, CS
Tinmouth, J
FitzGerald, JM
Ayas, NT
Simel, DL
Schulzer, M
Mak, E
Yoshida, EM
AF Udell, Jacob A.
Wang, Charlie S.
Tinmouth, Jill
FitzGerald, J. Mark
Ayas, Najib T.
Simel, David L.
Schulzer, Michael
Mak, Edwin
Yoshida, Eric M.
TI Does This Patient With Liver Disease Have Cirrhosis?
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID CHRONIC HEPATITIS-C; ALANINE AMINOTRANSFERASE RATIO; SIMPLE NONINVASIVE
INDEXES; STANDARD LABORATORY TESTS; VIRUS-COINFECTED PATIENTS; CHRONIC
VIRAL-HEPATITIS; ASPARTATE-AMINOTRANSFERASE; PREDICTING CIRRHOSIS;
AST/ALT RATIO; INFECTED PATIENTS
AB Context Among adult patients with liver disease, the ability to identify those most likely to have cirrhosis noninvasively is challenging.
Objective To identify simple clinical indicators that can exclude or detect cirrhosis in adults with known or suspected liver disease.
Data Sources We searched MEDLINE and EMBASE(1966 to December 2011) and reference lists from retrieved articles, previous reviews, and physical examination textbooks.
Study Selection We retained 86 studies of adequate quality that evaluated the accuracy of clinical findings for identifying histologically proven cirrhosis.
Data Extraction Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality. Random-effects meta-analyses were used to calculate summary LRs across studies.
Results Among the 86 studies, 19 533 patients were included in this meta-analysis, among whom 4725 had biopsy-proven cirrhosis (prevalence rate, 24%; 95% CI, 20%-28%). Many physical examination and simple laboratory tests increase the likelihood of cirrhosis, though the presence of ascites (LR, 7.2; 95% CI, 2.9-12), a platelet count <160 x 10(3)/mu L (LR, 6.3; 95% CI, 4.3-8.3), spider nevi (LR, 4.3; 95% CI 2.4-6.2), or a combination of simple laboratory tests with the Bonacini cirrhosis discriminant score >7 (LR, 9.4; 95% CI, 2.6-37) are the most frequently studied, reliable, and informative results. For lowering the likelihood of cirrhosis, the most useful findings are a Lok index <0.2 (a score created from the platelet count, serum aspartate aminotransferase and alanine aminotransferase, and prothrombin international normalized ratio; LR, 0.09; 95% CI, 0.03-0.31); a platelet count >= 160 x 10(3)/mu L (LR, 0.29; 95% CI, 0.20-0.39); or the absence of hepatomegaly (LR, 0.37; 95% CI, 0.24-0.51). The overall impression of the clinician was not as informative as the individual findings or laboratory combinations.
Conclusions For identifying cirrhosis, the presence of a variety of clinical findings or abnormalities in a combination of simple laboratory tests that reflect the underlying pathophysiology increase its likelihood. To exclude cirrhosis, combinations of normal laboratory findings are most useful. JAMA. 2012;307(8):832-842
C1 [Udell, Jacob A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
[Udell, Jacob A.] Harvard Univ, Sch Med, Boston, MA USA.
[Wang, Charlie S.; Tinmouth, Jill] Sunnybrook Hlth Sci Ctr, Dept Med, Div Gastroenterol, Toronto, ON M4N 3M5, Canada.
[Wang, Charlie S.; Tinmouth, Jill] Univ Toronto, Toronto, ON, Canada.
[Wang, Charlie S.] Brantford Gen Hosp, Dept Med, Div Gastroenterol, Brantford, ON, Canada.
[FitzGerald, J. Mark; Ayas, Najib T.] Vancouver Gen Hosp, Div Respirol, Dept Med, Vancouver, BC, Canada.
[Mak, Edwin] Univ British Columbia, Pacific Parkinson Res Ctr, Vancouver, BC V5Z 1M9, Canada.
[FitzGerald, J. Mark; Ayas, Najib T.; Schulzer, Michael] Vancouver Coastal Hlth Res Inst, Ctr Clin Epidemiol & Evaluat, Vancouver, BC, Canada.
[Simel, David L.] Duke Univ, Dept Med, Durham Vet Affairs Med Ctr, Durham, NC USA.
[Yoshida, Eric M.] Vancouver Gen Hosp, Dept Med, Div Gastroenterol, Vancouver, BC, Canada.
RP Udell, JA (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA.
EM judell@partners.org
FU Canadian Association of Gastroenterology-Axcan Pharma Inc; Canadian
Institutes for Health Research (CIHR); Canadian Foundation for Women's
Health; CHEST Foundation-Respiratory Association of Metropolitan
Chicago; Canadian Institutes for Health Research Industry-Partnered
(Astra-Zeneca); BC Lung Association; Michael Smith Foundation; VCHRI
FX This study was funded by a Canadian Association of
Gastroenterology-Axcan Pharma Inc Resident Research Grant awarded to Dr
Wang. Dr Udell is a recipient of a Postdoctoral Research Fellowship from
the Canadian Institutes for Health Research (CIHR) and Canadian
Foundation for Women's Health, and a CHEST Foundation-Respiratory
Association of Metropolitan Chicago Clinical Research Award in Women's
Health. Dr Tinmouth holds a Canadian Institutes for Health Research
Industry-Partnered (Astra-Zeneca) New Investigator Award. Dr FitzGerald
is a recipient of a Canadian Institute for Health Research and BC Lung
Association Scientist award, and a Michael Smith Foundation
Distinguished Scholar Award. Dr Ayas is supported by an Established
Clinician Scientist Award from the VCHRI. Dr Yoshida has no competing
funding or support interests associated with this work.
NR 147
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U1 0
U2 11
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 FEB 22
PY 2012
VL 307
IS 8
BP 832
EP 842
DI 10.1001/jama.2012.186
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 896FQ
UT WOS:000300551300026
PM 22357834
ER
PT J
AU Mittal, S
Wong, IY
Deen, WM
Toner, M
AF Mittal, Sukant
Wong, Ian Y.
Deen, William M.
Toner, Mehmet
TI Antibody-Functionalized Fluid-Permeable Surfaces for Rolling Cell
Capture at High Flow Rates
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID CIRCULATING TUMOR-CELLS; ON-A-CHIP; MICROFLUIDIC SYSTEMS; CANCER-CELLS;
ADHESION; IMMOBILIZATION; PARALLEL; SEPARATION; DIFFUSION; APTAMERS
AB Adhesion-based cell capture on surfaces in microfluidic devices forms the basis of numerous biomedical diagnostics and in vitro assays. However, the performance of these platforms is partly limited by interfacial phenomena that occur at low Reynolds numbers. In contrast, cell homing to porous vasculature is highly effective in vivo during inflammation, stem cell trafficking, and cancer metastasis. Here, we show that a porous, fluid-permeable surface functionalized with cell-specific antibodies promotes efficient and selective cell capture in vitro. This architecture is advantageous due to enhanced transport as streamlines are diverted toward the surface. Moreover, specific cell-surface interactions are promoted due to reduced shear, allowing gentle cell rolling and arrest. Together, these synergistic effects enable highly effective cell capture at flow rates more than an order of magnitude larger than those provided by existing devices with solid surfaces.
C1 [Mittal, Sukant; Wong, Ian Y.; Toner, Mehmet] Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, BioMEMS Resource Ctr, Boston, MA 02114 USA.
[Mittal, Sukant; Wong, Ian Y.; Toner, Mehmet] Harvard Univ, Sch Med, Boston, MA USA.
[Mittal, Sukant; Toner, Mehmet] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Deen, William M.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
RP Toner, M (reprint author), Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, BioMEMS Resource Ctr, Boston, MA 02114 USA.
EM mehmet_toner@hms.harvard.edu
RI Wong, Ian/G-1611-2012
OI Wong, Ian/0000-0002-9439-2548
FU National Institute of Biomedical Imaging and Bioengineering
[P41-EB002503]
FX This work was supported by the National Institute of Biomedical Imaging
and Bioengineering under grant P41-EB002503 (BioMEMS Resource Center).
I.Y.W. is the Merck Fellow of the Damon Runyon Cancer Research
Foundation (DRG-2065-10).
NR 54
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Z9 24
U1 1
U2 42
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD FEB 22
PY 2012
VL 102
IS 4
BP 721
EP 730
DI 10.1016/j.bpj.2011.12.044
PG 10
WC Biophysics
SC Biophysics
GA 900WE
UT WOS:000300921600002
PM 22385842
ER
PT J
AU Stetler, RA
Gao, YQ
Zhang, LL
Weng, ZF
Zhang, F
Hu, XM
Wang, SP
Vosler, P
Cao, GD
Sun, DD
Graham, SH
Chen, J
AF Stetler, R. Anne
Gao, Yanqin
Zhang, Lili
Weng, Zhongfang
Zhang, Feng
Hu, Xiaoming
Wang, Suping
Vosler, Peter
Cao, Guodong
Sun, Dandan
Graham, Steven H.
Chen, Jun
TI Phosphorylation of HSP27 by Protein Kinase D Is Essential for Mediating
Neuroprotection against Ischemic Neuronal Injury
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID HEAT-SHOCK-PROTEIN; CEREBRAL-ISCHEMIA; BRAIN-INJURY; CELL-DEATH;
SERINE-82 PHOSPHORYLATION; UP-REGULATION; CYTOCHROME-C; APOPTOSIS;
HEAT-SHOCK-PROTEIN-27; ACTIVATION
AB Heat shock protein 27 (HSP27) (or HSPB1) exerts cytoprotection against many cellular insults, including cerebral ischemia. We previously identified apoptosis signal-regulating kinase 1 (ASK1) as a critical downstream target of HSP27 conferring the neuroprotective effects of HSP27 against neuronal ischemia. However, the function of HSP27 is highly influenced by posttranslational modification, with differential cellular effects based on phosphorylation at specific serine residues. The role of phosphorylation in neuronal ischemic neuroprotection is currently unknown. We have created transgenic mice and viral vectors containing HSP27 mutated at three critical serine residues (Ser15, Ser78, and Ser82) to either alanine (HSP27-A, nonphosphorylatable) or aspartate (HSP27-D, phosphomimetic) residues. Under both in vitro and in vivo neuronal ischemic settings, overexpression of wild-type HSP27 (HSP27) and HSP27-D, but not HSP27-A, was neuroprotective and inhibited downstream ASK1 signaling pathways. Consistently, overexpressed HSP27 was phosphorylated by endogenous mechanisms when neurons were under ischemic stress, and single-point mutations identified Ser15 and Ser82 as critical for neuroprotection. Using a panel of inhibitors and gene knockdown approaches, we identified the upstream kinase protein kinase D (PKD) as the primary kinase targeting HSP27 directly for phosphorylation. PKD and HSP27 coimmunoprecipitated, and inhibition or knockdown of PKD abrogated the neuroprotective effects of HSP27 as well as the interaction with and inhibition of ASK1 signaling. Together, these data demonstrate that HSP27 requires PKD-mediated phosphorylation for its suppression of ASK1 cell death signaling and neuroprotection against ischemic injury.
C1 [Stetler, R. Anne; Gao, Yanqin; Zhang, Lili; Weng, Zhongfang; Zhang, Feng; Hu, Xiaoming; Wang, Suping; Vosler, Peter; Cao, Guodong; Sun, Dandan; Graham, Steven H.; Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA.
[Stetler, R. Anne; Gao, Yanqin; Zhang, Lili; Weng, Zhongfang; Zhang, Feng; Hu, Xiaoming; Wang, Suping; Vosler, Peter; Cao, Guodong; Sun, Dandan; Graham, Steven H.; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA.
[Stetler, R. Anne; Zhang, Lili; Weng, Zhongfang; Zhang, Feng; Hu, Xiaoming; Wang, Suping; Vosler, Peter; Cao, Guodong; Sun, Dandan; Graham, Steven H.; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA.
[Stetler, R. Anne; Gao, Yanqin; Cao, Guodong; Chen, Jun] Fudan Univ, Sch Med, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China.
[Stetler, R. Anne; Gao, Yanqin; Cao, Guodong; Chen, Jun] Fudan Univ, Sch Med, Inst Brain Sci, Shanghai 200032, Peoples R China.
RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA.
EM yqgao@shmu.edu.cn; chenj2@upmc.edu
RI Gao, Yanqin/I-6790-2016
OI Gao, Yanqin/0000-0002-4915-9819
FU NIH-NINDS [NS43802, NS45048, NS36736, NS56118]; Veterans Affairs Merit
Review grant; Chinese Natural Science Foundation [30670642, 30870794,
81020108021]; American Heart Association [10SDG2560122, 10POST4150028];
NIH [1F30NS057886]
FX This work was supported by NIH-NINDS Grants NS43802, NS45048, NS36736,
and NS56118, and Veterans Affairs Merit Review grant (J.C.); and Chinese
Natural Science Foundation Grants 30670642, 30870794, and 81020108021
(Y.G.). F.Z. and X. H. were supported American Heart Association Grants
10SDG2560122 and 10POST4150028, respectively. P. V. was supported by NIH
National Research Service Award Fellowship 1F30NS057886. We thank Dr.
Qiming Wang (University of Pittsburgh, Pittsburgh, PA) for providing the
PKD inhibitor and the anti-PKD3 antibody. We thank Carol Culver for
editorial assistance and Pat Strickler for secretarial support. The
contents of this article do not represent the views of the Department of
Veterans Affairs or the United States Government.
NR 38
TC 29
Z9 31
U1 0
U2 7
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 22
PY 2012
VL 32
IS 8
BP 2667
EP 2682
DI 10.1523/JNEUROSCI.5169-11.2012
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA 898DT
UT WOS:000300716600011
PM 22357851
ER
PT J
AU Chu, CJ
Kramer, MA
Pathmanathan, J
Bianchi, MT
Westover, MB
Wizon, L
Cash, SS
AF Chu, Catherine J.
Kramer, Mark A.
Pathmanathan, Jay
Bianchi, Matt T.
Westover, M. Brandon
Wizon, Lauren
Cash, Sydney S.
TI Emergence of Stable Functional Networks in Long-Term Human
Electroencephalography
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID GRAPH-THEORETICAL ANALYSIS; HUMAN SLEEP ELECTROENCEPHALOGRAM; DEFAULT
MODE NETWORK; RESTING HUMAN BRAIN; CORTICAL NETWORKS; PHASE
SYNCHRONIZATION; ALZHEIMERS-DISEASE; COHERENCE ANALYSIS;
EVOKED-POTENTIALS; MEMORY PROCESSES
AB Functional connectivity networks have become a central focus in neuroscience because they reveal key higher-dimensional features of normal and abnormal nervous system physiology. Functional networks reflect activity-based coupling between brain regions that may be constrained by relatively static anatomical connections, yet these networks appear to support tremendously dynamic behaviors. Within this growing field, the stability and temporal characteristics of functional connectivity brain networks have not been well characterized. We evaluated the temporal stability of spontaneous functional connectivity networks derived from multi-day scalp encephalogram (EEG) recordings in five healthy human subjects. Topological stability and graph characteristics of networks derived from averaged data epochs ranging from 1 s to multiple hours across different states of consciousness were compared. We show that, although functional networks are highly variable on the order of seconds, stable network templates emerge after as little as similar to 100 s of recording and persist across different states and frequency bands (albeit with slightly different characteristics in different states and frequencies). Within these network templates, the most common edges are markedly consistent, constituting a network "core." Although average network topologies persist across time, measures of global network connectivity, density and clustering coefficient, are state and frequency specific, with sparsest but most highly clustered networks seen during sleep and in the gamma frequency band. These findings support the notion that a core functional organization underlies spontaneous cortical processing and may provide a reference template on which unstable, transient, and rapidly adaptive long-range assemblies are overlaid in a frequency-dependent manner.
C1 [Chu, Catherine J.; Pathmanathan, Jay; Bianchi, Matt T.; Westover, M. Brandon; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Chu, Catherine J.; Pathmanathan, Jay; Bianchi, Matt T.; Westover, M. Brandon; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Kramer, Mark A.; Wizon, Lauren] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
RP Chu, CJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 175 Cambridge St,Suite 340, Boston, MA 02114 USA.
EM cchushore@partners.org
RI Kramer, Mark/A-1291-2014
FU National Institutes of Health/National Institute of Neurological
Disorders and Stroke [NS062092]; Child Neurology Foundation; American
Academy of Neurology; Harvard/Massachusetts Institute of Technology
Health Sciences and Technology, Beth Israel Deaconess Medical Center;
Pfizer; Merck; Burroughs Wellcome Fund
FX S.S.C. and M. B. W. are supported by National Institutes of
Health/National Institute of Neurological Disorders and Stroke Grant
NS062092. C.J.C. is supported by the Child Neurology Foundation, the
American Academy of Neurology, and the Clinical Investigator Training
Program: Harvard/Massachusetts Institute of Technology Health Sciences
and Technology, Beth Israel Deaconess Medical Center, in collaboration
with Pfizer and Merck. M. A. K. holds a Career Award at the Scientific
Interface from the Burroughs Wellcome Fund.
NR 73
TC 39
Z9 39
U1 1
U2 12
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 22
PY 2012
VL 32
IS 8
BP 2703
EP 2713
DI 10.1523/JNEUROSCI.5669-11.2012
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 898DT
UT WOS:000300716600014
PM 22357854
ER
PT J
AU Farra, R
Sheppard, NF
McCabe, L
Neer, RM
Anderson, JM
Santini, JT
Cima, MJ
Langer, R
AF Farra, Robert
Sheppard, Norman F., Jr.
McCabe, Laura
Neer, Robert M.
Anderson, James M.
Santini, John T., Jr.
Cima, Michael J.
Langer, Robert
TI First-in-Human Testing of a Wirelessly Controlled Drug Delivery
Microchip
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID PARATHYROID-HORMONE 1-34; MULTI-RESERVOIR ARRAY; IN-VITRO RELEASE; BONE;
OSTEOPOROSIS; FRACTURES; DEVICE
AB The first clinical trial of an implantable microchip-based drug delivery device is discussed. Human parathyroid hormone fragment (1-34) [hPTH(1-34)] was delivered from the device in vivo. hPTH(1-34) is the only approved anabolic osteoporosis treatment, but requires daily injections, making patient compliance an obstacle to effective treatment. Furthermore, a net increase in bone mineral density requires intermittent or pulsatile hPTH(1-34) delivery, a challenge for implantable drug delivery products. The microchip-based devices, containing discrete doses of lyophilized hPTH(1-34), were implanted in eight osteoporotic postmenopausal women for 4 months and wirelessly programmed to release doses from the device once daily for up to 20 days. A computer-based programmer, operating in the Medical Implant Communications Service band, established a bidirectional wireless communication link with the implant to program the dosing schedule and receive implant status confirming proper operation. Each woman subsequently received hPTH(1-34) injections in escalating doses. The pharmacokinetics, safety, tolerability, and bioequivalence of hPTH(1-34) were assessed. Device dosing produced similar pharmacokinetics to multiple injections and had lower coefficients of variation. Bone marker evaluation indicated that daily release from the device increased bone formation. There were no toxic or adverse events due to the device or drug, and patients stated that the implant did not affect quality of life.
C1 [Farra, Robert; Sheppard, Norman F., Jr.; McCabe, Laura] MicroCHIPS Inc, Waltham, MA 02451 USA.
[Neer, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA.
[Anderson, James M.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.
[Santini, John T., Jr.] Demand Therapeut Inc, Tyngsboro, MA 01879 USA.
[Cima, Michael J.] MIT, Dept Mat Sci & Engn, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Langer, Robert] MIT, Dept Chem Engn, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
RP Farra, R (reprint author), MicroCHIPS Inc, Waltham, MA 02451 USA.
EM rfarra@mchips.com
FU MicroCHIPS, Inc.
FX This study was sponsored by MicroCHIPS, Inc.
NR 27
TC 69
Z9 69
U1 6
U2 78
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 22
PY 2012
VL 4
IS 122
AR 122ra21
DI 10.1126/scitranslmed.3003276
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 901GQ
UT WOS:000300952100003
PM 22344516
ER
PT J
AU Rana, S
Powe, CE
Salahuddin, S
Verlohren, S
Perschel, FH
Levine, RJ
Lim, KH
Wenger, JB
Thadhani, R
Karumanchi, SA
AF Rana, Sarosh
Powe, Camille E.
Salahuddin, Saira
Verlohren, Stefan
Perschel, Frank H.
Levine, Richard J.
Lim, Kee-Hak
Wenger, Julia B.
Thadhani, Ravi
Karumanchi, S. Ananth
TI Angiogenic Factors and the Risk of Adverse Outcomes in Women With
Suspected Preeclampsia
SO CIRCULATION
LA English
DT Article
DE adverse maternal and perinatal outcomes; hypertension; pre-eclampsia;
proteinuria; triage; vascular endothelial growth factors
ID RANDOMIZED CONTROLLED-TRIAL; GROWTH-FACTOR; GESTATIONAL HYPERTENSION;
DEVELOP PREECLAMPSIA; EXPECTANT MANAGEMENT; SOLUBLE ENDOGLIN; PREGNANCY;
COMPLICATIONS; IDENTIFICATION; PREDICT
AB Background-An imbalance in circulating angiogenic factors plays a central role in the pathogenesis of preeclampsia.
Methods and Results-We prospectively studied 616 women who were evaluated for suspected preeclampsia. We measured plasma levels of antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) at presentation and examined for an association between the sFlt1/PlGF ratio and subsequent adverse maternal and perinatal outcomes within 2 weeks. The median sFlt1/PlGF ratio at presentation was elevated in participants who experienced any adverse outcome compared with those who did not (47.0 [25th-75th percentile, 15.5-112.2] versus 10.8 [25th-75th percentile, 4.1-28.6]; P<0.0001). Among those presenting at <34 weeks (n = 167), the results were more striking (226.6 [25th-75th percentile, 50.4-547.3] versus 4.5 [25th-75th percentile, 2.0-13.5]; P<0.0001), and the risk was markedly elevated when the highest sFlt1/PlGF ratio tertile was compared with the lowest (odds ratio, 47.8; 95% confidence interval, 14.6-156.6). Among participants presenting at <34 weeks, the addition of sFlt1/PlGF ratio to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (area under the curve, 0.93 for hypertension, proteinuria, and sFlt1/PlGF versus 0.84 for hypertension and proteinuria alone; P=0.001). Delivery occurred within 2 weeks of presentation in 86.0% of women with an sFlt1/PlGF ratio >= 85 compared with 15.8% of women with an sFlt1/PlGF ratio <85 (hazard ratio, 15.2; 95% confidence interval, 8.0-28.7).
Conclusions-In women with suspected preeclampsia presenting at <34 weeks, circulating sFlt1/PlGF ratio predicts adverse outcomes occurring within 2 weeks. The accuracy of this test is substantially better than that of current approaches and may be useful in risk stratification and management. Additional studies are warranted to validate these findings. (Circulation. 2012; 125:911-919.)
C1 [Rana, Sarosh; Salahuddin, Saira; Lim, Kee-Hak; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02215 USA.
[Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Powe, Camille E.; Wenger, Julia B.; Thadhani, Ravi] Harvard Univ, Sch Med, Boston, MA USA.
[Powe, Camille E.; Wenger, Julia B.; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA.
[Verlohren, Stefan] Campus Virchow Clin, Dept Obstet, Berlin, Germany.
[Perschel, Frank H.] Charite, Dept Lab Med Clin Chem & Pathobiochem, D-13353 Berlin, Germany.
[Levine, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Rana, S (reprint author), Beth Israel Deaconess Med Ctr, Div Maternal Fetal Med, Dept Obstet & Gynecol, 330 Brookline Ave,Kirstein 382, Boston, MA 02215 USA.
EM srana1@bidmc.harvard.edu
OI Verlohren, Stefan/0000-0003-3507-8636
FU Harvard Diversity and Community Partnership Faculty; Howard Hughes
Medical Institute; Medical Research Council [G0601295]
FX Dr Rana is supported by a Harvard Diversity and Community Partnership
Faculty Fellowship Award. Dr Powe was supported by Howard Hughes Medical
Institute Medical Research Training Fellowship (2009-2010). Dr
Karumanchi is an investigator for the Howard Hughes Medical Institute.
The study was also partially supported by the Medical Research Council
(Grant no: G0601295).
NR 33
TC 170
Z9 178
U1 4
U2 21
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 21
PY 2012
VL 125
IS 7
BP 911
EP U199
DI 10.1161/CIRCULATIONAHA.111.054361
PG 15
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 901GC
UT WOS:000300949800017
PM 22261192
ER
PT J
AU Jarosiewicz, B
Schummers, J
Malik, WQ
Brown, EN
Sur, M
AF Jarosiewicz, Beata
Schummers, James
Malik, Wasim Q.
Brown, Emery N.
Sur, Mriganka
TI Functional Biases in Visual Cortex Neurons with Identified Projections
to Higher Cortical Targets
SO CURRENT BIOLOGY
LA English
DT Article
ID FERRET MUSTELA-PUTORIUS; LATERAL GENICULATE-NUCLEUS; ORIENTATION
SELECTIVITY; CORTICOCORTICAL CONNECTIONS; SUPRASYLVIAN CORTEX; RESPONSE
PROPERTIES; MOTION PERCEPTION; AREA MT; CAT; CELLS
AB Background: Visual perception involves information flow from lower- to higher-order cortical areas, which are known to process different kinds of information. How does this functional specialization arise? As a step toward addressing this question, we combined fluorescent retrograde tracing with in vivo two-photon calcium imaging to simultaneously compare the tuning properties of neighboring neurons in areas 17 and 18 of ferret visual cortex that have different higher cortical projection targets.
Results: Neurons projecting to the posterior suprasylvian sulcus (PSS) were more direction selective and preferred shorter stimuli, higher spatial frequencies, and higher temporal frequencies than neurons projecting to area 21, anticipating key differences between the functional properties of the target areas themselves. These differences could not be explained by a correspondence between anatomical and functional clustering within early visual cortex, and the largest differences were in properties generated within early visual cortex (direction selectivity and length preference) rather than in properties present in its retinogeniculate inputs.
Conclusions: These projection cell groups, and hence the higher-order visual areas to which they project, likely obtain their functional properties not from biased retinogeniculate inputs but from highly specific circuitry within the cortex.
C1 [Jarosiewicz, Beata; Schummers, James; Sur, Mriganka] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
[Malik, Wasim Q.; Brown, Emery N.; Sur, Mriganka] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Brown, Emery N.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Malik, Wasim Q.; Brown, Emery N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
RP Jarosiewicz, B (reprint author), Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
EM jarosiew@gmail.com; msur@mit.edu
FU Ruth L. Kirschstein National Research Service Award [5F32NS054390]; NIH
[EY018648, EY07023, DP1 OD003646, EB006385]
FX The authors would like to thank Amanda Mower, Beau Cronin, Ian
Wicker-sham, Ethan Meyers, Paul Manger, Nicolas Masse, Hongbo Yu,
Brandon Farley, Caroline Runyan, and Travis Emery for their
contributions. This work was supported by Ruth L. Kirschstein National
Research Service Award 5F32NS054390 (B.J.), NIH grants EY018648 and
EY07023 (M.S.), and NIH grants DP1 OD003646 and EB006385 (E.N.B.).
NR 51
TC 17
Z9 17
U1 1
U2 4
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 FEB 21
PY 2012
VL 22
IS 4
BP 269
EP 277
DI 10.1016/j.cub.2012.01.011
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 896TW
UT WOS:000300595300018
PM 22305753
ER
PT J
AU Moriguchi, H
Zhang, Y
Mihara, M
Sato, C
AF Moriguchi, Hisashi
Zhang, Yue
Mihara, Makoto
Sato, Chifumi
TI A therapeutic method for the direct reprogramming of human liver cancer
cells with only chemicals (Retracted article. See vol. 2, 839, 2012)
SO SCIENTIFIC REPORTS
LA English
DT Article
ID HEPATOCELLULAR-CARCINOMA CELLS; AKR1B10; RETINOIDS; SMOKERS; MARKER
AB Various methods for the direct reprogramming of human somatic cells have been developed. However, a therapeutic method to reprogram and eliminate human solid tumor cells has not been developed. Here we show a novel therapeutic method to reprogram and eliminate human solid tumor cells with chemicals. This therapeutic method may be applicable to various human solid tumor cells that express aldo-keto reductase family 1 member B10 (AKR1B10) and retinoid X receptors (RXRs).
C1 [Moriguchi, Hisashi; Mihara, Makoto] Univ Tokyo, Sch Med, Dept Plast & Reconstruct Surg, Div iPS Cell Res & Applicat, Tokyo 113, Japan.
[Moriguchi, Hisashi] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Moriguchi, Hisashi; Zhang, Yue] Harvard Univ, Sch Med, Boston, MA USA.
[Zhang, Yue] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA USA.
[Sato, Chifumi] Tokyo Med & Dent Univ, Grad Sch Hlth Sci, Dept Analyt Hlth Sci, Tokyo, Japan.
RP Moriguchi, H (reprint author), Univ Tokyo, Sch Med, Dept Plast & Reconstruct Surg, Div iPS Cell Res & Applicat, Tokyo 113, Japan.
EM moriguchi-tky@umin.ac.jp
NR 15
TC 4
Z9 4
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 21
PY 2012
VL 2
AR 280
DI 10.1038/srep00280
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 896RB
UT WOS:000300586700001
PM 22355790
ER
PT J
AU Polyak, K
Vogt, PK
AF Polyak, Kornelia
Vogt, Peter K.
TI Progress in breast cancer research
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID HETEROGENEITY
C1 [Polyak, Kornelia] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Sch, Boston, MA 02215 USA.
[Polyak, Kornelia] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Vogt, Peter K.] Scripps Res Inst, La Jolla, CA 92037 USA.
RP Polyak, K (reprint author), Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Sch, Boston, MA 02215 USA.
EM kornelia_polyak@dfci.harvard.edu; pkvogt@scripps.edu
FU NCI NIH HHS [R01 CA078230, R01 CA151574, R01 CA153124]
NR 31
TC 8
Z9 9
U1 1
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 FEB 21
PY 2012
VL 109
IS 8
BP 2715
EP 2717
DI 10.1073/pnas.1201091109
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895KM
UT WOS:000300495100018
PM 22331869
ER
PT J
AU Jin, K
Kong, XJ
Shah, T
Penet, MF
Wildes, F
Sgroi, DC
Ma, XJ
Huang, Y
Kallioniemi, A
Landberg, G
Bieche, I
Wu, XY
Lobie, PE
Davidson, NE
Bhujwalla, ZM
Zhu, T
Sukumar, S
AF Jin, Kideok
Kong, Xiangjun
Shah, Tariq
Penet, Marie-France
Wildes, Flonne
Sgroi, Dennis C.
Ma, Xiao-Jun
Huang, Yi
Kallioniemi, Anne
Landberg, Goran
Bieche, Ivan
Wu, Xinyan
Lobie, Peter E.
Davidson, Nancy E.
Bhujwalla, Zaver M.
Zhu, Tao
Sukumar, Saraswati
TI The HOXB7 protein renders breast cancer cells resistant to tamoxifen
through activation of the EGFR pathway
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID GROWTH-FACTOR-RECEPTOR; ESTROGEN-RECEPTOR; ENDOCRINE THERAPY;
RANDOMIZED-TRIAL; DOUBLE-BLIND; EXPRESSION; GENE; ALPHA; AMPLIFICATION;
FULVESTRANT
AB Multiple factors including long-term treatment with tamoxifen are involved in the development of selective estrogen receptor (ER) modulator resistance in ER alpha-positive breast cancer. Many underlying molecular events that confer resistance are known but a unifying theme is yet to be revealed. In this report, we provide evidence that HOXB7 overexpression renders MCF-7 cells resistant to tamoxifen via cross-talk between receptor tyrosine kinases and ER alpha signaling. HOXB7 is an ER alpha-responsive gene. Extended treatment of MCF-7 cells with tamoxifen resulted in progressively increasing levels of HOXB7 expression, along with EGFR and EGFR ligands. Up-regulation of EGFR occurs through direct binding of HOXB7 to the EGFR promoter, enhancing transcriptional activity. Finally, higher expression levels of HOXB7 in the tumor significantly correlated with poorer disease-free survival in ER alpha-positive patients with breast cancer on adjuvant tamoxifen monotherapy. These studies suggest that HOXB7 acts as a key regulator, orchestrating a major group of target molecules in the oncogenic hierarchy. Functional antagonism of HOXB7 could circumvent tamoxifen resistance.
C1 [Kong, Xiangjun; Zhu, Tao] Hefei Natl Lab Phys Sci, Hefei 230027, Anhui, Peoples R China.
[Jin, Kideok; Huang, Yi; Wu, Xinyan; Davidson, Nancy E.; Bhujwalla, Zaver M.; Sukumar, Saraswati] Johns Hopkins Univ, Breast Canc Program, Dept Oncol, Sch Med, Baltimore, MD 21231 USA.
[Shah, Tariq; Penet, Marie-France; Wildes, Flonne; Bhujwalla, Zaver M.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Sch Med, Baltimore, MD 21231 USA.
[Sgroi, Dennis C.] Harvard Univ, Dept Pathol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ma, Xiao-Jun] AviaraDx, Carlsbad, CA 92010 USA.
[Kallioniemi, Anne] Univ Tampere, Canc Genet Lab, FIN-33014 Tampere, Finland.
[Landberg, Goran] Univ Manchester, Breakthrough Breast Canc Res Unit, Sch Canc & Enabling Sci, Paterson Inst Canc Res, Manchester M20 4BX, Lancs, England.
[Bieche, Ivan] Hosp Rene Huguenin, Inst Curie, F-92210 St Cloud, France.
[Lobie, Peter E.] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 119077, Singapore.
[Lobie, Peter E.] Natl Univ Singapore, Dept Pharmacol, Singapore 119077, Singapore.
RP Zhu, T (reprint author), Hefei Natl Lab Phys Sci, Hefei 230027, Anhui, Peoples R China.
EM zhut@ustc.edu.cn; saras@jhmi.edu
OI Kallioniemi, Anne/0000-0003-3552-8158
FU National Institutes of Health [P50-CA88843]; Susan G. Komen Postdoctoral
Fellowships; National Key Scientific Program of China [2010CB912804,
2007CB914801, 2011CBA01103]; National Natural Science Foundation of
China [30971492, 30725015]
FX We thank Dr. Ben H. Park for generously providing the ERIN cell line,
Drs. Richard Santen (University of Virginia, Charlottesville, VA) and V.
Craig Jordan (Georgetown University, Washington, DC) for the LTED and
TAMLT cell lysates, and Dr. Cynthia Zahnow and Hexin Chen for reviewing
the manuscript. This work was supported by Specialized Programs Of
Research Excellence (SPORE) in Breast Cancer: National Institutes of
Health Grant P50-CA88843 (to S.S.), Susan G. Komen Postdoctoral
Fellowships (to T.Z. and K.J.), the National Key Scientific Program of
China (2010CB912804, 2007CB914801, and 2011CBA01103), and the National
Natural Science Foundation of China (30971492 and 30725015) (to T.Z.).
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SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 21
PY 2012
VL 109
IS 8
BP 2736
EP 2741
DI 10.1073/pnas.1018859108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895KM
UT WOS:000300495100022
PM 21690342
ER
PT J
AU Chiba, N
Comaills, V
Shiotani, B
Takahashi, F
Shimada, T
Tajima, K
Winokur, D
Hayashida, T
Willers, H
Brachtel, E
Vivanco, MD
Haber, DA
Zou, L
Maheswaran, S
AF Chiba, Naokazu
Comaills, Valentine
Shiotani, Bunsyo
Takahashi, Fumiyuki
Shimada, Toshiyuki
Tajima, Ken
Winokur, Daniel
Hayashida, Tetsu
Willers, Henning
Brachtel, Elena
Vivanco, Maria d. M.
Haber, Daniel A.
Zou, Lee
Maheswaran, Shyamala
TI Homeobox B9 induces epithelial-to-mesenchymal transition-associated
radioresistance by accelerating DNA damage responses
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID GROWTH-FACTOR-BETA; BREAST-CANCER; MAMMALIAN-CELLS; ATM; RADIATION;
TUMORIGENESIS; CHECKPOINT; EMT; MICROENVIRONMENT; BARRIER
AB Homeobox 9 (HOXB9), a nontransforming transcription factor overexpressed in breast cancer, alters tumor cell fate and promotes tumor progression and metastasis. Here we show that HOXB9 confers resistance to ionizing radiation by promoting DNA damage response. In nonirradiated cells, HOXB9 induces spontaneous DNA damage, phosphorylated histone 2AX and p53 binding protein 1 foci, and increases baseline ataxia telangiectasia mutated (ATM) phosphorylation. Upon ionizing radiation, ATM is hyperactivated in HOXB9-expressing cells during the early stages of the double-stranded DNA break (DSB) response, accelerating accumulation of phosphorylated histone 2AX, mediator of DNA-damage checkpoint 1, and p53 binding protein 1, at DSBs and enhances DSB repair. The effect of HOXB9 on the response to ionizing radiation requires the baseline ATM activity before irradiation and epithelial-to-mesenchymal transition induced by TGF-beta, a HOXB9 transcriptional target. Our results reveal the impact of a HOXB9-TGF-beta-ATMaxis on checkpoint activation and DNA repair, suggesting that TGF-beta may be a key factor that links tumor microenvironment, tumor cell fate, DNA damage response, and radioresistance in a subset of HOXB9-overexpressing breast tumors.
C1 [Chiba, Naokazu; Shiotani, Bunsyo; Takahashi, Fumiyuki; Shimada, Toshiyuki; Tajima, Ken; Winokur, Daniel; Hayashida, Tetsu; Haber, Daniel A.; Zou, Lee; Maheswaran, Shyamala] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Chiba, Naokazu; Takahashi, Fumiyuki; Shimada, Toshiyuki; Tajima, Ken; Hayashida, Tetsu; Maheswaran, Shyamala] Massachusetts Gen Hosp, Dept Surg, Charlestown, MA 02129 USA.
[Willers, Henning] Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA 02129 USA.
[Brachtel, Elena] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Comaills, Valentine; Vivanco, Maria d. M.] Ctr Cooperat Res Biosci, Cell Biol & Stem Cell Unit, Derio Bizkaia 48160, Spain.
RP Zou, L (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
EM zou.lee@mgh.harvard.edu; maheswaran@helix.mgh.harvard.edu
RI cancer, biogune/H-7276-2012; Vivanco, Maria/G-2393-2011
OI Vivanco, Maria/0000-0002-9540-247X
FU National Institutes of Health/National Cancer Institute [CA89138];
National Cancer Institute; [PDF0600282]; [KG090412]; [GM076388]
FX We thank Drs. Isselbacher and Ellisen for critical reading of the
manuscript. This work was supported by National Institutes of
Health/National Cancer Institute Grant CA89138, National Cancer
Institute Federal Share Program and Income (L.Z. and S.M.), and by Susan
G. Komen for the Cure Grants PDF0600282 and KG090412 (to S.M.) and
GM076388 (to L.Z.).
NR 26
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PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 21
PY 2012
VL 109
IS 8
BP 2760
EP 2765
DI 10.1073/pnas.1018867108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895KM
UT WOS:000300495100026
PM 21930940
ER
PT J
AU Maruyama, R
Shipitsin, M
Choudhury, S
Wu, ZH
Protopopov, A
Yao, J
Lo, PK
Bessarabova, M
Ishkin, A
Nikolsky, Y
Liu, XS
Sukumar, S
Polyak, K
AF Maruyama, Reo
Shipitsin, Michail
Choudhury, Sibgat
Wu, Zhenhua
Protopopov, Alexei
Yao, Jun
Lo, Pang-Kuo
Bessarabova, Marina
Ishkin, Alex
Nikolsky, Yuri
Liu, X. Shirley
Sukumar, Saraswati
Polyak, Kornelia
TI Altered antisense-to-sense transcript ratios in breast cancer
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID NONCODING RNAS; GENOME; EXPRESSION; CELLS
AB Transcriptome profiling studies suggest that a large fraction of the genome is transcribed and many transcripts function independent of their protein coding potential. The relevance of noncoding RNAs (ncRNAs) in normal physiological processes and in tumorigenesis is increasingly recognized. Here, we describe consistent and significant differences in the distribution of sense and antisense transcripts between normal and neoplastic breast tissues. Many of the differentially expressed antisense transcripts likely represent long ncRNAs. A subset of genes that mainly generate antisense transcripts in normal but not cancer cells is involved in essential metabolic processes. These findings suggest fundamental differences in global RNA regulation between normal and cancer cells that might play a role in tumorigenesis.
C1 [Maruyama, Reo; Shipitsin, Michail; Choudhury, Sibgat; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wu, Zhenhua; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Protopopov, Alexei] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Maruyama, Reo; Shipitsin, Michail; Choudhury, Sibgat; Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Maruyama, Reo; Shipitsin, Michail; Choudhury, Sibgat; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Wu, Zhenhua; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Yao, Jun] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Lo, Pang-Kuo; Sukumar, Saraswati] Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA.
[Bessarabova, Marina; Ishkin, Alex] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow 119331, Russia.
[Nikolsky, Yuri] GeneGo Inc, St Joseph, MI 49085 USA.
[Polyak, Kornelia] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM kornelia_polyak@dfci.harvard.edu
FU Novartis Pharmaceuticals, Inc.; National Cancer Institute [CA89393];
Department of Defense [W81XWH-07-1-0294]; Avon Foundation; Breast Cancer
Research Foundation; Susan G. Komen Foundation; Terri Brodeur Breast
Cancer Foundation
FX Conflict of interest statement: K.P. receives research support from and
is a consultant to Novartis Pharmaceuticals, Inc. K.P. is also on the
Scientific Advisory Board of Metamark Genetics, Inc. and Theracrine,
Inc. Y.N. is a founder and employee of GeneGo, Inc.; We thank members of
our laboratories for their critical reading of this manuscript and
useful discussions. We greatly appreciate the help of Dr. Andrea
Richardson (Brigham and Women's Hospital) in the acquisition of tissue
samples and the Arthur and Rochelle Belfer Center for Cancer Genomics
for array hybridization. This study was supported by the National Cancer
Institute Specialized Program in Research Excellence in Breast Cancer at
the Dana-Farber/Harvard University Cancer Center (Grant CA89393), the
Department of Defense (Grant W81XWH-07-1-0294), and the Avon Foundation
as well as by Breast Cancer Research Foundation grants (to K. P.), Susan
G. Komen Foundation fellowships (to M. S. and R. M.), and a Terri
Brodeur Breast Cancer Foundation Fellowship (to S.C.).
NR 23
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PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 21
PY 2012
VL 109
IS 8
BP 2820
EP 2824
DI 10.1073/pnas.1010559107
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895KM
UT WOS:000300495100036
PM 21098291
ER
PT J
AU Luo, TP
Masson, K
Jaffe, JD
Silkworth, W
Ross, NT
Scherer, CA
Scholl, C
Frohling, S
Carr, SA
Stern, AM
Schreiber, SL
Golub, TR
AF Luo, Tuoping
Masson, Kristina
Jaffe, Jacob D.
Silkworth, Whitney
Ross, Nathan T.
Scherer, Christina A.
Scholl, Claudia
Froehling, Stefan
Carr, Steven A.
Stern, Andrew M.
Schreiber, Stuart L.
Golub, Todd R.
TI STK33 kinase inhibitor BRD-8899 has no effect on KRAS-dependent cancer
cell viability
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID ONCOGENE ADDICTION; THERAPY; RAS; SELECTIVITY; DISCOVERY; TARGET; DRUG
AB Approximately 30% of human cancers harbor oncogenic gain-of-function mutations in KRAS. Despite interest in KRAS as a therapeutic target, direct blockade of KRAS function with small molecules has yet to be demonstrated. Based on experiments that lower mRNA levels of protein kinases, KRAS-dependent cancer cells were proposed to have a unique requirement for the serine/threonine kinase STK33. Thus, it was suggested that small-molecule inhibitors of STK33 might have therapeutic benefit in these cancers. Here, we describe the development of selective, low nanomolar inhibitors of STK33's kinase activity. The most potent and selective of these, BRD8899, failed to kill KRAS-dependent cells. While several explanations for this result exist, our data are most consistent with the view that inhibition of STK33's kinase activity does not represent a promising anti-KRAS therapeutic strategy.
C1 [Luo, Tuoping; Masson, Kristina; Jaffe, Jacob D.; Silkworth, Whitney; Ross, Nathan T.; Scherer, Christina A.; Carr, Steven A.; Stern, Andrew M.; Schreiber, Stuart L.; Golub, Todd R.] Broad Inst Harvard & MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA.
[Luo, Tuoping; Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Scholl, Claudia; Froehling, Stefan] Univ Hosp Ulm, Dept Internal Med 3, D-89081 Ulm, Germany.
[Schreiber, Stuart L.; Golub, Todd R.] Howard Hughes Med Inst, Bethesda, MD 20817 USA.
[Golub, Todd R.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA.
RP Schreiber, SL (reprint author), Broad Inst Harvard & MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA.
EM stuart_schreiber@harvard.edu; golub@broadinstitute.org
FU Starr Cancer Consortium; National Institute of General Medical Sciences
[GM38627]; Swedish Research Council (Vetenskapsradet); German Research
Foundation; National Institutes of Health (NIH) [RL1-GM084437,
RL1-CA133834, RL1-HG004671, UL1-DE019585]
FX We thank members of the Broad Institute Chemical Biology Platform for
high throughput screening assistance. We also thank D. Gary Gilliland at
Merck Research Laboratories and Robert J. Gould at Epizyme for helpful
advice. This study was supported by a Starr Cancer Consortium grant. In
addition, T. L. was supported by a grant from the National Institute of
General Medical Sciences (GM38627 awarded to S. L. S.), K. M. was
supported by the Swedish Research Council (Vetenskapsradet), and C. S.
was supported by an Emmy Noether Fellowship from the German Research
Foundation. Support for these studies was also provided by the National
Institutes of Health (NIH) Genomics Based Drug Discovery-Driving Medical
Projects Grant RL1-GM084437 and RL1-CA133834, administratively linked to
NIH grants RL1-HG004671 and UL1-DE019585.
NR 24
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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 FEB 21
PY 2012
VL 109
IS 8
BP 2860
EP 2865
DI 10.1073/pnas.1120589109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895KM
UT WOS:000300495100043
PM 22323609
ER
PT J
AU Russell, MK
Longoni, M
Wells, J
Maalouf, FI
Tracy, AA
Loscertales, M
Ackerman, KG
Pober, BR
Lage, K
Bult, CJ
Donahoe, PK
AF Russell, Meaghan K.
Longoni, Mauro
Wells, Julie
Maalouf, Faouzi I.
Tracy, Adam A.
Loscertales, Maria
Ackerman, Kate G.
Pober, Barbara R.
Lage, Kasper
Bult, Carol J.
Donahoe, Patricia K.
TI Congenital diaphragmatic hernia candidate genes derived from embryonic
transcriptomes
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE pleuroperitoneal folds; expression profiling; diaphragm development
ID SET ENRICHMENT ANALYSIS; MAMMALIAN DIAPHRAGM; MOUSE DEVELOPMENT; SCALE
ANALYSIS; HUMAN CANCERS; EXPRESSION; PROTEINS; DEFECTS; HOX; PBX
AB Congenital diaphragmatic hernia (CDH) is a common (1 in 3,000 live births) major congenital malformation that results in significant morbidity and mortality. The discovery of CDH loci using standard genetic approaches has been hindered by its genetic heterogeneity. We hypothesized that gene expression profiling of developing embryonic diaphragms would help identify genes likely to be associated with diaphragm defects. We generated a time series of whole-transcriptome expression profiles from laser captured embryonic mouse diaphragms at embryonic day (E)11.5 and E12.5 when experimental perturbations lead to CDH phenotypes, and E16.5 when the diaphragm is fully formed. Gene sets defining biologically relevant pathways and temporal expression trends were identified by using a series of bioinformatic algorithms. These developmental sets were then compared with a manually curated list of genes previously shown to cause diaphragm defects in humans and in mouse models. Our integrative filtering strategy identified 27 candidates for CDH. We examined the diaphragms of knockout mice for one of the candidate genes, pre-B-cell leukemia transcription factor 1 (Pbx1), and identified a range of previously undetected diaphragmatic defects. Our study demonstrates the utility of genetic characterization of normal development as an integral part of a disease gene identification and prioritization strategy for CDH, an approach that can be extended to other diseases and developmental anomalies.
C1 [Russell, Meaghan K.; Longoni, Mauro; Maalouf, Faouzi I.; Tracy, Adam A.; Loscertales, Maria; Pober, Barbara R.; Lage, Kasper; Donahoe, Patricia K.] Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA.
[Wells, Julie; Bult, Carol J.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Ackerman, Kate G.] Univ Rochester, Dept Pediat, Sch Med & Dent, Rochester, NY 14642 USA.
[Ackerman, Kate G.] Univ Rochester, Sch Med & Dent, Dept Biomed Genet, Rochester, NY 14642 USA.
[Pober, Barbara R.] Childrens Hosp Boston, Boston, MA 02115 USA.
[Pober, Barbara R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Lage, Kasper; Donahoe, Patricia K.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Lage, Kasper; Donahoe, Patricia K.] Broad Inst, Cambridge, MA 02142 USA.
[Lage, Kasper] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
[Lage, Kasper] Univ Copenhagen, Ctr Prot Res, DK-2200 Copenhagen, Denmark.
RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA.
EM pdonahoe@partners.org
RI Congregado, Miguel/B-9062-2009; Longoni, Mauro/I-2526-2013
OI Congregado, Miguel/0000-0002-2404-0176;
FU NHLBI NIH HHS [K08 HL076286, R01 HL085459]; NICHD NIH HHS [P01 HD068250]
NR 69
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PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 21
PY 2012
VL 109
IS 8
BP 2978
EP 2983
DI 10.1073/pnas.1121621109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895KM
UT WOS:000300495100063
PM 22315423
ER
PT J
AU Pillai, SK
Abdel-Mohsen, M
Guatelli, J
Skasko, M
Monto, A
Fujimoto, K
Yukl, S
Greene, WC
Kovari, H
Rauch, A
Fellay, J
Battegay, M
Hirschel, B
Witteck, A
Bernasconi, E
Ledergerber, B
Gunthard, HF
Wong, JK
AF Pillai, Satish K.
Abdel-Mohsen, Mohamed
Guatelli, John
Skasko, Mark
Monto, Alexander
Fujimoto, Katsuya
Yukl, Steven
Greene, Warner C.
Kovari, Helen
Rauch, Andri
Fellay, Jacques
Battegay, Manuel
Hirschel, Bernard
Witteck, Andrea
Bernasconi, Enos
Ledergerber, Bruno
Guenthard, Huldrych F.
Wong, Joseph K.
CA Swiss HIV Cohort Study
TI Role of retroviral restriction factors in the interferon-alpha-mediated
suppression of HIV-1 in vivo
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIRETROVIRAL ACTIVITY; REVERSE
TRANSCRIPTION; CYTIDINE DEAMINATION; ANTIVIRAL PROTEIN; VIF PROTEIN;
T-CELLS; C VIRUS; APOBEC3G; HYPERMUTATION
AB The antiviral potency of the cytokine IFN-alpha has been long appreciated but remains poorly understood. A number of studies have suggested that induction of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies the IFN-alpha-mediated suppression of HIV-1 replication in vitro. We sought to characterize the as-yet-undefined relationship between IFN-alpha treatment, retroviral restriction factors, and HIV-1 in vivo. APOBEC3G, APOBEC3F, and BST-2 expression levels were measured in HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naive individuals before, during, and after pegylated IFN-alpha/ribavirin (IFN-alpha/riba) combination therapy. IFN-alpha/riba therapy decreased HIV-1 viral load by -0.921 (+/- 0.858) log(10) copies/mL in HIV/HCV-coinfected patients. APOBEC3G/3F and BST-2 mRNA expression was significantly elevated during IFN-alpha/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load during treatment (P < 0.05, Pearson's r). APOBEC3 induction during treatment was correlated with degree of viral hypermutation (P < 0.03, Spearman's rho), and evolution of the HIV-1 accessory protein viral protein U (Vpu) during IFN-alpha/riba treatment was suggestive of increased BST-2-mediated selection pressure. These data suggest that host restriction factors play a critical role in the antiretroviral capacity of IFN-alpha in vivo, and warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.
C1 [Pillai, Satish K.; Abdel-Mohsen, Mohamed; Monto, Alexander; Yukl, Steven; Greene, Warner C.; Wong, Joseph K.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Pillai, Satish K.; Monto, Alexander; Fujimoto, Katsuya; Yukl, Steven; Wong, Joseph K.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA.
[Guatelli, John; Skasko, Mark] Univ Calif San Diego, Vet Affairs San Diego Healthcare Syst, Dept Med, La Jolla, CA 92093 USA.
[Greene, Warner C.] Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
[Kovari, Helen; Ledergerber, Bruno; Guenthard, Huldrych F.] Univ Zurich, Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, CH-8091 Zurich, Switzerland.
[Rauch, Andri] Univ Bern, Univ Hosp Berne, Div Infect Dis, CH-3010 Bern, Switzerland.
[Fellay, Jacques] Univ Lausanne Hosp, Div Infect Dis, CH-1011 Lausanne, Switzerland.
[Fellay, Jacques] Univ Lausanne Hosp, Inst Microbiol, CH-1011 Lausanne, Switzerland.
[Battegay, Manuel] Univ Basel Hosp, Div Infect Dis, CH-4031 Basel, Switzerland.
[Hirschel, Bernard] Univ Hosp Geneva, Div Infect Dis, CH-1211 Geneva, Switzerland.
[Witteck, Andrea] Cantonal Hosp St Gallen, Div Infect Dis, CH-9007 St Gallen, Switzerland.
[Bernasconi, Enos] Reg Hosp Lugano, Div Infect Dis, CH-6903 Lugano, Switzerland.
RP Pillai, SK (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
EM satish.pillai@ucsf.edu
RI Infektiologie, USZ/A-6921-2011; SHCS, all/G-4072-2011; SHCS, int. coll.
A/G-4083-2011; gunthard, huldrych/F-1724-2011; Fellay,
Jacques/A-6681-2009; Ledergerber, Bruno/B-5656-2009; Fujimoto,
Katsuya/G-2835-2012
OI gunthard, huldrych/0000-0002-1142-6723; Fellay,
Jacques/0000-0002-8240-939X; Ledergerber, Bruno/0000-0002-6881-4401;
FU National Institutes of Health [1K01DA024654, AI081668]; American
Recovery and Reinvestment Act (ARRA); Swiss HIV Cohort Study Project
[594]; Swiss National Science Foundation [324730-130865, R01NS051132,
R21MH083573, R56AI91573, 33CSC0-108787]; Swiss HIV Cohort Study Research
Foundation
FX We thank the patients who participate in the Swiss HIV Cohort Study and
the physicians and study nurses for excellent patient care. This study
was supported by National Institutes of Health Grant 1K01DA024654 (to S.
K. P.), Grant AI081668, and an American Recovery and Reinvestment Act
(ARRA) supplement (to J.G.). Additional support was provided by Swiss
HIV Cohort Study Project 594; the Veterans Affairs Merit Review (K. F.,
S.Y., and J.K.W.); and Swiss National Science Foundation Grants
324730-130865 (to H. F. G.), R01NS051132, R21MH083573, and R56AI91573.
The Swiss HIV Cohort Study is supported by Swiss National Science
Foundation Grant 33CSC0-108787 and the Swiss HIV Cohort Study Research
Foundation.
NR 56
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 21
PY 2012
VL 109
IS 8
BP 3035
EP 3040
DI 10.1073/pnas.1111573109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895KM
UT WOS:000300495100073
PM 22315404
ER
PT J
AU Grad, YH
Lipsitch, M
Feldgarden, M
Arachchi, HM
Cerqueira, GC
FitzGerald, M
Godfrey, P
Haas, BJ
Murphy, CI
Russ, C
Sykes, S
Walker, BJ
Wortman, JR
Young, S
Zeng, QD
Abouelleil, A
Bochicchio, J
Chauvin, S
DeSmet, T
Gujja, S
McCowan, C
Montmayeur, A
Steelman, S
Frimodt-Moller, J
Petersen, AM
Struve, C
Krogfelt, KA
Bingen, E
Weill, FX
Lander, ES
Nusbaum, C
Birren, BW
Hung, DT
Hanage, WP
AF Grad, Yonatan H.
Lipsitch, Marc
Feldgarden, Michael
Arachchi, Harindra M.
Cerqueira, Gustavo C.
FitzGerald, Michael
Godfrey, Paul
Haas, Brian J.
Murphy, Cheryl I.
Russ, Carsten
Sykes, Sean
Walker, Bruce J.
Wortman, Jennifer R.
Young, Sarah
Zeng, Qiandong
Abouelleil, Amr
Bochicchio, James
Chauvin, Sara
DeSmet, Timothy
Gujja, Sharvari
McCowan, Caryn
Montmayeur, Anna
Steelman, Scott
Frimodt-Moller, Jakob
Petersen, Andreas M.
Struve, Carsten
Krogfelt, Karen A.
Bingen, Edouard
Weill, Francois-Xavier
Lander, Eric S.
Nusbaum, Chad
Birren, Bruce W.
Hung, Deborah T.
Hanage, William P.
TI Genomic epidemiology of the Escherichia coli O104:H4 outbreaks in
Europe, 2011
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE food-borne outbreak; Shiga toxin; enteroaggregative E. coli;
enterohemorrhagic E. coli
ID HEMOLYTIC-UREMIC SYNDROME; DNA-SEQUENCING DATA; FRAMEWORK; GERMANY;
FRANCE
AB The degree to which molecular epidemiology reveals information about the sources and transmission patterns of an outbreak depends on the resolution of the technology used and the samples studied. Isolates of Escherichia coli O104:H4 from the outbreak centered in Germany in May-July 2011, and the much smaller outbreak in southwest France in June 2011, were indistinguishable by standard tests. We report a molecular epidemiological analysis using multiplatform whole-genome sequencing and analysis of multiple isolates from the German and French outbreaks. Isolates from the German outbreak showed remarkably little diversity, with only two single nucleotide polymorphisms (SNPs) found in isolates from four individuals. Surprisingly, we found much greater diversity (19 SNPs) in isolates from seven individuals infected in the French outbreak. The German isolates form a clade within the more diverse French outbreak strains. Moreover, five isolates derived from a single infected individual from the French outbreak had extremely limited diversity. The striking difference in diversity between the German and French outbreak samples is consistent with several hypotheses, including a bottleneck that purged diversity in the German isolates, variation in mutation rates in the two E. coli outbreak populations, or uneven distribution of diversity in the seed populations that led to each outbreak.
C1 [Feldgarden, Michael; Arachchi, Harindra M.; Cerqueira, Gustavo C.; FitzGerald, Michael; Godfrey, Paul; Haas, Brian J.; Murphy, Cheryl I.; Russ, Carsten; Sykes, Sean; Walker, Bruce J.; Wortman, Jennifer R.; Young, Sarah; Zeng, Qiandong; Abouelleil, Amr; Bochicchio, James; Chauvin, Sara; DeSmet, Timothy; Gujja, Sharvari; McCowan, Caryn; Montmayeur, Anna; Steelman, Scott; Lander, Eric S.; Nusbaum, Chad; Birren, Bruce W.; Hung, Deborah T.] Broad Inst Harvard, Cambridge, MA 02142 USA.
[Grad, Yonatan H.; Hung, Deborah T.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Grad, Yonatan H.; Lipsitch, Marc; Hanage, William P.] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Dept Epidemiol, Boston, MA 02115 USA.
[Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Feldgarden, Michael; Arachchi, Harindra M.; Cerqueira, Gustavo C.; FitzGerald, Michael; Godfrey, Paul; Haas, Brian J.; Murphy, Cheryl I.; Russ, Carsten; Sykes, Sean; Walker, Bruce J.; Wortman, Jennifer R.; Young, Sarah; Zeng, Qiandong; Abouelleil, Amr; Bochicchio, James; Chauvin, Sara; DeSmet, Timothy; Gujja, Sharvari; McCowan, Caryn; Montmayeur, Anna; Steelman, Scott; Lander, Eric S.; Nusbaum, Chad; Birren, Bruce W.; Hung, Deborah T.] MIT, Cambridge, MA 02142 USA.
[Frimodt-Moller, Jakob] Hillerod Sygehus, Dept Clin Microbiol, DK-3400 Hillerod, Denmark.
[Frimodt-Moller, Jakob; Petersen, Andreas M.; Struve, Carsten; Krogfelt, Karen A.] Statens Serum Inst, Dept Microbial Surveillance & Res, DK-2300 Copenhagen, Denmark.
[Petersen, Andreas M.] Hvidovre Univ Hosp, Dept Gastroenterol, DK-2650 Hvidovre, Denmark.
[Bingen, Edouard] Hop Robert Debre, AP HP, Microbiol Serv, Lab Associe,Ctr Natl Reference Escherichia Coli &, F-75019 Paris, France.
[Bingen, Edouard] Univ Paris Diderot, EA3105, F-75505 Paris, France.
[Weill, Francois-Xavier] Inst Pasteur, Ctr Natl Reference Escherichia Coli & Shigella, Unite Bacteries Pathogenes Enter, F-75015 Paris, France.
[Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
[Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA.
RP Lander, ES (reprint author), Broad Inst Harvard, Cambridge, MA 02142 USA.
EM lander@broadinstitute.org; whanage@hsph.harvard.edu
RI Krogfelt , Karen Angeliki/O-8145-2016;
OI Krogfelt , Karen Angeliki/0000-0001-7536-3453; Wortman,
Jennifer/0000-0002-8713-1227; Weill,
Francois-Xavier/0000-0001-9941-5799; Montmayeur,
Anna/0000-0002-8132-1716; Petersen, Andreas Munk/0000-0003-0531-0553;
Frimodt-Moller, Jakob/0000-0002-7585-636X; Lipsitch,
Marc/0000-0003-1504-9213
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services
[HHSN272200900018C]; Broad Institute; National Institute of General
Medical Sciences [U54GM088558]; National Institutes of Allergy and
Infectious Disease [AI007061]; Danish Council for Strategic Research
[09-063070]; Institut de Veille Sanitaire
FX We thank Flemming Scheutz from the World Health Organization
Collaborating Centre for Reference and Research on Escherichia coli and
Klebsiella, Department of Microbiological Surveillance and Research,
Statens Serum Institut, Copenhagen, Denmark for the valuable
contribution of strains and discussion; R. T. Chandler for his insights;
all members of the Broad Biological Samples Platform and the Genome
Sequencing Platform; Lynne Aftuck, Scott Anderson, Patrick Cahill, Marc
Chevrette, Julio Diaz, Danielle Dionne, Sheli Dookran, Rachel Erlich,
Stephanie Grandbois, Lisa Green, Andrew Hollinger, Laurie Holmes, Andrew
Hoss, Edward Kelliher, Sharon Kim, Purnima Kompella, Tony LaCasse,
Matthew Lee, Niall J. Lennon, Dana Robbins, Alyssa Rosenthal, Elizabeth
Ryan, Brian Sogoloff, Todd Sparrow, Alvin Tam, Austin Tzou, Cole Walsh,
and Emily Wheeler for sequencing and technical support; and Lucia
Alvarado-Balderrama, Aaron Berlin, Gary Gearin, Sante Gnerre, Giles
Hall, Alma Imavovic, David B. Jaffe, Annie Lui, Iain MacCallum, J.
Pendexter Macdonald, Matthew Pearson, Margaret Priest, Dariusz
Przbylski, Andrew Roberts, Filipe J. Ribeiro, Sakina Saif, Ted Sharpe,
Terry Shea, Narmada Shenoy, and Shuangye Yin for computational and
analysis support. This project has been funded in part with federal
funds from the National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Department of Health and Human Services,
under Contract HHSN272200900018C (to B. W. B.), and the Infectious
Disease Program of the Broad Institute; National Institute of General
Medical Sciences Award U54GM088558 (to M. L. and W. P. H.); National
Institutes of Allergy and Infectious Disease T32 Grant AI007061 (to
Y.H.G.); Danish Council for Strategic Research Grant 09-063070 (to K. A.
K.); and the Institut de Veille Sanitaire (F.-X.W. and E.B.).
NR 23
TC 107
Z9 113
U1 2
U2 27
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 21
PY 2012
VL 109
IS 8
BP 3065
EP 3070
DI 10.1073/pnas.1121491109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895KM
UT WOS:000300495100078
PM 22315421
ER
PT J
AU Ching, SN
Purdon, PL
Vijayan, S
Kopell, NJ
Brown, EN
AF Ching, ShiNung
Purdon, Patrick L.
Vijayan, Sujith
Kopell, Nancy J.
Brown, Emery N.
TI A neurophysiological-metabolic model for burst suppression
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID CEREBRAL-BLOOD-FLOW; GENERAL-ANESTHESIA; MITOCHONDRIAL OSCILLATIONS;
HEMORRHAGIC-SHOCK; OHTAHARA-SYNDROME; BRAIN PROTECTION; ALTERED STATES;
EEG; HYPOTHERMIA; PHYSIOLOGY
AB Burst suppression is an electroencepholagram (EEG) pattern in which high-voltage activity alternates with isoelectric quiescence. It is characteristic of an inactivated brain and is commonly observed at deep levels of general anesthesia, hypothermia, and in pathological conditions such as coma and early infantile encephalopathy. We propose a unifying mechanism for burst suppression that accounts for all of these conditions. By constructing a biophysical computational model, we show how the prevailing features of burst suppression may arise through the interaction between neuronal dynamics and brain metabolism. In each condition, the model suggests that a decrease in cerebral metabolic rate, coupled with the stabilizing properties of ATP-gated potassium channels, leads to the characteristic epochs of suppression. Consequently, the model makes a number of specific predictions of experimental and clinical relevance.
C1 [Ching, ShiNung; Purdon, Patrick L.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Ching, ShiNung; Purdon, Patrick L.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Brown, Emery N.] MIT, Div Hlth Sci & Technol, Harvard Massachusetts Inst Technol, Cambridge, MA 02139 USA.
[Vijayan, Sujith; Kopell, Nancy J.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Purdon, Patrick L.; Brown, Emery N.] Harvard Univ, Sch Med, Cambridge, MA 02115 USA.
RP Ching, SN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
EM shinung@neurostat.mit.edu; nk@bu.edu
FU National Institutes of Health [DP1-OD003646, K25-NS057580,
DP2-OD006454]; National Science Foundation [DMS-1042134, DMS-0717670]
FX This study was supported by National Institutes of Health Grants
DP1-OD003646, K25-NS057580, and DP2-OD006454 and National Science
Foundation Grants DMS-1042134 and DMS-0717670.
NR 49
TC 67
Z9 67
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 FEB 21
PY 2012
VL 109
IS 8
BP 3095
EP 3100
DI 10.1073/pnas.1121461109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895KM
UT WOS:000300495100083
PM 22323592
ER
PT J
AU Larson, JL
Yuan, GC
AF Larson, Jessica L.
Yuan, Guo-Cheng
TI Chromatin States Accurately Classify Cell Differentiation Stages
SO PLOS ONE
LA English
DT Article
ID EMBRYONIC STEM-CELLS; HUMAN GENOME; HISTONE MODIFICATIONS;
GENE-EXPRESSION; PLURIPOTENT; EPIGENOMICS; DISTINCT; IDENTIFICATION;
SIGNATURE; ENHANCERS
AB Gene expression is controlled by the concerted interactions between transcription factors and chromatin regulators. While recent studies have identified global chromatin state changes across cell-types, it remains unclear to what extent these changes are co-regulated during cell-differentiation. Here we present a comprehensive computational analysis by assembling a large dataset containing genome-wide occupancy information of 5 histone modifications in 27 human cell lines (including 24 normal and 3 cancer cell lines) obtained from the public domain, followed by independent analysis at three different representations. We classified the differentiation stage of a cell-type based on its genome-wide pattern of chromatin states, and found that our method was able to identify normal cell lines with nearly 100% accuracy. We then applied our model to classify the cancer cell lines and found that each can be unequivocally classified as differentiated cells. The differences can be in part explained by the differential activities of three regulatory modules associated with embryonic stem cells. We also found that the "hotspot'' genes, whose chromatin states change dynamically in accordance to the differentiation stage, are not randomly distributed across the genome but tend to be embedded in multi-gene chromatin domains, and that specialized gene clusters tend to be embedded in stably occupied domains.
C1 [Larson, Jessica L.; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Larson, JL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA.
EM gcyuan@jimmy.harvard.edu
FU HSPH; United States National Institutes of Health [HG005085]; NIH
[GM074897]
FX This work was supported by an HSPH Career Incubator Award and the United
States National Institutes of Health grant HG005085 to GCY, and by a NIH
training grant (GM074897) to JLL. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 40
TC 5
Z9 5
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 FEB 20
PY 2012
VL 7
IS 2
AR e31414
DI 10.1371/journal.pone.0031414
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 926YY
UT WOS:000302871500042
PM 22363642
ER
PT J
AU Meyerhardt, JA
Li, L
Sanoff, HK
Carpenter, W
Schrag, D
AF Meyerhardt, Jeffrey A.
Li, Ling
Sanoff, Hanna K.
Carpenter, William
Schrag, Deborah
TI Effectiveness of Bevacizumab With First-Line Combination Chemotherapy
for Medicare Patients With Stage IV Colorectal Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RANDOMIZED-TRIAL; PHASE-III; PLUS FLUOROURACIL; IRINOTECAN; LEUCOVORIN;
OXALIPLATIN; FOLFIRI; BOLUS; FLUOROPYRIMIDINES; MULTICENTER
AB Purpose
Clinical trials have shown that adding bevacizumab to cytotoxic chemotherapy improves survival for patients with colorectal cancer, although its effectiveness in the Medicare population is uncertain.
Patients and Methods
Using the Surveillance, Epidemiology, and End Results (SEER) -Medicare linked database, we identified 2,526 patients with stage IV colorectal cancer diagnosed between 2002 and 2007 who received first-line combination chemotherapy with a fluoropyrimidine and either irinotecan (33%) or oxaliplatin (67%). Thirty-six percent of patients received bevacizumab with first-line therapy. The primary outcome was overall survival. Secondary outcomes were bevacizumab-associated toxicities, including the incidence of stroke, myocardial infarction, and GI perforation.
Results
In the primary cohort inclusive of patients diagnosed between 2002 and 2007, bevacizumab with combination chemotherapy was associated with improved overall survival (adjusted hazard ratio [HR], 0.85; 95% CI, 0.78 to 0.93), although the effect was more modest when restricted to years 2004 to 2007 (HR, 0.93; 95% CI, 0.84 to 1.02). The observed survival advantage of bevacizumab was more apparent with irinotecan-based chemotherapy (HR, 0.80; 95% CI, 0.66 to 0.97) than with oxaliplatin-based chemotherapy (HR, 0.96; 95% CI, 0.86 to 1.07). Combination chemotherapy with bevacizumab, versus combination chemotherapy without bevacizumab, was associated with increased risk of stroke (4.9% v 2.5%, respectively; P < .01) and GI perforation (2.3% v 1.0%, respectively; P < .01). Cardiac events and venous thrombosis were not increased with bevacizumab.
Conclusion
The addition of bevacizumab to cytotoxic combination chemotherapy was associated with small improvement in overall survival as well as increased risk of stroke and perforation, but not cardiac events, among Medicare beneficiaries with stage IV colorectal cancer. J Clin Oncol 30:608-615. (c) 2012 by American Society of Clinical Oncology
C1 [Meyerhardt, Jeffrey A.; Li, Ling; Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Sanoff, Hanna K.] Univ Virginia, Charlottesville, VA USA.
[Carpenter, William] Univ N Carolina, Chapel Hill, NC USA.
RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM jmeyerhardt@partners.org
RI Carpenter, William/E-5125-2013
FU Agency for Healthcare Research and Quality, US Department of Health and
Human Services [HHSA290-2005-0016-I-TO7-WA4, 36-BWH-1]
FX Supported by Contract No. HHSA290-2005-0016-I-TO7-WA4, 36-BWH-1 from the
Agency for Healthcare Research and Quality, US Department of Health and
Human Services, as part of the Developing Evidence to Inform Decisions
About Effectiveness program.
NR 25
TC 56
Z9 57
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 FEB 20
PY 2012
VL 30
IS 6
BP 608
EP 615
DI 10.1200/JCO.2011.38.9650
PG 8
WC Oncology
SC Oncology
GA 923MQ
UT WOS:000302623800018
PM 22253466
ER
PT J
AU Hoang, T
Dahlberg, SE
Schiller, JH
Mehta, MP
Fitzgerald, TJ
Belinsky, SA
Johnson, DH
AF Hoang, Tien
Dahlberg, Suzanne E.
Schiller, Joan H.
Mehta, Minesh P.
Fitzgerald, Thomas J.
Belinsky, Steven A.
Johnson, David H.
TI Randomized Phase III Study of Thoracic Radiation in Combination With
Paclitaxel and Carboplatin With or Without Thalidomide in Patients With
Stage III Non-Small-Cell Lung Cancer: The ECOG 3598 Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID COOPERATIVE-ONCOLOGY-GROUP; SEQUENTIAL CHEMORADIOTHERAPY; DOUBLE-BLIND;
TRIAL; CONCURRENT; CHEMOTHERAPY; CISPLATIN; THERAPY; SURVIVAL
AB Purpose
The primary objective of this study was to compare the survival of patients with unresectable stage III non-small-cell lung cancer (NSCLC) treated with combined chemoradiotherapy with or without thalidomide.
Patients and Methods
Patients were randomly assigned to the control arm (PC) involving two cycles of induction paclitaxel 225 mg/m(2) and carboplatin area under the curve (AUC) 6 followed by 60 Gy thoracic radiation administered concurrently with weekly paclitaxel 45 mg/m(2) and carboplatin AUC 2, or to the experimental arm (TPC), receiving the same treatment in combination with thalidomide at a starting dose of 200 mg daily. The protocol allowed an increase in thalidomide dose up to 1,000 mg daily based on patient tolerability.
Results
A total of 546 patients were eligible, including 275 in the PC arm and 271 in the TPC arm. Median overall survival, progression-free survival, and overall response rate were 15.3 months, 7.4 months, and 35.0%, respectively, for patients in the PC arm, in comparison with 16.0 months (P = .99), 7.8 months (P = .96), and 38.2% (P = .47), respectively, for patients in the TPC arm. Overall, there was higher incidence of grade 3 toxicities in patients treated with thalidomide. Several grade 3 or higher events were observed more often in the TPC arm, including thromboembolism, fatigue, depressed consciousness, dizziness, sensory neuropathy, tremor, constipation, dyspnea, hypoxia, hypokalemia, rash, and edema. Low-dose aspirin did not reduce the thromboembolic rate.
Conclusion
The addition of thalidomide to chemoradiotherapy increased toxicities but did not improve survival in patients with locally advanced NSCLC. J Clin Oncol 30:616-622. (c) 2012 by American Society of Clinical Oncology
C1 [Hoang, Tien; Schiller, Joan H.; Mehta, Minesh P.] Univ Wisconsin, Madison, WI USA.
[Dahlberg, Suzanne E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Fitzgerald, Thomas J.] Qual Assurance Review Ctr, Lincoln, RI USA.
[Belinsky, Steven A.] Lovelace Resp Res Inst, Albuquerque, NM USA.
[Johnson, David H.] Vanderbilt Univ, Nashville, TN USA.
RP Hoang, T (reprint author), Wisconsin Inst Med Res, 1111 Highland Ave, Madison, WI 53705 USA.
EM txh@medicine.wisc.edu
OI mehta, minesh/0000-0002-4812-5713
FU Public Health Service [CA23318, CA66636, CA21115, CA21076, CA49957,
CA029511]; National Cancer Institute, National Institutes of Health, and
Department of Health and Human Services
FX Coordinated by the Eastern Cooperative Oncology Group and supported in
part by Public Health Service Grants No. CA23318, CA66636, CA21115,
CA21076, CA49957, and CA029511 and grants from the National Cancer
Institute, National Institutes of Health, and Department of Health and
Human Services.
NR 20
TC 24
Z9 26
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 FEB 20
PY 2012
VL 30
IS 6
BP 616
EP 622
DI 10.1200/JCO.2011.36.9116
PG 7
WC Oncology
SC Oncology
GA 923MQ
UT WOS:000302623800019
PM 22271472
ER
PT J
AU Mullins, CD
Montgomery, R
Abernethy, AP
Hussain, A
Pearson, SD
Tunis, S
AF Mullins, C. Daniel
Montgomery, Russ
Abernethy, Amy P.
Hussain, Arif
Pearson, Steven D.
Tunis, Sean
TI Recommendations for Clinical Trials of Off-Label Drugs Used to Treat
Advanced-Stage Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID PARTICIPATION
AB Purpose
To provide recommendations to trialists and sponsors that guide the design and implementation of prospective postapproval clinical trials for oncology drugs used outside US Food and Drug Administration-labeled indications for treatment of late-stage cancers.
Methods
A meeting was hosted by the Center for Medical Technology Policy in Baltimore, MD, on November 12, 2009. Discussions during the meeting and key informant interviews were conducted before and after this stakeholder meeting. Peer review by multidisciplinary stakeholders was followed by a public comment period. Input was received from patient advocacy groups, medical oncologists, pharmaceutical companies, the US Food and Drug Administration, Centers for Medicare and Medicaid Services, the National Cancer Institute, foreign government agencies involved in health technology assessment, public and private payers, drug compendia, clinical research entities, statisticians, academics, and the American Society of Clinical Oncology.
Results
To address the needs of patients and their clinical providers, compendia, payers, and policy makers, recommendations are proposed to guide the design of future prospective trials for off-label use of oncology drugs across four areas: trial design and data analysis, patient and site recruitment, comparators, and outcomes.
Conclusion
The US Food and Drug Administration provides guidance to the pharmaceutical industry and others designing randomized clinical trials for regulatory approval. However, a gap exists for postregulatory decision makers, including patients, prescribers, and payers, because regulatory trials do not answer the questions most relevant to them. Therefore, guidance is needed for trials performed in the postapproval environment for these postapproval decision makers. J Clin Oncol 30:661-666. (c) 2012 by American Society of Clinical Oncology
C1 [Mullins, C. Daniel] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA.
[Hussain, Arif] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Hussain, Arif] Baltimore Vet Affairs Med Ctr, Baltimore, MD USA.
[Montgomery, Russ] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Mullins, C. Daniel; Montgomery, Russ; Tunis, Sean] Ctr Med Technol Policy, Baltimore, MD USA.
[Abernethy, Amy P.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA.
[Abernethy, Amy P.] Duke Univ, Sch Med, Durham, NC USA.
[Pearson, Steven D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pearson, Steven D.] Harvard Univ, Sch Med, Boston, MA USA.
RP Mullins, CD (reprint author), Univ Maryland, Sch Pharm, 220 Arch St,12th Floor, Baltimore, MD 21201 USA.
EM dmullins@rx.umaryland.edu
FU Amgen; Bayer Pharmaceuticals; Genentech; sanofi-aventis
FX Supported by unrestricted contributions from Amgen, Bayer
Pharmaceuticals, Genentech, and sanofi-aventis.
NR 15
TC 12
Z9 12
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 FEB 20
PY 2012
VL 30
IS 6
BP 661
EP 666
DI 10.1200/JCO.2011.35.5198
PG 6
WC Oncology
SC Oncology
GA 923MQ
UT WOS:000302623800025
PM 22253467
ER
PT J
AU Cauley, S
Balakrishnan, V
Klimeck, G
Koh, CK
AF Cauley, Stephen
Balakrishnan, Venkataramanan
Klimeck, Gerhard
Koh, Cheng-Kok
TI A two-dimensional domain decomposition technique for the simulation of
quantum-scale devices
SO JOURNAL OF COMPUTATIONAL PHYSICS
LA English
DT Article
DE NEGF; Parallel; Density of states; Atomistic
ID ALGORITHM; MATRICES; INVERSE
AB The simulation of realistically sized devices under the Non-Equilibrium Greens Function (NEGF) formalism typically requires prohibitive amounts of memory and computation time. In order to meet the rising computational challenges associated with quantum-scale device simulation we offer a 2-D domain decomposition technique. This technique is applicable to a large class of atomistic and spatial simulation problems. Considering a decomposition along both the cross section and length of the device, the framework presented in this work ensures efficient distribution of both memory and computation based upon the underlying device structure. As an illustration we stably generate the density of states and transmission, under the NEGF formalism, for the atomistic-based simulation of square 5 nm cross section silicon nanowires consisting of over one million atomic orbitals. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Cauley, Stephen] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA.
[Balakrishnan, Venkataramanan; Klimeck, Gerhard; Koh, Cheng-Kok] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA.
RP Cauley, S (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA.
EM stcauley@nmr.mgh.harvard.edu; ragu@ecn.purdue.edu; gekco@purdue.edu;
chengkok@ecn.purdue.edu
RI Cauley, Stephen/P-1386-2014; Klimeck, Gerhard/A-1414-2012
OI Klimeck, Gerhard/0000-0001-7128-773X
FU NSF [CCF-1065318]
FX This work was partially supported by NSF grant CCF-1065318.
NR 19
TC 5
Z9 5
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0021-9991
J9 J COMPUT PHYS
JI J. Comput. Phys.
PD FEB 20
PY 2012
VL 231
IS 4
BP 1293
EP 1313
DI 10.1016/j.jcp.2011.10.006
PG 21
WC Computer Science, Interdisciplinary Applications; Physics, Mathematical
SC Computer Science; Physics
GA 894XZ
UT WOS:000300462100012
ER
PT J
AU Van Gulck, E
Vlieghe, E
Vekemans, M
Van Tendeloo, VFI
Van De Velde, A
Smits, E
Anguille, S
Cools, N
Goossens, H
Mertens, L
De Haes, W
Wong, J
Florence, E
Vanham, G
Berneman, ZN
AF Van Gulck, Ellen
Vlieghe, Erika
Vekemans, Marc
Van Tendeloo, Viggo F. I.
Van De Velde, Ann
Smits, Evelien
Anguille, Sebastien
Cools, Nathalie
Goossens, Herman
Mertens, Liesbet
De Haes, Winni
Wong, Johnsson
Florence, Eric
Vanham, Guido
Berneman, Zwi N.
TI mRNA-based dendritic cell vaccination induces potent antiviral T-cell
responses in HIV-1-infected patients
SO AIDS
LA English
DT Article
DE dendritic cells; HIV-1; immunotherapy; mRNA electroporation; therapeutic
vaccination
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHRONIC HIV-1 INFECTION; VIRAL LOAD;
AUTOLOGOUS HIV-1; PROTEINS; INDUCTION; VACCINES; ASSAY; GAG;
NONPROGRESSORS
AB Background: In an effort to raise protective antiviral immunity, dendritic cell immunotherapy was evaluated in six adults infected with human immunodeficiency virus (HIV)-1 and stable under highly active antiretroviral therapy (HAART).
Design and methods: Autologous monocyte-derived dendritic cells electroporated with mRNA encoding Gag and a chimeric Tat-Rev-Nef protein were administered, whereas patients remained on HAART. Feasibility, safety, immunogenicity and antiviral responses were investigated.
Results: Dendritic cell vaccine preparation and administration were successful in all patients and only mild adverse events were seen. There was a significant increase postdendritic cell as compared to pre-dendritic cell vaccination in magnitude and breadth of HIV-1-specific interferon (IFN)-gamma response, in particular to Gag, and in T-cell proliferation. Breadth of IFN-gamma response and T-cell proliferation were both correlated with CD4(+) and CD8(+) polyfunctional T-cell responses. Importantly, dendritic cell vaccination induced or increased the capacity of autologous CD8(+) T cells to inhibit superinfection of CD4(+) T cells with the vaccine-related IIIB virus and some but not all other HIV-1 strains tested. This HIV-1-inhibitory activity, indicative of improved antiviral response, was correlated with magnitude and breadth of Gag-specific IFN-gamma response.
Conclusions: Therapeutic immunization with dendritic cells was safe and successful in raising antiviral cellular immune responses, including effector CD8(+) T cells with virus inhibitory activity. The stimulation of those potent immunological and antiviral effects, which have been associated with control of HIV-1, underscores the potential of dendritic cell vaccination in the treatment of HIV-1. The incomplete nature of the response in some patients helped to identify potential targets for future improvement, that is increasing antigenic spectrum and enhancing T-cell response. (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Van Tendeloo, Viggo F. I.; Van De Velde, Ann; Smits, Evelien; Anguille, Sebastien; Cools, Nathalie; Berneman, Zwi N.] Antwerp Univ Hosp UZA, Ctr Cell Therapy & Regenerat Med CCRG, B-2650 Edegem, Belgium.
[Van Tendeloo, Viggo F. I.; Van De Velde, Ann; Smits, Evelien; Anguille, Sebastien; Cools, Nathalie; Berneman, Zwi N.] Antwerp Univ Hosp UZA, Div Hematol, B-2650 Edegem, Belgium.
[Van Gulck, Ellen; De Haes, Winni; Vanham, Guido] Inst Trop Med, Virol Unit, Div Microbiol, Dept Biomed Sci, B-2000 Antwerp, Belgium.
[Vlieghe, Erika; Vekemans, Marc; Mertens, Liesbet; Florence, Eric] Inst Trop Med, Dept Clin Sci, Med Serv, HIV & STD Unit, B-2000 Antwerp, Belgium.
[Van Tendeloo, Viggo F. I.; Van De Velde, Ann; Smits, Evelien; Anguille, Sebastien; Cools, Nathalie; Goossens, Herman; Berneman, Zwi N.] Univ Antwerp, Fac Med & Hlth Sci, Vaccine & Infect Dis Inst, B-2020 Antwerp, Belgium.
[Wong, Johnsson] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA.
[Vanham, Guido] Univ Antwerp, Fac Pharmaceut Biomed & Vet Sci, B-2020 Antwerp, Belgium.
[Vanham, Guido] Free Univ Brussels VUB, Fac Med & Pharm, Brussels, Belgium.
RP Berneman, ZN (reprint author), Antwerp Univ Hosp UZA, Ctr Cell Therapy & Regenerat Med CCRG, Wilrijkstr 10, B-2650 Edegem, Belgium.
EM Zwi.Berneman@uza.be
RI Smits, Evelien/E-9654-2012; Cools, Nathalie/A-1211-2010; Smits,
Evelien/A-3520-2014
OI Cools, Nathalie/0000-0002-0459-901X; Smits, Evelien/0000-0001-9255-3435
FU Interuniversity Attraction Poles (IAP) of Belgian Science Policy
[P6/41]; Agency for Innovation by Science and Technology (IWT) [60511];
Antwerp University Hospital; Flemish Government
FX The work was supported by the Interuniversity Attraction Poles (IAP
grant no. P6/41) of Belgian Science Policy; by grant no. 60511 of the
Agency for Innovation by Science and Technology (IWT); by the Fund for
Cell Therapy of the Antwerp University Hospital and by a grant of the
Methusalem program of the Flemish Government to the University of
Antwerp and to H.G. E.S. and N.C. hold a postdoctoral fellowship and
S.A. a PhD fellowship of the Research Foundation Flanders
(FWO-Vlaanderen). W.D.H. holds a PhD fellowship of the IWT. The
technical assistance of Barbara Stein, Griet Nijs, Celine Merlin and
Derek Atkinson is gratefully acknowledged.
NR 38
TC 33
Z9 34
U1 3
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD FEB 20
PY 2012
VL 26
IS 4
BP F1
EP F12
DI 10.1097/QAD.0b013e32834f33e8
PG 12
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 894FC
UT WOS:000300411500001
PM 22156965
ER
PT J
AU Buxbaum, JD
Betancur, C
Bozdagi, O
Dorr, NP
Elder, GA
Hof, PR
AF Buxbaum, Joseph D.
Betancur, Catalina
Bozdagi, Ozlem
Dorr, Nate P.
Elder, Gregory A.
Hof, Patrick R.
TI Optimizing the phenotyping of rodent ASD models: enrichment analysis of
mouse and human neurobiological phenotypes associated with high-risk
autism genes identifies morphological, electrophysiological,
neurological, and behavioral features
SO MOLECULAR AUTISM
LA English
DT Article
DE Systems biology; mouse behavior; autism; autism spectrum disorders;
genetically modified mice; forward genetics; reverse genetics
ID COMPONENTS; PROTEOME
AB Background: There is interest in defining mouse neurobiological phenotypes useful for studying autism spectrum disorders (ASD) in both forward and reverse genetic approaches. A recurrent focus has been on high-order behavioral analyses, including learning and memory paradigms and social paradigms. However, well-studied mouse models, including for example Fmr1 knockout mice, do not show dramatic deficits in such high-order phenotypes, raising a question as to what constitutes useful phenotypes in ASD models.
Methods: To address this, we made use of a list of 112 disease genes etiologically involved in ASD to survey, on a large scale and with unbiased methods as well as expert review, phenotypes associated with a targeted disruption of these genes in mice, using the Mammalian Phenotype Ontology database. In addition, we compared the results with similar analyses for human phenotypes.
Findings: We observed four classes of neurobiological phenotypes associated with disruption of a large proportion of ASD genes, including: (1) Changes in brain and neuronal morphology; (2) electrophysiological changes; (3) neurological changes; and (4) higher-order behavioral changes. Alterations in brain and neuronal morphology represent quantitative measures that can be more widely adopted in models of ASD to understand cellular and network changes. Interestingly, the electrophysiological changes differed across different genes, indicating that excitation/inhibition imbalance hypotheses for ASD would either have to be so non-specific as to be not falsifiable, or, if specific, would not be supported by the data. Finally, it was significant that in analyses of both mouse and human databases, many of the behavioral alterations were neurological changes, encompassing sensory alterations, motor abnormalities, and seizures, as opposed to higher-order behavioral changes in learning and memory and social behavior paradigms.
Conclusions: The results indicated that mutations in ASD genes result in defined groups of changes in mouse models and support a broad neurobiological approach to phenotyping rodent models for ASD, with a focus on biochemistry and molecular biology, brain and neuronal morphology, and electrophysiology, as well as both neurological and additional behavioral analyses. Analysis of human phenotypes associated with these genes reinforced these conclusions, supporting face validity for these approaches to phenotyping of ASD models. Such phenotyping is consistent with the successes in Fmr1 knockout mice, in which morphological changes recapitulated human findings and electrophysiological deficits resulted in molecular insights that have since led to clinical trials. We propose both broad domains and, based on expert review of more than 50 publications in each of the four neurobiological domains, specific tests to be applied to rodent models of ASD.
C1 [Buxbaum, Joseph D.; Bozdagi, Ozlem] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA.
[Buxbaum, Joseph D.; Bozdagi, Ozlem; Dorr, Nate P.; Elder, Gregory A.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[Buxbaum, Joseph D.; Hof, Patrick R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
[Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Buxbaum, Joseph D.; Elder, Gregory A.; Hof, Patrick R.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA.
[Elder, Gregory A.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
[Betancur, Catalina] INSERM, U952, F-75005 Paris, France.
[Betancur, Catalina] CNRS, UMR 7224, F-75005 Paris, France.
[Betancur, Catalina] Univ Paris 06, F-75005 Paris, France.
[Elder, Gregory A.] James J Peters VA Med Ctr, Neurol Serv, Bronx, NY 10468 USA.
RP Buxbaum, JD (reprint author), Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, 1 Gustave L Levy Pl, New York, NY 10029 USA.
EM joseph.buxbaum@mssm.edu
OI Buxbaum, Joseph/0000-0001-8898-8313; Betancur,
Catalina/0000-0002-3327-4804
FU Seaver Foundation; Simons Foundation; NIMH [MH093725]; INSERM
FX This work was supported by the Seaver Foundation (JDB, OB, PRH), the
Simons Foundation (JDB, OB, PRH), the NIMH (MH093725; JDB, OB, PRH), and
INSERM (CB). OB is a Seaver Fellow. JDB is the G Harold and Leila Y
Mathers Professor at Mount Sinai.
NR 9
TC 14
Z9 14
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2040-2392
J9 MOL AUTISM
JI Mol. Autism
PD FEB 20
PY 2012
VL 3
AR 1
DI 10.1186/2040-2392-3-1
PG 8
WC Genetics & Heredity; Neurosciences
SC Genetics & Heredity; Neurosciences & Neurology
GA 254RH
UT WOS:000327184000001
PM 22348382
ER
PT J
AU Baselga, J
Bradbury, I
Eidtmann, H
Di Cosimo, S
de Azambuja, E
Aura, C
Gomez, H
Dinh, P
Fauria, K
Van Dooren, V
Aktan, G
Goldhirsch, A
Chang, TW
Horvath, Z
Coccia-Portugal, M
Domont, J
Tseng, LM
Kunz, G
Sohn, JH
Semiglazov, V
Lerzo, G
Palacova, M
Probachai, V
Pusztai, L
Untch, M
Gelber, RD
Piccart-Gebhart, M
AF Baselga, Jose
Bradbury, Ian
Eidtmann, Holger
Di Cosimo, Serena
de Azambuja, Evandro
Aura, Claudia
Gomez, Henry
Dinh, Phuong
Fauria, Karine
Van Dooren, Veerle
Aktan, Gursel
Goldhirsch, Aron
Chang, Tsai-Wang
Horvath, Zsolt
Coccia-Portugal, Maria
Domont, Julien
Tseng, Ling-Min
Kunz, Georg
Sohn, Joo Hyuk
Semiglazov, Vladimir
Lerzo, Guillermo
Palacova, Marketa
Probachai, Volodymyr
Pusztai, Lajos
Untch, Michael
Gelber, Richard D.
Piccart-Gebhart, Martine
CA NeoALTTO Study Team
TI Lapatinib with trastuzumab for HER2-positive early breast cancer
(NeoALTTO): a randomised, open-label, multicentre, phase 3 trial
SO LANCET
LA English
DT Article
ID ADJUVANT CHEMOTHERAPY; INHIBITOR; PLUS; APOPTOSIS; GW572016; CELLS;
WOMEN; ERBB2
AB Background The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer. We argue that the two anti-HER2 agents given together would be better than single-agent therapy.
Methods In this parallel groups, randomised, open-label, phase 3 study undertaken between Jan 5, 2008, and May 27, 2010, women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were randomly assigned to oral lapatinib (1500 mg), intravenous trastuzumab (loading dose 4 mg/kg, subsequent doses 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab. Treatment allocation was by stratified, permuted blocks randomisation, with four stratification factors. Anti-HER2 therapy alone was given for the first 6 weeks; weekly paclitaxel (80 mg/m(2)) was then added to the regimen for a further 12 weeks, before definitive surgery was undertaken. After surgery, patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks. The primary endpoint was the rate of pathological complete response (pCR), analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00553358.
Findings 154 patients received lapatinib, 149 trastuzumab, and 152 the combination. pCR rate was significantly higher in the group given lapatinib and trastuzumab (78 of 152 patients [51.3%; 95% CI 43.1-59.5]) than in the group given trastuzumab alone (44 of 149 patients [29.5%; 22.4-37.5]; difference 21.1%, 9.1-34.2, p=0.0001). We recorded no significant difference in pCR between the lapatinib (38 of 154 patients [24.7%, 18.1-32.3]) and the trastuzumab (difference -4.8%, -17.6 to 8.2, p=0.34) groups. No major cardiac dysfunctions occurred. Frequency of grade 3 diarrhoea was higher with lapatinib (36 patients [23.4%]) and lapatinib plus trastuzumab (32 [21.1%]) than with trastuzumab (three [2.0%]). Similarly, grade 3 liver-enzyme alterations were more frequent with lapatinib (27 [17.5%]) and lapatinib plus trastuzumab (15 [9.9%]) than with trastuzumab (11 [7.4%]).
Interpretation Dual inhibition of HER2 might be a valid approach to treatment of HER2-positive breast cancer in the neoadjuvant setting.
C1 [Baselga, Jose] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Baselga, Jose; Di Cosimo, Serena; Fauria, Karine] SOLTI Breast Canc Res Grp, Barcelona, Spain.
[Bradbury, Ian] Frontier Sci Scotland, Kincraig, Scotland.
[Bradbury, Ian] Queens Univ Belfast, Belfast, Antrim, North Ireland.
[Eidtmann, Holger] Univ Hosp Kiel, Kiel, Germany.
[Di Cosimo, Serena] Vall dHebron Univ Hosp, Breast Canc Ctr, Barcelona, Spain.
[Aura, Claudia] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain.
[de Azambuja, Evandro; Van Dooren, Veerle] Inst Jules Bordet, Breast European Adjuvant Study Team, B-1000 Brussels, Belgium.
[Dinh, Phuong] Inst Jules Bordet, Breast Int Grp, B-1000 Brussels, Belgium.
[Piccart-Gebhart, Martine] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium.
[Gomez, Henry] Inst Nacl Enfermedades Neoplas, Lima, Peru.
[Aktan, Gursel] GlaxoSmithKline, Collegeville, PA USA.
[Goldhirsch, Aron] European Inst Oncol, Milan, Italy.
[Goldhirsch, Aron] St Anna Clin, Swiss Ctr Breast Hlth, Lugano, Switzerland.
[Chang, Tsai-Wang] Natl Cheng Kung Univ Hosp, Tainan 70428, Taiwan.
[Horvath, Zsolt] Natl Inst Oncol, Budapest, Hungary.
[Coccia-Portugal, Maria] Eastleigh Breast Care Ctr, Pretoria, South Africa.
[Domont, Julien] Inst Gustave Roussy, Villejuif, France.
[Tseng, Ling-Min] Natl Yang Ming Univ, Taipei Vet Gen Hosp, Taipei 112, Taiwan.
[Kunz, Georg] St Johannes Hosp, Dortmund, Germany.
[Sohn, Joo Hyuk] Yonsei Univ, Coll Med, Seoul, South Korea.
[Semiglazov, Vladimir] Petrov Res Inst Oncol, St Petersburg, Russia.
[Lerzo, Guillermo] Invest Clin Ciudad Autonoma Buenos Aires, Buenos Aires, DF, Argentina.
[Palacova, Marketa] Masarykuv Onkol Ustav, Brno, Czech Republic.
[Probachai, Volodymyr] City Clin Hosp, Dnepropetrovsk, Ukraine.
[Pusztai, Lajos] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Untch, Michael] Charite, Clin Gynaecol Gynaecol Oncol & Obstet, Breast Canc Ctr, D-13353 Berlin, Germany.
[Gelber, Richard D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA.
RP Baselga, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House 108, Boston, MA 02114 USA.
EM jbaselga@partners.org
RI Kwong, Ava/D-8005-2013; Horvath, Zsolt/B-9524-2012; Serena, Di
Cosimo/E-9418-2017;
OI Kwong, Ava/0000-0002-6968-9489; Serena, Di Cosimo/0000-0002-4666-8052;
Semiglazov, Vladimir/0000-0003-0077-9619; Gomez,
Henry/0000-0003-2660-1843; Ciruelos, Eva /0000-0002-2796-1042
FU GlaxoSmithKline; Roche; Novartis; Amgen; Abbott; AstraZeneca; Pfizer;
Sanofi; Bristol-Myers Squibb
FX JB has received honoraria from Roche. IB's institution has received
funding from GlaxoSmithKline and Roche. HE has been a speaker and
received travel grants from GlaxoSmithKline. SDC has been a speaker for
GlaxoSmithKline. EdA has served on an advisory board and received a
travelling grant from GlaxoSmithKline, and has been a speaker for Roche.
KF's institution has received travelling grants from GlaxoSmithKline.
VVD's and T-WC's institutions have received research funding from
GlaxoSmithKline. AG has received honoraria from GlaxoSmithKline and
Roche. T-WC has been a speaker for GlaxoSmithKline, Roche, Novartis, and
Amgen; and has received consultancy funding from GlaxoSmithKline, Roche,
Abbott, AstraZeneca, Novartis, and Amgen. LP has received consultancy
fees from Pfizer, Sanofi, and Bristol-Myers Squibb; and research grants
from Bristol-Myers Squibb and AstraZeneca. RDG's institution has
received research funding from GlaxoSmithKline and Roche. MP-G has
received honoraria from GlaxoSmithKline and Roche, and her institution
has received research funding from GlaxoSmithKline. GA is a salaried
employee of GlaxoSmithKline and retains stock and stock options at the
company. The other authors declare that they have no conflicts of
interest.
NR 30
TC 499
Z9 529
U1 8
U2 77
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD FEB 18
PY 2012
VL 379
IS 9816
BP 633
EP 640
DI 10.1016/S0140-6736(11)61847-3
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 897ES
UT WOS:000300629000034
PM 22257673
ER
PT J
AU Graewe, B
De Weerd, P
Farivar, R
Castelo-Branco, M
AF Graewe, Britta
De Weerd, Peter
Farivar, Reza
Castelo-Branco, Miguel
TI Stimulus Dependency of Object-Evoked Responses in Human Visual Cortex:
An Inverse Problem for Category Specificity
SO PLOS ONE
LA English
DT Article
ID EVENT-RELATED POTENTIALS; FACE PERCEPTION; ELECTROMAGNETIC TOMOGRAPHY;
UNFAMILIAR FACES; MOTION-ONSET; N170; RECOGNITION; BRAIN; ERPS; TEXTURE
AB Many studies have linked the processing of different object categories to specific event-related potentials (ERPs) such as the face-specific N170. Despite reports showing that object-related ERPs are influenced by visual stimulus features, there is consensus that these components primarily reflect categorical aspects of the stimuli. Here, we re-investigated this idea by systematically measuring the effects of visual feature manipulations on ERP responses elicited by both structure-from-motion (SFM)-defined and luminance-defined object stimuli. SFM objects elicited a novel component at 200-250 ms (N250) over parietal and posterior temporal sites. We found, however, that the N250 amplitude was unaffected by restructuring SFM stimuli into meaningless objects based on identical visual cues. This suggests that this N250 peak was not uniquely linked to categorical aspects of the objects, but is strongly determined by visual stimulus features. We provide strong support for this hypothesis by parametrically manipulating the depth range of both SFM- and luminance-defined object stimuli and showing that the N250 evoked by SFM stimuli as well as the well-known N170 to static faces were sensitive to this manipulation. Importantly, this effect could not be attributed to compromised object categorization in low depth stimuli, confirming a strong impact of visual stimulus features on object-related ERP signals. As ERP components linked with visual categorical object perception are likely determined by multiple stimulus features, this creates an interesting inverse problem when deriving specific perceptual processes from variations in ERP components.
C1 [Graewe, Britta; De Weerd, Peter] Maastricht Univ, Fac Psychol & Neurosci, Dept Cognit Neurosci, Maastricht, Netherlands.
[Graewe, Britta] Univ Coimbra, Inst Biomeed Res Light & Image, Visual Neurosci Lab, Coimbra, Portugal.
[De Weerd, Peter] Radboud Univ Nijmegen, Donders Inst Brain Behav & Cognit, NL-6525 ED Nijmegen, Netherlands.
[Farivar, Reza] Harvard Univ, Sch Med, Charlestown, MA USA.
[Farivar, Reza] Massachusetts Gen Hosp, A Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Castelo-Branco, Miguel] Univ Coimbra, IBILI, Visual Neurosci Lab, Coimbra, Portugal.
RP Graewe, B (reprint author), Maastricht Univ, Fac Psychol & Neurosci, Dept Cognit Neurosci, Maastricht, Netherlands.
EM britta.graewe@maastrichtuniversity.nl
RI Castelo-Branco, Miguel/E-5689-2010;
OI Castelo-Branco, Miguel/0000-0003-4364-6373
FU Foundation for Science and Technology Portugal [SFRH/BD/37385/2007,
PTDC/SAU/NEU/68483/2006, PIC/IC/82986/2007]; Bial Foundation [94/06];
BIN (Brain Imaging Network of Portugal)
FX This work was supported by a grant to BG, MC-B and PDW
(SFRH/BD/37385/2007), Grants PTDC/SAU/NEU/68483/2006 and
PIC/IC/82986/2007 from the Foundation for Science and Technology
Portugal (http://www.fct.pt/) and the Bial Foundation 94/06
(http://www.bial.com/en/bial_foundation.11/grants.18/grants.a38.html).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.; The authors
acknowledge the support of the BIN (Brain Imaging Network of Portugal).
We would like to thank Jose Rebola for his help with creating the
luminance-defined stimuli and Valerie Goffaux for valuable comments
during manuscript revision.
NR 59
TC 4
Z9 4
U1 1
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 FEB 17
PY 2012
VL 7
IS 2
AR e30727
DI 10.1371/journal.pone.0030727
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 926TC
UT WOS:000302853600062
PM 22363479
ER
PT J
AU Kamat, A
Misra, V
Cassol, E
Ancuta, P
Yan, ZY
Li, C
Morgello, S
Gabuzda, D
AF Kamat, Anupa
Misra, Vikas
Cassol, Edana
Ancuta, Petronela
Yan, Zhenyu
Li, Cheng
Morgello, Susan
Gabuzda, Dana
TI A Plasma Biomarker Signature of Immune Activation in HIV Patients on
Antiretroviral Therapy
SO PLOS ONE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS-INFECTION; HEPATITIS-C-VIRUS; T-CELL-ACTIVATION;
NATURAL-KILLER-CELLS; DISEASE PROGRESSION; INTERFERON-GAMMA; MICROBIAL
TRANSLOCATION; SIGMA-1 RECEPTORS; DENDRITIC CELLS; CRACK-COCAINE
AB Background: Immune activation is a strong predictor of disease progression in HIV infection. Combinatorial plasma biomarker signatures that represent surrogate markers of immune activation in both viremic and aviremic HIV patients on combination antiretroviral therapy (cART) have not been defined. Here, we identify a plasma inflammatory biomarker signature that distinguishes between both viremic and aviremic HIV patients on cART and healthy controls and examine relationships of this signature to markers of disease progression.
Methods: Multiplex profiling and ELISA were used to detect 15 cytokines/chemokines, soluble IL-2R (sIL-2R), and soluble CD14 (sCD14) in plasma from 57 HIV patients with CD4 nadir <300 cells/mu l and 29 healthy controls. Supervised and unsupervised analyses were used to identify biomarkers explaining variance between groups defined by HIV status or drug abuse. Relationships between biomarkers and disease markers were examined by Spearman correlation.
Results: The majority (91%) of HIV subjects were on cART, with 38% having undetectable viral loads (VL). Hierarchical clustering identified a biomarker cluster in plasma consisting of two interferon-stimulated gene products (CXCL9 and CXCL10), T cell activation marker (sIL-2R), and monocyte activation marker (sCD14) that distinguished both viremic and aviremic HIV patients on cART from controls (p<0.0001) and were top-ranked in variables important in projection plots. IL-12 and CCL4 were also elevated in viremic and aviremic patients compared to controls (p<0.05). IL-12 correlated with IFN alpha, IFN gamma, CXCL9, and sIL-2R (p<0.05). CXCL10 correlated positively with plasma VL and percentage of CD16+ monocytes, and inversely with CD4 count (p = 0.001, <0.0001, and 0.04, respectively).
Conclusion: A plasma inflammatory biomarker signature consisting of CXCL9, CXCL10, sIL-2R, and sCD14 may be useful as a surrogate marker to monitor immune activation in both viremic and aviremic HIV patients on cART during disease progression and therapeutic responses.
C1 [Kamat, Anupa; Misra, Vikas; Cassol, Edana; Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Kamat, Anupa; Cassol, Edana; Gabuzda, Dana] Harvard Univ, Sch Med, Boston, MA USA.
[Ancuta, Petronela] Univ Montreal, Dept Microbiol & Immunol, Fac Med, CHUM Res Ctr, Montreal, PQ H3C 3J7, Canada.
[Yan, Zhenyu; Li, Cheng] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA.
[Morgello, Susan] Mt Sinai Med Ctr, New York, NY 10029 USA.
RP Kamat, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
EM dana_gabuzda@dfci.harvard.edu
FU National Institutes of Health [DA30985, DA28994, U01MH083501,
R24MH59724, U01MH083506, R24MH59745, U01MH083507, R24 NS45491,
5U01MH083500, NS38841, U01MH083545, N01MH32002]; Canadian Institutes of
Health Research (CIHR); Fonds de la Recherche en Sante Quebec (FRSQ);
CNS HIV Antiretroviral Therapy Effects Research (CHARTER) [N01MH22005];
Harvard Center for AIDS Research and Dana-Farber Cancer
Institute/Harvard Center for Cancer Research
FX This work was supported by National Institutes of Health Grants DA30985
and DA28994 to Dr. Gabuzda. Dr. Cassol was supported by a fellowship
award from Canadian Institutes of Health Research (CIHR). Dr. Ancuta was
supported by a Salary Award from Fonds de la Recherche en Sante Quebec
(FRSQ). National NeuroAIDS Tissue Consortium (NNTC) sites were supported
by National Institutes of Health Grants U01MH083501, R24MH59724,
U01MH083506, R24MH59745, U01MH083507, R24 NS45491, 5U01MH083500,
NS38841, U01MH083545, and N01MH32002. CNS HIV Antiretroviral Therapy
Effects Research (CHARTER) was supported by N01MH22005. Core facilities
were supported by the Harvard Center for AIDS Research and Dana-Farber
Cancer Institute/Harvard Center for Cancer Research grants. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 75
TC 44
Z9 44
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 17
PY 2012
VL 7
IS 2
AR e30881
DI 10.1371/journal.pone.0030881
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 926TC
UT WOS:000302853600080
PM 22363505
ER
PT J
AU Singh, A
Sweeney, MF
Yu, M
Burger, A
Greninger, P
Benes, C
Haber, DA
Settleman, J
AF Singh, Anurag
Sweeney, Michael F.
Yu, Min
Burger, Alexa
Greninger, Patricia
Benes, Cyril
Haber, Daniel A.
Settleman, Jeff
TI TAK1 Inhibition Promotes Apoptosis in KRAS-Dependent Colon Cancers
SO CELL
LA English
DT Article
ID ONCOGENIC KRAS; BETA-CATENIN; C-ELEGANS; CELLS; RAS; PROTEIN;
PROGRESSION; EXPRESSION; PATHWAY; ADDICTION
AB Colon cancers frequently harbor KRAS mutations, yet only a subset of KRAS mutant colon cancer cell lines are dependent upon KRAS signaling for survival. In a screen for kinases that promote survival of KRAS-dependent colon cancer cells, we found that the TAK1 kinase (MAP3K7) is required for tumor cell viability. The induction of apoptosis by RNAi-mediated depletion or pharmacologic inhibition of TAK1 is linked to its suppression of hyperactivated Wnt signaling, evident in both endogenous and genetically reconstituted cells. In APC mutant/KRAS-dependent cells, KRAS stimulates BMP-7 secretion and BMP signaling, leading to TAK1 activation and enhancement of Wnt-dependent transcription. An in vitro-derived "TAK1 dependency signature'' is enriched in primary human colon cancers with mutations in both APC and KRAS, suggesting potential clinical utility in stratifying patient populations. Together, these findings identify TAK1 inhibition as a potential therapeutic strategy for a treatment-refractory subset of colon cancers exhibiting aberrant KRAS and Wnt pathway activation.
C1 [Singh, Anurag; Sweeney, Michael F.; Yu, Min; Burger, Alexa; Greninger, Patricia; Benes, Cyril; Haber, Daniel A.; Settleman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Singh, Anurag; Sweeney, Michael F.; Yu, Min; Burger, Alexa; Greninger, Patricia; Benes, Cyril; Haber, Daniel A.; Settleman, Jeff] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
EM haber@helix.mgh.harvard.edu; settleman.jeffrey@gene.com
RI Singh, Anurag/C-7347-2014
OI Singh, Anurag/0000-0003-4705-8683
FU NIH [K99 CA149169, R01 CA109447, R01 CA129933]; Lustgarten Foundation
FX This work was supported by NIH K99 CA149169 to A.S. as well as NIH R01
CA109447 and a Lustgarten Foundation grant to J.S. and NIH R01 CA129933
to D.A.H. We are grateful to Randall Peterson, David Ting, and Andre
Bernards for critical evaluation and comments on the manuscript. We
thank Laura Libby and Brian Brannigan for technical assistance with
mouse xenograft experiments and KRAS/BRAF sequencing analyses,
respectively. We thank Vijay Yajnik for providing TOP-FLASH reporter
plasmids. Finally, we also thank Kevin Haigis, Moon Yee Hang, Miguel
Rivera, Jianmin Zhang, Mingzhu Liu, and Matt Zubrowski for intellectual
and technical advice.
NR 36
TC 95
Z9 100
U1 1
U2 17
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD FEB 17
PY 2012
VL 148
IS 4
BP 639
EP 650
DI 10.1016/j.cell.2011.12.033
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 897DH
UT WOS:000300622400007
PM 22341439
ER
PT J
AU Hu, J
Hwang, SS
Liesa, M
Gan, BY
Sahin, E
Jaskelioff, M
Ding, ZH
Ying, HQ
Boutin, AT
Zhang, HL
Johnson, S
Ivanova, E
Kost-Alimova, M
Protopopov, A
Wang, YA
Shirihai, OS
Chin, L
DePinho, RA
AF Hu, Jian
Hwang, Soyoon Sarah
Liesa, Marc
Gan, Boyi
Sahin, Ergun
Jaskelioff, Mariela
Ding, Zhihu
Ying, Haoqiang
Boutin, Adam T.
Zhang, Hailei
Johnson, Shawn
Ivanova, Elena
Kost-Alimova, Maria
Protopopov, Alexei
Wang, Yaoqi Alan
Shirihai, Orian S.
Chin, Lynda
DePinho, Ronald A.
TI Antitelomerase Therapy Provokes ALT and Mitochondrial Adaptive
Mechanisms in Cancer
SO CELL
LA English
DT Article
ID OXIDATIVE DNA-DAMAGE; TELOMERE DYSFUNCTION; MRE11/RAD50/NBS1 COMPLEX;
DEPENDENT APOPTOSIS; STEM-CELLS; DEFICIENCY; MICE; SUPPRESSION;
METABOLISM; GLUTAMINE
AB To assess telomerase as a cancer therapeutic target and determine adaptive mechanisms to telomerase inhibition, we modeled telomerase reactivation and subsequent extinction in T cell lymphomas arising in Atm(-/)-mice engineered with an inducible telomerase reverse transcriptase allele. Telomerase reactivation in the setting of telomere dysfunction enabled full malignant progression with alleviation of telomere dysfunction-induced checkpoints. These cancers possessed copy number alterations targeting key loci in human T cell lymphomagenesis. Upon telomerase extinction, tumor growth eventually slowed with reinstatement of telomere dysfunction-induced checkpoints, yet growth subsequently resumed as tumors acquired alternative lengthening of telomeres (ALT) and aberrant transcriptional networks centering on mitochondrial biology and oxidative defense. ALT+ tumors acquired amplification/overexpression of PGC-1 beta, a master regulator of mitochondrial biogenesis and function, and they showed marked sensitivity to PGC-1 beta or SOD2 knockdown. Genetic modeling of telomerase extinction reveals vulnerabilities that motivate coincidental inhibition of mitochondrial maintenance and oxidative defense mechanisms to enhance antitelomerase cancer therapy.
C1 [Hu, Jian; Hwang, Soyoon Sarah; Ying, Haoqiang; Boutin, Adam T.; Kost-Alimova, Maria; Protopopov, Alexei; Wang, Yaoqi Alan; DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA.
[Gan, Boyi] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA.
[Hu, Jian; Hwang, Soyoon Sarah; Gan, Boyi; Sahin, Ergun; Jaskelioff, Mariela; Ding, Zhihu; Ying, Haoqiang; Boutin, Adam T.; Zhang, Hailei; Ivanova, Elena; Kost-Alimova, Maria; Protopopov, Alexei; Wang, Yaoqi Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Hu, Jian; Hwang, Soyoon Sarah; Gan, Boyi; Sahin, Ergun; Jaskelioff, Mariela; Ding, Zhihu; Ying, Haoqiang; Boutin, Adam T.; Zhang, Hailei; Johnson, Shawn; Ivanova, Elena; Kost-Alimova, Maria; Protopopov, Alexei; Wang, Yaoqi Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Hu, Jian; Gan, Boyi; Sahin, Ergun; Jaskelioff, Mariela; Ding, Zhihu; Ying, Haoqiang; Boutin, Adam T.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA 02115 USA.
[Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Liesa, Marc; Shirihai, Orian S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
RP DePinho, RA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
EM rdepinho@mdanderson.org
OI Liesa Roig, Marc/0000-0002-5909-8570
FU leukemia and lymphoma society; Helen Hay Whitney fellowship; Fundacion
Ramon Areces; NIH [R01-DK074778, R01-DK56690, R01CA84628, U01CA141508]
FX We thank S. Jiang, R. Narurkar, and E. Fletcher-Sananikone for excellent
mouse husbandry and care, and all members of DePinho and Chin labs for
helpful discussion. We also thank Yingchui Liu for the Cox model
analysis. J.H. and B.G. were supported by the leukemia and lymphoma
society fellowship. A.T.B. is supported by the Helen Hay Whitney
fellowship. M. L. is supported by the Fundacion Ramon Areces fellowship.
O.S.S. is supported by R01 (R01-DK074778 and R01-DK56690) grants from
NIH. L.C. and R.A.D. are supported by R01 (R01CA84628) and U01
(U01CA141508) grants from NIH. R.A.D. is an Ellison Foundation for
Medical Research Senior Scholar and an American Cancer Society Research
Professor.
NR 50
TC 96
Z9 99
U1 1
U2 35
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD FEB 17
PY 2012
VL 148
IS 4
BP 651
EP 663
DI 10.1016/j.cell.2011.12.028
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 897DH
UT WOS:000300622400008
PM 22341440
ER
PT J
AU Zhang, BC
Kracker, S
Yasuda, T
Casola, S
Vanneman, M
Homig-Holzel, C
Wang, Z
Derudder, E
Li, S
Chakraborty, T
Cotter, SE
Koyama, S
Currie, T
Freeman, GJ
Kutok, JL
Rodig, SJ
Dranoff, G
Rajewsky, K
AF Zhang, Baochun
Kracker, Sven
Yasuda, Tomoharu
Casola, Stefano
Vanneman, Matthew
Homig-Holzel, Cornelia
Wang, Zhe
Derudder, Emmanuel
Li, Shuang
Chakraborty, Tirtha
Cotter, Shane E.
Koyama, Shohei
Currie, Treeve
Freeman, Gordon J.
Kutok, Jeffery L.
Rodig, Scott J.
Dranoff, Glenn
Rajewsky, Klaus
TI Immune Surveillance and Therapy of Lymphomas Driven by Epstein-Barr
Virus Protein LMP1 in a Mouse Model
SO CELL
LA English
DT Article
ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; NF-KAPPA-B; CYTOTOXIC
T-LYMPHOCYTES; CELL-DEVELOPMENT; RECEPTOR SIGNALS; TRANSGENIC MICE;
IFN-GAMMA; IN-VITRO; RESPONSES; EXPRESSION
AB B cells infected by Epstein-Barr virus (EBV), a transforming virus endemic in humans, are rapidly cleared by the immune system, but some cells harboring the virus persist for life. Under conditions of immunosuppression, EBV can spread from these cells and cause life-threatening pathologies. We have generated mice expressing the transforming EBV latent membrane protein 1 (LMP1), mimicking a constitutively active CD40 coreceptor, specifically in B cells. Like human EBV-infected cells, LMP1(+) B cells were efficiently eliminated by T cells, and breaking immune surveillance resulted in rapid, fatal lymphoproliferation and lymphomagenesis. The lymphoma cells expressed ligands for a natural killer (NK) cell receptor, NKG2D, andcould betargetedby anNKG2D-Fc fusion protein. These experiments indicate a central role for LMP1 in the surveillance and transformation of EBV-infected B cells in vivo, establish a preclinical model for B cell lymphomagenesis in immunosuppressed patients, and validate a new therapeutic approach.
C1 [Zhang, Baochun; Kracker, Sven; Yasuda, Tomoharu; Casola, Stefano; Wang, Zhe; Derudder, Emmanuel; Li, Shuang; Chakraborty, Tirtha; Rajewsky, Klaus] Harvard Univ, Program Cellular & Mol Med, Childrens Hosp, Sch Med, Boston, MA 02115 USA.
[Zhang, Baochun; Kracker, Sven; Yasuda, Tomoharu; Casola, Stefano; Wang, Zhe; Derudder, Emmanuel; Li, Shuang; Chakraborty, Tirtha; Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Casola, Stefano; Homig-Holzel, Cornelia; Rajewsky, Klaus] Univ Cologne, Inst Genet, D-50674 Cologne, Germany.
[Vanneman, Matthew; Koyama, Shohei; Freeman, Gordon J.; Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Vanneman, Matthew; Koyama, Shohei; Freeman, Gordon J.; Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA.
[Vanneman, Matthew; Koyama, Shohei; Freeman, Gordon J.; Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA.
[Cotter, Shane E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Cotter, Shane E.] Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Sch Med, Boston, MA 02115 USA.
[Currie, Treeve; Kutok, Jeffery L.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Rajewsky, K (reprint author), Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany.
EM klaus.rajewsky@mdc-berlin.de
OI Zhang, Baochun/0000-0003-1759-1161; Koyama, Shohei/0000-0002-6897-9417
FU NIH [CA098285, CA078378, AI56299]; Leukemia and Lymphoma SCOR; Leukemia
and Lymphoma Society; JSPS; Astellas Foundation for Research on
Metabolic Disorders
FX We thank Dr. S. Cobbold for the anti-CD4, -CD8, and -Thy1 hybridomas;
Dr. L. Lanier for the CX5 hybridoma; Dr. R. Schreiber for anti-TNF alpha
(TN3-19.12) and anti-IFN gamma (H22) antibodies; Drs. E. Cahir-McFarland
and E. Kieff for MSCV-IRES-GFP- and MSCV-LMP1-IRES-GFP-expressing
vectors; Dr. D. Raulet for NKG2D-/- mice; Mr. P. Sage and Dr.
A. Sharpe for CIITA-/- mice; Drs. U. Basu, F. Meng, and F.
Alt for the anti-AID antibody; and Dr. M. Schmidt-Supprian for the
JH probe. We thank the NIH Tetramer Facility at Emory
University for the PE-conjugated mCD1d-PBS57 tetramer. We are grateful
to M. Bamberg, J. Xia, D. Ghitza, C. Grosse, X. Chen, A. Pellerin, J.
Grundy, and J. Wang for technical assistance; M. Ottaviano for
administrative assistance; S. Koralov for help with sequence analysis
and intracellular cytokine staining; S. Peng for HPRT primers; K.
Kochert for advice on statistics; and D. Calado, M. Janz, K.
Wucherpfennig, and all Rajewsky lab members for critical comments and
suggestions. This work was supported by NIH grants CA098285, CA078378,
and AI56299 and a Leukemia and Lymphoma SCOR. B.Z. is supported by a
postdoctoral fellowship of the Leukemia and Lymphoma Society. T.Y is
supported by a JSPS Postdoctoral Fellowship for Research Abroad and by
the Astellas Foundation for Research on Metabolic Disorders.
NR 50
TC 53
Z9 55
U1 0
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD FEB 17
PY 2012
VL 148
IS 4
BP 739
EP 751
DI 10.1016/j.cell.2011.12.031
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 897DH
UT WOS:000300622400015
PM 22341446
ER
PT J
AU Qiao, DH
Meyer, K
Friedl, A
AF Qiao, Dianhua
Meyer, Kristy
Friedl, Andreas
TI Glypican-1 Stimulates Skp2 Autoinduction Loop and G(1)/S Transition in
Endothelial Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ANAPHASE PROMOTING COMPLEX/CYCLOSOME; RESTRICTION POINT CONTROL;
TGF-BETA; CANCER-CELLS; CYCLIN D1; C-MYC; CDK INHIBITORS; S-PHASE;
GROWTH; DEGRADATION
AB The heparan sulfate proteoglycan glypican-1 (GPC1) is involved in tumorigenesis and angiogenesis and is overexpressed frequently in tumor and endothelial cells (ECs) in human gliomas. We demonstrated previously that in brain EC, GPC1 regulates mitotic cyclins and securin as well as mitosis and that GPC1 is required for progression through the cell cycle. To characterize the molecular mechanism underlying cell cycle regulation by GPC1, we systematically investigated its effects on key G(1)/S checkpoint regulators and on major signaling pathways reportedly activated by Dally (Division abnormally delayed) the Drosophila GPC1 homologue. We found that elevated GPC1 affected a wide range of G(1)/S checkpoint regulators, leading to inactivation of the G(1)/S checkpoint and increased S phase entry, apparently by activating the mitogen-independent Skp2 autoinduction loop. Specifically, GPC1 suppressed CDK inhibitors (CKIs), including p21, p27, p16, and p19, and the D cyclins, and induced CDK2 and Skp2. GPC1 may trigger the Skp2 autoinduction loop at least partially by suppressing p21 transcription as knockdown of p21 by RNAi can mimic the effect of GPC1 on the cell cycle regulators related to the loop. Moreover, multiple mitogenic signaling pathways, including ERK MAPK, Wnt and BMP signaling, were significantly stimulated by GPC1 as has been reported for Dally in Drosophila. Notably, the c-Myc oncoprotein, which is frequently up-regulated by both ERK and Wnt signaling and functions as a potent transcription repressor for CKIs as well as D cyclins, was also significantly induced by GPC1. These findings provide mechanistic insights into how GPC1 regulates the cell cycle and proliferation.
C1 [Qiao, Dianhua; Meyer, Kristy; Friedl, Andreas] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53705 USA.
[Friedl, Andreas] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Dept Vet Affairs Med Ctr, Madison, WI 53705 USA.
RP Friedl, A (reprint author), WIMR Room 6051,1111 Highland Ave, Madison, WI 53705 USA.
EM afriedl@wisc.edu
NR 51
TC 15
Z9 16
U1 1
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 17
PY 2012
VL 287
IS 8
BP 5898
EP 5909
DI 10.1074/jbc.M111.325282
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 897HE
UT WOS:000300638000064
PM 22203671
ER
PT J
AU Bergwitz, C
Rasmussen, MD
DeRobertis, C
Wee, MJ
Sinha, S
Chen, HH
Huang, J
Perrimon, N
AF Bergwitz, Clemens
Rasmussen, Matthew D.
DeRobertis, Charles
Wee, Mark J.
Sinha, Sumi
Chen, Hway H.
Huang, Joanne
Perrimon, Norbert
TI Roles of Major Facilitator Superfamily Transporters in Phosphate
Response in Drosophila
SO PLOS ONE
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; INORGANIC-PHOSPHATE; SACCHAROMYCES-CEREVISIAE;
VASCULAR CALCIFICATION; KINASE; CELLS; MELANOGASTER; CALCIUM; DIETARY;
FAMILY
AB The major facilitator superfamily (MFS) transporter Pho84 and the type III transporter Pho89 are responsible for metabolic effects of inorganic phosphate in yeast. While the Pho89 ortholog Pit1 was also shown to be involved in phosphate-activated MAPK in mammalian cells, it is currently unknown, whether orthologs of Pho84 have a role in phosphate-sensing in metazoan species. We show here that the activation of MAPK by phosphate observed in mammals is conserved in Drosophila cells, and used this assay to characterize the roles of putative phosphate transporters. Surprisingly, while we found that RNAi-mediated knockdown of the fly Pho89 ortholog dPit had little effect on the activation of MAPK in Drosophila S2R+ cells by phosphate, two Pho84/SLC17A1-9 MFS orthologs (MFS10 and MFS13) specifically inhibited this response. Further, using a Xenopus oocyte assay, we show that MSF13 mediates uptake of [P-33]-orthophosphate in a sodium-dependent fashion. Consistent with a role in phosphate physiology, MSF13 is expressed highest in the Drosophila crop, midgut, Malpighian tubule, and hindgut. Altogether, our findings provide the first evidence that Pho84 orthologs mediate cellular effects of phosphate in metazoan cells. Finally, while phosphate is essential for Drosophila larval development, loss of MFS13 activity is compatible with viability indicating redundancy at the levels of the transporters.
C1 [Bergwitz, Clemens; DeRobertis, Charles; Wee, Mark J.; Sinha, Sumi; Chen, Hway H.; Huang, Joanne] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Perrimon, Norbert] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA.
[Rasmussen, Matthew D.] MIT, Comp Sci & Artificial Intelligence Lab, Boston, MA USA.
RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
EM cbergwitz@partners.org
FU Harvard Catalyst; National institutes of Health, NIDDK [5K08DK078361]
FX Funding was provided by Harvard Catalyst, http://catalyst.harvard.edu/
and
http://www.google.com/url?sa=t&rct=j&rct=j&q=&q=&esrc=s&esrc=s&source=we
b&source=web&cd=3&cd=3&ved=0CC0QFjAC&url=http%3A%2F%2Fcatalyst.harvard.e
du%2Fservices%2Fpilotfunding%2Fdoc%2FHarvardCatalystyr2pilotawardees.pdf
&ei=Q7LoTsvbA4Hs0gGX_bX-CQ&usg=AFQjCNH5urQAzoFgECvnBx7291P3xQFYyQ&sig2=2
txR0jw1srrB3xu-3HwW4A, and the National institutes of Health, NIDDK
5K08DK078361. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 51
TC 9
Z9 10
U1 0
U2 19
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 16
PY 2012
VL 7
IS 2
AR e31730
DI 10.1371/journal.pone.0031730
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 925XS
UT WOS:000302796200093
PM 22359624
ER
PT J
AU Corey, KE
Zheng, H
Mendez-Navarro, J
Delgado-Borrego, A
Dienstag, JL
Chung, RT
AF Corey, Kathleen E.
Zheng, Hui
Mendez-Navarro, Jorge
Delgado-Borrego, Aymin
Dienstag, Jules L.
Chung, Raymond T.
CA HALT-C Trial Grp
TI Serum Vitamin D Levels Are Not Predictive of the Progression of Chronic
Liver Disease in Hepatitis C Patients with Advanced Fibrosis
SO PLOS ONE
LA English
DT Article
ID METABOLIC BONE-DISEASE; GROWTH-FACTOR-I; PARATHYROID-HORMONE; MINERAL
DENSITY; PROLIFERATION; CIRRHOSIS; INSULIN; MECHANISMS; EXPRESSION
AB In animal models and human cross-sectional studies, vitamin D deficiency has been associated with liver disease progression. Vitamin D supplementation has been suggested as a treatment to prevent disease progression. We sought to evaluate the role of vitamin D levels in predicting chronic liver disease development. We conducted a nested case-control study of vitamin D levels in subjects with (cases) and without (controls) liver histologic progression or clinical decompensation over the course of the HALT-C Trial. Vitamin D levels were measured at 4 points over 45 months. 129 cases and 129 aged-matched controls were included. No difference in baseline vitamin D levels were found between cases and controls. (44.8 ng/mL vs. 44.0 ng/mL, P = 0.74). Vitamin D levels declined in cases and controls over time (P = 0.0005), however, there was no difference in the level of decline (P = 0.37). Among study subjects with diabetes mellitius, baseline vitamin D levels were higher in cases, 49.9 ng/mL, than controls, 36.3 ng/mL. (P = 0.03) In addition, baseline vitamin D levels were higher in black case subjects, 32.7 ng/mL, than in black control subjects, 25.2 ng/mL (P = 0.08) No difference in vitamin D levels was found between patients with and without progression of hepatitis C-associated liver disease over 4 years. Our data do not suggest any role for vitamin D supplementation in patients with advanced chronic hepatitis C and raise the possibility that higher vitamin D levels may be associated with disease progression.
C1 [Corey, Kathleen E.; Mendez-Navarro, Jorge; Dienstag, Jules L.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Delgado-Borrego, Aymin] Univ Miami, Div Pediat Gastroenterol, Miami, FL USA.
[Corey, Kathleen E.; Dienstag, Jules L.; Chung, Raymond T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Corey, KE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
EM rtchung@partners.org
FU American College of Gastroenterology; National Institute of Diabetes &
Digestive & Kidney Diseases; National Institute of Allergy and
Infectious Diseases; National Cancer Institute; National Center for
Minority Health and Health Disparities; General Clinical Research Center
from the National Center for Research Resources, National Institutes of
Health; Clinical and Translational Science Center from the National
Center for Research Resources, National Institutes of Health;
Hoffmann-La Roche, Inc.; National Institutes of Health; University of
Massachusetts Medical Center, Worcester, MA [N01-DK-9-2326]; University
of Connecticut Health Center, Farmington, CT [M01RR-06192]; Saint Louis
University School of Medicine, St Louis, MO [N01-DK-9-2324];
Massachusetts General Hospital, Boston, MA [N01-DK-9-2319, M01RR-01066,
1 UL1 RR025758-01]; University of Colorado Denver, School of Medicine,
Aurora, CO [N01-DK-9-2327, M01RR-00051, 1 UL1 RR 025780-01]; University
of California - Irvine, Irvine, CA [N01-DK-9-2320, M01RR-00827];
University of Texas Southwestern Medical Center, Dallas, TX
[N01-DK-9-2321, M01RR-00633, 1 UL1 RR024982-01]; University of Southern
California, Los Angeles, CA [N01-DK-9-2325, M01RR-00043]; University of
Michigan Medical Center, Ann Arbor, MI [N01-DK-9-2323, M01RR-00042, 1
UL1 RR024986]; Virginia Commonwealth University Health System, Richmond,
VA [N01-DK-9-2322, M01RR-00065]; University of Washington, Seattle, WA
[N01-DK-9-2318]; New England Research Institutes, Watertown, MA
[N01-DK-9-2328]
FX This work was principally supported by a grant from the American College
of Gastroenterology. Additional support was provided by the National
Institute of Diabetes & Digestive & Kidney Diseases, the National
Institute of Allergy and Infectious Diseases, the National Cancer
Institute, the National Center for Minority Health and Health
Disparities and by General Clinical Research Center and Clinical and
Translational Science Center grants from the National Center for
Research Resources, National Institutes of Health. The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Center for Research Resources or the
National Institutes of Health. Additional funding to conduct this study
was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research
and Development Agreement with the National Institutes of Health.
Additional grants and contracts supporting the HALT-C Study are listed
in the Acknowledgement section. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.; University of Massachusetts Medical Center, Worcester, MA:
(Contract N01-DK-9-2326) Gyongyi Szabo, MD, Barbara F. Banner, MD,
Maureen Cormier, RN, Donna Giansiracusa, RN; University of Connecticut
Health Center, Farmington, CT: (Grant M01RR-06192) Herbert L. Bonkovsky,
MD, Gloria Borders, RN, Michelle Kelley, RN, ANP; Saint Louis University
School of Medicine, St Louis, MO: (Contract N01-DK-9-2324) Adrian M. Di
Bisceglie, MD, Bruce Bacon, MD, Brent Neuschwander-Tetri, MD, Elizabeth
M. Brunt, MD, Debra King, RN; Massachusetts General Hospital, Boston,
MA: (Contract N01-DK-9-2319, Grant M01RR-01066; Grant 1 UL1 RR025758-01,
Harvard Clinical and Translational Science Center) Andrea E. Reid, MD,
Atul K. Bhan, MD, Wallis A. Molchen, David P. Lundmark; University of
Colorado Denver, School of Medicine, Aurora, CO: (Contract
N01-DK-9-2327, Grant M01RR-00051, Grant 1 UL1 RR 025780-01), Gregory T.
Everson, MD, Thomas Trouillot, MD, Marcelo Kugelmas, MD, S. Russell
Nash, MD, Jennifer DeSanto, RN, Carol McKinley, RN; University of
California - Irvine, Irvine, CA: (Contract N01-DK-9-2320, Grant
M01RR-00827) Timothy R. Morgan, MD, John C. Hoefs, MD, John R. Craig,
MD, M. Mazen Jamal, MD, MPH, Muhammad Sheikh, MD, Choon Park, RN;
University of Texas Southwestern Medical Center, Dallas, TX: (Contract
N01-DK-9-2321, Grant M01RR-00633, Grant 1 UL1 RR024982-01, North and
Central Texas Clinical and Translational Science Initiative) William M.
Lee, MD, Thomas E. Rogers, MD, Peter F. Malet, MD, Janel Shelton, Nicole
Crowder, LVN, Rivka Elbein, RN, BSN, Nancy Liston, MPH; University of
Southern California, Los Angeles, CA: (Contract N01-DK-9-2325, Grant
M01RR-00043) Karen L. Lindsay, MD, MMM, Sugantha Govindarajan, MD, Carol
B. Jones, RN, Susan L. Milstein, RN; University of Michigan Medical
Center, Ann Arbor, MI: (Contract N01-DK-9-2323, Grant M01RR-00042, Grant
1 UL1 RR024986, Michigan Center for Clinical and Health Research) Anna
S. Lok, MD, Robert J. Fontana, MD, Joel K. Greenson, MD, Pamela A.
Richtmyer, LPN, CCRC, R. Tess Bonham, BS; Virginia Commonwealth
University Health System, Richmond, VA: (Contract N01-DK-9-2322, Grant
M01RR-00065) Mitchell L. Shiffman, MD, Richard K. Sterling, MD, MSc,
Melissa J. Contos, MD, A. Scott Mills, MD, Charlotte Hofmann, RN, Paula
Smith, RN; University of Washington, Seattle, WA: (Contract
N01-DK-9-2318) Chihiro Morishima, MD, David R. Gretch, MD, PhD, Minjun
Chung Apodaca, BS, ASCP, Rohit Shankar, BC, ASCP, Natalia Antonov, M.
Ed.; New England Research Institutes, Watertown, MA: (Contract
N01-DK-9-2328) Kristin K. Snow, MSc, ScD, Anne M. Stoddard, ScD, May
Yang, MPH
NR 28
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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 FEB 16
PY 2012
VL 7
IS 2
AR e27144
DI 10.1371/journal.pone.0027144
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 925XS
UT WOS:000302796200001
PM 22359532
ER
PT J
AU He, DG
Li, H
Yusuf, N
Elmets, CA
Athar, M
Katiyar, SK
Xu, H
AF He, Donggou
Li, Hui
Yusuf, Nabiha
Elmets, Craig A.
Athar, Mohammad
Katiyar, Santosh K.
Xu, Hui
TI IL-17 Mediated Inflammation Promotes Tumor Growth and Progression in the
Skin
SO PLOS ONE
LA English
DT Article
ID CD8(+) T-CELLS; INTERLEUKIN-17 FAMILY-MEMBERS; MYELOID SUPPRESSOR-CELLS;
CHEMICAL CARCINOGENESIS; IMMUNE SUPPRESSION; MOUSE SKIN; CANCER;
METASTASIS; MICROENVIRONMENT; TUMORIGENESIS
AB The mechanism for inflammation associated tumor development is a central issue for tumor biology and immunology and remains to be fully elucidated. Although IL-17 is implicated in association with inflammation mediated carcinogenesis, mechanisms are largely elusive. In the current studies, we showed that IL-17 receptor-A gene deficient (IL-17R-/-) mice were resistant to chemical carcinogen-induced cutaneous carcinogenesis, a well-established inflammation associated tumor model in the skin. The deficiency in IL-17R increased the infiltration of CD8+ T cells whereas it inhibited the infiltration of CD11b+ myeloid cells and development of myeloid derived suppressor cells. Inflammation induced skin hyperplasia and production of pro-tumor inflammatory molecules were inhibited in IL-17R-/- mice. We found that pre-existing inflammation in the skin increased the susceptibility to tumor growth, which was associated with increased development of tumor specific IL-17 producing T cells. This inflammation induced susceptibility to tumor growth was abrogated in IL-17R-/- mice. Finally, neutralizing IL-17 in mice that had already developed chemical carcinogen induced skin tumors could inhibit inflammation mediated tumor progression at late stages. These results demonstrate that IL-17 mediated inflammation is an important mechanism for inflammation mediated promotion of tumor development. The study has major implications for targeting IL-17 in prevention and treatment of tumors.
C1 [He, Donggou; Li, Hui; Yusuf, Nabiha; Elmets, Craig A.; Athar, Mohammad; Katiyar, Santosh K.; Xu, Hui] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA.
[Yusuf, Nabiha; Elmets, Craig A.; Athar, Mohammad; Katiyar, Santosh K.; Xu, Hui] Univ Alabama Birmingham, Skin Dis Res Ctr, Birmingham, AL USA.
[Yusuf, Nabiha; Elmets, Craig A.; Katiyar, Santosh K.; Xu, Hui] Birmingham VA Med Ctr, Birmingham, AL USA.
RP He, DG (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA.
EM xuhui@uab.edu
FU United States National Institutes of Health [ES017494, CA138998,
AI071041, AR46256]
FX This publication was made possible by grants (AI071041 and AR46256 [HX]
and ES017494 and CA138998 [MA]) from the United States 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 63
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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 FEB 16
PY 2012
VL 7
IS 2
AR e32126
DI 10.1371/journal.pone.0032126
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 925XS
UT WOS:000302796200131
PM 22359662
ER
PT J
AU Zhang, LL
Hong, Z
Lin, WY
Shao, RX
Goto, K
Hsu, VW
Chung, RT
AF Zhang, Leiliang
Hong, Zhi
Lin, Wenyu
Shao, Run-Xuan
Goto, Kaku
Hsu, Victor W.
Chung, Raymond T.
TI ARF1 and GBF1 Generate a PI4P-Enriched Environment Supportive of
Hepatitis C Virus Replication
SO PLOS ONE
LA English
DT Article
ID GENOTYPE 1 INFECTION; 4-KINASE III ALPHA; TELAPREVIR; PEGINTERFERON;
REGULATORS; RIBAVIRIN; LIPIDS; TRAFFICKING; RECRUITMENT; PHOSPHATASE
AB Cellular levels of phosphatidylinositol 4-phosphate (PI4P) have been shown to be upregulated during RNA replication of several viruses, including the HCV replicon model. However, whether PI4P is required in an infectious HCV model remains unknown. Moreover, it is not established whether the host transport machinery is sequestered by the generation of PI4P during HCV infection. Here we found that PI4P was enriched in HCV replication complexes when Huh7.5.1 cells were infected with JFH1. HCV replication was inhibited upon overexpression of the PI4P phosphatase Sac1. The PI4P kinase PI4KIII beta was also found to be required for HCV replication. Moreover, the vesicular transport proteins ARF1 and GBF1 colocalized with PI4KIII beta and were both required for HCV replication. During authentic HCV infection, PI4P plays an integral role in virus replication.
C1 [Zhang, Leiliang; Hong, Zhi] Chinese Acad Med Sci, Inst Pathogen Biol, Beijing 100730, Peoples R China.
[Zhang, Leiliang; Hong, Zhi] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Zhang, Leiliang; Lin, Wenyu; Shao, Run-Xuan; Goto, Kaku; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA USA.
[Hsu, Victor W.] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Sch Med, Boston, MA 02115 USA.
[Hsu, Victor W.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Zhang, LL (reprint author), Chinese Acad Med Sci, Inst Pathogen Biol, Beijing 100730, Peoples R China.
EM rtchung@partners.org
FU National Institutes of Health (NIH) [AI069939, AI082630, DK078772];
Institute of Pathogen Biology, Chinese Academy of Medical Sciences
[2011IPB108]; NIH-MGH Center for Human Immunology
FX This work was supported by grants AI069939, AI082630 and DK078772 (to
RTC) from the National Institutes of Health (NIH), 2011IPB108 from
Intramural Research Program of the Institute of Pathogen Biology,
Chinese Academy of Medical Sciences (to LZ), and NIH-MGH Center for
Human Immunology Pilot/Feasibility Study Grant (to WL). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 46
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Z9 30
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 FEB 16
PY 2012
VL 7
IS 2
AR e32135
DI 10.1371/journal.pone.0032135
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 925XS
UT WOS:000302796200132
PM 22359663
ER
PT J
AU Freudenreich, O
Basgoz, N
Fernandez-Robles, C
Larvie, M
Misdraji, J
AF Freudenreich, Oliver
Basgoz, Nesli
Fernandez-Robles, Carlos
Larvie, Mykol
Misdraji, Joseph
TI Case 5-2012: A 39-Year-Old Man with a Recent Diagnosis of HIV Infection
and Acute Psychosis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ANTIRETROVIRAL THERAPY; 1ST-EPISODE SCHIZOPHRENIA; EXTRAPYRAMIDAL
SYMPTOMS; AIDS; TUBERCULOSIS; PHENOMENOLOGY; MANAGEMENT; DEMENTIA
C1 [Freudenreich, Oliver; Fernandez-Robles, Carlos] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Larvie, Mykol] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Basgoz, Nesli] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
[Freudenreich, Oliver; Fernandez-Robles, Carlos] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Basgoz, Nesli] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Larvie, Mykol] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Misdraji, Joseph] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Freudenreich, O (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
NR 32
TC 1
Z9 1
U1 1
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 16
PY 2012
VL 366
IS 7
BP 648
EP 657
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 892IL
UT WOS:000300279800012
PM 22335743
ER
PT J
AU Moran, CJ
Forcione, D
Katz, A
AF Moran, Christopher J.
Forcione, David
Katz, Aubrey
TI Case 32-2011: A Man with Recurrent Pancreatitis REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID ERCP; GUIDELINE
C1 [Moran, Christopher J.; Forcione, David; Katz, Aubrey] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Moran, CJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 4
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 FEB 16
PY 2012
VL 366
IS 7
BP 670
EP 670
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 892IL
UT WOS:000300279800028
ER
PT J
AU Emmendorfer, T
Glassman, PA
Moore, V
Leadholm, TC
Good, CB
Cunningham, F
AF Emmendorfer, Thomas
Glassman, Peter A.
Moore, Von
Leadholm, Thomas C.
Good, Chester B.
Cunningham, Francesca
TI Monitoring adverse drug reactions across a nationwide health care system
using information technology
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Article
DE Databases; Department of Veterans Affairs; Drugs, adverse reactions;
Information; Quality assurance; Records; Technology
ID AMBULATORY-CARE; EVENTS; VETERANS
AB Purpose. The improvement and linkage of two Department of Veterans Affairs (VA) databases for monitoring adverse drug reactions (ADRs) are described, with a discussion of the potential implications for improved medication safety within the VA health care system.
Summary. Before 2007, VA had limited capability to track and evaluate ADRs across its nationwide network of health care facilities. Since then, VA has established a standardized monitoring system that has improved the reporting, analysis, and trending of ADRs reported by providers and pharmacists at individual VA facilities. The enhanced system has two components with distinct but complementary functions: the Adverse Reaction Tracking database, which is derived by extracting text-based, patient-specific information entered into the VA electronic medical record system by clinicians at the point of care; and the VA Adverse Drug Event Reporting System (VA ADERS), an external web-based portal that contains aggregated data from 146 VA facilities, with standardized coding of reported events. Both databases allow for ADR reporting at the local, regional, and national levels. The VA ADERS database permits rapid electronic reporting of certain ADRs to the federal MedWatch program. The two databases can be used in tandem for more comprehensive assessments of ADR patterns and reporting rates and to generate a wide range of benchmarking data.
Conclusion. In recent years, the refinement of two databases for ADR reporting has increased VA's capability to systematically monitor, track, and report ADRs across its national network of health care facilities. Linking the two databases has further strengthened those capabilities, enhancing medication safety practices and aiding in pharmacovigilance.
C1 [Emmendorfer, Thomas; Glassman, Peter A.] VA Pharm Benefits Management Serv, VA Ctr Medicat Safety, Hines, IL 60141 USA.
[Glassman, Peter A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Leadholm, Thomas C.] VA PBM Serv, VA ADERS, Tucson, AZ USA.
[Leadholm, Thomas C.] Consolidated Mail Outpatient Pharm, Tucson, AZ USA.
[Good, Chester B.] VA Pittsburgh Healthcare Syst, Sect Gen Med, Pittsburgh, PA USA.
RP Emmendorfer, T (reprint author), VA Pharm Benefits Management Serv, VA Ctr Medicat Safety, 1st Ave,1 Block,N Cermak Rd,Bldg 37,Room 139, Hines, IL 60141 USA.
EM thomas.emmendorfer@va.gov
NR 13
TC 6
Z9 6
U1 0
U2 7
PU AMER SOC HEALTH-SYSTEM PHARMACISTS
PI BETHESDA
PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA
SN 1079-2082
J9 AM J HEALTH-SYST PH
JI Am. J. Health-Syst. Pharm.
PD FEB 15
PY 2012
VL 69
IS 4
BP 321
EP 328
DI 10.2146/ajhp110026
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 943LM
UT WOS:000304123500011
PM 22302257
ER
PT J
AU Engler, DA
Gupta, S
Growdon, WB
Drapkin, RI
Nitta, M
Sergent, PA
Allred, SF
Gross, J
Deavers, MT
Kuo, WL
Karlan, BY
Rueda, BR
Orsulic, S
Gershenson, DM
Birrer, MJ
Gray, JW
Mohapatra, G
AF Engler, David A.
Gupta, Sumeet
Growdon, Whitfield B.
Drapkin, Ronny I.
Nitta, Mai
Sergent, Petra A.
Allred, Serena F.
Gross, Jenny
Deavers, Michael T.
Kuo, Wen-Lin
Karlan, Beth Y.
Rueda, Bo R.
Orsulic, Sandra
Gershenson, David M.
Birrer, Michael J.
Gray, Joe W.
Mohapatra, Gayatry
TI Genome Wide DNA Copy Number Analysis of Serous Type Ovarian Carcinomas
Identifies Genetic Markers Predictive of Clinical Outcome
SO PLOS ONE
LA English
DT Article
ID GYNECOLOGIC-ONCOLOGY-GROUP; HIGH-RESOLUTION ANALYSIS; TUMOR-SUPPRESSOR;
LOW-GRADE; EXPRESSION PROFILES; BREAST-CANCER; CYCLIN-E; C-MYC;
COLORECTAL-CANCER; SIGNALING PATHWAY
AB Ovarian cancer is the fifth leading cause of cancer death in women. Ovarian cancers display a high degree of complex genetic alterations involving many oncogenes and tumor suppressor genes. Analysis of the association between genetic alterations and clinical endpoints such as survival will lead to improved patient management via genetic stratification of patients into clinically relevant subgroups. In this study, we aim to define subgroups of high-grade serous ovarian carcinomas that differ with respect to prognosis and overall survival. Genome-wide DNA copy number alterations (CNAs) were measured in 72 clinically annotated, high-grade serous tumors using high-resolution oligonucleotide arrays. Two clinically annotated, independent cohorts were used for validation. Unsupervised hierarchical clustering of copy number data derived from the 72 patient cohort resulted in two clusters with significant difference in progression free survival (PFS) and a marginal difference in overall survival (OS). GISTIC analysis of the two clusters identified altered regions unique to each cluster. Supervised clustering of two independent large cohorts of high-grade serous tumors using the classification scheme derived from the two initial clusters validated our results and identified 8 genomic regions that are distinctly different among the subgroups. These 8 regions map to 8p21.3, 8p23.2, 12p12.1, 17p11.2, 17p12, 19q12, 20q11.21 and 20q13.12; and harbor potential oncogenes and tumor suppressor genes that are likely to be involved in the pathogenesis of ovarian carcinoma. We have identified a set of genetic alterations that could be used for stratification of high-grade serous tumors into clinically relevant treatment subgroups.
C1 [Engler, David A.; Allred, Serena F.] Brigham Young Univ, Dept Stat, Provo, UT 84602 USA.
[Nitta, Mai; Mohapatra, Gayatry] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Gupta, Sumeet] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Growdon, Whitfield B.; Sergent, Petra A.; Rueda, Bo R.] Massachusetts Gen Hosp, Dept Vincent Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA.
[Drapkin, Ronny I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Kuo, Wen-Lin; Gray, Joe W.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA.
[Gross, Jenny; Karlan, Beth Y.; Orsulic, Sandra] Cedars Sinai Med Ctr, Womens Canc Res Inst, Los Angeles, CA 90048 USA.
[Deavers, Michael T.; Gershenson, David M.] Univ Texas MD Anderson Canc Ctr, Dept Pathol & Gynecol Oncol, Houston, TX 77030 USA.
[Birrer, Michael J.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
RP Engler, DA (reprint author), Brigham Young Univ, Dept Stat, Provo, UT 84602 USA.
EM gmohapatra@partners.org
RI Drapkin, Ronny/E-9944-2016
OI Drapkin, Ronny/0000-0002-6912-6977
FU Office of Science, Office of Biological & Environmental Research, of the
U. S. Department of Energy [DE-AC02-05CH11231]; National Cancer
Institute [P50 CA 83639, RC4 CA 156551]; Dana Farber/Harvard Cancer
Center Ovarian SPORE [P50 CA105009]; Ovarian Cancer Research Fund;
Michael Wall Gynecologic Oncology Research Fund
FX This work was supported by the Director, Office of Science, Office of
Biological & Environmental Research, of the U. S. Department of Energy
under Contract No. DE-AC02-05CH11231, the National Cancer Institute
grant P50 CA 83639 (JWG), the National Cancer Institute grant RC4 CA
156551 (MJB), Dana Farber/Harvard Cancer Center Ovarian SPORE P50
CA105009 (SO and BRR), Ovarian Cancer Research Fund (SO and BRR), and by
the Michael Wall Gynecologic Oncology Research Fund (GM). The GOG
component was supported by the National Cancer Institute grants to the
Gynecologic Oncology Group (GOG) Administrative Office (Philip DiSaia
U10 CA027469), GOG Tissue Bank (Philip DiSaia U10CA027469 and U24
CA011479), and the GOG Statistical Data Center (John Blessing U10
CA037517). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 106
TC 18
Z9 18
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 15
PY 2012
VL 7
IS 2
AR e30996
DI 10.1371/journal.pone.0030996
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 925DP
UT WOS:000302741300033
PM 22355333
ER
PT J
AU Wurster, AL
Precht, P
Becker, KG
Wood, WH
Zhang, YQ
Wang, Z
Pazin, MJ
AF Wurster, Andrea L.
Precht, Patricia
Becker, Kevin G.
Wood, William H., III
Zhang, Yongqing
Wang, Zhong
Pazin, Michael J.
TI IL-10 transcription is negatively regulated by BAF180, a component of
the SWI/SNF chromatin remodeling enzyme
SO BMC IMMUNOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; HELPER-CELL DIFFERENTIATION; DISEASE
SUSCEPTIBILITY LOCI; EMBRYONIC STEM-CELLS; GENE-EXPRESSION; T-CELLS;
THYMOCYTE DEVELOPMENT; FACTOR GATA-3; CYCLE CONTROL; CHIP-SEQ
AB Background: SWI/SNF chromatin remodeling enzymes play a critical role in the development of T helper lymphocytes, including Th2 cells, and directly program chromatin structure at Th2 cytokine genes. Different versions of SWI/SNF complexes, including BAF and PBAF, have been described based on unique subunit composition. However, the relative role of BAF and PBAF in Th cell function and cytokine expression has not been reported.
Results: Here we examine the role of the PBAF SWI/SNF complex in Th cell development and gene expression using mice deficient for a PBAF-specific component, BAF180. We find that T cell development in the thymus and lymphoid periphery is largely normal when the BAF180 gene is deleted late in thymic development. However, BAF180-deficient Th2 cells express high levels of the immunoregulatory cytokine IL-10. BAF180 binds directly to regulatory elements in the Il-10 locus but is replaced by BAF250 BAF complexes in the absence of BAF180, resulting in increased histone acetylation and CBP recruitment to the IL-10 locus.
Conclusions: These results demonstrate that BAF180 is a repressor of IL-10 transcription in Th2 cells and suggest that the differential recruitment of different SWI/SNF subtypes can have direct consequences on chromatin structure and gene transcription.
C1 [Becker, Kevin G.; Wood, William H., III; Zhang, Yongqing] NIA, Gene Express & Genom Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Wang, Zhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
[Wurster, Andrea L.; Precht, Patricia; Pazin, Michael J.] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Pazin, MJ (reprint author), NHGRI, NIH, 5635 Fishers Lane, Bethesda, MD 20892 USA.
EM pazinm@mail.nih.gov
OI Becker, Kevin/0000-0002-6794-6656; Pazin, Michael/0000-0002-7561-3640
FU NIH, National Institute on Aging [1 Z01 AG000524]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging, 1 Z01 AG000524. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 87
TC 6
Z9 7
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2172
J9 BMC IMMUNOL
JI BMC Immunol.
PD FEB 15
PY 2012
VL 13
AR 9
DI 10.1186/1471-2172-13-9
PG 19
WC Immunology
SC Immunology
GA 919JX
UT WOS:000302322300001
PM 22336179
ER
PT J
AU Wong, JS
Iorns, E
Rheault, MN
Ward, TM
Rashmi, P
Weber, U
Lippman, ME
Faul, C
Mlodzik, M
Mundel, P
AF Wong, Jenny S.
Iorns, Elizabeth
Rheault, Michelle N.
Ward, Toby M.
Rashmi, Priyanka
Weber, Ursula
Lippman, Marc E.
Faul, Christian
Mlodzik, Marek
Mundel, Peter
TI Rescue of tropomyosin deficiency in Drosophila and human cancer cells by
synaptopodin reveals a role of tropomyosin alpha in RhoA stabilization
SO EMBO JOURNAL
LA English
DT Article
DE actin filaments; cell migration; oskar mRNA; RhoA; Smurf1
ID OSKAR MESSENGER-RNA; ACTIN CYTOSKELETON; POSTERIOR LOCALIZATION; KIDNEY
PODOCYTES; EPITHELIAL-CELLS; BINDING PROTEIN; EXPRESSION; OOCYTE;
ORGANIZATION; POLARITY
AB Tropomyosins are widespread actin-binding proteins that influence numerous cellular functions including actin dynamics, cell migration, tumour suppression, and Drosophila oocyte development. Synaptopodin is another actin-binding protein with a more restricted expression pattern in highly dynamic cell compartments such as kidney podocyte foot processes, where it promotes RhoA signalling by blocking the Smurf1-mediated ubiquitination of RhoA. Here, we show that synaptopodin has a shorter half-life but shares functional properties with the highly stable tropomyosin. Transgenic expression of synaptopodin restores oskar mRNA localization in Drosophila oocytes mutant for TmII, thereby rescuing germline differentiation and fertility. Synaptopodin restores stress fibres in tropomyosin-deficient human MDA-MB 231 breast cancer cells and TPM alpha-depleted fibroblasts. Gene silencing of TPM alpha but not TPM beta causes loss of stress fibres by promoting Smurf1-mediated ubiquitination and proteasomal degradation of RhoA. Functionally, overexpression of synaptopodin or RhoA(K6,7R) significantly reduces MDA-MB 231 cell migration. Our findings elucidate RhoA stabilization by structurally unrelated actin-binding proteins as a conserved mechanism for regulation of stress fibre dynamics and cell motility in a cell type-specific fashion. The EMBO Journal (2012) 31, 1028-1040. doi: 10.1038/emboj.2011.464; Published online 13 December 2011
C1 [Wong, Jenny S.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Iorns, Elizabeth; Ward, Toby M.; Lippman, Marc E.; Faul, Christian] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA.
[Rheault, Michelle N.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
[Rashmi, Priyanka; Mundel, Peter] Harvard Univ, Sch Med, Boston, MA USA.
[Rashmi, Priyanka; Mundel, Peter] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Weber, Ursula; Mlodzik, Marek] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY USA.
RP Mundel, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol,Dept Med, 149 13th St,Room 8-203, Charlestown, MA 02129 USA.
EM mundel.peter@mgh.harvard.edu
OI Rheault, Michelle/0000-0003-2494-3970; Iorns,
Elizabeth/0000-0002-5515-1258
FU Child Health Research Center [HD052890]; NIH [DK57683, DK062472,
EY14597]
FX We thank Miklos Erdelyi, Szeged, Hungary for providing oskar plasmid and
TmII mutant flies; the Drosophila stock center, Bloomington, IN, USA for
fly strains; and Sophy Okello, New York, NY, USA for transgenic
injections. We thank Anna Greka, Boston, MA, USA for help with confocal
microscopy. We also thank Peter Gunning Westmead, Australia for Tm1
cDNA; Tadaomi Takenawa, Tokyo, Japan for GST-RhoA(T19N) cDNA; Jeffrey
Wrana, Toronto, Canada for RhoA(K6,7R) cDNA; Keiji Tanaka, Tokyo, Japan
for HA-ubiquitin cDNA; and Takeshi Imamura (The JFCR Cancer Institute,
Tokyo, Japan) for wild-type Smurf1 and catalytically inactive
Smurf1(C710A) cDNAs. MNR was supported by a Child Health Research Center
grant HD052890. This work was supported by NIH grants DK57683 and
DK062472 to PM and EY14597 to MM. This manuscript has been used by JSW
to fulfil the requirements for obtaining a PhD degree from the Graduate
School at the Mount Sinai School of Medicine, New York, NY, USA.
NR 54
TC 12
Z9 12
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD FEB 15
PY 2012
VL 31
IS 4
BP 1028
EP 1040
DI 10.1038/emboj.2011.464
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 900FN
UT WOS:000300872100022
PM 22157816
ER
PT J
AU Cooper, RJ
Gagnon, L
Goldenholz, DM
Boas, DA
Greve, DN
AF Cooper, R. J.
Gagnon, Louis
Goldenholz, Daniel M.
Boas, David A.
Greve, Douglas N.
TI The utility of near-infrared spectroscopy in the regression of
low-frequency physiological noise from functional magnetic resonance
imaging data
SO NEUROIMAGE
LA English
DT Article
DE Near-infrared spectroscopy; Functional magnetic resonance imaging;
Low-frequency oscillations; Resting state
ID EVENT-RELATED FMRI; SURFACE-BASED ANALYSIS; HUMAN BRAIN; BOLD SIGNAL;
RESPONSE FUNCTION; NEURONAL-ACTIVITY; CONCURRENT FMRI; BALLOON MODEL;
ACTIVATION; NIRS
AB Near-infrared spectroscopy (NIRS) signals have been shown to correlate with resting-state BOLD-fMRI data across the whole brain volume, particularly at frequencies below 0.1 Hz. While the physiological origins of this correlation remain unclear, its existence may have a practical application in minimizing the background physiological noise present in BOLD-fMRI recordings. We performed simultaneous, resting-state fMRI and 28-channel NIRS in seven adult subjects in order to assess the utility of NIRS signals in the regression of physiological noise from fMRI data. We calculated the variance of the residual error in a general linear model of the baseline fMRI signal, and the reduction of this variance achieved by including NIRS signals in the model. In addition, we introduced a sequence of simulated hemodynamic response functions (HRFs) into the resting-state fMRI data of each subject in order to quantify the effectiveness of NIRS signals in optimizing the recovery of that HRF. For comparison, these calculations were also performed using a pulse and respiration RETROICOR model. Our results show that the use of 10 or more NIRS channels can reduce variance in the residual error by as much as 36% on average across the whole cortex. However the same number of low-pass filtered white noise regressors is shown to produce a reduction of 19%. The RETROICOR model obtained a variance reduction of 6.4%. Our HRF simulation showed that the mean-squared error (MSE) between the recovered and true HRFs is reduced by 21% on average when 10 NIRS channels are applied and by introducing an optimized time lag between the NIRS and fMRI time series, a single NIRS channel can provide an average MSE reduction of 14%. The RETROICOR model did not provide a significant change in MSE. By each of the metrics calculated, NIRS recording is shown to be of significant benefit to the regression of low-frequency physiological noise from fMRI data. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Cooper, R. J.; Gagnon, Louis; Goldenholz, Daniel M.; Boas, David A.; Greve, Douglas N.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA USA.
[Gagnon, Louis] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Gagnon, Louis] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
RP Cooper, RJ (reprint author), Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA USA.
EM rcooper@nmr.mgh.harvard.edu
OI Goldenholz, Daniel/0000-0002-8370-2758
FU NIH [P41-RR14075, R01-EB006385]; Fond Quebecois de Recherche sur la
Nature et les Technologies
FX This work was supported by NIH grants P41-RR14075 and R01-EB006385. L
Gagnon is supported by the Fond Quebecois de Recherche sur la Nature et
les Technologies.
NR 42
TC 17
Z9 17
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 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD FEB 15
PY 2012
VL 59
IS 4
BP 3128
EP 3138
DI 10.1016/j.neuroimage.2011.11.028
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 903BG
UT WOS:000301090100007
PM 22119653
ER
PT J
AU Gutchess, AH
Schacter, DL
AF Gutchess, Angela H.
Schacter, Daniel L.
TI The neural correlates of gist-based true and false recognition
SO NEUROIMAGE
LA English
DT Article
DE Memory; False recognition; Gist; fMRI; Hippocampus
ID CONSTRUCTIVE EPISODIC SIMULATION; FUZZY-TRACE THEORY; EVENT-RELATED
FMRI; COGNITIVE NEUROSCIENCE; FUTURE EVENTS; SOURCE MEMORY;
OLDER-ADULTS; PATTERN SEPARATION; LOBE CONTRIBUTIONS; YOUNGER ADULTS
AB When information is thematically related to previously studied information, gist-based processes contribute to false recognition. Using functional MRI, we examined the neural correlates of gist-based recognition as a function of increasing numbers of studied exemplars. Sixteen participants incidentally encoded small, medium, and large sets of pictures, and we compared the neural response at recognition using parametric modulation analyses. For hits, regions in middle occipital, middle temporal, and posterior parietal cortex linearly modulated their activity according to the number of related encoded items. For false alarms, visual, parietal, and hippocampal regions were modulated as a function of the encoded set size. The present results are consistent with prior work in that the neural regions supporting veridical memory also contribute to false memory for related information. The results also reveal that these regions respond to the degree of relatedness among similar items, and implicate perceptual and constructive processes in gist-based false memory. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Gutchess, Angela H.] Brandeis Univ, Dept Psychol, Waltham, MA 02454 USA.
[Gutchess, Angela H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Schacter, Daniel L.] Harvard Univ, Cambridge, MA 02138 USA.
RP Gutchess, AH (reprint author), Brandeis Univ, Dept Psychol, MS 062,POB 549110, Waltham, MA 02454 USA.
EM gutchess@brandeis.edu
OI Schacter, Daniel/0000-0002-2460-6061
FU National Institutes of Health [NIMH R01 MH60941, NIA F32 AG026920];
National Center for Research Resources [P41 RR14075]; MIND Institute
FX The authors gratefully acknowledge support from the National Institutes
of Health, grants NIMH R01 MH60941 (to DLS) and NIA F32 AG026920 (to
AHG). Portions of this research were conducted when A.H.G. was a fellow
of the American Federation for Aging Research. The Athinoula A. Martinos
Center for Biomedical Imaging is supported by the National Center for
Research Resources (grant P41 RR14075) and by the MIND Institute. We
thank Elizabeth Kensinger and Rachel Garoff Eaton for helpful
discussions, and Donna Rose Addis for generously sharing her expertise
and insights.
NR 68
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U1 2
U2 30
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD FEB 15
PY 2012
VL 59
IS 4
BP 3418
EP 3426
DI 10.1016/j.neuroimage.2011.11.078
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 903BG
UT WOS:000301090100038
PM 22155331
ER
PT J
AU Dykstra, AR
Chan, AM
Quinn, BT
Zepeda, R
Keller, CJ
Cormier, J
Madsen, JR
Eskandar, EN
Cash, SS
AF Dykstra, Andrew R.
Chan, Alexander M.
Quinn, Brian T.
Zepeda, Rodrigo
Keller, Corey J.
Cormier, Justine
Madsen, Joseph R.
Eskandar, Emad N.
Cash, Sydney S.
TI Individualized localization and cortical surface-based registration of
intracranial electrodes
SO NEUROIMAGE
LA English
DT Article
DE Electrocorticography; Image registration; Epilepsy; CT; MRI
ID BRAIN-COMPUTER-INTERFACE; SUBDURAL ELECTRODES; EPILEPSY SURGERY;
FUNCTIONAL ARCHITECTURE; DIGITAL PHOTOGRAPHY; COORDINATE SYSTEM; CORTEX;
MRI; COREGISTRATION; RECONSTRUCTION
AB In addition to its widespread clinical use, the intracranial electroencephalogram (iEEG) is increasingly being employed as a tool to map the neural correlates of normal cognitive function as well as for developing neuroprosthetics. Despite recent advances, and unlike other established brain-mapping modalities (e.g. functional MRI, magneto- and electroencephalography), registering the iEEG with respect to neuroanatomy in individuals and coregistering functional results across subjects remains a significant challenge. Here we describe a method which coregisters high-resolution preoperative MRI with postoperative computerized tomography (CT) for the purpose of individualized functional mapping of both normal and pathological (e.g., interictal discharges and seizures) brain activity. Our method accurately (within 3 mm, on average) localizes electrodes with respect to an individual's neuroanatomy. Furthermore, we outline a principled procedure for either volumetric or surface-based group analyses. We demonstrate our method in five patients with medically-intractable epilepsy undergoing invasive monitoring of the seizure focus prior to its surgical removal. The straight-forward application of this procedure to all types of intracranial electrodes, robustness to deformations in both skull and brain, and the ability to compare electrode locations across groups of patients makes this procedure an important tool for basic scientists as well as clinicians. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Dykstra, Andrew R.] MIT, Harvard Mit Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA.
[Chan, Alexander M.] MIT, Harvard Mit Div Hlth Sci & Technol, Program Med Engn & Med Phys, Cambridge, MA 02139 USA.
[Dykstra, Andrew R.; Chan, Alexander M.; Zepeda, Rodrigo; Keller, Corey J.; Cormier, Justine; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Cort Physiol Lab, Boston, MA 02114 USA.
[Dykstra, Andrew R.; Chan, Alexander M.; Zepeda, Rodrigo; Keller, Corey J.; Cormier, Justine; Madsen, Joseph R.; Eskandar, Emad N.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA USA.
[Quinn, Brian T.] NYU, Sch Med, New York, NY USA.
[Madsen, Joseph R.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
RP Dykstra, AR (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA.
EM adykstra@mit.edu
OI Keller, Corey/0000-0003-0529-3490
FU NIBIB NIH HHS [T32 EB001680, T32 EB001680-06A2]; NIDCD NIH HHS [T32
DC000038, T32 DC000038-15, T32 DC000038-15S1, T32 DC000038-16, T32
DC000038-17, T32 DC000038-18, T32 DC000038-19, T32 DC000038-20]; NINDS
NIH HHS [R01 NS062092, R01 NS062092-01A2, R01 NS062092-02, R01
NS062092-03]
NR 42
TC 47
Z9 47
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD FEB 15
PY 2012
VL 59
IS 4
BP 3563
EP 3570
DI 10.1016/j.neuroimage.2011.11.046
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 903BG
UT WOS:000301090100052
PM 22155045
ER
PT J
AU Gagnon, L
Yucel, MA
Dehaes, M
Cooper, RJ
Perdue, KL
Selb, J
Huppert, TJ
Hoge, RD
Boas, DA
AF Gagnon, Louis
Yuecel, Meryem A.
Dehaes, Mathieu
Cooper, Robert J.
Perdue, Katherine L.
Selb, Juliette
Huppert, Theodore J.
Hoge, Richard D.
Boas, David A.
TI Quantification of the cortical contribution to the NIRS signal over the
motor cortex using concurrent NIRS-fMRI measurements
SO NEUROIMAGE
LA English
DT Article
DE NIRS-fMRI; Pial vasculature; Balloon Model; Monte Carlo simulations
ID NEAR-INFRARED SPECTROSCOPY; CEREBRAL OXYGEN-METABOLISM; BRAIN
ACTIVATION; BALLOON MODEL; BLOOD-VOLUME; RESPONSES; DYNAMICS; BOLD;
FLOW; RESOLUTION
AB Near-Infrared Spectroscopy (NIRS) measures the functional hemodynamic response occurring at the surface of the cortex. Large pial veins are located above the surface of the cerebral cortex. Following activation, these veins exhibit oxygenation changes but their volume likely stays constant. The back-reflection geometry of the NIRS measurement renders the signal very sensitive to these superficial pial veins. As such, the measured NIRS signal contains contributions from both the cortical region as well as the pial vasculature. In this work, the cortical contribution to the NIRS signal was investigated using (1) Monte Carlo simulations over a realistic geometry constructed from anatomical and vascular MRI and (2) multimodal NIRS-BOLD recordings during motor stimulation. A good agreement was found between the simulations and the modeling analysis of in vivo measurements. Our results suggest that the cortical contribution to the deoxyhemoglobin signal change (Delta HbR) is equal to 16-22% of the cortical contribution to the total hemoglobin signal change (Delta HbT). Similarly, the cortical contribution of the oxyhemoglobin signal change (,Delta HbO) is equal to 73-79% of the cortical contribution to the Delta HbT signal. These results suggest that Delta HbT is far less sensitive to pial vein contamination and therefore, it is likely that the Delta HbT signal provides better spatial specificity and should be used instead of Delta HbO or Delta HbR to map cerebral activity with NIRS. While different stimuli will result in different pial vein contributions, our finger tapping results do reveal the importance of considering the pial contribution. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Gagnon, Louis; Yuecel, Meryem A.; Cooper, Robert J.; Selb, Juliette; Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA.
[Gagnon, Louis; Boas, David A.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Gagnon, Louis] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Dehaes, Mathieu] Harvard Univ, Sch Med, Boston, MA USA.
[Dehaes, Mathieu] Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA 02115 USA.
[Perdue, Katherine L.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.
[Huppert, Theodore J.] Univ Pittsburgh, Dept Radiol & Bioengn, Pittsburgh, PA USA.
[Hoge, Richard D.] Univ Montreal, Dept Physiol & Biomed Engn, Montreal, PQ, Canada.
[Hoge, Richard D.] Univ Montreal, CRIUGM, Montreal, PQ, Canada.
RP Gagnon, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA.
EM lgagnon@nmr.mgh.harvard.edu
RI Perdue, Katherine/D-4306-2013;
OI Perdue, Katherine/0000-0003-2846-3149; Cooper,
Robert/0000-0001-6696-8020
FU NIH [P41-RR14075, R01-EB006385]; Fonds Quebecois sur la Nature et les
Technologies
FX We want to thank Qianqian Fang for providing the Monte Carlo code used
in this study as well as providing useful advice. The authors are also
grateful to Sungho Tak, Yunjie Tong, Blaise deB. Frederick and Evgeniya
Kirilina for fruitful discussions. This work was supported by NIH grants
P41-RR14075 and R01-EB006385. L. Gagnon was supported by the Fonds
Quebecois sur la Nature et les Technologies.
NR 32
TC 73
Z9 73
U1 2
U2 14
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD FEB 15
PY 2012
VL 59
IS 4
BP 3933
EP 3940
DI 10.1016/j.neuroimage.2011.10.054
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 903BG
UT WOS:000301090100086
PM 22036999
ER
PT J
AU Tobin, MJ
AF Tobin, Martin J.
TI Extubation and the Myth of "Minimal Ventilator Settings"
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID PRESSURE SUPPORT VENTILATION; MECHANICAL VENTILATION; WEANING PATIENTS;
FAILURE; AIRWAY
C1 [Tobin, Martin J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA.
[Tobin, Martin J.] Loyola Univ Chicago, Stritch Sch Med, Hines, IL USA.
RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA.
NR 13
TC 22
Z9 22
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD FEB 15
PY 2012
VL 185
IS 4
BP 349
EP 350
DI 10.1164/rccm.201201-0050ED
PG 3
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 897EY
UT WOS:000300629900003
PM 22336673
ER
PT J
AU Desmedt, C
Majjaj, S
Kheddoumi, N
Singhal, SK
Haibe-Kains, B
El Ouriaghli, F
Chaboteaux, C
Michiels, S
Lallemand, F
Journe, F
Duvillier, H
Loi, S
Quackenbush, J
Dekoninck, S
Blanpain, C
Lagneaux, L
Houhou, N
Delorenzi, M
Larsimont, D
Piccart, M
Sotiriou, C
AF Desmedt, Christine
Majjaj, Samira
Kheddoumi, Naima
Singhal, Sandeep K.
Haibe-Kains, Benjamin
El Ouriaghli, Frank
Chaboteaux, Carole
Michiels, Stefan
Lallemand, Francoise
Journe, Fabrice
Duvillier, Hughes
Loi, Sherene
Quackenbush, John
Dekoninck, Sophie
Blanpain, Cedric
Lagneaux, Laurence
Houhou, Nawal
Delorenzi, Mauro
Larsimont, Denis
Piccart, Martine
Sotiriou, Christos
TI Characterization and Clinical Evaluation of CD10(+) Stroma Cells in the
Breast Cancer Microenvironment
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GENE-EXPRESSION SIGNATURES; IN-SITU; TUMOR MICROENVIRONMENT; METASTASIS;
PROGRESSION; CARCINOMAS; TRANSITION; RESISTANCE; SURVIVAL; SUBTYPES
AB Purpose: There is growing evidence that interaction between stromal and tumor cells is pivotal in breast cancer progression and response to therapy. Based on earlier research suggesting that during breast cancer progression, striking changes occur in CD10(+) stromal cells, we aimed to better characterize this cell population and its clinical relevance.
Experimental Design: We developed a CD10(+) stroma gene expression signature (using HG U133 Plus 2.0) on the basis of the comparison of CD10 cells isolated from tumoral (n = 28) and normal (n = 3) breast tissue. We further characterized the CD10(+) cells by coculture experiments of representative breast cancer cell lines with the different CD10(+) stromal cell types (fibroblasts, myoepithelial, and mesenchymal stem cells). We then evaluated its clinical relevance in terms of in situ to invasive progression, invasive breast cancer prognosis, and prediction of efficacy of chemotherapy using publicly available data sets.
Results: This 12-gene CD10(+) stroma signature includes, among others, genes involved in matrix remodeling (MMP11, MMP13, and COL10A1) and genes related to osteoblast differentiation (periostin). The coculture experiments showed that all 3 CD10(+) cell types contribute to the CD10(+) stroma signature, although mesenchymal stem cells have the highest CD10(+) stroma signature score. Of interest, this signature showed an important role in differentiating in situ from invasive breast cancer, in prognosis of the HER2(+) subpopulation of breast cancer only, and potentially in nonresponse to chemotherapy for those patients.
Conclusions: Our results highlight the importance of CD10(+) cells in breast cancer prognosis and efficacy of chemotherapy, particularly within the HER2(+) breast cancer disease. Clin Cancer Res; 18(4); 1004-14. (C)2012 AACR.
C1 [Desmedt, Christine; Majjaj, Samira; Kheddoumi, Naima; Singhal, Sandeep K.; Haibe-Kains, Benjamin; El Ouriaghli, Frank; Chaboteaux, Carole; Michiels, Stefan; Lallemand, Francoise; Loi, Sherene; Sotiriou, Christos] Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab JC Heuson, B-1000 Brussels, Belgium.
[Journe, Fabrice] Univ Libre Bruxelles, Inst Jules Bordet, Lab Oncol & Expt Surg, B-1000 Brussels, Belgium.
[Duvillier, Hughes] Univ Libre Bruxelles, Inst Jules Bordet, Dept Flow Cytometry, B-1000 Brussels, Belgium.
[Dekoninck, Sophie; Blanpain, Cedric] Inst Jules Bordet, Interdisciplinary Res Inst IRIBHM, B-1000 Brussels, Belgium.
[Lagneaux, Laurence] Inst Jules Bordet, Dept Expt Hematol, B-1000 Brussels, Belgium.
[Larsimont, Denis] Inst Jules Bordet, Dept Pathol, B-1000 Brussels, Belgium.
[Piccart, Martine; Sotiriou, Christos] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium.
[Haibe-Kains, Benjamin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Computat Biol & Funct Genom Lab,Ctr Canc Computat, Boston, MA 02115 USA.
[Houhou, Nawal; Delorenzi, Mauro] CHU Vaudois, Dept Format & Rech, CH-1011 Lausanne, Switzerland.
RP Desmedt, C (reprint author), Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab JC Heuson, 125 Bld Waterloo, B-1000 Brussels, Belgium.
EM christine.desmedt@bordet.be
RI Michiels, Stefan/L-1516-2013; Loi, Sherene/H-1979-2016; Haibe-Kains,
Benjamin/D-3702-2011;
OI Michiels, Stefan/0000-0002-6963-2968; Loi, Sherene/0000-0001-6137-9171;
Haibe-Kains, Benjamin/0000-0002-7684-0079; Desmedt,
Christine/0000-0002-5223-5579
FU MEDIC Foundation; Les Amis de l'Institut Bordet; Fonds National de la
Recherche Scientifique; Brussels Region
FX This project was supported by the MEDIC Foundation, Les Amis de
l'Institut Bordet, the "Fonds National de la Recherche Scientifique,"
and the Brussels Region (Impulse Programme 2007).
NR 36
TC 22
Z9 23
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD FEB 15
PY 2012
VL 18
IS 4
BP 1004
EP 1014
DI 10.1158/1078-0432.CCR-11-0383
PG 11
WC Oncology
SC Oncology
GA 897EO
UT WOS:000300628100011
PM 22235100
ER
PT J
AU Chau, BN
Xin, CY
Hartner, J
Ren, SY
Castano, AP
Linn, G
Li, J
Tran, PT
Kaimal, V
Huang, XQ
Chang, AN
Li, SY
Kalra, A
Grafals, M
Portilla, D
MacKenna, DA
Orkin, SH
Duffield, JS
AF Chau, B. Nelson
Xin, Cuiyan
Hartner, Jochen
Ren, Shuyu
Castano, Ana P.
Linn, Geoffrey
Li, Jian
Tran, Phong T.
Kaimal, Vivek
Huang, Xinqiang
Chang, Aaron N.
Li, Shenyang
Kalra, Aarti
Grafals, Monica
Portilla, Didier
MacKenna, Deidre A.
Orkin, Stuart H.
Duffield, Jeremy S.
TI MicroRNA-21 Promotes Fibrosis of the Kidney by Silencing Metabolic
Pathways
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID ACTIVATED RECEPTOR-ALPHA; MEMBRANE-PROTEIN; OXIDATIVE STRESS; PEROXISOME
PROLIFERATORS; MPV17-LIKE PROTEIN; ENERGY-METABOLISM; EXPRESSION DATA;
RENAL FIBROSIS; INJURY; MICE
AB Scarring of the kidney is a major public health concern, directly promoting loss of kidney function. To understand the role of microRNA (miRNA) in the progression of kidney scarring in response to injury, we investigated changes in miRNA expression in two kidney fibrosis models and identified 24 commonly up-regulated miRNAs. Among them, miR-21 was highly elevated in both animal models and in human transplanted kidneys with nephropathy. Deletion of miR-21 in mice resulted in no overt abnormality. However, miR-21(-/-) mice suffered far less interstitial fibrosis in response to kidney injury, a phenotype duplicated in wild-type mice treated with anti-miR-21 oligonucleotides. Global derepression of miR-21 target mRNAs was readily detectable in miR-21(-/-) kidneys after injury. Analysis of gene expression profiles up-regulated in the absence of miR-21 identified groups of genes involved in metabolic pathways, including the lipid metabolism pathway regulated by peroxisome proliferator-activated receptor-alpha (Ppar alpha), a direct miR-21 target. Overexpression of Ppar alpha prevented ureteral obstruction-induced injury and fibrosis. Ppar alpha deficiency abrogated the antifibrotic effect of anti-miR-21 oligonucleotides. miR-21 also regulated the redox metabolic pathway. The mitochondrial inhibitor of reactive oxygen species generation Mpv17l was repressed by miR-21, correlating closely with enhanced oxidative kidney damage. These studies demonstrate that miR-21 contributes to fibrogenesis and epithelial injury in the kidney in two mouse models and is a candidate target for antifibrotic therapies.
C1 [Chau, B. Nelson; Li, Jian; Tran, Phong T.; Kaimal, Vivek; Huang, Xinqiang; Chang, Aaron N.; MacKenna, Deidre A.] Regulus Therapeut, San Diego, CA 92121 USA.
[Xin, Cuiyan; Ren, Shuyu; Linn, Geoffrey; Duffield, Jeremy S.] Univ Washington, Div Nephrol, Ctr Lung Biol, Dept Med, Seattle, WA 98109 USA.
[Xin, Cuiyan; Ren, Shuyu; Linn, Geoffrey; Duffield, Jeremy S.] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98109 USA.
[Hartner, Jochen; Orkin, Stuart H.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Hartner, Jochen; Castano, Ana P.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Li, Shenyang; Portilla, Didier] Univ Arkansas Med Sci, Div Nephrol, Little Rock, AR 72205 USA.
[Kalra, Aarti] Lahey Clin Med Ctr, Div Pathol, Burlington, MA 01805 USA.
[Grafals, Monica] Lahey Clin Med Ctr, Div Transplantat, Burlington, MA 01805 USA.
[Grafals, Monica] Tufts Univ, Boston, MA 02110 USA.
RP Chau, BN (reprint author), Regulus Therapeut, San Diego, CA 92121 USA.
EM nchau@regulusrx.com; jeremysd@u.washington.edu
FU NIH [DK73299, DK84077, DK87389, DK75976]; Genzyme GRIP; University of
Washington; Regulus Therapeutics; Veterans Affairs Merit Award
FX Funding: The Duffield Lab is funded by NIH grants DK73299, DK84077, and
DK87389; Genzyme GRIP Award; University of Washington; and a research
agreement from Regulus Therapeutics. D. P. is funded by NIH grant
DK75976 and a Veterans Affairs Merit Award.
NR 58
TC 85
Z9 92
U1 3
U2 26
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 15
PY 2012
VL 4
IS 121
AR 121ra18
DI 10.1126/scitranslmed.3003205
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 898HR
UT WOS:000300732600002
PM 22344686
ER
PT J
AU Wang, Y
Shi, M
Chung, KA
Zabetian, CP
Leverenz, JB
Berg, D
Srulijes, K
Trojanowski, JQ
Lee, VMY
Siderowf, AD
Hurtig, H
Litvan, I
Schiess, MC
Peskind, ER
Masuda, M
Hasegawa, M
Lin, XM
Pan, C
Galasko, D
Goldstein, DS
Jensen, PH
Yang, H
Cain, KC
Zhang, J
AF Wang, Yu
Shi, Min
Chung, Kathryn A.
Zabetian, Cyrus P.
Leverenz, James B.
Berg, Daniela
Srulijes, Karin
Trojanowski, John Q.
Lee, Virginia M. -Y.
Siderowf, Andrew D.
Hurtig, Howard
Litvan, Irene
Schiess, Mya C.
Peskind, Elaine R.
Masuda, Masami
Hasegawa, Masato
Lin, Xiangmin
Pan, Catherine
Galasko, Douglas
Goldstein, David S.
Jensen, Poul Henning
Yang, Hui
Cain, Kevin C.
Zhang, Jing
TI Phosphorylated alpha-Synuclein in Parkinson's Disease
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID PROGRESSIVE SUPRANUCLEAR PALSY; MULTIPLE-SYSTEM ATROPHY; HUMAN
CEREBROSPINAL-FLUID; RICHARDSONS-SYNDROME; CONSENSUS STATEMENT;
ALZHEIMERS-DISEASE; PSP-PARKINSONISM; LEWY BODIES; DIAGNOSIS;
NEURODEGENERATION
AB Phosphorylated alpha-synuclein (PS-129), a protein implicated in the pathogenesis of Parkinson's disease (PD), was identified by mass spectrometry in human cerebrospinal fluid (CSF). A highly sensitive and specific assay was established and used to measure PS-129 together with total alpha-synuclein in the CSF of patients with PD, other parkinsonian disorders such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), and healthy individuals (a total of similar to 600 samples). PS-129 CSF concentrations correlated weakly with PD severity and, when combined with total alpha-synuclein concentrations in CSF, contributed to distinguishing PD from MSA and PSP. Further rigorous validation in independent cohorts of patients, especially those where samples have been collected longitudinally, will determine whether the concentration of PS-129 in CSF will be useful for diagnosing PD and for monitoring PD severity and progression.
C1 [Wang, Yu; Shi, Min; Lin, Xiangmin; Pan, Catherine; Yang, Hui; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA.
[Wang, Yu] Huazhong Univ Sci & Technol, Dept Neurosurg, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Hubei, Peoples R China.
[Chung, Kathryn A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
[Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA.
[Zabetian, Cyrus P.; Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98104 USA.
[Leverenz, James B.; Peskind, Elaine R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA.
[Leverenz, James B.; Peskind, Elaine R.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA.
[Berg, Daniela; Srulijes, Karin] Univ Tubingen, Dept Neurodegenerat, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany.
[Berg, Daniela; Srulijes, Karin] Univ Tubingen, German Ctr Neurodegenerat Dis, D-72076 Tubingen, Germany.
[Trojanowski, John Q.; Lee, Virginia M. -Y.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Inst Aging,Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA.
[Siderowf, Andrew D.; Hurtig, Howard] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19107 USA.
[Litvan, Irene] Univ Louisville, Sch Med, Div Movement Disorders, Louisville, KY 40202 USA.
[Schiess, Mya C.] Univ Texas Hlth Sci Ctr, Dept Neurol, Houston, TX 77030 USA.
[Masuda, Masami; Hasegawa, Masato] Tokyo Metropolitan Inst Med Sci, Dept Neuropathol & Cell Biol, Setagaya Ku, Tokyo 1568585, Japan.
[Goldstein, David S.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Goldstein, David S.] NINDS, Clin Neurocardiol Sect, Community Networks Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
[Jensen, Poul Henning] Aarhus Univ, Dept Med Chem, DK-8000 Aarhus C, Denmark.
[Cain, Kevin C.] Univ Washington, Dept Biostat, Seattle, WA 98105 USA.
RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA.
EM zhangj@uw.edu
RI Shi, Min/G-6165-2012;
OI Shi, Min/0000-0002-6901-2558; , xiangmin/0000-0001-9128-689X
FU NIH [AG025327, AG033398, ES004696-5897, ES007033-6364, NS057567,
NS060252, NS062684, NS065070, NS053488]; Lundbeck Foundation; European
Community [241791]; Avid Radiopharmaceuticals
FX Funding: The investigation was supported by the NIH (grants AG025327,
AG033398, ES004696-5897, ES007033-6364, NS057567, and NS060252 to J.Z.;
NS062684 to J.Z., C. P.Z., and J.B.L.; NS065070 to C. P.Z.; and NS053488
to J.Q.T., V.M.-Y.L., and A. D. S.), the Lundbeck Foundation, and the
European Community's Seventh Framework Programme (FP7/2007-2013) under
grant agreement no. 241791 (to P.H.J.).; Competing interests: A. D. S.
serves as a consultant for Teva Neuroscience and has grant support from
Avid Radiopharmaceuticals not related to this investigation. J.B.L.
serves as a consultant for Bayer, Novartis, and Teva Neuroscience. The
other authors declare that they have no competing interests.
NR 32
TC 30
Z9 30
U1 2
U2 19
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 15
PY 2012
VL 4
IS 121
AR 121ra20
DI 10.1126/scitranslmed.3002566
PG 8
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 898HR
UT WOS:000300732600004
PM 22344688
ER
PT J
AU Yue, XM
Biederman, I
Mangini, MC
von der Malsburg, C
Amir, O
AF Yue, Xiaomin
Biederman, Irving
Mangini, Michael C.
von der Malsburg, Christoph
Amir, Ori
TI Predicting the psychophysical similarity of faces and non-face complex
shapes by image-based measures
SO VISION RESEARCH
LA English
DT Article
DE Scaling shape similarity; Face discrimination; Gabor filtering; Shape
discriminability
ID LATERAL OCCIPITAL COMPLEX; HUMAN EXTRASTRIATE CORTEX; INFERIOR TEMPORAL
CORTEX; OBJECT RECOGNITION; VISUAL AWARENESS; VIEWPOINT INVARIANCE;
FEATURES; AREA; ARCHITECTURE; RESPONSES
AB Shape representation is accomplished by a series of cortical stages in which cells in the first stage (V1) have local receptive fields tuned to contrast at a particular scale and orientation, each well modeled as a Gabor filter. In succeeding stages, the representation becomes largely invariant to Gabor coding (Kobatake & Tanaka, 1994). Because of the non-Gabor tuning in these later stages, which must be engaged for a behavioral response (Tong, 2003; Tong et al., 1998), a V1-based measure of shape similarity based on Gabor filtering would not be expected to be highly correlated with human performance when discriminating complex shapes (faces and teeth-like blobs) that differ metrically on a two-choice, match-to-sample task. Here we show that human performance is highly correlated with Gabor-based image measures (Gabor simple and complex cells), with values often in the mid 0.90s, even without discounting the variability in the speed and accuracy of performance not associated with the similarity of the distractors. This high correlation is generally maintained through the stages of HMAX, a model that builds upon the Gabor metric and develops units for complex features and larger receptive fields. This is the first report of the psychophysical similarity of complex shapes being predictable from a biologically motivated, physical measure of similarity. As accurate as these measures were for accounting for metric variation, a simple demonstration showed that all were insensitive to viewpoint invariant (nonaccidental) differences in shape. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Yue, Xiaomin] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Biederman, Irving; Amir, Ori] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA.
[Biederman, Irving; Amir, Ori] Univ So Calif, Neurosci Program, Los Angeles, CA 90089 USA.
[Mangini, Michael C.] Concordia Coll, Dept Psychol, Morehead, MN 56562 USA.
[von der Malsburg, Christoph] Frankfurt Inst Adv Studies, D-60438 Frankfurt, Germany.
RP Yue, XM (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA.
EM xiaomin@nmr.mgh.harvard.edu
FU National Science Foundation [0531177, 0617699]
FX This work was supported by the National Science Foundation Grant numbers
0531177 and 0617699 to I.B. We thank Bosco Tjan for helpful discussions.
NR 31
TC 13
Z9 13
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD FEB 15
PY 2012
VL 55
BP 41
EP 46
DI 10.1016/j.visres.2011.12.012
PG 6
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 899GK
UT WOS:000300804200006
PM 22248730
ER
PT J
AU Yeo, KK
Li, S
Amsterdam, EA
Wang, TY
Bhatt, DL
Saucedo, JF
Kontos, MC
Roe, MT
French, WJ
AF Yeo, Khung Keong
Li, Shuang
Amsterdam, Ezra A.
Wang, Tracy Y.
Bhatt, Deepak L.
Saucedo, Jorge F.
Kontos, Michael C.
Roe, Matthew T.
French, William J.
TI Comparison of Clinical Characteristics, Treatments and Outcomes of
Patients With ST-Elevation Acute Myocardial Infarction With Versus
Without New or Presumed New Left Bundle Branch Block (from NCDR (R))
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID CORONARY-ARTERY DISEASE; ACUTE HEART-FAILURE; MORTALITY; TROPONIN;
THERAPY
AB Guidelines recommend urgent reperfusion for patients with new left bundle branch block (LBBB), similar to patients with ST-segment elevation myocardial infarction (STEMI). However, there are limited contemporary data comparing these 2 groups of patients. Patients presenting with acute STEMI or presumed new LBBB (nLBBB) enrolled in the Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry Get With the Guidelines (GWTG) from January 2007 to March 2009 were evaluated for clinical characteristics, treatment patterns, and outcomes. Logistic generalized estimating equation modeling was used to examine associated risk-adjusted mortality. Of 46,006 patients with either STEMI or nLBBB, 44,405 (96.5%) had STEMI, and 1,601 (3.5%) had nLBBB. Overall, patients with nLBBB had more baseline co-morbidities compared to those with STEMI. Compared to patients with STEMI, those with nLBBB were less likely to receive acute reperfusion (93.9% vs 48.3% p < 0.0001) and were less likely to have door-to-balloon times <= 90 minutes (76.8% vs 34.5%, p < 0.0001). Mortality rates were higher for patients with nLBBB compared to those with STEMI (13.3% vs 5.6%, p < 0.0001). After multivariate adjustment, nLBBB was not associated with an increased risk for in-hospital mortality (odds ratio 0.91, 95% confidence interval 0.75 to 1.12, p = 0.38). In conclusion, patients with nLBBB were clinically different from those with STEMI, with significantly more co-morbidities, and were less likely to receive emergent reperfusion therapy. Despite these differences, adjusted mortality rates were similar between patients with nLBBB and those with STEMI. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:497-501)
C1 [French, William J.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA.
[Yeo, Khung Keong; Amsterdam, Ezra A.] Univ Calif Davis, Davis Med Ctr, Sacramento, CA 95817 USA.
[Li, Shuang; Wang, Tracy Y.; Roe, Matthew T.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA.
[Saucedo, Jorge F.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Kontos, Michael C.] Virginia Commonwealth Univ, Richmond, VA USA.
RP French, WJ (reprint author), Harbor UCLA Med Ctr, Torrance, CA 90509 USA.
EM wjfrench@ucla.edu
FU Society of Chest Pain Centers, Dublin, Ohio; American College of
Emergency Physicians, Irving, Texas; Society of Hospital Medicine,
Philadelphia, Pennsylvania; Bristol-Myers Squibb/Sanofi Pharmaceuticals;
American College of Cardiology Foundation's National Cardiovascular Data
Registry; Bristol-Myers Squibb/Sanofi; Schering Plough, Kenilworth, New
Jersey; Medicines Company, Parsippany, New Jersey; Heartscape
Technologies, Bothell, Washington; Canyon Pharmaceuticals, Columbia,
Maryland; Eli Lilly/Daiichi Sankyo Alliance; AstraZeneca, Wilmington,
Delaware; Bristol-Myers Squibb, New York, New York; Eisai, Research
Triangle Park, North Carolina; Ethicon, Blue Ash, Ohio; Medtronic,
Minneapolis, Minnesota; Sanofi-Aventis, Paris, France; Medicines
Company; AstraZeneca; Bristol-Myers Squibb; Sanofi-Aventis; Eli Lilly &
Company, Indianapolis, Indiana; Merck/Schering-Plough, Whitehouse
Station, New Jersey; Abbott Laboratories, Abbott Park, Illinois; Eli
Lilly Company; Merck/Schering-Plough; GlaxoSmithKline, London, United
Kingdom; Novartis AG, Basel, Switzerland
FX ACTION Registry-GWTG is an initiative of the American College of
Cardiology Foundation, Bethesda, Maryland, and the American Heart
Association, Dallas, Texas, with partnering support from the Society of
Chest Pain Centers, Dublin, Ohio, the American College of Emergency
Physicians, Irving, Texas, and the Society of Hospital Medicine,
Philadelphia, Pennsylvania. The registry is sponsored in part by the
Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership. This research
was supported by the American College of Cardiology Foundation's
National Cardiovascular Data Registry. The views expressed in this
report represent those of the authors and do not necessarily represent
the official views of the National Cardiovascular Data Registry or its
associated professional societies, identified at http://www.ncdr.com.;
Dr. Wang has received research support from Bristol-Myers Squibb/Sanofi
Partnership; Schering Plough, Kenilworth, New Jersey; The Medicines
Company, Parsippany, New Jersey; Heartscape Technologies, Bothell,
Washington; Canyon Pharmaceuticals, Columbia, Maryland; and Eli
Lilly/Daiichi Sankyo Alliance. Dr. Bhatt has received institutional
research support from AstraZeneca, Wilmington, Delaware; Bristol-Myers
Squibb, New York, New York; Eisai, Research Triangle Park, North
Carolina; Ethicon, Blue Ash, Ohio; Medtronic, Minneapolis, Minnesota;
Sanofi-Aventis, Paris, France; and The Medicines Company. Dr. Saucedo
has received institutional research support from AstraZeneca;
Bristol-Myers Squibb; Sanofi-Aventis; The Medicines Company; Eli Lilly &
Company, Indianapolis, Indiana; Merck/Schering-Plough, Whitehouse
Station, New Jersey; and Abbott Laboratories, Abbott Park, Illinois. Dr.
Kontos is a member of the speakers bureaus of and is a consultant for
Sanofi-Aventis and Astellas Pharma, Deerfield, Illinois. Dr. Roe has
received research funding from Eli Lilly & Company, Bristol-Myers
Squibb, Sanofi-Aventis, and Merck/Schering-Plough. Dr. Roe has received
consulting fees or honoraria from GlaxoSmithKline, London, United
Kingdom; Novartis AG, Basel, Switzerland; Eli Lilly & Company;
Bristol-Myers Squibb; Sanofi-Aventis; Merck/Schering-Plough, and
AstraZeneca.
NR 11
TC 10
Z9 10
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD FEB 15
PY 2012
VL 109
IS 4
BP 497
EP 501
DI 10.1016/j.amjcard.2011.09.040
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 896SO
UT WOS:000300591900009
PM 22152973
ER
PT J
AU Rienstra, M
Sun, JX
Magnani, JW
Sinner, MF
Lubitz, SA
Sullivan, LM
Ellinor, PT
Benjamin, EJ
AF Rienstra, Michiel
Sun, Jenny X.
Magnani, Jared W.
Sinner, Moritz F.
Lubitz, Steven A.
Sullivan, Lisa M.
Ellinor, Patrick T.
Benjamin, Emelia J.
TI White Blood Cell Count and Risk of Incident Atrial Fibrillation (From
the Framingham Heart Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; CARDIOTHORACIC SURGERY;
LEUKOCYTE COUNT; STATIN THERAPY; MORTALITY; INFLAMMATION; ASSOCIATION;
PREDICTOR; COHORT
AB Several studies have reported that inflammatory markers are associated with atrial fibrillation (AF). The white blood cell (WBC) count is a widely available and broadly used marker of systemic inflammation. We sought to investigate the association between an increased WBC count and incident AF and whether this association is mediated by smoking, myocardial infarction, and heart failure. We examined the participants in the Framingham Heart Study original cohort. Cox proportional hazard regression analysis was used to examine the relation between the WBC count and incident AF during a 5-year follow-up period. We adjusted for standard AF risk factors, smoking, previous myocardial infarction, and interim myocardial infarction and heart failure before the incident AF. Our sample consisted of 936 participants (mean age 76 +/- 6 years and 61% women). The median WBC count was 6.4 x 10(9)/L (25th to 75th percentile 5.6 x 10(9)/L to 7.8 x 10(9)/L). During a median 5-year follow-up period, 82 participants (9%) developed new-onset AF. After adjusting for standard risk factors for AF, an increased WBC count was significantly associated with incident AF, with a hazard ratio per SD (0.26 x 10(9)/L) increase of 2.22 (95% confidence interval 1.10 to 4.48; p = 0.03). We found no substantive differences adjusting for smoking, previous myocardial infarction, interim myocardial infarction, or heart failure. In conclusion, in our community-based sample, an increased WBC count was associated with incident AF during 5 years of follow-up. Our findings provide additional evidence for the relation between systemic inflammation and AF. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:533-537)
C1 [Rienstra, Michiel; Magnani, Jared W.; Sinner, Moritz F.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Rienstra, Michiel; Magnani, Jared W.; Sinner, Moritz F.; Benjamin, Emelia J.] Boston Univ, Framingham, MA USA.
[Rienstra, Michiel; Sinner, Moritz F.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Sun, Jenny X.; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA.
[Sinner, Moritz F.] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany.
RP Benjamin, EJ (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
EM emelia@bu.edu
OI Sullivan, Lisa/0000-0003-0726-7149; Benjamin,
Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland
[N01-HC-25195]; Boston University School of Medicine, Boston,
Massachusetts; Netherlands Organization for Scientific Research, The
Hague, The Netherlands [825.09.020]; American Heart Association (Dallas,
Texas) [09FTF2190028]; German Heart Foundation (Frankfurt, Germany);
National Institutes of Health, Bethesda, Maryland [1R01 HL092577,
1RC1HL101056, 1R01HL102214, R01AG028321, 6R01-NS 17950, 5R21DA027021,
5RO1HL104156, 1K24HL105780]; Evans Center for Interdisciplinary
Biomedical Research ARC on Atrial Fibrillation Initiative (Boston
University, Boston, Massachusetts)
FX The Framingham Heart Study is supported by grant N01-HC-25195 from the
National Heart, Lung, and Blood Institute, Bethesda, Maryland and by
Boston University School of Medicine, Boston, Massachusetts. Dr.
Rienstra is supported by Rubicon grant 825.09.020 from The Netherlands
Organization for Scientific Research, The Hague, The Netherlands; Dr.
Magnani is supported by American Heart Association Award 09FTF2190028
(Dallas, Texas). Dr. Sinner is supported by the German Heart Foundation
(Frankfurt, Germany). This work was supported by grant 1R01 HL092577
from the National Institutes of Health, Bethesda, Maryland to Drs.
Benjamin and Ellinor, grants 1RC1HL101056, 1R01HL102214, and R01AG028321
and support via grant 6R01-NS 17950 to Dr. Benjamin, and grants
5R21DA027021, 5RO1HL104156, 1K24HL105780 to Dr. Ellinor. This study was
partially supported by the Evans Center for Interdisciplinary Biomedical
Research ARC on Atrial Fibrillation Initiative (Boston University,
Boston, Massachusetts).
NR 32
TC 27
Z9 30
U1 0
U2 3
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD FEB 15
PY 2012
VL 109
IS 4
BP 533
EP 537
DI 10.1016/j.amjcard.2011.09.049
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 896SO
UT WOS:000300591900016
PM 22100030
ER
PT J
AU Gore, JL
Wright, JL
Daratha, KB
Roberts, KP
Lin, DW
Wessells, H
Porter, M
AF Gore, John L.
Wright, Jonathan L.
Daratha, Kenn B.
Roberts, Kenneth P.
Lin, Daniel W.
Wessells, Hunter
Porter, Michael
TI Hospital-level variation in the quality of urologic cancer surgery
SO CANCER
LA English
DT Article
DE prostate carcinoma; kidney carcinoma; bladder carcinoma; quality of care
ID OUTCOMES ASSESSMENT PROGRAM; RADICAL PROSTATECTOMY; BLADDER-CANCER;
KIDNEY-CANCER; OPERATIVE MORTALITY; CYSTECTOMY; VOLUME; CARE;
COMPLICATIONS
AB BACKGROUND: Unexplained variation in outcomes after common surgeries raises concerns about the quality and appropriateness of surgical care. Understanding variation in surgical outcomes may identify processes that could affect the quality of surgical and postoperative care. The authors of this report examined hospital-level variation in outcomes after inpatient urologic oncology procedures. METHODS: Patients who underwent radical cystectomy, radical nephrectomy, and radical prostatectomy were identified from the Washington State Comprehensive Hospital Abstract Reporting System for the years 2003 through 2007. The postoperative length of stay (LOS) was measured, and LOS that exceeded the 75th percentile was classified as prolonged. The occurrence of Agency for Healthcare Quality patient safety indicators (PSIs), readmissions, and deaths also were measured. Analyses were adjusted for patient age and comorbidity in random effects, multilevel, multivariable models that assessed hospital-level outcomes. RESULTS: The authors identified 853 patients from 37 hospitals who underwent cystectomy, 3018 patients who underwent nephrectomy from 51 hospitals, and 8228 patients who underwent prostatectomy from 51 hospitals. Complications captured by PSIs were rare. Hospital-level variation was most profound for LOS outcomes after nephrectomy and prostatectomy (variance in prolonged LOS, 8.1% and 26.7%, respectively), thromboembolic events after nephrectomy (8% of variance), and mortality after cystectomy (7.1% of variance). CONCLUSIONS: Hospital-level variation confounds the care of urologic cancer patients in the state of Washington. The authors concluded that transparent reporting of surgical outcomes and local quality-improvement initiatives should be considered to ameliorate the observed variation and improve the quality of cystectomy, nephrectomy, and prostatectomy care. Cancer 2012;118:987-96. Published 2011 by the American Cancer Society*.
C1 [Gore, John L.; Wright, Jonathan L.; Lin, Daniel W.; Wessells, Hunter; Porter, Michael] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA.
[Wright, Jonathan L.; Lin, Daniel W.; Porter, Michael] Vet Affairs Puget Sound Hlth Care Syst, Div Urol, Seattle, WA USA.
[Daratha, Kenn B.] Washington State Univ, Coll Nursing, Spokane, WA USA.
[Roberts, Kenneth P.] Washington State Univ, Washington Wyoming Alaska Montana Idaho WWAMI Med, Spokane, WA USA.
RP Gore, JL (reprint author), Univ Washington, Sch Med, Dept Urol, 1959 NE Pacific St,Box 356510, Seattle, WA 98195 USA.
EM jlgore@u.washington.edu
RI Roberts, Ken/D-5701-2012;
OI Gore, John/0000-0002-2847-5062
FU National Center for Research Resources, National Institutes of Health
[UL1RR025014]; Veterans Affairs Puget Sound Health Care System, Seattle,
Washington
FX This work was supported by grant UL1RR025014 from the National Center
for Research Resources, National Institutes of Health. This material
also is the result of work supported in part by resources from the
Veterans Affairs Puget Sound Health Care System, Seattle, Washington.
NR 32
TC 11
Z9 11
U1 0
U2 3
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 FEB 15
PY 2012
VL 118
IS 4
BP 987
EP 996
DI 10.1002/cncr.26373
PG 10
WC Oncology
SC Oncology
GA 886EF
UT WOS:000299834300016
PM 21792864
ER
PT J
AU Patel, YR
Carr, KA
Magjuka, D
Mohammadi, Y
Dropcho, EF
Reed, AD
Moore, ML
Waddell, MJ
Shedd-Steele, R
Sweeney, CJ
Hahn, NM
AF Patel, Yash R.
Carr, Katherine A.
Magjuka, David
Mohammadi, Yousef
Dropcho, Edward F.
Reed, Angela D.
Moore, Marietta L.
Waddell, Mary Jane
Shedd-Steele, Rivienne
Sweeney, Christopher J.
Hahn, Noah M.
TI Successful recruitment of healthy African American men to genomic
studies from high-volume community health fairs
SO CANCER
LA English
DT Article
DE African American; genomic research; healthy population; demographics;
community health fairs
ID PROSTATE-SPECIFIC ANTIGEN; DIGITAL RECTAL EXAMINATION; MARITAL
STABILITY; RACIAL-DIFFERENCES; CANCER STATISTICS; CHURCH ATTENDANCE;
CLINICAL-TRIALS; MARRIAGE; RACE; PARTICIPATION
AB BACKGROUND: Study of genomic data obtained from patient biospecimens is frequent in research of subjects with prostate and other epithelial malignancies. Understanding of the characteristics of healthy men who participate in genomic research is limited. METHODS: Patients were identified through the Prostate Cancer Genetic Risk Evaluation of SNPs Study and the Indiana University Cancer Biomarker Study, 2 population-based biomarker and cohort studies. Between 2006 and 2010, healthy Caucasian (n = 774) and healthy African American (n 381) men were recruited and enrolled at high-volume free community health fairs. Each participant completed a demographic questionnaire and provided a blood sample for genomic research investigations. Frequency differences between demographic features of healthy African American and Caucasian men were compared and analyzed by 2-sample t test and multivariate logistic regression after adjusting potential confounding variables with significance at the P <. 05 level. Features examined included: age, body mass index (BMI), income, education, marital status, tobacco, alcohol, family history, prostate-specific antigen (PSA) level, and prior prostate cancer screening history. RESULTS: Significant differences between healthy Caucasian and African American men participating in genomic research included: marital status (married, 69% Caucasian vs 46% African American, P <<. 001), mean age (years, 58 Caucasian vs 54 African American, P <. 001), mean BMI (kg/m(2), 30.9 Caucasian vs 32.3 African American, P = .004), annual income (P = .038), education (P = .002), and mean PSA (ng/mL, 1.2 Caucasian vs 2.0 African American, P = .005). CONCLUSIONS: Significant demographic differences exist between healthy Caucasian and African American men choosing to participate in genomic research. These differences may be important in designing genomic research study recruitment strategies. Cancer 2012;118:1075-82. (C) 2011 American Cancer Society.
C1 [Patel, Yash R.; Carr, Katherine A.; Magjuka, David; Mohammadi, Yousef; Dropcho, Edward F.; Reed, Angela D.; Moore, Marietta L.; Waddell, Mary Jane; Shedd-Steele, Rivienne; Sweeney, Christopher J.; Hahn, Noah M.] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA.
[Sweeney, Christopher J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Hahn, NM (reprint author), Indiana Univ, Melvin & Bren Simon Canc Ctr, Indiana Canc Pavil Room RT445,535 Barnhill Dr, Indianapolis, IN 46202 USA.
EM nhahn@iupui.edu
FU Walther Cancer Research Institute; Clarian Health Partners; Indiana
University School of Medicine
FX Supported by grant funding from the Walther Cancer Research Institute
and Clarian Health Partners, and institutional research support from the
Indiana University School of Medicine.
NR 49
TC 1
Z9 1
U1 0
U2 8
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 FEB 15
PY 2012
VL 118
IS 4
BP 1075
EP 1082
DI 10.1002/cncr.26328
PG 8
WC Oncology
SC Oncology
GA 886EF
UT WOS:000299834300026
PM 21766294
ER
PT J
AU Friedl, P
Hubbell, J
Livingston, D
Mihich, E
AF Friedl, Peter
Hubbell, Jeff
Livingston, David
Mihich, Enrico
TI Twenty-Third Annual Pezcoller Symposium: Engineering Influences in
Cancer Research
SO CANCER RESEARCH
LA English
DT Editorial Material
AB The cross-disciplinary focus of the meeting highlighted recent progress in physical and genetic analysis and engineering of cancer disease models. As the central theme, mechanical forces affecting cell signaling, growth, differentiation, and metastasis were discussed with emphasis on the tumor microenvironment and cellular immunity, taking into account novel nanotechnology, biosensing, and intravital microscopy tools to monitor animal cancer models and human cancer. Emerging themes were the role of extracellular matrix imposing mechanical mechanisms on tumor cell function, including microenvironmental cues controlling the movement of tumor and immune cells, advanced genetic animal models for cancer that better recapitulate human disease, and preclinical and clinical molecular imaging of tumor architecture and stiffness, as well as novel nanotechnologies for anticancer drug delivery. Cancer Res; 72(4); 841-4. (C) 2012 AACR.
C1 [Livingston, David; Mihich, Enrico] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Friedl, Peter] NCMLS, Nijmegen, Netherlands.
[Hubbell, Jeff] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
RP Mihich, E (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM enrico_mihich@dfci.harvard.edu
RI Hubbell, Jeffrey/A-9266-2008; Friedl, Peter/A-8961-2010
OI Hubbell, Jeffrey/0000-0003-0276-5456;
NR 0
TC 1
Z9 1
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2012
VL 72
IS 4
BP 841
EP 844
DI 10.1158/0008-5472.CAN-11-3080
PG 4
WC Oncology
SC Oncology
GA 897ET
UT WOS:000300629100003
PM 22237623
ER
PT J
AU Flynn, RL
Chang, S
Zou, L
AF Flynn, Rachel Litman
Chang, Sandy
Zou, Lee
TI RPA and POT1 Friends or foes at telomeres?
SO CELL CYCLE
LA English
DT Article
DE RPA; POT1; telomere; ATR; checkpoint
ID SINGLE-STRANDED-DNA; REPLICATION PROTEIN-A; ABERRANT HOMOLOGOUS
RECOMBINATION; REPEAT-CONTAINING RNA; FISSION YEAST; MAMMALIAN
TELOMERES; BINDING-PROTEIN; CHROMOSOME ENDS; BREAK REPAIR; CELL-CYCLE
AB Telomere maintenance in cycling cells relies on both DNA replication and capping by the protein complex shelterin. Two single-stranded DNA (ssDNA)-binding proteins, replication protein A (RPA) and protection of telomere 1 (POT1) play critical roles in DNA replication and telomere capping, respectively. While RPA binds to ssDNA in a non-sequence-specific manner, POT1 specifically recognizes single-stranded TTAGGG telomeric repeats. Loss of POT1 leads to aberrant accumulation of RPA at telomeres and activation of the ataxia telangiectasia and Rad3-related kinase (ATR)-mediated checkpoint response, suggesting that POT1 antagonizes RPA binding to telomeric ssDNA. The requirement for both POT1 and RPA in telomere maintenance and the antagonism between the two proteins raises the important question of how they function in concert on telomeric ssDNA. Two interesting models were proposed by recent studies to explain the regulation of POT1 and RPA at telomeres. Here, we discuss how these models help unravel the coordination, and also the antagonism, between POT1 and RPA during the cell cycle.
C1 [Flynn, Rachel Litman; Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
[Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Chang, Sandy] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA.
RP Zou, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
EM zou.lee@mgh.harvard.edu
FU ACS [0902501]; NIH [CA129037, GM076388]
FX R.L.F. is supported the ACS fellowship 0902501. S.C. is supported by the
NIH grant CA129037. L.Z. is supported by the NIH grant GM076388. L.Z. is
the Jim and Ann Orr MGH Research Scholar and a Scholar of the Ellison
Medical Foundation.
NR 50
TC 8
Z9 8
U1 0
U2 7
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD FEB 15
PY 2012
VL 11
IS 4
BP 652
EP 657
DI 10.4161/cc.11.4.19061
PG 6
WC Cell Biology
SC Cell Biology
GA 897CY
UT WOS:000300621400013
PM 22373525
ER
PT J
AU Coon, TA
Glasser, JR
Mallampalli, RK
Chen, BB
AF Coon, Tiffany A.
Glasser, Jennifer R.
Mallampalli, Rama K.
Chen, Bill B.
TI Novel E3 ligase component FBXL7 ubiquitinates and degrades Aurora A,
causing mitotic arrest
SO CELL CYCLE
LA English
DT Article
DE F-box protein; centrosome; mitosis; Aurora A
ID SPINDLE ASSEMBLY CHECKPOINT; F-BOX PROTEINS; HUMAN-CELLS; REGULATORY
ENZYME; B DEGRADATION; IDENTIFICATION; MITOSIS; CANCER; CYTOKINESIS;
ANEUPLOIDY
AB Aurora family kinases play pivotal roles in several steps during mitosis. Specifically, Aurora A kinase is an important regulator of bipolar mitotic spindle formation and chromosome segregation. Like other members of the Aurora family, Aurora A kinase is also regulated by post-translational modifications. Here, we show that a previously undescribed E3 ligase component belonging to the SCF (Skp-Cullin1-F-box protein) E3 ligase family, SCFFBXL7, impairs cell proliferation by mediating Aurora A polyubiquitination and degradation. Both Aurora A and FBXL7 co-localize within the centrosome during spindle formation. FBXL7 ectopic expression led to G(2)/M phase arrest in transformed epithelia, resulting in the appearance of tetraploidy and mitotic arrest with circular monopolar spindles and multipolar spindle formation. Interestingly, FBXL7 specifically interacts with Aurora A during mitosis but not in interphase, suggesting a regulatory role for FBXL7 in controlling Aurora A abundance during mitosis.
C1 [Coon, Tiffany A.; Glasser, Jennifer R.; Mallampalli, Rama K.; Chen, Bill B.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15260 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, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15260 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 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 40
TC 18
Z9 20
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD FEB 15
PY 2012
VL 11
IS 4
BP 721
EP 729
DI 10.4161/cc.11.4.19171
PG 9
WC Cell Biology
SC Cell Biology
GA 897CY
UT WOS:000300621400022
PM 22306998
ER
PT J
AU Trowbridge, JJ
Sinha, AU
Zhu, N
Li, MJ
Armstrong, SA
Orkin, SH
AF Trowbridge, Jennifer J.
Sinha, Amit U.
Zhu, Nan
Li, Mingjie
Armstrong, Scott A.
Orkin, Stuart H.
TI Haploinsufficiency of Dnmt1 impairs leukemia stem cell function through
derepression of bivalent chromatin domains
SO GENES & DEVELOPMENT
LA English
DT Article
DE DNA methylation; leukemia stem cell; Dnmt1; bivalent chromatin
ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM; H3K79 METHYLATION; DNA;
CANCER; METHYLTRANSFERASE; GENES; HYPOMETHYLATION; PROGENITOR; PROFILES
AB Epigenetic mechanisms regulating leukemia stem cells (LSCs) are an attractive target for therapy of blood cancers. Here, we report that conditional knockout of the DNA methyltransferase Dnmt1 blocked development of leukemia, and haploinsufficiency of Dnmt1 was sufficient to delay progression of leukemogenesis and impair LSC self-renewal without altering normal hematopoiesis. Haploinsufficiency of Dnmt1 resulted in tumor suppressor gene derepression associated with reduced DNA methylation and bivalent chromatin marks. These results suggest that LSCs depend on not only active expression of leukemogenic programs, but also DNA methylation-mediated silencing of bivalent domains to enforce transcriptional repression.
C1 [Trowbridge, Jennifer J.; Sinha, Amit U.; Zhu, Nan; Li, Mingjie; Armstrong, Scott A.; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol,Div Hemat, Childrens Hosp Boston,Harvard Stem Cell Inst, Boston, MA 02115 USA.
[Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol,Div Hemat, Childrens Hosp Boston,Harvard Stem Cell Inst, 44 Binney St, Boston, MA 02115 USA.
EM orkin@bloodgroup.tch.harvard.edu
FU Leukemia and Lymphoma Society; Children's Leukemia Research Foundation;
ASH; NIH [CA105423]; GO [CA148222]; HSCI
FX We thank members of the Orkin and Armstrong laboratories for helpful
discussion, and John Daley, Suzan Lazo-Kallanian, and Rob Smith of the
DFCI HemNeo Flow Facility. J.J.T. was supported by a fellowship from the
Leukemia and Lymphoma Society, the Children's Leukemia Research
Foundation, and ASH Scholar award. This work was supported by NIH U01
grant CA105423 (to S.H.O.), GO grant RC2 CA148222 (to S.H.O. and S. A.
A.), and the HSCI blood program (S.H.O. and S. A. A.). S.H.O. is an
Investigator of the HHMI.
NR 25
TC 61
Z9 63
U1 0
U2 4
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD FEB 15
PY 2012
VL 26
IS 4
BP 344
EP 349
DI 10.1101/gad.184341.111
PG 6
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 897EH
UT WOS:000300626800005
PM 22345515
ER
PT J
AU Miles, WO
Tschop, K
Herr, A
Ji, JY
Dyson, NJ
AF Miles, Wayne O.
Tschoep, Katrin
Herr, Anabel
Ji, Jun-Yuan
Dyson, Nicholas J.
TI Pumilio facilitates miRNA regulation of the E2F3 oncogene
SO GENES & DEVELOPMENT
LA English
DT Article
DE cancer; E2F3; Pumilio; miRNA
ID HUNCHBACK MESSENGER-RNA; GERMLINE STEM-CELLS; DROSOPHILA-MELANOGASTER;
BLADDER-CANCER; TRANSLATIONAL REPRESSION; CAENORHABDITIS-ELEGANS;
TRANSCRIPTION FACTOR; BINDING PROTEINS; PUM2 GENES; S-PHASE
AB E2F transcription factors are important regulators of cell proliferation and are frequently dysregulated in human malignancies. To identify novel regulators of E2F function, we used Drosophila as a model system to screen for mutations that modify phenotypes caused by reduced levels of dE2F1. This screen identified components of the Pumilio translational repressor complex (Pumilio, Nanos, and Brain tumor) as suppressors of dE2F1-RNAi phenotypes. Subsequent experiments provided evidence that Pumilio complexes repress dE2F1 levels and that this mechanism of post-transcriptional regulation is conserved in human cells. The human Pumilio homologs Pum 1 and Pum 2 repress the translation of E2F3 by binding to the E2F3 39 untranslated region (UTR) and also enhance the activity of multiple E2F3 targeting microRNAs (miRNAs). E2F3 is an oncogene with strong proliferative potential and is regularly dysregulated or overexpressed in cancer. Interestingly, Pumilio/miRNA-mediated regulation of E2F3 is circumvented in cancer cells in several different ways. Bladder carcinomas selectively downregulate miRNAs that cooperate with Pumilio to target E2F3, and multiple tumor cell lines shorten the 39 end of the E2F3 mRNA, removing the Pumilio regulatory elements. These studies suggest that Pumilio-miRNA repression of E2F3 translation provides an important level of E2F regulation that is frequently abrogated in cancer cells.
C1 [Miles, Wayne O.; Tschoep, Katrin; Herr, Anabel; Ji, Jun-Yuan; Dyson, Nicholas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Lab Mol Oncol, Charlestown, MA 02129 USA.
RP Dyson, NJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Lab Mol Oncol, Charlestown, MA 02129 USA.
EM dyson@helix.mgh.harvard.edu
FU National Institutes of Health (NIH) [R01GM053203]
FX We thank Dr. Spyros Artanavis-Tsakonas for providing fly stocks. We also
thank A. Gladden, A. Walker, H. Najafi-Shoushtari, S. Vasudevan, A.
Naar, and J. Walker for careful reading of the manuscript, and all
members of the Naar and Dyson laboratories for helpful comments and
discussions. This work was supported by National Institutes of Health
(NIH) grant R01GM053203 to N.J.D. N.J.D. is the Saltonstall Scholar of
the Massachusetts General Hospital Cancer Center.
NR 57
TC 42
Z9 46
U1 0
U2 5
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD FEB 15
PY 2012
VL 26
IS 4
BP 356
EP 368
DI 10.1101/gad.182568.111
PG 13
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 897EH
UT WOS:000300626800007
PM 22345517
ER
PT J
AU Yaroslavsky, AN
Patel, R
Salomatina, E
Li, CQ
Lin, C
Al-Arashi, M
Neel, V
AF Yaroslavsky, Anna N.
Patel, Rakesh
Salomatina, Elena
Li, Chunqiang
Lin, Charles
Al-Arashi, Munir
Neel, Victor
TI High-contrast mapping of basal cell carcinomas
SO OPTICS LETTERS
LA English
DT Article
ID NONMELANOMA SKIN CANCERS; CONFOCAL MICROSCOPY; POLARIZED-LIGHT;
EXCISIONS; SURGERY
AB Because of low optical contrast in the visible spectral range, accurate detection of basal cell carcinomas (BCC) remains a challenging problem. In this letter, we experimentally demonstrate that reflectance confocal imaging in the vicinity of 1300 nm can be used for the detection of BCC without exogenous contrast agents. We present high- contrast reflectance confocal images of thick fresh skin tissues with clearly delineated cancer and discuss possible reasons for causing decreased scattering of BCC. Comparison with histopathology confirms that tumors scatter less and exhibit lower pixel values in the images, as compared to benign skin structures. The results demonstrate the feasibility of real- time noninvasive detection of BCC using intrinsic differences in scattering between tumors and normal skin. (C) 2012 Optical Society of America
C1 [Yaroslavsky, Anna N.; Patel, Rakesh] Univ Massachusetts, Lowell, MA 01854 USA.
[Yaroslavsky, Anna N.; Salomatina, Elena; Li, Chunqiang; Lin, Charles; Al-Arashi, Munir; Neel, Victor] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Yaroslavsky, AN (reprint author), Univ Massachusetts, Lowell, MA 01854 USA.
EM Anna_Yaroslavsky@uml.edu
NR 21
TC 6
Z9 6
U1 1
U2 4
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 0146-9592
J9 OPT LETT
JI Opt. Lett.
PD FEB 15
PY 2012
VL 37
IS 4
BP 644
EP 646
PG 3
WC Optics
SC Optics
GA 898AF
UT WOS:000300706500067
PM 22344134
ER
PT J
AU Morrow, WR
Frazier, EA
Mahle, WT
Harville, TO
Pye, SE
Knecht, KR
Howard, EL
Smith, RN
Saylors, RL
Garcia, X
Jaquiss, RDB
Woodle, ES
AF Morrow, William Robert
Frazier, Elizabeth A.
Mahle, William T.
Harville, Terry O.
Pye, Sherry E.
Knecht, Kenneth R.
Howard, Emily L.
Smith, R. Neal
Saylors, Robert L.
Garcia, Xiomara
Jaquiss, Robert D. B.
Woodle, E. Steve
TI Rapid Reduction in Donor-Specific Anti-Human Leukocyte Antigen
Antibodies and Reversal of Antibody-Mediated Rejection With Bortezomib
in Pediatric Heart Transplant Patients
SO TRANSPLANTATION
LA English
DT Article
DE Antibody-mediated rejection; Pediatric heart transplant; Donor-specific
antibodies
ID PANEL-REACTIVE ANTIBODY; PROTEASOME INHIBITOR BORTEZOMIB; VENTRICULAR
ASSIST DEVICE; CORONARY-ARTERY-DISEASE; CARDIAC TRANSPLANTATION; HUMORAL
REJECTION; CROSS-MATCH; ALLOGRAFT-REJECTION; PLASMAPHERESIS; THERAPY
AB Background. High titer donor-specific antibodies (DSA) and positive crossmatch in cardiac transplant recipients is associated with increased mortality from antibody-mediated rejection (AMR). Although treatment to reduce antihuman leukocyte antigen antibodies using plasmapheresis, intravenous immunoglobulin, and rituximab has been reported to be beneficial, in practice these are often ineffective. Moreover, these interventions do not affect the mature antibody producing plasma cell. Bortezomib, a proteasome inhibitor active against plasma cells, has been shown to reduce DSA in renal transplant patients with AMR. We report here the first use of bortezomib for cardiac transplant recipients in four pediatric heart recipients with biopsy-proven AMR, hemodynamic compromise, positive crossmatch, and high titer class I DSA.
Methods. Patients received four intravenous dose of bortezomib (1.3 mg/m(2)) over 2 weeks with plasmapheresis and rituximab. DSA specificity and strength (mean fluorescence intensity) was determined with Luminex. All had received previous treatment with plasmapheresis, intravenous immunoglobulin, and rituximab that was ineffective.
Results. AMR resolved in all patients treated with bortezomib with improvement in systolic function, conversion of biopsy to C4d negative in three patients and IgG negative in one patient, and a prompt, precipitous reduction in DSAs. In three patients who received plasmapheresis before bortezomib, plasmapheresis failed to reduce DSA. In one case, DSA increased after bortezomib but decreased after retreatment.
Conclusions. Bortezomib reduces DSA and may be an important adjunct to treatment of AMR in cardiac transplant recipients. Bortezomib may also be useful in desensitization protocols and in prevention of AMR in sensitized patients with positive crossmatch and elevated DSA.
C1 [Morrow, William Robert; Frazier, Elizabeth A.; Harville, Terry O.; Pye, Sherry E.; Knecht, Kenneth R.; Howard, Emily L.; Saylors, Robert L.; Garcia, Xiomara] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Cardiol Sect, Little Rock, AR 72205 USA.
[Mahle, William T.] Childrens Healthcare Atlanta, Sibley Heart Ctr, Atlanta, GA USA.
[Smith, R. Neal] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Jaquiss, Robert D. B.] Duke Univ, Sch Med, Dept Surg, Durham, NC USA.
[Woodle, E. Steve] Univ Cincinnati, Dept Surg, Div Transplantat, Cincinnati, OH 45267 USA.
RP Knecht, KR (reprint author), 1 Childrens Way,Slot 512-3, Little Rock, AR 72202 USA.
EM krknecht@uams.edu
FU NIAID NIH HHS [U19 AI102405]
NR 37
TC 45
Z9 46
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD FEB 15
PY 2012
VL 93
IS 3
BP 319
EP 324
DI 10.1097/TP.0b013e31823f7eea
PG 6
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 891CF
UT WOS:000300193200019
PM 22179403
ER
PT J
AU LaRocque, RC
Rao, SR
Lee, J
Ansdell, V
Yates, JA
Schwartz, BS
Knouse, M
Cahill, J
Hagmann, S
Vinetz, J
Connor, BA
Goad, JA
Oladele, A
Alvarez, S
Stauffer, W
Walker, P
Kozarsky, P
Franco-Paredes, C
Dismukes, R
Rosen, J
Hynes, NA
Jacquerioz, F
McLellan, S
Hale, D
Sofarelli, T
Schoenfeld, D
Marano, N
Brunette, G
Jentes, ES
Yanni, E
Sotir, MJ
Ryan, ET
AF LaRocque, Regina C.
Rao, Sowmya R.
Lee, Jennifer
Ansdell, Vernon
Yates, Johnnie A.
Schwartz, Brian S.
Knouse, Mark
Cahill, John
Hagmann, Stefan
Vinetz, Joseph
Connor, Bradley A.
Goad, Jeffery A.
Oladele, Alawode
Alvarez, Salvador
Stauffer, William
Walker, Patricia
Kozarsky, Phyllis
Franco-Paredes, Carlos
Dismukes, Roberta
Rosen, Jessica
Hynes, Noreen A.
Jacquerioz, Frederique
McLellan, Susan
Hale, DeVon
Sofarelli, Theresa
Schoenfeld, David
Marano, Nina
Brunette, Gary
Jentes, Emily S.
Yanni, Emad
Sotir, Mark J.
Ryan, Edward T.
CA Global TravEpiNet Consortium
TI Global TravEpiNet: A National Consortium of Clinics Providing Care to
International Travelers-Analysis of Demographic Characteristics, Travel
Destinations, and Pretravel Healthcare of High-Risk US International
Travelers, 2009-2011
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID UNITED-STATES; SURVEILLANCE; DISEASES
AB Background. International travel poses a risk of destination-specific illness and may contribute to the global spread of infectious diseases. Despite this, little is known about the health characteristics and pretravel healthcare of US international travelers, particularly those at higher risk of travel-associated illness.
Methods. We formed a national consortium (Global TravEpiNet) of 18 US clinics registered to administer yellow fever vaccination. We collected data regarding demographic and health characteristics, destinations, purpose of travel, and pretravel healthcare from 13 235 international travelers who sought pretravel consultation at these sites from January 2009 through January 2011.
Results. The destinations and itineraries of Global TravEpiNet travelers differed from those of the overall population of US international travelers. The majority of Global TravEpiNet travelers were visiting low-or lower-middle-income countries, and Africa was the most frequently visited region. Seventy-five percent of travelers were visiting malaria-endemic countries, and 38% were visiting countries endemic for yellow fever. Fifty-nine percent of travelers reported >= 1 medical condition. Atovaquone/proguanil was the most commonly prescribed antimalarial drug, and most travelers received an antibiotic for self-treatment of travelers' diarrhea. Hepatitis A and typhoid were the most frequently administered vaccines.
Conclusions. Data from Global TravEpiNet provide insight into the characteristics and pretravel healthcare of US international travelers who are at increased risk of travel-associated illness due to itinerary, purpose of travel, or existing medical conditions. Improved understanding of this epidemiologically significant population may help target risk-reduction strategies and interventions to limit the spread of infections related to global travel.
C1 [LaRocque, Regina C.] Massachusetts Gen Hosp, Div Infect Dis, Travelers Advice & Immunizat Ctr, Boston, MA 02114 USA.
[LaRocque, Regina C.; Ryan, Edward T.] Harvard Univ, Sch Med, Boston, MA USA.
[Rao, Sowmya R.; Schoenfeld, David] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Lee, Jennifer] NW Mem Hosp, Travel & Immunizat Ctr, Chicago, IL 60611 USA.
[Ansdell, Vernon; Yates, Johnnie A.] Kaiser Permanente Honolulu, Travel Med Clin, Honolulu, HI USA.
[Schwartz, Brian S.] Univ Calif San Francisco, Travel Med & Immunizat Clin, San Francisco, CA 94143 USA.
[Knouse, Mark] Lehigh Valley Hlth Network, Allentown, PA USA.
[Cahill, John] St Lukes Roosevelt, Travel & Immunizat Ctr, New York, NY USA.
[Hagmann, Stefan] Albert Einstein Coll Med, Bronx Ctr Travel & Int Hlth, New York, NY USA.
[Vinetz, Joseph] Univ Calif San Diego, Dept Med, Div Infect Dis, Travel Clin, La Jolla, CA 92093 USA.
[Connor, Bradley A.] Cornell Univ, New York Ctr Travel & Trop Med, New York, NY 10021 USA.
[Goad, Jeffery A.] Univ So Calif, Int Travel Med Clin, Los Angeles, CA USA.
[Oladele, Alawode] DeKalb Cty Board Hlth Travel Serv, Decatur, GA USA.
[Alvarez, Salvador] Mayo Clin, Jacksonville, FL 32224 USA.
[Stauffer, William; Walker, Patricia] HealthPartners Travel Med Clin, St Paul, MN USA.
[Kozarsky, Phyllis; Franco-Paredes, Carlos; Dismukes, Roberta] Emory Univ, Atlanta, GA 30322 USA.
[Rosen, Jessica] Georgetown Univ, Washington, DC USA.
[Hynes, Noreen A.] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA.
[Jacquerioz, Frederique; McLellan, Susan] Tulane Univ, New Orleans, LA 70118 USA.
[Hale, DeVon; Sofarelli, Theresa] Univ Utah, Int Travel Clin, Salt Lake City, UT USA.
[Marano, Nina; Brunette, Gary; Jentes, Emily S.; Yanni, Emad; Sotir, Mark J.] Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Atlanta, GA USA.
RP LaRocque, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Travelers Advice & Immunizat Ctr, GRJ 504,55 Fruit St, Boston, MA 02114 USA.
EM rclarocque@partners.org
OI Vinetz, Joseph/0000-0001-8344-2004
FU US Centers for Disease Control and Prevention (CDC) [U19CI000514,
U01CK000175]; Salix Pharmaceuticals; Elsevier Publishing; Novartis
Vaccines; GlaxoSmithKline; Merck
FX This work was supported by grants from the US Centers for Disease
Control and Prevention (CDC; U19CI000514 and U01CK000175).; B. A. C. has
received grant support from Salix Pharmaceuticals, royalties from
Elsevier Publishing, and payment for lectures from Novartis Vaccines,
GlaxoSmithKline, and Salix Pharmaceuticals. J. A. G. has received
payment for lectures from Merck. P. K. has consulted for Crucell
Biologics, has received payment for lectures from GlaxoSmithKline, has
received royalties from Elsevier Publishing, and has received an
honorarium for the development of educational materials from Sanofi. All
other authors report no potential conflicts.
NR 19
TC 49
Z9 49
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD FEB 15
PY 2012
VL 54
IS 4
BP 455
EP 462
DI 10.1093/cid/cir839
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 888YM
UT WOS:000300040600003
PM 22144534
ER
PT J
AU Godinez-Puig, V
Frangos, J
Hollmann, TJ
Dryden-Peterson, S
Matulonis, U
Lipworth, AD
AF Godinez-Puig, Victoria
Frangos, Jason
Hollmann, Travis J.
Dryden-Peterson, Scott
Matulonis, Ursula
Lipworth, Adam D.
TI Rash in a Patient With Ovarian Cancer
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID CARCINOMA-ERYSIPELOIDES; BREAST; SKIN; METASTASIS; PAX8
C1 [Frangos, Jason; Lipworth, Adam D.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
[Godinez-Puig, Victoria] Univ Nacl Autonoma Mexico, Sch Med, Mexico City 04510, DF, Mexico.
[Hollmann, Travis J.] Brigham & Womens Hosp, Dept Pathol, Div Dermatopathol, Boston, MA 02115 USA.
[Dryden-Peterson, Scott] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA.
[Matulonis, Ursula] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Lipworth, AD (reprint author), Brigham & Womens Hosp, Dept Dermatol, 221 Longwood Ave, Boston, MA 02115 USA.
EM alipworth@partners.org
NR 19
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD FEB 15
PY 2012
VL 54
IS 4
BP 538
EP +
DI 10.1093/cid/cir775
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 888YM
UT WOS:000300040600014
PM 22294566
ER
PT J
AU Ji, GX
Gu, AH
Wang, YB
Huang, C
Hu, F
Zhou, Y
Song, L
Wang, XR
AF Ji, Guixiang
Gu, Aihua
Wang, Yubang
Huang, Cong
Hu, Fan
Zhou, Yong
Song, Ling
Wang, Xinru
TI Genetic variants in antioxidant genes are associated with sperm DNA
damage and risk of male infertility in a Chinese population
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Oxidative stress; Antioxidant genes; Polymorphisms; Male infertility;
DNA fragmentation; 8-Hydroxydeoxyguanosine; Free radicals
ID MANGANESE SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; HUMAN SPERMATOZOA;
PREGNANCY LOSS; IN-VITRO; MEN; FRAGMENTATION; FERTILIZATION; SEMEN;
OVEREXPRESSION
AB To test the hypothesis that polymorphisms in antioxidant genes are more susceptible to sperm DNA damage and male infertility, we examined 11 single-nucleotide polymorphism from six antioxidant genes (GPX1, CA) PON1, NQO1, SOD2/MnSOD, and SOD3) in 580 infertility cases and 580 controls from a Chinese population-based case-control study (NJMU Infertility Study). Genotypes were determined using the OpenArray platform. Sperm DNA fragmentation was detected using the Tdt-mediated dUTP nick-end labeling assay, and the level of 8-hydroxydeoxyguanosine (8-OHdG) in sperm DNA was measured using immunofluorescence. The adjusted odds ratio and 95% confidence interval (CI) were estimated using unconditional logistic regression. The results indicated that the PON1 Arg192Glu (rs662) and SOD2 Val16Ala (rs4880) variant genotypes were associated with a significantly higher risk of male infertility. In addition, subjects carrying variant genotypes of both loci had a twofold (95% CI, 1.42-2.90) increase in the risk of male infertility, indicating a significant gene-gene interaction between these two loci (P for multiplicative interaction = 0.045). Moreover, linear regression analysis showed that individuals carrying the PON1 Arg192Glu (rs662) or SOD2 Val16Ala (rs4880) variants have significantly higher levels of sperm DNA fragmentation and 8-OHdG. These data suggest that genetic variations in antioxidant genes may contribute to oxidative sperm DNA damage and male infertility. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Ji, Guixiang; Gu, Aihua; Huang, Cong; Song, Ling; Wang, Xinru] Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Modern Toxicol, Nanjing 210029, Jiangsu, Peoples R China.
[Ji, Guixiang; Gu, Aihua; Huang, Cong; Song, Ling; Wang, Xinru] Nanjing Med Univ, Inst Toxicol, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China.
[Ji, Guixiang] Minist Environm Protect, Key Lab Pesticide Environm Assessment & Pollut Co, Nanjing Inst Environm Sci, Nanjing 210042, Jiangsu, Peoples R China.
[Wang, Yubang] Nanjing Med Univ, Sch Publ Hlth, Safety Assessment & Res Ctr Drugs Jiangsu Prov, Nanjing 210029, Jiangsu, Peoples R China.
[Hu, Fan] Nanjing Med Univ, Anal Ctr, Nanjing 210029, Jiangsu, Peoples R China.
[Zhou, Yong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Gu, AH (reprint author), Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Modern Toxicol, Nanjing 210029, Jiangsu, Peoples R China.
EM aihuagu@njmu.edu.cn; xrwang@njmu.edu.cn
FU National Basic Research Program of China (973 Program) [2009CB941703,
2011CB944304]; National Natural Science Foundation of China [30930079];
National Science Foundation of China [81172694, 30901210]; Priority
Academic Program Development of Jiangsu Higher Education Institutions
FX This study was supported in part by the National Basic Research Program
of China (973 Program, 2009CB941703 and 2011CB944304), The Key Project
of the National Natural Science Foundation of China (30930079), and the
National Science Foundation of China (Grant No. 81172694 and 30901210).
This project was funded by the Priority Academic Program Development of
Jiangsu Higher Education Institutions. We thank C. Chen for statistical
analysis.
NR 50
TC 20
Z9 22
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD FEB 15
PY 2012
VL 52
IS 4
BP 775
EP 780
DI 10.1016/j.freeradbiomed.2011.11.032
PG 6
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 886OF
UT WOS:000299863000007
PM 22206979
ER
PT J
AU Thadhani, R
Appelbaum, E
Pritchett, Y
Chang, YC
Wenger, J
Tamez, H
Bhan, I
Agarwal, R
Zoccali, C
Wanner, C
Lloyd-Jones, D
Cannata, J
Thompson, BT
Andress, D
Zhang, WY
Packham, D
Singh, B
Zehnder, D
Shah, A
Pachika, A
Manning, WJ
Solomon, SD
AF Thadhani, Ravi
Appelbaum, Evan
Pritchett, Yili
Chang, Yuchiao
Wenger, Julia
Tamez, Hector
Bhan, Ishir
Agarwal, Rajiv
Zoccali, Carmine
Wanner, Christoph
Lloyd-Jones, Donald
Cannata, Jorge
Thompson, B. Taylor
Andress, Dennis
Zhang, Wuyan
Packham, David
Singh, Bhupinder
Zehnder, Daniel
Shah, Amil
Pachika, Ajay
Manning, Warren J.
Solomon, Scott D.
TI Vitamin D Therapy and Cardiac Structure and Function in Patients With
Chronic Kidney Disease The PRIMO Randomized Controlled Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID LEFT-VENTRICULAR MASS; GLOMERULAR-FILTRATION-RATE; D-RECEPTOR
ACTIVATION; LEFT ATRIAL VOLUME; CARDIOVASCULAR MAGNETIC-RESONANCE;
RENIN-ANGIOTENSIN SYSTEM; HEART-FAILURE; D DEFICIENCY; RENAL-FUNCTION;
1,25-DIHYDROXYVITAMIN D-3
AB Context Vitamin D is associated with decreased cardiovascular-related morbidity and mortality, possibly by modifying cardiac structure and function, yet firm evidence for either remains lacking.
Objective To determine the effects of an active vitamin D compound, paricalcitol, on left ventricular mass over 48 weeks in patients with an estimated glomerular filtration rate of 15 to 60 mL/min/1.73 m(2).
Design, Setting, and Participants Multinational, double-blind, randomized placebo-controlled trial among 227 patients with chronic kidney disease, mild to moderate left ventricular hypertrophy, and preserved left ventricular ejection fraction, conducted in 11 countries from July 2008 through September 2010.
Intervention Participants were randomly assigned to receive oral paricalcitol, 2 mu g/d (n=115), or matching placebo (n=112).
Main Outcome Measures Change in left ventricular mass index over 48 weeks by cardiovascular magnetic resonance imaging. Secondary end points included echo-cardiographic changes in left ventricular diastolic function.
Results Treatment with paricalcitol reduced parathyroid hormone levels within 4 weeks and maintained levels within the normal range throughout the study duration. At 48 weeks, the change in left ventricular mass index did not differ between treatment groups (paricalcitol group, 0.34 g/m(2.7) [95% CI, -0.14 to 0.83 g/m(2.7)] vs placebo group, -0.07 g/m(2.7) [95% CI, -0.55 to 0.42 g/m(2.7)]). Doppler measures of diastolic function including peak early diastolic lateral mitral annular tissue velocity (paricalcitol group, -0.01 cm/s [95% CI, -0.63 to 0.60 cm/s] vs placebo group, -0.30 cm/s [95% CI, -0.93 to 0.34 cm/s]) also did not differ. Episodes of hypercalcemia were more frequent in the paricalcitol group compared with the placebo group.
Conclusion Forty-eight week therapy with paricalcitol did not alter left ventricular mass index or improve certain measures of diastolic dysfunction in patients with chronic kidney disease.
C1 [Thadhani, Ravi; Wenger, Julia; Tamez, Hector; Bhan, Ishir] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA.
[Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA.
[Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Appelbaum, Evan; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Perfuse Cardiovasc Magnet Resonance Core Lab, Boston, MA 02215 USA.
[Appelbaum, Evan; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA.
[Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA.
[Shah, Amil; Pachika, Ajay; Solomon, Scott D.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA.
[Andress, Dennis; Zhang, Wuyan; Pachika, Ajay] Abbott Labs, Abbott Pk, IL 60064 USA.
[Agarwal, Rajiv] Indiana Univ Sch Med, Dept Med, Indianapolis, IN USA.
[Zoccali, Carmine] Inst Biomed & Immunol Mol Alberto Monroy Clin Epi, Nephrol Dialysis & Transplantat Unit, Reggio Di Calabria, Italy.
[Zoccali, Carmine] Inst Biomed & Immunol Mol Alberto Monroy Clin Epi, CNR, Reggio Di Calabria, Italy.
[Wanner, Christoph] Univ Wurzburg, Univ Hosp, Dept Med, Div Nephrol, Wurzburg, Germany.
[Lloyd-Jones, Donald] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Cannata, Jorge] Hosp Univ Cent Asturias, Inst Reina Sofia Invest, Serv Metab Oseo & Mineral, Inst Carlos III, Oviedo, Spain.
[Packham, David] Royal Melbourne Hosp, Dept Nephrol, Reservoir Private Hosp, Melbourne Renal Res Grp, Melbourne, Vic 3050, Australia.
[Packham, David] Austin Hosp, Dept Nephrol, Melbourne, Vic 3084, Australia.
[Singh, Bhupinder] SW Kidney Inst, Tempe, AZ USA.
[Zehnder, Daniel] Univ Warwick, Warwick Med Sch, Clin Sci Res Inst, Coventry CV4 7AL, W Midlands, England.
RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, 55 Fruit St,Bulfinch 127, Boston, MA 02114 USA.
EM thadhani.r@mgh.harvard.edu
RI Lloyd-Jones, Donald/C-5899-2009; Solomon, Scott/I-5789-2013;
Cannata-Andia, Jorge/L-2260-2013;
OI Zoccali, Carmine/0000-0002-6616-1996
FU Abbott Laboratories; Pfizer; Roche
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Thadhani reported receiving a
coordinating grant from Abbott Laboratories to the Massachusetts General
Hospital and speaker's fees and travel support from Abbott Laboratories.
Drs Pritchett, Andress, and Zhang are employees of Abbott Laboratories
and may own Abbott stock or options. Dr Agarwal reported receiving
honoraria for serving on the speaker's bureau and steering committees of
Abbott Laboratories. Dr Zoccali reported receiving consulting/honorarium
fees and travel support from Abbott Laboratories, honoraria for lectures
from Genzyme, Roche, Amgen, Abbott Laboratories, and Malesci and
research grants from Pfizer, Roche, and Abbott Laboratories. Drs Wanner
and Packham serve on an advisory board and have received travel support
from Abbott Laboratories. Dr Wanner has received research support and
speakers fees from Abbott Laboratories. Dr Zehnder reported receiving
honoraria for serving on a steering committee and for lectures from
Abbott Laboratories and receiving grants from Abbott Laboratories. Dr
Manning received travel support for a CMR meeting from Abbott
Laboratories. Dr Solomon is supported by a research grant from Abbott
Laboratories to the Brigham and Women's Hospital. No other disclosures
were reported.
NR 62
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Z9 218
U1 2
U2 18
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 FEB 15
PY 2012
VL 307
IS 7
BP 674
EP 684
DI 10.1001/jama.2012.120
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 892HY
UT WOS:000300278500024
PM 22337679
ER
PT J
AU Imataki, O
Ansen, S
Tanaka, M
Butler, MO
Berezovskaya, A
Milstein, MI
Kuzushima, K
Nadler, LM
Hirano, N
AF Imataki, Osamu
Ansen, Sascha
Tanaka, Makito
Butler, Marcus O.
Berezovskaya, Alla
Milstein, Matthew I.
Kuzushima, Kiyotaka
Nadler, Lee M.
Hirano, Naoto
TI IL-21 Can Supplement Suboptimal Lck-Independent MAPK Activation in a
STAT-3-Dependent Manner in Human CD8(+) T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CHRONIC VIRAL-INFECTION; MHC CLASS-I; ALPHA-3 DOMAIN MUTANTS;
BETA-CHAIN; EFFECTOR FUNCTION; CTL ACTIVATION; TUMOR-ANTIGENS; REACTIVE
CTL; AVIDITY; CORECEPTOR
AB Although both MHC class II/CD8 alpha double-knockout and CD8 beta null mice show a defect in the development of MHC class I-restricted CD8(+) T cells in the thymus, they possess low numbers of high-avidity peripheral CTL with limited clonality and are able to contain acute and chronic infections. These in vivo data suggest that the CD8 coreceptor is not absolutely necessary for the generation of Ag-specific CTL. Lack of CD8 association causes partial TCR signaling because of the absence of CD8/Lck recruitment to the proximity of the MHC/TCR complex, resulting in suboptimal MAPK activation. Therefore, there should exist a signaling mechanism that can supplement partial TCR activation caused by the lack of CD8 association. In this human study, we have shown that CD8-independent stimulation of Ag-specific CTL previously primed in the presence of CD8 coligation, either in vivo or in vitro, induced severely impaired in vitro proliferation. When naive CD8(+) T cells were primed in the absence of CD8 binding and subsequently restimulated in the presence of CD8 coligation, the proliferation of Ag-specific CTL was also severely hampered. However, when CD8-independent T cell priming and restimulation were supplemented with IL-21, Ag-specific CD8(+) CTL expanded in two of six individuals tested. We found that IL-21 rescued partial MAPK activation in a STAT3- but not STAT1-dependent manner. These results suggest that CD8 coligation is critical for the expansion of postthymic peripheral Ag-specific CTL in humans. However, STAT3-mediated IL-21 signaling can supplement partial TCR signaling caused by the lack of CD8 association. The Journal of Immunology, 2012, 188: 1609-1619.
C1 [Hirano, Naoto] Ontario Canc Inst, Immune Therapy Program, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2M9, Canada.
[Imataki, Osamu; Ansen, Sascha; Tanaka, Makito; Butler, Marcus O.; Berezovskaya, Alla; Milstein, Matthew I.; Nadler, Lee M.; Hirano, Naoto] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Imataki, Osamu; Ansen, Sascha; Tanaka, Makito; Butler, Marcus O.; Nadler, Lee M.; Hirano, Naoto] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA.
[Kuzushima, Kiyotaka] Aichi Canc Ctr, Res Inst, Aichi 4648681, Japan.
[Imataki, Osamu; Ansen, Sascha; Tanaka, Makito; Butler, Marcus O.; Nadler, Lee M.; Hirano, Naoto] Harvard Univ, Dept Med, Sch Med, Boston, MA 02215 USA.
[Hirano, Naoto] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada.
RP Hirano, N (reprint author), Ontario Canc Inst, Immune Therapy Program, Campbell Family Inst Breast Canc Res, 610 Univ Ave, Toronto, ON M5G 2M9, Canada.
EM nhirano@uhnres.utoronto.ca
FU National Institutes of Health [K22CA129240, R01CA148673]; Cancer
Research Institute; American Society of Hematology
FX This work was supported by National Institutes of Health Grants
K22CA129240 and R01CA148673 (to N.H.). M.T., M.O.B., and L.M.N. were
supported by funds from the Cancer Research Institute. N.H. was
supported by the American Society of Hematology Scholar Award.
NR 68
TC 8
Z9 8
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD FEB 15
PY 2012
VL 188
IS 4
BP 1609
EP 1619
DI 10.4049/jimmunol.1003446
PG 11
WC Immunology
SC Immunology
GA 890IT
UT WOS:000300139000006
PM 22238455
ER
PT J
AU Yui, N
Lu, HJ
Bouley, R
Brown, D
AF Yui, Naofumi
Lu, Hua Jenny
Bouley, Richard
Brown, Dennis
TI AQP2 is necessary for vasopressin- and forskolin-mediated filamentous
actin depolymerization in renal epithelial cells
SO BIOLOGY OPEN
LA English
DT Article
DE AQP2; Vasopressin; Actin cytoskeleton
AB Remodeling of the actin cytoskeleton is required for vasopressin (VP)-induced aquaporin 2 (AQP2) trafficking. Here, we asked whether VP and forskolin (FK)-mediated F-actin depolymerization depends on AQP2 expression. Using various MDCK and LLC-PK1 cell lines with different AQP2 expression levels, we performed F-actin quantification and immunofluorescence staining after VP/FK treatment. In MDCK cells, in which AQP2 is delivered apically, VP/FK mediated F-actin depolymerization was significantly correlated with AQP2 expression levels. A decrease of apical membrane associated F-actin was observed upon VP/FK treatment in AQP2 transfected, but not in untransfected cells. There was no change in basolateral actin staining under these conditions. In LLC-PK1 cells, which deliver AQP2 basolaterally, a significant VP/FK mediated decrease in F-actin was also detected only in AQP2 transfected cells. This depolymerization response to VP/FK was significantly reduced by siRNA knockdown of AQP2. By immunofluorescence, an inverse relationship between plasma membrane AQP2 and membrane-associated F-actin was observed after VP/FK treatment again only in AQP2 transfected cells. This is the first report showing that VP/FK mediated F-actin depolymerization is dependent on AQP2 protein expression in renal epithelial cells, and that this is not dependent on the polarity of AQP2 membrane insertion. (C) 2011. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0).
C1 [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Brown, D (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA.
EM brown.dennis@mgh.harvard.edu
FU NIH [DK38452, DK75940]; Gottschalk research grant (American Society of
Nephrology)
FX This work was supported by NIH grant DK38452 (DB, RB), DK75940, and a
Gottschalk research grant (American Society of Nephrology). We thank Dr
S. Uchida and Dr S. Sasaki (Tokyo Medical and Dental University) for
their providing us MDCK clones. We thank Dr M. Knepper (NIH) for
providing the pS261 AQP2 polyclonal antibody.
NR 43
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U2 4
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 2046-6390
J9 BIOL OPEN
JI Biol. Open
PD FEB 15
PY 2012
VL 1
IS 2
BP 101
EP 108
DI 10.1242/bio.2011042
PG 8
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA V36HZ
UT WOS:000209204700005
PM 23213402
ER
PT J
AU Julg, B
Poole, D
Ghebremichael, M
Castilla, C
Altfeld, M
Sunpath, H
Murphy, RA
Walker, BD
AF Julg, Boris
Poole, Danielle
Ghebremichael, Musie
Castilla, Carmen
Altfeld, Marcus
Sunpath, Henry
Murphy, Richard A.
Walker, Bruce D.
TI Factors Predicting Discordant Virological and Immunological Responses to
Antiretroviral Therapy in HIV-1 Clade C Infected Zulu/Xhosa in South
Africa
SO PLOS ONE
LA English
DT Article
ID CD4 CELL COUNT; 1-INFECTED PATIENTS; RECOVERY; COHORT; SUPPRESSION;
INDIVIDUALS; COMMUNITY; OUTCOMES; SEX
AB Factors predicting suboptimal CD4 cell recovery have been studied in HIV clade-B infected US and European populations. It is, however, uncertain to what extent these results are applicable to HIV clade-C infected African populations. Multivariate analysis using logistic regression and longitudinal analyses using mixed models were employed to assess the impact of age, gender, baseline CD4 cell count, hemoglobin, body mass index (BMI), tuberculosis and other opportunistic co-infections, and frequencies of regimen change on CD4 cell recovery at 12 and 30 months and on overtime change in CD4 cells among 442 virologically suppressed South Africans. Despite adequate virological response 37% (95% CI:32%-42%) and 83% (95% CI:79%-86%) of patients on antiretroviral therapy failed to restore CD4 cell counts >= 200 cells/mm(3) after 12 and >= 500 cells/mm(3) after 30 months, respectively, in this South African cohort. Critical risk factors for inadequate recovery were older age (p = 0.001) and nadir CD4 cell count at ART initiation (p < 0.0001), while concurrent TB co-infection, BMI, baseline hemoglobin, gender and antiretroviral regimen were not significant risk factors. These data suggest that greater efforts are needed to identify and treat HAART-eligible patients prior to severe CD4 cell decline or achievement of advanced age.
C1 [Julg, Boris; Poole, Danielle; Ghebremichael, Musie; Altfeld, Marcus; Walker, Bruce D.] MIT, Ragon Inst MGH, Boston, MA USA.
[Julg, Boris; Poole, Danielle; Altfeld, Marcus; Walker, Bruce D.] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Durban, South Africa.
[Julg, Boris; Poole, Danielle; Altfeld, Marcus; Walker, Bruce D.] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, Durban, South Africa.
[Ghebremichael, Musie] Harvard Univ, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Ghebremichael, Musie] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Castilla, Carmen] Univ Med & Dent New Jersey, Newark, NJ 07103 USA.
[Sunpath, Henry] McCord Hosp, Durban, South Africa.
[Murphy, Richard A.] Doctors Borders, Operat Support Unit, New York, NY USA.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Julg, B (reprint author), MIT, Ragon Inst MGH, Boston, MA USA.
EM bjulg@partners.org
FU Mark and Lisa Schwartz Foundation; Doris Duke Distinguished Clinical
Scientist Award; Howard Hughes Medical Institute; National Institutes of
Health [AI30914]; Ragon Institute of MGH, MIT and Harvard; McCord
Hospital; CDC
FX Financial support was provided by the Ragon Institute of MGH, MIT and
Harvard, the Mark and Lisa Schwartz Foundation, a Doris Duke
Distinguished Clinical Scientist Award to MA, and The Howard Hughes
Medical Institute (to BDW). Further support was provided by National
Institutes of Health grant AI30914 to BDW. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.; We wish to thank Roma Maharaj, Ansuri
Singh and Fiona Samed from Sinikithemba ARV clinic at McCord hospital
for their assistance in the collection of data; we wish to furthermore
thank Claire Kerry and the management of McCord Hospital for support of
this study. The Sinikithemba ARV clinic at Mc Cord hospital is a PEPFAR
and CDC funded programme.
NR 22
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Z9 7
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 FEB 14
PY 2012
VL 7
IS 2
AR e31161
DI 10.1371/journal.pone.0031161
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 925CF
UT WOS:000302737400011
PM 22348047
ER
PT J
AU Monje, M
Dietrich, J
AF Monje, Michelle
Dietrich, Joerg
TI Cognitive side effects of cancer therapy demonstrate a functional role
for adult neurogenesis
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Review
DE Hippocampal neurogenesis; Radiation; Chemotherapy; White matter; Late
effects; "Chemobrain"
ID CENTRAL-NERVOUS-SYSTEM; LONG-TERM SURVIVORS; HIPPOCAMPAL NEUROGENESIS;
BREAST-CANCER; ADJUVANT CHEMOTHERAPY; DENTATE GYRUS; CRANIAL
IRRADIATION; CELL-PROLIFERATION; RADIATION-THERAPY; BRAIN IRRADIATION
AB Cancer therapies frequently result in a spectrum of neurocognitive deficits that include impaired learning, memory, attention and speed of information processing. Damage to dynamic neural progenitor cell populations in the brain are emerging as important etiologic factors. Radiation and chemotherapy-induced damage to neural progenitor populations responsible for adult hippocampal neurogenesis and for maintenance of subcortical white matter integrity are now believed to play major roles in the neurocognitive impairment many cancer survivors experience. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Monje, Michelle] Stanford Univ, Med Ctr, Dept Neurol, Div Child Neurol, Palo Alto, CA 94304 USA.
[Dietrich, Joerg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr,Dept Neurol, Boston, MA 02114 USA.
[Dietrich, Joerg] Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA.
RP Monje, M (reprint author), Stanford Univ, Med Ctr, Dept Neurol, Div Child Neurol, 750 Welch Rd,Suite 317, Palo Alto, CA 94304 USA.
EM mmonje@stanford.edu; jdietrich1@partners.org
FU National Institutes of Health, National Institute of Neurological
Disorders and Stroke (NINDS) [1K08NS070926 - 01]; Paul Calabresi Career
Development Award for Clinical Oncology; Stephen E. and Catherine Pappas
Foundation
FX The authors gratefully acknowledge support from the National Institutes
of Health, National Institute of Neurological Disorders and Stroke
(NINDS) grant 1K08NS070926 - 01 (MM.), Paul Calabresi Career Development
Award for Clinical Oncology (J.D.), and the Stephen E. and Catherine
Pappas Foundation Award for Brain Tumor Research (J.D.).
NR 60
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U1 0
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD FEB 14
PY 2012
VL 227
IS 2
SI SI
BP 376
EP 379
DI 10.1016/j.bbr.2011.05.012
PG 4
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 907FU
UT WOS:000301404000010
PM 21621557
ER
PT J
AU Meirelles, K
Benedict, LA
Dombkowski, D
Pepin, D
Preffer, FI
Teixeira, J
Tanwar, PS
Young, RH
MacLaughlin, DT
Donahoe, PK
Wei, XL
AF Meirelles, Katia
Benedict, Leo Andrew
Dombkowski, David
Pepin, David
Preffer, Frederic I.
Teixeira, Jose
Tanwar, Pradeep Singh
Young, Robert H.
MacLaughlin, David T.
Donahoe, Patricia K.
Wei, Xiaolong
TI Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin
but inhibited by Mullerian inhibiting substance
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE chemotherapy with cisplatin; pluripotency factors
ID STEM-CELLS; TGF-BETA; CHEMOTHERAPEUTIC-AGENTS; MESENCHYMAL TRANSITION;
EPITHELIAL-CELLS; DUCT REGRESSION; MESSENGER-RNA; CYCLE ARREST; HUMAN
TUMORS; II RECEPTOR
AB Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad-) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+ Ecad- cells. Similarly, proliferation of the 3+ Ecad- cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3-Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+ Ecad- subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+ Ecad- cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR-5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics.
C1 [Meirelles, Katia; Benedict, Leo Andrew; Pepin, David; MacLaughlin, David T.; Donahoe, Patricia K.; Wei, Xiaolong] Massachusetts Gen Hosp, Dept Surg, Pediat Surg Res Labs, Boston, MA 02114 USA.
[Dombkowski, David; Preffer, Frederic I.] Massachusetts Gen Hosp, Flow Cytometry Lab, Boston, MA 02114 USA.
[Preffer, Frederic I.; Young, Robert H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Teixeira, Jose; Tanwar, Pradeep Singh] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA.
[Teixeira, Jose; Tanwar, Pradeep Singh] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Dept Surg, Pediat Surg Res Labs, Boston, MA 02114 USA.
EM pdonahoe@partners.org; xwei2@partners.org
OI Teixeira, Jose/0000-0002-6438-5064
FU National Research Service [T32 CA071345-13]; Tufts Medical Center;
Massachusetts General Hospital Executive Committee on Research Award;
Surdna-Gar Foundation; National Institute of Child Health and Human
Development [R01HD052701]; National Center for Research Resources
[1S10RR023440-01A1, 1S10RR020936-01]; National Institutes of Health [R01
CA17393]; Harvard Stem Cell Institute; Department of Defense; Julie Fund
FX We thank Ms. Caroline Coletti for editorial support; Dr. George Daley
for Let-7 primers; Dr. Samuel C. Mok for HOSE-4 and -6; Dr. Denise C.
Connolly for MOVCAR-7 and -8 cell lines; Scott Monsma at Primorigen for
conjugated LIN28 monoclonal antibody; and Dr. Peter R. Mueller
(Department of Radiology, Massachusetts General Hospital and Harvard
Medical School) for providing de-identified discarded specimens from
ovarian cancer patients (MGH IRB 2007P001918/6 and Dana-Farber Cancer
Institute IRB 02051). These studies were supported by National Research
Service Award T32 CA071345-13 (to K.M.); a Kiwanis Award from Tufts
Medical Center (to L.A.B.); a Massachusetts General Hospital Executive
Committee on Research Award and the Surdna-Gar Foundation (X.W.);
National Institute of Child Health and Human Development Grant
R01HD052701 (to J.T.); National Center for Research Resources Grants
1S10RR023440-01A1 and 1S10RR020936-01 (to F.P.); National Institutes of
Health Grant R01 CA17393 (to P.K.D. and D.T.M.); the Harvard Stem Cell
Institute; the Department of Defense Ovarian Cancer Research Program;
the Julie Fund (P.K.D.); and gifts from Commons Development, the McBride
Family Foundation, and the Austen Foundation.
NR 54
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U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 14
PY 2012
VL 109
IS 7
BP 2358
EP 2363
DI 10.1073/pnas.1120733109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895IH
UT WOS:000300489200044
PM 22308459
ER
PT J
AU Kebede, M
Ferdaoussi, M
Mancini, A
Alquier, T
Kulkarni, RN
Walker, MD
Poitout, V
AF Kebede, Melkam
Ferdaoussi, Mourad
Mancini, Arturo
Alquier, Thierry
Kulkarni, Rohit N.
Walker, Michael D.
Poitout, Vincent
TI Glucose activates free fatty acid receptor 1 gene transcription via
phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of
pancreas-duodenum homeobox-1
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID STIMULATED INSULIN-SECRETION; LINKED N-ACETYLGLUCOSAMINE; BETA-CELLS;
GLCNAC TRANSFERASE; POSTTRANSLATIONAL MODIFICATION; IN-VIVO; GPR40;
EXPRESSION; NUCLEAR; GLYCOSYLATION
AB The G protein-coupled free fatty acid receptor-1 (FFA1/GPR40) plays a major role in the regulation of insulin secretion by fatty acids. GPR40 is considered a potential therapeutic target to enhance insulin secretion in type 2 diabetes; however, its mode of regulation is essentially unknown. The aims of this study were to test the hypothesis that glucose regulates GPR40 gene expression in pancreatic beta-cells and to determine the mechanisms of this regulation. We observed that glucose stimulates GPR40 gene transcription in pancreatic beta-cells via increased binding of pancreas-duodenum homeobox-1 (Pdx-1) to the A-box in the HR2 region of the GPR40 promoter. Mutation of the Pdx-1 binding site within the HR2 abolishes glucose activation of GPR40 promoter activity. The stimulation of GPR40 expression and Pdx-1 binding to the HR2 in response to glucose are mimicked by N-acetyl glucosamine, an intermediate of the hexosamine biosynthesis pathway, and involve PI3K-dependent O-GlcNAcylation of Pdx-1 in the nucleus. We demonstrate that O-GlcNAc transferase (OGT) interacts with the product of the PI3K reaction, phosphatidylinositol 3,4,5-trisphosphate (PIP3), in the nucleus. This interaction enables OGT to catalyze O-GlcNAcylation of nuclear proteins, including Pdx-1. We conclude that glucose stimulates GPR40 gene expression at the transcriptional level through Pdx-1 binding to the HR2 region and via a signaling cascade that involves an interaction between OGT and PIP3 at the nuclear membrane. These observations reveal a unique mechanism by which glucose metabolism regulates the function of transcription factors in the nucleus to induce gene expression.
C1 [Kebede, Melkam; Ferdaoussi, Mourad; Mancini, Arturo; Alquier, Thierry; Poitout, Vincent] Univ Montreal, CRCHUM, Montreal Diabet Res Ctr, Montreal, PQ H3T 1J4, Canada.
[Kebede, Melkam; Ferdaoussi, Mourad; Mancini, Arturo; Alquier, Thierry; Poitout, Vincent] Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.
[Poitout, Vincent] Univ Montreal, Dept Nutr, Montreal, PQ H3T 1J4, Canada.
[Poitout, Vincent] Univ Montreal, Dept Biochem, Montreal, PQ H3T 1J4, Canada.
[Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA.
[Walker, Michael D.] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
RP Poitout, V (reprint author), Univ Montreal, CRCHUM, Montreal Diabet Res Ctr, Montreal, PQ H3T 1J4, Canada.
EM vincent.poitout@umontreal.ca
OI Alquier, Thierry/0000-0001-8171-802X; Poitout,
Vincent/0000-0002-6555-5053
FU University of Alberta; Coordinating Center of the National Institutes of
Health/National Institute of Diabetes and Digestive and Kidney Diseases;
Canadian Institutes of Health Research [MOP-86545]; National Institutes
of Health [R01-DK67536]; Canadian Diabetes Association; Diabete Quebec;
Centre de Recherche du Centre Hospitalier de l'Universite de Montreal
FX We thank Drs. James Shapiro and Tatsuya Kin from the University of
Alberta and the Coordinating Center of the National Institutes of
Health/National Institute of Diabetes and Digestive and Kidney
Diseases-supported Integrated Islet Distribution Program for providing
isolated human islets. This study was supported by the Canadian
Institutes of Health Research Grant MOP-86545 (to V.P.) and National
Institutes of Health Grant R01-DK67536 (to R.N.K.). M.K. is the
recipient of a postdoctoral fellowship from the Canadian Diabetes
Association. M.F. is the recipient of postdoctoral fellowships from
Diabete Quebec and from the Centre de Recherche du Centre Hospitalier de
l'Universite de Montreal. V.P. holds the Canada Research Chair in
Diabetes and Pancreatic Beta-cell Function.
NR 41
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U1 0
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 14
PY 2012
VL 109
IS 7
BP 2376
EP 2381
DI 10.1073/pnas.1114350109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895IH
UT WOS:000300489200047
PM 22308370
ER
PT J
AU Oksenych, V
Alt, FW
Kumar, V
Schwer, B
Wesemann, DR
Hansen, E
Patel, H
Su, A
Guo, CG
AF Oksenych, Valentyn
Alt, Frederick W.
Kumar, Vipul
Schwer, Bjoern
Wesemann, Duane R.
Hansen, Erica
Patel, Harin
Su, Arthur
Guo, Chunguang
TI Functional redundancy between repair factor XLF and damage response
mediator 53BP1 in V(D)J recombination and DNA repair
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE ataxia telangiectasia-mutated; double-strand DNA break repair; NHEJ1;
Cernunnos
ID CLASS-SWITCH RECOMBINATION; END-JOINING PATHWAY; LIGASE IV DEFICIENCY;
DOUBLE-STRAND BREAKS; CHROMOSOMAL TRANSLOCATIONS; HOMOLOGOUS
RECOMBINATION; DEFECTIVE NEUROGENESIS; GENOMIC INSTABILITY; CELLS;
SUPPRESSION
AB The classical nonhomologous DNA end-joining (C-NHEJ) double-strand break (DSB) repair pathway in mammalian cells maintains genome stability and is required for V(D)J recombination and lymphocyte development. Mutations in the XLF C-NHEJ factor or ataxia telangiectasia-mutated (ATM) DSB response protein cause radiosensitivity and immunodeficiency in humans. Although potential roles for XLF in C-NHEJ are unknown, ATM activates a general DSB response by phosphorylating substrates, including histone H2AX and 53BP1, which are assembled into chromatin complexes around DSBs. In mice, C-NHEJ, V(D) J recombination, and lymphocyte development are, at most, modestly impaired in the absence of XLF or ATM, but are severely impaired in the absence of both. Redundant functions of XLF and ATM depend on ATM kinase activity; correspondingly, combined XLF and H2AX deficiency severely impairs V(D) J recombination, even though H2AX deficiency alone has little impact on this process. These and other findings suggest that XLF may provide functions that overlap more broadly with assembled DSB response factors on chromatin. As one test of this notion, we generated mice and cells with a combined deficiency for XLF and 53BP1. In this context, 53BP1 deficiency, although leading to genome instability, has only modest effects on V(D) J recombination or lymphocyte development. Strikingly, we find that combined XLF/53BP1 deficiency in mice severely impairs C-NHEJ, V(D) J recombination, and lymphocyte development while also leading to general genomic instability and growth defects. We conclude that XLF is functionally redundant with multiple members of the ATM-dependent DNA damage response in facilitating C-NHEJ and discuss implications of our findings for potential functions of these factors.
C1 [Oksenych, Valentyn; Alt, Frederick W.; Kumar, Vipul; Schwer, Bjoern; Wesemann, Duane R.; Hansen, Erica; Patel, Harin; Su, Arthur; Guo, Chunguang] Harvard Univ, Sch Med, Dept Genet, Childrens Hosp,Immune Dis Inst,Howard Hughes Med, Boston, MA 02115 USA.
[Wesemann, Duane R.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Dept Med, Boston, MA 02115 USA.
RP Alt, FW (reprint author), Harvard Univ, Sch Med, Dept Genet, Childrens Hosp,Immune Dis Inst,Howard Hughes Med, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu; cguo@idi.harvard.edu
OI Oksenych, Valentyn/0000-0002-5088-3791
FU National Institutes of Health [AI076210, K08AI89972]; American
Association of Allergy Asthma and Immunology; CSL Behring; Burroughs
Wellcome Fund
FX We thank Dr. B. Sleckman for providing 53BP1-/- mice with a
Bcl2 transgene. This work is supported by National Institutes of Health
Grant AI076210 (to F. W. A.). D. R. W. is supported by National
Institutes of Health Grant K08AI89972 and by an award from the American
Association of Allergy Asthma and Immunology and CSL Behring and holds a
Career Award for Medical Scientists from the Burroughs Wellcome Fund. F.
W. A. is an investigator of the Howard Hughes Medical Institute. C. G.
is a fellow of Cancer Research Institute.
NR 28
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U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 14
PY 2012
VL 109
IS 7
BP 2455
EP 2460
DI 10.1073/pnas.1121458109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895IH
UT WOS:000300489200061
PM 22308489
ER
PT J
AU Gewurz, BE
Towfic, F
Mar, JC
Shinners, NP
Takasaki, K
Zhao, B
Cahir-McFarland, ED
Quackenbush, J
Xavier, RJ
Kieff, E
AF Gewurz, Benjamin E.
Towfic, Fadi
Mar, Jessica C.
Shinners, Nicholas P.
Takasaki, Kaoru
Zhao, Bo
Cahir-McFarland, Ellen D.
Quackenbush, John
Xavier, Ramnik J.
Kieff, Elliott
TI Genome-wide siRNA screen for mediators of NF-kappa B activation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE lymphoma; inflammation; signaling; oncogene; cytokine
ID EPSTEIN-BARR-VIRUS; MEMBRANE-PROTEIN 1; CHAIN ASSEMBLY COMPLEX;
SIGNAL-TRANSDUCTION; NEUROTROPHIN RECEPTOR; IMMUNE-SYSTEM; CELL
LYMPHOMA; TNF-ALPHA; IKK-ALPHA; PATHWAY
AB Although canonical NF kappa B is frequently critical for cell proliferation, survival, or differentiation, NF kappa B hyperactivation can cause malignant, inflammatory, or autoimmune disorders. Despite intensive study, mammalian NF kappa B pathway loss-of-function RNAi analyses have been limited to specific protein classes. We therefore undertook a human genome-wide siRNA screen for novel NF kappa B activation pathway components. Using an Epstein Barr virus latent membrane protein (LMP1) mutant, the transcriptional effects of which are canonical NF kappa B-dependent, we identified 155 proteins significantly and substantially important for NF kappa B activation in HEK293 cells. These proteins included many kinases, phosphatases, ubiquitin ligases, and deubiquinating enzymes not previously known to be important for NF kappa B activation. Relevance to other canonical NF kappa B pathways was extended by finding that 118 of the 155 LMP1 NF-kappa B activation pathway components were similarly important for IL-1 beta-, and 79 for TNF alpha-mediated NF kappa B activation in the same cells. MAP3K8, PIM3, and six other enzymes were uniquely relevant to LMP1-mediated NF kappa B activation. Most novel pathway components functioned upstream of I kappa B kinase complex (IKK) activation. Robust siRNA knockdown effects were confirmed for all mRNAs or proteins tested. Although multiple ZC3H-family proteins negatively regulate NF kappa B, ZC3H13 and ZC3H18 were activation pathway components. ZC3H13 was critical for LMP1, TNF alpha, and IL-1 beta NF kappa B-dependent transcription, but not for IKK activation, whereas ZC3H18 was critical for IKK activation. Down-modulators of LMP1 mediated NF kappa B activation were also identified. These experiments identify multiple targets to inhibit or stimulate LMP1-, IL-1 beta-, or TNF alpha-mediated canonical NF kappa B activation.
C1 [Gewurz, Benjamin E.; Shinners, Nicholas P.; Takasaki, Kaoru; Zhao, Bo; Cahir-McFarland, Ellen D.; Kieff, Elliott] Brigham & Womens Hosp, Dept Med & Microbiol & Mol Genet, Channing Lab, Boston, MA 02115 USA.
[Gewurz, Benjamin E.; Shinners, Nicholas P.; Takasaki, Kaoru; Zhao, Bo; Cahir-McFarland, Ellen D.; Kieff, Elliott] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Towfic, Fadi; Mar, Jessica C.; Xavier, Ramnik J.] Harvard Univ, Ctr Computat & Integrat Biol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Towfic, Fadi; Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Mar, Jessica C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
RP Kieff, E (reprint author), Brigham & Womens Hosp, Dept Med & Microbiol & Mol Genet, Channing Lab, Boston, MA 02115 USA.
EM ekieff@rics.bwh.harvard.edu
RI Zhao, Bo/B-3852-2014
FU National Cancer Institute [K08CA140780, R01CA085180, R01CA47006,
5T32CA009031]; National Human Genome Research Institute
[HGS5P50HG004233]; National Institute of Allergy and Infectious Diseases
[U54AI057159]; National Institute of Diabetes, Digestive, and Kidney
Diseases [R01043351, R0183756]; National Center for Research Resources
[UL1RR025758]; [R01AI062773]
FX We thank E. Davis (MD Anderson) for I kappa B alpha-Photinus and Renilla
luciferase vectors and technical assistance; T. Yasui (Osaka University)
for Tet-On DsRed; D. Hill and M. Vidal (Harvard Medical School) for
split YFP expression vectors; W. Khan (University of Miami) for a GST-I
kappa B alpha expression vector; D. Portal for help with figure
preparation; D. Boehm for helpful discussions and technical assistance,
and G. Hoffman, A. Brass, J. Smith, C. Shamu, D. Wrobel, S. Rudnicki, S.
Johnston, M. Padi, E. Bennett, M. Sowa, and J. W. Harper for helpful
discussions. B. E. G. is a fellow of the Leukemia and Lymphoma Society
and the Karin Grunebaum Cancer Foundation. This research was supported
by National Cancer Institute Grants K08CA140780 (to B. E. G.),
R01CA085180 (to E. K.), R01CA47006 (to E. K.), and 5T32CA009031 (to
N.S.), by National Human Genome Research Institute Grant HGS5P50HG004233
(to E. K. and J.Q.), by National Institute of Allergy and Infectious
Diseases Grants U54AI057159 to the New England Regional Center of
Excellence in Biodefense and Emerging Infectious Diseases and
R01AI062773 (to R.J.X.), by National Institute of Diabetes, Digestive,
and Kidney Diseases Grants R01043351 and R0183756 (to R.J.X.), and by
National Center for Research Resources Harvard Catalyst Grant
UL1RR025758 (to B.E.G.).
NR 57
TC 29
Z9 29
U1 1
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 FEB 14
PY 2012
VL 109
IS 7
BP 2467
EP 2472
DI 10.1073/pnas.1120542109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895IH
UT WOS:000300489200063
PM 22308454
ER
PT J
AU Boboila, C
Oksenych, V
Gostissa, M
Wang, JH
Zha, S
Zhang, Y
Chai, H
Lee, CS
Jankovic, M
Saez, LMA
Nussenzweig, MC
McKinnon, PJ
Alt, FW
Schwer, B
AF Boboila, Cristian
Oksenych, Valentyn
Gostissa, Monica
Wang, Jing H.
Zha, Shan
Zhang, Yu
Chai, Hua
Lee, Cheng-Sheng
Jankovic, Mila
Saez, Liz-Marie Albertorio
Nussenzweig, Michel C.
McKinnon, Peter J.
Alt, Frederick W.
Schwer, Bjoern
TI Robust chromosomal DNA repair via alternative end-joining in the absence
of X-ray repair cross-complementing protein 1 (XRCC1)
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID CLASS-SWITCH RECOMBINATION; STRAND BREAK REPAIR; LIGASE-III; B-CELLS;
V(D)J RECOMBINATION; SOMATIC HYPERMUTATION; MAMMALIAN-CELLS;
TRANSLOCATIONS; PATHWAY; MECHANISMS
AB Classical nonhomologous DNA end-joining (C-NHEJ), which is a major DNA double-strand break (DSB) repair pathway in mammalian cells, plays a dominant role in joining DSBs during Ig heavy chain (IgH) class switch recombination (CSR) in activated B lymphocytes. However, in B cells deficient for one or more requisite C-NHEJ factors, such as DNA ligase 4 (Lig4) or XRCC4, end-joining during CSR occurs by a distinct alternative end-joining (A-EJ) pathway. A-EJ also has been implicated in joining DSBs found in oncogenic chromosomal translocations. DNA ligase 3 (Lig3) and its cofactor XRCC1 are widely considered to be requisite A-EJ factors, based on biochemical studies or extrachromosomal substrate end-joining studies. However, potential roles for these factors in A-EJ of endogenous chromosomal DSBs have not been tested. Here, we report that Xrcc1 inactivation via conditional gene-targeted deletion in WT or XRCC4-deficient primary B cells does not have an impact on either CSR or IgH/c-myc translocations in activated B lymphocytes. Indeed, homozygous deletion of Xrcc1 does not impair A-EJ of I-SceI-induced DSBs in XRCC4-deficient pro-B-cell lines. Correspondingly, substantial depletion of Lig3 in Lig4-deficient primary B cells or B-cell lines does not impair A-EJ of CSR-mediated DSBs or formation of IgH/c-myc translocations. Our findings firmly demonstrate that XRCC1 is not a requisite factor for A-EJ of chromosomal DSBs and raise the possibility that DNA ligase 1 (Lig1) may contribute more to A-EJ than previously considered.
C1 [Boboila, Cristian; Oksenych, Valentyn; Gostissa, Monica; Wang, Jing H.; Zha, Shan; Zhang, Yu; Chai, Hua; Lee, Cheng-Sheng; Alt, Frederick W.; Schwer, Bjoern] Harvard Univ, Program Cellular & Mol Med, Howard Hughes Med Inst, Childrens Hosp Boston,Med Sch, Boston, MA 02115 USA.
[Boboila, Cristian; Oksenych, Valentyn; Gostissa, Monica; Wang, Jing H.; Zha, Shan; Zhang, Yu; Chai, Hua; Lee, Cheng-Sheng; Alt, Frederick W.; Schwer, Bjoern] Harvard Univ, Dept Genet, Immune Dis Inst, Sch Med, Boston, MA 02115 USA.
[Jankovic, Mila; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, Howard Hughes Med Inst, New York, NY 10065 USA.
[Saez, Liz-Marie Albertorio] Univ Puerto Rico, Dept Biol, Mayaguez, PR 00680 USA.
[McKinnon, Peter J.] St Jude Childrens Hosp, Dept Genet, Memphis, TN 38105 USA.
RP Alt, FW (reprint author), Harvard Univ, Program Cellular & Mol Med, Howard Hughes Med Inst, Childrens Hosp Boston,Med Sch, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu; schwer@idi.harvard.edu
RI Wang, Jing/M-7813-2015;
OI Wang, Jing/0000-0003-4343-2527; Oksenych, Valentyn/0000-0002-5088-3791
FU National Institutes of Health [AI031541, CA092625, NS-37956, CA-21765,
AI037526, 5T32CA009382, 5T32CA009382-26]; Leukemia and Lymphoma Society
of America; Cancer Research Institute
FX We thank Maria-Vivienne Boboila for stimulating discussions and critical
reading of the manuscript; Erica Hansen, Grace Yuen, and Duane Wesemann
for help with experiments and suggestions; Ralph Scully for providing
the I-SceI vectors; and Kefei Yu for providing the Lig4 null CH12F3
cells. This work was supported by National Institutes of Health Grants
AI031541 and CA092625 (to F. W. A.), NS-37956 and CA-21765 (to P.J.M.),
and AI037526 (to M.C.N.). B. S. was supported by National Institutes of
Health Training Grant 5T32CA009382. J.H.W. was supported by a Leukemia
and Lymphoma Society of America Special Fellowship and by National
Institutes of Health Training Grant 5T32CA009382-26. C. B. was supported
by a Cancer Research Institute training grant. Y.Z. was supported by a
Cancer Research Institute postdoctoral fellowship. M. G. is a V
Foundation Scholar. F. W. A. and M.C.N. are investigators of the Howard
Hughes Medical Institute.
NR 53
TC 50
Z9 51
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 14
PY 2012
VL 109
IS 7
BP 2473
EP 2478
DI 10.1073/pnas.1121470109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895IH
UT WOS:000300489200064
PM 22308491
ER
PT J
AU Cortez-Retamozo, V
Etzrodt, M
Newton, A
Rauch, PJ
Chudnovskiy, A
Berger, C
Ryan, RJH
Iwamoto, Y
Marinelli, B
Gorbatov, R
Forghani, R
Novobrantseva, TI
Koteliansky, V
Figueiredo, JL
Chen, JW
Anderson, DG
Nahrendorf, M
Swirski, FK
Weissleder, R
Pittet, MJ
AF Cortez-Retamozo, Virna
Etzrodt, Martin
Newton, Andita
Rauch, Philipp J.
Chudnovskiy, Aleksey
Berger, Cedric
Ryan, Russell J. H.
Iwamoto, Yoshiko
Marinelli, Brett
Gorbatov, Rostic
Forghani, Reza
Novobrantseva, Tatiana I.
Koteliansky, Victor
Figueiredo, Jose-Luiz
Chen, John W.
Anderson, Daniel G.
Nahrendorf, Matthias
Swirski, Filip K.
Weissleder, Ralph
Pittet, Mikael J.
TI Origins of tumor-associated macrophages and neutrophils
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cancer immunity; tumor microenvironment
ID DENDRITIC CELLS; PROGENITOR CELLS; INFLAMMATORY MONOCYTES;
SUPPRESSOR-CELLS; IMMUNE-SYSTEM; CANCER; MICE; CHEMOTHERAPY;
SPLENECTOMY; METASTASIS
AB Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) can control cancer growth and exist in almost all solid neoplasms. The cells are known to descend from immature monocytic and granulocytic cells, respectively, which are produced in the bone marrow. However, the spleen is also a recently identified reservoir of monocytes, which can play a significant role in the inflammatory response that follows acute injury. Here, we evaluated the role of the splenic reservoir in a genetic mouse model of lung adenocarcinoma driven by activation of oncogenic Kras and inactivation of p53. We found that high numbers of TAM and TAN precursors physically relocated from the spleen to the tumor stroma, and that recruitment of tumor-promoting spleen-derived TAMs required signaling of the chemokine receptor CCR2. Also, removal of the spleen, either before or after tumor initiation, reduced TAM and TAN responses significantly and delayed tumor growth. The mechanism by which the spleen was able to maintain its reservoir capacity throughout tumor progression involved, in part, local accumulation in the splenic red pulp of typically rare extramedullary hematopoietic stem and progenitor cells, notably granulocyte and macrophage progenitors, which produced CD11b(+) Ly-6C(hi) monocytic and CD11b(+) Ly-6G(hi) granulocytic cells locally. Splenic granulocyte and macrophage progenitors and their descendants were likewise identified in clinical specimens. The present study sheds light on the origins of TAMs and TANs, and positions the spleen as an important extramedullary site, which can continuously supply growing tumors with these cells.
C1 [Cortez-Retamozo, Virna; Etzrodt, Martin; Newton, Andita; Rauch, Philipp J.; Chudnovskiy, Aleksey; Berger, Cedric; Iwamoto, Yoshiko; Marinelli, Brett; Gorbatov, Rostic; Forghani, Reza; Figueiredo, Jose-Luiz; Chen, John W.; Nahrendorf, Matthias; Swirski, Filip K.; Weissleder, Ralph; Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Cortez-Retamozo, Virna; Etzrodt, Martin; Newton, Andita; Rauch, Philipp J.; Chudnovskiy, Aleksey; Berger, Cedric; Iwamoto, Yoshiko; Marinelli, Brett; Gorbatov, Rostic; Forghani, Reza; Figueiredo, Jose-Luiz; Chen, John W.; Nahrendorf, Matthias; Swirski, Filip K.; Weissleder, Ralph; Pittet, Mikael J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Ryan, Russell J. H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Novobrantseva, Tatiana I.; Koteliansky, Victor] Alnylam Pharmaceut, Cambridge, MA 02142 USA.
[Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Weissleder, Ralph] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02115 USA.
RP Pittet, MJ (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
EM mpittet@mgh.harvard.edu
RI Etzrodt, Martin/P-3325-2015
OI Etzrodt, Martin/0000-0003-1928-3904
FU Alnylam Pharmaceuticals; National Institutes of Health [P50-CA86355,
R01-AI084880, R56-AI084880, U54-CA126515]; American Association for
Cancer Research; Boehringer Ingelheim Fonds
FX T.I.N. and V.K. are Alnylam Pharmaceuticals employees, and D.G.A.
receives funding from, and is a consultant with, Alnylam
Pharmaceuticals.; We thank T. Jacks (Massachusetts Institute of
Technology), R. Weinberg (Whitehead Institute, Cambridge, MA), and E.
Meylan and M. Winslow (Massachusetts Institute of Technology) for
helpful discussions; K. Hassard, S. Holder, and the Massachusetts
General Hospital surgical pathology accessioners for assistance with
human tissue collection; J. Sullivan and R. Kohler (Massachusetts
General Hospital) for imaging; M. Maier, H. Epstein-Barash, and W.
Cantley for medium-scale siRNA synthesis and formulation (Alnylam); and
M. Waring (Ragon Institute, Massachusetts General Hospital) for sorting
cells. This work was supported, in part, by National Institutes of
Health Grants P50-CA86355, R01-AI084880, and R56-AI084880 (to M. J. P.)
and National Institutes of Health Grant U54-CA126515 (to R. W.). M. E.
was supported by the American Association for Cancer Research Centennial
Predoctoral Fellowship and the Boehringer Ingelheim Fonds.
NR 43
TC 170
Z9 176
U1 11
U2 60
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 14
PY 2012
VL 109
IS 7
BP 2491
EP 2496
DI 10.1073/pnas.1113744109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895IH
UT WOS:000300489200067
PM 22308361
ER
PT J
AU Tsuji-Takechi, K
Negishi-Koga, T
Sumiya, E
Kukita, A
Kato, S
Maeda, T
Pandolfi, PP
Moriyama, K
Takayanagi, H
AF Tsuji-Takechi, Kaori
Negishi-Koga, Takako
Sumiya, Eriko
Kukita, Akiko
Kato, Shigeaki
Maeda, Takahiro
Pandolfi, Pier Paolo
Moriyama, Keiji
Takayanagi, Hiroshi
TI Stage-specific functions of leukemia/lymphoma-related factor (LRF) in
the transcriptional control of osteoclast development
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID BONE HOMEOSTASIS; GENE-EXPRESSION; POZ DOMAIN; DIFFERENTIATION; NFATC1;
POKEMON; PROTEIN; CANCER; MICE; OVEREXPRESSION
AB Cell fate determination is tightly regulated by transcriptional activators and repressors. Leukemia/lymphoma-related factor (LRF; encoded by Zbtb7a), known as a POK (POZ/BTB and Kruppel) family transcriptional repressor, is induced during the development of bone-resorbing osteoclasts, but the physiological significance of LRF in bone metabolism and the molecular mechanisms underlying the transcriptional regulation of osteoclastogenesis by LRF have not been elucidated. Here we show that LRF negatively regulates osteoclast differentiation by repressing nuclear factor of activated T cells c1 (NFATc1) induction in the early phase of osteoclast development, while positively regulating osteoclast-specific genes by functioning as a coactivator of NFATc1 in the bone resorption phase. The stage-specific distinct functions of LRF were demonstrated in two lines of conditional knockout mice in which LRF was deleted in the early or late phase of osteoclast development. Thus, this study shows that LRF plays stage-specific distinct roles in osteoclast differentiation, exemplifying the delicate transcriptional regulation at work in lineage commitment.
C1 [Tsuji-Takechi, Kaori; Negishi-Koga, Takako; Sumiya, Eriko; Takayanagi, Hiroshi] Tokyo Med & Dent Univ, Dept Cell Signaling, Grad Sch Med & Dent Sci, Bunkyo Ku, Tokyo 1138549, Japan.
[Tsuji-Takechi, Kaori; Negishi-Koga, Takako; Sumiya, Eriko; Moriyama, Keiji; Takayanagi, Hiroshi] Int Res Ctr Mol Sci Tooth & Bone Dis, Global Ctr Excellence Program, Bunkyo Ku, Tokyo 1138549, Japan.
[Tsuji-Takechi, Kaori; Moriyama, Keiji] Tokyo Med & Dent Univ, Dept Maxillofacial Orthognath, Grad Sch Med & Dent Sci, Bunkyo Ku, Tokyo 1138549, Japan.
[Negishi-Koga, Takako; Sumiya, Eriko; Takayanagi, Hiroshi] Japan Sci & Technol Agcy, Takayanagi Osteonetwork Project, Bunkyo Ku, Tokyo 1138549, Japan.
[Kukita, Akiko] Saga Univ, Fac Med, Dept Microbiol, Saga 8498501, Japan.
[Kato, Shigeaki] Univ Tokyo, Inst Mol & Cellular Biosci, Grad Sch Med, Bunkyo Ku, Tokyo 1130032, Japan.
[Maeda, Takahiro; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Canc Ctr,Canc Genet Program, Dept Med & Pathol,Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Takayanagi, Hiroshi] Univ Western Australia, Ctr Orthopaed Res, Sch Surg, Nedlands, WA 6009, Australia.
RP Takayanagi, H (reprint author), Tokyo Med & Dent Univ, Dept Cell Signaling, Grad Sch Med & Dent Sci, Bunkyo Ku, Tokyo 1138549, Japan.
EM taka.csi@tmd.ac.jp
FU Japan Science and Technology; Japan Society for the Promotion of
Science; Ministry of Education, Culture, Sports, Science and Technology
of Japan
FX We thank T. Kitamura and M. Matsumoto for kindly providing the
retroviral vectors and Plat-E cells, and the reporter plasmid pCtsk-luc,
respectively; and M. Shinohara, N. Komatsu, A. Terashima, T. Ando, Y.
Kunisawa, Y. Ogihara, and A. Suematsu for discussion and technical
assistance. This work was supported in part by a grant from Exploratory
Research for Advanced Technology, Takayanagi Osteonetwork Project from
Japan Science and Technology; a Grant-in-Aid for Scientific Research B;
a Grant-in-Aid for Young Scientist A; a Grant-in-Aid for Challenging
Exploratory Research from the Japan Society for the Promotion of
Science; and a grant from the Global Center of Excellence Program from
the Ministry of Education, Culture, Sports, Science and Technology of
Japan.
NR 36
TC 8
Z9 8
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 14
PY 2012
VL 109
IS 7
BP 2561
EP 2566
DI 10.1073/pnas.1116042109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 895IH
UT WOS:000300489200079
PM 22308398
ER
PT J
AU Dominy, JE
Vazquez, F
Puigserver, P
AF Dominy, John E.
Vazquez, Francisca
Puigserver, Pere
TI Glycine Decarboxylase Cleaves a "Malignant" Metabolic Path to Promote
Tumor Initiation
SO CANCER CELL
LA English
DT Editorial Material
ID STEM-CELLS; CANCER
AB Tumor-initiating cells (TICs) are thought to be critical for promoting tumorigenesis. In a recent Cell article, Zhang and colleagues found that non-small cell lung cancer TICs overexpress the metabolic enzyme glycine decarboxylase, which leads to increases in pyrimidine synthesis and is critical for proliferation and tumor initiation.
C1 [Dominy, John E.; Puigserver, Pere] Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA 02115 USA.
[Vazquez, Francisca] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Dominy, John E.; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Vazquez, Francisca] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
RP Puigserver, P (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA 02115 USA.
EM pere_puigserver@dfci.harvard.edu
NR 10
TC 3
Z9 3
U1 1
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD FEB 14
PY 2012
VL 21
IS 2
BP 143
EP 145
DI 10.1016/j.ccr.2012.01.019
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 895DI
UT WOS:000300476000004
PM 22340586
ER
PT J
AU Corrales-Medina, VF
Musher, DM
Wells, GA
Chirinos, JA
Chen, L
Fine, MJ
AF Corrales-Medina, Vicente F.
Musher, Daniel M.
Wells, George A.
Chirinos, Julio A.
Chen, Li
Fine, Michael J.
TI Cardiac Complications in Patients With Community-Acquired Pneumonia
Incidence, Timing, Risk Factors, and Association With Short-Term
Mortality
SO CIRCULATION
LA English
DT Article
DE pneumonia; complications; heart failure; arrhythmias, cardiac;
myocardial infarction
ID ACUTE CORONARY SYNDROMES; MYOCARDIAL-INFARCTION; HOSPITALIZED-PATIENTS;
CLINICAL-OUTCOMES; ACUTE INFECTION; UNITED-STATES; IMPACT; HEART;
SURVIVAL; EVENTS
AB Background-Community-acquired pneumonia (CAP) affects > 5 million adults each year in the United States. Although incident cardiac complications occur in patients with community-acquired pneumonia, their incidence, timing, risk factors, and associations with short-term mortality are not well understood.
Methods and Results-A total of 1343 inpatients and 944 outpatients with community-acquired pneumonia were followed up prospectively for 30 days after presentation. Incident cardiac complications (new or worsening heart failure, new or worsening arrhythmias, or myocardial infarction) were diagnosed in 358 inpatients (26.7%) and 20 outpatients (2.1%). Although most events (89.1% in inpatients, 75% in outpatients) were diagnosed within the first week, more than half of them were recognized in the first 24 hours. Factors associated with their diagnosis included older age (odds ratio [OR] = 1.03; 95% confidence interval [CI], 1.02-1.04), nursing home residence (OR, 1.8; 95% CI, 1.2-2.9), history of heart failure (OR, 4.3; 95% CI, 3.0-6.3), prior cardiac arrhythmias (OR, 1.8; 95% CI, 1.2-2.7), previously diagnosed coronary artery disease (OR, 1.5; 95% CI, 1.04-2.0), arterial hypertension (OR, 1.5; 95% CI, 1.1-2.1), respiratory rate >= 30 breaths per minute (OR, 1.6; 95% CI, 1.1-2.3), blood pH < 7.35 (OR, 3.2; 95% CI, 1.8 -5.7), blood urea nitrogen >= 30 mg/dL (OR, 1.5; 95% CI, 1.1-2.2), serum sodium < 130 mmol/L (OR, 1.8; 95% CI, 1.02-3.1), hematocrit < 30% (OR, 2.0; 95% CI, 1.3-3.2), pleural effusion on presenting chest x-ray (OR, 1.6; 95% CI, 1.1-2.4), and inpatient care (OR, 4.8; 95% CI, 2.8-8.3). Incident cardiac complications were associated with increased risk of death at 30 days after adjustment for baseline Pneumonia Severity Index score (OR, 1.6; 95% CI, 1.04-2.5).
Conclusions-Incident cardiac complications are common in patients with community-acquired pneumonia and are associated with increased short-term mortality. Older age, nursing home residence, preexisting cardiovascular disease, and pneumonia severity are associated with their occurrence. Further studies are required to test risk stratification and prevention and treatment strategies for cardiac complications in this population. (Circulation. 2012; 125: 773-781.)
C1 [Wells, George A.] Univ Ottawa, Dept Med, Ottawa, ON, Canada.
[Corrales-Medina, Vicente F.; Wells, George A.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
[Wells, George A.; Chen, Li] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON, Canada.
[Musher, Daniel M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Musher, Daniel M.] Baylor Coll Med, Dept Mol Virol, Houston, TX 77030 USA.
[Musher, Daniel M.] Baylor Coll Med, Dept Microbiol, Houston, TX 77030 USA.
[Musher, Daniel M.] Michael E DeBakey VA Med Ctr, Med Care Line Infect Dis Sect, Houston, TX USA.
[Chirinos, Julio A.] Philadelphia VA Med Ctr, Div Cardiol, Philadelphia, PA USA.
[Chirinos, Julio A.] Univ Penn, Philadelphia, PA 19104 USA.
[Fine, Michael J.] Univ Pittsburgh, Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Fine, Michael J.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA.
RP Corrales-Medina, VF (reprint author), 1053 Carling Ave,CPC 470, Ottawa, ON K1Y 4E9, Canada.
EM vcorrales@toh.on.ca
OI Corrales-Medina, Vicente/0000-0002-9691-491X
FU Agency for Healthcare Research and Quality; Department of Medicine of
the Ottawa Hospital; Ottawa Hospital Research Institute
FX The PORT study was funded by the Agency for Healthcare Research and
Quality. Dr Corrales-Medina is supported by a research priority grant
from the Department of Medicine of the Ottawa Hospital and a Junior
Investigator Award from the Ottawa Hospital Research Institute.
NR 33
TC 103
Z9 108
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 14
PY 2012
VL 125
IS 6
BP 773
EP U92
DI 10.1161/CIRCULATIONAHA.111.040766
PG 13
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 896XR
UT WOS:000300605200015
PM 22219349
ER
PT J
AU Cella, D
Bushmakin, AG
Cappelleri, JC
Charbonneau, C
Michaelson, MD
Motzer, RJ
AF Cella, D.
Bushmakin, A. G.
Cappelleri, J. C.
Charbonneau, C.
Michaelson, M. D.
Motzer, R. J.
TI Baseline quality of life as a prognostic survival tool in patients
receiving sunitinib for metastatic renal cell carcinoma
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE metastatic renal cell carcinoma; quality of life; prognostic tool;
sunitinib; survival; Weibull model
ID INTERFERON-ALPHA; TARGETED THERAPY; KIDNEY CANCER; SYMPTOMS;
THROMBOCYTOSIS; VALIDATION; SORAFENIB; TRIAL; SCALE
AB BACKGROUND: In a randomized phase III trial of sunitinib vs interferon-alfa (IFN-alpha) in metastatic renal cell carcinoma (mRCC), better baseline quality of life (QoL) was predictive of longer survival. Using this dataset, we have developed a novel prognostic tool that establishes a relationship between baseline QoL scores and median survival time.
METHODS: Baseline QoL was assessed using the FACT-Kidney Symptom Index-15 item (FKSI-15), its disease-related symptoms (FKSI-DRS) subscale, and the Functional Assessment of Cancer Therapy-General (FACT-G) scale. Weibull models estimated median progression-free survival (mPFS) and overall survival (mOS) as a function of baseline QoL.
RESULTS: Longer PFS and OS were associated with higher baseline FKSI-15, FKSI-DRS, and FACT-G scores (P<0.05), and baseline FKSI-15 score was the best predictor of survival. For example, for a baseline FKSI-15 score of 60, the predicted mPFS was 67.9 weeks, and predicted mOS was 240.6 weeks. The magnitude of benefit was greater with sunitinib vs IFN-alpha for a given baseline QoL score.
CONCLUSION: This novel tool indicates that baseline FKSI-15 scores were linked to mPFS and mOS in a clear and interpretable way. The results support evaluation of patient-reported QoL symptoms at baseline as a prognostic indicator of survival in clinical research and practice.
C1 [Cella, D.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL USA.
[Bushmakin, A. G.; Cappelleri, J. C.] Pfizer Oncol, Global Res & Dev, New London, CT USA.
[Charbonneau, C.] Pfizer Oncol, Global Outcomes Res, New York, NY USA.
[Michaelson, M. D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Motzer, R. J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Cella, D (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL USA.
EM d-cella@northwestern.edu
OI Michaelson, Dror/0000-0001-9249-6338
FU Pfizer
FX We would like to thank all of the participating patients and their
families, as well as the investigators, research nurses, study
coordinators, and operations staff. This study was sponsored by Pfizer.
Medical writing support was provided by Rachel Mason at ACUMED
(Tytherington, UK) and was funded by Pfizer.
NR 24
TC 11
Z9 11
U1 3
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD FEB 14
PY 2012
VL 106
IS 4
BP 646
EP 650
DI 10.1038/bjc.2011.589
PG 5
WC Oncology
SC Oncology
GA 892RL
UT WOS:000300303200006
PM 22240794
ER
PT J
AU Tanizaki, J
Okamoto, I
Takezawa, K
Sakai, K
Azuma, K
Kuwata, K
Yamaguchi, H
Hatashita, E
Nishio, K
Janne, PA
Nakagawa, K
AF Tanizaki, J.
Okamoto, I.
Takezawa, K.
Sakai, K.
Azuma, K.
Kuwata, K.
Yamaguchi, H.
Hatashita, E.
Nishio, K.
Janne, P. A.
Nakagawa, K.
TI Combined effect of ALK and MEK inhibitors in EML4-ALK-positive
non-small-cell lung cancer cells
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE EML4-ALK; non-small-cell lung cancer; apoptosis; BIM; survivin
ID EML4-ALK FUSION GENE; ANAPLASTIC LYMPHOMA; KINASE; IDENTIFICATION
AB BACKGROUND: Although most non-small-cell lung cancer (NSCLC) patients with the echinoderm microtubule-associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion gene - benefit from ALK tyrosine kinase inhibitors (ALK-TKIs), the efficacy of these drugs varies greatly among individuals.
METHODS: The antitumour action of ALK-TKIs in EML4-ALK-positive NSCLC cell lines was evaluated from their effects on cell proliferation, signal transduction, and apoptosis.
RESULTS: The ALK-TKI TAE684 inhibited cell proliferation and induced apoptosis, in association with inhibition of STAT3 and ERK phosphorylation, in EML4-ALK-positive H3122 cells. TAE684 inhibited STAT3 phosphorylation, but not ERK phosphorylation, and it showed little effect on cell proliferation or apoptosis, in EML4-ALK-positive H2228 cells. The combination of TAE684 and a MEK inhibitor-induced marked apoptosis accompanied by inhibition of STAT3 and ERK pathways in H2228 cells. Such dual interruption of STAT3 and ERK pathways induced downregulation of the antiapoptotic protein survivin and upregulation of the proapoptotic protein BIM.
CONCLUSION: Our results indicate that interruption of both STAT3-survivin and ERK-BIM pathways is required for induction of apoptosis in NSCLC harbouring EML4-ALK, providing a rationale for combination therapy with ALK and MEK inhibitors in EML4-ALK-positive NSCLC patients for whom ALK inhibitors alone are ineffective.
C1 [Tanizaki, J.; Okamoto, I.; Takezawa, K.; Sakai, K.; Azuma, K.; Kuwata, K.; Yamaguchi, H.; Hatashita, E.; Nakagawa, K.] Kinki Univ, Dept Med Oncol, Fac Med, Osaka 5898511, Japan.
[Nishio, K.] Kinki Univ, Dept Genome Biol, Fac Med, Osaka 5898511, Japan.
[Janne, P. A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA.
[Janne, P. A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
RP Okamoto, I (reprint author), Kinki Univ, Dept Med Oncol, Fac Med, 377-2 Ohno Higashi, Osaka 5898511, Japan.
EM chi-okamoto@dotd.med.kindai.ac.jp
NR 11
TC 17
Z9 22
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD FEB 14
PY 2012
VL 106
IS 4
BP 763
EP 767
DI 10.1038/bjc.2011.586
PG 5
WC Oncology
SC Oncology
GA 892RL
UT WOS:000300303200022
PM 22240786
ER
PT J
AU Brennan, JM
Dai, D
Patel, MR
Rao, SV
Armstrong, EJ
Messenger, JC
Curtis, JP
Shunk, KA
Anstrom, KJ
Eisenstein, EL
Weintraub, WS
Peterson, ED
Douglas, PS
Hillegass, WB
AF Brennan, J. Matthew
Dai, David
Patel, Manesh R.
Rao, Sunil V.
Armstrong, Ehrin J.
Messenger, John C.
Curtis, Jeptha P.
Shunk, Kendrick A.
Anstrom, Kevin J.
Eisenstein, Eric L.
Weintraub, William S.
Peterson, Eric D.
Douglas, Pamela S.
Hillegass, William B.
TI Characteristics and Long-Term Outcomes of Percutaneous Revascularization
of Unprotected Left Main Coronary Artery Stenosis in the United States
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE long-term outcomes; percutaneous revascularization; unprotected left
main coronary artery stenosis
ID DRUG-ELUTING STENTS; CARDIAC-SURGERY; DISEASE; REGISTRY; INTERVENTION;
IMPACT; SAFETY
AB Objectives This study sought to assess percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) stenosis in routine U. S. clinical practice.
Background Percutaneous coronary intervention for ULMCA stenosis is controversial; however, current use and outcomes of ULMCA PCI in routine U. S. clinical practice have not been described.
Methods We evaluated 5,627 patients undergoing ULMCA PCI at 693 centers within the National Cardiovascular Data Registry Catheterization Percutaneous Coronary Intervention Registry for temporal trends in PCI use (2004 to 2008), patient characteristics, and in-hospital mortality. Thirty-month mortality and composite major adverse events (death, myocardial infarction, and revascularization) with drug-eluting versus bare-metal stents were compared using inverse probability weighted (IPW) hazard ratios (HRs) in a nonrandomized Medicare-linked (age >= 65 years) patient cohort (n = 2,765).
Results ULMCA PCI was performed in 4.3% of patients with ULMCA stenosis. Unadjusted in-hospital mortality rates ranged from 2.9% for elective cases to 45.1% for emergent/salvage cases. By 30 months, 57.9% of the elderly ULMCA PCI population experienced death, myocardial infarction, or revascularization, and 42.7% died. Patients receiving drug-eluting stents (versus bare-metal stents) had a lower 30-month mortality (IPW HR: 0.84, 95% confidence interval [CI]: 0.73 to 0.96), but the composite of major adverse events were similar (IPW HR: 0.95, 95% CI: 0.84 to 1.06).
Conclusions In the United States, ULMCA PCI is performed in <5% of patients with ULMCA disease and is generally reserved for those at high procedural risk. Adverse events are common in elderly patients and are related to patient and procedural characteristics, including stent type. (J Am Coll Cardiol 2012;59:648-54) (C) 2012 by the American College of Cardiology Foundation
C1 [Brennan, J. Matthew; Dai, David; Patel, Manesh R.; Rao, Sunil V.; Anstrom, Kevin J.; Eisenstein, Eric L.; Peterson, Eric D.; Douglas, Pamela S.] Duke Univ, Med Ctr, Duke Clin Res Inst, Dept Med, Durham, NC 27705 USA.
[Armstrong, Ehrin J.] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA.
[Shunk, Kendrick A.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA.
[Armstrong, Ehrin J.; Shunk, Kendrick A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Messenger, John C.] Univ Colorado Denver Sch Med, Dept Med, Aurora, CO USA.
[Curtis, Jeptha P.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA.
[Weintraub, William S.] Christiana Care Hosp, Dept Med, Newark, DE USA.
[Hillegass, William B.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
RP Brennan, JM (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Dept Med, 2400 Pratt St,Suite 800, Durham, NC 27705 USA.
EM brenn009@mc.duke.edu
FU Agency for Healthcare Research and Quality, United States Department of
Health and Human Services, Rockville, Maryland [ID 24-DKE-3,
HHSAA290-2005-0032-TO4-WA2]; Cordis Corporation; Medtronic, Inc.;
ACC-NCDR; Abbott Vascular; Alexion; AstraZeneca; Bristol-Myers Squibb;
Eli Lilly; Innocoll Pharmaceuticals; Medtronic; PfizerProctor Gamble;
Bristol-Myers Squibb/Sanofi-Aventis; Merck; Lilly; Johnson Johnson;
Society of Thoracic Surgeons; American College of Cardiology; National
Cardiovascular Data Registry, American College of Cardiology,
Washington, DC; Siemens Medical Systems; SurgiVision; Revascular
Therapeutics
FX This project was sponsored by the Agency for Healthcare Research and
Quality, United States Department of Health and Human Services,
Rockville, Maryland, as part of the Cardiovascular Consortium and funded
under Project ID 24-DKE-3 and Work Assignment Number
HHSAA290-2005-0032-TO4-WA2 as part of the Developing Evidence to Inform
Decisions about Effectiveness (DEcIDE) program. Dr. Patel is a
consultant for Bayer Healthcare, Ortho-McNeil Jansen, and Genzyme. Dr.
Rao has received research funding from Cordis Corporation. Dr. Messenger
is the site principal investigator for the Resolute and EDUCATE studies;
and has received funding from Medtronic, Inc. Dr. Curtis receives salary
support from the ACC-NCDR; and has equity holding in Medtronic. Dr.
Shunk has received research funding from Abbott Vascular and Siemens
Medical Systems and consulting fees from SurgiVision and Revascular
Therapeutics. Dr. Anstrom has received research funding and salary
support from Alexion, AstraZeneca, Bristol-Myers Squibb, Eli Lilly,
Innocoll Pharmaceuticals, Medtronic, Pfizer, and Proctor & Gamble;
serves on the data safety monitoring boards of Pfizer and Vertex; and
receives consulting fees from Abbott Vascular, Ikaria, Pacific
Therapeutics, Bristol-Myers Squibb, and AstraZeneca. Mr. Eisenstein has
received research funding from Medtronic and Eli Lilly. Dr. Peterson has
received research funding from Bristol-Myers Squibb/Sanofi-Aventis,
Merck, Lilly, Johnson & Johnson, Society of Thoracic Surgeons, and
American College of Cardiology. All other authors have reported that
they have no relationships relevant to the contents of this paper to
disclose. 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 by the United States
Department of Health and Human Services. Additional support was obtained
from the National Cardiovascular Data Registry, American College of
Cardiology, Washington, DC.
NR 18
TC 28
Z9 32
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 14
PY 2012
VL 59
IS 7
BP 648
EP 654
DI 10.1016/j.jacc.2011.10.883
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 893YN
UT WOS:000300393900004
PM 22322080
ER
PT J
AU Greenspon, AJ
Prutkin, JM
Sohail, MR
Vikram, HR
Baddour, LM
Danik, SB
Peacock, J
Falces, C
Miro, JM
Blank, E
Naber, C
Carrillo, RG
Tseng, CH
Uslan, DZ
AF Greenspon, Arnold J.
Prutkin, Jordan M.
Sohail, Muhammad R.
Vikram, Holenarasipur R.
Baddour, Larry M.
Danik, Stephan B.
Peacock, James
Falces, Carlos
Miro, Jose M.
Blank, Elisabeth
Naber, Christoph
Carrillo, Roger G.
Tseng, Chi-Hong
Uslan, Daniel Z.
TI Timing of the Most Recent Device Procedure Influences the Clinical
Outcome of Lead-Associated Endocarditis Results of the MEDIC
(Multicenter Electrophysiologic Device Infection Cohort)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE endocarditis; implantable cardioverter-defibrillator; permanent
pacemaker
ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; STAPHYLOCOCCUS-AUREUS
BACTEREMIA; PERMANENT PACEMAKER; MYOCARDIAL-INFARCTION; TEMPORAL TRENDS;
MANAGEMENT; COMPLICATIONS; BENEFICIARIES; RISK; EXTRACTION
AB Objectives The purpose of this study was to determine whether the timing of the most recent cardiac implantable electronic device (CIED) procedure, either a permanent pacemaker or implantable cardioverter-defibrillator, influences the clinical presentation and outcome of lead-associated endocarditis (LAE).
Background The CIED infection rate has increased at a time of increased device use. LAE is associated with significant morbidity and mortality.
Methods The clinical presentation and course of LAE were evaluated by the MEDIC (Multicenter Electrophysiologic Device Cohort) registry, an international registry enrolling patients with CIED infection. Consecutive LAE patients enrolled in the Multicenter Electrophysiologic Device Cohort registry between January 2009 and May 2011 were analyzed. The clinical features and outcomes of 2 groups were compared based on the time from the most recent CIED procedure (early, <6 months; late, >6 months).
Results The Multicenter Electrophysiologic Device Cohort registry entered 145 patients with LAE (early = 43, late = 102). Early LAE patients presented with signs and symptoms of local pocket infection, whereas a remote source of bacteremia was present in 38% of patients with late LAE but only 8% of early LAE (p < 0.01). Staphylococcal species were the most frequent pathogens in both early and late LAE. Treatment consisted of removal of all hardware and intravenous administration of antibiotics. In-hospital mortality was low (early = 7%, late = 6%).
Conclusions The clinical presentation of LAE is influenced by the time from the most recent CIED procedure. Although clinical manifestations of pocket infection are present in the majority of patients with early LAE, late LAE should be considered in any CIED patient who presents with fever, bloodstream infection, or signs of sepsis, even if the device pocket appears uninfected. Prompt recognition and management may improve outcomes. (J Am Coll Cardiol 2012;59:681-7) (C) 2012 by the American College of Cardiology Foundation
C1 [Greenspon, Arnold J.] Thomas Jefferson Univ Hosp, Cardiac Electrophysiol Lab, Jefferson Heart Inst, Philadelphia, PA 19107 USA.
[Prutkin, Jordan M.] Univ Washington, Seattle, WA 98195 USA.
[Sohail, Muhammad R.; Baddour, Larry M.] Mayo Clin, Coll Med, Rochester, MN USA.
[Vikram, Holenarasipur R.] Mayo Clin, Phoenix, AZ USA.
[Danik, Stephan B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Peacock, James] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Falces, Carlos; Miro, Jose M.] Univ Barcelona, Hosp Clin, IDIBAPS, Barcelona, Spain.
[Blank, Elisabeth; Naber, Christoph] Elisabeth Hosp, Essen, Germany.
[Carrillo, Roger G.] Univ Miami, Miami, FL USA.
[Tseng, Chi-Hong; Uslan, Daniel Z.] Univ Calif Los Angeles, Los Angeles, CA USA.
RP Greenspon, AJ (reprint author), Thomas Jefferson Univ Hosp, Cardiac Electrophysiol Lab, Jefferson Heart Inst, 925 Chestnut St, Philadelphia, PA 19107 USA.
EM arnold.greenspon@jefferson.edu
RI Carrillo, Roger/C-2231-2015; Sohail, Muhammad/K-1803-2016;
OI Carrillo, Roger/0000-0002-0443-8689; Sohail,
Muhammad/0000-0001-6355-0526; Falces, Carlos/0000-0002-3483-3786
FU American Heart Association; St. Jude Medical
FX This study was funded, in part, by a grant from the American Heart
Association (Dr. Uslan, Primary Investigator). Dr. Greenspon has
received speaker honoraria from Medtronic, Boston Scientific, and St.
Jude Medical. Dr. Sohail is a consultant to TyRx. Dr. Carrillo is a
consultant to Spectranetics; is on the Speaker's Bureau of St. Jude
Medical and Boston Scientific; and is the recipient of a research grant
from St. Jude Medical. Dr. Uslan is a consultant to Medtronic and TyRx;
and has received honoraria from Biotronik. All other authors have
reported that they have no relationships relevant to the contents of
this paper to disclose.
NR 33
TC 36
Z9 37
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 FEB 14
PY 2012
VL 59
IS 7
BP 681
EP 687
DI 10.1016/j.jacc.2011.11.011
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 893YN
UT WOS:000300393900009
PM 22322085
ER
PT J
AU DiGiovanna, J
Carpaneto, J
Micera, S
Merfeld, DM
AF DiGiovanna, Jack
Carpaneto, Jacopo
Micera, Silvestro
Merfeld, Daniel M.
TI Alignment of angular velocity sensors for a vestibular prosthesis
SO JOURNAL OF NEUROENGINEERING AND REHABILITATION
LA English
DT Article
DE Vestibular prosthetics; sensor alignment; neuro-prosthetics
ID SEMICIRCULAR CANAL PROSTHESIS; ELECTRICAL-STIMULATION; ADAPTATION;
SYSTEM
AB Vestibular prosthetics transmit angular velocities to the nervous system via electrical stimulation. Head-fixed gyroscopes measure angular motion, but the gyroscope coordinate system will not be coincident with the sensory organs the prosthetic replaces. Here we show a simple calibration method to align gyroscope measurements with the anatomical coordinate system. We benchmarked the method with simulated movements and obtain proof-of-concept with one healthy subject. The method was robust to misalignment, required little data, and minimal processing.
C1 [DiGiovanna, Jack; Micera, Silvestro] ETH, Automat Control Lab, Neuroprosthet Control Grp, CH-8092 Zurich, Switzerland.
[Carpaneto, Jacopo; Micera, Silvestro] Scuola Super Sant Anna, BioRobot Inst, Pisa, Italy.
[Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA.
[Merfeld, Daniel M.] Harvard Univ, Sch Med, Boston, MA USA.
RP DiGiovanna, J (reprint author), ETH, Automat Control Lab, Neuroprosthet Control Grp, Phys Str 3,ETL K24, CH-8092 Zurich, Switzerland.
EM digiovanna@control.ee.ethz.ch
FU EU [225929]
FX We thank Vito Monaco for invaluable assistance in validating angular
velocity calculations based on marker data. We also thank Dr. Andrea
Gesi for donating the bite-bar apparatus used in this study. Financial
support for the authors was provided in part by the EU Future & Emerging
Technologies Open Scheme, Project 225929 (CLONS).
NR 20
TC 5
Z9 5
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-0003
J9 J NEUROENG REHABIL
JI J. NeuroEng. Rehabil.
PD FEB 13
PY 2012
VL 9
AR 14
DI 10.1186/1743-0003-9-14
PG 13
WC Engineering, Biomedical; Neurosciences; Rehabilitation
SC Engineering; Neurosciences & Neurology; Rehabilitation
GA 951YL
UT WOS:000304756500001
PM 22329908
ER
PT J
AU Bentink, S
Haibe-Kains, B
Risch, T
Fan, JB
Hirsch, MS
Holton, K
Rubio, R
April, C
Chen, J
Wickham-Garcia, E
Liu, J
Culhane, A
Drapkin, R
Quackenbush, J
Matulonis, UA
AF Bentink, Stefan
Haibe-Kains, Benjamin
Risch, Thomas
Fan, Jian-Bing
Hirsch, Michelle S.
Holton, Kristina
Rubio, Renee
April, Craig
Chen, Jing
Wickham-Garcia, Eliza
Liu, Joyce
Culhane, Aedin
Drapkin, Ronny
Quackenbush, John
Matulonis, Ursula A.
TI Angiogenic mRNA and microRNA Gene Expression Signature Predicts a Novel
Subtype of Serous Ovarian Cancer
SO PLOS ONE
LA English
DT Article
ID GYNECOLOGIC-ONCOLOGY-GROUP; ILLUMINA MICROARRAY; STAGE-III; PHASE-II;
SURVIVAL; PACLITAXEL; PROFILES; CHEMOTHERAPY; BEVACIZUMAB; VALIDATION
AB Ovarian cancer is the fifth leading cause of cancer death for women in the U.S. and the seventh most fatal worldwide. Although ovarian cancer is notable for its initial sensitivity to platinum-based therapies, the vast majority of patients eventually develop recurrent cancer and succumb to increasingly platinum-resistant disease. Modern, targeted cancer drugs intervene in cell signaling, and identifying key disease mechanisms and pathways would greatly advance our treatment abilities. In order to shed light on the molecular diversity of ovarian cancer, we performed comprehensive transcriptional profiling on 129 advanced stage, high grade serous ovarian cancers. We implemented a, re-sampling based version of the ISIS class discovery algorithm (rISIS: robust ISIS) and applied it to the entire set of ovarian cancer transcriptional profiles. rISIS identified a previously undescribed patient stratification, further supported by micro-RNA expression profiles, and gene set enrichment analysis found strong biological support for the stratification by extracellular matrix, cell adhesion, and angiogenesis genes. The corresponding "angiogenesis signature'' was validated in ten published independent ovarian cancer gene expression datasets and is significantly associated with overall survival. The subtypes we have defined are of potential translational interest as they may be relevant for identifying patients who may benefit from the addition of anti-angiogenic therapies that are now being tested in clinical trials.
C1 [Bentink, Stefan; Haibe-Kains, Benjamin; Risch, Thomas; Holton, Kristina; Rubio, Renee; Culhane, Aedin; Quackenbush, John] Dana Farber Canc Inst, Dept Biostatist & Computat Biol, Boston, MA 02115 USA.
[Liu, Joyce; Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Fan, Jian-Bing; April, Craig; Chen, Jing; Wickham-Garcia, Eliza] Illumina Inc, San Diego, CA USA.
[Hirsch, Michelle S.; Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Div Womans & Perinatal Pathol, Boston, MA 02115 USA.
[Drapkin, Ronny; Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Bentink, Stefan; Haibe-Kains, Benjamin; Culhane, Aedin; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Hirsch, Michelle S.; Liu, Joyce; Drapkin, Ronny; Matulonis, Ursula A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Bentink, S (reprint author), Dana Farber Canc Inst, Dept Biostatist & Computat Biol, Boston, MA 02115 USA.
EM johnq@jimmy.harvard.edu
RI Haibe-Kains, Benjamin/D-3702-2011; Drapkin, Ronny/E-9944-2016
OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Drapkin,
Ronny/0000-0002-6912-6977
FU Dana-Farber/Harvard Cancer Center; Claudia Adams Barr Foundation;
Kittredge Foundation; Dana-Farber Cancer Institute; National Cancer
Institute [3P50 CA105009-05S1]
FX This work was supported by grants from the Dana-Farber/Harvard Cancer
Center Women's Cancer Program, the Claudia Adams Barr Foundation, the
Kittredge Foundation, and the Dana-Farber Cancer Institute High Tech
Fund. Additional support was provided by a grant from the National
Cancer Institute (3P50 CA105009-05S1). The DASL assays were provided by
Illumina, Inc. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 36
TC 39
Z9 41
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 13
PY 2012
VL 7
IS 2
AR e30269
DI 10.1371/journal.pone.0030269
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 925BB
UT WOS:000302733900005
PM 22348002
ER
PT J
AU Weigert, O
Lane, AA
Bird, L
Kopp, N
Chapuy, B
van Bodegom, D
Toms, AV
Marubayashi, S
Christie, AL
McKeown, M
Paranal, RM
Bradner, JE
Yoda, A
Gaul, C
Vangrevelinghe, E
Romanet, V
Murakami, M
Tiedt, R
Ebel, N
Evrot, E
De Pover, A
Regnier, CH
Erdmann, D
Hofmann, F
Eck, MJ
Sallan, SE
Levine, RL
Kung, AL
Baffert, F
Radimerski, T
Weinstock, DM
AF Weigert, Oliver
Lane, Andrew A.
Bird, Liat
Kopp, Nadja
Chapuy, Bjoern
van Bodegom, Diederik
Toms, Angela V.
Marubayashi, Sachie
Christie, Amanda L.
McKeown, Michael
Paranal, Ronald M.
Bradner, James E.
Yoda, Akinori
Gaul, Christoph
Vangrevelinghe, Eric
Romanet, Vincent
Murakami, Masato
Tiedt, Ralph
Ebel, Nicolas
Evrot, Emeline
De Pover, Alain
Regnier, Catherine H.
Erdmann, Dirk
Hofmann, Francesco
Eck, Michael J.
Sallan, Stephen E.
Levine, Ross L.
Kung, Andrew L.
Baffert, Fabienne
Radimerski, Thomas
Weinstock, David M.
TI Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90
inhibition
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; B-CELL LYMPHOMAS; POLYCYTHEMIA-VERA;
TYROSINE KINASE; ANTITUMOR-ACTIVITY; BCR-ABL; MYELOPROLIFERATIVE
DISORDERS; ACTIVATING MUTATION; MYELOID METAPLASIA; CANCER
AB Enzymatic inhibitors of Janus kinase 2 (JAK2) are in clinical development for the treatment of myeloproliferative neoplasms (MPNs), B cell acute lymphoblastic leukemia (B-ALL) with rearrangements of the cytokine receptor subunit cytokine receptor-like factor 2 (CRLF2), and other tumors with constitutive JAK2 signaling. In this study, we identify G935R, Y931C, and E864K mutations within the JAK2 kinase domain that confer resistance across a panel of JAK inhibitors, whether present in cis with JAK2 V617F (observed in MPNs) or JAK2 R683G (observed in B-ALL). G935R, Y931C, and E864K do not reduce the sensitivity of JAK2-dependent cells to inhibitors of heat shock protein 90 (HSP90), which promote the degradation of both wild-type and mutant JAK2. HSP90 inhibitors were 100-1,000-fold more potent against CRLF2-rearranged B-ALL cells, which correlated with JAK2 degradation and more extensive blockade of JAK2/STAT5, MAP kinase, and AKT signaling. In addition, the HSP90 inhibitor AUY922 prolonged survival of mice xenografted with primary human CRLF2-rearranged B-ALL further than an enzymatic JAK2 inhibitor. Thus, HSP90 is a promising therapeutic target in JAK2-driven cancers, including those with genetic resistance to JAK enzymatic inhibitors.
C1 [Weigert, Oliver; Lane, Andrew A.; Bird, Liat; Kopp, Nadja; Chapuy, Bjoern; van Bodegom, Diederik; McKeown, Michael; Paranal, Ronald M.; Bradner, James E.; Yoda, Akinori; Weinstock, David M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Toms, Angela V.; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Christie, Amanda L.; Sallan, Stephen E.; Kung, Andrew L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA.
[Marubayashi, Sachie; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol Pathogenesis Program, New York, NY 10065 USA.
[Marubayashi, Sachie; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10065 USA.
[Gaul, Christoph; Vangrevelinghe, Eric; Romanet, Vincent; Murakami, Masato; Tiedt, Ralph; Ebel, Nicolas; Evrot, Emeline; De Pover, Alain; Regnier, Catherine H.; Erdmann, Dirk; Hofmann, Francesco; Baffert, Fabienne; Radimerski, Thomas] Novartis Inst Biomed Res, CH-4057 Basel, Switzerland.
[Toms, Angela V.; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Kung, Andrew L.; Weinstock, David M.] Harvard Univ, Sch Med, Dept Biol & Biomed Sci, Boston, MA 02115 USA.
EM thomas.radimerski@novartis.com; dweinstock@partners.org
OI Regnier, Catherine/0000-0002-4386-1324; Kung, Andrew/0000-0002-9091-488X
FU Deutsche Forschungsgemeinschaft; NCI [1R01CA151898-01]; DFCI/Novartis;
Novartis
FX O. Weigert is supported by the Deutsche Forschungsgemeinschaft. This
work was supported by NCI 1R01CA151898-01 (D.M. Weinstock) and the
DFCI/Novartis Drug Discovery Program (D.M. Weinstock).; C. Gaul, E.
Vangrevelinghe, V. Romanet, M. Murakami, R. Teidt, N. Ebel, E. Evrot, A.
De Pover, C. H. Regnier, D. Erdmann, F. Hofmann, F. Baffert, and T.
Radimerski are employed by the Novartis Institute for Biomedical
Research. M.J. Eck, A. L. Kung, and D.M. Weinstock are paid consultants
and receive research support from Novartis.
NR 55
TC 81
Z9 83
U1 2
U2 13
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD FEB 13
PY 2012
VL 209
IS 2
BP 259
EP 273
DI 10.1084/jem.20111694
PG 15
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 914IO
UT WOS:000301943200008
PM 22271575
ER
PT J
AU Hur, KY
So, JS
Ruda, V
Frank-Kamenetsky, M
Fitzgerald, K
Koteliansky, V
Iwawaki, T
Glimcher, LH
Lee, AH
AF Hur, Kyu Yeon
So, Jae-Seon
Ruda, Vera
Frank-Kamenetsky, Maria
Fitzgerald, Kevin
Koteliansky, Victor
Iwawaki, Takao
Glimcher, Laurie H.
Lee, Ann-Hwee
TI IRE1 alpha activation protects mice against acetaminophen-induced
hepatotoxicity
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID INDUCED LIVER-INJURY; TRANSCRIPTION FACTOR XBP-1; INDUCED
HEPATIC-NECROSIS; ENDOPLASMIC-RETICULUM; MESSENGER-RNA; ER STRESS;
TRANSMEMBRANE PROTEIN; TERMINAL KINASE; OXIDATIVE STRESS; IRE1
AB The mammalian stress sensor IRE1 alpha plays a central role in the unfolded protein, or endoplasmic reticulum (ER), stress response by activating its downstream transcription factor XBP1 via an unconventional splicing mechanism. IRE1 alpha can also induce the degradation of a subset of mRNAs in a process termed regulated IRE1-dependent decay (RIDD). Although diverse mRNA species can be degraded by IRE1 alpha in vitro, the pathophysiological functions of RIDD are only beginning to be explored. Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure in young adults in the United States and is primarily caused by CYP1A2-, CYP2E1-, and CYP3A4-driven conversion of APAP into hepatotoxic metabolites. We demonstrate here that genetic ablation of XBP1 results in constitutive IRE1 alpha activation in the liver, leading to RIDD of Cyp1a2 and Cyp2e1 mRNAs, reduced JNK activation, and protection of mice from APAP-induced hepatotoxicity. A pharmacological ER stress inducer that activated IRE1 alpha suppressed the expression of Cyp1a2 and Cyp2e1 in WT, but not IRE1 alpha-deficient mouse liver, indicating the essential role of IRE1 alpha in the down-regulation of these mRNAs upon ER stress. Our study reveals an unexpected function of RIDD in drug metabolism.
C1 [Hur, Kyu Yeon; So, Jae-Seon; Glimcher, Laurie H.; Lee, Ann-Hwee] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Ruda, Vera] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Ruda, Vera] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Ruda, Vera] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Frank-Kamenetsky, Maria; Fitzgerald, Kevin; Koteliansky, Victor] Alnylam Pharmaceut, Cambridge, MA 02142 USA.
[Iwawaki, Takao] Inst Phys & Chem Res, Iwawaki Initiat Res Unit, Wako, Saitama 3510198, Japan.
[Iwawaki, Takao] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan.
[Iwawaki, Takao] Gunma Univ, Adv Sci Res Leaders Dev Unit, Gunma 3718511, Japan.
[Glimcher, Laurie H.; Lee, Ann-Hwee] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Glimcher, Laurie H.] MIT, Ragon Inst MGH, Boston, MA 02115 USA.
[Glimcher, Laurie H.] Harvard, Boston, MA 02115 USA.
EM lglimche@hsph.harvard.edu; ahlee@hsph.harvard.edu
FU National Institutes of Health [AI32412, DK082448, DK089211]; American
Heart Association
FX This study was supported by National Institutes of Health grants AI32412
(L.H. Glimcher), DK082448 (L.H. Glimcher), and DK089211 (A.-H. Lee), and
a grant from the American Heart Association (A.-H. Lee).
NR 60
TC 55
Z9 56
U1 1
U2 8
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD FEB 13
PY 2012
VL 209
IS 2
BP 307
EP 318
DI 10.1084/jem.20111298
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 914IO
UT WOS:000301943200011
PM 22291093
ER
PT J
AU Schubert, DA
Gordo, S
Sabatino, JJ
Vardhana, S
Gagnon, E
Sethi, DK
Seth, NP
Choudhuri, K
Reijonen, H
Nepom, GT
Evavold, BD
Dustin, ML
Wucherpfennig, KW
AF Schubert, David A.
Gordo, Susana
Sabatino, Joseph J., Jr.
Vardhana, Santosh
Gagnon, Etienne
Sethi, Dhruv K.
Seth, Nilufer P.
Choudhuri, Kaushik
Reijonen, Helena
Nepom, Gerald T.
Evavold, Brian D.
Dustin, Michael L.
Wucherpfennig, Kai W.
TI Self-reactive human CD4 T cell clones form unusual immunological
synapses
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID SUPRAMOLECULAR ACTIVATION CLUSTER; THYMIC EPITHELIAL-CELLS;
KINASE-C-THETA; PEPTIDE-MHC; RECEPTOR MICROCLUSTERS; ADHESION MOLECULES;
NEGATIVE SELECTION; ACTIN CYTOSKELETON; IN-VITRO; HLA-DM
AB Recognition of self-peptide-MHC (pMHC) complexes by CD4 T cells plays an important role in the pathogenesis of many autoimmune diseases. We analyzed formation of immunological synapses (IS) in self-reactive T cell clones from patients with multiple sclerosis and type 1 diabetes. All self-reactive T cells contained a large number of phosphorylated T cell receptor (TCR) microclusters, indicative of active TCR signaling. However, they showed little or no visible pMHC accumulation or transport of TCR-pMHC complexes into a central supramolecular activation cluster (cSMAC). In contrast, influenza-specific T cells accumulated large quantities of pMHC complexes in microclusters and a cSMAC, even when presented with 100-fold lower pMHC densities. The self-reactive T cells also maintained a high degree of motility, again in sharp contrast to virus-specific T cells. 2D affinity measurements of three of these self-reactive T cell clones demonstrated a normal off-rate but a slow on-rate of TCR binding to pMHC. These unusual IS features may facilitate escape from negative selection by self-reactive T cells encountering very small amounts of self-antigen in the thymus. However, these same features may enable acquisition of effector functions by self-reactive T cells encountering large amounts of self-antigen in the target organ of the autoimmune disease.
C1 [Schubert, David A.; Gordo, Susana; Gagnon, Etienne; Sethi, Dhruv K.; Seth, Nilufer P.; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
[Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA.
[Sabatino, Joseph J., Jr.; Evavold, Brian D.] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Vardhana, Santosh; Choudhuri, Kaushik; Dustin, Michael L.] Helen L & Martin S Kimmel Ctr Biol & Med, Skirball Inst Biomol Med, Program Mol Pathogenesis, New York, NY 10016 USA.
[Vardhana, Santosh; Choudhuri, Kaushik; Dustin, Michael L.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
[Reijonen, Helena; Nepom, Gerald T.] Benaroya Res Inst Virginia Mason, Seattle, WA 98101 USA.
EM kai_wucherpfennig@dfci.harvard.edu
OI Vardhana, Santosha/0000-0002-3100-1298; Nepom,
Gerald/0000-0002-8063-1464; Dustin, Michael/0000-0003-4983-6389
FU National Institutes of Health [PO1 AI045757]; Cancer Research Institute;
Ernst-Schering Foundation; Generalitat de Catalunya - AGAUR; National
Multiple Sclerosis Society
FX This work was supported by grants from the National Institutes of Health
(PO1 AI045757 to K.W. Wucherpfennig and M. L. Dustin) and by
postdoctoral fellowships from the Cancer Research Institute (to D. A.
Schubert and E. Gagnon), the Ernst-Schering Foundation (to D. A.
Schubert), the Generalitat de Catalunya - AGAUR (to S. Gordo), and the
National Multiple Sclerosis Society (to D.K. Sethi).
NR 64
TC 33
Z9 34
U1 1
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD FEB 13
PY 2012
VL 209
IS 2
BP 335
EP 352
DI 10.1084/jem.20111485
PG 18
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 914IO
UT WOS:000301943200013
PM 22312112
ER
PT J
AU Partridge, AH
AF Partridge, Ann H.
TI Ovarian Suppression for Prevention of Premature Menopause and
Infertility: Empty Promise or Effective Therapy?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID PREMENOPAUSAL BREAST-CANCER; ADJUVANT CHEMOTHERAPY; PROGNOSTIC IMPACT;
YOUNG-WOMEN; AMENORRHEA; FERTILITY; TRIAL
C1 [Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Partridge, Ann H.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Partridge, AH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 14
TC 10
Z9 11
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
BP 479
EP 481
DI 10.1200/JCO.2011.37.9883
PG 3
WC Oncology
SC Oncology
GA 923MH
UT WOS:000302622900011
PM 22231046
ER
PT J
AU Roberts, AW
Seymour, JF
Brown, JR
Wierda, WG
Kipps, TJ
Khaw, SL
Carney, DA
He, SZ
Huang, DCS
Xiong, H
Cui, Y
Busman, TA
McKeegan, EM
Krivoshik, AP
Enschede, SH
Humerickhouse, R
AF Roberts, Andrew W.
Seymour, John F.
Brown, Jennifer R.
Wierda, William G.
Kipps, Thomas J.
Khaw, Seong Lin
Carney, Dennis A.
He, Simon Z.
Huang, David C. S.
Xiong, Hao
Cui, Yue
Busman, Todd A.
McKeegan, Evelyn M.
Krivoshik, Andrew P.
Enschede, Sari H.
Humerickhouse, Rod
TI Substantial Susceptibility of Chronic Lymphocytic Leukemia to BCL2
Inhibition: Results of a Phase I Study of Navitoclax in Patients With
Relapsed or Refractory Disease
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID BH3 MIMETIC ABT-737; CELL-DEATH; ANTAGONIST ABT-737; LYMPHOMA-CELLS;
FAMILY; CANCER; APOPTOSIS; CHEMOTHERAPY; SENSITIVITY; RESISTANCE
AB Purpose
BCL2 overexpression is a hallmark of chronic lymphocytic leukemia (CLL). The novel BH3 mimetic navitoclax (ABT-263) specifically inhibits BCL2 and related proteins BCL-x(L) and BCL-w, potently inducing apoptosis of CLL cells in vitro. A phase I trial in patients with CLL was conducted to evaluate the safety, pharmacokinetics, and biologic activity of oral navitoclax.
Patients and Methods
Twenty-nine patients with relapsed or refractory CLL received daily navitoclax for 14 days (10, 110, 200, or 250 mg/d; n = 15) or 21 days (125, 200, 250, or 300 mg/d; n = 14) of each 21-day cycle. Dose escalation decisions were informed by continual reassessment methodology.
Results
Lymphocytosis was reduced by more than 50% in 19 of 21 patients with baseline lymphocytosis. Among 26 patients treated with navitoclax >= 110 mg/d, nine (35%) achieved a partial response and seven maintained stable disease for more than 6 months. Median treatment duration was 7 months (range, 1 to >= 29 months). Median progression-free survival was 25 months. Activity was observed in patients with fludarabine-refractory disease, bulky adenopathy, and del(17p) CLL. Thrombocytopenia due to BCL-x(L) inhibition was the major dose-limiting toxicity and was dose-related. Low MCL1 expression and high BIM:MCL1 or BIM: BCL2 ratios in leukemic cells correlated with response. We determined that the navitoclax dose of 250 mg/d in a continuous dosing schedule was optimal for phase II studies.
Conclusion
BCL2 is a valid therapeutic target in CLL, and its inhibition by navitoclax warrants further evaluation as monotherapy and in combination in this disease. J Clin Oncol 30: 488-496. (C) 2011 by American Society of Clinical Oncology
C1 [Roberts, Andrew W.] Royal Melbourne Hosp, Dept Clin Haematol, Parkville, Vic 3050, Australia.
[Roberts, Andrew W.; Khaw, Seong Lin; He, Simon Z.; Huang, David C. S.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
[Roberts, Andrew W.; Huang, David C. S.] Australian Canc Res Fdn Ctr Therapeut Target Disc, Parkville, Vic, Australia.
[Roberts, Andrew W.; Seymour, John F.; Khaw, Seong Lin; Carney, Dennis A.; He, Simon Z.; Huang, David C. S.] Univ Melbourne, Parkville, Vic 3052, Australia.
[Seymour, John F.; Carney, Dennis A.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wierda, William G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Kipps, Thomas J.] Moores Univ Calif, San Diego Canc Ctr, La Jolla, CA USA.
[Xiong, Hao; Cui, Yue; Busman, Todd A.; McKeegan, Evelyn M.; Krivoshik, Andrew P.; Enschede, Sari H.; Humerickhouse, Rod] Abbott Labs, Abbott Pk, IL 60064 USA.
RP Roberts, AW (reprint author), Royal Melbourne Hosp, Dept Clin Haematol, 2 Ctr,Grattan St, Parkville, Vic 3050, Australia.
EM roberts@wehi.edu.au
RI Roberts, Andrew/C-6736-2012; Huang, David/C-7586-2013
OI Roberts, Andrew/0000-0002-7341-5720;
FU Abbott Laboratories; Celgene; Genzyme; GlaxoSmithKline; Genentech;
National Health and Medical Research Council of Australia; Victorian
Cancer Agency; Leukaemia Foundation Australia; Australian Cancer
Research Foundation; Leukemia and Lymphoma Society
FX Research Funding: Andrew W. Roberts, Abbott Laboratories; Jennifer R.
Brown, Celgene, Genzyme; William G. Wierda, GlaxoSmithKline, Abbott
Laboratories; Thomas J. Kipps, Abbott Laboratories; Supported by Abbott
Laboratories and Genentech. Additional support for correlative studies
was provided by National Health and Medical Research Council of
Australia, Victorian Cancer Agency, Leukaemia Foundation Australia,
Australian Cancer Research Foundation, and the Leukemia and Lymphoma
Society.
NR 34
TC 300
Z9 302
U1 0
U2 29
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
BP 488
EP 496
DI 10.1200/JCO.2011.34.7898
PG 9
WC Oncology
SC Oncology
GA 923MH
UT WOS:000302622900013
PM 22184378
ER
PT J
AU Choueiri, TK
Ross, RW
Jacobus, S
Vaishampayan, U
Yu, EY
Quinn, DI
Hahn, NM
Hutson, TE
Sonpavde, G
Morrissey, SC
Buckle, GC
Kim, WY
Petrylak, DP
Ryan, CW
Eisenberger, MA
Mortazavi, A
Bubley, GJ
Taplin, ME
Rosenberg, JE
Kantoff, PW
AF Choueiri, Toni K.
Ross, Robert W.
Jacobus, Susanna
Vaishampayan, Ulka
Yu, Evan Y.
Quinn, David I.
Hahn, Noah M.
Hutson, Thomas E.
Sonpavde, Guru
Morrissey, Stephanie C.
Buckle, Geoffrey C.
Kim, William Y.
Petrylak, Daniel P.
Ryan, Christopher W.
Eisenberger, Mario A.
Mortazavi, Amir
Bubley, Glenn J.
Taplin, Mary-Ellen
Rosenberg, Jonathan E.
Kantoff, Philip W.
TI Double-Blind, Randomized Trial of Docetaxel Plus Vandetanib Versus
Docetaxel Plus Placebo in Platinum-Pretreated Metastatic Urothelial
Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID TRANSITIONAL-CELL CARCINOMA; PHASE-II TRIAL; EPIDERMAL-GROWTH-FACTOR;
ADVANCED BLADDER-CANCER; 2ND-LINE TREATMENT; PROGNOSTIC-FACTORS;
ONCOLOGY-GROUP; LUNG-CANCER; PACLITAXEL; CHEMOTHERAPY
AB Purpose
Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy.
Patients and Methods
The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m(2) intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60% improvement in median PFS with 80% power and one-sided alpha at 5%. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives.
Results
In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95% CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11% v 0%) and diarrhea (7% v 0%). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3% and OS was 5.2 months.
Conclusion
In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal. J Clin Oncol 30: 507-512. (C) 2011 by American Society of Clinical Oncology
C1 [Choueiri, Toni K.; Ross, Robert W.; Jacobus, Susanna; Morrissey, Stephanie C.; Buckle, Geoffrey C.; Taplin, Mary-Ellen; Rosenberg, Jonathan E.; Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Bubley, Glenn J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Vaishampayan, Ulka] Karmanos Canc Inst, Detroit, MI USA.
[Yu, Evan Y.] Univ Washington, Seattle, WA 98195 USA.
[Quinn, David I.] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
[Hahn, Noah M.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA.
[Hutson, Thomas E.] Baylor Sammons Canc Ctr, Dallas, TX USA.
[Sonpavde, Guru] Baylor Coll Med, Houston, TX 77030 USA.
[Kim, William Y.] Univ N Carolina, Chapel Hill, NC USA.
[Petrylak, Daniel P.] Columbia Univ, Med Ctr, New York, NY USA.
[Ryan, Christopher W.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Eisenberger, Mario A.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Mortazavi, Amir] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA.
[Mortazavi, Amir] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
RP Choueiri, TK (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,DANA 1230, Boston, MA 02215 USA.
EM Toni_Choueiri@dfci.harvard.edu
RI Quinn, David/F-4343-2015
OI Quinn, David/0000-0002-1411-0417
FU AstraZeneca; Dana-Farber Cancer Institute; sanofi-aventis; Bristol-Myers
Squibb; Pfizer; Millennium Pharmaceuticals; Celgene; Genentech; Merck;
Novartis
FX Supported by AstraZeneca and Friends of Dana-Farber Cancer Institute.;
Research Funding: Ulka Vaishampayan, sanofi-aventis; Evan Y. Yu,
AstraZeneca; Noah M. Hahn, sanofi-aventis, Bristol-Myers Squibb,
AstraZeneca, Pfizer, Millennium Pharmaceuticals, Celgene, Genentech,
Merck, Novartis
NR 28
TC 81
Z9 81
U1 1
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 FEB 10
PY 2012
VL 30
IS 5
BP 507
EP 512
DI 10.1200/JCO.2011.37.7002
PG 6
WC Oncology
SC Oncology
GA 923MH
UT WOS:000302622900015
PM 22184381
ER
PT J
AU Barry, MJ
Gallagher, PM
Skinner, JS
Fowler, FJ
AF Barry, Michael J.
Gallagher, Patricia M.
Skinner, Jonathan S.
Fowler, Floyd J., Jr.
TI Adverse Effects of Robotic-Assisted Laparoscopic Versus Open Retropubic
Radical Prostatectomy Among a Nationwide Random Sample of Medicare-Age
Men
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; CANCER; OUTCOMES; SATISFACTION; SURGERY; UROLOGY;
URINARY
AB Purpose
Robotic-assisted laparoscopic radical prostatectomy is eclipsing open radical prostatectomy among men with clinically localized prostate cancer. The objective of this study was to compare the risks of problems with continence and sexual function following these procedures among Medicare-age men.
Patients and Methods
A population-based random sample was drawn from the 20% Medicare claims files for August 1, 2008, through December 31, 2008. Participants had hospital and physician claims for radical prostatectomy and diagnostic codes for prostate cancer and reported undergoing either a robotic or open surgery. They received a mail survey that included self-ratings of problems with continence and sexual function a median of 14 months postoperatively.
Results
Completed surveys were obtained from 685 (86%) of 797 eligible participants, and 406 and 220 patients reported having had robotic or open surgery, respectively. Overall, 189 (31.1%; 95% CI, 27.5% to 34.8%) of 607 men reported having a moderate or big problem with continence, and 522 (88.0%; 95% CI, 85.4% to 90.6%) of 593 men reported having a moderate or big problem with sexual function. In logistic regression models predicting the log odds of a moderate or big problem with postoperative continence and adjusting for age and educational level, robotic prostatectomy was associated with a nonsignificant trend toward greater problems with continence (odds ratio [ OR] 1.41; 95% CI, 0.97 to 2.05). Robotic prostatectomy was not associated with greater problems with sexual function (OR, 0.87; 95% CI, 0.51 to 1.49).
Conclusion
Risks of problems with continence and sexual function are high after both procedures. Medicare-age men should not expect fewer adverse effects following robotic prostatectomy. J Clin Oncol 30:513-518. (C) 2012 by American Society of Clinical Oncology
C1 [Barry, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Gallagher, Patricia M.; Fowler, Floyd J., Jr.] Univ Massachusetts, Boston, MA 02125 USA.
[Barry, Michael J.; Fowler, Floyd J., Jr.] Fdn Informed Med Decis Making, Boston, MA USA.
[Skinner, Jonathan S.] Dartmouth Coll, Hanover, NH 03755 USA.
[Skinner, Jonathan S.] Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA.
RP Barry, MJ (reprint author), Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM mbarry@partners.org
FU National Institute on Aging [2 P01 AG019783-08]
FX Supported by Grant No. 2 P01 AG019783-08 from the National Institute on
Aging.
NR 28
TC 77
Z9 79
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 FEB 10
PY 2012
VL 30
IS 5
BP 513
EP 518
DI 10.1200/JCO.2011.36.8621
PG 6
WC Oncology
SC Oncology
GA 923MH
UT WOS:000302622900016
PM 22215756
ER
PT J
AU Walensky, LD
AF Walensky, Loren D.
TI From Mitochondrial Biology to Magic Bullet: Navitoclax Disarms BCL-2 in
Chronic Lymphocytic Leukemia
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID BH3 MIMETIC ABT-737; CHROMOSOME-TRANSLOCATION; INHIBITOR; APOPTOSIS;
PROTEINS; FAMILY; MCL-1; RESISTANCE; MUTAGENESIS; LIGANDS
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Walensky, LD (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
FU NCI NIH HHS [R01 CA050239]
NR 26
TC 18
Z9 20
U1 1
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
BP 554
EP 557
DI 10.1200/JCO.2011.37.9339
PG 4
WC Oncology
SC Oncology
GA 923MH
UT WOS:000302622900022
PM 22184389
ER
PT J
AU Wen, PY
Schiff, D
Cloughesy, TF
Reardon, DA
Batchelor, TT
DeAngelis, LM
AF Wen, Patrick Y.
Schiff, David
Cloughesy, Timothy F.
Reardon, David A.
Batchelor, Tracy T.
DeAngelis, Lisa M.
TI Toward a Better Dialogue Between Neuro-Oncologists and Phase I
Investigators Response
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Wen, Patrick Y.; Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wen, Patrick Y.; Reardon, David A.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Schiff, David] Univ Virginia, Charlottesville, VA USA.
[Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Batchelor, Tracy T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Wen, PY (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
BP 563
EP 564
DI 10.1200/JCO.2011.40.1513
PG 3
WC Oncology
SC Oncology
GA 923MH
UT WOS:000302622900027
ER
PT J
AU Lee, HJ
Mariappan, MM
Feliers, D
Cavaglieri, RC
Sataranatarajan, K
Abboud, HE
Choudhury, GG
Kasinath, BS
AF Lee, Hak Joo
Mariappan, Meenalakshmi M.
Feliers, Denis
Cavaglieri, Rita C.
Sataranatarajan, Kavithalakshmi
Abboud, Hanna E.
Choudhury, Goutam Ghosh
Kasinath, Balakuntalam S.
TI Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis
by Activating AMP-activated Protein Kinase in Renal Epithelial Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MESSENGER-RNA TRANSLATION; CYSTATHIONINE-GAMMA-LYASE;
DIABETIC-NEPHROPATHY; MYOCARDIAL-ISCHEMIA; REPERFUSION INJURY; SULFANE
SULFUR; KNOCKOUT MICE; HYPERTROPHY; GROWTH; RAT
AB Hydrogen sulfide, a signaling gas, affects several cell functions. We hypothesized that hydrogen sulfide modulates high glucose (30 mM) stimulation of matrix protein synthesis in glomerular epithelial cells. High glucose stimulation of global protein synthesis, cellular hypertrophy, and matrix laminin and type IV collagen content was inhibited by sodium hydrosulfide (NaHS), an H2S donor. High glucose activation of mammalian target of rapamycin (mTOR) complex 1 (mTORC1), shown by phosphorylation of p70S6 kinase and 4E-BP1, was inhibited by NaHS. High glucose stimulated mTORC1 to promote key events in the initiation and elongation phases of mRNA translation: binding of eIF4A to eIF4G, reduction in PDCD4 expression and inhibition of its binding to eIF4A, eEF2 kinase phosphorylation, and dephosphorylation of eEF2; these events were inhibited by NaHS. The role of AMP-activated protein kinase (AMPK), an inhibitor of protein synthesis, was examined. NaHS dose-dependently stimulated AMPK phosphorylation and restored AMPK phosphorylation reduced by high glucose. Compound C, an AMPK inhibitor, abolished NaHS modulation of high glucose effect on events in mRNA translation as well as global and matrix protein synthesis. NaHS induction of AMPK phosphorylation was inhibited by siRNA for calmodulin kinase kinase beta, but not LKB1, upstream kinases for AMPK; STO-609, a calmodulin kinase kinase beta inhibitor, had the same effect. Renal cortical content of cystathionine beta-synthase and cystathionine gamma-lyase, hydrogen sulfide-generating enzymes, was significantly reduced in mice with type 1 diabetes or type 2 diabetes, coinciding with renal hypertrophy and matrix accumulation. Hydrogen sulfide is a newly identified modulator of protein synthesis in the kidney, and reduction in its generation may contribute to kidney injury in diabetes.
C1 [Lee, Hak Joo; Mariappan, Meenalakshmi M.; Feliers, Denis; Cavaglieri, Rita C.; Sataranatarajan, Kavithalakshmi; Abboud, Hanna E.; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Lee, Hak Joo; Mariappan, Meenalakshmi M.; Sataranatarajan, Kavithalakshmi; Abboud, Hanna E.; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
RP Kasinath, BS (reprint author), 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM kasinath@uthscsa.edu
FU National Institutes of Health [DK077295, RC2AG036613, DK050190];
Veterans Affairs Medical Research Service; Juvenile Diabetes Research
Foundation [1-2010-141, 1-2008-185]; Veterans Affairs Research Career
Scientist Award
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK077295 and RC2AG036613 (to B. S. K.) and DK050190 (to G.
G. C.). This work was also supported by a grant from the Veterans
Affairs Medical Research Service (to B. S. K. and G. G. C.) and Juvenile
Diabetes Research Foundation Grants 1-2010-141 (to D. F.) and 1-2008-185
(to G. G. C.).; Recipient of a Veterans Affairs Research Career
Scientist Award.
NR 65
TC 39
Z9 42
U1 0
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 10
PY 2012
VL 287
IS 7
BP 4451
EP 4461
DI 10.1074/jbc.M111.278325
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 896YX
UT WOS:000300608500009
PM 22158625
ER
PT J
AU Maeno, Y
Li, Q
Park, K
Rask-Madsen, C
Gao, BB
Matsumoto, M
Liu, YJ
Wu, IH
White, MF
Feener, EP
King, GL
AF Maeno, Yasuhiro
Li, Qian
Park, Kyoungmin
Rask-Madsen, Christian
Gao, Benbo
Matsumoto, Motonobu
Liu, Yingjie
Wu, I-Hsien
White, Morris F.
Feener, Edward P.
King, George L.
TI Inhibition of Insulin Signaling in Endothelial Cells by Protein Kinase
C-induced Phosphorylation of p85 Subunit of Phosphatidylinositol
3-Kinase (PI3K)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SUBSTRATE-1 TYROSINE PHOSPHORYLATION; RECEPTOR SUBSTRATE-1;
NITRIC-OXIDE; DIABETIC COMPLICATIONS; GENE-EXPRESSION; PAI-1 GENE;
IN-VIVO; ACTIVATION; GROWTH; RESISTANCE
AB The regulation of endothelial function by insulin is consistently abnormal in insulin-resistant states and diabetes. Protein kinase C (PKC) activation has been reported to inhibit insulin signaling selectively in endothelial cells via the insulin receptor substrate/PI3K/Akt pathway to reduce the activation of endothelial nitric-oxide synthase (eNOS). In this study, it was observed that PKC activation differentially inhibited insulin receptor substrate 1/2 (IRS1/2) signaling of insulin's activation of PI3K/eNOS by decreasing only tyrosine phosphorylation of IRS2. In addition, PKC activation, by general activator and specifically by angiotensin II, increased the phosphorylation of p85/PI3K, which decreases its association with IRS1 and activation. Thr-86 of p85/PI3K was identified to be phosphorylated by PKC activation and confirmed to affect IRS1-mediated activation of Akt/eNOS by insulin and VEGF using a deletion mutant of the Thr-86 region of p85/PI3K. Thus, PKC and angiotensin-induced phosphorylation of Thr-86 of p85/PI3K may partially inhibit the activation of PI3K/eNOS by multiple cytokines and contribute to endothelial dysfunction in metabolic disorders.
C1 [Maeno, Yasuhiro; Li, Qian; Park, Kyoungmin; Rask-Madsen, Christian; Gao, Benbo; Matsumoto, Motonobu; Liu, Yingjie; Wu, I-Hsien; Feener, Edward P.; King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol, Boston, MA 02115 USA.
[White, Morris F.] Childrens Hosp Boston, Boston, MA 02115 USA.
RP King, GL (reprint author), Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, Dianne Nunnally Hoppes Lab Diabet Complicat, 1 Joslin Pl, Boston, MA 02215 USA.
EM George.king@joslin.harvard.edu
FU National Institutes of Health from NIDDK [R01-DK53105]; National
Institutes of Health from NIDDK (DERC) [P30-DK36836-21]; American
Diabetes Association [1-08-RA-93]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01-DK53105 from NIDDK and P30-DK36836-21 from NIDDK
(DERC). This work was also supported by American Diabetes Association
Grant 1-08-RA-93.
NR 37
TC 23
Z9 24
U1 1
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 10
PY 2012
VL 287
IS 7
BP 4518
EP 4530
DI 10.1074/jbc.M111.286591
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 896YX
UT WOS:000300608500015
PM 22158866
ER
PT J
AU Hedrich, CM
Rauen, T
Kis-Toth, K
Kyttaris, VC
Tsokos, GC
AF Hedrich, Christian M.
Rauen, Thomas
Kis-Toth, Katalin
Kyttaris, Vasileios C.
Tsokos, George C.
TI cAMP-responsive Element Modulator alpha (CREM alpha) Suppresses IL-17F
Protein Expression in T Lymphocytes from Patients with Systemic Lupus
Erythematosus (SLE)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID IL-2 PRODUCTION; HETERODIMERIC CYTOKINE; AUTOIMMUNE-DISEASES;
HOST-DEFENSE; CELLS; GENE; BINDING; TRANSCRIPTION; PROMOTER;
IDENTIFICATION
AB The proinflammatory cytokines IL-17A and IL-17F are primarily produced by Th17 lymphocytes. Both are involved in host defense mechanisms against bacterial and fungal pathogens and contribute to the development of various autoimmune diseases. T lymphocytes from patients with systemic lupus erythematosus (SLE) display increased expression of transcription factor cAMP-responsive element modulator alpha (CREM alpha), which has been documented to account for aberrant T cell function and contributes to the pathogenesis of SLE. Here, we provide evidence that IL-17F expression is reduced in SLE T cells. We demonstrate that CREM alpha binds to a yet unidentified CRE site within the proximal promoter. This results in reduced IL-17F expression in SLE T lymphocytes and is independent of activating epigenetic patterns (increased histone H3 Lys-18 acetylation, reduced histone H3 Lys-27 trimethylation, and CpG-DNA demethylation). Forced CREM alpha expression in human T lymphocytes results in reduced IL-17F expression. Our findings demonstrate extended involvement of CREM alpha in cytokine dysregulation in SLE by contributing to a disrupted balance between IL-17A and IL-17F. An increased IL-17A/IL-17F ratio may aggravate the proinflammatory phenotype of SLE.
C1 [Hedrich, Christian M.; Rauen, Thomas; Kis-Toth, Katalin; Kyttaris, Vasileios C.; Tsokos, George C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Rheumatol,Dept Med, Boston, MA 02115 USA.
[Rauen, Thomas] Rhein Westfal TH Aachen, Dept Nephrol & Clin Immunol, D-50062 Aachen, Germany.
RP Tsokos, GC (reprint author), Beth Israel Deaconess Med Ctr CLS 937, Div Rheumatol, Dept Med, 330 Brookline Ave, Boston, MA 02115 USA.
EM chedrich@bidmc.harvard.edu; gtsokos@bidmc.harvard.edu
FU National Institutes of Health [K23 AR055672, R01 AI42269, R01 AI49954,
R01 AI85567]; Deutsche Forschungsgemeinschaft [RA1927-1/1]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants K23 AR055672 (to V. C. K.) and R01 AI42269, R01 AI49954,
and R01 AI85567 (to G. C. T.). This work was also supported by Deutsche
Forschungsgemeinschaft Grant RA1927-1/1 (to T. R.).
NR 37
TC 26
Z9 26
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 10
PY 2012
VL 287
IS 7
BP 4715
EP 4725
DI 10.1074/jbc.M111.323261
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 896YX
UT WOS:000300608500033
PM 22184122
ER
PT J
AU Yu, M
Mazor, T
Huang, H
Huang, HT
Kathrein, KL
Woo, AJ
Chouinard, CR
Labadorf, A
Akie, TE
Moran, TB
Xie, HF
Zacharek, S
Taniuchi, I
Roeder, RG
Kim, CF
Zon, LI
Fraenkel, E
Cantor, AB
AF Yu, Ming
Mazor, Tali
Huang, Hui
Huang, Hsuan-Ting
Kathrein, Katie L.
Woo, Andrew J.
Chouinard, Candace R.
Labadorf, Adam
Akie, Thomas E.
Moran, Tyler B.
Xie, Huafeng
Zacharek, Sima
Taniuchi, Ichiro
Roeder, Robert G.
Kim, Carla F.
Zon, Leonard I.
Fraenkel, Ernest
Cantor, Alan B.
TI Direct Recruitment of Polycomb Repressive Complex 1 to Chromatin by Core
Binding Transcription Factors
SO MOLECULAR CELL
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; ADULT HEMATOPOIESIS; RUNX1; DIFFERENTIATION;
CBFA2; MICE; HAPLOINSUFFICIENCY; TRANSFORMATION; MEGAKARYOCYTE;
MAINTENANCE
AB Polycomb repressive complexes (PRCs) play key roles in developmental epigenetic regulation. Yet the mechanisms that target PRCs to specific loci in mammalian cells remain incompletely understood. In this study we show that Bmi1, a core component of Polycomb Repressive Complex 1 (PRC1), binds directly to the Runx1/CBF beta transcription factor complex. Genome-wide studies in megakaryocytic cells demonstrate significant chromatin occupancy overlap between the PRC1 core component Ring1b and Runx1/CBF beta and functional regulation of a considerable fraction of commonly bound genes. Bmi1/Ring1b and Runx1/CBF beta deficiencies generate partial phenocopies of one another in vivo. We also show that Ring1b occupies key Runx1 binding sites in primary murine thymocytes and that this occurs via PRC2-independent mechanisms. Genetic depletion of Runx1 results in reduced Ring1b binding at these sites in vivo. These findings provide evidence for site-specific PRC1 chromatin recruitment by core binding transcription factors in mammalian cells.
C1 [Mazor, Tali; Chouinard, Candace R.; Labadorf, Adam; Fraenkel, Ernest] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Mazor, Tali; Chouinard, Candace R.; Labadorf, Adam; Fraenkel, Ernest] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[Yu, Ming; Huang, Hui; Huang, Hsuan-Ting; Kathrein, Katie L.; Woo, Andrew J.; Akie, Thomas E.; Moran, Tyler B.; Xie, Huafeng; Zacharek, Sima; Kim, Carla F.; Zon, Leonard I.; Cantor, Alan B.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA.
[Yu, Ming; Huang, Hui; Huang, Hsuan-Ting; Kathrein, Katie L.; Woo, Andrew J.; Akie, Thomas E.; Moran, Tyler B.; Xie, Huafeng; Zacharek, Sima; Kim, Carla F.; Zon, Leonard I.; Cantor, Alan B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Taniuchi, Ichiro] RIKEN, Res Ctr Allergy & Immunol, Lab Transcript Regulat, Yokohama, Kanagawa 2300045, Japan.
[Roeder, Robert G.] Rockefeller Univ, Lab Biochem & Mol Biol, New York, NY 10065 USA.
[Kim, Carla F.; Zon, Leonard I.; Cantor, Alan B.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Zon, Leonard I.] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Fraenkel, E (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM fraenkel-admin@mit.edu; alan.cantor@childrens.harvard.edu
RI Taniuchi, Ichiro/N-6399-2015;
OI Taniuchi, Ichiro/0000-0002-9853-9068; Fraenkel,
Ernest/0000-0001-9249-8181
FU Wendy Will Case Cancer Fund; American Heart Association; NIH
[R01-HL082952, U54-CA112967, R01-GM089903, P30-ES002109]; Eugene Bell
Career Development Chair; National Science Foundation [DB1-0821391]
FX M.Y. is supported by a grant from the Wendy Will Case Cancer Fund and an
American Heart Association postdoctoral fellowship award. A.B.C. is
supported by a grant from the NIH (R01-HL082952). E.F. is the recipient
of the Eugene Bell Career Development Chair and is supported by NIH
Grants U54-CA112967 and R01-GM089903. This work used computing resources
funded by the National Science Foundation under Award No. DB1-0821391,
and sequencing support from the NIH (P30-ES002109). The authors would
like to thank D. Gary Gilliland, Stuart Orkin, and Maarten van Lohuizen
for providing knockout mouse strains and Ross Tomaino and Steven Gygi at
the Taplin Mass Spectrometry Facility for assistance with protein
identification.
NR 50
TC 91
Z9 93
U1 1
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD FEB 10
PY 2012
VL 45
IS 3
BP 330
EP 343
DI 10.1016/j.molcel.2011.11.032
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 895FH
UT WOS:000300481100008
PM 22325351
ER
PT J
AU Agarwal, N
Boucher, KM
Maughan, B
Hussain, SA
Kaufman, DS
Lorusso, V
Moore, MJ
Galsky, MD
Sonpavde, G
AF Agarwal, Neeraj
Boucher, Kenneth M.
Maughan, Benjamin
Hussain, Syed A.
Kaufman, Donald S.
Lorusso, Vito
Moore, Malcolm J.
Galsky, Matt D.
Sonpavde, Guru
CA SWOG
TI Pooled analysis of phase II trials evaluating weekly or conventional
cisplatin as first-line therapy for advanced urothelial carcinoma (UC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
Huntsman Canc Inst, Salt Lake City, UT USA.
Univ Utah, Salt Lake City, UT USA.
Canc Res UK Inst Canc Studies, Birmingham, W Midlands, England.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Vito Fazzi Hosp, Med Oncol Unit, Lecce, Italy.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
US Oncol Res LLC, McKesson Specialty Hlth, The Woodlands, TX USA.
Mt Sinai Med Ctr, Tisch Canc Inst, New York, NY 10029 USA.
Deke Slayton Canc Ctr, Webster, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 308
PG 2
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400307
PM 28143134
ER
PT J
AU Aizer, A
Paly, JJ
Zietman, AL
D'Amico, AV
Nguyen, PL
Beard, C
Rao, SK
Kaplan, ID
Hirsch, MS
Wu, CL
Efstathiou, JA
AF Aizer, Ayal
Paly, Jonathan J.
Zietman, Anthony L.
D'Amico, Anthony Victor
Nguyen, Paul Linh
Beard, Clair
Rao, Sandhya K.
Kaplan, Irving D.
Hirsch, Michelle S.
Wu, Chin-Lee
Efstathiou, Jason Alexander
TI Multidisciplinary care and pursuit of active surveillance in low-risk
prostate cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 131
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400132
PM 28143227
ER
PT J
AU Bian, S
Kuban, DA
Levy, LB
Oh, JH
Castle, K
Pugh, T
Choi, S
McGuire, SE
Frank, SJ
Nguyen, PL
Lee, A
Hoffman, KE
AF Bian, Shelly
Kuban, Deborah A.
Levy, Lawrence B.
Oh, Jeong Hoon
Castle, Katherine
Pugh, Thomas
Choi, Seungtaek
McGuire, Sean E.
Frank, Steven J.
Paul Linh Nguyen
Lee, Andrew
Hoffman, Karen Elizabeth
TI Effect of adding short-term androgen deprivation therapy to
dose-escalated radiation therapy on failure-free survival for select men
with intermediate-risk prostate cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Baylor Coll Med, Houston, TX 77030 USA.
Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
Univ Texas MD Anderson Canc Ctr, Dept Internal Med, Houston, TX 77030 USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 176
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400177
PM 28143155
ER
PT J
AU Bosco, JLF
Halpenny, B
Berry, DL
AF Bosco, Jaclyn Lee Fong
Halpenny, Barbara
Berry, Donna Lynn
TI Personal preferences and treatment choice in an intervention trial of
men newly diagnosed with localized prostate cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 [Bosco, Jaclyn Lee Fong; Halpenny, Barbara; Berry, Donna Lynn] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 170
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400171
PM 28143171
ER
PT J
AU Cho, E
Je, Y
Choueiri, TK
AF Cho, Eunyoung
Je, Youjin
Choueiri, Toni K.
TI Analgesic use and the risk of renal cell carcinoma (RCC): Results from a
large up-to-date meta-analysis.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 395
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400394
PM 28143284
ER
PT J
AU Cho, E
Joh, HK
Choueiri, TK
AF Cho, Eunyoung
Joh, Hee-Kyung
Choueiri, Toni K.
TI ABO blood group and risk of renal cell cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 371
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400370
PM 28143240
ER
PT J
AU Choueiri, TK
Pal, SK
McDermott, DF
Ramies, DA
Morrissey, S
Lee, Y
Miles, D
Holland, JS
Dutcher, JP
AF Choueiri, Toni K.
Pal, Sumanta Kumar
McDermott, David F.
Ramies, David A.
Morrissey, Stephanie
Lee, Yihua
Miles, Dale
Holland, Jaymes S.
Dutcher, Janice P.
TI Activity of cabozantinib (XL184) in patients (pts) with metastatic,
refractory renal cell carcinoma (RCC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA.
City Hope Natl Med Ctr, Duarte, CA USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Exelixis, San Francisco, CA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
St Lukes Roosevelt Hosp, New York, NY USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 364
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400363
ER
PT J
AU Choueiri, TK
Xie, WL
Harshman, LC
Bjarnason, GA
Knox, JJ
MacKenzie, MJ
Wood, L
Vaishampayan, UN
Tan, MH
Rha, SY
Donskov, F
Agarwal, N
Kollmannsberger, CK
North, SA
Rini, BI
Heng, DYC
AF Choueiri, Toni K.
Xie, Wanling
Harshman, Lauren Christine
Bjarnason, Georg A.
Knox, Jennifer J.
MacKenzie, Mary J.
Wood, Lori
Vaishampayan, Ulka N.
Tan, Min-Han
Rha, Sun Young
Donskov, Frede
Agarwal, Neeraj
Kollmannsberger, Christian K.
North, Scott A.
Rini, Brian I.
Heng, Daniel Yick Chin
TI Conditional survival (CS) for patients with metastatic renal cell
carcinoma (mRCC) treated with vascular endothelial growth factor
(VEGF)-targeted therapy (TT): Results from the International mRCC
Database Consortium.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Stanford Univ, Sch Med, Stanford, CA 94305 USA.
Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
London Reg Canc Program, London, ON, Canada.
Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Natl Canc Ctr, Singapore, Singapore.
Yonsei Univ, Coll Med, Severance Hosp, Seoul, South Korea.
Aarhus Univ Hosp, DK-8000 Aarhus, Denmark.
Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 358
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400357
PM 28143033
ER
PT J
AU Choueiri, TK
Vaishampayan, UN
Rosenberg, JE
Logan, T
Harzstark, AL
Rini, BI
Srinivas, S
Adams, LM
Sherman, LJ
Ottesen, LH
McDermott, DF
Bottaro, DP
Linehan, WM
Srinivasan, R
AF Choueiri, Toni K.
Vaishampayan, Ulka N.
Rosenberg, Jonathan E.
Logan, Theodore
Harzstark, Andrea Lynne
Rini, Brian I.
Srinivas, Sandy
Adams, Laurel M.
Sherman, Laurie Jill
Ottesen, Lone Harild
McDermott, David F.
Bottaro, Donald P.
Linehan, W. Marston
Srinivasan, Ramaprasad
TI A phase II and biomarker study (MET111644) of the dual Met/VEGFR-2
inhibitor foretinib in patients with sporadic and hereditary papillary
renal cell carcinoma: Final efficacy, safety, and PD results.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
Stanford Med Ctr, Stanford, CA USA.
GlaxoSmithKline, Res Triangle Pk, NC USA.
GlaxoSmithKline, Philadelphia, PA USA.
GlaxoSmithKline Oncol R&D, Uxbridge, Middx, England.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 355
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400354
ER
PT J
AU Drazer, MW
Prasad, SM
Huo, DZ
Schonberg, MA
Eggener, SE
AF Drazer, Michael W.
Prasad, Sandip M.
Huo, Dezheng
Schonberg, Mara A.
Eggener, Scott E.
TI Impact of US Preventive Services Task Force recommendation on screening
for prostate cancer in men age 75 or older
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Chicago, Chicago, IL 60637 USA.
Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 216
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400217
PM 28142963
ER
PT J
AU Duarte, C
Sarkisian, N
Nguyen, PL
Garroutte, E
Hurwitz, MD
AF Duarte, Catherine
Sarkisian, Natasha
Paul Linh Nguyen
Garroutte, Eva
Hurwitz, Mark D.
TI Impact of race on prostate cancer selection and cause-specific
mortality: A SEER database analysis
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Boston Coll, Chestnut Hill, MA 02167 USA.
Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 248
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400249
PM 28143253
ER
PT J
AU Efstathiou, JA
Paulus, R
Smith, MR
Jones, CU
Leibenhaut, MH
Husain, SM
Rotman, M
Souhami, L
Sandler, HM
Shipley, WU
AF Efstathiou, Jason Alexander
Paulus, Rebecca
Smith, Matthew R.
Jones, Christopher U.
Leibenhaut, Mark H.
Husain, Siraj M.
Rotman, Marvin
Souhami, Luis
Sandler, Howard Mark
Shipley, William U.
TI Cardiovascular mortality following short-term androgen deprivation in
clinically localized prostate cancer: An analysis of RTOG 94-08
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RTOG, Philadelphia, PA USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Radiol Associates Sacramento, Sacramento, CA USA.
Baker Canc Ctr, Calgary, AB, Canada.
SUNY Hlth Sci Ctr, Brooklyn, NY USA.
McGill Univ, Montreal, PQ, Canada.
Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 18
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400020
PM 28142889
ER
PT J
AU Gagnon, RC
Liu, Y
Choueiri, TK
Martin, AM
Rosenberg, JE
Signoretti, S
Pandite, LN
AF Gagnon, Robert C.
Liu, Yuan
Choueiri, Toni K.
Martin, Anne-Marie
Rosenberg, Jonathan E.
Signoretti, Sabina
Pandite, Lini N.
TI Assessment of a cell-line-derived HIF1 alpha gene signature in tumor
tissue from a metastatic renal cell carcinoma (RCC) trial of pazopanib.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 GlaxoSmithKline, Collegeville, PA USA.
GlaxoSmithKline, Res & Dev, Collegeville, PA USA.
Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Med Sch, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
GlaxoSmithKline, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 408
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400407
PM 28143103
ER
PT J
AU Gray, PJ
Fedewa, SA
Shipley, WU
Efstathiou, JA
Virgo, KS
Zietman, AL
AF Gray, Phillip J.
Fedewa, Stacey A.
Shipley, William U.
Efstathiou, Jason Alexander
Virgo, Katherine S.
Zietman, Anthony L.
TI Receipt of aggressive therapies for muscle-invasive bladder cancer:
Results from the National Cancer Data Base
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Radiat Oncol Program, Boston, MA USA.
Amer Canc Soc, Atlanta, GA 30329 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 272
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400272
PM 28143299
ER
PT J
AU Gray, PJ
Paly, JJ
Sanda, MG
Sandler, HM
Michalski, JM
Talcott, JA
Coen, J
Shipley, WU
Zietman, AL
Bekelman, JE
Efstathiou, JA
AF Gray, Phillip J.
Paly, Jonathan J.
Sanda, Martin G.
Sandler, Howard Mark
Michalski, Jeff M.
Talcott, James Austin
Coen, John
Shipley, William U.
Zietman, Anthony L.
Bekelman, Justin E.
Efstathiou, Jason Alexander
CA PROST-QA Consortium
TI Bowel and bladder toxicity patterns in patients with prostate cancer
treated with proton beam versus intensity-modulated radiation therapy
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Radiat Oncol Program, Boston, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
Washington Univ, Sch Med, St Louis, MO USA.
Continuum Canc Care Consortium, New York, NY USA.
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
RI Sanda, Martin/B-2023-2015
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 22
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400024
PM 28142916
ER
PT J
AU Guancial, EA
Werner, L
Stack, E
Lis, R
Signoretti, S
Loda, M
Gallardo, E
Rojo, F
Lloreta, J
Regan, MM
Park, R
O'Brien, R
Berman, DM
Bellmunt, J
Rosenberg, JE
AF Guancial, Elizabeth Ann
Werner, Lillian
Stack, Edward
Lis, Rosina
Signoretti, Sabina
Loda, Massimo
Gallardo, Enrique
Rojo, Federico
Lloreta, Jose
Regan, Meredith M.
Park, Rachel
O'Brien, Robert
Berman, David M.
Bellmunt, Joaquim
Rosenberg, Jonathan E.
TI Association of DNA repair factors with overall survival in advanced
urothelial carcinoma treated with platinum-based chemotherapy
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA.
Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
Corporacio Parc Tauli, Sabadell, Spain.
IMIM Hosp del Mar, Canc Res Grp, Barcelona, Spain.
Univ Hosp del Mar IMIM, Barcelona, Spain.
Johns Hopkins Univ Sch Med, Baltimore, MD USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Brigham & Womens Hos, Boston, MA 02115 USA.
RI Lloreta, J/I-2112-2014; Rojo, Federico/S-6551-2016
OI Lloreta, J/0000-0003-1644-9470;
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 291
PG 2
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400290
PM 28143170
ER
PT J
AU Hattangadi, JA
Chen, MH
Sun, L
D'Amico, AV
AF Hattangadi, Jona Ashok
Chen, Ming-Hui
Sun, Leon
D'Amico, Anthony Victor
TI Early detection of high-grade prostate cancer using digital rectal
examination in men with a normal PSA and risk of death.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Radiat Oncol Program, Boston, MA USA.
Univ Connecticut, Storrs, CT USA.
NIH, Bethesda, MD 20892 USA.
Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 147
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400148
PM 28143304
ER
PT J
AU Heng, DYC
Lee, JL
Harshman, LC
Bjarnason, GA
Razak, AR
MacKenzie, MJ
Wood, L
Vaishampayan, UN
Tan, MH
Rha, SY
Donskov, F
Agarwal, N
Kollmannsberger, CK
North, SA
Rini, BI
Choueiri, TK
AF Heng, Daniel Yick Chin
Lee, Jae-Lyun
Harshman, Lauren Christine
Bjarnason, Georg A.
Razak, Albiruni R.
MacKenzie, Mary J.
Wood, Lori
Vaishampayan, Ulka N.
Tan, Min-Han
Rha, Sun Young
Donskov, Frede
Agarwal, Neeraj
Kollmannsberger, Christian K.
North, Scott A.
Rini, Brian I.
Choueiri, Toni K.
CA Int mRCC Database Consortium
TI A population-based overview of sequences of targeted therapy in
metastatic renal cell carcinoma (mRCC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada.
Univ Ulsan, Coll Med, Dept Oncol, Asan Med Ctr, Seoul, South Korea.
Stanford Univ, Sch Med, Stanford, CA 94305 USA.
Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
London Reg Canc Program, London, ON, Canada.
Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Natl Canc Ctr, Singapore, Singapore.
Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea.
Aarhus Univ Hosp, DK-8000 Aarhus, Denmark.
Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 387
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400386
PM 28143319
ER
PT J
AU Heng, DYC
Choueiri, TK
Lee, JL
Harshman, LC
Bjarnason, GA
Knox, JJ
MacKenzie, MJ
Vaishampayan, UN
Tan, MH
Rha, SY
Donskov, F
Agarwal, N
Kollmannsberger, CK
North, SA
Rini, BI
Wood, L
AF Heng, Daniel Yick Chin
Choueiri, Toni K.
Lee, Jae-Lyun
Harshman, Lauren Christine
Bjarnason, Georg A.
Knox, Jennifer J.
MacKenzie, Mary J.
Vaishampayan, Ulka N.
Tan, Min-Han
Rha, Sun Young
Donskov, Frede
Agarwal, Neeraj
Kollmannsberger, Christian K.
North, Scott A.
Rini, Brian I.
Wood, Lori
CA Int mRCC Database Consortium
TI A multicentered population-based analysis of outcomes of patients with
metastatic renal cell carcinoma (mRCC) who do not meet eligibility
criteria for clinical trials.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA.
Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea.
Stanford Univ, Sch Med, Stanford, CA 94305 USA.
Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
London Reg Canc Program, London, ON, Canada.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Natl Canc Ctr, Singapore, Singapore.
Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea.
Aarhus Univ Hosp, DK-8000 Aarhus, Denmark.
Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 353
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400352
PM 28143049
ER
PT J
AU Hutson, TE
Dang, LH
Lauer, RC
Starodub, A
Hauke, RJ
Logan, T
Bylow, KA
Galsky, MD
Bibby, DC
Kremmidiotis, G
Doolin, EE
Lavranos, TC
Leske, AF
Hahn, NM
Sonpavde, G
Sweeney, C
Sarantopoulos, J
AF Hutson, Thomas E.
Dang, Long H.
Lauer, Richard C.
Starodub, Alexander
Hauke, Ralph J.
Logan, Theodore
Bylow, Kathryn A.
Galsky, Matt D.
Bibby, David C.
Kremmidiotis, Gabriel
Doolin, Elizabeth E.
Lavranos, Tina C.
Leske, Annabell F.
Hahn, Noah M.
Sonpavde, Guru
Sweeney, Christopher
Sarantopoulos, John
CA Hoosier Oncology Grp
TI Phase I/II study of a BNC105P/everolimus regimen for progressive
metastatic renal cell carcinoma (mRCC) following prior tyrosine kinase
inhibitors (Hoosier Oncology Group).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 US Oncol Res LLC, McKesson Specialty Hlth, The Woodlands, TX USA.
Baylor Sammons Canc Ctr Texas Oncol PA, Dallas, TX USA.
Univ Florida, Gainesville, FL USA.
Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA.
Goshen Ctr Canc Care, Goshen, IN USA.
Nebraska Canc Specialists, Omaha, NE USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Med Coll Wisconsin, Milwaukee, WI 53226 USA.
Mt Sinai Med Ctr, Tisch Canc Inst, New York, NY 10029 USA.
Bionomics Ltd, Thebarton, Australia.
Deke Slayton Canc Ctr, Webster, TX USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, San Antonio, TX 78229 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 373
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400372
PM 28143228
ER
PT J
AU Katz, LM
Efstathiou, JA
Opraseuth, J
Killoran, J
Paly, JJ
Weathers, R
Stovall, M
Beard, C
AF Katz, Leah Minnie
Efstathiou, Jason Alexander
Opraseuth, Jonathan
Killoran, Joseph
Paly, Jonathan J.
Weathers, Rita
Stovall, Marilyn
Beard, Clair
TI Normal tissue exposure during retroperitoneal radiotherapy for pure
seminoma of the testis.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 334
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400333
PM 28142971
ER
PT J
AU Klein, EA
Thompson, I
Tangen, CM
Lucia, MS
Goodman, P
Minasian, LM
Ford, LG
Parnes, HL
Gaziano, JM
Karp, DD
Lieber, MM
Walther, PJ
Parsons, JK
Chin, J
Darke, AK
Lippman, SM
Goodman, GE
Meyskens, FL
Baker, LH
AF Klein, Eric A.
Thompson, Ian
Tangen, Catherine M.
Lucia, M. Scott
Goodman, Phyllis
Minasian, Lori M.
Ford, Leslie G.
Parnes, Howard L.
Gaziano, J. Michael
Karp, Daniel D.
Lieber, Michael M.
Walther, Philip John
Parsons, J. Kellogg
Chin, Joseph
Darke, Amy K.
Lippman, Scott Michael
Goodman, Gary E.
Meyskens, Frank L.
Baker, Laurence H.
TI Vitamin E and the risk of prostate cancer: Updated results of the
Selenium and Vitamin E Cancer Prevention Trial (SELECT)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
Univ Colorado, Sch Med, Aurora, CO USA.
SWOG Stat Ctr, Seattle, WA USA.
NCI, Bethesda, MD 20892 USA.
NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Mayo Clin, Rochester, MN USA.
Duke Univ, Med Ctr, Durham, NC USA.
Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
London Hlth Sci Ctr, London, ON, Canada.
Swedish Canc Inst, Seattle, WA USA.
Chao Family Comprehens Canc Ctr, Orange, CA USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 7
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400009
PM 28143337
ER
PT J
AU Mak, RH
Hunt, D
Shipley, WU
Efstathiou, JA
Tester, WJ
Hagan, MP
Kaufman, DS
Heney, NM
Zietman, AL
AF Mak, Raymond H.
Hunt, Daniel
Shipley, William U.
Efstathiou, Jason Alexander
Tester, William J.
Hagan, Michael P.
Kaufman, Donald S.
Heney, Niall M.
Zietman, Anthony L.
TI Long-term outcomes in patients with muscle-invasive bladder cancer after
bladder-preserving combined-modality therapy: A pooled analysis of RTOG
8802, 8903, 9506, 9706, 9906, and 0233
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
Radiat Therapy Oncol Grp, Philadelphia, PA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Albert Einstein Med Ctr, Philadelphia, PA 19141 USA.
Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 264
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400265
PM 28143313
ER
PT J
AU Murciano-Goroff, YR
Wolfsberger, LD
Parekh, A
Fennessy, FM
Tuncali, K
Orio, PF
Niedermayr, T
Suh, WW
Devlin, PM
Tempany, CM
Nguyen, PL
AF Murciano-Goroff, Yonina R.
Wolfsberger, Luciant D.
Parekh, Arti
Fennessy, Fiona M.
Tuncali, Kemal
Orio, Peter F.
Niedermayr, Thomas
Suh, W. Warren
Devlin, Phillip M.
Tempany, Clare M.
Paul Linh Nguyen
TI Variability in prostate volume as determined by MRI versus ultrasound
and its impact on treatment recommendations for patients with
favorable-risk prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
Canc Ctr Santa Barbara, Santa Barbara, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 249
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400250
PM 28143244
ER
PT J
AU Paly, JJ
Efstathiou, JA
Hedgire, S
Chung, PWM
O'Malley, M
Shah, A
Bekelman, JE
Harisinghani, M
Zietman, AL
Shipley, WU
Beard, C
AF Paly, Jonathan J.
Efstathiou, Jason Alexander
Hedgire, Sandeep
Chung, Peter W. M.
O'Malley, Martin
Shah, Anand
Bekelman, Justin E.
Harisinghani, Mukesh
Zietman, Anthony L.
Shipley, William U.
Beard, Clair
TI Mapping patterns of nodal metastases in seminoma: Rethinking
radiotherapy fields
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada.
Univ Toronto, Toronto, ON, Canada.
Princess Margaret Hosp, Dept Med Imaging, Toronto, ON M4X 1K9, Canada.
Hosp Univ Penn, Philadelphia, PA 19104 USA.
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 324
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400323
PM 28143011
ER
PT J
AU Parekh, A
Chen, MH
Hoffman, KE
Choueiri, TK
Hu, JC
Bennett, CL
Kattan, MW
Sartor, AO
Stein, K
D'Amico, AV
Nguyen, PL
AF Parekh, Arti
Chen, Ming-Hui
Hoffman, Karen Elizabeth
Choueiri, Toni K.
Hu, Jim C.
Bennett, Charles L.
Kattan, Michael W.
Sartor, A. Oliver
Stein, Karen
D'Amico, Anthony Victor
Paul Linh Nguyen
TI Incidence of reduced penis size among men with recurrent prostate cancer
previously treated with surgery, radiation plus androgen deprivation, or
radiation alone
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Connecticut, Storrs, CT USA.
Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol Surg, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
South Carolina Coll Pharm, Charleston, SC USA.
Hollings Canc Ctr, Charleston, SC USA.
Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
Tulane Univ, Dept Med, New Orleans, LA 70118 USA.
Tulane Univ, Dept Urol, New Orleans, LA 70118 USA.
Eisai Pharmaceut, Woodcliff Lake, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 38
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400040
PM 28142900
ER
PT J
AU Nguyen, PL
Chen, MH
Zhang, YY
Tempany, CM
Cormack, RA
Beard, C
Hurwitz, MD
Suh, WW
D'Amico, AV
AF Paul Linh Nguyen
Chen, Ming-Hui
Zhang, Yuanye
Tempany, Clare M.
Cormack, Robert A.
Beard, Clair
Hurwitz, Mark D.
Suh, W. Warren
D'Amico, Anthony Victor
TI Long-term results of MRI-guided partial prostate brachytherapy for
favorable-risk prostate cancer: Implications for focal therapy.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Connecticut, Storrs, CT USA.
Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
Canc Ctr Santa Barbara, Santa Barbara, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 114
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400115
PM 28143026
ER
PT J
AU Petrylak, DP
Kantoff, PW
Mega, AE
Dreicer, R
Frank, RC
Shore, ND
Morris, S
Olson, WC
Israel, RJ
AF Petrylak, Daniel Peter
Kantoff, Philip W.
Mega, Anthony E.
Dreicer, Robert
Frank, Richard C.
Shore, Neal D.
Morris, Stephen
Olson, William C.
Israel, Robert Joseph
TI Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A
phase I trial in men with prostate cancer previously treated with
taxane.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Brown Univ, Oncol Grp, Providence, RI 02912 USA.
Cleveland Clin, Cleveland, OH 44106 USA.
Norwalk Med Grp, Norwalk, CT USA.
Carolina Urol Res Ctr, Myrtle Beach, SC USA.
Progen Pharmaceut Inc, Tarrytown, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 107
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400108
PM 28143055
ER
PT J
AU Psutka, SP
McGovern, FJ
Mueller, P
McDougal, WS
Gervais, D
Feldman, AS
AF Psutka, Sarah P.
McGovern, Francis J.
Mueller, Peter
McDougal, W. Scott
Gervais, Debra
Feldman, Adam S.
TI Long-term durable oncologic outcomes after radiofrequency ablation for
T1 renal cell carcinoma.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 384
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400383
PM 28143317
ER
PT J
AU Psutka, SP
Olumi, AF
Feldman, AS
Saylor, PJ
Kaufman, DS
Lee, RJ
AF Psutka, Sarah P.
Olumi, Aria F.
Feldman, Adam S.
Saylor, Philip James
Kaufman, Donald S.
Lee, Richard J.
TI Pathologic down-staging and complete pathologic response with
gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive
urothelial carcinoma of the bladder
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 307
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400306
PM 28143141
ER
PT J
AU Qu, AQ
Cheng, SC
Atkins, MB
Signoretti, S
Choueiri, TK
AF Qu, Angela Q.
Cheng, SuChun
Atkins, Michael B.
Signoretti, Sabina
Choueiri, Toni K.
TI Carbonic anhydrase IX (CAIX) as a potential biomarker of efficacy in
metastatic clear-cell renal cell carcinoma (mccRCC) in patients (pts)
receiving sorafenib: Analysis of a randomized controlled trial (TARGET).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Dana Farber Harvard Canc Ctr, Boston, MA USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 352
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400351
PM 28143040
ER
PT J
AU Richards, CJ
Je, YJ
Schutz, FAB
Choueiri, TK
AF Richards, Christopher J.
Je, Youjin
Schutz, Fabio A. B.
Choueiri, Toni K.
TI Meta-analysis of randomized control trials for the incidence and risk of
treatment-related mortality in patients with cancer treated with
vascular endothelial growth factor tyrosine kinase inhibitors.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Sch Med, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 349
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400348
PM 28143053
ER
PT J
AU Rini, BI
Escudier, BJ
Michaelson, MD
Negrier, S
Gore, ME
Oudard, S
Clark, J
Tarazi, JC
Rosbrook, B
Kim, S
Motzer, RJ
AF Rini, Brian I.
Escudier, Bernard J.
Michaelson, M. Dror
Negrier, Sylvie
Gore, Martin Eric
Oudard, Stephane
Clark, Joseph
Tarazi, Jamal Christo
Rosbrook, Brad
Kim, Sinil
Motzer, Robert John
TI Phase III AXIS trial for second-line metastatic renal cell carcinoma
(mRCC): Effect of prior first-line treatment duration and axitinib dose
titration on axitinib efficacy.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
Inst Gustave Roussy, Villejuif, France.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Leon Berard Canc Ctr, Lyon, France.
Royal Marsden Hosp, London SW3 6JJ, England.
Georges Pompidou European Hosp, Paris, France.
Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
Pfizer Oncol, La Jolla, CA USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 354
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400353
PM 28143045
ER
PT J
AU Roach, M
Yan, Y
Lawton, CA
Hsu, ICJ
Lustig, RA
Jones, CU
Rotman, M
Zeitzer, KL
Werner-Wasik, M
Kim, H
Thomas, CR
Shipley, WU
Sandler, HM
AF Roach, Mack
Yan, Yan
Lawton, Colleen Anne
Hsu, I-Chow Joe
Lustig, Robert A.
Jones, Christopher U.
Rotman, Marvin
Zeitzer, Kenneth Lee
Werner-Wasik, Maria
Kim, Harold
Thomas, Charles R.
Shipley, William U.
Sandler, Howard Mark
TI Radiation Therapy Oncology Group (RTOG) 9413: Randomized trial comparing
whole pelvic radiotherapy (WPRT) to prostate only (PORT) and neoadjuvant
hormone therapy (NHT) to adjuvant hormone therapy (AHT).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Calif San Francisco, San Francisco, CA 94143 USA.
Radiat Therapy Oncol Grp, Philadelphia, PA USA.
Med Coll Wisconsin, Milwaukee, WI 53226 USA.
Hosp Univ Penn, Philadelphia, PA 19104 USA.
Radiol Associates Sacramento, Sacramento, CA USA.
SUNY Hlth Sci Ctr, Brooklyn, NY USA.
Albert Einstein Med Ctr, Philadelphia, PA 19141 USA.
Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 96
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400097
PM 28143343
ER
PT J
AU Rudman, SM
Gray, KP
Kasperzyk, J
Pitt, M
Giovannucci, E
Loda, M
Mucci, L
Sweeney, C
AF Rudman, Sarah Maria
Gray, Kathryn P.
Kasperzyk, Julie
Pitt, Michael
Giovannucci, Edward
Loda, Massimo
Mucci, Lorelei
Sweeney, Christopher
TI Association of metabolic syndrome with reduced survival among men
receiving androgen deprivation therapy for nonmetastatic prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Guys Hosp, Div Canc Studies, Kings Coll London, London SE1 9RT, England.
Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA USA.
Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
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
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 56
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400058
PM 28142922
ER
PT J
AU Saylor, PJ
Karoly, ED
Smith, MR
AF Saylor, Philip James
Karoly, Edward D.
Smith, Matthew Raymond
TI Changes in plasma metabolomic profiles during the first 3 months of
androgen-deprivation therapy for prostate cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Metabolon Inc, Morrisville, NC USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 116
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400117
PM 28143032
ER
PT J
AU Scher, HI
Fizazi, K
Saad, F
Taplin, ME
Sternberg, CN
Miller, K
De Wit, R
Mulders, P
Hirmand, M
Selby, B
De Bono, JS
AF Scher, Howard I.
Fizazi, Karim
Saad, Fred
Taplin, Mary-Ellen
Sternberg, Cora N.
Miller, Kurt
De Wit, Ronald
Mulders, Peter
Hirmand, Mohammad
Selby, Bryan
De Bono, Johann Sebastian
CA AFFIRM Investigators
TI Effect of MDV3100, an androgen receptor signaling inhibitor (ARSI), on
overall survival in patients with prostate cancer postdocetaxel: Results
from the phase III AFFIRM study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Univ Paris Sud, Inst Gustave Roussy, Villejuif, France.
Univ Montreal Hosp Ctr, Montreal, PQ, Canada.
Dana Farber Canc Inst, Boston, MA 02115 USA.
San Camillo Hosp, Rome, Italy.
Forlanini Hosp, Rome, Italy.
Charite, Dept Urol, D-13353 Berlin, Germany.
Erasmus Univ, Med Ctr, Rotterdam, Netherlands.
Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
Medivation, San Francisco, CA USA.
Inst Canc Res, Sutton, Surrey, England.
Royal Marsden Hosp, Sutton, Surrey, England.
RI Mulders, Peter/H-8076-2014
NR 0
TC 11
Z9 11
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA LBA1
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400002
PM 28142898
ER
PT J
AU Sharma, J
Gray, KP
Nakabayashi, M
Petrozziello, G
Evan, C
Fichorova, R
Kantoff, PW
Sweeney, C
AF Sharma, Jaya
Gray, Kathryn P.
Nakabayashi, Mari
Petrozziello, Gillian
Evan, Carolyn
Fichorova, Raina
Kantoff, Philip W.
Sweeney, Christopher
TI Use of elevated insulin-like growth factor binding protein-1 (IGFBP-1)
to predict outcomes in men with metastatic prostate cancer treated with
androgen-deprivation therapy (ADT).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
IBCSG Stat Ctr, Boston, MA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
RI Fichorova, Raina/G-9969-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 191
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400192
PM 28143201
ER
PT J
AU Sharma, J
Gray, KP
Nakabayashi, M
Petrozziello, G
Evan, C
Fichorova, R
Kantoff, PW
Sweeney, C
AF Sharma, Jaya
Gray, Kathryn P.
Nakabayashi, Mari
Petrozziello, Gillian
Evan, Carolyn
Fichorova, Raina
Kantoff, Philip W.
Sweeney, Christopher
TI Use of elevated baseline IL-8, CCL-2, and TNF alpha to predict for
shorter overall survival (OS) in men with metastatic prostate cancer
initiating androgen-deprivation therapy (ADT)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
RI Fichorova, Raina/G-9969-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 13
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400015
PM 28142894
ER
PT J
AU Small, AC
Tsao, CK
Moshier, E
Godbold, J
Sonpavde, G
Oh, WK
Galsky, MD
AF Small, Alexander C.
Tsao, Che-Kai
Moshier, Erin
Godbold, James
Sonpavde, Guru
Oh, William K.
Galsky, Matt D.
TI Prevalence and characteristics of patients with metastatic prostate
cancer who receive no anticancer therapy.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA.
Texas Oncol, Houston, TX USA.
Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 101
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400102
PM 28143086
ER
PT J
AU Small, EJ
Weinberg, VK
Ryan, CJ
Higano, CS
Lin, AM
Maruca, Y
Alumkal, JJ
Yu, EY
Rosenberg, JE
Beer, TM
AF Small, Eric Jay
Weinberg, Vivian K.
Ryan, Charles J.
Higano, Celestia S.
Lin, Amy Mimi
Maruca, Yvonne
Alumkal, Joshi J.
Yu, Evan Y.
Rosenberg, Jonathan E.
Beer, Tomasz M.
TI A prospective randomized phase II trial evaluating maintenance GM-CSF in
an intermittent chemotherapy (chemo) regimen for metastatic
castration-resistant prostate cancer (mCRPC): A DoD prostate cancer
clinical trials consortium trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Calif San Francisco, San Francisco, CA 94143 USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA.
Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 35
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400037
PM 28142903
ER
PT J
AU Smith, MR
Saad, F
Shore, ND
Oudard, S
Miller, K
Tombal, B
Sieber, P
Fizazi, K
Van Veldhuizen, PJ
Damiao, R
Marx, GM
Morote, J
Feng, A
Dansey, R
Goessl, CD
AF Smith, Matthew R.
Saad, Fred
Shore, Neal D.
Oudard, Stephane
Miller, Kurt
Tombal, Bertrand
Sieber, Paul
Fizazi, Karim
Van Veldhuizen, Peter J.
Damiaeo, Ronaldo
Marx, Gavin M.
Morote, Juan
Feng, Amy
Dansey, Roger
Goessl, Carsten Dietrich
TI Effect of denosumab on prolonging bone-metastasis-free survival (BMFS)
in men with nonmetastatic castrate-resistant prostate cancer (CRPC)
presenting with aggressive PSA kinetics
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Univ Montreal Hosp Ctr, Montreal, PQ, Canada.
Carolina Urol Res Ctr, Myrtle Beach, SC USA.
Georges Pompidou European Hosp, Paris, France.
Charite, Dept Urol, D-13353 Berlin, Germany.
Catholic Univ Louvain, Clin Univ St Luc, B-1200 Brussels, Belgium.
Urol Associates Lancaster Ltd, Lancaster, PA USA.
Univ Paris Sud, Inst Gustave Roussy, Villejuif, France.
Kansas City VA Med Ctr, Kansas City, MO USA.
Hosp Univ Pedro Ernesto, Rio De Janeiro, Brazil.
Sydney Haematol Oncol Clin, Sydney, NSW, Australia.
Vall dHebron Univ Hosp, Dept Urol, Barcelona, Spain.
Amgen Inc, Thousand Oaks, CA 91320 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 6
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400008
PM 28143335
ER
PT J
AU Srinivasan, R
Bottaro, DP
Choueiri, TK
Vaishampayan, UN
Rosenberg, JE
Logan, T
Harzstark, AL
Rini, BI
Srinivas, S
Adams, LM
Laubscher, K
Ottesen, LH
McDermott, DF
Linehan, WM
AF Srinivasan, Ramaprasad
Bottaro, Donald P.
Choueiri, Toni K.
Vaishampayan, Ulka N.
Rosenberg, Jonathan E.
Logan, Theodore
Harzstark, Andrea Lynne
Rini, Brian I.
Srinivas, Sandy
Adams, Laurel M.
Laubscher, Kevin
Ottesen, Lone Harild
McDermott, David F.
Linehan, W. Marston
TI Correlation of germline MET mutation with response to the dual
Met/VEGFR-2 inhibitor foretinib in patients with sporadic and hereditary
papillary renal cell carcinoma: Results from a multicenter phase II
study (MET111644).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
Stanford Med Ctr, Stanford, CA USA.
GlaxoSmithKline, Res Triangle Pk, NC USA.
GlaxoSmithKline Oncol R&D, Uxbridge, Middx, England.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 372
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400371
PM 28143239
ER
PT J
AU Tadros, NN
Farris, PE
Shannon, J
Beer, TM
Garzotto, M
AF Tadros, Nicholas N.
Farris, Paige E.
Shannon, Jackilen
Beer, Tomasz M.
Garzotto, Mark
TI The safety of prostate biopsy procedures in the research setting: A
10-year multicenter experience.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Portland VA Med Ctr, Portland, OR USA.
Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 87
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400089
PM 28143351
ER
PT J
AU Tsao, CK
Moshier, E
Small, AC
Sonpavde, G
Godbold, J
Oh, WK
Galsky, MD
AF Tsao, Che-Kai
Moshier, Erin
Small, Alexander C.
Sonpavde, Guru
Godbold, James
Oh, William K.
Galsky, Matt D.
TI Cytoreductive nephrectomy in the United States: Patterns of care and
patient characteristics.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA.
Texas Oncol, Houston, TX USA.
Baylor Coll Med, Dept Med, Sect Med Oncol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 366
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400365
PM 28143249
ER
PT J
AU Wang, Y
Choueiri, TK
Lee, JL
Tan, MH
Rha, SY
North, SA
Kollmannsberger, CK
Heng, DYC
AF Wang, Ying
Choueiri, Toni K.
Lee, Jae-Lyun
Tan, Min-Han
Rha, Sun Young
North, Scott A.
Kollmannsberger, Christian K.
Heng, Daniel Yick Chin
TI Vascular endothelial growth factor (VEGF) therapy in metastatic renal
cell carcinoma (mRCC): Differences between Asian and non-Asian patients.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Calgary, Calgary, AB, Canada.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA.
Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea.
Natl Canc Ctr, Singapore, Singapore.
Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea.
Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2012
VL 30
IS 5
SU S
MA 451
PG 1
WC Oncology
SC Oncology
GA V31OH
UT WOS:000208892400450
PM 28142982
ER
PT J
AU Singh, JA
AF Singh, Jasvinder A.
TI Can racial disparities in optimal gout treatment be reduced? Evidence
from a randomized trial
SO BMC MEDICINE
LA English
DT Editorial Material
DE Gout; Disparity; Race; treatment; Febuxostat; Allopurinol; randomized;
African-American
ID ACUTE MYOCARDIAL-INFARCTION; SERUM URATE; INDEPENDENT IMPACT; JOINT
ARTHROPLASTY; UNITED-STATES; CARE; HYPERURICEMIA; ALLOPURINOL;
POPULATION; PREVALENCE
AB There is a disproportionate burden of gout in African-Americans in the U. S. due to a higher disease prevalence and lower likelihood of receiving urate-lowering therapy (ULT), compared to Caucasians. There is an absence of strong data as to whether the response to ULT differs by race/ethnicity. BMC Musculoskeletal Disorders recently published a secondary analyses of the CONFIRMS trial, a large randomized controlled, double-blind trial of 2,269 gout patients. The authors reported that the likelihood of achieving the primary study efficacy end-point of achieving serum urate < 6 mg/dl was similar between African-Americans and Caucasians, for all three treatment arms (Febuxostat 40 mg and 80 mg and allopurinol 300/200 mg). More importantly, rates were similar in subgroups of patients with mild or moderate renal insufficiency. Adverse event rates were similar, as were the rates of gout flares. These findings constitute a convincing evidence to pursue aggressive ULT in gout patients, regardless of race/ethnicity. This approach will likely help to narrow the documented racial disparities in gout care. Please see related article: http://www.biomedcentral.com/1471-2474/13/15
C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Med Serv, Birmingham VA Med Ctr, Birmingham, AL 35294 USA.
[Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 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 Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA.
[Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA.
[Singh, Jasvinder A.] Univ Alabama Birmingham, Fac Off Tower 805B, Birmingham, AL 35294 USA.
RP Singh, JA (reprint author), Univ Alabama Birmingham, Med Serv, Birmingham VA Med Ctr, Birmingham, AL 35294 USA.
EM Jasvinder.md@gmail.com
OI singh, jasvinder/0000-0003-3485-0006
NR 26
TC 3
Z9 3
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD FEB 9
PY 2012
VL 10
AR 15
DI 10.1186/1741-7015-10-15
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 932ZA
UT WOS:000303327800001
PM 22316088
ER
PT J
AU Bungartz, G
Land, H
Scadden, DT
Emerson, SG
AF Bungartz, Gerd
Land, Hannah
Scadden, David T.
Emerson, Stephen G.
TI NF-Y is necessary for hematopoietic stem cell proliferation and survival
SO BLOOD
LA English
DT Article
ID SELF-RENEWAL; CYCLIN B1; CBF/NF-Y; IN-VIVO; TRANSCRIPTION; NOTCH1; GENE;
EXPRESSION; COMPLEX; BMI-1
AB HSC function depends on the tight control of proliferation and the balance between self-renewal and differentiation. Here, we report that the trimeric transcription factor NF-Y is critical for the survival of cycling, but not quiescent HSCs. With the use of a conditional knockout mouse model, we demonstrate that NF-Ya deletion creates an accumulation of HSCs in G(2)/M and prompts apoptosis, causing hematopoietic failure and death of the animal. These defects are accompanied by the dysregulation of multiple genes that influence cell cycle control (cyclin b1 and p21), apoptosis (Bcl-2), and self-renewal (HoxB4, Notch1, Bmi-1) and are independent of p53. Our results identify NF-Y as a pivotal upstream participant in a regulatory network necessary for the preservation of cycling HSCs. (Blood. 2012; 119(6): 1380-1389)
C1 [Bungartz, Gerd; Land, Hannah; Emerson, Stephen G.] Haverford Coll, Haverford, PA 19041 USA.
[Bungartz, Gerd; Emerson, Stephen G.] Univ Penn, Sch Med, Div Hematol Oncol, Philadelphia, PA 19104 USA.
[Bungartz, Gerd; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Bungartz, Gerd; Scadden, David T.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Bungartz, Gerd; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
RP Emerson, SG (reprint author), Haverford Coll, 370 Lancaster Ave, Haverford, PA 19041 USA.
EM scadden.david@MGH.Harvard.edu; semerson@haverford.edu
FU National Institute of Health [5R01CA090833]; Deutsche
Forschungs-Gemeinschaft; Leukemia & Lymphoma Society
FX This work was supported by the National Institute of Health (grant
5R01CA090833, S.G.E.) and grants from the Deutsche
Forschungs-Gemeinschaft and the Leukemia & Lymphoma Society (G.B.).
NR 38
TC 27
Z9 27
U1 2
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 FEB 9
PY 2012
VL 119
IS 6
BP 1380
EP 1389
DI 10.1182/blood-2011-06-359406
PG 10
WC Hematology
SC Hematology
GA 894IR
UT WOS:000300420900014
PM 22072554
ER
PT J
AU Azab, AK
Quang, P
Azab, F
Pitsillides, C
Thompson, B
Chonghaile, T
Patton, JT
Maiso, P
Monrose, V
Sacco, A
Ngo, HT
Flores, LM
Lin, CP
Magnani, JL
Kung, AL
Letai, A
Carrasco, R
Roccaro, AM
Ghobrial, IM
AF Azab, Abdel Kareem
Quang, Phong
Azab, Feda
Pitsillides, Costas
Thompson, Brian
Chonghaile, Triona
Patton, John T.
Maiso, Patricia
Monrose, Val
Sacco, Antonio
Ngo, Hai T.
Flores, Ludmila M.
Lin, Charles P.
Magnani, John L.
Kung, Andrew L.
Letai, Anthony
Carrasco, Ruben
Roccaro, Aldo M.
Ghobrial, Irene M.
TI P-selectin glycoprotein ligand regulates the interaction of multiple
myeloma cells with the bone marrow microenvironment
SO BLOOD
LA English
DT Article
ID SIALYL-LEWIS-X; BIOLOGICAL EVALUATION; INHIBITORS; ADHESION; DESIGN;
METASTASIS; ANTAGONIST; THERAPY; PSGL-1; TARGET
AB Interactions between multiple myeloma (MM) cells and the BM microenvironment play a critical role in the pathogenesis of MM and in the development of drug resistance by MM cells. Selectins are involved in extravasation and homing of leukocytes to target organs. In the present study, we focused on adhesion dynamics that involve P-selectin glycoprotein ligand-1 (PSGL-1) on MM cells and its interaction with selectins in the BM microenvironment. We show that PSGL-1 is highly expressed on MM cells and regulates the adhesion and homing of MM cells to cells in the BM microenvironment in vitro and in vivo. This interaction involves both endothelial cells and BM stromal cells. Using loss-of-function studies and the small-molecule pan-selectin inhibitor GMI-1070, we show that PSGL-1 regulates the activation of integrins and downstream signaling. We also document that this interaction regulates MM-cell proliferation in coculture with BM microenvironmental cells and the development of drug resistance. Furthermore, inhibiting this interaction with GMI-1070 enhances the sensitization of MM cells to bortezomib in vitro and in vivo. These data highlight the critical contribution of PSGL-1 to the regulation of growth, dissemination, and drug resistance in MM in the context of the BM microenvironment. (Blood. 2012; 119(6): 1468-1478)
C1 [Azab, Abdel Kareem; Quang, Phong; Azab, Feda; Chonghaile, Triona; Maiso, Patricia; Monrose, Val; Sacco, Antonio; Ngo, Hai T.; Flores, Ludmila M.; Kung, Andrew L.; Letai, Anthony; Carrasco, Ruben; Roccaro, Aldo M.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pitsillides, Costas; Thompson, Brian; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Patton, John T.; Magnani, John L.] GlycoMimetics Inc, Gaithersburg, MD USA.
RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 548A, Boston, MA 02115 USA.
EM irene_ghobrial@dfci.harvard.edu
RI Ni Chonghaile, Triona/L-9418-2015; Sacco, Antonio/K-4681-2016;
OI Ni Chonghaile, Triona/0000-0002-3041-4031; Sacco,
Antonio/0000-0003-2945-9416; Maiso, Patricia/0000-0003-3745-1924;
Roccaro, Aldo/0000-0002-1872-5128; Kung, Andrew/0000-0002-9091-488X
FU Multiple Myeloma Research Foundation; National Institutes of Health
[R01CA125690, 1R01CA152607]
FX This study was supported in part by the Multiple Myeloma Research
Foundation and by the National Institutes of Health (grants R01CA125690
and 1R01CA152607).
NR 37
TC 38
Z9 39
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 9
PY 2012
VL 119
IS 6
BP 1468
EP 1478
DI 10.1182/blood-2011-07-368050
PG 11
WC Hematology
SC Hematology
GA 894IR
UT WOS:000300420900023
PM 22096244
ER
PT J
AU Srinivasan, M
Flynn, R
Price, A
Ranger, A
Browning, JL
Taylor, PA
Ritz, J
Antin, JH
Murphy, WJ
Luznik, L
Shlomchik, MJ
Panoskaltsis-Mortari, A
Blazar, BR
AF Srinivasan, Mathangi
Flynn, Ryan
Price, Andrew
Ranger, Ann
Browning, Jeffrey L.
Taylor, Patricia A.
Ritz, Jerome
Antin, Joseph H.
Murphy, William J.
Luznik, Leo
Shlomchik, Mark J.
Panoskaltsis-Mortari, Angela
Blazar, Bruce R.
TI Donor B-cell alloantibody deposition and germinal center formation are
required for the development of murine chronic GVHD and bronchiolitis
obliterans
SO BLOOD
LA English
DT Article
ID VERSUS-HOST-DISEASE; BONE-MARROW TRANSPLANTATION; SALIVARY-GLAND
INVOLVEMENT; CD4(+) T-CELLS; AUTOIMMUNE-DISEASE; MONOCLONAL-ANTIBODY;
MODEL; MICE; IMMUNOTHERAPY; RESPONSES
AB Chronic GVHD (cGVHD) poses a significant risk for HSCT patients. Preclinical development of new therapeutic modalities has been hindered by models with pathologic findings that may not simulate the development of human cGVHD. Previously, we have demonstrated that cGVHD induced by allogeneic HSCT after a conditioning regimen of cyclophosphamide and total-body radiation results in pulmonary dysfunction and airway obliteration, which leads to bronchiolitis obliterans (BO), which is pathognomonic for cGVHD of the lung. We now report cGVHD manifestations in a wide spectrum of target organs, including those with mucosal surfaces. Fibrosis was demonstrated in the lung and liver and was associated with CD4(+) (T) cells and B220(+) B-cell infiltration and alloantibody deposition. Donor bone marrow obtained from mice incapable of secreting IgG alloantibody resulted in less BO and cGVHD. Robust germinal center reactions were present at the time of cGVHD disease initiation. Blockade of germinal center formation with a lymphotoxin-receptor-immunoglobulin fusion protein suppressed cGVHD and BO. We conclude that cGVHD is caused in part by alloantibody secretion, which is associated with fibrosis and cGVHD manifestations including BO, and that treatment with a lymphotoxin-beta receptorimmunoglobulin fusion protein could be beneficial for cGVHD prevention and therapy. (Blood. 2012; 119(6): 1570-1580)
C1 [Srinivasan, Mathangi; Flynn, Ryan; Price, Andrew; Taylor, Patricia A.; Panoskaltsis-Mortari, Angela; Blazar, Bruce R.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
[Srinivasan, Mathangi; Flynn, Ryan; Price, Andrew; Taylor, Patricia A.; Panoskaltsis-Mortari, Angela; Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA.
[Ranger, Ann; Browning, Jeffrey L.] Biogen Idec Inc, Dept Immunobiol, Cambridge, MA USA.
[Ritz, Jerome; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ritz, Jerome; Antin, Joseph H.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Murphy, William J.] Univ Calif Davis Canc Ctr & Sch Med, Dept Dermatol, Sacramento, CA USA.
[Luznik, Leo] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Luznik, Leo] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Shlomchik, Mark J.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA.
[Shlomchik, Mark J.] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA.
RP Blazar, BR (reprint author), Univ Minnesota, Masonic Canc Ctr, MMC 109,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM blaza001@umn.edu
OI Browning, Jeffrey/0000-0001-9168-5233; Ritz, Jerome/0000-0001-5526-4669
FU National Center for Research Resources Shared Instrumentation [1 S10
RR16851]; National Institutes of Health [P01 CA142106-06A1]
FX The authors thank Dr Qing Zhou and Dr Christine Goetz for their
technical assistance and discussions. They acknowledge the use of the
confocal microscope made available through a National Center for
Research Resources Shared Instrumentation Grant (#1 S10 RR16851).; This
work was supported in part by National Institutes of Health grant P01
CA142106-06A1.
NR 43
TC 73
Z9 76
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 9
PY 2012
VL 119
IS 6
BP 1570
EP 1580
DI 10.1182/blood-2011-07-364414
PG 11
WC Hematology
SC Hematology
GA 894IR
UT WOS:000300420900034
PM 22072556
ER
PT J
AU Kachadourian, R
Day, BJ
Pugazhenti, S
Franklin, CC
Genoux-Bastide, E
Mahaffey, G
Gauthier, C
Di Pietro, A
Boumendjel, A
AF Kachadourian, Remy
Day, Brian J.
Pugazhenti, Subbiah
Franklin, Christopher C.
Genoux-Bastide, Estelle
Mahaffey, Gregory
Gauthier, Charlotte
Di Pietro, Attilio
Boumendjel, Ahcene
TI A Synthetic Chalcone as a Potent Inducer of Glutathione Biosynthesis
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID GLUTAMATE-CYSTEINE LIGASE; CANCER RESISTANCE PROTEIN; HEME OXYGENASE-1;
IN-VITRO; CELLS; EXPRESSION; KINASE; INHIBITOR; NRF2; 2'-HYDROXYCHALCONE
AB Chalcones continue to attract considerable interest due to their anti-inflammatory and antiangiogenic properties. We recently reported the ability of 2',5'-dihydroxychalcone (2',5'-DHC) to induce both breast cancer resistance protein-mediated export of glutathione (GSH) and c-Jun N-terminal kinase-mediated increased intracellular GSH levels. Herein, we report a structure-activity relationship study of a series of 30 synthetic chalcone derivatives with hydroxyl, methoxyl, and halogen (F andCl) substituents and their ability to increase intracellular GSH levels. This effect was drastically improved with one or two electrowithdrawing groups on phenyl ring B and up to three methoxyl and/or hydroxyl groups on phenyl ring A. The optimal structure, 2-chloro-4',6'-dimethoxy-2'-hydroxychalcone, induced both a potent NF-E2-related factor 2-mediated transcriptional response and an increased formation of glutamate cysteine ligase holoenzyme, as shown using a human breast cancer cell line stably expressing a luciferase reporter gene driven by antioxidant response elements.
C1 [Kachadourian, Remy; Day, Brian J.; Pugazhenti, Subbiah] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA.
[Kachadourian, Remy; Day, Brian J.; Pugazhenti, Subbiah] Univ Colorado, Dept Med, Aurora, CO 80045 USA.
[Day, Brian J.; Franklin, Christopher C.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO 80045 USA.
[Pugazhenti, Subbiah; Mahaffey, Gregory] Denver VA Med Ctr, Denver, CO 80220 USA.
[Genoux-Bastide, Estelle; Boumendjel, Ahcene] UJF Grenoble 1, CNRS, Dept Pharmacochim Mol, UMR 5063, F-38041 Grenoble, France.
[Gauthier, Charlotte; Di Pietro, Attilio] Univ Lyon 1, Inst Biol & Chim Prot, Equipe Labellisee Ligue 2009, BMSSI,UMR5086, F-69367 Lyon 7, France.
RP Kachadourian, R (reprint author), Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA.
EM remyka@gmail.com
FU NIH [HL755223, HL84469, ES015678, ES017582]; VA Merit Review
[NEUD-004-07F]; Ligue Nationale Contre le Cancer (Equipe Labelisee
Ligue)
FX We are grateful to Madeleine Blanc and Chantal Beney for technical
assistance in the synthesis of the chalcones. We also thank Dr. Joe M.
McCord (University of Colorado, Aurora) for providing the MCF-7/AREc32
cell line generated by Dr. C. Roland Wolf (University of Dundee, United
Kingdom). This work was supported by NIH Grants HL755223, HL84469,
ES015678, and ES017582 to B.J.D. and VA Merit Review NEUD-004-07F to
S.P. C.G. is the recipient of a doctoral fellowship from the Ligue
Nationale Contre le Cancer (Equipe Labelisee Ligue 2009). B.J.D. is a
consultant for and holds equity in Aeolus Pharmaceuticals that is
commercially developing metalloporphyrins as human therapeutic agents.
NR 41
TC 20
Z9 20
U1 1
U2 17
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD FEB 9
PY 2012
VL 55
IS 3
BP 1382
EP 1388
DI 10.1021/jm2016073
PG 7
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 888DV
UT WOS:000299984900033
PM 22239485
ER
PT J
AU Hu, Y
Park, KK
Yang, L
Wei, X
Yang, Q
Cho, KS
Thielen, P
Lee, AH
Cartoni, R
Glimcher, LH
Chen, DF
He, ZG
AF Hu, Yang
Park, Kevin K.
Yang, Liu
Wei, Xin
Yang, Qiang
Cho, Kin-Sang
Thielen, Peter
Lee, Ann-Hwee
Cartoni, Romain
Glimcher, Laurie H.
Chen, Dong Feng
He, Zhigang
TI Differential Effects of Unfolded Protein Response Pathways on Axon
Injury-Induced Death of Retinal Ganglion Cells
SO NEURON
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; TRANSCRIPTION FACTOR XBP-1; ENDOPLASMIC-RETICULUM;
MESSENGER-RNA; ER STRESS; RETINITIS-PIGMENTOSA; OCULAR HYPERTENSION;
OXIDATIVE STRESS; MOUSE MODELS; OPTIC-NERVE
AB Loss of retinal ganglion cells (RGCs) accounts for visual function deficits after optic nerve injury, but how axonal insults lead to neuronal death remains elusive. By using an optic nerve crush model that results in the death of the majority of RGCs, we demonstrate that axotomy induces differential activation of distinct pathways of the unfolded protein response in axotomized RGCs. Optic nerve injury provokes a sustained CCAAT/enhancer binding homologous protein (CHOP) upregulation, and deletion of CHOP promotes RGC survival. In contrast, IRE/XBP-1 is only transiently activated, and forced XBP-1 activation dramatically protects RGCs from axon injury-induced death. Importantly, such differential activations of CHOP and XBP-1 and their distinct effects on neuronal cell death are also observed in RGCs with other types of axonal insults, such as vincristine treatment and intraocular pressure elevation, suggesting a new protective strategy for neurodegeneration associated with axonal damage.
C1 [Hu, Yang; Park, Kevin K.; Yang, Liu; Cartoni, Romain; He, Zhigang] Harvard Univ, Sch Med, FM Kirby Neurobiol Ctr, Childrens Hosp, Boston, MA 02115 USA.
[Hu, Yang; Park, Kevin K.; Yang, Liu; Cartoni, Romain; He, Zhigang] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Wei, Xin; Yang, Qiang; Cho, Kin-Sang; Chen, Dong Feng] Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA.
[Thielen, Peter; Lee, Ann-Hwee; Glimcher, Laurie H.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Thielen, Peter; Lee, Ann-Hwee; Glimcher, Laurie H.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Hu, Yang] Temple Univ, Sch Med, Shriners Hosp Pediat Res Ctr, Philadelphia, PA 19140 USA.
[Park, Kevin K.] Univ Miami, Sch Med, Miami Project Cure Paralysis, Miami, FL 33136 USA.
[Chen, Dong Feng] Boston Healthcare Syst, Ctr Innovat Visual Rehabil, Vet Affairs, Boston, MA 02130 USA.
RP Hu, Y (reprint author), Harvard Univ, Sch Med, FM Kirby Neurobiol Ctr, Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA.
EM yanghu@temple.edu; dongfeng.chen@schepens.harvard.edu;
zhigang.he@childrens.harvard.edu
FU National Eye Institute; Miami Project to Cure Paralysis; Department of
Veterans Affairs; National Institutes of Health (NIH) [AI32412]; NIH
National Research Service
FX We thank B. Xu and L. Connolly for technical support. Our work was
supported by grants from the National Eye Institute (Z.H.), Miami
Project to Cure Paralysis (K.K.P.), Department of Veterans Affairs
(D.F.C.), National Institutes of Health (NIH) grant AI32412, and a grant
from an anonymous foundation (L.H.G.). Y.H. was supported by an NIH
National Research Service Award Postdoctoral Fellowship. Y.H., K.K.P.,
L.Y., Q.Y., X.W., P.T., and A.H.L. performed the experiments and
analyzed the data. Y.H., L.H.G., D.F.C., and Z.H. designed experiments
and prepared the manuscript.
NR 47
TC 51
Z9 53
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD FEB 9
PY 2012
VL 73
IS 3
BP 445
EP 452
DI 10.1016/j.neuron.2011.11.026
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 890JJ
UT WOS:000300140600007
PM 22325198
ER
EF