FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Stuart, GL
Shorey, RC
Moore, TM
Ramsey, SE
Kahler, CW
O'Farrell, TJ
Strong, DR
Temple, JR
Monti, PM
AF Stuart, Gregory L.
Shorey, Ryan C.
Moore, Todd M.
Ramsey, Susan E.
Kahler, Christopher W.
O'Farrell, Timothy J.
Strong, David R.
Temple, Jeff R.
Monti, Peter M.
TI Randomized clinical trial examining the incremental efficacy of a
90-minute motivational alcohol intervention as an adjunct to standard
batterer intervention for men
SO ADDICTION
LA English
DT Article
DE Batterer intervention; brief alcohol intervention; intimate partner
violence; motivational interviewing; partner abuse; randomized clinical
trial; treatment outcome
ID INTIMATE PARTNER VIOLENCE; SUBSTANCE USE; METAANALYSIS; AGGRESSION;
CONSUMPTION
AB Aims The efficacy of batterer intervention programs to reduce intimate partner violence (IPV) is questionable, with individuals with alcohol problems particularly unlikely to benefit. We examined whether adding adjunctive alcohol intervention to batterer intervention reduced the likelihood of substance use and violence relative to batterer intervention alone.
Design Randomized clinical trial.
Setting Batterer intervention programs in Rhode Island, USA.
Participants A total of 252 hazardous drinking men in batterer intervention programs. Participants were randomized to receive 40 hours of standard batterer program (SBP) or the SBP plus a 90-minute alcohol intervention (SBP+BAI). None withdrew due to adverse effects. Data were collected at baseline, 3-, 6- and 12-month follow-up, with follow-up rates of 95, 89 and 82%, respectively.
Measurements Substance use was measured with a well-validated calendar-assisted interview. Violence was measured with a validated questionnaire. Arrest records were obtained for all participants. The primary substance use outcome was drinks per drinking day (DPDD) and the primary violence outcome was frequency of any physical IPV.
Findings Relative to SBP alone, men receiving SBP+BAI reported consuming fewer DPDD at 3-month follow-up [B=-1.36, 95% confidence interval (CI):-2.65, -0.04, P=0.04] but not 6- or 12-month follow-up. In secondary analyses, men receiving SBP+BAI reported significantly greater abstinence at 3- (B=0.09, 95% CI:0.03, 0.14, P=0.002) and 6-month (B=0.06, 95% CI:0.01, 0.11, P=0.01) follow-up but not 12-month follow-up. There were no significant differences in physical IPV between men receiving SBP and men receiving SBP+BAI. In secondary analyses, men receiving SBP+BAI reported less severe physical aggression at 3-month (IRR=0.18, 95% CI:0.05, 0.65, P=0.009) but not 6- or 12-month follow-up. Men receiving SBP+BAI reported less severe psychological aggression (B=-1.24, 95% CI:-2.47, -0.02, P=0.04) and fewer injuries to partners at 3- and 6-month follow-up (IRR=0.33, 95% CI:0.12, 0.92, P=0.03), with differences fading by 12 months.
Conclusions Men with a history of intimate partner violence and hazardous drinking who received a batterer intervention plus an alcohol intervention showed improved alcohol and violence outcomes initially, but improvements faded by 12 months.
C1 [Stuart, Gregory L.; Shorey, Ryan C.; Moore, Todd M.] Univ Tennessee, Knoxville, TN 37996 USA.
[Stuart, Gregory L.; Shorey, Ryan C.; Moore, Todd M.] Butler Hosp, Knoxville, TN USA.
[Ramsey, Susan E.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Ramsey, Susan E.] Rhode Isl Hosp, Providence, RI USA.
[Kahler, Christopher W.; Monti, Peter M.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
[O'Farrell, Timothy J.] VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA USA.
[O'Farrell, Timothy J.] Harvard Univ, Sch Med, Brockton, MA 02401 USA.
[Strong, David R.] Brown Univ, Warren Alpert Med Sch, San Diego, CA USA.
[Strong, David R.] Butler Hosp, San Diego, CA USA.
[Temple, Jeff R.] UTMB Hlth, Galveston, TX USA.
RP Stuart, GL (reprint author), Univ Tennessee, Dept Psychol, 310C Austin Peay Bldg, Knoxville, TN 37996 USA.
EM gstuart@utk.edu
RI Temple, Jeff/A-7666-2009
OI Temple, Jeff/0000-0003-3193-0510
FU National Institute on Alcohol Abuse and Alcoholism [R01AA014193,
K24AA019707, K05AA019681]
FX This work was supported by grants from the National Institute on Alcohol
Abuse and Alcoholism (R01AA014193 and K24AA019707, Stuart, Principal
Investigator; K05AA019681, Monti, Principal Investigator). There were no
contractual constraints on publishing. All authors report no competing
interests.
NR 41
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U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD AUG
PY 2013
VL 108
IS 8
BP 1376
EP 1384
DI 10.1111/add.12142
PG 9
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 180SN
UT WOS:000321616800005
PM 23414253
ER
PT J
AU Pine-Abata, H
McNeill, A
Raw, M
Bitton, A
Rigotti, N
Murray, R
AF Pine-Abata, Hembadoon
McNeill, Ann
Raw, Martin
Bitton, Asaf
Rigotti, Nancy
Murray, Rachael
TI A survey of tobacco dependence treatment guidelines in 121 countries
SO ADDICTION
LA English
DT Article
DE Article 14; Article 14 guidelines; FCTC; national treatment guidelines;
survey; tobacco dependence treatment
AB Aims To report progress among Parties to the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) in developing national tobacco treatment guidelines in accordance with FCTC Article 14 guideline recommendations.
Design Cross-sectional study.
Setting Electronic survey from December 2011 to August 2012; participants were asked to complete either an online or attached Microsoft Word questionnaire.
Participants One hundred and sixty-three of the 173 Parties to the FCTC at the time of our survey.
Measurements The 51-item questionnaire contained 30 items specifically on guidelines. Questions covered the areas of guidelines writing process, content, key recommendations and other characteristics.
Findings One hundred and twenty-one countries (73%) responded. Fifty-three countries (44%) had guidelines, ranging from 75% among high-income countries to 11% among low-income countries. Nearly all guidelines recommended brief advice (93%), intensive specialist support (93%) and medications (96%), while 66% recommended quitlines. Fifty-seven percent had a dissemination strategy, 76% stated funding source and 68% had professional endorsement.
Conclusion Fewer than half of the Parties to the WHO FCTC have developed national tobacco treatment guidelines, but, where guidelines exist, they broadly follow FCTC Article 14 guideline recommendations.
C1 [Pine-Abata, Hembadoon; Raw, Martin; Murray, Rachael] Univ Nottingham, UK Ctr Tobacco Control Studies, Div Epidemiol & Publ Hlth, Nottingham NG5 1PB, England.
[McNeill, Ann] Kings Coll London, UK Ctr Tobacco Control Studies, Inst Psychiat, Natl Addict Ctr, London, England.
[Bitton, Asaf] Harvard Univ, Brigham & Womens Hosp, Dept Hlth Care Policy, Div Gen Med,Med Sch, Boston, MA 02115 USA.
[Rigotti, Nancy] Harvard Univ, Sch Med, Boston, MA USA.
[Rigotti, Nancy] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, Boston, MA 02114 USA.
RP Pine-Abata, H (reprint author), Univ Nottingham, UK Ctr Tobacco Control Studies, Div Epidemiol & Publ Hlth, City Hosp, Clin Sci Bldg, Nottingham NG5 1PB, England.
EM mcxhp@nottingham.ac.uk
FU University of Nottingham; UK Centre for Tobacco Control Studies
(UKCTCS), a centre for public health research excellence; British Heart
Foundation; Cancer Research UK; Economic and Social Research Council;
Medical Research Council; National Institute of Health Research; Society
for the Study of Addiction; Framework Convention Alliance
FX This study was funded jointly by the University of Nottingham and the UK
Centre for Tobacco Control Studies (UKCTCS), a centre for public health
research excellence funded by the British Heart Foundation, Cancer
Research UK, the Economic and Social Research Council, the Medical
Research Council and the National Institute of Health Research. This
funding is gratefully acknowledged. MR's time on this project was funded
by the Society for the Study of Addiction and the Framework Convention
Alliance, to whom we are extremely grateful. We thank Jacques Le Houezec
and Vicky Baldi for translating the questionnaire into French and
Spanish respectively. Finally, we sincerely thank the country contacts
who completed the survey, and the many other organisations and people
who helped us identify them.
NR 9
TC 8
Z9 8
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD AUG
PY 2013
VL 108
IS 8
BP 1470
EP 1475
DI 10.1111/add.12158
PG 6
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 180SN
UT WOS:000321616800017
PM 23437892
ER
PT J
AU Pine-Abata, H
McNeill, A
Murray, R
Bitton, A
Rigotti, N
Raw, M
AF Pine-Abata, Hembadoon
McNeill, Ann
Murray, Rachael
Bitton, Asaf
Rigotti, Nancy
Raw, Martin
TI A survey of tobacco dependence treatment services in 121 countries
SO ADDICTION
LA English
DT Article
DE FCTC; Article 14; Article 14 guidelines; survey; tobacco dependence
treatment; treatment systems
ID SMOKING-CESSATION SUPPORT; TRIAL; GUIDELINES; CYTISINE; COST
AB Aims To report progress among Parties to the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) in developing tobacco dependence treatment systems in accordance with FCTC Article 14 and the Article 14 guidelines recommendations.
Design Cross-sectional study.
Setting Electronic survey from December 2011 to August 2012.
Participants One hundred and sixty-three of the 174 Parties to the FCTC at the time of our survey.
Measurements The 51-item questionnaire contained 21 items specifically on treatment systems. Questions covered the availability of basic treatment infrastructure and national cessation support systems.
Findings We received responses from 121 (73%) of the 166 countries surveyed. Fewer than half of the countries had national treatment guidelines (n=53, 44%), a government official responsible for tobacco dependence treatment (n=49, 41%), an official national treatment strategy (n=53, 44%) or provided tobacco cessation support for health workers (n=55, 46%). More than half encouraged brief advice in existing health care services (n=68, 56%), while only 44 (36%) had quitlines and only 20 (17%) had a network of treatment support covering the whole country. Low- and middle-income countries had less tobacco dependence treatment provision than high-income countries.
Conclusion Most countries, especially low- and middle-income countries, have not yet implemented the recommendations of FCTC Article 14 or the FCTC Article 14 guidelines.
C1 [Pine-Abata, Hembadoon; Murray, Rachael; Raw, Martin] Univ Nottingham, UK Ctr Tobacco Control Studies, Div Epidemiol & Publ Hlth, Nottingham NG5 1PB, England.
[McNeill, Ann] Kings Coll London, UK Ctr Tobacco Control Studies, Natl Addict Ctr, Inst Psychiat, London, England.
[Bitton, Asaf] Harvard Univ, Brigham & Womens Hosp, Div Gen Med, Dept Hlth Care Policy,Med Sch, Boston, MA 02115 USA.
[Rigotti, Nancy] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Rigotti, Nancy] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, Boston, MA 02114 USA.
RP Pine-Abata, H (reprint author), Univ Nottingham, UK Ctr Tobacco Control Studies, Div Epidemiol & Publ Hlth, City Hosp, Clin Sci Bldg, Nottingham NG5 1PB, England.
EM mcxhp@nottingham.ac.uk
FU University of Nottingham; UK Centre for Tobacco Control Studies
(UKCTCS), a centre for public health research excellence; British Heart
Foundation; Cancer Research UK; Economic and Social Research Council;
Medical Research Council; National Institute of Health Research; Society
for the Study of Addiction; Framework Convention Alliance
FX This study was funded jointly by the University of Nottingham and the UK
Centre for Tobacco Control Studies (UKCTCS), a centre for public health
research excellence which is funded by the British Heart Foundation,
Cancer Research UK, the Economic and Social Research Council, the
Medical Research Council and the National Institute of Health Research.
This funding is gratefully acknowledged. M.R.'s time on this project was
funded by the Society for the Study of Addiction and the Framework
Convention Alliance, to whom we are extremely grateful. We thank Jacques
Le Houezec and Vicky Baldi for translating the questionnaire into French
and Spanish, respectively. Finally, we sincerely thank the country
contacts who completed the survey, and the many other organizations and
people who helped us identify them.
NR 27
TC 37
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U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD AUG
PY 2013
VL 108
IS 8
BP 1476
EP 1484
DI 10.1111/add.12172
PG 9
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 180SN
UT WOS:000321616800018
PM 23451932
ER
PT J
AU Mimiaga, MJ
Reisner, SL
Closson, EF
Perry, N
Perkovich, B
Nguyen, T
Trang, NNN
Lan, HX
Thien, DD
Mayer, KH
Colby, D
AF Mimiaga, Matthew J.
Reisner, Sari L.
Closson, Elizabeth F.
Perry, Nicholas
Perkovich, Brandon
Thi Nguyen
Trang, Nguyen N. N.
Lan, Hang X.
Dinh Duc Thien
Mayer, Kenneth H.
Colby, Donn
TI Self-perceived HIV risk and the use of risk reduction strategies among
men who engage in transactional sex with other men in Ho Chi Minh City,
Vietnam
SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV
LA English
DT Article
DE HIV; Vietnam; prevention; male sex workers; transactional sex
ID PREVENTION; PREVALENCE
AB An emerging HIV epidemic can be seen among men who have sex with men (MSM) in Vietnam, with prevalence as high as 18%. Transactional sex represents a risk factor for HIV transmission/acquisition among MSM globally, particularly in urban contexts, but remains largely underinvestigated in Ho Chi Minh City (HCMC), Vietnam. In 2010, 23 MSM who reported exchanging sex for money in the last month completed a brief survey and semistructured qualitative interview at The Life Centre, a non-governmental organization in HCMC, to assess sociodemographics, individual- and structural-level HIV risk factors and explore acceptable future prevention interventions. Participants' mean age was 24 years. Equal proportions of respondents self-identified as heterosexual/straight, homosexual/gay, and bisexual. Participants had a mean of 158 male clients in the past year, with a median of 60 male clients in the past year (interquartile range [IQR]=70) and reported inconsistent condom use and inaccurate perceptions of HIV risk. Nearly half of the sample reported engaging in unprotected anal sex with a male partner in the past 12 months and one-third with a male client. Major themes that emerged for HIV prevention interventions with male sex workers were those that: (1) focused on individual factors (drug and alcohol use, barriers to condom use, knowledge of asymptomatic STIs, enhancement of behavioral risk-reduction skills, and addressing concomitant mental health issues); (2) incorporated interpersonal and relational contexts (led by peer educators, built interpersonal skills, attended to partner type and intimacy dynamics); and (3) considered the exogenous environments in which individual choices/relationships operate (stigma of being MSM in Vietnam, availability of alternative economic opportunities, and varied sexual venues). HIV prevention efforts are needed that address the specific needs of MSM who engage in transactional sex in HCMC. Universally, MSM endorsed HIV prevention interventions, suggesting a need and desire for efforts in this context.
C1 [Mimiaga, Matthew J.; Perry, Nicholas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
[Mimiaga, Matthew J.; Reisner, Sari L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Mimiaga, Matthew J.; Reisner, Sari L.; Closson, Elizabeth F.; Perkovich, Brandon; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Perkovich, Brandon] Harvard Univ, Cambridge, MA USA.
[Thi Nguyen; Colby, Donn] Harvard Med Sch AIDS Initiat Vietnam HAIVN, Ho Chi Minh City, Vietnam.
[Trang, Nguyen N. N.; Lan, Hang X.; Dinh Duc Thien] Ctr Promot Qual Life, Life Ctr, Ho Chi Minh City, Vietnam.
[Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
RP Mimiaga, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
EM mmimiaga@partners.org
OI colby, donn/0000-0003-3931-5926
FU NCATS NIH HHS [UL1 TR000170]; NCRR NIH HHS [1 UL1 RR 025758-02, UL1
RR025758]
NR 16
TC 10
Z9 10
U1 2
U2 10
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0954-0121
EI 1360-0451
J9 AIDS CARE
JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv
PD AUG 1
PY 2013
VL 25
IS 8
BP 1039
EP 1044
DI 10.1080/09540121.2012.748873
PG 6
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychology, Multidisciplinary; Respiratory System; Social Sciences,
Biomedical
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychology; Respiratory System; Biomedical Social Sciences
GA 184JU
UT WOS:000321886700015
PM 23252673
ER
PT J
AU Sonnenberg, A
AF Sonnenberg, A.
TI Review article: historic changes of Helicobacter pylori-associated
diseases
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
ID GASTROESOPHAGEAL-REFLUX DISEASE; PERFORATED PEPTIC-ULCER;
COLORECTAL-CANCER; DUODENAL-ULCER; UNITED-STATES; TIME TRENDS;
BIRTH-COHORT; HOSPITAL ADMISSIONS; GASTRIC-CANCER; ESOPHAGEAL
ADENOCARCINOMA
AB BackgroundThe long-term time trends of multiple gastrointestinal diseases are characterised by a striking rise and fall. These temporal changes provide important clues about disease aetiology.
AimTo highlight the importance of Helicobacter pylori infection in shaping the temporal trends of many common gastrointestinal diseases.
MethodsLiterature review of the time trends associated with common digestive diseases.
ResultsThe general trends of gastric ulcer, duodenal ulcer, gastric cancer, colon cancer, rectum cancer have all been shaped by a similar underlying birth-cohort phenomenon. Mortality associated with these diagnoses increased in all generations born during the nineteenth century. It peaked among generations born shortly before the turn of the century and then decreased in all subsequent generations born throughout the twentieth century. These patterns can be observed in the incidence, hospitalisation and mortality data from many different countries. They reflect similar rising and falling trends of H. pylori infection in the general population. Diseases that are inversely associated with H. pylori, such as reflux disease, erosive oesophagitis, Barrett's oesophagus, and oesophageal adenocarcinoma, have seen a striking rise during the recent decline of H. pylori infection.
ConclusionThe temporal variations of H. pylori infection have affected the occurrence of gastroenterology's most common disorders.
C1 [Sonnenberg, A.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA.
RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3 GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM sonnenbe@ohsu.edu
NR 105
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U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD AUG
PY 2013
VL 38
IS 4
BP 329
EP 342
DI 10.1111/apt.12380
PG 14
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 182VU
UT WOS:000321773700001
PM 23786250
ER
PT J
AU Monach, PA
Warner, RL
Tomasson, G
Specks, U
Stone, JH
Ding, L
Fervenza, FC
Fessler, BJ
Hoffman, GS
Ikle, D
Kallenberg, CGM
Krischer, J
Langford, CA
Mueller, M
Seo, P
St Clair, EW
Spiera, R
Tchao, N
Ytterberg, SR
Johnson, KJ
Merkel, PA
AF Monach, Paul A.
Warner, Roscoe L.
Tomasson, Gunnar
Specks, Ulrich
Stone, John H.
Ding, Linna
Fervenza, Fernando C.
Fessler, Barri J.
Hoffman, Gary S.
Ikle, David
Kallenberg, Cees G. M.
Krischer, Jeffrey
Langford, Carol A.
Mueller, Mark
Seo, Philip
St Clair, E. William
Spiera, Robert
Tchao, Nadia
Ytterberg, Steven R.
Johnson, Kent J.
Merkel, Peter A.
TI Serum proteins reflecting inflammation, injury and repair as biomarkers
of disease activity in ANCA-associated vasculitis
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
DE Autoimmune Diseases; Chemokines; Cytokines
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SOLUBLE ADHESION MOLECULES; ANTINEUTROPHIL
CYTOPLASMIC ANTIBODIES; C-REACTIVE PROTEIN; B-CELL CHEMOKINE;
WEGENERS-GRANULOMATOSIS; FOLLOW-UP; E-SELECTIN; MATRIX
METALLOPROTEINASES; ELEVATED PRODUCTION
AB Objective To identify circulating proteins that distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner complementary to markers of systemic inflammation.
Methods Twenty-eight serum proteins representing diverse aspects of the biology of AAV were measured before and 6months after treatment in a large clinical trial of AAV. Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were available for comparison. The primary outcome was the ability of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for Wegener's granulomatosis (BVAS/WG)3 at screening) from remission (BVAS/WG=0 at month 6), using areas under receiver operating characteristic (ROC) curve (AUC).
Results All subjects had severe active vasculitis (median BVAS/WG=8) at screening. In the 137 subjects in remission at month 6, 24 of the 28 markers showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) best discriminated active AAV from remission (AUC>0.8) and from healthy controls (AUC>0.9). Correlations among these markers and with ESR or CRP were low.
Conclusions Many markers are elevated in severe active AAV and decline with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from remission better than the other markers studied, including ESR and CRP. These proteins are particularly promising candidates for future studies to address unmet needs in the assessment of patients with AAV.
C1 [Monach, Paul A.; Tomasson, Gunnar; Merkel, Peter A.] Boston Univ, Sch Med, Vasculitis Ctr, Rheumatol Sect, Boston, MA USA.
[Monach, Paul A.; Tomasson, Gunnar; Merkel, Peter A.] Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA USA.
[Warner, Roscoe L.; Johnson, Kent J.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Specks, Ulrich] Mayo Clin, Coll Med, Div Pulm & Crit Care Med, Rochester, MN USA.
[Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA.
[Ding, Linna] Natl Inst Allergy & Infect Dis, Bethesda, MD USA.
[Fervenza, Fernando C.] Mayo Clin, Coll Med, Div Nephrol & Hypertens, Rochester, MN USA.
[Fessler, Barri J.] Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, MN USA.
[Hoffman, Gary S.] Cleveland Clin, Ctr Vasculitis Care & Res, Cleveland, OH 44106 USA.
[Ikle, David] Rho, Chapel Hill, NC USA.
[Kallenberg, Cees G. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Rheumatol & Clin Immunol, Groningen, Netherlands.
[Krischer, Jeffrey] Univ S Florida, Coll Med, Dept Pediat, Tampa, FL 33612 USA.
[Mueller, Mark] Immune Tolerance Network, Bethesda, MD USA.
[Seo, Philip] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA.
[St Clair, E. William] Duke Univ, Div Rheumatol & Immunol, Durham, NC USA.
[Spiera, Robert] Hosp Special Surg, Div Rheumatol, New York, NY 10021 USA.
[Tchao, Nadia] Immune Tolerance Network, San Francisco, CA USA.
[Ytterberg, Steven R.] Mayo Clin, Coll Med, Div Rheumatol, Rochester, MN USA.
[Merkel, Peter A.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA.
RP Merkel, PA (reprint author), Univ Penn, Div Rheumatol, 8th Floor Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA.
EM pmerkel@upenn.edu
FU Vasculitis Clinical Research Consortium; National Institute of Arthritis
and Musculoskeletal and Skin Diseases [U54AR057319, RC1 AR058303, P60
AR047785]; National Center for Research Resources [U54 RR019497];
National Institute of Neurological Disorders and Stroke [NS064808];
Office of Rare Diseases Research; Immune Tolerance Network (NIH) [N01
AI15416]; National Institute of Allergy and Infectious Diseases;
Juvenile Diabetes Research Foundation; Genentech; Biogen Idec; National
Center for Research Resources (NCRR), at Johns Hopkins University
[RR024150-01]; NCRR [RR025005]; Boston University; National Institutes
of Health [M01 RR00533]; Arthritis Foundation; [K24 AR049185]; [K23
AR052820]; [K24 AR02224]
FX This work was sponsored by the Vasculitis Clinical Research Consortium
which has received support from the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (U54AR057319, RC1 AR058303 and P60
AR047785), the National Center for Research Resources (U54 RR019497),
the National Institute of Neurological Disorders and Stroke (NS064808),
and the Office of Rare Diseases Research. The RAVE Trial was performed
with the support of the Immune Tolerance Network (NIH Contract N01
AI15416), an international clinical research consortium supported by the
National Institute of Allergy and Infectious Diseases and the Juvenile
Diabetes Research Foundation (see online appendix for the list of all
members of the RAVE-ITN Research Group). Genentech and Biogen Idec
provided the study medications and partial funding. At the Mayo Clinic
and Foundation, the trial was supported by a Clinical and Translational
Science Award from the National Center for Research Resources (NCRR)
(RR024150-01), at Johns Hopkins University, by grants from the NCRR
(RR025005) and career development awards (K24 AR049185 to JHS, and K23
AR052820 to PS), and at Boston University, by a Clinical and
Translational Science Award (RR 025771), grants from the National
Institutes of Health (M01 RR00533) and a career development award (K24
AR02224 to Dr Peter A Merkel). Dr Paul A Monach was supported by an
Arthritis Investigator Award from the Arthritis Foundation.
NR 54
TC 22
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U1 0
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD AUG
PY 2013
VL 72
IS 8
BP 1342
EP 1350
DI 10.1136/annrheumdis-2012-201981
PG 9
WC Rheumatology
SC Rheumatology
GA 176WW
UT WOS:000321338400015
PM 22975753
ER
PT J
AU Kwak, YG
Jacoby, GA
Hooper, DC
AF Kwak, Yee Gyung
Jacoby, George A.
Hooper, David C.
TI Induction of Plasmid-Carried qnrS1 in Escherichia coli by Naturally
Occurring Quinolones and Quorum-Sensing Signal Molecules
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID PSEUDOMONAS-AERUGINOSA; SALMONELLA-ENTERICA; VIBRIO-SPLENDIDUS;
RESISTANCE; SYSTEM; COMMUNICATION; DETERMINANTS; AUTOINDUCER;
EXPRESSION; MECHANISM
AB Naturally occurring quinolone and quinolone-like compounds, such as quinine, 2-hydroxyquinoline, 4-hydroxyquinoline, and 2-heptyl-3-hydroxy-4(1H)-quinolone, increased expression of qnrS1 in Escherichia coli 2.3- to 11.2-fold, similar to the synthetic quinolone ciprofloxacin. In contrast, chromosomal qnrVS1 of Vibrio splendidus was not induced by these compounds. Molecules associated with quorum sensing, such as N-3-hydroxybutyryl-homoserine lactone (HSL), N-hexanoyl-HSL, and N-3-(oxododecanoyl)-HSL, did not show an induction effect on either qnrS1 or qnrVS1 at the tested concentrations.
C1 [Kwak, Yee Gyung; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Kwak, Yee Gyung; Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA.
[Kwak, Yee Gyung] Inje Univ, Coll Med, Pusan, South Korea.
[Jacoby, George A.] Lahey Hosp & Med Ctr, Burlington, MA USA.
RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
EM dhooper@partners.org
OI Kwak, Yee Gyung/0000-0002-4713-8045
FU Inje Research and Scholarship Foundation of the Inje University College
of Medicine; National Institutes of Health, U.S. Public Health Service
[R01 AI057576]
FX This work was supported by the Inje Research and Scholarship Foundation
(to Y.G.K. in 2011) of the Inje University College of Medicine and by
grant R01 AI057576 (to D.C.H. and G.A.J.) from the National Institutes
of Health, U.S. Public Health Service.
NR 23
TC 5
Z9 5
U1 0
U2 12
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 AUG
PY 2013
VL 57
IS 8
BP 4031
EP 4034
DI 10.1128/AAC.00337-13
PG 4
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 182RO
UT WOS:000321761800074
PM 23689721
ER
PT J
AU Beard, CJ
Travis, LB
Chen, MH
Arvold, ND
Nguyen, PL
Martin, NE
Kuban, DA
Ng, AK
Hoffman, KE
AF Beard, Clair J.
Travis, Lois B.
Chen, Ming-Hui
Arvold, Nils D.
Nguyen, Paul L.
Martin, Neil E.
Kuban, Deborah A.
Ng, Andrea K.
Hoffman, Karen E.
TI Outcomes in stage I testicular seminoma: A population-based study of
9193 patients
SO CANCER
LA English
DT Article
DE testicular cancer; seminoma; radiotherapy; survivor; second malignant
neoplasm; cardiovascular disease; suicide; all-cause mortality
ID LONG-TERM SURVIVORS; GERM-CELL TUMORS; CARDIOVASCULAR-DISEASE;
CANCER-PATIENTS; 2ND CANCERS; MORTALITY; RADIOTHERAPY; LIFE;
SURVEILLANCE; CHEMOTHERAPY
AB BACKGROUND Few studies have quantified temporal patterns of cause-specific mortality in contemporary cohorts of men with early-stage seminoma. Given that several management strategies can be applied in these patients, each resulting in excellent long-term survival, it is important to evaluate associated long-term sequelae. In particular, data describing long-term risks of cardiovascular disease (CVD) are conflicting.
METHODS We identified 9193 men diagnosed with stage I seminoma (ages 15-70 years) in the population-based SEER registries (1973-2001). We calculated survival estimates, standardized mortality ratios (SMRs), and adjusted hazard rates (AHRs).
RESULTS During 121,037 person-years of follow-up (median, 12.3 years), 915 deaths (SMR, 1.23; 95% CI, 1.16-1.32) were reported, with significant excesses for suicide (n=39; SMR, 1.45; 95% CI, 1.06-1.98), infection (n=58; SMR, 2.32; 95% CI, 1.80-3.00), and second malignant neoplasms (SMNs; n=291; SMR, 1.81; 95% CI, 1.61-2.03), but not CVD (n=201; SMR, 0.91; 95% CI, 0.80-1.05). After radiotherapy (78% patients), CVD deaths were not increased (n=158; SMR, 0.89; 95% CI, 0.76-1.04), in contrast to SMN deaths (n=246; SMR, 1.89; 95% CI, 1.67-2.14). SMN mortality was higher among patients administered radiotherapy than among those not given radiotherapy (AHR, 1.36; 95% CI, 0.99-1.88; P=.059), with a cumulative 15-year risk of 2.64% (95% CI, 2.19-3.16). Suicide, although rare, accounted for 1 in 230 deaths.
CONCLUSIONS Modern radiotherapy as applied in this large population-based study is not associated with excess CVD mortality. Although increased all-cause mortality exists, cumulative SMN risk is considerably smaller than reported in historical series, but additional follow-up will be required to characterize long-term trends. The increased risk of suicide, previously unreported in men with stage I seminoma, requires confirmation. Cancer 2013;119:2771-2777. (c) 2013 American Cancer Society.
C1 [Beard, Clair J.; Arvold, Nils D.; Nguyen, Paul L.; Martin, Neil E.; Ng, Andrea K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Travis, Lois B.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rubin Ctr Canc Survivorship, Rochester, NY 14642 USA.
[Travis, Lois B.] Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Rochester, NY 14642 USA.
[Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA.
[Kuban, Deborah A.; Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
RP Beard, CJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.
EM cbeard@lroc.harvard.edu
RI Martin, Neil/E-2193-2014
OI Martin, Neil/0000-0002-8164-8516
FU National Cancer Institute [R01-CA157823-01A1-NCI]
FX Dr. Travis was supported by National Cancer Institute
R01-CA157823-01A1-NCI.
NR 38
TC 22
Z9 22
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD AUG 1
PY 2013
VL 119
IS 15
BP 2771
EP 2777
DI 10.1002/cncr.28086
PG 7
WC Oncology
SC Oncology
GA 185OB
UT WOS:000321977500017
PM 23633409
ER
PT J
AU de Groot, NL
van Haalen, HGM
Spiegel, BMR
Laine, L
Lanas, A
Focks, JJ
Siersema, PD
van Oijen, MGH
AF de Groot, N. L.
van Haalen, H. G. M.
Spiegel, B. M. R.
Laine, L.
Lanas, A.
Focks, J. Jaspers
Siersema, P. D.
van Oijen, M. G. H.
TI Gastroprotection in Low-Dose Aspirin Users for Primary and Secondary
Prevention of ACS: Results of a Cost-Effectiveness Analysis Including
Compliance
SO CARDIOVASCULAR DRUGS AND THERAPY
LA English
DT Article
DE Cost-effectiveness; QALY; Aspirin; Proton pump inhibitor; Dyspepsia;
Gastrointestinal bleeding; Compliance
ID PROTON PUMP INHIBITORS; CORONARY-ARTERY-DISEASE; NONSTEROIDAL
ANTIINFLAMMATORY DRUGS; ST-SEGMENT ELEVATION; QUALITY-OF-LIFE;
RANDOMIZED CONTROLLED-TRIALS; ISCHEMIC-HEART-DISEASE; LONG-TERM
ADHERENCE; ESOMEPRAZOLE 20 MG; ACETYLSALICYLIC-ACID
AB Low-dose aspirin (ASA) increases the risk of upper gastrointestinal (GI) complications. Proton pump inhibitors (PPIs) reduce these upper GI side effects, yet patient compliance to PPIs is low. We determined the cost-effectiveness of gastroprotective strategies in low-dose ASA users considering ASA and PPI compliance.
Using a Markov model we compared four strategies: no medication, ASA monotherapy, ASA+PPI co-therapy and a fixed combination of ASA and PPI for primary and secondary prevention of ACS. The risk of acute coronary syndrome (ACS), upper GI bleeding and dyspepsia was modeled as a function of compliance and the relative risk of developing these events while using medication. Costs, quality adjusted life years and number of ACS events were evaluated, applying a variable risk of upper GI bleeding. Probabilistic sensitivity analyses were performed.
For our base case patients using ASA for primary prevention of ACS no medication was superior to ASA monotherapy. PPI co-therapy was cost-effective (incremental cost-effectiveness ratio [ICER] a,not sign10,314) compared to no medication. In secondary prevention, PPI co-therapy was cost-effective (ICER a,not sign563) while the fixed combination yielded an ICER < a,not sign20,000 only in a population with elevated risk for upper GI bleeding or moderate PPI compliance. PPI co-therapy had the highest probability to be cost-effective in all scenarios. PPI use lowered the overall number of ACS.
Considering compliance, PPI co-therapy is likely to be cost-effective in patients taking low dose ASA for primary and secondary prevention of ACS, given low PPI prices. In secondary prevention, a fixed combination seems cost-effective in patients with elevated risk for upper GI bleeding or in those with moderate PPI compliance. Both strategies reduced the number of ACS compared to ASA monotherapy.
C1 [de Groot, N. L.; van Haalen, H. G. M.; Siersema, P. D.; van Oijen, M. G. H.] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, NL-3508 GA Utrecht, Netherlands.
[Spiegel, B. M. R.] Vet Affairs Greater Los Angeles Hlth Care Syst, Div Gastroenterol & Hepatol, Los Angeles, CA USA.
[Spiegel, B. M. R.; van Oijen, M. G. H.] Univ Calif Los Angeles, Vet Affairs Ctr Outcomes Res & Educ CORE, Los Angeles, CA USA.
[Laine, L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA.
[Lanas, A.] Univ Zaragoza, Sch Med, Aragon Hlth Res Inst IIS Aragon, CIBERehd, Zaragoza, Spain.
[Focks, J. Jaspers] Radboud Univ Nijmegen, Med Ctr, Dept Cardiol, NL-6525 ED Nijmegen, Netherlands.
RP de Groot, NL (reprint author), Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, POB 85500 Internal Code F02-618, NL-3508 GA Utrecht, Netherlands.
EM n.l.degroot-3@umcutrecht.nl
FU AstraZeneca
FX This study was sponsored by an unrestricted educational grant from
AstraZeneca.
NR 68
TC 6
Z9 6
U1 1
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0920-3206
J9 CARDIOVASC DRUG THER
JI Cardiovasc. Drugs Ther.
PD AUG
PY 2013
VL 27
IS 4
BP 341
EP 357
DI 10.1007/s10557-013-6448-y
PG 17
WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy
SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy
GA 183AS
UT WOS:000321786600010
PM 23417566
ER
PT J
AU Calderone, DJ
Hoptman, MJ
Martinez, A
Nair-Collins, S
Mauro, CJ
Bar, M
Javitt, DC
Butler, PD
AF Calderone, Daniel J.
Hoptman, Matthew J.
Martinez, Antgona
Nair-Collins, Sangeeta
Mauro, Cristina J.
Bar, Moshe
Javitt, Daniel C.
Butler, Pamela D.
TI Contributions of Low and High Spatial Frequency Processing to Impaired
Object Recognition Circuitry in Schizophrenia
SO CEREBRAL CORTEX
LA English
DT Article
DE cortical circuitry; magnocellular; object recognition; schizophrenia;
visual
ID LATERAL OCCIPITAL COMPLEX; TOP-DOWN FACILITATION; HUMAN VISUAL-CORTEX;
NMDA-RECEPTOR ACTIVITY; PERCEPTUAL ORGANIZATION; HUMAN BRAIN; SENSORY
CONTRIBUTIONS; CONTRAST SENSITIVITY; PARVOCELLULAR CONTRIBUTIONS;
INFEROTEMPORAL CORTEX
AB Patients with schizophrenia exhibit cognitive and sensory impairment, and object recognition deficits have been linked to sensory deficits. The frame and fill model of object recognition posits that low spatial frequency (LSF) information rapidly reaches the prefrontal cortex (PFC) and creates a general shape of an object that feeds back to the ventral temporal cortex to assist object recognition. Visual dysfunction findings in schizophrenia suggest a preferential loss of LSF information. This study used functional magnetic resonance imaging (fMRI) and resting state functional connectivity (RSFC) to investigate the contribution of visual deficits to impaired object framing circuitry in schizophrenia. Participants were shown object stimuli that were intact or contained only LSF or high spatial frequency (HSF) information. For controls, fMRI revealed preferential activation to LSF information in precuneus, superior temporal, and medial and dorsolateral PFC areas, whereas patients showed a preference for HSF information or no preference. RSFC revealed a lack of connectivity between early visual areas and PFC for patients. These results demonstrate impaired processing of LSF information during object recognition in schizophrenia, with patients instead displaying increased processing of HSF information. This is consistent with findings of a preference for local over global visual information in schizophrenia.
C1 [Calderone, Daniel J.; Hoptman, Matthew J.; Martinez, Antgona; Nair-Collins, Sangeeta; Mauro, Cristina J.; Javitt, Daniel C.; Butler, Pamela D.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA.
[Calderone, Daniel J.; Hoptman, Matthew J.; Butler, Pamela D.] NYU, Sch Med, Dept Psychiat, New York, NY USA.
[Calderone, Daniel J.; Hoptman, Matthew J.; Nair-Collins, Sangeeta; Javitt, Daniel C.; Butler, Pamela D.] CUNY, Dept Psychol, New York, NY 10021 USA.
[Martinez, Antgona] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Mauro, Cristina J.] Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY USA.
[Bar, Moshe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA USA.
[Bar, Moshe] Bar Ilan Univ, Gonda Ctr Brain Res, IL-52100 Ramat Gan, Israel.
[Javitt, Daniel C.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
RP Calderone, DJ (reprint author), 140 Old Orangeburg Rd, Orangeburg, NY 10962 USA.
EM dcalderone@nki.rfmh.org
RI Hoptman, Matthew/N-1035-2014
OI Hoptman, Matthew/0000-0003-4485-6102
FU National Institutes of Health [RO1 MH084848, R21 MH084031, R37 MH049334,
P50 MH086385]; NCRR High End Instrumentation grant [S10 RR022972];
Graduate Center of the City University of New York
FX This work was supported by the National Institutes of Health (RO1
MH084848 to P. D. B. and M.J.H., R21 MH084031 to M.J. H., and R37
MH049334 and P50 MH086385 to D.C.J.), and the scanner used in this study
was funded in part by S10 RR022972 NCRR High End Instrumentation grant
to Craig A. Branch, PhD) and the Graduate Center of the City University
of New York (Doctoral Student Research Grant to D.J.C.
NR 118
TC 19
Z9 20
U1 0
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD AUG
PY 2013
VL 23
IS 8
BP 1849
EP 1858
DI 10.1093/cercor/bhs169
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 182OS
UT WOS:000321754200008
PM 22735157
ER
PT J
AU Kamba, A
Lee, IA
Mizoguchi, E
AF Kamba, A.
Lee, I. -A.
Mizoguchi, E.
TI Potential Association Between TLR4 and Chitinase 3-Like 1
(CHI3L1/YKL-40) Signaling on Colonic Epithelial Cells in Inflammatory
Bowel Disease and Colitis-Associated Cancer
SO CURRENT MOLECULAR MEDICINE
LA English
DT Article
DE Autoimmunity; chitinase; colitis-associated cancer; mammalian
inflammation; microbiota
ID TOLL-LIKE RECEPTOR-4; NECROSIS-FACTOR-ALPHA; COLORECTAL-CANCER; NEGATIVE
REGULATOR; DROSOPHILA TOLL; GENE-EXPRESSION; INTESTINAL INFLAMMATION;
ARTICULAR CHONDROCYTES; ULCERATIVE-COLITIS; HUMAN MACROPHAGES
AB Inflammatory bowel disease (IBD) is a group of inflammatory disorders in the small and large intestines. Several studies have proved that persistent and disregulated host/microbial interactions are required for the development of IBD. It is well known that chronic IBD is strongly associated with an increased risk of developing colorectal cancer by 0.5-1% annually, 8-10 years after the initial diagnosis. To detect the tiny dysplasia or early stage of cancer in chronic IBD patients, a tremendous amount of effort is currently directed for improving colonoscopic technology and noninvasive serological marker development. However, there is only a limited amount of data available to understand the exact mechanism of how long term chronic colitis is connected to the development of colorectal tumors. Recently, our group has identified significantly increased expression of chitinase 3-like 1 (CHI3L1) molecule in non-dysplastic mucosa from patients with IBD and remote dysplasia/cancer, compared to patients with IBD without dysplasia or healthy controls. CHI3L1 seems to contribute to the proliferation, migration, and neoplastic progression of colonic epithelial cells (CECs) under inflammatory conditions. Furthermore, the TLR4-mediated intracellular signaling cascade is likely to interact with CHI3L1 signaling in CECs. In this review article, we have concisely summarized the cellular and molecular mechanisms underlining the development of IBD and colitis-associated cancer, with particular focus on the TLR4- and CHI3L1-signaling pathways in CECs.
C1 [Kamba, A.; Lee, I. -A.; Mizoguchi, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA.
[Mizoguchi, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
RP Mizoguchi, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, GRJ 825D,55 Fruit St, Boston, MA 02114 USA.
EM emizoguchi@partners.org
FU National Institute of Health [DK 80070, DK74454, DK64289, DK43351]; Eli
and Edythe L. Broad Medical Foundation; American Gastroenterological
Association Foundation; National Research Foundation of Korea Fellowship
Award
FX We would like to thank Mr. Terry Danford Lott for his excellent
assistance in preparing this manuscript. This work has been supported by
National Institute of Health (DK 80070, DK74454, DK64289 and DK43351),
and grants from the Eli and Edythe L. Broad Medical Foundation and
American Gastroenterological Association Foundation to E. Mizoguchi.
I.A. Lee has been supported by the National Research Foundation of Korea
Fellowship Award.
NR 112
TC 8
Z9 11
U1 1
U2 7
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1566-5240
J9 CURR MOL MED
JI Curr. Mol. Med.
PD AUG
PY 2013
VL 13
IS 7
BP 1110
EP 1121
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 180UJ
UT WOS:000321623900006
PM 23170831
ER
PT J
AU Cotman, SL
Karaa, A
Staropoli, JF
Sims, KB
AF Cotman, Susan L.
Karaa, Amel
Staropoli, John F.
Sims, Katherine B.
TI Neuronal Ceroid Lipofuscinosis: Impact of Recent Genetic Advances and
Expansion of the Clinicopathologic Spectrum
SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
LA English
DT Review
DE Neuronal ceroid lipofuscinosis; NCL; Batten disease; Kufs disease;
Parkinson's disease; Parkinsonism; Frontotemporal lobar degeneration;
FTLD; Endosome; Lysosome; Lysosomal disease; Subunit c; Saposin;
Progranulin; DNAJC5; CSP alpha; CLN6; Cathepsin F; KCTD7; ATP13A2
ID PALMITOYL-PROTEIN THIOESTERASE; PROGRESSIVE MYOCLONIC EPILEPSY;
CATHEPSIN-D DEFICIENCY; P-TYPE ATPASE; BATTEN-DISEASE; TRANSMEMBRANE
PROTEIN; KUFS-DISEASE; CSP-ALPHA; NEURODEGENERATIVE DISORDER;
FRONTOTEMPORAL DEMENTIA
AB Neuronal ceroid lipofuscinosis (NCL), first clinically described in 1826 and pathologically defined in the 1960s, refers to a group of disorders mostly diagnosed in the childhood years that involve the accumulation of lysosomal storage material with characteristic ultrastructure and prominent neurodegenerative features including vision loss, seizures, motor and cognitive function deterioration, and often times, psychiatric disturbances. All NCL disorders evidence early morbidity and treatment options are limited to symptomatic and palliative care. While distinct genetic forms of NCL have long been recognized, recent genetic advances are considerably widening the NCL genotypic and phenotypic spectrum, highlighting significant overlap with other neurodegenerative diseases. This review will discuss these recent advances and the expanded potential for increased awareness and new research that will ultimately lead to effective treatments for NCL and related disorders.
C1 [Cotman, Susan L.; Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA.
[Karaa, Amel] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Staropoli, John F.] Massachusetts Gen Hosp, Dept Pathol, Ctr Human Genet Res, Boston, MA 02114 USA.
[Karaa, Amel] Harvard Univ, Sch Med, Clin Genet Program, Boston, MA 02115 USA.
RP Cotman, SL (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA.
EM cotman@helix.mgh.harvard.edu
FU NINDS NIH HHS [K08 NS079359, R01 NS073813]
NR 93
TC 21
Z9 22
U1 0
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1528-4042
J9 CURR NEUROL NEUROSCI
JI Curr. Neurol. Neurosci. Rep.
PD AUG
PY 2013
VL 13
IS 8
AR 366
DI 10.1007/s11910-013-0366-z
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 188DA
UT WOS:000322171000003
PM 23775425
ER
PT J
AU Mathisen, DJ
AF Mathisen, Douglas J.
TI Challenging conventional wisdom
SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
LA English
DT Editorial Material
DE 'Routine' chest tube; Thoracoscopic; Pulmonary resection
C1 Massachusetts Gen Hosp, Dept Gen Thorac Surg, Boston, MA 02114 USA.
RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Dept Gen Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA.
EM dmathisen@partners.org
NR 1
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1010-7940
EI 1873-734X
J9 EUR J CARDIO-THORAC
JI Eur. J. Cardio-Thorac. Surg.
PD AUG
PY 2013
VL 44
IS 2
BP 230
EP 230
DI 10.1093/ejcts/ezs706
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 183PD
UT WOS:000321828300020
PM 23324795
ER
PT J
AU Faje, A
Nachtigall, L
AF Faje, Alexander
Nachtigall, Lisa
TI Current treatment options for hyperprolactinemia
SO EXPERT OPINION ON PHARMACOTHERAPY
LA English
DT Review
DE dopamine agonist; hyperprolactinemia; prolactinoma
ID SECRETING PITUITARY-ADENOMAS; ENDOTHELIAL GROWTH-FACTOR; PLASMA
PROLACTIN CONCENTRATIONS; METASTATIC BREAST-CANCER;
BROMOCRIPTINE-RESISTANT PROLACTINOMAS; SOMATOSTATIN RECEPTOR SUBTYPES;
GLYCOSYLATED HUMAN-PROLACTIN; CARDIAC-VALVE REGURGITATION; DOPAMINE
AGONIST THERAPY; VALVULAR HEART-DISEASE
AB Introduction: Hyperprolactinemia is a prevalent cause of oligo-amenorrhea, and prolactinomas are the most common type of functional pituitary tumor. Untreated hyperprolactinemia can lead to bone loss and impair gonadal function and fertility. Normalization of prolactin improves bone mass and restores gonadal function in a majority of patients.
Areas covered: This article contains an overview of hyperprolactinemia with an emphasis on pharmacologic, surgical and radiation treatment options. Discussion focuses on the efficacy and safety of available treatments and comments on new and emerging therapies.
Expert opinion: Dopamine agonists, usually cabergoline, remain the primary choice for initial treatment of hyperprolactinemia. Surgery may also be an appropriate alternative in certain circumstances. Monotherapy with dopamine agonists is often successful at controlling prolactin levels and tumor size, but adjunctive treatments may be necessary for resistant or aggressive prolactinomas.
C1 [Faje, Alexander] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Nachtigall, Lisa] Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA.
RP Nachtigall, L (reprint author), Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, 0 Emerson Pl, Boston, MA 02114 USA.
EM lnachtigall@partners.org
NR 191
TC 1
Z9 2
U1 3
U2 23
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-6566
EI 1744-7666
J9 EXPERT OPIN PHARMACO
JI Expert Opin. Pharmacother.
PD AUG
PY 2013
VL 14
IS 12
BP 1611
EP 1625
DI 10.1517/14656566.2013.806488
PG 15
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 183OE
UT WOS:000321825400005
PM 23738973
ER
PT J
AU Sullivan, JL
Meterko, M
Baker, E
Stolzmann, K
Adjognon, O
Ballah, K
Parker, VA
AF Sullivan, Jennifer L.
Meterko, Mark
Baker, Errol
Stolzmann, Kelly
Adjognon, Omonyele
Ballah, Konique
Parker, Victoria A.
TI Reliability and Validity of a Person-Centered Care Staff Survey in
Veterans Health Administration Community Living Centers
SO GERONTOLOGIST
LA English
DT Article
DE Person-centered care; Long-term care; Measurement
ID QUALITY-OF-LIFE; NURSING-HOME; VALIDATION; OUTCOMES; PROGRAM
AB Purpose: The objective of this study was to test and revise a staff assessment of person-centered care (PCC) within the Veterans Health Administration (VA) Community Living Center (CLC) setting. Design and Methods: Starting with measures of PCC initially developed through the Better Jobs Better Care (BJBC) study, we conducted cognitive interviews with CLC staff to assess applicability to the VA setting. We then (a) modified the questionnaire based on respondent feedback, (b) administered the revised survey via Internet to 265 staff at 8 VA CLCs, and (c) examined the psychometric properties of the revised 50-item BJBC PCC instrument using multitrait analysis. Results: Scale reliabilities met the criterion for group comparisons (alpha levels ranged from 0.84 to 0.91). The pattern of item correlations and intra- and interscale correlations indicating convergent and discriminant validity, respectively, were both 100%. Implications: Our results support the broader use of the BJBC survey within VA. In addition, given the high levels of internal consistency reliability of the current scales, it is likely that a psychometrically sound short form of the instrument could be created. Further research on construct and convergent validity are warranted to support the broader application of the instrument.
C1 [Sullivan, Jennifer L.; Meterko, Mark; Baker, Errol; Stolzmann, Kelly; Adjognon, Omonyele; Ballah, Konique; Parker, Victoria A.] VA Boston Healthcare Syst, COLMR, Boston, MA 02130 USA.
[Sullivan, Jennifer L.; Meterko, Mark; Parker, Victoria A.] Boston Univ, Sch Publ Hlth Hlth Policy & Management, Boston, MA 02215 USA.
[Ballah, Konique] Brigham & Womens Hosp, Transplant Adm, Boston, MA 02115 USA.
RP Sullivan, JL (reprint author), VA Boston Healthcare Syst, COLMR, 150 South Huntington Ave 152M, Boston, MA 02130 USA.
EM jennifer.sullivan@va.gov
OI Parker, Victoria/0000-0002-7632-9174
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U1 17
U2 20
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD AUG
PY 2013
VL 53
IS 4
BP 596
EP 607
DI 10.1093/geront/gns140
PG 12
WC Gerontology
SC Geriatrics & Gerontology
GA 182CF
UT WOS:000321717400007
PM 23197392
ER
PT J
AU Seyyedi, M
Eddington, DK
Nadol, JB
AF Seyyedi, Mohammad
Eddington, Donald K.
Nadol, Joseph B., Jr.
TI Effect of monopolar and bipolar electric stimulation on survival and
size of human spiral ganglion cells as studied by postmortem
histopathology
SO HEARING RESEARCH
LA English
DT Article
ID NEONATALLY DEAFENED CATS; COCHLEAR IMPLANTATION; AUDITORY-NERVE;
GUINEA-PIG; NEUROTROPHIC FACTOR; HEARING-LOSS; INNER-EAR; NEURONS;
DEGENERATION; PATTERNS
AB The spiral ganglion cell (SGC) is the target of electrical stimulation in cochlear implants. This study is designed to test the hypothesis that chronic electrical stimulation tends to preserve SGCs in implanted hearing-impaired ears. A total of 26 pairs of temporal bones were studied from 26 individuals who in life suffered bilateral profound hearing impairment that was symmetric (in degree of impairment and etiology) across ears and then underwent unilateral cochlear implantation. The subjects were divided in two groups by stimulus configuration: bipolar (n = 16) or monopolar (n = 10). The temporal bones were prepared for histological review by standard methods and two measures of SGC status were made by cochlear segment: count and maximal cross-sectional area. Within-subject comparison of the measures between the implanted-stimulated and the unimplanted ears showed: (1) for both stimulus configurations, the mean (across subjects and segments) of the count difference (implanted ear - unimplanted ear) was significantly less than zero; (2) the mean (across subject) count difference for cochlear segments I, II and III (segments with electrode contacts in the implanted ear) was significantly less negative than the mean difference for cochlear segment IV (no electrode in implanted ear) for bipolar but not for monopolar stimulation; (3) neither implantation-stimulation nor stimulus configuration significantly influenced the measures of maximum cross-sectional cell area. The SGC count results are consistent with the hypothesis that implantation results in a propensity across the whole cochlea for SGCs to degenerate and with chronic bipolar stimulation ameliorating this propensity in those cochlear segments with electrodes present. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Seyyedi, Mohammad; Eddington, Donald K.; Nadol, Joseph B., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Seyyedi, Mohammad; Eddington, Donald K.; Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Seyyedi, Mohammad; Eddington, Donald K.; Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA.
[Eddington, Donald K.; Nadol, Joseph B., Jr.] MIT, Speech & Hearing Biosci & Technol Program, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM joseph_nadol@meei.harvard.edu
FU National Institute of Deafness and Other Communication Disorders
[R01-DC000152]
FX This work was supported by grant R01-DC000152 from the National
Institute of Deafness and Other Communication Disorders.
NR 42
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U1 0
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
J9 HEARING RES
JI Hear. Res.
PD AUG
PY 2013
VL 302
BP 9
EP 16
DI 10.1016/j.heares.2013.04.007
PG 8
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA 186OZ
UT WOS:000322055300002
PM 23660399
ER
PT J
AU Yakoob, MY
Bateman, BT
Ho, E
Hernandez-Diaz, S
Franklin, JM
Goodman, JE
Hoban, RA
AF Yakoob, Mohammad Y.
Bateman, Brian T.
Ho, Eugenia
Hernandez-Diaz, Sonia
Franklin, Jessica M.
Goodman, Julie E.
Hoban, Rebecca A.
TI The Risk of Congenital Malformations Associated With Exposure to
-Blockers Early in Pregnancy: A Meta-Analysis
SO HYPERTENSION
LA English
DT Article
DE -blockers; cleft lip; palate; congenital anomalies; heart defects;
congenital; neural tube defects; pregnancy; trimester; first
ID ANTIHYPERTENSIVE MEDICATION USE; GESTATIONAL-AGE NEWBORNS; DIABETIC
PREGNANCIES; PRECONCEPTION CARE; DRUGS; POPULATION; INFANTS; WOMEN;
OUTCOMES; DEFECTS
AB -blockers are commonly used during the first trimester of pregnancy. Data about risks of congenital anomalies in offspring have not been summarized. We performed a meta-analysis to determine teratogenicity of -blockers in early pregnancy. A systematic literature search was performed using PubMed, EMBASE, Cochrane Clinical Trials, and hand search. Meta-analyses were performed using random-effects models based on odds ratios (ORs). Prespecified subgroup analyses were performed to explore heterogeneity. Randomized controlled trials or observational studies examining risks of congenital malformations associated with first trimester -blocker exposure compared with no exposure were included. Thirteen population-based case-control or cohort studies were identified. Based on meta-analyses, first-trimester oral -blocker use showed no increased odds of all or major congenital anomalies (OR=1.00; 95% confidence interval, 0.91-1.10; 5 studies). However, in analyses examining organ-specific malformations, increased odds of cardiovascular defects (OR=2.01; 95% confidence interval, 1.18-3.42; 4 studies), cleft lip/palate (OR=3.11; 95% confidence interval, 1.79-5.43; 2 studies), and neural tube defects (OR=3.56; 95% confidence interval, 1.19-10.67; 2 studies) were observed. The effects on severe hypospadias were nonsignificant (1 study). Causality is difficult to interpret given the small number of heterogeneous studies and possibility of biases. Given the frequency of this exposure in pregnancy, further research is needed.
C1 [Yakoob, Mohammad Y.; Hernandez-Diaz, Sonia; Goodman, Julie E.] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA.
[Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Bateman, Brian T.; Franklin, Jessica M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02115 USA.
[Ho, Eugenia] Childrens Hosp Boston, Dept Pediat Neurol, Boston, MA USA.
[Hoban, Rebecca A.] Rush Univ, Sect Neonatol, Chicago, IL 60612 USA.
RP Yakoob, MY (reprint author), 203 Pk Dr,Unit 223A, Boston, MA 02215 USA.
EM myyakoob@mail.harvard.edu
FU NIH [R01 HD059861-01A1]; Agency of Healthcare Research and Qualit [RO1
HS018533]
FX IRB approval/informed consent is not applicable as this article involves
a meta-analysis only of previously published articles involving
de-identified data. This was an unfunded study. Sonia Hernandez-Diaz is
the Principal Investigator (PI) of NIH R01 HD046595-01A1 on
teratogenicity of drugs commonly used in pregnancy and NIH R01
HD059861-01A1 grant on phthalates in medications and risk of male
genital malformations. She receives sponsorships from Agency of
Healthcare Research and Quality (Grant RO1 HS018533) on antidepressants
use in pregnancy and postpartum, and is involved in projects funded by
pharmaceutical companies related to North American Antiepileptic Drug
Pregnancy Registry. The other authors report no conflicts.
NR 30
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U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD AUG
PY 2013
VL 62
IS 2
BP 375
EP 381
DI 10.1161/HYPERTENSIONAHA.111.00833
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 185IY
UT WOS:000321962300029
PM 23753416
ER
PT J
AU Hess, DR
Kondili, D
Burns, E
Bittner, EA
Schmidt, UH
AF Hess, Dean R.
Kondili, Dhimiter
Burns, Edward
Bittner, Edward A.
Schmidt, Ulrich H.
TI A 5-year observational study of lung-protective ventilation in the
operating room: A single-center experience
SO JOURNAL OF CRITICAL CARE
LA English
DT Article
DE Anesthesia; Knowledge transfer; Lung-protective ventilation; Tidal
volume; Positive end-expiratory pressure
ID RESPIRATORY-DISTRESS-SYNDROME; TIDAL VOLUME VENTILATION; RANDOMIZED
CONTROLLED-TRIAL; MECHANICAL VENTILATION; GENERAL-ANESTHESIA;
RISK-FACTOR; INJURY; ATELECTASIS; MANAGEMENT; STRATEGY
AB Purpose: We assessed the evolution of lung-protective ventilation strategies during anesthesia and identified factors associated with the selection of a nonprotective ventilation strategy.
Methods: This retrospective observational study covered a 5-year period from March 2006 to March 2011. It included 45 575 adult patients who underwent intubation de novo in the operating room. We considered a tidal volume (V-T) greater than 10 mL/kg of ideal body weight (IBW) and/or positive end-expiratory pressure (PEEP) less than 5 cm H2O as not lung protective. We evaluated the use of nonprotective ventilation strategies over time in men and women, by American Society of Anesthesiologists classification, and for elective vs emergent surgery.
Results: Over the duration of the study, there was a significant reduction in the percentage of patients receiving a V-T greater than 10 mL/kg IBW (28.5%-16.3%, P < .001), zero PEEP (27.5%-18.2%, P < .001), and V-T greater than 10 mL/kg IBW with PEEP less than 5 cm H2O (13.4%-8.0%, P < .001). The odds of receiving nonprotective ventilation were greater for women than for men, in the first year compared with the last year, and for elective compared with emergent surgery.
Conclusion: Although use of nonprotective ventilation decreased over time, an important percentage of patients continue to receive nonprotective ventilation. (c) 2013 Elsevier Inc. All rights reserved.
C1 [Hess, Dean R.; Bittner, Edward A.; Schmidt, Ulrich H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Kondili, Dhimiter; Burns, Edward] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Hess, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
EM dhess@partners.org
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U1 0
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0883-9441
J9 J CRIT CARE
JI J. Crit. Care
PD AUG
PY 2013
VL 28
IS 4
AR 533.e9
DI 10.1016/j.jcrc.2012.11.014
PG 7
WC Critical Care Medicine
SC General & Internal Medicine
GA 181UQ
UT WOS:000321694900038
PM 23369521
ER
PT J
AU Volpp, KG
Small, DS
Romano, PS
Itani, KMF
Rosen, AK
Even-Shoshan, O
Wang, YL
Bellini, L
Halenar, MJ
Korovaichuk, S
Zhu, JS
Silber, JH
AF Volpp, Kevin G.
Small, Dylan S.
Romano, Patrick S.
Itani, Kamal M. F.
Rosen, Amy K.
Even-Shoshan, Orit
Wang, Yanli
Bellini, Lisa
Halenar, Michael J.
Korovaichuk, Sophia
Zhu, Jingsan
Silber, Jeffrey H.
TI Teaching Hospital Five-Year Mortality Trends in the Wake of Duty Hour
Reforms
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE patient outcomes; mortality; duty hour reform; ACGME; administrative
data
ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; MEDICARE BENEFICIARIES;
EDUCATION; IMPACT
AB The Accreditation Council for Graduate Medical Education (ACGME) implemented duty hour regulations for residents in 2003 and again in 2011. While previous studies showed no systematic impacts in the first 2 years post-reform, the impact on mortality in subsequent years has not been examined.
To determine whether duty hour regulations were associated with changes in mortality among Medicare patients in hospitals of different teaching intensity after the first 2 years post-reform.
Observational study using interrupted time series analysis with data from July 1, 2000 to June 30, 2008. Logistic regression was used to examine the change in mortality for patients in more versus less teaching-intensive hospitals before (2000-2003) and after (2003-2008) duty hour reform, adjusting for patient comorbidities, time trends, and hospital site.
Medicare patients (n = 13,678,956) admitted to short-term acute care non-federal hospitals with principal diagnoses of acute myocardial infarction (AMI), gastrointestinal bleeding, or congestive heart failure (CHF); or a diagnosis-related group (DRG) classification of general, orthopedic, or vascular surgery.
All-location mortality within 30 days of hospital admission.
In medical and surgical patients, there were no consistent changes in the odds of mortality at more vs. less teaching intensive hospitals in post-reform years 1-3. However, there were significant relative improvements in mortality for medical patients in the fourth and fifth years post-reform: Post4 (OR 0.88, 95 % CI [0.93-0.94]); Post5 (OR 0.87, [0.82-0.92]) and for surgical patients in the fifth year post-reform: Post5 (OR 0.91, [0.85-0.96]).
Duty hour reform was associated with no significant change in mortality in the early years after implementation, and with a trend toward improved mortality among medical patients in the fourth and fifth years. It is unclear whether improvements in outcomes long after implementation can be attributed to the reform, but concerns about worsening outcomes seem unfounded. (C) Society of General Internal Medicine 2013
C1 [Volpp, Kevin G.; Halenar, Michael J.] Vet Adm Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA.
[Volpp, Kevin G.; Bellini, Lisa; Halenar, Michael J.; Zhu, Jingsan] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Volpp, Kevin G.; Silber, Jeffrey H.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA.
[Volpp, Kevin G.; Zhu, Jingsan] Univ Penn, Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA.
[Small, Dylan S.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA.
[Romano, Patrick S.] Univ Calif Davis, Sch Med, Div Gen Med, Sacramento, CA 95817 USA.
[Romano, Patrick S.] Univ Calif Davis, Sch Med, Ctr Healthcare Policy & Res, Sacramento, CA 95817 USA.
[Itani, Kamal M. F.] VA Boston Healthcare Syst, Dept Surg, Boston, MA USA.
[Itani, Kamal M. F.] Boston Univ, Boston, MA 02215 USA.
[Rosen, Amy K.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA.
[Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Even-Shoshan, Orit; Wang, Yanli; Korovaichuk, Sophia; Silber, Jeffrey H.] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA.
[Silber, Jeffrey H.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Silber, Jeffrey H.] Univ Penn, Dept Anesthesiol & Crit Care, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Even-Shoshan, Orit; Silber, Jeffrey H.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
RP Volpp, KG (reprint author), Vet Adm Hosp, Ctr Hlth Equ Res & Promot, 1120 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM Volpp70@wharton.upenn.edu
RI Romano, Patrick/N-4225-2014
OI Romano, Patrick/0000-0001-6749-3979
FU NHLBI [R01 HL094593-01]
FX This work was funded by grant R01 HL094593-01 from the NHLBI.
NR 36
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U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD AUG
PY 2013
VL 28
IS 8
BP 1048
EP 1055
DI 10.1007/s11606-013-2401-9
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 184DZ
UT WOS:000321869000014
PM 23592241
ER
PT J
AU Austad, KE
Avorn, J
Franklin, JM
Kowal, MK
Campbell, EG
Kesselheim, AS
AF Austad, Kirsten E.
Avorn, Jerry
Franklin, Jessica M.
Kowal, Mary K.
Campbell, Eric G.
Kesselheim, Aaron S.
TI Changing Interactions Between Physician Trainees and the Pharmaceutical
Industry: A National Survey
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE pharmaceutical industry; undergraduate medical education; drug
promotion; conflict of interest
ID MEDICAL-STUDENTS EXPOSURE; RESPONSE RATES; EDUCATION; ATTITUDES;
REPRESENTATIVES; BEHAVIOR; SCHOOL
AB Increasingly, medical school policies limit pharmaceutical representatives' access to students and gifts from drugmakers, but little is known about how these policies affect student attitudes toward industry.
To assess interactions between trainees and the pharmaceutical industry, and to determine whether learning environment characteristics influence students' practices and attitudes.
We conducted a cross-sectional survey with a nationally-representative sample of first- and fourth-year medical students and third-year residents, stratified by medical school, including a parts per thousand yen 14 randomly selected trainees at each level per school.
We measured frequency of industry interactions and attitudes regarding how such interactions affect medical training and the profession. Chi-squared tests assessed bivariate linear trend, and hierarchical logistic regression models were fitted to assess associations between trainees' attitudes and their schools' National Institutes of Health (NIH) funding levels and American Medical Student Association (AMSA) PharmFree Scorecard grades reflecting industry-related conflict of interest policies.
Among 1,610 student (49.3 % response rate) and 739 resident (43.1 %) respondents, industry-sponsored gifts were common, rising from 33.0 % (first-year students) to 56.8 % (fourth-year students) and 54 % (residents) (p < 0.001). These gifts included meals outside the hospital (reported by 5 % first-year students, 13.4 % fourth-year students, 27.5 % residents (p < 0.001)) and free drug samples (reported by 7.4 % first-year students, 14.1 % fourth-year students, 14.3 % residents (p < 0.001)). The perception that industry interactions lead to bias was prevalent, but the belief that physicians receive valuable education through these interactions increased (64.1 % to 67.5 % to 79.8 %, p < 0.001). Students in schools receiving more NIH funding reported industry gifts less often (OR = 0.51, 95 % CI: 0.38-0.68, p < 0.001), but the strength of institutional conflict of interest policies was not associated with this variable.
Despite recent policy changes, a substantial number of trainees continue to receive gifts from pharmaceutical representatives. We found no relation between these outcomes and a school's policies concerning interactions with industry. (C) Society of General Internal Medicine 2013
C1 [Austad, Kirsten E.; Avorn, Jerry; Franklin, Jessica M.; Kowal, Mary K.; Kesselheim, Aaron S.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02120 USA.
[Austad, Kirsten E.; Avorn, Jerry; Franklin, Jessica M.; Kowal, Mary K.; Campbell, Eric G.; Kesselheim, Aaron S.] Harvard Univ, Sch Med, Boston, MA 02120 USA.
[Austad, Kirsten E.; Kesselheim, Aaron S.] Harvard Univ, Edmond J Safra Ctr Eth, Cambridge, MA 02138 USA.
[Campbell, Eric G.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
RP Kesselheim, AS (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA.
EM akesselheim@partners.org
OI Franklin, Jessica/0000-0002-8941-4116
FU Edmond J. Safra Center for Ethics at Harvard University; Agency for
Healthcare Research Quality [K08HS18465-01]; Robert Wood Johnson
Foundation
FX The authors would like to thank Prof. Lawrence Lessig of Harvard Law
School for his helpful comments on the study, and to acknowledge useful
input from members of the Research Ethics Program of the Harvard
Clinical and Translational Science Center. Study funded by a grant from
the Edmond J. Safra Center for Ethics at Harvard University. Dr.
Kesselheim is supported by a career development award from the Agency
for Healthcare Research & Quality (K08HS18465-01), and a Robert Wood
Johnson Foundation Investigator Award in Health Policy Research. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 35
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U1 1
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD AUG
PY 2013
VL 28
IS 8
BP 1064
EP 1071
DI 10.1007/s11606-013-2361-0
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 184DZ
UT WOS:000321869000016
PM 23444007
ER
PT J
AU Hauer, KE
Soni, K
Cornett, P
Kohlwes, J
Hollander, H
Ranji, SR
ten Cate, O
Widera, E
Calton, B
O'Sullivan, PS
AF Hauer, Karen E.
Soni, Krishan
Cornett, Patricia
Kohlwes, Jeff
Hollander, Harry
Ranji, Sumant R.
ten Cate, Olle
Widera, Eric
Calton, Brook
O'Sullivan, Patricia S.
TI Developing Entrustable Professional Activities as the Basis for
Assessment of Competence in an Internal Medicine Residency: A
Feasibility Study
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE clinical competence; assessment; education; medical; graduate medical
education
ID CARE; ENVIRONMENT; INPATIENT; EDUCATION
AB Graduate medical education programs assess trainees' performance to determine readiness for unsupervised practice. Entrustable professional activities (EPAs) are a novel approach for assessing performance of core professional tasks.
To describe a pilot and feasibility evaluation of two EPAs for competency-based assessment in internal medicine (IM) residency.
Post-graduate year-1 interns (PGY-1s) and attendings at a large internal medicine (IM) residency program.
Two Entrustable professional activities (EPA) assessments (Discharge, Family Meeting) were piloted.
Twenty-eight out of 43 (65.1 %) PGY-1 s and 32/43 (74.4 %) attendings completed surveys about the Discharge EPA experience. Most who completed the EPA assessment (10/12, 83.8 %, PGY-1s; 9/11, 83.3 %, attendings) agreed it facilitated useful feedback discussions. For the Family Meeting EPA, 16/26 (61.5 %) PGY-1s completed surveys, and most who participated (9/12 PGY1s, 75 %) reported it improved attention to family meeting education, although only half recommended continuing the EPA assessment.
From piloting two EPA assessments in a large IM residency, we recognized our reminder systems and time dedicated for completing EPA requirements as inadequate. Collaboration around patient safety and palliative care with relevant clinical services has enhanced implementation and buy-in. We will evaluate how well EPA-based assessment serves the intended purpose of capturing trainees' trustworthiness to conduct activities unsupervised. (C) Society of General Internal Medicine 2013
C1 [Hauer, Karen E.; Soni, Krishan; Hollander, Harry; Ranji, Sumant R.; ten Cate, Olle; Calton, Brook; O'Sullivan, Patricia S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Cornett, Patricia; Kohlwes, Jeff; Widera, Eric] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA.
[ten Cate, Olle] Univ Utrecht, Dept Med, Utrecht, Netherlands.
RP Hauer, KE (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
EM Karen.hauer@ucsf.edu
OI O'Sullivan, Patricia/0000-0002-8706-4095; ten Cate,
Olle/0000-0002-6379-8780
FU American Board of Internal Medicine
FX Dr. Hauer received support from the American Board of Internal Medicine.
There was no additional funding specific to this project.
NR 19
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U1 1
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD AUG
PY 2013
VL 28
IS 8
BP 1110
EP 1114
DI 10.1007/s11606-013-2372-x
PG 5
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 184DZ
UT WOS:000321869000022
PM 23595926
ER
PT J
AU Sheth, SA
Eskandar, EN
Dougherty, DD
AF Sheth, Sameer A.
Eskandar, Emad N.
Dougherty, Darin D.
TI Obsessive-compulsive disorder and cingulotomy RESPONSE
SO JOURNAL OF NEUROSURGERY
LA English
DT Letter
C1 [Sheth, Sameer A.] Columbia Univ, NewYork Presbyterian Hosp, New York, NY 10027 USA.
[Eskandar, Emad N.; Dougherty, Darin D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Sheth, SA (reprint author), Columbia Univ, NewYork Presbyterian Hosp, New York, NY 10027 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD AUG
PY 2013
VL 119
IS 2
BP 526
EP 526
PG 1
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 187CL
UT WOS:000322094400042
PM 24063045
ER
PT J
AU Seif, F
Patel, SR
Walia, H
Rueschman, M
Bhatt, DL
Gottlieb, DJ
Lewis, EF
Patil, SP
Punjabi, NM
Babineau, DC
Redline, S
Mehra, R
AF Seif, Fadi
Patel, Sanjay R.
Walia, Harneet
Rueschman, Michael
Bhatt, Deepak L.
Gottlieb, Daniel J.
Lewis, Eldrin F.
Patil, Susheel P.
Punjabi, Naresh M.
Babineau, Denise C.
Redline, Susan
Mehra, Reena
TI Association between obstructive sleep apnea severity and endothelial
dysfunction in an increased background of cardiovascular burden
SO JOURNAL OF SLEEP RESEARCH
LA English
DT Article
DE cardiovascular disease; endothelial dysfunction; sleep apnea
ID OXIDATIVE STRESS; BRACHIAL-ARTERY; HEART HEALTH; NITRIC-OXIDE;
RISK-FACTORS; VASODILATION; HYPERTENSION; IMPAIRMENT; REACTIVITY;
AMPLITUDE
AB The objective of this study is to examine whether increasing obstructive sleep apnea (OSA) severity is associated with worsening endothelial function. The design is a cross-sectional examination of the baseline assessment of a multi-centre randomized controlled clinical trial examining the effects of oxygen, continuous positive airway pressure (CPAP) therapy or lifestyle modifications on cardiovascular biomarkers. Participants were recruited from cardiology clinics at four sites. Participants with an apnea-hypopnea index (AHI) of 15-50 and known cardio/cerebrovascular disease (CVD) or CVD risk factors were included. OSA severity indices [oxygen desaturation index (ODI), AHI and percentage of sleep time below 90% oxygen saturation (total sleep time < 90)] and a measure of endothelium-mediated vasodilatation [Framingham reactive hyperaemia index (F-RHI) derived from peripheral arterial tonometry (PAT)] were assessed. The sample included 267 individuals with a mean AHI of 25.0 +/- 8.5 SD and mean F-RHI 0.44 +/- 0.38. In adjusted models, the slope of the relationship between ODI and F-RHI differed above and below an ODI of 24.6 (P = 0.04), such that above an ODI of 24.6 there was a marginally significant decline in the geometric mean of the PAT ratio by 3% [95% confidence interval (CI): 0%, 5%; P = 0.05], while below this point, there was a marginally significant incline in the geometric mean of the PAT ratio by 13% (95% CI: 0%, 27%; P = 0.05) per 5-unit increase in ODI. A similar pattern was observed between AHI and F-RHI. No relation was noted with total sleep time < 90 and F-RHI. There was evidence of a graded decline in endothelial function in association with higher levels of intermittent hypoxaemia.
C1 [Seif, Fadi; Walia, Harneet; Mehra, Reena] Case Sch Med, Dept Med, Cleveland, OH USA.
[Patel, Sanjay R.; Rueschman, Michael; Bhatt, Deepak L.; Gottlieb, Daniel J.; Lewis, Eldrin F.; Redline, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Patel, Sanjay R.; Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Bhatt, Deepak L.; Gottlieb, Daniel J.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA.
[Patil, Susheel P.; Punjabi, Naresh M.] Johns Hopkins Univ, Baltimore, MD USA.
[Babineau, Denise C.] Case Western Reserve Univ, Ctr Clin Invest, Cleveland, OH 44106 USA.
[Mehra, Reena] Case Sch Med, Case Comprehens Canc Ctr, Case Ctr Transdisciplinary Res Energet & Canc, Cleveland, OH USA.
RP Mehra, R (reprint author), Case Western Reserve Univ, 11100 Euclid Ave, Cleveland, OH 44106 USA.
EM reena.mehra@case.edu
OI Mehra, Reena/0000-0002-6222-2675; Patel, Sanjay/0000-0002-9142-5172
FU NIH National Heart Lung Blood Institute [RC2 HL101417, K23 HL079114];
American Heart Association [0530188N]; Central Society of Clinical
Research; NHLBI [K08 HL081385]; NCI [1U54CA116867]; NIH [M01 RR00080]
FX This study was supported by NIH National Heart Lung Blood Institute RC2
HL101417 and K23 HL079114, NIH M01 RR00080, American Heart Association
National Scientist Development Award 0530188N, Central Society of
Clinical Research, NHLBI K08 HL081385 and NCI 1U54CA116867. The project
described was also supported by UL1 RR024989 from the National Center
for Research Resources (NCRR), a component of the National Institutes of
Health (NIH) and its contents are solely the responsibility of the
authors and do not necessarily represent the official view of NCRR or
NIH.
NR 31
TC 12
Z9 13
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0962-1105
J9 J SLEEP RES
JI J. Sleep Res.
PD AUG
PY 2013
VL 22
IS 4
BP 443
EP 451
DI 10.1111/jsr.12026
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 182VP
UT WOS:000321773200012
PM 23331757
ER
PT J
AU Cheng, P
Casement, MD
Chen, CF
Hoffmann, RF
Armitage, R
Deldin, PJ
AF Cheng, Philip
Casement, Melynda D.
Chen, Chiau-Fang
Hoffmann, Robert F.
Armitage, Roseanne
Deldin, Patricia J.
TI Sleep-disordered breathing in major depressive disorder
SO JOURNAL OF SLEEP RESEARCH
LA English
DT Article
DE major depressive disorder; sleep-disordered breathing
AB Individuals with major depressive disorder often experience obstructive sleep apnea. However, the relationship between depression and less severe sleep-disordered breathing is unclear. This study examined the rate of sleep-disordered breathing in depression after excluding those who had clinically significant sleep apnea (>5 apneas.h(-1)). Archival data collected between 1991 and 2005 were used to assess the prevalence of sleep-disordered breathing events in 60 (31 depressed; 29 healthy controls) unmedicated participants. Respiratory events were automatically detected using a program developed in-house measuring thermal nasal air-flow and chest pressure. Results show that even after excluding participants with clinically significant sleep-disordered breathing, individuals with depression continue to exhibit higher rates of sleep-disordered breathing compared with healthy controls (depressed group: apnea-hypopnea index mean = 0.524, SE = 0.105; healthy group: apnea-hypopnea index mean = 0.179, SE = 0.108). Exploratory analyses were also conducted to assess for rates of exclusion in depression studies due to sleep-disordered breathing. Study exclusion of sleep-disordered breathing was quantified based on self-report during telephone screening, and via first night polysomnography. Results from phone screening data reveal that individuals reporting depression were 5.86 times more likely to report a diagnosis of obstructive sleep apnea than presumptive control participants. Furthermore, all of the participants excluded for severe sleep-disordered breathing detected on the first night were participants with depression. These findings illustrate the importance of understanding the relationship between sleep-disordered breathing and depression, and suggest that screening and quantification of sleep-disordered breathing should be considered in depression research.
C1 [Cheng, Philip; Chen, Chiau-Fang; Hoffmann, Robert F.; Armitage, Roseanne; Deldin, Patricia J.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Casement, Melynda D.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Casement, Melynda D.] Boston Univ, Med Ctr, Boston, MA USA.
RP Deldin, PJ (reprint author), Univ Michigan, 530 Church St, Ann Arbor, MI 48109 USA.
EM pjdeldin@umich.edu
OI Casement, Melynda/0000-0002-5906-0994
FU National Institute of Mental Health (NIMH) [R01-MH061515, T32-MH019836]
FX This research was supported in part by National Institute of Mental
Health (NIMH) Grant R01-MH061515, awarded to Roseanne Armitage. Support
for the second author was provided by NIMH Institutional Training Grant
T32-MH019836. The content of this manuscript is solely the
responsibility of the authors, and does not necessarily represent the
official views of NIMH or NIH. The authors would also like to thank the
UM Department of Psychology, Department of Psychiatry, and the
Depression Center for their continued support.
NR 10
TC 4
Z9 4
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0962-1105
J9 J SLEEP RES
JI J. Sleep Res.
PD AUG
PY 2013
VL 22
IS 4
BP 459
EP 462
DI 10.1111/jsr.12029
PG 4
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 182VP
UT WOS:000321773200014
PM 23350718
ER
PT J
AU Roberts, DS
Lin, HW
Herrmann, BS
Lee, DJ
AF Roberts, Daniel S.
Lin, Harrison W.
Herrmann, Barbara S.
Lee, Daniel J.
TI Differential cochlear implant outcomes in older adults
SO LARYNGOSCOPE
LA English
DT Article
DE Cochlear Implant outcomes; elderly; octogenarians
ID SPEECH RECOGNITION; ELDERLY-PATIENTS; PERFORMANCE; QUALITY; PREDICTORS;
PERCEPTION; HEARING
AB Objectives/Hypothesis The goals of this study were to analyze whether cochlear implant (CI) users over 65 years of age have different surgical and audiological outcomes when compared to younger adult CI users and to identify reasons for these possible differences.
Study Design Retrospective single-institution study.
Methods Records of 113 postlingually deafened adults with unilateral cochlear implants were reviewed. Preoperative and postoperative speech perception scores, and medical and epidemiological data were recorded and analyzed.
Results Speech perception ability was significantly poorer in CI users over 65 years of age compared to younger adult patients (P = .012). Patients over the age of 80 years accounted for these findings (P = .017). Older patients were less likely to have a family history of hearing deficits. A history of noise exposure and idiopathic cause of hearing loss did not correlate with audiological outcomes. A family history of hearing loss was associated with a trend toward better speech recognition (P = .062). Older patients did not experience more vestibular symptoms or other complications compared to younger patients.
Conclusions Patients over the age of 80 years had lower speech perception scores than other adult CI recipients but did not have higher rates of dizziness or vertigo after surgery. A family history of hearing loss was associated with a trend toward better speech recognition, possibly representing a new prognostic variable. These findings provide important information that will aid clinicians in counseling older CI candidates.
C1 [Roberts, Daniel S.; Lin, Harrison W.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Herrmann, Barbara S.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA.
[Roberts, Daniel S.; Lin, Harrison W.; Herrmann, Barbara S.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM daniel_lee@meei.harvard.edu
FU Massachusetts Eye and Ear Department of Otolaryngology
FX Support for this research was from the Massachusetts Eye and Ear
Department of Otolaryngology fund for resident research.
NR 22
TC 18
Z9 19
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD AUG
PY 2013
VL 123
IS 8
BP 1952
EP 1956
DI 10.1002/lary.23676
PG 5
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 185XN
UT WOS:000322004400024
PM 23737286
ER
PT J
AU Davids, MS
Letai, A
Brown, JR
AF Davids, Matthew S.
Letai, Anthony
Brown, Jennifer R.
TI Overcoming stroma-mediated treatment resistance in chronic lymphocytic
leukemia through BCL-2 inhibition
SO LEUKEMIA & LYMPHOMA
LA English
DT Article
DE Chronic lymphocytic leukemia; apoptosis; B cell lymphoma/leukemia 2
(BCL-2); microenvironment
ID NAVITOCLAX; PATHWAY
AB Despite recent advances in the treatment of chronic lymphocytic leukemia (CLL) with chemoimmunotherapy, many patients with CLL are older or frail and cannot tolerate aggressive chemotherapy. Even those who can inevitably develop resistance due to factors such as deletion of pro-apoptotic factors like TP53 or the support of pro-survival signals from the stromal microenvironment. Using BH3 profiling, we found that CLL cells co-cultured with stroma are less primed to undergo apoptosis in response to BCL-2 inhibition. Currently, several approaches to BCL-2 inhibition with well-tolerated oral agents are in development in the clinic. Dosing of navitoclax (ABT-263) was complicated by thrombocytopenia due to BCL-XL inhibition, but the BCL-2 specific inhibitor ABT-199 (GDC-0199) should avoid this issue, and may overcome stroma-mediated resistance to apoptosis. We are developing BH3 profiling as a biomarker to predict response to novel therapies such as ABT-199, and to identify resistance mechanisms to new agents being studied in CLL.
C1 [Davids, Matthew S.; Letai, Anthony; Brown, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
RP Davids, MS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,M232, Boston, MA 02215 USA.
EM matthew_davids@dfci.harvard.edu
FU NCI NIH HHS [T32 CA009172]
NR 13
TC 12
Z9 11
U1 0
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1042-8194
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD AUG
PY 2013
VL 54
IS 8
BP 1823
EP 1825
DI 10.3109/10428194.2013.796051
PG 3
WC Oncology; Hematology
SC Oncology; Hematology
GA 182SG
UT WOS:000321763800048
PM 23614795
ER
PT J
AU Jambunathan, K
Watson, DS
Najvar, LK
Wiederhold, NP
Kirkpatrick, WR
Patterson, TF
Askew, DS
Kodukula, K
Galande, AK
AF Jambunathan, Kalyani
Watson, Douglas S.
Najvar, Laura K.
Wiederhold, Nathan P.
Kirkpatrick, William R.
Patterson, Thomas F.
Askew, David S.
Kodukula, Krishna
Galande, Amit K.
TI Prolyl endopeptidase activity in bronchoalveolar lavage fluid: a novel
diagnostic biomarker in a guinea pig model of invasive pulmonary
aspergillosis
SO MEDICAL MYCOLOGY
LA English
DT Article
DE fluorogenic probes; invasive aspergillosis; proteolytic enzymes;
combinatorial library; broncheoalveolar lavage fluid
ID NEUTROPENIC PATIENTS; FUNGAL-INFECTIONS; FUMIGATUS; ENZYME;
GALACTOMANNAN; IDENTIFICATION; IMMUNOASSAY; MANAGEMENT; SUBSTRATE;
PROTEASES
AB Improved diagnostics are needed to detect invasive pulmonary aspergillosis, a life-threatening infection caused by the pathogenic fungus Aspergillus fumigatus. We are investigating secreted fungal proteases as novel biomarkers for the diagnosis of this disease. Although the A. fumigatus genome encodes a multitude of secreted proteases, few have been experimentally characterized. Here, we employed an unbiased combinatorial library of internally quenched fluorogenic probes to detect infection-associated proteolysis in the lungs of guinea pigs experimentally infected with A. fumigatus. Comparative protease activity profiling revealed a prolyl endopeptidase activity that is reproducibly induced during infection but is not observed in healthy animals. This proteolytic activity was found in four independent animal experiments involving two A. fumigatus isolates. We synthesized a small, focused fluorogenic probe library to define the substrate specificity of the prolyl endopeptidase substrate motif and to identify optimal Probe sequences. These efforts resulted in the identification of a panel of six individual substrate-based fluorescent probes capable of detecting infection in guinea pigs with high statistical significance (P < 0.005 in most cases). Receiver operating characteristic analyses demonstrated that this fluorogenic assay could detect A. fumigatus infection-associated proteolysis with comparable sensitivity and specificity as existing diagnostic procedures, suggesting that further optimization of the methodology may lead to improved diagnostics options for invasive pulmonary aspergillosis.
C1 [Jambunathan, Kalyani; Watson, Douglas S.; Kodukula, Krishna; Galande, Amit K.] SRI Int, Biosci Div, Harrisonburg, VA 22802 USA.
[Najvar, Laura K.; Wiederhold, Nathan P.; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Askew, David S.] Univ Cincinnati, Coll Med, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA.
[Najvar, Laura K.; Kirkpatrick, William R.; Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX USA.
RP Galande, AK (reprint author), SRI Int, Biosci Div, 140 Res Dr, Harrisonburg, VA 22802 USA.
EM amit.galande@sri.com
OI Wiederhold, Nathan/0000-0002-2225-5122
FU National Institute of Allergy and Infectious Diseases (NIAID)
[R21AI08502, N01AI30041, HHSN2722010000381]; Commonwealth of Virginia
FX The authors wish to acknowledge the encouragement and guidance of Dr Joe
Perrone, Director of Diagnostics at SRI Biosciences, and Dr Walter Moos,
Vice President of SRI Biosciences. This work was supported by grant
R21AI08502 and contract N01AI30041 and HHSN2722010000381 from the
National Institute of Allergy and Infectious Diseases (NIAID). SRI
International's Center for Advanced Drug Research was established
through funding support from the Commonwealth of Virginia.
NR 43
TC 3
Z9 4
U1 0
U2 11
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1369-3786
J9 MED MYCOL
JI Med. Mycol.
PD AUG
PY 2013
VL 51
IS 6
BP 592
EP 602
DI 10.3109/13693786.2012.761360
PG 11
WC Infectious Diseases; Mycology; Veterinary Sciences
SC Infectious Diseases; Mycology; Veterinary Sciences
GA 183CG
UT WOS:000321790600006
PM 23356446
ER
PT J
AU Sheedy, FJ
Grebe, A
Rayner, KJ
Kalantari, P
Ramkhelawon, B
Carpenter, SB
Becker, CE
Ediriweera, HN
Mullick, AE
Golenbock, DT
Stuart, LM
Latz, E
Fitzgerald, KA
Moore, KJ
AF Sheedy, Frederick J.
Grebe, Alena
Rayner, Katey J.
Kalantari, Parisa
Ramkhelawon, Bhama
Carpenter, Susan B.
Becker, Christine E.
Ediriweera, Hasini N.
Mullick, Adam E.
Golenbock, Douglas T.
Stuart, Lynda M.
Latz, Eicke
Fitzgerald, Katherine A.
Moore, Kathryn J.
TI CD36 coordinates NLRP3 inflammasome activation by facilitating
intracellular nucleation of soluble ligands into particulate ligands in
sterile inflammation
SO NATURE IMMUNOLOGY
LA English
DT Article
ID SCAVENGER-RECEPTOR-A; AMYLOID-BETA; ALZHEIMERS-DISEASE; CHOLESTEROL
CRYSTALS; NALP3 INFLAMMASOME; MICE; CELLS; PROTEIN; MACROPHAGES; PEPTIDE
AB Particulate ligands, including cholesterol crystals and amyloid fibrils, induce production of interleukin 1 beta (IL-1 beta) dependent on the cytoplasmic sensor NLRP3 in atherosclerosis, Alzheimer's disease and diabetes. Soluble endogenous ligands, including oxidized low-density lipoprotein (LDL), amyloid-beta and amylin peptides, accumulate in such diseases. Here we identify an endocytic pathway mediated by the pattern-recognition receptor CD36 that coordinated the intracellular conversion of those soluble ligands into crystals or fibrils, which resulted in lysosomal disruption and activation of the NLRP3 inflammasome. Consequently, macrophages that lacked CD36 failed to elicit IL-1 beta production in response to those ligands, and targeting CD36 in atherosclerotic mice resulted in lower serum concentrations of IL-1 beta and accumulation of cholesterol crystals in plaques. Collectively, our findings highlight the importance of CD36 in the accrual and nucleation of NLRP3 ligands from within the macrophage and position CD36 as a central regulator of inflammasome activation in sterile inflammation.
C1 [Sheedy, Frederick J.; Rayner, Katey J.; Ramkhelawon, Bhama; Ediriweera, Hasini N.; Moore, Kathryn J.] NYU, Sch Med, Marc & Ruti Bell Program Vasc Biol & Dis, Dept Med,Leon H Charney Div Cardiol, New York, NY 10012 USA.
[Grebe, Alena; Latz, Eicke] Univ Bonn, Inst Innate Immun, Bonn, Germany.
[Kalantari, Parisa; Carpenter, Susan B.; Golenbock, Douglas T.; Latz, Eicke; Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Dept Infect Dis & Immunol, Worcester, MA USA.
[Becker, Christine E.; Stuart, Lynda M.] Harvard Univ, Sch Med, Dept Pediat, Lab Dev Immunol,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Mullick, Adam E.] ISIS Pharmaceut, Carlsbad, CA 92008 USA.
[Latz, Eicke] German Ctr Neurodegenerat Dis, Bonn, Germany.
RP Moore, KJ (reprint author), NYU, Sch Med, Marc & Ruti Bell Program Vasc Biol & Dis, Dept Med,Leon H Charney Div Cardiol, New York, NY 10012 USA.
EM kathryn.moore@nyumc.edu
RI Latz, Eicke/H-3951-2014;
OI Latz, Eicke/0000-0003-1488-5666; Mullick, Adam/0000-0003-4600-961X;
Moore, kathryn/0000-0003-2505-2547; Sheedy,
Frederick/0000-0003-2645-8493
FU US National Institutes of Health [R01HL117334, R01AG032349, U24
AI082660, R01 AI079198, 5R01HL093262-02, 1R01HL112661-01, AI083713];
American Heart Association [11POST7400075]
FX We thank F. Maxfield (Weill Cornell Medical College) for Lalistat.
Supported by the US National Institutes of Health (R01HL117334 and
R01AG032349 to K.J.M.; U24 AI082660 to L.M.S. and K.J.M.; R01 AI079198
to L.M.S.; 5R01HL093262-02 and 1R01HL112661-01 to E.L.; and AI083713 to
K.A.F. and E.L.) and the American Heart Association (11POST7400075 to
F.J.S.).
NR 54
TC 161
Z9 172
U1 3
U2 40
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD AUG
PY 2013
VL 14
IS 8
BP 812
EP +
DI 10.1038/ni.2639
PG 11
WC Immunology
SC Immunology
GA 185ZN
UT WOS:000322010600010
PM 23812099
ER
PT J
AU A-Gonzalez, N
Guillen, JA
Gallardo, G
Diaz, M
de la Rosa, JV
Hernandez, IH
Casanova-Acebes, M
Lopez, F
Tabraue, C
Beceiro, S
Hong, C
Lara, PC
Andujar, M
Arai, S
Miyazaki, T
Li, SL
Corbi, AL
Tontonoz, P
Hidalgo, A
Castrillo, A
AF A-Gonzalez, Noelia
Guillen, Jose A.
Gallardo, German
Diaz, Mercedes
de la Rosa, Juan V.
Hernandez, Irene H.
Casanova-Acebes, Maria
Lopez, Felix
Tabraue, Carlos
Beceiro, Susana
Hong, Cynthia
Lara, Pedro C.
Andujar, Miguel
Arai, Satoko
Miyazaki, Toru
Li, Senlin
Corbi, Angel L.
Tontonoz, Peter
Hidalgo, Andres
Castrillo, Antonio
TI The nuclear receptor LXR alpha controls the functional specialization of
splenic macrophages
SO NATURE IMMUNOLOGY
LA English
DT Article
ID LIVER-X-RECEPTORS; DENDRITIC CELLS; MARGINAL-ZONE; IMMUNE-RESPONSE;
GENE-EXPRESSION; MYELOID CELLS; B-CELLS; MONOCYTES; SPLEEN; INFLAMMATION
AB Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXR alpha was essential for the differentiation of macrophages in the marginal zone (MZ) of the spleen. LXR-deficient mice were defective in the generation of MZ and metallophilic macrophages, which resulted in abnormal responses to blood-borne antigens. Myeloid-specific expression of LXR alpha or adoptive transfer of wild-type monocytes restored the MZ microenvironment in LXR alpha-deficient mice. Our results demonstrate that signaling via LXR alpha in myeloid cells is crucial for the generation of splenic MZ macrophages and identify an unprecedented role for a nuclear receptor in the generation of specialized macrophage subsets.
C1 [A-Gonzalez, Noelia; Guillen, Jose A.; Diaz, Mercedes; Hernandez, Irene H.; Beceiro, Susana; Castrillo, Antonio] Univ Autonoma Madrid, Consejo Super Invest Cient, Inst Invest Biomed Alberto Sols Madrid, Madrid, Spain.
[A-Gonzalez, Noelia; Guillen, Jose A.; Gallardo, German; Diaz, Mercedes; de la Rosa, Juan V.; Hernandez, Irene H.; Lopez, Felix; Tabraue, Carlos; Beceiro, Susana; Castrillo, Antonio] Univ Las Palmas Gran Canaria, Consejo Super Invest Cient, Inst Invest Biomed Alberto Sols Madrid, Unidad Asociada Biomed, Las Palmas Gran Canaria, Spain.
[Casanova-Acebes, Maria; Hidalgo, Andres] Ctr Nacl Invest Cardiovasc, Dept Epidemiol Atherothrombosis & Imaging, Madrid, Spain.
[Hong, Cynthia; Tontonoz, Peter] Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA.
[Lara, Pedro C.] Hosp Univ Gran Canaria Dr Negrin, Serv Oncol Radioterap, Las Palmas Gran Canaria, Spain.
[Andujar, Miguel] Hosp Univ Materno Infantil Las Palmas, Serv Patol, Las Palmas Gran Canaria, Spain.
[Arai, Satoko; Miyazaki, Toru] Univ Tokyo, Fac Med, Ctr Dis Biol & Integrat Med, Lab Mol Biomed Pathogenesis, Tokyo 113, Japan.
[Li, Senlin] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Li, Senlin] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Li, Senlin] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Corbi, Angel L.] CSIC, Ctr Invest Biol, Madrid, Spain.
RP Castrillo, A (reprint author), Univ Autonoma Madrid, Consejo Super Invest Cient, Inst Invest Biomed Alberto Sols Madrid, Madrid, Spain.
EM acastrillo@iib.uam.es
RI Corbi, Angel/B-7194-2011; Tabraue, Carlos/D-7126-2015; Alonso Gonzalez ,
Noelia/H-4488-2015; Hidalgo, Andres/L-5643-2014
OI Corbi, Angel/0000-0003-1980-5733; Tabraue, Carlos/0000-0001-9920-8116;
Alonso Gonzalez , Noelia/0000-0003-0533-5216; Hidalgo,
Andres/0000-0001-5513-555X
FU Spanish Ministry of Research and Innovation [SAF2008-00057]; Ministry of
Economy and Competitiveness [SAF2011-29244, SAF2009-11037]; European
Union [IRG246655]; Howard Hughes Medical Institute; US National
Institutes of Health [HL-066088, HL-030568]; Subprograma Ramon y Cajal
[RYC-2007-00697]; Formacion de Personal Investigador [BES-2010-032828,
BES-2009-012191]; Universidad Las Palmas de Gran Canaria
FX We thank D. Mangelsdorf (University of Texas Southwestern Medical
Center) for LXR alpha- and LXR beta-sufficient wild-type
(Nr1h3+/+ Nr1h2+/+) mice, LXR alpha-deficient
(Nr1h3-/-) mice, LXR alpha-deficient (Nr1h2-/-)
mice and LXR-deficient (Nr1h3-/-Nr1h2-/-) mice;
the Institut Clinique de la Souris for Nr1h3fl/fl mice; D.
Kioussis (Medical Research Council) and S. Gonzalez (Centro Nacional de
Investigaciones Cardiovasculares) for Vav-Cre mice; S. Gordon and M.
Stacey (University of Oxford) for antibody to F4/80 (anti-F4/80) and
anti-CD169; G. Randolph (Washington University St. Louis) for
discussions and anti-TREML4 from the R. Steinman laboratory (Rockefeller
University); M. Kosco-Vilbois (NovImmune) for anti-FDC-M1 and
anti-FDC-M2; J. Collins and T. Willson (GlaxoSmithKline) for the
synthetic ligands of LXR (GW3965) and retinoid X receptor (LG268); N.
Ruddle, C. Glass, N. Spann, A. Chawla, G. Lemke, D. Hume, L. Hedrick, A.
Lazarus and L. Bosca for comments; and Servicio Microscopia Electronica
(University of Las Palmas de Gran Canaria) for electron microscopy.
Supported by the Spanish Ministry of Research and Innovation
(SAF2008-00057 to A.C.), the Ministry of Economy and Competitiveness
(SAF2011-29244 to A.C. and SAF2009-11037 to A.H.), Framework Programme 7
of the European Union (International Reintegration Grant IRG246655 to A.
H.), the Howard Hughes Medical Institute (P.T.), the US National
Institutes of Health (HL-066088 and HL-030568 to P.T.), Subprograma
Ramon y Cajal (RYC-2007-00697 to A. H.), Formacion de Personal
Investigador (BES-2010-032828 to M. C.-A. and BES-2009-012191 to I.H.H.)
and Universidad Las Palmas de Gran Canaria (J.V.d.l.R.).
NR 47
TC 32
Z9 34
U1 3
U2 20
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD AUG
PY 2013
VL 14
IS 8
BP 831
EP +
DI 10.1038/ni.2622
PG 11
WC Immunology
SC Immunology
GA 185ZN
UT WOS:000322010600012
PM 23770640
ER
PT J
AU Posthuma, R
Weinstein, MM
Iyer, S
Alperin, M
Wakamatsu, MM
Pulliam, SJ
AF Posthuma, R.
Weinstein, M. M.
Iyer, S.
Alperin, M.
Wakamatsu, M. M.
Pulliam, S. J.
TI CLINICAL APPLICATION OF THE IUGA/ICS CLASSIFICATION SYSTEM FOR
MESH-RELATED COMPLICATIONS
SO NEUROUROLOGY AND URODYNAMICS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the International-Continence-Society (ICS)
CY AUG 26-30, 2013
CL Barcelona, SPAIN
SP Int Continence Soc (ICS)
C1 [Posthuma, R.; Weinstein, M. M.; Iyer, S.; Wakamatsu, M. M.; Pulliam, S. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Alperin, M.] Univ Calif San Diego, San Diego, CA 92103 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0733-2467
J9 NEUROUROL URODYNAM
JI Neurourol. Urodyn.
PD AUG
PY 2013
VL 32
IS 6
MA 253
BP 876
EP 877
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 178HP
UT WOS:000321437700254
ER
PT J
AU Limaye, S
Riley, S
Zhao, SH
O'Neill, A
Posner, M
Adkins, D
Jaffa, Z
Clark, J
Haddad, R
AF Limaye, Sewanti
Riley, Sarah
Zhao, Sihai
O'Neill, Anne
Posner, Marshall
Adkins, Douglas
Jaffa, Zachary
Clark, John
Haddad, Robert
TI A randomized phase II study of docetaxel with or without vandetanib in
recurrent or metastatic squamous cell carcinoma of head and neck (SCCHN)
SO ORAL ONCOLOGY
LA English
DT Article
DE Recurrent/metastatic; Head and neck cancer; Palliative chemotherapy;
Targeted therapy
ID LUNG-CANCER; COMBINATION CHEMOTHERAPY; PLUS DOCETAXEL; ACTIVE-DRUG;
ANGIOGENESIS; BEVACIZUMAB; CISPLATIN; TRIAL; ERLOTINIB; THERAPY
AB Objectives: There are limited chemotherapeutic options for advanced recurrent or metastatic SCCHN. The efficacy and toxicity of docetaxel with or without vandetanib was investigated in these patients.
Materials and Methods: Patients with pathologically confirmed, recurrent or metastatic SCCHN who had progressed on platinum based therapy given as definitive or palliative treatment, were randomized in this open label, multicenter phase II study of docetaxel (75 mg/m2 IV Q3 weeks) with or without vandetanib (100 mg PO daily). The primary objective was response rate (RR) and secondary objectives were progression free survival (PFS), overall survival (OS), disease control rate (DCR) and duration of response (DOR).
Results: 29 analyzable patients were enrolled, 14 in docetaxel arm and 15 in combined arm. PR was achieved in 1 patient in the docetaxel arm and 2 patients in the combined arm. The objective RR was 7% (1/14) (95% CI 0.2-33.8%) in the single and 13% (2/15) (95% CI 1.6-40.4%) combined arm. The median PFS was 3.21 (95% CI 3.0-22.0) and 9 (95% CI (5.86-18.1) weeks; median OS was 26.8(95% CI 17.7-100.7+) and 24.1 (95% CI, 16.4-171.1+) weeks. Most common adverse events were fatigue, dysphagia, diarrhea or constipation, cytopenias and alopecia.
Conclusions: Although an initial benefit in response was noted and statistical criteria met there was only a minor trend towards improved PFS for the combined arm. The study was designed with low threshold for activity in each arm and results were deemed not to be of enough clinical significance in this group of patients to continue accrual. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Limaye, Sewanti; Riley, Sarah; Jaffa, Zachary; Haddad, Robert] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Limaye, Sewanti; Riley, Sarah; Jaffa, Zachary; Haddad, Robert] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Zhao, Sihai; O'Neill, Anne] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Posner, Marshall] Mt Sinai Sch Med, New York, NY 10029 USA.
[Adkins, Douglas] Washington Univ, Sch Med, St Louis, MO 63110 USA.
[Clark, John] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Limaye, S (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM SewantiA_limaye@dfci.harvard.edu
FU AstraZeneca
FX AstraZeneca.
NR 30
TC 13
Z9 14
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
J9 ORAL ONCOL
JI Oral Oncol.
PD AUG
PY 2013
VL 49
IS 8
BP 835
EP 841
DI 10.1016/j.oraloncology.2013.04.010
PG 7
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA 178HS
UT WOS:000321438100020
PM 23727257
ER
PT J
AU Snorrason, I
Olafsson, RP
Flessner, CA
Keuthen, NJ
Franklin, ME
Woods, DW
AF Snorrason, Ivar
Olafsson, Ragnar P.
Flessner, Christopher A.
Keuthen, Nancy J.
Franklin, Martin E.
Woods, Douglas W.
TI The Skin Picking Impact Scale: Factor structure, validity and
development of a short version
SO SCANDINAVIAN JOURNAL OF PSYCHOLOGY
LA English
DT Article
DE Skin picking impact scale; pathological skin picking; psychogenic
excoriation; factor analysis; validity; reliability; psychosocial impact
ID CLINICAL CHARACTERISTICS; ECONOMIC-IMPACT; FIT INDEXES; SAMPLE;
TRICHOTILLOMANIA; PHENOMENOLOGY; POPULATION; TESTS
AB In the present study, we examined the psychometric properties of the Skin Picking Impact Scale (SPIS; Keuthen, Deckersbach, Wilhelm etal., 2001), a 10 item self-report questionnaire designed to assess the psychosocial impact of skin picking disorder (SPD). Participants were 650 individuals who met criteria for SPD in an online survey. Exploratory and confirmatory factor analyses demonstrated a unitary factor structure with high internal consistency (alpha = 0.94). Consequently, we constructed an abbreviated 4-item version that retained good internal consistency (alpha = 0.87) and a robust factor structure. Both the short and the full versions demonstrated discriminant and convergent/concurrent validity. In conclusion, the findings indicate that both versions are psychometrically sound measures of SPD related psychosocial impact; however, some potential limitations of the full scale are discussed.
C1 [Snorrason, Ivar; Woods, Douglas W.] Univ Wisconsin Milwaukee, Dept Psychol, Milwaukee, WI 53211 USA.
[Olafsson, Ragnar P.] Univ Iceland, Sch Hlth Sci, Landspitali Univ Hosp, Div Psychiat, IS-101 Reykjavik, Iceland.
[Olafsson, Ragnar P.] Univ Iceland, Sch Hlth Sci, Fac Psychol, IS-101 Reykjavik, Iceland.
[Flessner, Christopher A.] Kent State Univ, Dept Psychol, Kent, OH USA.
[Keuthen, Nancy J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA.
[Franklin, Martin E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
RP Snorrason, I (reprint author), Univ Wisconsin Milwaukee, Dept Psychol, 2441 East Hartford Ave, Milwaukee, WI 53211 USA.
EM ivarsnorrason@gmail.com
RI Flessner, Christopher/K-1483-2015
NR 24
TC 5
Z9 6
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0036-5564
J9 SCAND J PSYCHOL
JI Scand. J. Psychol.
PD AUG
PY 2013
VL 54
IS 4
BP 344
EP 348
DI 10.1111/sjop.12057
PG 5
WC Psychology, Multidisciplinary
SC Psychology
GA 182PM
UT WOS:000321756200011
PM 23682651
ER
PT J
AU Pugh, TD
Conklin, MW
Evans, TD
Polewski, MA
Barbian, HJ
Pass, R
Anderson, BD
Colman, RJ
Eliceiri, KW
Keely, PJ
Weindruch, R
Beasley, TM
Anderson, RM
AF Pugh, Thomas D.
Conklin, Matthew W.
Evans, Trent D.
Polewski, Michael A.
Barbian, Hannah J.
Pass, Rachelle
Anderson, Bradley D.
Colman, Ricki J.
Eliceiri, Kevin W.
Keely, Patricia J.
Weindruch, Richard
Beasley, T. Mark
Anderson, Rozalyn M.
TI A shift in energy metabolism anticipates the onset of sarcopenia in
rhesus monkeys
SO AGING CELL
LA English
DT Article
DE aging; metabolism; mitochondria; NAD; PGC-1; skeletal muscle; rhesus
monkeys
ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; SKELETAL-MUSCLE; FLUORESCENCE
MICROSCOPY; CALORIE RESTRICTION; BODY-COMPOSITION; IN-VIVO; AGE; SIRT1;
ADAPTATION; BIOLOGY
AB Age-associated skeletal muscle mass loss curtails quality of life and may contribute to defects in metabolic homeostasis in older persons. The onset of sarcopenia occurs in middle age in rhesusmacaques although the trigger has yet to be identified. Here, we show that a shift in metabolism occurs in advance of the onset of sarcopenia in rhesus vastuslateralis. Multiphoton laser-scanning microscopy detects a shift in the kinetics of photon emission from autofluorescent metabolic cofactors NADH and FAD. Lifetime of both fluorophores is shortened at mid-age, and this is observed in both free and bound constituent pools. Levels of FAD and free NADH are increased and the NAD/NADH redox ratio is lower. Concomitant with this, expression of fiber-type myosin isoforms is altered resulting in a shift in fiber-type distribution, activity of cytochrome c oxidase involved in mitochondrial oxidative phosphorylation is significantly lower, and the subcellular organization of mitochondria in oxidative fibers is compromised. A regulatory switch involving the transcriptional coactivator PGC-1 directs metabolic fuel utilization and governs the expression of structural proteins. Age did not significantly impact total levels of PGC-1; however, its subcellular localization was disrupted, suggesting that PGC-1 activities may be compromised. Consistent with this, intracellular lipid storage is altered and there is shift to larger lipid droplet size that likely reflects a decline in lipid turnover or a loss in efficiency of lipid metabolism. We suggest that changes in energy metabolism contribute directly to skeletal muscle aging in rhesus monkeys.
C1 [Pugh, Thomas D.; Evans, Trent D.; Polewski, Michael A.; Barbian, Hannah J.; Pass, Rachelle; Anderson, Bradley D.; Weindruch, Richard; Anderson, Rozalyn M.] Univ Wisconsin, Dept Med, Madison, WI 53706 USA.
[Conklin, Matthew W.; Eliceiri, Kevin W.] Univ Wisconsin, Lab Opti& Computat Instrumen, Madison, WI 53706 USA.
[Colman, Ricki J.; Anderson, Rozalyn M.] Univ Wisconsin, Natl Primate Res Ctr, Madison, WI 53715 USA.
[Keely, Patricia J.] Univ Wisconsin, Dept Cell & Regenerat Biol, Madison, WI 53706 USA.
[Weindruch, Richard; Anderson, Rozalyn M.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA.
[Beasley, T. Mark] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
RP Anderson, RM (reprint author), VA Hosp, GRECC D5214,2500 Overlook Terrace, Madison, WI 53705 USA.
EM rmanderson@medicine.wisc.edu
OI Eliceiri, Kevin/0000-0001-8678-670X
FU NIA [P01AG011915]; NIH [UL1RR025011, R01CA13659, R01AG037000];
Department of Medicine, School of Medicine and Public Health, UW Madison
FX We would like to acknowledge Scott Baum and Susan McKiernan for
assistance with sample procurement. We also thank staff at LOCI for
assistance with imaging instrumentation. Funding for this study was
provided by NIA grant P01AG011915, NIH UL1RR025011, NIH R01CA13659, NIH
R01AG037000, and the Department of Medicine, School of Medicine and
Public Health, UW Madison. The study was conducted with the use of
resources and facilities at the William S. Middleton Memorial Veterans
Hospital, Madison WI.
NR 48
TC 14
Z9 14
U1 2
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD AUG
PY 2013
VL 12
IS 4
BP 672
EP 681
DI 10.1111/acel.12091
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 182WP
UT WOS:000321775800015
PM 23607901
ER
PT J
AU Trickett, EJ
Beehler, S
AF Trickett, Edison J.
Beehler, Sarah
TI The Ecology of Multilevel Interventions to Reduce Social Inequalities in
Health
SO AMERICAN BEHAVIORAL SCIENTIST
LA English
DT Article
DE multilevel; interventions; inequality; health
ID PUBLIC-HEALTH; TRANSDISCIPLINARY RESEARCH; PROMOTION PROGRAMS; NETWORK
ANALYSIS; COMMUNITY; DISPARITIES; SCIENCE; OBESITY; EQUITY; IMPACT
AB Health inequities persist and, in some cases, are increasing. Multilevel interventions involve efforts to change aspects of social contexts related to the creation and maintenance of health inequities among varied groups. Momentum for conducting multilevel interventions to achieve health equity is found across professional fields as well as scientific and funding organizations. This article discusses the rationale for multilevel interventions, briefly reviews their evolution over time with respect to health inequities, and provides an ecological way of thinking about some of the conceptual and pragmatic challenges they raise for social science. This perspective frames community interventions as multilevel, ecologically based, collaboratively conducted, culturally situated, and designed to increase community capacity. Implications of this perspective are drawn for the development, implementation, and evaluation of multilevel interventions.
C1 [Trickett, Edison J.] Univ Illinois, Chicago, IL 60607 USA.
[Trickett, Edison J.] Univ Illinois, Dept Psychol, Community & Prevent Res Div, Chicago, IL 60607 USA.
[Beehler, Sarah] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Jamaica Plain, MA USA.
RP Trickett, EJ (reprint author), Univ Illinois, 1007 West Harrison St, Chicago, IL 60607 USA.
EM trickett@uic.edu
NR 93
TC 14
Z9 14
U1 1
U2 33
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0002-7642
J9 AM BEHAV SCI
JI Am. Behav. Sci.
PD AUG
PY 2013
VL 57
IS 8
SI SI
BP 1227
EP 1246
DI 10.1177/0002764213487342
PG 20
WC Psychology, Clinical; Social Sciences, Interdisciplinary
SC Psychology; Social Sciences - Other Topics
GA 181XR
UT WOS:000321704500011
ER
PT J
AU Harte, CB
Liverant, GI
Sloan, DM
Kamholz, BW
Rosebrock, LE
Fava, M
Kaplan, GB
AF Harte, Christopher B.
Liverant, Gabrielle I.
Sloan, Denise M.
Kamholz, Barbara W.
Rosebrock, Laina E.
Fava, Maurizio
Kaplan, Gary B.
TI Association Between Smoking and Heart Rate Variability Among Individuals
with Depression
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Smoking; Depression; Heart rate variability; Cardiac autonomic
regulation; Autonomic nervous system
ID ACUTE MYOCARDIAL-INFARCTION; COMORBIDITY SURVEY REPLICATION;
CORONARY-ARTERY DISEASE; CIGARETTE-SMOKING; SPECTRAL-ANALYSIS;
SHORT-TERM; MAJOR DEPRESSION; MORTALITY; POPULATION; CESSATION
AB Both depression and smoking have been independently associated with lower heart rate variability (HRV), suggesting dysregulation of cardiac autonomic function. However, no studies have systematically explored the effects of smoking on HRV among depressed patients.
This study examined differences in HRV based on smoking status among depressed individuals.
Electrophysiological data were examined among 77 adult outpatients without a history of myocardial infarction, who met criteria for major depressive disorder or dysthymia. Frequency domain [low frequency (LF), high frequency (HF), LF/HF ratio, respiratory sinus arrhythmia (RSA)] parameters of HRV, and heart rate and inter-beat interval (IBI) data were compared between depressed smokers (n = 34) and depressed nonsmokers (n = 44).
After controlling for covariates, depressed smokers, compared to depressed nonsmokers, displayed significantly lower LF, HF, and RSA.
Among depressed patients, smoking is associated with significantly lower HRV, indicating dysregulated autonomic modulation of the heart.
C1 [Harte, Christopher B.; Liverant, Gabrielle I.; Sloan, Denise M.; Kamholz, Barbara W.; Rosebrock, Laina E.; Kaplan, Gary B.] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Harte, Christopher B.; Liverant, Gabrielle I.; Sloan, Denise M.; Kamholz, Barbara W.; Kaplan, Gary B.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Sloan, Denise M.] Natl Ctr PTSD, Boston, MA USA.
[Kamholz, Barbara W.] Boston Univ, Boston, MA 02215 USA.
[Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA.
RP Harte, CB (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 116-B4, Boston, MA 02130 USA.
EM christopher.harte@va.gov
OI Sloan, Denise/0000-0002-0962-478X; Harte,
Christopher/0000-0002-8097-7369
NR 41
TC 6
Z9 6
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD AUG
PY 2013
VL 46
IS 1
BP 73
EP 80
DI 10.1007/s12160-013-9476-8
PG 8
WC Psychology, Multidisciplinary
SC Psychology
GA 180GC
UT WOS:000321580800011
PM 23436273
ER
PT J
AU Clark, DJ
Kautz, SA
Bauer, AR
Chen, YT
Christou, EA
AF Clark, David J.
Kautz, Steven A.
Bauer, Andrew R.
Chen, Yen-Ting
Christou, Evangelos A.
TI Synchronous EMG Activity in the Piper Frequency Band Reveals the
Corticospinal Demand of Walking Tasks
SO ANNALS OF BIOMEDICAL ENGINEERING
LA English
DT Article
DE Walking; Electromyography; Motor control; Nervous system; Locomotion
ID EVOKED MOTOR-RESPONSES; CORTICOMUSCULAR COHERENCE; HUMAN GAIT; DEPENDENT
MODULATION; MUSCLE-ACTIVITY; SURFACE EMG; EEG-EMG; CORTEX; OSCILLATIONS;
DRIVE
AB Evidence indicates that the frequency-domain characteristics of surface electromyogram (EMG) signals are modulated according to the contributing sources of neural drive. Modulation of inter-muscular EMG synchrony within the Piper frequency band (30-60 Hz) during movement tasks has been linked to drive from the corticospinal tract. However, it is not known whether EMG synchrony is sufficiently sensitive to detect task-dependent differences in the corticospinal contribution to leg muscle activation during walking. We investigated this question in seventeen healthy older men and women. It was hypothesized that, relative to typical steady state walking, Piper band EMG synchrony of the triceps surae muscle group would be reduced for dual-task walking (because of competition for cortical resources), similar for fast walking (because walking speed is directed by an indirect locomotor pathway rather than by the corticospinal tract), and increased when taking a long step (because voluntary gait pattern modifications are directed by the corticospinal tract). Each of these hypotheses was confirmed. These findings support the use of frequency-domain analysis of EMG in future investigations into the corticospinal contribution to control of healthy and disordered human walking.
C1 [Clark, David J.; Bauer, Andrew R.] Malcom Randall VA Med Ctr, Brain Rehabil Res Ctr, Gainesville, FL 32608 USA.
[Clark, David J.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL 32610 USA.
[Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA.
[Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA.
[Chen, Yen-Ting; Christou, Evangelos A.] Univ Florida, Dept Appl Physiol & Kinesiol, Gainesville, FL 32611 USA.
RP Clark, DJ (reprint author), Malcom Randall VA Med Ctr, Brain Rehabil Res Ctr, 1601 SW Archer Rd 151A, Gainesville, FL 32608 USA.
EM davidclark@ufl.edu
OI Kautz, Steven/0000-0003-3151-8235
FU US Department of Veterans Affairs Rehabilitation Research and
Development Service [B7176W]; National Institute on Aging
[P30-AG028740-04, R01 AG-031769]
FX This work was supported by the US Department of Veterans Affairs
Rehabilitation Research and Development Service (B7176W to DJC) and by
the National Institute on Aging (P30-AG028740-04 to DJC and R01
AG-031769 to EAC).
NR 50
TC 6
Z9 7
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0090-6964
J9 ANN BIOMED ENG
JI Ann. Biomed. Eng.
PD AUG
PY 2013
VL 41
IS 8
BP 1778
EP 1786
DI 10.1007/s10439-013-0832-4
PG 9
WC Engineering, Biomedical
SC Engineering
GA 179IT
UT WOS:000321514300019
PM 23740367
ER
PT J
AU de Souza, P
Rathkopf, D
Smith, M
Mulders, P
Mainwaring, P
North, S
Griffin, T
Park, Y
Molina, A
Ryan, C
AF de Souza, Paul
Rathkopf, Dana
Smith, Matthew
Mulders, Peter
Mainwaring, Paul
North, Scott
Griffin, Thomas
Park, Youn
Molina, Arturo
Ryan, Charles
TI Long-term safety and efficacy analysis of abiraterone acetate (AA) plus
prednisone (P) in study COU-AA-302for metastatic castration-resistant
prostate cancer
SO BJU INTERNATIONAL
LA English
DT Meeting Abstract
C1 [de Souza, Paul] Univ Western Sydney, Penrith, NSW 1797, Australia.
[Rathkopf, Dana] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Smith, Matthew] Massachusetts Gen Hosp Canc Ctr, Boston, MA USA.
[Mulders, Peter] Radboud Univ Nijmegen Med Ctr, Nijmegen, Netherlands.
[North, Scott] Cross Canc Inst, Edmonton, AB, Canada.
[Griffin, Thomas; Molina, Arturo] Janssen Res & Dev, Los Angeles, CA USA.
[Park, Youn] Janssen Res & Dev, Raritan, NJ USA.
[Ryan, Charles] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RI Mulders, Peter/H-8076-2014
NR 1
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD AUG
PY 2013
VL 112
SU 1
SI SI
BP 13
EP 13
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 185LK
UT WOS:000321969100032
ER
PT J
AU DeAngelo, DJ
Mesa, RA
Fiskus, W
Tefferi, A
Paley, C
Wadleigh, M
Ritchie, EK
Snyder, DS
Begna, K
Ganguly, S
Ondovik, MS
Rine, J
Bhalla, KN
AF DeAngelo, Daniel J.
Mesa, Ruben A.
Fiskus, Warren
Tefferi, Ayalew
Paley, Carole
Wadleigh, Martha
Ritchie, Ellen K.
Snyder, David S.
Begna, Kebede
Ganguly, Siddhartha
Ondovik, Michael S.
Rine, Jessica
Bhalla, Kapil N.
TI Phase II trial of panobinostat, an oral pan-deacetylase inhibitor in
patients with primary myelofibrosis, post-essential thrombocythaemia,
and post-polycythaemia vera myelofibrosis
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE myelofibrosis; myeloproliferative neoplasms; panobinostat; histone
deacetylase inhibitors
ID CHRONIC MYELOPROLIFERATIVE NEOPLASMS; JAK2 INHIBITOR; CELLS; EFFICACY;
THERAPY; LBH589; EZH2
AB Myelofibrosis (MF) is a Philadelphia chromosome-negative stem cell myeloproliferative neoplasm (MPN) associated with cytopenias, splenomegaly, constitutional symptoms, and poor prognosis. MF patients commonly express JAK2 V617F mutation and activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling. Agents targeting the JAK/STAT pathway have demonstrated efficacy in patients with MF. This study evaluated panobinostat, a pan-deacetylase inhibitor that depletes JAK2 V617F levels and JAK/STAT signalling in MPN cells, in patients with primary MF, post-essential thrombocythaemia MF, and post-polycythaemia vera MF. Patients received panobinostat 40 mg administered three times per week. Dose reductions were permitted for toxicities. The primary endpoint was response rate at 6 months using International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) consensus criteria. Analyses of peripheral blood cells from treated patients revealed that panobinostat inhibited JAK/STAT signalling, decreased inflammatory cytokine levels, and decreased JAK2 V617F allelic burden. However, panobinostat was poorly tolerated at the dose and schedule evaluated, and only 16 of 35 patients completed 2 cycles of treatment. One patient (3%) achieved an IWG-MRT response. Common adverse events were thrombocytopenia (71 center dot 4%) and diarrhoea (80 center dot 0%). Although molecular correlative analyses suggested that panobinostat inhibits key intracellular targets, limited clinical activity was observed because of poor tolerance.
C1 [DeAngelo, Daniel J.; Wadleigh, Martha] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Mesa, Ruben A.] Mayo Clin, Scottsdale, AZ USA.
[Fiskus, Warren; Ganguly, Siddhartha; Bhalla, Kapil N.] Methodist Hosp Res Inst, Cockrell Ctr Adv Therapeut, Houstony, TX USA.
[Tefferi, Ayalew] Mayo Clin, Rochester, MN USA.
[Paley, Carole; Ondovik, Michael S.; Rine, Jessica] Novartis Pharmaceut, E Hanover, NJ USA.
[Ritchie, Ellen K.] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA.
[Snyder, David S.] City Hope Natl Med Ctr, Duarte, CA USA.
RP DeAngelo, DJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana D1B30, Boston, MA 02215 USA.
EM daniel_deangelo@dfci.harvard.edu; knbhalla@tmhs.org
FU Novartis Pharmaceuticals Corporation
FX This study was funded by Novartis Pharmaceuticals Corporation. The
authors thank Ghulam Warsi, PhD, for assistance with statistical
analysis; Robyn Scherber for analysis of the MF-SAF data; and William
Fazzone, PhD, for medical editorial assistance with this manuscript.
Financial support for medical editorial assistance was provided by
Novartis Pharmaceuticals Corporation.
NR 27
TC 35
Z9 35
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD AUG
PY 2013
VL 162
IS 3
BP 326
EP 335
DI 10.1111/bjh.12384
PG 10
WC Hematology
SC Hematology
GA 180BV
UT WOS:000321568800006
PM 23701016
ER
PT J
AU Chasman, D
Schurks, M
Anttila, V
Kurth, T
AF Chasman, D.
Schuerks, M.
Anttila, V.
Kurth, T.
TI Preferential Association of Migraine Loci with Migraine Characterized by
Specific Traits on a Population Basis
SO CEPHALALGIA
LA English
DT Meeting Abstract
CT International Headache Congress
CY JUN 27-30, 2013
CL Boston, MA
SP Int Headache Soc, Amer Headache Soc
C1 [Chasman, D.; Kurth, T.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Schuerks, M.] Univ Hosp, Essen, Germany.
[Anttila, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kurth, T.] INSERM, U708, Bordeaux, France.
[Kurth, T.] Univ Bordeaux, Bordeaux, France.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0333-1024
J9 CEPHALALGIA
JI Cephalalgia
PD AUG
PY 2013
VL 33
IS 11
BP 986
EP 987
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 176VJ
UT WOS:000321333800062
ER
PT J
AU Tritos, NA
Hamrahian, AH
King, D
Greenspan, SL
Cook, DM
Jonsson, PJ
Koltowska-Haggstrom, M
Biller, BMK
AF Tritos, Nicholas A.
Hamrahian, Amir H.
King, Donna
Greenspan, Susan L.
Cook, David M.
Jonsson, Peter J.
Koltowska-Haggstrom, Maria
Biller, Beverly M. K.
TI Predictors of the effects of 4years of growth hormone replacement on
bone mineral density in patients with adult-onset growth hormone
deficiency - a KIMS database analysis
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID GH REPLACEMENT; HYPOPITUITARY PATIENTS; BODY-COMPOSITION; GLUCOCORTICOID
REPLACEMENT; POSTMENOPAUSAL WOMEN; METABOLISM; THERAPY; OSTEOPOROSIS;
MULTICENTER; GENDER
AB Objective Growth hormone (GH) replacement may increase bone mineral density (BMD) in GH-deficient (GHD) adults. The goal of this study was to identify predictors of BMD response to GH replacement in GH naive adults.
Design and measurements This was a retrospective analysis of data extracted from KIMS (Pfizer International Metabolic Database), an international pharmacoepidemiological survey of adult GHD patients from 31 countries.
Patients A total of 231 GH naive adults were identified (115 women and 116 men) who had BMD measured on the same densitometer in the lumbar spine (LS) and/or femoral neck (FN) both at baseline and after 4 years of GH replacement.
Results After 4 years, there was a median (10th, 90th percentile) 4.6% (-5.2%, 12.2%) increase in LS BMD over baseline (P = 0.0001). There was a positive correlation between per cent change in LS BMD and age at the onset of pituitary disease (r = 0.25, P = 0.001). There was no change in FN BMD over baseline [0.0% (-7.3%, 8.5%)]. On multivariate analysis, older age at the onset of pituitary disease predicted a greater increase in LS BMD on GH replacement (r = 0.55, P < 0.0001).
Conclusions In a population of GH naive adults, GH replacement led to a significant increase in LS BMD over baseline, but no change in FN BMD. The potential for greater BMD improvement on GH replacement therapy in adults with disease of later onset should be considered when making treatment decisions in this patient population.
C1 [Tritos, Nicholas A.; Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Tritos, Nicholas A.; Biller, Beverly M. K.] Harvard Univ, Sch Med, Boston, MA USA.
[Hamrahian, Amir H.] Cleveland Clin, Dept Diabet Endocrinol & Metab, Cleveland, OH 44106 USA.
[King, Donna] Pfizer Inc, New York, NY USA.
[Greenspan, Susan L.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Cook, David M.] Oregon Hlth & Sci Univ, Dept Endocrinol, Portland, OR 97201 USA.
[Jonsson, Peter J.; Koltowska-Haggstrom, Maria] Pfizer Inc, Pfizer Endocrine Care, Sollentuna, Sweden.
RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 0 Emerson Pl,Suite 112, Boston, MA 02114 USA.
EM ntritos@partners.org
FU Pfizer, Inc.; Pfizer; Ipsen; Novartis; Eli Lilly; Warner Chilcott;
Tarsa; Novo Nordisk; Serono
FX KIMS is sponsored by Pfizer, Inc. N.A.T., A.H.H., S.L.G., D.M.C. and
B.M.K.B. were not compensated for their contributions to this
manuscript.; N.A.T. has been a recipient of research funding from Pfizer
and Ipsen, and received consulting fees from Pfizer; spouse is an
employee of Pfizer. A.H.H. has been a recipient of lecture fees from
Novartis, Ipsen and Pfizer, and has served as consultant to Ipsen and
Pfizer. S.L.G. has been a recipient of research funding from Eli Lilly,
Warner Chilcott, Tarsa, and has consulted and served on an advisory
board for Amgen and Merck. D.K., P.J.J. and M.K-H. are full-time
employees of Pfizer. B.M.K.B. has been a recipient of research funding
from Pfizer, Novo Nordisk and Serono, has served on an advisory board
with consulting fees from Pfizer and Novo Nordisk.
NR 34
TC 5
Z9 5
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD AUG
PY 2013
VL 79
IS 2
BP 178
EP 184
DI 10.1111/cen.12132
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 180CP
UT WOS:000321570800006
PM 23278636
ER
PT J
AU Bredella, MA
McManus, S
Misra, M
AF Bredella, Miriam A.
McManus, Shilpa
Misra, Madhusmita
TI Impact of metformin monotherapy versus metformin with
oestrogen-progesterone on lipids in adolescent girls with polycystic
ovarian syndrome
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID COMBINED ORAL-CONTRACEPTIVES; INSULIN-SENSITIZING AGENTS;
HYPERINSULINEMIC HYPERANDROGENISM; MYOCARDIAL-INFARCTION;
FLUTAMIDE-METFORMIN; 2 FORMS; WOMEN; THERAPY; TESTOSTERONE; METAANALYSIS
AB Objective Hyperinsulinaemia is an important determinant of the polycystic ovarian syndrome (PCOS). In addition to lifestyle measures, therapeutic strategies include the use of oestrogen-progesterone combination pills (EP), and insulin sensitizers such as metformin, either alone or in combination. Data are limited regarding the impact of metformin alone vs metformin with EP on cardiometabolic risk in overweight adolescents with PCOS. We hypothesized that metformin alone would lead to an improvement in HbA1C and lipid levels in overweight adolescent girls with PCOS compared with meformin with EP.
Study design Retrospective clinic-based therapy.
Patients and measurements We examined the effects of therapy with metformin alone (n = 14) vs metformin with EP (n = 13) on HbA1C and lipid parameters over 10-14 months in 27 overweight girls, drawn from a clinic population of adolescents with PCOS.
Results The groups did not differ for age, body mass index (BMI), HbA1C or baseline lipids. After at least 10 months, the metformin only group compared with the metformin and EP group had a decrease in total cholesterol (-0.605 +/- 0.100 vs 0.170 +/- 0.348 mM, P = 0.02, nonparametric test) and triglycerides (-0.342 +/- 0.184 vs 0.262 +/- 0.133 mM, P = 0.02), despite similar changes in BMI (-1.6 +/- 0.7 vs 0.6 +/- 2.1 kg/m(2), P = 0.25) and HbA1C (0.03 +/- 0.06 vs 0.03 +/- 0.13%, P = 0.99). Differences between groups remained significant after controlling for baseline parameters and for changes in BMI.
Conclusion Metformin alone more effectively improves lipid parameters than metformin with EP in adolescent PCOS, as indicated by a decrease in total cholesterol and triglycerides. This effect is not related to BMI changes.
C1 [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Bredella, Miriam A.; McManus, Shilpa; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA.
[McManus, Shilpa; Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA.
[Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, Boston, MA 02114 USA.
EM mmisra@partners.org
FU NICHD NIH HHS [K24 HD071843]
NR 25
TC 8
Z9 12
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD AUG
PY 2013
VL 79
IS 2
BP 199
EP 203
DI 10.1111/cen.12028
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 180CP
UT WOS:000321570800009
PM 22928702
ER
PT J
AU Wiggs, JL
Howell, GR
Linkroum, K
Abdrabou, W
Hodges, E
Braine, CE
Pasquale, LR
Hannon, GJ
Haines, JL
John, SWM
AF Wiggs, J. L.
Howell, G. R.
Linkroum, K.
Abdrabou, W.
Hodges, E.
Braine, C. E.
Pasquale, L. R.
Hannon, G. J.
Haines, J. L.
John, S. W. M.
TI Variations in COL15A1 and COL18A1 influence age of onset of primary open
angle glaucoma
SO CLINICAL GENETICS
LA English
DT Article
DE collagen; glaucoma; modifying gene; myocilin
ID AMINO-ACID SUBSTITUTIONS; GENETIC-HETEROGENEITY; GLN368STOP MUTATION;
MYOCILIN MUTATION; COLLAGEN-XV; MOUSE MODEL; POLYMORPHISM; EXPRESSION;
ENDOSTATIN; MODIFIER
AB Primary open angle glaucoma (POAG) is a genetically and phenotypically complex disease that is a leading cause of blindness worldwide. Previously we completed a genome-wide scan for early-onset POAG that identified a locus on 9q22 (GLC1J). To identify potential causative variants underlying GLC1J, we used targeted DNA capture followed by high throughput sequencing of individuals from four GLC1J pedigrees, followed by Sanger sequencing to screen candidate variants in additional pedigrees. A mutation likely to cause early-onset glaucoma was not identified, however COL15A1 variants were found in the youngest affected members of 7 of 15 pedigrees with variable disease onset. In addition, the most common COL15A1 variant, R163H, influenced the age of onset in adult POAG cases. RNA in situ hybridization of mouse eyes shows that Col15a1 is expressed in the multiple ocular structures including ciliary body, astrocytes of the optic nerve and cells in the ganglion cell layer. Sanger sequencing of COL18A1, a related multiplexin collagen, identified a rare variant, A1381T, in members of three additional pedigrees with early-onset disease. These results suggest genetic variation in COL15A1 and COL18A1 can modify the age of onset of both early and late onset POAG.
C1 [Wiggs, J. L.; Linkroum, K.; Abdrabou, W.; Pasquale, L. R.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Wiggs, J. L.; Linkroum, K.; Abdrabou, W.; Pasquale, L. R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Howell, G. R.; Braine, C. E.; John, S. W. M.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Hodges, E.; Hannon, G. J.] Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
[Hodges, E.; Hannon, G. J.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA.
[Haines, J. L.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA.
[John, S. W. M.] Howard Hughes Med Inst, Bar Harbor, ME USA.
RP Wiggs, JL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM janey_wiggs@meei.harvard.edu
FU NIH [EY00947, EY015872, EY010886, P30 Ey014104, EY011721, EY021525]; Pew
Foundation; Kathryn Davis and family
FX This work was supported by NIH EY00947 (J. L. W.), EY015872 (J. L. W.),
EY010886 (J. L. W.), P30 Ey014104 (J. L. W.), NIH EY011721 (S. W. M.
J.), NIH EY021525 (G. R. H.), the Pew Foundation and Kathryn Davis and
family. S. W. M. J. is an investigator of the Howard Hughes Medical
Institute.
NR 40
TC 9
Z9 9
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD AUG
PY 2013
VL 84
IS 2
BP 167
EP 174
DI 10.1111/cge.12176
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 179CN
UT WOS:000321495800010
PM 23621901
ER
PT J
AU Branda, JA
Strle, F
Strle, K
Sikand, N
Ferraro, MJ
Steere, AC
AF Branda, John A.
Strle, Franc
Strle, Klemen
Sikand, Nikhil
Ferraro, Mary Jane
Steere, Allen C.
TI Performance of United States Serologic Assays in the Diagnosis of Lyme
Borreliosis Acquired in Europe
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE Lyme; Borrelia burgdorferi; VlsE; C6; diagnosis
ID BURGDORFERI SENSU-LATO; LINKED IMMUNOSORBENT ASSAYS; STANDARDIZED
WESTERN BLOTS; VARIABLE SURFACE-ANTIGEN; C6 PEPTIDE ELISA;
INTERPRETATION CRITERIA; ANTIBODY-RESPONSE; ERYTHEMA MIGRANS; DISEASE;
VLSE
AB Background. Physicians in the United States sometimes need to evaluate a patient for suspected Lyme borreliosis (LB) who may have acquired the infection in Europe. Using serum samples from European LB patients, we compared the performance of European and US serodiagnostic tests, including newer-generation assays containing Vmp-like sequence, expressed or its C6 peptide.
Methods. The sensitivity of each assay was determined using 64 serum samples from LB patients with early or late disease manifestations who acquired the infection in Europe. Specificity was measured using 100 sera from healthy subjects from a nonendemic area.
Results. For the detection of European-acquired infection, conventional 2-tiered testing (enzyme-linked immunosorbent assay [ ELISA] followed by immunoblotting) using US assays had an overall sensitivity and specificity of 52% and 100%, compared with 81% (P = .0007) and 99% (P = 1.00) using analogous European tests. The sensitivity of a US C6 ELISA used as a stand-alone test (88% overall) was statistically comparable to that of conventional 2-tiered testing using European tests (P = .47) and was 100% specific. Similarly, an alternative 2-tiered algorithm using a standard US ELISA followed by a C6 ELISA was comparably sensitive (84% overall) compared with conventional 2-tiered testing using European assays (P = .82), and specificity remained 100%.
Conclusions. European assays outperformed analogous US assays in a conventional 2-tiered testing algorithm. However, a C6 ELISA used as a stand-alone test or in the second tier of a 2-tiered algorithm performed comparably to conventional 2-tiered testing using European assays, and can be used for evaluation of any patient, regardless of travel history.
C1 [Branda, John A.; Ferraro, Mary Jane] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ferraro, Mary Jane; Steere, Allen C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Strle, Klemen; Sikand, Nikhil; Steere, Allen C.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Strle, Franc] Univ Med Ctr Ljubljana, Dept Infect Dis, Ljubljana, Slovenia.
RP Branda, JA (reprint author), Massachusetts Gen Hosp, Clin Microbiol Lab, GRB 526,55 Fruit St, Boston, MA 02114 USA.
EM branda.john@mgh.harvard.edu
FU Department of Pathology, Massachusetts General Hospital, Boston
FX This work was funded by an Austin L. Vickery Jr award from the
Department of Pathology, Massachusetts General Hospital, Boston.
NR 40
TC 27
Z9 27
U1 1
U2 10
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 AUG 1
PY 2013
VL 57
IS 3
BP 333
EP 340
DI 10.1093/cid/cit235
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 182IA
UT WOS:000321733700002
PM 23592827
ER
PT J
AU Demircay, E
Hornicek, FJ
Mankin, HJ
Degroot, H
AF Demircay, Emre
Hornicek, Francis John, Jr.
Mankin, Henry J.
Degroot, Henry, III
TI Malignant Lymphoma of Bone: A Review of 119 Patients
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Review
ID PROGNOSTIC-FACTORS
AB Lymphoma of bone is uncommon. As a result of this, many aspects of primary lymphoma of bone (PLB) are controversial: the definition, treatment strategies, response criteria, and prognostic factors.
We sought to determine the following in an analysis from a single center over a four-decade period: (1) 5-year disease-free survival of patients with PLB as well as those with systemic lymphoma with bone involvement; and (2) whether prognostic factors (sex, site of tumor, age) were associated with 5-year survival.
A total of 119 patients with lymphoma involving the musculoskeletal system were retrospectively evaluated. Among these, 94 patients who had a minimum followup of 6 months (mean, 67 months; range, 6 months to 34 years) were further analyzed for the skeletal site of involvement, the orthopaedic intervention(s) needed, and survival. The overall median age was 45 years (range, 7-87 years). The female-to-male ratio was 1:1.53. There were 70 (65 unifocal, five multifocal) patients with PLB. The femur was the most frequent site involved. Appendicular skeleton involvement was substantially higher in patients with PLB. Thirty-four (36%) patients had at least one surgical intervention. Fourteen patients (41%) needed more than one major surgical intervention.
The disease-free 5-year survival for patients with PLB was 81% and for the patients with systemic lymphoma with bone involvement, it was 44%. The disease-free 5-year survival of the patients with PLB younger than 60 years old and 60 years old or older was 90% and 62%, respectively. Age was the only prognostic factor on survival of patients with PLB.
Orthopaedic intervention was usually needed for pathologic fractures, avascular necrosis, spinal cord compression, or for the lesions of the weightbearing bones compromising stability or joint motion. The potential for long-term survival suggests the use of implants and techniques that have the best chance of long-term success.
Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
C1 [Demircay, Emre] Baskent Univ, Dept Orthoped Surg, Sch Med, TR-34662 Istanbul, Turkey.
[Hornicek, Francis John, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Mankin, Henry J.] Harvard Univ, Sch Med, Boston, MA USA.
[Degroot, Henry, III] Newton Wellesley Hosp, Newton Lower Falls, MA 02162 USA.
RP Demircay, E (reprint author), Baskent Univ, Dept Orthoped Surg, Sch Med, Oymaci SN 7, TR-34662 Istanbul, Turkey.
EM emredemircay@hotmail.com
NR 18
TC 11
Z9 11
U1 0
U2 5
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 AUG
PY 2013
VL 471
IS 8
BP 2684
EP 2690
DI 10.1007/s11999-013-2991-x
PG 7
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 179VM
UT WOS:000321549600041
PM 23591933
ER
PT J
AU Maahs, DM
Caramori, L
Cherney, DZI
Galecki, AT
Gao, CY
Jalal, D
Perkins, BA
Pop-Busui, R
Rossing, P
Mauer, M
Doria, A
AF Maahs, David M.
Caramori, Luiza
Cherney, David Z. I.
Galecki, Andrzej T.
Gao, Chuanyun
Jalal, Diana
Perkins, Bruce A.
Pop-Busui, Rodica
Rossing, Peter
Mauer, Michael
Doria, Alessandro
CA PERL Consortium
TI Uric Acid Lowering to Prevent Kidney Function Loss in Diabetes: The
Preventing Early Renal Function Loss (PERL) Allopurinol Study
SO CURRENT DIABETES REPORTS
LA English
DT Article
DE Uric acid; Kidney disease; Diabetes; Diabetic kidney disease; Glomerular
filtration rate; Allopurinol; Diabetic nephropathy; Randomized clinical
trial; Type 1 diabetes; PERL trial
ID GLOMERULAR-FILTRATION-RATE; TOXIC EPIDERMAL NECROLYSIS;
STEVENS-JOHNSON-SYNDROME; BLOOD-PRESSURE; ENDOTHELIAL DYSFUNCTION;
METABOLIC SYNDROME; FUNCTION DECLINE; ESSENTIAL-HYPERTENSION;
INDEPENDENT MECHANISM; CARDIOVASCULAR RISK
AB Diabetic kidney disease causes significant morbidity and mortality among people with type 1 diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately curb this problem and therefore a major need for novel treatment approaches exists. Multiple observations link serum uric acid levels to kidney disease development and progression in diabetes and strongly argue that uric acid lowering should be tested as one such novel intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the completion of appropriate trials at earlier stages.
C1 [Maahs, David M.] Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA.
[Maahs, David M.; Jalal, Diana] Univ Colorado Denver, Div Renal Dis & Hypertens, Aurora, CO USA.
[Caramori, Luiza; Mauer, Michael] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
[Caramori, Luiza; Mauer, Michael] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Cherney, David Z. I.; Perkins, Bruce A.] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Cherney, David Z. I.] Univ Toronto, Div Nephrol, Toronto, ON, Canada.
[Galecki, Andrzej T.] Univ Michigan, Sch Med, Inst Gerontol, Div Geriatr, Ann Arbor, MI USA.
[Galecki, Andrzej T.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Gao, Chuanyun] Joslin Diabet Ctr, Joslin Clin, Boston, MA 02215 USA.
[Perkins, Bruce A.] Univ Toronto, Div Endocrinol, Toronto, ON, Canada.
[Pop-Busui, Rodica] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA.
[Rossing, Peter] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
[Rossing, Peter] Univ Aarhus, HEALTH, Aarhus, Denmark.
[Rossing, Peter] Univ Copenhagen, NNF CBMR, Copenhagen, Denmark.
[Doria, Alessandro] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA.
[Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA.
EM alessandro.doria@joslin.harvard.edu
OI rossing, peter/0000-0002-1531-4294
FU NIDDK [DK075360]; Juvenile Diabetes Research Foundation; NIH [R03
DK094484, R34 DK097808]; Juvenile Diabetes Research Foundation (JDRF)
[17-2012-377]
FX Dr. Maahs was supported by a grant from NIDDK (DK075360). Dr. Caramori
is supported by a Career Development Award from the Juvenile Diabetes
Research Foundation. This project was supported by NIH grants R03
DK094484 and R34 DK097808, and by grant 17-2012-377 from the Juvenile
Diabetes Research Foundation (JDRF). Its contents are the authors' sole
responsibility and do not necessarily represent official NIH or JDRF
views.
NR 81
TC 45
Z9 47
U1 1
U2 7
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1534-4827
J9 CURR DIABETES REP
JI Curr. Diabetes Rep.
PD AUG
PY 2013
VL 13
IS 4
BP 550
EP 559
DI 10.1007/s11892-013-0381-0
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 179JR
UT WOS:000321517000011
PM 23649945
ER
PT J
AU Stanton, RC
AF Stanton, Robert C.
TI Combination Use of Angiotensin Converting Enzyme Inhibitors and
Angiotensin Receptor Blockers in Diabetic Kidney Disease
SO CURRENT DIABETES REPORTS
LA English
DT Article
DE Diabetic kidney disease; ACE inhibitors; Angiotensin receptor blockers
ID ALDOSTERONE SYSTEM; ACE-INHIBITION; END-POINTS; NEPHROPATHY; BLOCKADE;
THERAPY; HYPERTENSION; PROGRESSION; LOSARTAN; OUTCOMES
AB Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) have played a major role in slowing the progression of diabetic kidney disease, since they lower urine protein levels, lower blood pressure, and slow progression. Studies have suggested that the combination of ACE-I and ARB offered greater benefits for patients with diabetic kidney disease. In 2008, the large ONTARGET study reported no benefit with combination therapy, as compared with monotherapy. This study has changed practice patterns, but few patients in this study had diabetic kidney disease. In this review, the data in favor of the combination use of these agents in patients with diabetic kidney disease and data against the combination are reviewed. At this time, there is little support for using the combination in diabetic patients with no kidney disease or early stage diabetic kidney disease. But there are patients who may benefit from combination use.
C1 [Stanton, Robert C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Boston, MA USA.
[Stanton, Robert C.] Joslin Diabet Ctr, Kidney & Hypertens Sect, Boston, MA 02215 USA.
RP Stanton, RC (reprint author), Joslin Diabet Ctr, Kidney & Hypertens Sect, 1 Joslin Pl, Boston, MA 02215 USA.
EM Robert.Stanton@joslin.harvard.edu
NR 39
TC 0
Z9 0
U1 0
U2 5
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1534-4827
EI 1539-0829
J9 CURR DIABETES REP
JI Curr. Diabetes Rep.
PD AUG
PY 2013
VL 13
IS 4
BP 567
EP 573
DI 10.1007/s11892-013-0391-y
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 179JR
UT WOS:000321517000013
PM 23653011
ER
PT J
AU Lipinski, B
Pretorius, E
AF Lipinski, Boguslaw
Pretorius, Etheresia
TI Iron-Induced Fibrin in Cardiovascular Disease
SO CURRENT NEUROVASCULAR RESEARCH
LA English
DT Article
DE Cardiovascular disease; fibrinogen; free radicals; inflammation; iron;
parafibrin; thrombosis
ID ERYTHROCYTE SEDIMENTATION-RATE; PERIPHERAL ARTERIAL-DISEASE; ACUTE
CORONARY SYNDROMES; SERUM-ALBUMIN; OXIDATIVE STRESS; HEART-DISEASE;
ATHEROSCLEROSIS; RISK; MECHANISMS; INFLAMMATION
AB Accumulating evidence within the last two decades indicates the association between cardiovascular disease (CVD) and chronic inflammatory state. Under normal conditions fibrin clots are gradually degraded by the fibrinolytic enzyme system, so no permanent insoluble deposits remain in the circulation. However, fibrinolytic therapy in coronary and cerebral thrombosis is ineffective unless it is installed within 3-5 hours of the onset. We have shown that trivalent iron (FeIII) initiates a hydroxyl radical-catalyzed conversion of fibrinogen into a fibrin-like polymer (parafibrin) that is remarkably resistant to the proteolytic dissolution and thus promotes its intravascular deposition. Here we suggest that the persistent presence of proteolysis-resistant fibrin clots causes chronic inflammation. We study the effects of certain amphiphilic substances on the iron-and thrombin-induced fibrinogen polymerization visualized using scanning electron microscopy. We argue that the culprit is an excessive accumulation of free iron in blood, known to be associated with CVD. The only way to prevent iron overload is by supplementation with iron chelating agents. However, administration of free radical scavengers as effective protection against persistent presence of fibrin-like deposits should also be investigated to contribute to the prevention of cardiovascular and other degenerative diseases.
C1 [Lipinski, Boguslaw] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA.
[Pretorius, Etheresia] Univ Pretoria, Fac Hlth Sci, Dept Physiol, ZA-0007 Arcadia, South Africa.
RP Pretorius, E (reprint author), Univ Pretoria, Fac Hlth Sci, Dept Physiol, Private Bag X323, ZA-0007 Arcadia, South Africa.
EM resia.pretorius@up.ac.za
NR 66
TC 14
Z9 14
U1 0
U2 7
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1567-2026
J9 CURR NEUROVASC RES
JI Curr. Neurovasc. Res.
PD AUG
PY 2013
VL 10
IS 3
BP 269
EP 274
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 173WW
UT WOS:000321114000011
PM 23721262
ER
PT J
AU Lancellotti, P
Nkomo, VT
Badano, LP
Bergler, J
Bogaert, J
Davin, L
Cosyns, B
Coucke, P
Dulgheru, R
Edvardsen, T
Gaemperli, O
Galderisi, M
Griffin, B
Heidenreich, PA
Nieman, K
Plana, JC
Port, SC
Scherrer-Crosbie, M
Schwartz, RG
Sebag, IA
Voigt, JU
Wann, S
Yang, PC
AF Lancellotti, Patrizio
Nkomo, Vuyisile T.
Badano, Luigi P.
Bergler, Jutta
Bogaert, Jan
Davin, Laurent
Cosyns, Bernard
Coucke, Philippe
Dulgheru, Raluca
Edvardsen, Thor
Gaemperli, Oliver
Galderisi, Maurizio
Griffin, Brian
Heidenreich, Paul A.
Nieman, Koen
Plana, Juan C.
Port, Steven C.
Scherrer-Crosbie, Marielle
Schwartz, Ronald G.
Sebag, Igal A.
Voigt, Jens-Uwe
Wann, Samuel
Yang, Phillip C.
CA European Soc Cardiol Working Grp N
TI Expert consensus for multi-modality imaging evaluation of cardiovascular
complications of radiotherapy in adults: a report from the European
Association of Cardiovascular Imaging and the American Society of
Echocardiography
SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
LA English
DT Article
DE radiotherapy; echocardiography; cardiac magnetic resonance; nuclear
cardiology; cardiac computed tomography; heart disease
ID CORONARY-ARTERY-DISEASE; LONG-TERM SURVIVORS; SPECKLE-TRACKING
ECHOCARDIOGRAPHY; COMPUTED-TOMOGRAPHY ANGIOGRAPHY; VENTRICULAR DIASTOLIC
FUNCTION; DIFFUSE MYOCARDIAL FIBROSIS; CONGESTIVE-HEART-FAILURE;
BREAST-CANCER PATIENTS; NATIVE VALVE DISEASE; HODGKINS-DISEASE
AB Cardiac toxicity is one of the most concerning side effects of anti-cancer therapy. The gain in life expectancy obtained with anti-cancer therapy can be compromised by increased morbidity and mortality associated with its cardiac complications. While radiosensitivity of the heart was initially recognized only in the early 1970s, the heart is regarded in the current era as one of the most critical dose-limiting organs in radiotherapy. Several clinical studies have identified adverse clinical consequences of radiation-induced heart disease (RIHD) on the outcome of long-term cancer survivors. A comprehensive review of potential cardiac complications related to radiotherapy is warranted. An evidence-based review of several imaging approaches used to detect, evaluate, and monitor RIHD is discussed. Recommendations for the early identification and monitoring of cardiovascular complications of radiotherapy by cardiac imaging are also proposed.
C1 [Lancellotti, Patrizio] Univ Liege Hosp, CHU Sart Tilman, Dept Cardiol, GIGA Cardiovasc Sci,Heart Valve Clin, B-4000 Liege, Belgium.
[Nkomo, Vuyisile T.] Mayo Clin, Div Cardiovasc Dis & Internal Med, Rochester, MN USA.
[Badano, Luigi P.] Univ Padua, Dept Cardiac Vasc & Thorac Sci, Padua, Italy.
[Bergler, Jutta] Med Univ Vienna, Dept Cardiol, Vienna, Austria.
[Bogaert, Jan] Catholic Univ Louvain, Dept Radiol, Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium.
[Davin, Laurent] CHU Sart Tilman, Dept Cardiovasc Imaging & Invas Cardiol, B-4000 Liege, Belgium.
[Cosyns, Bernard] UZ Brussel, Ctr Voor Hart Vaatziekten CHVZ, Dept Cardiol, B-1090 Brussels, Belgium.
[Coucke, Philippe] Univ Hosp, CHU Liege, Dept Radiotherapy, Liege, Belgium.
[Dulgheru, Raluca] Univ Med & Pharm Carol Davila, Emergency Univ Hosp, Dept Cardiol, Bucharest, Romania.
[Edvardsen, Thor] Oslo Univ Hosp, Rikshosp, Dept Cardiol, Oslo, Norway.
[Gaemperli, Oliver] Univ Zurich Hosp, Ctr Cardiovasc, CH-8091 Zurich, Switzerland.
[Galderisi, Maurizio] Federico II Univ Hosp, Cardioangiol CCU, Dept Clin & Expt Med, Naples, Italy.
[Griffin, Brian; Plana, Juan C.] Cleveland Clin, Dept Cardiovasc Med, Sect Cardiovasc Imaging, Cleveland, OH 44106 USA.
[Heidenreich, Paul A.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Heidenreich, Paul A.] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
[Nieman, Koen] Erasmus Univ, Med Ctr, Dept Cardiol, Rotterdam, Netherlands.
[Nieman, Koen] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands.
[Port, Steven C.] Aurora Hlth Care, Aurora Cardiovasc Serv, Milwaukee, WI USA.
[Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA.
[Schwartz, Ronald G.] Univ Rochester, Med Ctr, Dept Med, Div Cardiol, Rochester, NY 14642 USA.
[Schwartz, Ronald G.] Univ Rochester, Med Ctr, Div Nucl Med, Dept Imaging Sci, Rochester, NY 14642 USA.
[Sebag, Igal A.] Sir Mortimer B Davis Jewish Hosp, Dept Med, Div Cardiol, Montreal, PQ H3T 1E2, Canada.
[Sebag, Igal A.] McGill Univ, Lady Davis Inst Med Res, Montreal, PQ, Canada.
[Voigt, Jens-Uwe] Catholic Univ Louvain, Univ Hosp Gasthuisberg, Dept Cardiovasc Dis, B-3000 Louvain, Belgium.
[Wann, Samuel] Columbia St Marys Healthcare Milwaukee, Heart Failure Program, Milwaukee, WI USA.
[Yang, Phillip C.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
RP Lancellotti, P (reprint author), Univ Liege Hosp, CHU Sart Tilman, Dept Cardiol, GIGA Cardiovasc Sci,Heart Valve Clin, B-4000 Liege, Belgium.
EM plancellotti@chu.ulg.ac.be
RI Edvardsen, Thor/F-4079-2012; bogaert, jan/E-6181-2012;
OI Edvardsen, Thor/0000-0002-3800-765X; Heidenreich,
Paul/0000-0001-7730-8490; Galderisi, Maurizio/0000-0003-0311-9069;
Badano, Luigi/0000-0002-0379-3283
NR 121
TC 61
Z9 63
U1 1
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2047-2404
J9 EUR HEART J-CARD IMG
JI Eur. Heart J.-Cardiovasc. Imaging
PD AUG
PY 2013
VL 14
IS 8
BP 721
EP 740
DI 10.1093/ehjci/jet123
PG 20
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 183QV
UT WOS:000321833100001
PM 23847385
ER
PT J
AU Martinez-Martin, P
Rojo-Abuin, JM
Dujardin, K
Pontone, GM
Weintraub, D
Forjaz, MJ
Starkstein, S
Leentjens, AFG
AF Martinez-Martin, P.
Rojo-Abuin, J. M.
Dujardin, K.
Pontone, G. M.
Weintraub, D.
Forjaz, M. J.
Starkstein, S.
Leentjens, A. F. G.
TI Designing a new scale to measure anxiety symptoms in Parkinson's
disease: item selection based on canonical correlation analysis
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Article
DE anxiety; assessment; canonical correlation; Parkinson's disease; rating
scales
ID PSYCHOMETRIC PROPERTIES; HOSPITAL ANXIETY; DEPRESSION SCALE;
RATING-SCALES; DISORDERS; INVENTORY; PREVALENCE; VALIDATION; MINI
AB Background and purpose: The lack of appropriate measures has hindered the research on anxiety syndromes in Parkinson's disease (PD). The objective of the present cross-sectional, international study was to identify shared elements and grouping of components from anxiety scales as a basis for designing a new scale for use in PD.
Methods: For this purpose, 342 consecutive PD patients were assessed by means of the Mini International Neuropsychiatric Inventory (depression and anxiety sections), the Clinical Global Impression of severity of the anxiety symptoms, the Hamilton Anxiety Rating Scale (HARS), the Neuropsychiatric Inventory (section E), the Beck Anxiety Inventory (BAI) and the Anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A).
Results: As the HADS-A showed a weak correlation with the HARS and BAI, it was not considered for more analyses. HARS and BAI exploratory factor analysis identified nine factors (62% of the variance), with only two of them combining items from both scales. Therefore, a canonical correlation model (a method to identify relations between components of two groups of variables) was built and it showed four factors grouping items from both scales: the first factor corresponded to 'generalized anxiety'; the second factor included muscular, sensory and autonomic 'non-specific somatic symptoms'; the third factor was dominated by 'respiratory symptoms'; and the fourth factor included 'cardiovascular symptoms'.
Conclusions: BAI is heavily focused on panic symptoms, whilst HARS is more focused towards generalized anxiety symptoms. The new scale should include additional components in order to assess both episodic and persistent anxiety as well as items for evaluation of avoidance behaviour.
C1 [Martinez-Martin, P.; Forjaz, M. J.] Carlos III Inst Hlth, Consortium Biomed Res Neurodegenerat Dis CIBERNED, Madrid, Spain.
[Rojo-Abuin, J. M.] Spanish Council Sci Res, Ctr Human & Social Sci, Dept Stat, Madrid, Spain.
[Dujardin, K.] Univ Lille 2, EA 4559, Lab Neurosci Fonct & Pathol, Lille, France.
[Pontone, G. M.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Weintraub, D.] Univ Penn, Pereleman Sch Med, Philadelphia, PA 19104 USA.
[Weintraub, D.] Philadelphia VA Med Ctr, PADRECC, Philadelphia, PA USA.
[Weintraub, D.] Philadelphia VA Med Ctr, MIRECC, Philadelphia, PA USA.
[Forjaz, M. J.] Carlos III Inst Hlth, Natl Sch Publ Hlth, Madrid, Spain.
[Forjaz, M. J.] Alzheimer Ctr Reina Sofia Fdn, Madrid 28031, Spain.
[Starkstein, S.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia.
[Starkstein, S.] Fremantle Hosp, Fremantle, WA, Australia.
[Leentjens, A. F. G.] Maastricht Univ Med Ctr, Dept Psychiat, Maastricht, Netherlands.
RP Martinez-Martin, P (reprint author), Alzheimer Ctr Reina Sofia Fdn, C Valderrebollo 5, Madrid 28031, Spain.
EM pmartinez@fundacioncien.es
OI Forjaz, Maria Joao/0000-0003-3935-962X
FU Michael J. Fox Foundation for Parkinson Research
FX This study was sponsored by a grant from the Michael J. Fox Foundation
for Parkinson Research (MJFF; www.michaeljfox.org).
NR 27
TC 9
Z9 9
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD AUG
PY 2013
VL 20
IS 8
BP 1198
EP 1203
DI 10.1111/ene.12160
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 176UM
UT WOS:000321331100018
PM 23581431
ER
PT J
AU Cheng, G
Kwee, TC
Basu, S
Alavi, A
AF Cheng, Gang
Kwee, Thomas C.
Basu, Sandip
Alavi, Abass
TI Critical considerations on the combined use of F-18-FDG and
F-18-fluoride for PET assessment of metastatic bone disease
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Editorial Material
ID POSITRON-EMISSION-TOMOGRAPHY; FDG-PET; LUNG-CANCER; SKELETAL
SCINTIGRAPHY; PROSTATE-CANCER; COMPLIMENTARY ROLE; CARCINOMA; MARROW;
SCAN; MALIGNANCY
C1 [Cheng, Gang] Philadelphia VA Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA.
[Kwee, Thomas C.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands.
[Basu, Sandip] Bhabha Atom Res Ctr, Radiat Med Ctr, Tata Mem Hosp Annexe, Bombay 400012, Maharashtra, India.
[Cheng, Gang; Alavi, Abass] Hosp Univ Penn, Dept Radiol, Div Nucl Med, Philadelphia, PA 19104 USA.
RP Alavi, A (reprint author), Hosp Univ Penn, Dept Radiol, Div Nucl Med, 3400 Spruce St, Philadelphia, PA 19104 USA.
EM abass.alavi@uphs.upenn.edu
NR 43
TC 5
Z9 5
U1 2
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD AUG
PY 2013
VL 40
IS 8
BP 1141
EP 1145
DI 10.1007/s00259-013-2459-y
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 179LE
UT WOS:000321521000002
PM 23695838
ER
PT J
AU Wai, B
Thai, WE
Brown, H
Truong, QA
AF Wai, Bryan
Thai, Wai-ee
Brown, Heather
Truong, Quynh A.
TI Novel phase-based noise reduction strategy for quantification of left
ventricular function and mass assessment by cardiac CT: Comparison with
cardiac magnetic resonance
SO EUROPEAN JOURNAL OF RADIOLOGY
LA English
DT Article
DE Left ventricular function; Left ventricular mass; Noise reduction;
Computed tomography
ID DUAL-SOURCE CT; PROGNOSTIC-SIGNIFICANCE; COMPUTED-TOMOGRAPHY;
ECHOCARDIOGRAPHY; ANGIOGRAPHY; ASSOCIATION; INFARCTION; DEATH
AB Background: Tube current modulation in retrospective ECG gated cardiac computed tomography (CT) results in increased image noise and may reduce the accuracy of left ventricular (LV) ejection fraction (EF) and mass assessment.
Objective: To examine the effects of a novel CT phase-based noise reduction (NR) algorithm on LV EF and mass quantification as compared to cardiac magnetic resonance (CMR).
Methods: In 40 subjects, we compared the LV EF and mass between CT and CMR. In a subset of 24 subjects with tube current modulated CT, the effect of phase-based noise reduction strategies on contrast-to-noise ratio (CNR) and the assessment of LV EF and mass was compared to CMR.
Results: There was excellent correlation between CT and CMR for EF (r = 0.94) and mass (r = 0.97). As compared to CMR, the limits of agreement improved with increasing strength of NR strategy. There was a systematic underestimation of LV mass by CT compared to CMR with no NR (-10.3 +/- 10.1 g) and low NR (-10.3 +/- 12.5 g), but was attenuated with high NR (-0.5 +/- 8.3 g). Studies without NR had lower CNR compared to low and high NR at both the ES phase and ED phase (all p < 0.01).
Conclusions: A high NR strategy on tube current modulated functional cardiac CT improves correlation of EF compared to CMR and reduces variability of EF and mass evaluation by increasing the CNR. In an effort to reduce radiation dose with tube current modulation, this strategy provides better image quality when LV function and mass quantification is needed. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Wai, Bryan; Thai, Wai-ee; Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol & Dept Radiol,Cardiac MR PET CT Progr, Boston, MA USA.
[Brown, Heather] Qi Imaging, Redwood City, CA USA.
RP Wai, B (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM bwai@partners.org
FU NIH [K23HL098370, L30HL093896]; Qi Imaging
FX Dr. Quynh Truong received support from NIH grant K23HL098370 and
L30HL093896 and research support from Qi Imaging.
NR 21
TC 3
Z9 4
U1 0
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 AUG
PY 2013
VL 82
IS 8
BP E337
EP E341
DI 10.1016/j.ejrad.2013.02.023
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 179CV
UT WOS:000321496900006
PM 23522745
ER
PT J
AU Perry, DJ
AF Perry, Donna J.
TI Transcendental Method for Research with Human Subjects: A Transformative
Phenomenology for the Human Sciences
SO FIELD METHODS
LA English
DT Article
DE research; method; qualitative; Lonergan; phenomenology
ID QUALITATIVE RESEARCH; CARING RESEARCH; RIGOR
AB This article provides an overview of a qualitative research method called transcendental method for research with human subjects. The method employs a transformative phenomenological approach and was developed using the philosophy of Bernard Lonergan. Reflective use of this method suggests that it has both investigational and interventional qualities, with transformative potential for both researcher and study participants.
C1 [Perry, Donna J.] Univ Massachusetts, Grad Sch Nursing, Worcester, MA 01655 USA.
[Perry, Donna J.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Inst Patient Care, Boston, MA 02114 USA.
RP Perry, DJ (reprint author), Univ Massachusetts, Grad Sch Nursing, 55 Lake Ave North, Worcester, MA 01655 USA.
EM DonnaJ.Perry@umassmed.edu
NR 26
TC 4
Z9 4
U1 3
U2 11
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1525-822X
J9 FIELD METHOD
JI Field Methods
PD AUG
PY 2013
VL 25
IS 3
BP 262
EP 282
DI 10.1177/1525822X12467105
PG 21
WC Anthropology; Social Sciences, Interdisciplinary
SC Anthropology; Social Sciences - Other Topics
GA 184NT
UT WOS:000321898700003
ER
PT J
AU Gorin, Y
Block, K
AF Gorin, Yves
Block, Karen
TI Nox4 and diabetic nephropathy: With a friend like this, who needs
enemies?
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Review
DE Diabetic complications; Diabetic nephropathy; Hyperglycemia; Oxidative
stress; NADPH oxidases of the Nox family; Nox4; Reactive oxygen species;
Glomerular cell injury; Tubulointerstitial cell injury; Free radicals
ID SMOOTH-MUSCLE-CELLS; INDUCED OXIDATIVE STRESS; TUBULAR EPITHELIAL-CELLS;
MESSENGER-RNA TRANSLATION; DINUCLEOTIDE PHOSPHATE OXIDASE; GLOMERULAR
MESANGIAL CELLS; OXYGEN SPECIES PRODUCTION; KINASE-C-BETA;
NADPH-OXIDASE; NAD(P)H OXIDASE
AB Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, a complication of diabetes in the kidney. NADPH oxidases of the Nox family are a major source of reactive oxygen species in the diabetic kidney and are critical mediators of redox signaling in glomerular and tubulointerstitial cells exposed to the diabetic milieu. Here, we present an overview of the current understanding of the roles of Nox catalytic and regulatory subunits in the processes that control mesangial cell, podocyte, and tubulointerstitial cell injury induced by hyperglycemia and other predominant factors enhanced in the diabetic milieu, including the renin-angiotensin system and transforming growth factor-beta. The role of the Nox isoform Nox4 in the redox processes that alter renal biology in diabetes is highlighted. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Gorin, Yves; Block, Karen] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Block, Karen] South Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX 78229 USA.
RP Gorin, Y (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
EM gorin@uthscsa.edu; block@uthscsa.edu
OI Gorin, Yves/0000-0003-4048-6925
FU Juvenile Diabetes Research Foundation Multiproject Grants; NIH [RO1 DK
079996, RO1 CA 131272]; Veterans Administration
FX This work was supported by Juvenile Diabetes Research Foundation
Multiproject Grants (Y.G. and K.B.), NIH RO1 DK 079996 (Y.G.), NIH RO1
CA 131272 (K.B.), and the Veterans Administration (K.B.).
NR 190
TC 33
Z9 35
U1 2
U2 39
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 AUG
PY 2013
VL 61
BP 130
EP 142
DI 10.1016/j.freeradbiomed.2013.03.014
PG 13
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 168EA
UT WOS:000320687300014
PM 23528476
ER
PT J
AU Khalili, H
Higuchi, LM
Ananthakrishnan, AN
Richter, JM
Feskanich, D
Fuchs, CS
Chan, AT
AF Khalili, Hamed
Higuchi, Leslie M.
Ananthakrishnan, Ashwin N.
Richter, James M.
Feskanich, Diane
Fuchs, Charles S.
Chan, Andrew T.
TI Oral contraceptives, reproductive factors and risk of inflammatory bowel
disease
SO GUT
LA English
DT Article
DE Inflammatory bowel disease; Crohn's disease; ulcerative colitis; oral
contraceptive use; reproductive factors; Nurses' Health Study; Crohn's
colitis; epidemiology; cancer epidemiology; health service research;
gastrointestinal haemorrhage; IBD clinical; cancer prevention;
cyclooxygenase-2; aspirin; non-steroidal anti-inflammatory drugs;
chemoprevention; adenoma; inflammation; adenocarcinoma
ID CROHNS-DISEASE; ULCERATIVE-COLITIS; CIGARETTE-SMOKING; BARRIER FUNCTION;
OLMSTED COUNTY; WOMEN; METAANALYSIS; VALIDITY; COHORT; REPRODUCIBILITY
AB Background
Oral contraceptive use has been associated with risk of Crohn's disease (CD) and ulcerative colitis (UC).
Objective
To determine whether this association is confounded or modified by other important lifestyle and reproductive factors.
Design
A prospective cohort study was carried out of 117?375 US women enrolled since 1976 in the Nurses Health Study I (NHS I) and 115?077 women enrolled since 1989 in the Nurses' Health Study II (NHS II) with no prior history of UC or CD. These women had provided information every 2years, on age at menarche, oral contraceptive use, parity, menopause status and other risk factors. Diagnoses of CD and UC were confirmed by review of medical records. Cox proportional hazards models were used to calculate HRs and 95% CIs.
Results
Among 232?452 women with over 5?030?196 person-years of follow-up, 315 cases of CD and 392 cases of UC were recorded through 2007 in NHS II and 2008 in NHS I. Compared with never users of oral contraceptives, the multivariate-adjusted HRs for CD were 2.82 (95% CI 1.65 to 4.82) among current users and 1.39 (95% CI 1.05 to 1.85) among past users. The association between oral contraceptives and UC differed according to smoking history (p(heterogeneity)=0.04). Age at menarche, age at first birth and parity were not associated with risk of UC or CD.
Conclusion
In two large prospective cohorts of US women, oral contraceptive use was associated with risk of CD. The association between oral contraceptive use and UC was limited to women with a history of smoking.
C1 [Khalili, Hamed; Ananthakrishnan, Ashwin N.; Richter, James M.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Khalili, Hamed; Higuchi, Leslie M.; Ananthakrishnan, Ashwin N.; Richter, James M.; Feskanich, Diane; 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.
[Feskanich, Diane; Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA.
RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 728A, Boston, MA 02114 USA.
EM achan@partners.org
FU Crohn's and Colitis Foundation of American (CCFA); National Institute of
Diabetes and Digestive and Kidney Diseases [K08 DK064256]; American
Gastroenterological Association; [R01 CA137178]; [R01 CA050385]; [P01
CA87969]; [P30 DK043351]
FX Funded by R01 CA137178, R01 CA050385, P01 CA87969, P30 DK043351, K08
DK064256. ATC is a Damon Runyon Cancer Research Foundation clinical
investigator. HK is supported by a career development award from the
Crohn's and Colitis Foundation of American (CCFA). LH is supported by
National Institute of Diabetes and Digestive and Kidney Diseases (K08
DK064256). ANA is supported by a career research scholars award from the
American Gastroenterological Association.
NR 41
TC 48
Z9 48
U1 0
U2 15
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 AUG
PY 2013
VL 62
IS 8
BP 1153
EP 1159
DI 10.1136/gutjnl-2012-302362
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 176WQ
UT WOS:000321337600011
PM 22619368
ER
PT J
AU Tucker-Seeley, RD
Harley, AE
Stoddard, AM
Sorensen, GG
AF Tucker-Seeley, Reginald D.
Harley, Amy E.
Stoddard, Anne M.
Sorensen, Glorian G.
TI Financial Hardship and Self-Rated Health Among Low-Income Housing
Residents
SO HEALTH EDUCATION & BEHAVIOR
LA English
DT Article
DE community health; health disparities; mental health; social
determinants; social inequalities
ID ECONOMIC HARDSHIP; LIFE-COURSE; PSYCHOLOGICAL DISTRESS; PERCEIVED
STRESS; AMERICANS; STRAIN; DISPARITIES; VALIDITY; POVERTY; IMPACT
AB Background. Self-rated health (SRH) has been shown to be predictive of morbidity and mortality. Evidence also shows that SRH is socioeconomically patterned, although this association differs depending on the indicator of socioeconomic status used. The purpose of this study was to determine the association between SRH and financial hardship among residents of low-income housing. Methods. We analyzed cross-sectional data from the Health in Common Study (N = 828), an observational study to investigate social and physical determinants of cancer risk-related behaviors among residents of low-income housing in three cities in the Boston metropolitan area. Modified Poisson regression models were used to obtain the relative risk of low SRH (fair or poor), adjusting for demographic and socioeconomic characteristics. Results. Unadjusted models revealed that the respondents reporting financial hardship were 53% more likely to report low SRH compared with those not reporting financial hardship. After controlling for demographic characteristics, socioeconomic characteristics, and psychological distress, the results showed that those reporting financial hardship were 44% more likely to report low SRH. Conclusion. Our results suggest that financial hardship is a robust predictor of SRH; and over and above the influence of demographic and traditional socioeconomic indicators, and even psychological distress, financial hardship remains strongly associated with low SRH. Additional research needs to be conducted to further elucidate this pathway and to better understand the determinants of variability in financial hardship among low-income housing residents to ensure the most appropriate policy levers (e.g., housing-related policy, food-related policy) are chosen to improve health outcomes in this population.
C1 [Tucker-Seeley, Reginald D.; Sorensen, Glorian G.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Harley, Amy E.] Univ Wisconsin, Milwaukee, WI 53201 USA.
[Stoddard, Anne M.] New England Res Inst, Watertown, MA 02172 USA.
RP Tucker-Seeley, RD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW666A, Boston, MA 02215 USA.
EM reginald_tucker-seeley@dfci.harvard.edu
FU NCI NIH HHS [K05 CA108663, 5K05CA108663-05, 5R01CA111310-04]
NR 35
TC 7
Z9 7
U1 3
U2 16
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1090-1981
J9 HEALTH EDUC BEHAV
JI Health Educ. Behav.
PD AUG
PY 2013
VL 40
IS 4
BP 442
EP 448
DI 10.1177/1090198112463021
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 185DI
UT WOS:000321945000008
PM 23104979
ER
PT J
AU Berkowitz, SA
Aragon, K
Hines, J
Seligman, H
Lee, S
Sarkar, U
AF Berkowitz, Seth A.
Aragon, Katherine
Hines, Jonas
Seligman, Hilary
Lee, Sei
Sarkar, Urmimala
TI Do Clinical Standards for Diabetes Care Address Excess Risk for
Hypoglycemia in Vulnerable Patients? A Systematic Review
SO HEALTH SERVICES RESEARCH
LA English
DT Article
DE Diabetes mellitus; quality and safety; health disparities; vulnerable
populations; clinical guidelines
ID QUALITY-OF-CARE; GLYCEMIC CONTROL; FOOD INSECURITY; SOCIOECONOMIC
POSITION; AMERICAN-COLLEGE; PROJECT DULCE; STATEMENT; MELLITUS;
MANAGEMENT; PERFORMANCE
AB Objective. To determine whether diabetes clinical standards consider increased hypoglycemia risk in vulnerable patients.
Data Sources. MEDLINE, the National Guidelines Clearinghouse, the National Quality Measures Clearinghouse, and supplemental sources.
Study Design. Systematic review of clinical standards (guidelines, quality metrics, or pay-for-performance programs) for glycemic control in adult diabetes patients. The primary outcome was discussion of increased risk for hypoglycemia in vulnerable populations.
Data Collection/Extraction Methods. Manuscripts identified were abstracted by two independent reviewers using prespecified inclusion/exclusion criteria and a standardized abstraction form.
Principal Findings. We screened 1,166 titles, and reviewed 220 manuscripts in full text. Forty-four guidelines, 17 quality metrics, and 8 pay-for-performance programs were included. Five (11 percent) guidelines and no quality metrics or pay-for-performance programs met the primary outcome.
Conclusions. Clinical standards do not substantively incorporate evidence about increased risk for hypoglycemia in vulnerable populations.
C1 [Berkowitz, Seth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Aragon, Katherine; Hines, Jonas; Seligman, Hilary; Lee, Sei; Sarkar, Urmimala] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Berkowitz, SA (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
EM SABerkowitz@partners.org
OI Berkowitz, Seth/0000-0003-1030-4297
FU Institutional National Research Service Award [T32HP10251]; Division of
General Internal Medicine at Massachusetts General Hospital; Agency for
Health Care Research and Quality [K08HS017594]; National Center for
Research Resources [KL2RR024130]; NIH/NCRR/OD UCSF-CTSI [KL2 RR024130];
National Center for Research Resources (a component of the NIH)
[KL2RR024130]; National Institute of Aging; American Federation for
Aging Research [K23AG040779]
FX Dr. Berkowitz was supported by an Institutional National Research
Service Award T32HP10251 and by the Division of General Internal
Medicine at Massachusetts General Hospital. Dr. Sarkar is support by the
Agency for Health Care Research and Quality (K08HS017594), and the
National Center for Research Resources (KL2RR024130). Dr. Seligman
receives support from NIH/NCRR/OD UCSF-CTSI grant number KL2 RR024130.
Its contents are solely the responsibility of the authors and do not
necessarily represent the official views of the NIH. Dr. Lee was
supported by the KL2RR024130 from the National Center for Research
Resources (a component of the NIH) and the Paul Beeson Career
Development Award from the National Institute of Aging and the American
Federation for Aging Research (K23AG040779). The funding sources had no
role in study design; in the collection, analysis, and interpretation of
data; in the writing of the report; or in the decision to submit the
manuscript for publication.
NR 38
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Z9 9
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-9124
EI 1475-6773
J9 HEALTH SERV RES
JI Health Serv. Res.
PD AUG
PY 2013
VL 48
IS 4
BP 1299
EP 1310
DI 10.1111/1475-6773.12048
PG 12
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 176IM
UT WOS:000321297600005
PM 23445498
ER
PT J
AU Werner, RM
Konetzka, RT
Polsky, D
AF Werner, Rachel M.
Konetzka, R. Tamara
Polsky, Daniel
TI The Effect of Pay-for-Performance in Nursing Homes: Evidence from State
Medicaid Programs
SO HEALTH SERVICES RESEARCH
LA English
DT Article
DE Quality of care; pay-for-performance; nursing home quality; long-term
care
ID RESIDENT ASSESSMENT INSTRUMENT; RISK-ADJUSTMENT; HEALTH-CARE; QUALITY;
IMPROVE; MDS
AB Objective. Pay-for-performance (P4P) is commonly used to improve health care quality in the United States and is expected to be frequently implemented under the Affordable Care Act. However, evidence supporting its use is mixed with few large-scale, rigorous evaluations of P4P. This study tests the effect of P4P on quality of care in a large-scale setting-the implementation of P4P for nursing homes by state Medicaid agencies.
Data Sources/Study Setting. 2001-2009 nursing home Minimum Data Set and Online Survey, Certification, and Reporting (OSCAR) datasets.
Study Design. Between 2001 and 2009, eight state Medicaid agencies adopted P4P programs in nursing homes. We use a difference-in-differences approach to test for changes in nursing home quality under P4P, taking advantage of the variation in timing of implementation across these eight states and using nursing homes in the 42 non-P4P states plus Washington, DC as contemporaneous controls.
Principal Findings. Quality improvement under P4P was inconsistent. While three clinical quality measures (the percent of residents being physically restrained, in moderate to severe pain, and developed pressure sores) improved with the implementation of P4P in states with P4P compared with states without P4P, other targeted quality measures either did not change or worsened. Of the two structural measures of quality that were tied to payment (total number of deficiencies and nurse staffing) deficiency rates worsened slightly under P4P while staffing levels did not change.
Conclusions. Medicaid-based P4P in nursing homes did not result in consistent improvements in nursing home quality. Expectations for improvement in nursing home care under P4P should be tempered.
C1 [Werner, Rachel M.] Philadelphia VAMC, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Werner, Rachel M.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Konetzka, R. Tamara] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Polsky, Daniel] Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Div Gen Internal Med, Philadelphia, PA 19104 USA.
RP Werner, RM (reprint author), 1230 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM rwerner@upenn.edu
FU National Institute on Aging [R01 AG034182-01]; VA HSR&D Career
Development Award
FX This research was funded by a grant from the National Institute on Aging
(R01 AG034182-01). Rachel Werner was supported in part by a VA HSR&D
Career Development Award. The authors gratefully thank Chris Wirtalla
for his outstanding programming and research assistance.
NR 38
TC 13
Z9 13
U1 3
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-9124
EI 1475-6773
J9 HEALTH SERV RES
JI Health Serv. Res.
PD AUG
PY 2013
VL 48
IS 4
BP 1393
EP 1414
DI 10.1111/1475-6773.12035
PG 22
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 176IM
UT WOS:000321297600010
PM 23398330
ER
PT J
AU Maciejewski, ML
Bryson, CL
Wang, V
Perkins, M
Liu, CF
AF Maciejewski, Matthew L.
Bryson, Chris L.
Wang, Virginia
Perkins, Mark
Liu, Chuan-Fen
TI Potential Bias in Medication Adherence Studies of Prevalent Users
SO HEALTH SERVICES RESEARCH
LA English
DT Article
DE Medication adherence; pharmaceutical policy; cost sharing; research
design; veterans; inclusion criteria
ID DRUG UTILIZATION; COPAYMENT INCREASE; RISK ADJUSTMENT; PERFORMANCE;
IMPACT; EXPENDITURES; COMORBIDITY; VETERANS; HEALTH
AB Purpose. We examined how the choice of historic medication use criteria for identifying prevalent users may bias estimated adherence changes associated with a medication copayment increase.
Methods. From pharmacy claims data in a retrospective cohort study, we identified 6,383 prevalent users of oral diabetes medications from four VA Medical Centers. Patients were included in this prevalent cohort if they had one fill both 3 months prior and 4-12 months prior to the index date, defined as the month in which medication copayments increased. To determine whether these historic medication use criteria introduced bias in the estimated response to a $5 medication copayment increase, we compared adherence trends from cohorts defined from different medication use criteria and from different index dates of copayment change. In an attempt to validate the prior observation of an upward trend in adherence prior to the date of the policy change, we replicated time series analyses varying the index dates prior to and following the date of the policy change, hypothesizing that the trend line associated with the policy change would differ from the trend lines that were not.
Results. Medication adherence trends differed when different medication use criteria were applied. Contrary to our expectations, similar adherence trends were observed when the same medication use criteria were applied at index dates when no copayment changes occurred.
Conclusion. To avoid introducing bias due to study design in outcomes assessments of medication policy changes, historic medication use inclusion criteria must be chosen carefully when constructing cohorts of prevalent users. Furthermore, while pharmacy data have enormous potential for population research and monitoring, there may be inherent logical flaws that limit cohort identification solely through administrative pharmacy records.
C1 [Maciejewski, Matthew L.; Wang, Virginia] Duke Univ, Dept Med, Div Gen Internal Med, Ctr Hlth Serv Res Primary Care,Durham VA Med Ctr, Durham, NC 27705 USA.
[Bryson, Chris L.; Perkins, Mark; Liu, Chuan-Fen] Univ Washington, Dept Med, Div Gen Internal Med, VA Puget Sound Hlth Care Syst,Northwest Ctr Outco, Seattle, WA USA.
RP Maciejewski, ML (reprint author), Duke Univ, Dept Med, Div Gen Internal Med, Ctr Hlth Serv Res Primary Care,Durham VA Med Ctr, Durham, NC 27705 USA.
EM matthew.maciejewski@va.gov
FU Office of Research and Development, Health Services Research and
Development Service, Department of Veterans Affairs [IIR 03-200];
Department of Veterans Affairs [RCS 10-391]; Takeda Pharmaceuticals;
Novartis; Surgical Review Corporation; Research Data and Assistance
Center (ResDAC) at the University of Minnesota
FX This work was supported by the Office of Research and Development,
Health Services Research and Development Service, Department of Veterans
Affairs, project number IIR 03-200. Dr. Maciejewski was also supported
by a Research Career Scientist award from the Department of Veterans
Affairs (RCS 10-391). The authors would like to acknowledge tremendously
helpful comments and editorial suggestions from the editors, two
reviewers, Hollis Weidenbacher and Jaclyn Lemon. Dr. Maciejewski has
received consultation funds from Takeda Pharmaceuticals, Novartis, the
Surgical Review Corporation, and the Research Data and Assistance Center
(ResDAC) at the University of Minnesota, and owns stock in Amgen via his
wife's employment at Amgen. The views expressed are those of the authors
and do not reflect the views of the Department of Veterans Affairs and
their affiliated institutions.
NR 25
TC 4
Z9 4
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-9124
J9 HEALTH SERV RES
JI Health Serv. Res.
PD AUG
PY 2013
VL 48
IS 4
BP 1468
EP 1486
DI 10.1111/1475-6773.12043
PG 19
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 176IM
UT WOS:000321297600014
PM 23402554
ER
PT J
AU Williams, VJ
Leritz, EC
Shepel, J
McGlinchey, RE
Milberg, WP
Rudolph, JL
Lipsitz, LA
Salat, DH
AF Williams, Victoria J.
Leritz, Elizabeth C.
Shepel, Juli
McGlinchey, Regina E.
Milberg, William P.
Rudolph, James L.
Lipsitz, Lewis A.
Salat, David H.
TI Interindividual variation in serum cholesterol is associated with
regional white matter tissue integrity in older adults
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE DTI; serum cholesterol; aging; cerebrovascular; white matter; fractional
anisotropy; diffusivity
ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE
IMAGES; ALZHEIMERS-DISEASE; DIFFUSION TENSOR; BLOOD-PRESSURE; COGNITIVE
FUNCTION; CORTICAL SURFACE; RISK-FACTORS; GEOMETRICALLY ACCURATE
AB Prior research has demonstrated links among vascular health and the occurrence of stroke, mild cognitive decline, and dementia in older adults. However, little is known about whether normal variation in vascular indicators may be related to changes in neural tissue integrity. Even less is known about how the brain is affected by cholesterol levels in the normal to moderate risk range, leading up to overt disease pathology. This study examined associations between serum lipid levels and DTI indicators of white matter (WM) structural integrity in a sample of 125 generally healthy older adults aged 43-87 years. Whole-brain voxelwise analysis, controlling for age and gender, revealed low density lipoprotein levels (LDL) as the most robust correlate of regional WM structural integrity of the measured lipids. Higher LDL was associated with decreased WM integrity in right frontal and temporal regions, the superior longitudinal fasciculus and internal/external capsules. Increasing LDL was associated with increased radial and axial diffusivity; however, more widespread statistical effects were found for radial diffusivity. These findings suggest that normal interindividual variation in lipid levels is associated with compromised regional WM integrity, even in individuals below clinical thresholds for hyperlipidemia. Given the prevalence of cholesterol-associated sequelae in older adults, and mounting evidence suggesting a vascular role in the etiology of dementia, the current data suggest that understanding the relationship between cholesterol and brain tissue microstructure may have important clinical implications for early detection of vascular-related cognitive disorders and optimal regulation of serum lipids to maintain neural health in older adults. Hum Brain Mapp, 2013. (c) 2012 Wiley Periodicals, Inc.
C1 [Williams, Victoria J.; Leritz, Elizabeth C.; Shepel, Juli; Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Vet NeRVe Ctr, Boston, MA USA.
[Williams, Victoria J.; Leritz, Elizabeth C.; Shepel, Juli; McGlinchey, Regina E.; Milberg, William P.; Rudolph, James L.; Salat, David H.] VA Boston Healthcare Syst, GRECC, Boston, MA USA.
[Williams, Victoria J.; Leritz, Elizabeth C.; Shepel, Juli; Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Williams, Victoria J.; Leritz, Elizabeth C.; Shepel, Juli; Lipsitz, Lewis A.; Salat, David H.] Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA.
[Leritz, Elizabeth C.; McGlinchey, Regina E.; Milberg, William P.; Salat, David H.] Harvard Univ, Sch Med, Boston, MA USA.
[Lipsitz, Lewis A.] Beth Israel Deaconess Med Ctr, Gerontol Div, Hebrew Senior Life Inst Aging Res, Boston, MA 02215 USA.
RP Salat, DH (reprint author), Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA.
EM salat@nmr.mgh.harvard.edu
RI McGlinchey, Regina/R-1971-2016
FU National Institute of Neurologic Disorders and Stroke [K23NS062148];
National Institute of Nursing Research [R01NR010827]; National Institute
on Aging [P60AG08812, P01AG004390, K01AG24898]; Medical Research Service
VA Merit Review Awards
FX Contract grant sponsor: National Institute of Neurologic Disorders and
Stroke; Contract grant number: K23NS062148; Contract grant sponsor:
National Institute of Nursing Research; Contract grant number:
R01NR010827; Contract grant sponsor: National Institute on Aging;
Contract grant number: P60AG08812, P01AG004390, K01AG24898; Contract
grant sponsor: Medical Research Service VA Merit Review Awards.
NR 80
TC 18
Z9 18
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD AUG
PY 2013
VL 34
IS 8
BP 1826
EP 1841
DI 10.1002/hbm.22030
PG 16
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 178GX
UT WOS:000321435100007
PM 22438182
ER
PT J
AU Wong, HKA
Veremeyko, T
Patel, N
Lemere, CA
Walsh, DM
Esau, C
Vanderburg, C
Krichevsky, AM
AF Wong, Hon-Kit Andus
Veremeyko, Tatiana
Patel, Nehal
Lemere, Cynthia A.
Walsh, Dominic M.
Esau, Christine
Vanderburg, Charles
Krichevsky, Anna M.
TI De-repression of FOXO3a death axis by microRNA-132 and-212 causes
neuronal apoptosis in Alzheimers disease
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; FORKHEAD TRANSCRIPTION FACTOR; MILD COGNITIVE
IMPAIRMENT; TUMOR-SUPPRESSOR PTEN; LONG-TERM DEPRESSION; NEUROTROPHIC
FACTOR; CELL-DEATH; HIPPOCAMPAL-NEURONS; CIRCADIAN-CLOCK; COCAINE INTAKE
AB Alzheimers disease (AD) is a multifactorial and fatal neurodegenerative disorder for which the mechanisms leading to profound neuronal loss are incompletely recognized. MicroRNAs (miRNAs) are recently discovered small regulatory RNA molecules that repress gene expression and are increasingly acknowledged as prime regulators involved in human brain pathologies. Here we identified two homologous miRNAs, miR-132 and miR-212, downregulated in temporal cortical areas and CA1 hippocampal neurons of human AD brains. Sequence-specific inhibition of miR-132 and miR-212 induces apoptosis in cultured primary neurons, whereas their overexpression is neuroprotective against oxidative stress. Using primary neurons and PC12 cells, we demonstrate that miR-132/212 controls cell survival by direct regulation of PTEN, FOXO3a and P300, which are all key elements of AKT signaling pathway. Silencing of these three target genes by RNAi abrogates apoptosis caused by the miR-132/212 inhibition. We further demonstrate that mRNA and protein levels of PTEN, FOXO3a, P300 and most of the direct pro-apoptotic transcriptional targets of FOXO3a are significantly elevated in human AD brains. These results indicate that the miR-132/miR-212/PTEN/FOXO3a signaling pathway contributes to AD neurodegeneration.
C1 [Wong, Hon-Kit Andus; Veremeyko, Tatiana; Lemere, Cynthia A.; Krichevsky, Anna M.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
[Wong, Hon-Kit Andus; Veremeyko, Tatiana; Lemere, Cynthia A.; Krichevsky, Anna M.] Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA.
[Patel, Nehal; Vanderburg, Charles] Massachusetts Gen Hosp, Harvard NeuroDiscovery Ctr, Charlestown, MA 02129 USA.
[Patel, Nehal] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Walsh, Dominic M.] Brigham & Womens Hosp, Ctr Neurol Dis, Lab Neurodegenerat Res, Harvard Inst Med, Boston, MA 02115 USA.
[Esau, Christine] Regulus Therapeut, San Diego, CA 92121 USA.
RP Krichevsky, AM (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM akrichevsky@rics.bwh.harvard.edu
RI Wong, Hon-Kit/G-3944-2014
OI Wong, Hon-Kit/0000-0003-0049-8454
FU Alzheimer's Association [NIRG-09-132844]
FX This work was supported by a grant from the Alzheimer's Association
(NIRG-09-132844).
NR 86
TC 69
Z9 75
U1 3
U2 29
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 1
PY 2013
VL 22
IS 15
BP 3077
EP 3092
DI 10.1093/hmg/ddt164
PG 16
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 178MR
UT WOS:000321452600010
PM 23585551
ER
PT J
AU Motai, Y
Yoshida, H
AF Motai, Yuichi
Yoshida, Hiroyuki
TI Principal Composite Kernel Feature Analysis: Data-Dependent Kernel
Approach
SO IEEE TRANSACTIONS ON KNOWLEDGE AND DATA ENGINEERING
LA English
DT Article
DE Principal component analysis; data-dependent kernel; nonlinear subspace;
manifold structures
ID SUPPORT VECTOR MACHINES; NEAREST-NEIGHBOR CLASSIFICATION; COMPUTER-AIDED
DIAGNOSIS; PROTEIN FOLD RECOGNITION; CT-COLONOGRAPHY; COLONIC POLYPS;
NEURAL-NETWORKS; CANCER; DISCRIMINANT; CLASSIFIERS
AB Principal composite kernel feature analysis (PC-KFA) is presented to show kernel adaptations for nonlinear features of medical image data sets (MIDS) in computer-aided diagnosis (CAD). The proposed algorithm PC-KFA has extended the existing studies on kernel feature analysis (KFA), which extracts salient features from a sample of unclassified patterns by use of a kernel method. The principal composite process for PC-KFA herein has been applied to kernel principal component analysis [34] and to our previously developed accelerated kernel feature analysis [20]. Unlike other kernel-based feature selection algorithms, PC-KFA iteratively constructs a linear subspace of a high-dimensional feature space by maximizing a variance condition for the nonlinearly transformed samples, which we call data-dependent kernel approach. The resulting kernel subspace can be first chosen by principal component analysis, and then be processed for composite kernel subspace through the efficient combination representations used for further reconstruction and classification. Numerical experiments based on several MID feature spaces of cancer CAD data have shown that PC-KFA generates efficient and an effective feature representation, and has yielded a better classification performance for the proposed composite kernel subspace using a simple pattern classifier.
C1 [Motai, Yuichi] Virginia Commonwealth Univ, Sch Engn, Sensory Intelligent Lab, Dept Elect & Comp Engn, Richmond, VA 23284 USA.
[Yoshida, Hiroyuki] Harvard Univ, Sch Med, Dept Radiol, 3D Imaging Res, Boston, MA 02114 USA.
[Yoshida, Hiroyuki] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Motai, Y (reprint author), Virginia Commonwealth Univ, Sch Engn, Sensory Intelligent Lab, Dept Elect & Comp Engn, POB 843068,601 West Main St, Richmond, VA 23284 USA.
EM ymotai@vcu.edu; yoshida.hiro@mgh.harvard.edu
FU American Cancer Society Institutional Research Grant through the Massey
Cancer Center; Virginia Commonwealth University; US National Science
Foundation ECCS [1054333]; USPHS from National Cancer Institute
[R01CA095279]
FX The authors would like to express gratitude for the support of this
research by the American Cancer Society Institutional Research Grant
through the Massey Cancer Center, Presidential Research Incentive
Program at Virginia Commonwealth University, US National Science
Foundation ECCS #1054333 (CAREER Award), and USPHS Grant R01CA095279
from National Cancer Institute. The work reported here would not be
possible without the help of many of the past and present members of the
laboratory, in particular, D. Ma, A. Docef, S. Myla, and L. Winter.
NR 75
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Z9 8
U1 3
U2 18
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
SN 1041-4347
J9 IEEE T KNOWL DATA EN
JI IEEE Trans. Knowl. Data Eng.
PD AUG
PY 2013
VL 25
IS 8
BP 1863
EP 1875
DI 10.1109/TKDE.2012.110
PG 13
WC Computer Science, Artificial Intelligence; Computer Science, Information
Systems; Engineering, Electrical & Electronic
SC Computer Science; Engineering
GA 175VF
UT WOS:000321261000014
ER
PT J
AU Trautner, BW
Patterson, JE
Petersen, NJ
Hysong, S
Horwitz, D
Chen, GJ
Grota, P
Naik, AD
AF Trautner, Barbara W.
Patterson, Jan E.
Petersen, Nancy J.
Hysong, Sylvia
Horwitz, Deborah
Chen, G. John
Grota, Patti
Naik, Aanand D.
TI Quality Gaps in Documenting Urinary Catheter Use and Infectious Outcomes
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Article
ID TRACT-INFECTION; CARE; PREVENTION; CONDOM
AB OBJECTIVE. To describe the frequency of use of all types of urinary catheters, including but not limited to indwelling catheters, as well as positive cultures associated with the various types. We also determined the accuracy of catheter-days reporting at our institution.
DESIGN. Prospective, observational trial based on patient-level review of the electronic medical record. Chart review was compared with standard methods of catheter surveillance and reporting by infection control personnel.
SETTING. Ten internal medicine and 5 long-term care wards in 2 tertiary care Veterans Affairs hospitals in Texas from July 2010 through June 2011.
PARTICIPANTS. The study included 7,866 inpatients.
METHODS. Measurements included patient bed-days; days of use of indwelling, external, suprapubic, and intermittent urinary catheters; number of urine cultures obtained and culture results; and infection control reports of indwelling catheter-days.
RESULTS. We observed 7,866 inpatients with 128,267 bed-days on acute medicine and extended care wards during the study. A urinary catheter was used on 36.9% of the total bed-days observed. Acute medicine wards collected more urine cultures per 1,000 bed-days than did the extended care wards (75.9 and 10.4 cultures per 1,000 bed-days, respectively; P < .0001). Catheter-days were divided among indwelling-catheter-days (47.8%), external-catheter-days (48.4%), and other (intermittent- and suprapubic-catheter-days, 3.8%). External catheters contributed to 376 (37.3%) of the 1,009 catheter-associated positive urine cultures. Urinary-catheter-days reported to the infection control department missed 20.1% of the actual days of indwelling catheter use, whereas 12.0% of their reported catheter-days were false.
CONCLUSIONS. Urinary catheter use was extremely common. External catheters accounted for a large portion of catheter-associated bacteriuria, and standard practices for tracking urinary-catheter-days were unreliable.
C1 [Trautner, Barbara W.; Petersen, Nancy J.; Hysong, Sylvia; Horwitz, Deborah; Chen, G. John; Naik, Aanand D.] Michael E DeBakey VA Med Ctr, Houston Vet Affairs Hlth Serv, Res & Dev Ctr Excellence, Houston, TX USA.
[Trautner, Barbara W.; Petersen, Nancy J.; Hysong, Sylvia; Horwitz, Deborah; Chen, G. John; Naik, Aanand D.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Petersen, Nancy J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Infect Dis, San Antonio, TX 78229 USA.
[Patterson, Jan E.; Grota, Patti] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Trautner, BW (reprint author), MEDVAMC HSR&D CoE 152, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM trautner@bcm.edu
RI Hysong, Sylvia/B-8420-2008
OI Hysong, Sylvia/0000-0002-9063-5207
FU VA Health Services Research and Development [IIR 09-104]; VA
Rehabilitation Research and Development [B4623]; National Institute of
Diabetes and Digestive and Kidney Diseases [DK092293]; VA Health
Services Research and Development Houston Center of Excellence
[HFP-090-20]
FX This work was supported by the VA Health Services Research and
Development (IIR 09-104); VA Rehabilitation Research and Development
(B4623); and the National Institute of Diabetes and Digestive and Kidney
Diseases (DK092293). This work was also partly supported by the VA
Health Services Research and Development Houston Center of Excellence
(HFP-090-20). B.W.T. had full access to all data in the study and takes
responsibility for the integrity of the data and accuracy of data
analysis.
NR 26
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U1 2
U2 12
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
EI 1559-6834
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD AUG
PY 2013
VL 34
IS 8
BP 793
EP 799
DI 10.1086/671267
PG 7
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 180RT
UT WOS:000321613900005
PM 23838219
ER
PT J
AU van Kollenburg, JAPAC
Vrahas, MS
Smith, RM
Guitton, TG
Ring, D
AF van Kollenburg, Johan A. P. A. C.
Vrahas, Mark S.
Smith, R. Malcolm
Guitton, Thierry G.
Ring, David
CA Sci Variation Grp
TI Diagnosis of union of distal tibia fractures: Accuracy and interobserver
reliability
SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED
LA English
DT Article
DE Distal tibia fracture; Open reduction and internal fixation;
Radiographs; Diagnosis of union; Reliability; Accuracy; Diagnostic
performance characteristics
ID PLAFOND FRACTURES; PILON FRACTURES; INTERNAL-FIXATION; OPEN REDUCTION
AB Decisions about return to activity and additional surgery are often made on the basis of radiographs obtained 3 months after injury. If radiographs 3 months after injury cannot reliably and accurately diagnose union, then patients may be needlessly disabled and might receive unnecessary treatments including surgery. We evaluated the accuracy and the reliability of the diagnosis of union or eventual union on radiographs obtained 3 months after open reduction and internal fixation of a fracture of the distal tibia by having 69 trauma surgeons evaluate radiographs of 33 consecutively treated patients in an online survey. Observers were also asked to judge specific criteria that are commonly used to diagnose fracture union. There was moderate interobserver reliability for the diagnosis of union or diagnosis of "eventual union". The interobserver agreement for the various specific radiographic signs of union varied between fair to moderate. The sensitivity of radiographs for diagnosis of "union or eventual union" of distal tibia fractures was 47%, the specificity was 73% and the accuracy was 68%. The prevalence adjusted positive predictive value was 25% and the negative predictive value was 88%. Diagnosis of union based on radiographs 3 months after injury is only moderately reliable and accurate but has a high negative predictive value. Decisions about activity level and additional treatment 3 months after injury should not be based on radiographs alone. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [van Kollenburg, Johan A. P. A. C.; Vrahas, Mark S.; Smith, R. Malcolm; Guitton, Thierry G.; Ring, David] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[van Kollenburg, Johan A. P. A. C.; Guitton, Thierry G.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
[Vrahas, Mark S.; Smith, R. Malcolm] Massachusetts Gen Hosp, Orthopaed Trauma Serv, Boston, MA 02114 USA.
RP Ring, D (reprint author), Harvard Univ, Sch Med, 55 Fruit St,YAW 2100, Boston, MA 02114 USA.
EM dring@partners.org
OI Borris, Lars/0000-0002-0527-1518; Guitton, Thierry/0000-0002-2599-1985
FU Biomet; Skeletal Dynamics
FX David Ring is a Consultant for Wright Medical and Skeletal Dynamics; has
research contracts with Biomet and Skeletal Dynamics; and receives
royalties from Wright Medical and has contracts for future royalties
with Medartis and Skeletal Dynamics.
NR 17
TC 1
Z9 1
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0020-1383
J9 INJURY
JI Injury-Int. J. Care Inj.
PD AUG
PY 2013
VL 44
IS 8
BP 1073
EP 1075
DI 10.1016/j.injury.2012.10.034
PG 3
WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery
SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery
GA 179CU
UT WOS:000321496700011
PM 23200031
ER
PT J
AU Saunders, GH
Frederick, MT
Silverman, S
Papesh, M
AF Saunders, Gabrielle H.
Frederick, Melissa Teahen
Silverman, Shienpei
Papesh, Melissa
TI Application of the health belief model: Development of the hearing
beliefs questionnaire (HBQ) and its associations with hearing health
behaviors
SO INTERNATIONAL JOURNAL OF AUDIOLOGY
LA English
DT Article
DE Rehabilitation of hearing impaired; health behavior; health care seeking
behavior; patient acceptance of health care; patient compliance; hearing
aids
ID HELP-SEEKING BEHAVIOR; OLDER-ADULTS; AID USE; PEOPLE; IMPAIRMENT;
REHABILITATION; POPULATION; COMPLAINTS; COMMUNITY; ATTITUDES
AB Objective : To develop a hearing beliefs questionnaire (HBQ) that assesses hearing beliefs within the constructs of the health belief model, and to investigate whether HBQ scores are associated with hearing health behaviors. Design: A 60-item version of the questionnaire was developed and completed by 223 participants who also provided information about their hearing health behaviors (help seeking, hearing-aid acquisition, and hearing-aid use). Study sample: Individuals aged between 22 and 90 years recruited from a primary care waiting area at a Veterans hospital. Seventy-six percent were male, 80% were Veterans. Results: A 26-item version of the HBQ with six scales was derived using factor analysis and reliability analyses. The scales measured: perceived susceptibility, perceived severity, perceived benefits, perceived barriers, perceived self-efficacy, and cues to action. HBQ scores differed significantly between individuals with different hearing health behaviors. Logistic regression analyses resulted in robust models of hearing health behaviors that correctly classified between 59% and 100% of participant hearing health behaviors. Conclusions: The HBM appears to be an appropriate framework for examining hearing health behaviors, and the HBQ is a valuable tool for assessing hearing health beliefs and predicting hearing health behaviors.
C1 [Saunders, Gabrielle H.; Frederick, Melissa Teahen; Silverman, Shienpei; Papesh, Melissa] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR USA.
[Saunders, Gabrielle H.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA.
RP Saunders, GH (reprint author), Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM gabrielle.saunders@va.gov
FU Unitron; Department of Veterans Affairs, Veterans Health Administration,
Rehabilitation Research and Development Service [C4844C]
FX This material is based upon work supported by Unitron and by the
Department of Veterans Affairs, Veterans Health Administration,
Rehabilitation Research and Development Service Grant # C4844C. Aspects
of these data were presented at the International Hearing Aid Research
Conference (IHCON), Lake Tahoe, USA, August 8-12, 2012, at the Academy
of Rehabilitative Audiology Institute, Providence, USA, September 9-11,
2012, and at the British Academy of Audiology, Manchester, UK, November
12-13, 2012.
NR 41
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U1 2
U2 20
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1499-2027
J9 INT J AUDIOL
JI Int. J. Audiol.
PD AUG
PY 2013
VL 52
IS 8
BP 558
EP 567
DI 10.3109/14992027.2013.791030
PG 10
WC Audiology & Speech-Language Pathology; Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Otorhinolaryngology
GA 181UJ
UT WOS:000321693900006
PM 23682849
ER
PT J
AU Sewell, MC
Luo, XD
Neugroschl, J
Sano, M
AF Sewell, Margaret C.
Luo, Xiaodong
Neugroschl, Judith
Sano, Mary
TI Detection of mild cognitive impairment and early stage dementia with an
audio-recorded cognitive scale
SO INTERNATIONAL PSYCHOGERIATRICS
LA English
DT Article
DE cognitive assessment; Alzheimer's disease; MCI; diagnostic accuracy
ID ALZHEIMERS-DISEASE
AB Background: Physicians often miss diagnosis of mild cognitive impairment (MCI) or early dementia and screening measures can be insensitive to very mild impairments. Other cognitive assessments may take too much time or be frustrating to seniors. This study examined the ability of an audio-recorded scale, developed in Australia, to detect MCI or mild Alzheimer's disease (AD) and compared cognitive domain-specific performance on the audio-recorded scale to in-person battery and common cognitive screens.
Method: Seventy-six patients from the Mount Sinai Alzheimer's Disease Research Center were recruited. Patients were aged 75 years or older, with clinical diagnosis of AD or MCI (n = 51) or normal control (n = 25). Participants underwent in-person neuropsychological testing followed by testing with the audio-recorded cognitive screen (ARCS).
Results: ARCS provided better discrimination between normal and impaired elderly individuals than either the Mini-Mental State Examination or the clock drawing test. The in-person battery and ARCS analogous variables were significantly correlated, most in the 0.4 to 0.7 range, including verbal memory, executive function/attention, naming, and verbal fluency. The area under the curve generated from the receiver operating characteristic curves indicated high and equivalent discrimination for ARCS and the in-person battery (0.972 vs. 0.988; p = 0.23).
Conclusion: The ARCS demonstrated better discrimination between normal controls and those with mild deficits than typical screening measures. Performance on cognitive domains within the ARCS was well correlated with the in-person battery. Completion of the ARCS was accomplished despite mild difficulty hearing the instructions even in very elderly participants, indicating that it may be a useful measure in primary care settings.
C1 [Sewell, Margaret C.; Luo, Xiaodong; Neugroschl, Judith; Sano, Mary] Icahn Sch Med Mt Sinai, Alzheimers Dis Res Ctr, New York, NY 10029 USA.
[Sano, Mary] James J Peters VA Med Ctr, Bronx, NY USA.
RP Sewell, MC (reprint author), Icahn Sch Med Mt Sinai, Alzheimers Dis Res Ctr, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA.
EM margaret.sewell@mssm.edu
FU National Institutes of Health [NIH U01 P50-AG005138-28]
FX The authors would like to express their gratitude to Talia Sandwick, BA,
for her work with subject recruitment and data collection. The authors
are also grateful to the National Institutes of Health for their grant
no. NIH U01 P50-AG005138-28.
NR 19
TC 0
Z9 0
U1 0
U2 17
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1041-6102
J9 INT PSYCHOGERIATR
JI Int. Psychogeriatr.
PD AUG
PY 2013
VL 25
IS 8
SI SI
BP 1325
EP 1333
DI 10.1017/S1041610213000598
PG 9
WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry;
Psychology
SC Psychology; Geriatrics & Gerontology; Psychiatry
GA 175WD
UT WOS:000321263400013
PM 23635663
ER
PT J
AU Hinton, DE
Ojserkis, RA
Jalal, B
Peou, S
Hofmann, SG
AF Hinton, Devon E.
Ojserkis, Rebecca A.
Jalal, Baland
Peou, Sonith
Hofmann, Stefan G.
TI Loving-Kindness in the Treatment of Traumatized Refugees and Minority
Groups: A Typology of Mindfulness and the Nodal Network Model of Affect
and Affect Regulation
SO JOURNAL OF CLINICAL PSYCHOLOGY
LA English
DT Article
DE acceptance; mindfulness; meditation; posttraumatic stress disorder;
cross-cultural
ID CULTURALLY ADAPTED CBT; EMOTION REGULATION; CAMBODIAN REFUGEES; ANXIETY
DISORDER; PTSD; MEDITATION; MECHANISMS; EXAMPLES; WORRY
AB This article discusses how loving-kindness can be used to treat traumatized refugees and minority groups, focusing on examples from our treatment, culturally adapted cognitive-behavioral therapy (CA-CBT). To show how we integrate loving-kindness with other mindfulness interventions and why loving-kindness should be an effective therapeutic technique, we present a typology of mindfulness states and the Nodal Network Model (NNM) of Affect and Affect Regulation. We argue that mindfulness techniques such as loving-kindness are therapeutic for refugees and minority populations because of their potential for increasing emotional flexibility, decreasing rumination, serving as emotional regulation techniques, and forming part of a new adaptive processing mode centered on psychological flexibility. We present a case to illustrate the clinical use of loving-kindness within the context of CA-CBT.
C1 [Hinton, Devon E.; Ojserkis, Rebecca A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hinton, Devon E.; Ojserkis, Rebecca A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Jalal, Baland] Univ Calif San Diego, San Diego, CA USA.
[Hofmann, Stefan G.] Boston Univ, Boston, MA 02215 USA.
RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA.
EM devon_hinton@hms.harvard.edu
RI Hofmann, Stefan/B-8769-2014
OI Hofmann, Stefan/0000-0002-3548-9681
NR 21
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U1 1
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9762
J9 J CLIN PSYCHOL
JI J. Clin. Psychol.
PD AUG
PY 2013
VL 69
IS 8
BP 817
EP 828
DI 10.1002/jclp.22017
PG 12
WC Psychology, Clinical
SC Psychology
GA 179AE
UT WOS:000321487800003
PM 23784718
ER
PT J
AU Alshouibi, EN
Kaye, EK
Cabral, HJ
Leone, CW
Garcia, RI
AF Alshouibi, E. N.
Kaye, E. K.
Cabral, H. J.
Leone, C. W.
Garcia, R. I.
TI Vitamin D and Periodontal Health in Older Men
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE periodontal disease; alveolar bone; probing depth; clinical attachment
loss; vitamin D intake; aging
ID D DEFICIENCY; CALCIUM SUPPLEMENTATION; SERUM CONCENTRATIONS; DISEASE
PROGRESSION; ASSOCIATION; POPULATION; UPDATE
AB Vitamin D, an anti-inflammatory mediator, has potential benefits for physical and oral health. Although it is produced endogenously, some individuals have a greater need for dietary and supplemental sources. This repeated-measures cross-sectional study assessed associations between total vitamin D intake and periodontal health in older men. Participants were 562 members of the Department of Veterans Affairs Dental Longitudinal Study, mean age 62.9 years, who were examined 1 to 4 times between 1986 and 1998. A calibrated examiner measured probing pocket depth (PPD) and attachment loss (AL) on each tooth. Alveolar bone loss (ABL) was determined from radiographs. Severe periodontal disease was defined as PPD 5 mm on 1 tooth and AL 6 mm at 2 sites (not on same tooth), and moderate-to-severe alveolar bone loss as ABL 40% at 3 sites. Generalized estimating equations were used to compute the odds ratios (OR) and 95% confidence intervals (95% CI) of having periodontal disease by level of vitamin D intake. Total vitamin D intake 800 IU was associated with lower odds of severe periodontal disease (OR = 0.67, 95% CI = 0.55-0.81) and moderate-to-severe ABL (OR = 0.54, 95% CI = 0.30-0.96) relative to intake < 400 IU/day. Vitamin D intake may protect against periodontal disease progression.
C1 [Alshouibi, E. N.] King Abdulaziz Univ, Fac Dent, Dept Prevent Sci, Jeddah 21413, Saudi Arabia.
[Alshouibi, E. N.; Kaye, E. K.; Garcia, R. I.] Boston Univ, Henry M Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02215 USA.
[Kaye, E. K.; Garcia, R. I.] VA Boston Healthcare Syst, Boston, MA USA.
[Cabral, H. J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Leone, C. W.] Boston Univ, Henry M Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02215 USA.
RP Kaye, EK (reprint author), Boston Univ, Henry M Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02215 USA.
EM kralle@bu.edu
OI Kaye, Elizabeth/0000-0001-7529-2501
FU National Institute of Dental and Craniofacial Research [K24 DE00419]; US
Department of Veterans Affairs; VA HSRD Service
FX This work was supported by the National Institute of Dental and
Craniofacial Research (K24 DE00419). The Dental Longitudinal Study and
Normative Aging Study are components of the Massachusetts Veterans
Epidemiology Research and Information Center, supported by the US
Department of Veterans Affairs Cooperative Studies Program. Dr. Garcia
was a recipient of a Veterans Affairs Career Development Award in Health
Services Research from the VA HSR&D Service. The views expressed in this
paper are those of the authors and do not necessarily represent the
views of the US Department of Veterans Affairs. The authors declare no
potential conflicts of interest with respect to the authorship and/or
publication of this article.
NR 24
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U1 2
U2 11
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 AUG
PY 2013
VL 92
IS 8
BP 689
EP 693
DI 10.1177/0022034513495239
PG 5
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 182JQ
UT WOS:000321738500004
PM 23788610
ER
PT J
AU Nelson, DB
Freeman, MP
Johnson, NL
McIntire, DD
Leveno, KJ
AF Nelson, David B.
Freeman, Marlene P.
Johnson, Neysa L.
McIntire, Donald D.
Leveno, Kenneth J.
TI A prospective study of postpartum depression in 17 648 parturients
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Edinburgh postnatal depression scale; postpartum depression; prospective
study
ID POSTNATAL DEPRESSION; PERINATAL DEPRESSION; SCALE EPDS; WOMEN; RISK;
PREGNANCY; VALIDATION; SYMPTOMS; COHORT; IMPACT
AB Objective: To assess perinatal antecedents to postpartum depression (PPD).
Methods: This was a prospective population-based, observational study of women screened for symptoms of depression using the Edinburgh Postnatal Depression Scale (EPDS) with scores >= 13 referred for psychiatric evaluation. Obstetric and neonatal outcomes were analyzed using univariable and multivariable analysis for associations with postpartum depressive symptoms.
Results: Of 25 050 women delivered, 17 648 (71%) completed EPDS questionnaires with 1106 (6.3%) scoring >= 13. Perinatal complications most associated with EPDS scores >= 13 included major malformation (adjusted OR 1.5; 95% CI, 1.1-2.3), neonatal death (adjusted OR 5.8; 95% CI, 2.9-11.4), stillbirth (adjusted OR 9.4; 95% CI, 6.0-14.8), and necrotizing enterocolitis (adjusted OR 21.7; 95% CI, 1.9-244.3). A total of 238 (22%) women kept their psychiatric referral appointment, and 111 (47%) were diagnosed with PPD. Perinatal factors were also found to be significantly associated with PPD.
Conclusions: PPD is significantly increased in women with adverse pregnancy outcomes, especially involving the infant.
C1 [Nelson, David B.; McIntire, Donald D.; Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA.
[Freeman, Marlene P.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA.
[Johnson, Neysa L.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
RP Nelson, DB (reprint author), Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM davidb.nelson@utsouthwestern.edu
NR 31
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Z9 6
U1 4
U2 11
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD AUG
PY 2013
VL 26
IS 12
BP 1155
EP 1161
DI 10.3109/14767058.2013.777698
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 183YQ
UT WOS:000321853600001
PM 23421404
ER
PT J
AU Keith, DA
Dodson, TB
Kaban, LB
AF Keith, David A.
Dodson, Thomas B.
Kaban, Leonard B.
TI Historical Review: First Facial Pain Patient Admitted to Massachusetts
General Hospital, February 1823 and First Case Series
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID TRIGEMINAL NEURALGIA; MICROVASCULAR DECOMPRESSION
AB Founded in 1811, the Massachusetts General Hospital recently celebrated its bicentennial. The War of 1812 delayed construction of the building so the first patient actually was admitted to the hospital 10 years later, on September 3, 1821. By 1823, the 60 hospital beds were full. Patient 66 was admitted on February 28, 1823, and his hospital course, as described in the admissions book, was transcribed for the Massachusetts General Hospital bicentennial celebration. That case history is reproduced and a case series of 6 similar patients published in 1828 by Dr John Warren, surgeon-in-chief and a founder of the hospital, is presented. In this report, the authors comment on the diagnosis, treatment, and outcome of these patients in the context of the contemporaneous health care environment and in light of the current knowledge of facial pain disorders. This article was adapted from the authors' commentary for the bicentennial celebration. (C) 2013 American Association of Oral and Maxillofacial Surgeons
C1 [Keith, David A.; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA.
[Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg,Ctr Appl Clin Inve, Boston, MA 02115 USA.
RP Keith, DA (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St, Boston, MA 02114 USA.
EM dkeith@partners.org
FU Massachusetts General Hospital Department of Oral and Maxillofacial
Surgery Education and Research Fund
FX This project was supported by the Massachusetts General Hospital
Department of Oral and Maxillofacial Surgery Education and Research
Fund.
NR 33
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD AUG
PY 2013
VL 71
IS 8
BP 1322
EP 1333
DI 10.1016/j.joms.2013.04.027
PG 12
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 182IQ
UT WOS:000321735300009
PM 23866949
ER
PT J
AU Kinard, BE
Chuang, SK
August, M
Dodson, TB
AF Kinard, Brian E.
Chuang, Sung-Kiang
August, Meredith
Dodson, Thomas B.
TI How Well Do We Manage the Odontogenic Keratocyst?
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID TERM-FOLLOW-UP; DECOMPRESSION; ENUCLEATION; RECURRENCE;
MARSUPIALIZATION; CRYOTHERAPY; STRATEGY; CYSTS
AB Purpose: To answer the clinical question: Among patients treated for odontogenic keratocysts (OKCs), what is the overall 5-year disease-free rate and what factors are associated with disease recurrence?
Materials and Methods: The investigators implemented a retrospective cohort study and enrolled a sample composed of patients presenting for the evaluation and management of previously untreated OKCs. The predictor variables were grouped into demographic, medical, radiographic, and operative categories. The primary outcome variable was time to lesion recurrence. Data analyses were performed using univariate and bivariate or multivariate Cox proportional hazards models.
Results: The study sample was composed of 31 patients (31 OKCs) with a mean age of 41.0 years. Of the 31 OKCs treated, 19 (61.3%) were treated with decompression with or without residual cystectomy and 12 (38.7%) were treated with enucleation with or without adjunctive therapy. There were 8 recurrences in 8 patients, with a median time to recurrence of 17.8 months (interquartile range, 13.4 to 26.4 months). The 5-year disease-free estimate was 51.2% (95% confidence interval, 37.2%-65.2%). Multiloculated lesions were 33.6 times more likely to recur than unilocular lesions.
Conclusion: This may be the first study looking at disease recurrence after treatment of OKCs using appropriate statistical analyses for a time-dependent outcome (disease recurrence). The risk for recurrent disease is higher in this report than in many other studies and raises the issue that other reports may have underestimated the risk for recurrent disease owing to inappropriate statistical methods for assessing time-dependent outcomes. (C) 2013 American Association of Oral and Maxillofacial Surgeons
C1 [Kinard, Brian E.] Emory Univ, Sch Med, Dept Oral & Maxillofacial Surg, Atlanta, GA USA.
[Chuang, Sung-Kiang; August, Meredith] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest,Dept Oral Surg, Boston, MA 02115 USA.
[Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest,Dept Maxillofacial Surg, Boston, MA 02115 USA.
RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren Bldg Suite 1201, Boston, MA 02114 USA.
EM tbdodson@partners.org
FU Massachusetts General Hospital Department of Oral and Maxillofacial
Surgery Education and Research Fund; Center for Applied Clinical
Investigation; Massachusetts General Physicians Organization
FX This project was supported in part by the Massachusetts General Hospital
Department of Oral and Maxillofacial Surgery Education and Research Fund
(to B. E. K.), the Center for Applied Clinical Investigation (to S.-K.C.
and T.B.D.), and the Massachusetts General Physicians Organization (to
S.-K.C., M.A., and T.B.D.).
NR 31
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U1 0
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD AUG
PY 2013
VL 71
IS 8
BP 1353
EP 1358
DI 10.1016/j.joms.2013.01.029
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 182IQ
UT WOS:000321735300013
PM 23623200
ER
PT J
AU Zhang, XY
Chen, DC
Xiu, MH
Tan, YL
Yang, FD
Zhang, LY
Zhang, LY
Haile, CN
Kosten, TR
AF Zhang, Xiang Yang
Chen, Da Chun
Xiu, Mei Hong
Tan, Yun Long
Yang, Fu De
Zhang, Laurence Y.
Zhang, Laura Y.
Haile, Colin N.
Kosten, Thomas R.
TI Clinical symptoms and cognitive impairment associated with male
schizophrenia relate to plasma manganese superoxide dismutase activity:
A case-control study
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Schizophrenia; Cognition; Oxidative stress; MnSOD; Psychopathology
ID NEVER-MEDICATED 1ST-EPISODE; OXIDATIVE STRESS; NEUROPSYCHOLOGICAL
STATUS; ANTIOXIDANT ENZYMES; REPEATABLE BATTERY; GENDER-DIFFERENCES;
FATTY-ACIDS; DEFICITS; PSYCHOSIS; BRAIN
AB Several lines of evidence suggest that excessive reactive oxygen species-induced oxidative damage may underlie cognitive impairment in psychiatric disorders. A growing body of evidence show that oxidative damage may relate to the range of cognitive deficits associated with schizophrenia. In this study we examine one of the primary antioxidant defense enzymes manganese superoxide dismutase (MnSOD), and whether it relates to cognitive deficits in schizophrenia. We recruited 185 chronic male schizophrenia patients and 132 male controls and compared results from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and plasma MnSOD activity between groups. Symptom severity in patients with schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS). Our results showed that MnSOD activities were significantly lower in patients than controls (p < 0.05). Cognitive scores on the RBANS and, nearly all of its five subscales (all p < 0.001) except for the Visuospatial/Constructional index were significantly lower in schizophrenia patients than normal controls. MnSOD was negatively correlated with the general psychopathology subscale of PANSS, PANSS total score, positive symptoms and RBANS total score in patients with schizophrenia. Our findings add to growing evidence that oxidative stress may be involved in the psychopathology of male schizophrenia, and its associated cognitive impairment (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Zhang, Xiang Yang; Kosten, Thomas R.] Michael E DeBakey VA Med Ctr, Menninger Dept Psychiat & Behav Sci, Baylor Coll Med, Houston, TX USA.
[Zhang, Xiang Yang; Chen, Da Chun; Xiu, Mei Hong; Tan, Yun Long; Yang, Fu De; Haile, Colin N.; Kosten, Thomas R.] Peking Univ, Beijing HuiLongGuan Hosp, Beijing 100871, Peoples R China.
[Zhang, Laurence Y.; Zhang, Laura Y.] Bellaire High Sch, Houston, TX USA.
RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM xyzhang@bcm.edu; kosten@bcm.edu
OI Haile, Colin/0000-0001-8293-7291
FU Stanley Medical Research Institute [03T-459, 05T-726]; Department of
Veterans Affairs; VISN [16]; Mental Illness Research, Education and
Clinical Center (MIRECC); United States National Institute of Health
[K05-DA0454, P50-DA18827, U01-MH79639]
FX This study was supported by the Stanley Medical Research Institute
(03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16,
Mental Illness Research, Education and Clinical Center (MIRECC), United
States National Institute of Health K05-DA0454, P50-DA18827 and
U01-MH79639. These sources had no further role in study design; in the
collection, analysis and interpretation of data; in the writing of the
report; and in the decision to submit the paper for publication.
NR 43
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U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD AUG
PY 2013
VL 47
IS 8
BP 1049
EP 1053
DI 10.1016/j.jpsychires.2013.03.014
PG 5
WC Psychiatry
SC Psychiatry
GA 173IU
UT WOS:000321073500009
PM 23611682
ER
PT J
AU McKay, JR
Van Horn, D
Rennert, L
Drapkin, M
Ivey, M
Koppenhaver, J
AF McKay, James R.
Van Horn, Deborah
Rennert, Lior
Drapkin, Michelle
Ivey, Megan
Koppenhaver, Janelle
TI Factors in sustained recovery from cocaine dependence
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Cocaine dependence; Cocaine abstinence; Recovery; Predictors; Treatment
response; Follow-up; Treatment
ID SUBSTANCE-ABUSE TREATMENT; ADDICTION SEVERITY INDEX; CONTINUING CARE;
FOLLOW-UP; PSYCHOMETRIC PROPERTIES; PSYCHOSOCIAL TREATMENT; DRINKING
TRAJECTORIES; OUTPATIENT TREATMENT; TREATMENT ATTRITION; INITIAL
ABSTINENCE
AB The goal was to identify factors that predicted sustained cocaine abstinence and transitions from cocaine use to abstinence over 24 months. Data from baseline assessments and multiple follow-ups were obtained from three studies of continuing care for patients in intensive outpatient programs (IOPs). In the combined sample, remaining cocaine abstinent and transitioning into abstinence at the next follow-up were predicted by older age, less education, and less cocaine and alcohol use at baseline, and by higher self-efficacy, commitment to abstinence, better social support, lower depression, and lower scores on other problem severity measures assessed during the follow-up. In addition, higher self-help participation, self-help beliefs, readiness to change, and coping assessed during the follow-up predicted transitions from cocaine use to abstinence. These results were stable over 24 months. Commitment to abstinence, self-help behaviors and beliefs, and self-efficacy contributed independently to the prediction of cocaine use transitions. Implications for treatment are discussed. Published by Elsevier Inc.
C1 [McKay, James R.; Van Horn, Deborah; Rennert, Lior; Drapkin, Michelle; Ivey, Megan; Koppenhaver, Janelle] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[McKay, James R.; Drapkin, Michelle] Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
RP McKay, JR (reprint author), Univ Penn, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA.
EM jimrache@mail.med.upenn.edu
FU NIAAA NIH HHS [R01 AA014850, R01 AA14850]; NIDA NIH HHS [K24 DA029062,
R01 DA020623]
NR 75
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U1 2
U2 18
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD AUG
PY 2013
VL 45
IS 2
BP 163
EP 172
DI 10.1016/j.jsat.2013.02.007
PG 10
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 173IH
UT WOS:000321072100002
PM 23561331
ER
PT J
AU McMillan, GP
Hanson, TE
Saunders, G
Gallun, FJ
AF McMillan, Garnett P.
Hanson, Timothy E.
Saunders, Gabrielle
Gallun, Frederick J.
TI A two-component circular regression model for repeated measures auditory
localization data
SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS
LA English
DT Article
DE Angular regression; Bimodal data; B-splines; Sound localization;
Symmetry models
ID BAYESIAN MODEL; DISTRIBUTIONS; SPLINES; TESTS
AB . Auditory localization experiments are conducted to evaluate human ability to locate the position of a source of sound, and to determine how population characteristics might affect this ability. These experiments generate data that are circular, bimodal and repeated, and have hypothesized symmetry patterns that should be included and tested within the modelling framework. We propose a two-part mixture of wrapped Cauchy densities for these bimodal angular data, with random effects to model correlation between repeated measures. The effects of signal position and types of symmetry in the signal response around the circle are modelled by using circular B-splines. The model is used to investigate the effects of age and hearing impairment on the ability to localize a low frequency signal.
C1 [McMillan, Garnett P.; Saunders, Gabrielle; Gallun, Frederick J.] Natl Ctr Rehabil Auditory Res, Portland, OR USA.
[Hanson, Timothy E.] Univ S Carolina, Columbia, SC 29208 USA.
RP McMillan, GP (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM Garnett.McMillan@va.gov
RI Gallun, Frederick/G-3792-2012; Hanson, Timothy/A-9127-2016
OI Gallun, Frederick/0000-0002-4145-2199;
FU Department of Veterans Affairs, Veterans Health Administration
'Rehabilitation research and development' grant [3040]
FX This work was supported by the Department of Veterans Affairs, Veterans
Health Administration 'Rehabilitation research and development' grant
3040. The authors thank Anna Forsline, MA, and M. Samantha Lewis, PhD,
for their assistance with data collection. We are grateful to Dr David
Draper and several reviewers for helpful advice on this paper. The
contents of this paper do not necessarily represent the views of the US
Department of Veterans Affairs or the US Government.
NR 33
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Z9 2
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0035-9254
J9 J R STAT SOC C-APPL
JI J. R. Stat. Soc. Ser. C-Appl. Stat.
PD AUG
PY 2013
VL 62
IS 4
BP 515
EP 534
DI 10.1111/rssc.12004
PG 20
WC Statistics & Probability
SC Mathematics
GA 181YL
UT WOS:000321706600001
ER
PT J
AU D'Amico, AV
AF D'Amico, Anthony V.
TI Adjuvant Versus Salvage Post-Prostatectomy Radiation Therapy: A Critical
Review of the Evidence
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
ID PROSTATE-CANCER; RISK; RADIOTHERAPY; TRIAL
C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
[D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.
NR 4
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD AUG
PY 2013
VL 190
IS 2
BP 450
EP 451
DI 10.1016/j.juro.2013.05.028
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 178HJ
UT WOS:000321436600017
PM 23688645
ER
PT J
AU Avci, P
Nyame, TT
Gupta, GK
Sadasivam, M
Hamblin, MR
AF Avci, Pinar
Nyame, Theodore T.
Gupta, Gaurav K.
Sadasivam, Magesh
Hamblin, Michael R.
TI Low-Level Laser Therapy for Fat Layer Reduction: A Comprehensive Review
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Review
DE body contouring; cellulite; cholesterol; fat; lipoplasty; LLLT;
liposuction
ID NEAR-IR RADIATION; ASSISTED LIPOSUCTION; DUAL-WAVELENGTH; SUBCUTANEOUS
FAT; MAMMALIAN-CELLS; CELLULITE; IRRADIATION; ENERGY; LIGHT; VIABILITY
AB Background and Objective Low-level laser (light) therapy (LLLT) is a noninvasive, nonthermal approach to disorders requiring reduction of pain and inflammation and stimulation of healing and tissue regeneration. Within the last decade, LLLT started being investigated as an adjuvant to liposuction, for noninvasive body contouring, reduction of cellulite, and improvement of blood lipid profile. LLLT may also aid autologous fat transfer procedures by enhancing the viability of adipocytes. However the underlying mechanism of actions for such effects still seems to be unclear. It is important, therefore, to understand the potential efficacy and proposed mechanism of actions of this new procedure for fat reduction.
Materials and Methods A review of the literature associated with applications of LLLT related to fat layer reduction was performed to evaluate the findings from pre-clinical and clinical studies with respect to the mechanism of action, efficacy, and safety.
Results The studies as of today suggest that LLLT has a potential to be used in fat and cellulite reduction as well as in improvement of blood lipid profile without any significant side effects. One of the main proposed mechanism of actions is based upon production of transient pores in adipocytes, allowing lipids to leak out. Another is through activation of the complement cascade which could cause induction of adipocyte apoptosis and subsequent release of lipids.
Conclusion Although the present studies have demonstrated safety and efficacy of LLLT in fat layer reduction, studies demonstrating the efficacy of LLLT as a stand-alone procedure are still inadequate. Moreover, further studies are necessary to identify the mechanism of action. Lasers Surg. Med. 45:349-357, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Avci, Pinar; Gupta, Gaurav K.; Sadasivam, Magesh; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Avci, Pinar; Gupta, Gaurav K.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA USA.
[Avci, Pinar] Semmelweis Univ, Sch Med, Dept Dermatol Dermatooncol & Venerol, H-1085 Budapest, Hungary.
[Nyame, Theodore T.] Harvard Univ, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA.
[Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA.
EM hamblin@helix.mgh.harvard.edu
OI Hamblin, Michael/0000-0001-6431-4605
FU US NIH [R01AI050875]
FX Contract grant sponsor: US NIH; Grant number: R01AI050875
NR 85
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U1 0
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0196-8092
J9 LASER SURG MED
JI Lasers Surg. Med.
PD AUG
PY 2013
VL 45
IS 6
BP 349
EP 357
DI 10.1002/lsm.22153
PG 9
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 182NY
UT WOS:000321751700001
PM 23749426
ER
PT J
AU Walker, SR
Nelson, EA
Yeh, JE
Pinello, L
Yuan, GC
Frank, DA
AF Walker, Sarah R.
Nelson, Erik A.
Yeh, Jennifer E.
Pinello, Luca
Yuan, Guo-Cheng
Frank, David A.
TI STAT5 Outcompetes STAT3 To Regulate the Expression of the Oncogenic
Transcriptional Modulator BCL6
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID B-CELL LYMPHOMA; BREAST-CANCER; SIGNALING PATHWAY; SERINE
PHOSPHORYLATION; HUMAN TUMORS; TRANSDUCER; ACTIVATION; BINDING;
AUTOREGULATION; IDENTIFICATION
AB Inappropriate activation of the transcription factors STAT3 and STAT5 has been shown to drive cancer pathogenesis through dysregulation of genes involved in cell survival, growth, and differentiation. Although STAT3 and STAT5 are structurally related, they can have opposite effects on key genes, including BCL6. BCL6, a transcriptional repressor, has been shown to be oncogenic in diffuse large B cell lymphoma. BCL6 also plays an important role in breast cancer pathogenesis, a disease in which STAT3 and STAT5 can be activated individually or concomitantly. To determine the mechanism by which these oncogenic transcription factors regulate BCL6 transcription, we analyzed their effects at the levels of chromatin and gene expression. We found that STAT3 increases expression of BCL6 and enhances recruitment of RNA polymerase II phosphorylated at a site associated with transcriptional initiation. STAT5, in contrast, represses BCL6 expression below basal levels and decreases the association of RNA polymerase II at the gene. Furthermore, the repression mediated by STAT5 is dominant over STAT3-mediated induction. STAT5 exerts this effect by displacing STAT3 from one of the two regulatory regions to which it binds. These findings may underlie the divergent biology of breast cancers containing activated STAT3 alone or in conjunction with activated STAT5.
C1 [Walker, Sarah R.; Nelson, Erik A.; Yeh, Jennifer E.; Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Walker, Sarah R.; Nelson, Erik A.; Frank, David A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Walker, Sarah R.; Nelson, Erik A.; Yeh, Jennifer E.; Frank, David A.] Harvard Univ, Sch Med, Boston, MA USA.
[Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Pinello, Luca; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM david_frank@dfci.harvard.edu
FU NIH [R01-CA160979]; Susan G. Komen for the Cure; BCRF-AACR grant for
Translational Breast Cancer Research; Brent Leahey Fund; Friends of the
Dana-Farber Cancer Institute
FX This work was supported by NIH grant R01-CA160979, Susan G. Komen for
the Cure, a BCRF-AACR grant for Translational Breast Cancer Research,
the Brent Leahey Fund, and Friends of the Dana-Farber Cancer Institute.
NR 33
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U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD AUG
PY 2013
VL 33
IS 15
BP 2879
EP 2890
DI 10.1128/MCB.01620-12
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 180SD
UT WOS:000321615500007
PM 23716595
ER
PT J
AU Liu, H
Li, WJ
Ahmad, M
Rose, ME
Miller, TM
Yu, M
Chen, J
Pascoe, JL
Poloyac, SM
Hickey, RW
Graham, SH
AF Liu, Hao
Li, Wenjin
Ahmad, Muzamil
Rose, Marie E.
Miller, Tricia M.
Yu, Mei
Chen, Jie
Pascoe, Jordan L.
Poloyac, Samuel M.
Hickey, Robert W.
Graham, Steven H.
TI Increased Generation of Cyclopentenone Prostaglandins after Brain
Ischemia and Their Role in Aggregation of Ubiquitinated Proteins in
Neurons
SO NEUROTOXICITY RESEARCH
LA English
DT Article
DE Cyclopentenone prostaglandins; Cell death; Ubiquitinated protein;
Ubiquitin proteasome system; Primary neuron; Temporary focal ischemia
ID 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); PARKINSONS-DISEASE;
NEURODEGENERATIVE DISEASES; THERAPEUTIC IMPLICATIONS; ENDOGENOUS
ELECTROPHILE; DEGRADATION PATHWAYS; AGGRESOME FORMATION; PROTEASOME
SYSTEM; HYDROLASE UCH-L1; J2
AB The cyclopentenone prostaglandin (CyPG) J(2) series, including prostaglandin J(2) (PGJ(2)), Delta(12)-PGJ(2), and 15-deoxy-a dagger(12,14)-prostaglandin J(2) (15d-PGJ(2)), are active metabolites of PGD(2), exerting multiple effects on neuronal function. However, the physiologic relevance of these effects remains uncertain as brain concentrations of CyPGs have not been precisely determined. In this study, we found that free PGD(2) and the J(2) series CyPGs (PGJ(2), Delta(12)-PGJ(2), and 15d-PGJ(2)) were increased in post-ischemic rat brain as detected by UPLC-MS/MS with 15d-PGJ(2) being the most abundant CyPG. These increases were attenuated by pre-treating with the cyclooxygenase (COX) inhibitor piroxicam. Next, effects of chronic exposure to 15d-PGJ(2) were examined by treating primary neurons with 15d-PGJ(2), CAY10410 (a 15d-PGJ(2) analog lacking the cyclopentenone ring structure), or vehicle for 24 to 96 h. Because we found that the concentration of free 15d-PGJ(2) decreased rapidly in cell culture medium, freshly prepared medium containing 15d-PGJ(2), CAY10410, or vehicle was changed twice daily to maintain steady extracellular concentrations. Incubation with 2.5 mu M 15d-PGJ(2), but not CAY10410, increased the neuronal cell death without the induction of caspase-3 or PARP cleavage, consistent with a primarily necrotic mechanism for 15d-PGJ(2)-induced cell death which was further supported by TUNEL assay results. Ubiquitinated protein accumulation and aggregation was observed after 96 h 15d-PGJ(2) incubation, accompanied by compromised 20S proteasome activity. Unlike another proteasome inhibitor, MG132, 15d-PGJ(2) treatment did not activate autophagy or induce aggresome formation. Therefore, the cumulative cytotoxic effects of increased generation of CyPGs after stroke may contribute to delayed post-ischemic neuronal injury.
C1 [Liu, Hao; Li, Wenjin; Ahmad, Muzamil; Rose, Marie E.; Pascoe, Jordan L.; Graham, Steven H.] VA Pittsburgh Healthcare, Geriatr Res Educ & Clin Ctr GR H 00, Pittsburgh, PA 15206 USA.
[Liu, Hao; Li, Wenjin; Ahmad, Muzamil; Rose, Marie E.; Yu, Mei; Chen, Jie; Pascoe, Jordan L.; Graham, Steven H.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA.
[Miller, Tricia M.; Poloyac, Samuel M.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
[Hickey, Robert W.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA.
RP Graham, SH (reprint author), VA Pittsburgh Healthcare, Geriatr Res Educ & Clin Ctr GR H 00, 7180 Highland Dr, Pittsburgh, PA 15206 USA.
EM sgra@pitt.edu
FU National Institutes of Health/National Institute of Neurological
Disorders and Stroke [R01NS37459]
FX This work was supported by the National Institutes of Health/National
Institute of Neurological Disorders and Stroke R01NS37459. The authors
thank Pat Strickler for secretarial support.
NR 53
TC 14
Z9 14
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1029-8428
J9 NEUROTOX RES
JI Neurotox. Res.
PD AUG
PY 2013
VL 24
IS 2
BP 191
EP 204
DI 10.1007/s12640-013-9377-4
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 170VN
UT WOS:000320882700009
PM 23355003
ER
PT J
AU McKenzie, T
Chen, Y
Shikora, S
Hodin, R
Moore, F
Lubitz, C
AF McKenzie, T.
Chen, Y.
Shikora, S.
Hodin, R.
Moore, F., Jr.
Lubitz, C.
TI Primary Hyperparathyroidism After Roux-en-Y Gastric Bypass: A Case
Series
SO OBESITY SURGERY
LA English
DT Meeting Abstract
CT 18th World Congress of the
International-Federation-for-the-Surgery-of-Obesity-and-Metabolic-Disord
ers (IFSO)
CY AUG 28-31, 2013
CL Istanbul, TURKEY
SP Int Federat Surg Obes & Metab Disorders (IFSO)
C1 [McKenzie, T.; Chen, Y.; Hodin, R.; Lubitz, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Shikora, S.; Moore, F., Jr.] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0960-8923
J9 OBES SURG
JI Obes. Surg.
PD AUG
PY 2013
VL 23
IS 8
BP 1033
EP 1033
PG 1
WC Surgery
SC Surgery
GA 177QC
UT WOS:000321389200055
ER
PT J
AU Lee, MK
Dodson, TB
Karimbux, NY
Nalliah, RP
Allareddy, V
AF Lee, Min Kyeong
Dodson, Thomas B.
Karimbux, Nadeem Y.
Nalliah, Romesh P.
Allareddy, Veerasathpurush
TI Effect of occurrence of infection-related never events on length of stay
and hospital charges in patients undergoing radical neck dissection for
head and neck cancer
SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY
LA English
DT Article
ID CLOSTRIDIUM-DIFFICILE INFECTION; NOSOCOMIAL INFECTIONS; IMPACT; SURGERY;
COMPLICATIONS; INTERVENTION; COSTS; CARE
AB Objective. To estimate the impact of infection-related never events (postoperative pneumonia, Clostridium difficile infection, infection with microorganisms resistant to penicillin, postoperative infections, and decubitus ulcers) following radical neck dissections for head and neck cancers.
Study Design. The 2008 Nationwide Inpatient Sample was used to select hospitalizations with HNC that underwent radical neck dissections. Predictor variables were occurrence of never events and other patient-and hospital-level factors. Outcome variables were hospitalization charges and length of stay (LOS). Regression analyses were used to measure the association between predictors and outcomes.
Results. Among 10,660 hospitalizations, prevalence of never events ranged from 0.2% to 5.0%. Mean hospitalization charge and LOS were $75,654 and 6.8 days, respectively. Never events were associated with 5.6-10.0 longer LOS and $49,153-$124,057 excess charges.
Conclusion. Occurrence of never events was associated with at least 5.6 longer hospital days and $49,153 charge compared with hospitalizations without a never event.
C1 [Lee, Min Kyeong] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
[Dodson, Thomas B.] Massachusetts Gen Hosp, Ctr Appl Clin Invest, Boston, MA 02114 USA.
[Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral Surg, Boston, MA 02114 USA.
[Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Maxillofacial Surg, Boston, MA 02114 USA.
[Dodson, Thomas B.; Nalliah, Romesh P.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Karimbux, Nadeem Y.] Tufts Univ, Sch Dent Med, Dept Periodontol, Boston, MA 02111 USA.
[Allareddy, Veerasathpurush] Boston Childrens Hosp, Dept Dent, Boston, MA USA.
RP Lee, MK (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA.
EM minkyminko@gmail.com
NR 24
TC 15
Z9 15
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-4403
J9 OR SURG OR MED OR PA
JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol.
PD AUG
PY 2013
VL 116
IS 2
BP 147
EP 158
DI 10.1016/j.oooo.2013.02.006
PG 12
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 182JL
UT WOS:000321737900015
PM 23591100
ER
PT J
AU Nicolatou-Galitis, O
Nikolaidi, A
Athanassiadis, I
Papadopoulou, E
Sonis, S
AF Nicolatou-Galitis, Ourania
Nikolaidi, Adamantia
Athanassiadis, Ilias
Papadopoulou, Erofili
Sonis, Stephen
TI Oral ulcers in patients with advanced breast cancer receiving
everolimus: a case series report on clinical presentation and management
SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY
LA English
DT Article
ID RENAL-CELL CARCINOMA; MAMMALIAN TARGET; MTOR INHIBITORS; APHTHOUS
ULCERS; STOMATITIS; RAPAMYCIN; THERAPY; TEMSIROLIMUS; INFECTION;
MUCOSITIS
AB Objective. We report the clinical features and management outcomes in 7 patients with everolimus-related stomatitis.
Study design. Fifteen women with hormone-receptor-positive advanced breast cancer receiving everolimus combined with exemestane were prospectively evaluated to assess the development of stomatitis. Oral ulcers were diagnosed based on established criteria.
Results. Seven patients developed stomatitis (46.6%). All patients were treated with topical dexamethasone solution, while everolimus was temporarily discontinued in 4 patients. Stomatitis resolved within 1-2 weeks. Two of the 4 patients, who had interrupted everolimus, developed recurrent stomatitis following drug resume and everolimus was again discontinued and restarted after 2 weeks. To date, 5 patients receive everolimus in full dose. The 2 patients, who developed recurrent stomatitis, received a reduced dose.
Conclusions. Everolimus-related oral ulcers were frequent and led to dose modifications. Controlled trials, endorsing a consensus in terminology, are needed to evaluate measures on prevention and management of this unique toxicity.
C1 [Nicolatou-Galitis, Ourania; Papadopoulou, Erofili] Univ Athens, Sch Dent, Clin Hosp Dent, Oral Oncol Unit, Athens 11527, Greece.
[Nikolaidi, Adamantia; Athanassiadis, Ilias] Mitera Hosp Ygeia, Dept Oncol, Athens, Greece.
[Sonis, Stephen] Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA.
[Sonis, Stephen] Dana Farber Canc Inst, Div Oral Med, Boston, MA 02115 USA.
RP Nicolatou-Galitis, O (reprint author), Univ Athens, Sch Dent, Clin Hosp Dent, Thivon 2, Athens 11527, Greece.
EM nicolatou.galitis@hotmail.com
NR 29
TC 9
Z9 10
U1 2
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-4403
J9 OR SURG OR MED OR PA
JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol.
PD AUG
PY 2013
VL 116
IS 2
BP E110
EP E116
DI 10.1016/j.oooo.2013.02.022
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 182JL
UT WOS:000321737900006
PM 23643584
ER
PT J
AU Carbone, LD
Chin, AS
Burns, SP
Svircev, JN
Hoenig, H
Heggeness, M
Weaver, F
AF Carbone, L. D.
Chin, A. S.
Burns, S. P.
Svircev, J. N.
Hoenig, H.
Heggeness, M.
Weaver, F.
TI Morbidity following lower extremity fractures in men with spinal cord
injury
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE Fractures; Men; Morbidity; Pressure ulcers; Spinal cord injury
ID HIP FRACTURE; TRACT-INFECTION; RISK-FACTORS; SCI QUERI; VETERANS;
MANAGEMENT; DISORDERS; IMPLEMENTATION; EPIDEMIOLOGY; OSTEOPOROSIS
AB The Veterans Affairs Spinal Cord Dysfunction Registry from 2002 to 2007 was reviewed to determine whether men with spinal cord injury (SCI) and lower extremity fractures had an increased risk of complications compared to those without fractures. We determined that fractures are associated with significant consequences, particularly during the first month postfracture.
Despite increasing longevity, patients with SCI have a substantial number of illnesses and comorbid conditions. Lower extremity fractures are frequent events in these patients. However, whether these fractures are associated with any increased risk of complications in SCI is not certain. The purpose of this report was to determine the impact of lower extremity fractures on morbidities in men with SCI.
A population-based, nested, case-control (1,027 cases and 1,027 propensity-matched controls) of men enrolled in the Veterans Affairs Spinal Cord Dysfunction Registry from fiscal years 2002 to 2007 was reviewed to determine whether lower extremity fractures were associated with an increased risk for complications.
In propensity score models matched for demographic (age, race) and SCI-related injury factors (level/completeness of SCI), Veterans Affairs-service connection status, and comorbidities, at 1 month following the fracture, there was an increased risk for respiratory infections, pressure ulcers, urinary tract infections, thromboembolic events, depression, and delirium (p a parts per thousand currency signaEuro parts per thousand 0.03 for all). Over 12 months, the only complication more common in fracture cases was pressure ulcers (p < 0.01), with an absolute difference of less than 2 % when compared to controls. There was no significant increased risk of cardiac arrhythmias at any time examined following fracture (a parts per thousand yen0.12).
Lower extremity fractures are associated with significant consequences in men with SCI during the first month postfracture, but they do not persist for a long term, except for pressure ulcers. Targeted interventions to prevent complications should be considered following lower extremity fractures in SCI, particularly in the first month following fracture.
C1 [Carbone, L. D.] Vet Affairs Med Ctr, Memphis, TN 38163 USA.
[Carbone, L. D.] Univ Tennessee, Ctr Hlth Sci, Dept Med, Div Rheumatol, Memphis, TN 38163 USA.
[Chin, A. S.; Weaver, F.] Edward J Hines Jr VA Hosp, Hines, IL USA.
[Burns, S. P.; Svircev, J. N.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Burns, S. P.; Svircev, J. N.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Hoenig, H.] Durham Vet Affairs Med Ctr, Durham, NC USA.
[Heggeness, M.] Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Heggeness, M.] Baylor Coll Med, Dept Orthoped, Houston, TX 77030 USA.
[Weaver, F.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA.
RP Carbone, LD (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Med, Div Rheumatol, Memphis, TN 38163 USA.
EM lcarbone@uthsc.edu
FU Department of Veterans Affairs, Veterans Health Administration, Health
Services Research and Development [IIR 08-033]
FX This work was supported by the Department of Veterans Affairs, Veterans
Health Administration, Health Services Research and Development #IIR
08-033.
NR 39
TC 10
Z9 10
U1 1
U2 10
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD AUG
PY 2013
VL 24
IS 8
BP 2261
EP 2267
DI 10.1007/s00198-013-2295-8
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 181GH
UT WOS:000321655500013
PM 23392311
ER
PT J
AU Zhao, W
Petit, E
Gafni, RI
Collins, MT
Robey, PG
Seton, M
Miller, KK
Mannstadt, M
AF Zhao, W.
Petit, E.
Gafni, R. I.
Collins, M. T.
Robey, P. G.
Seton, M.
Miller, K. K.
Mannstadt, M.
TI Mutations in NOTCH2 in patients with Hajdu-Cheney syndrome
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE Acroosteolysis; Exome sequencing; Hajdu-Cheney syndrome; NOTCH2;
Osteoporosis
ID OSTEOPOROSIS; ACTIVATION; DISORDER
AB The Hajdu-Cheney syndrome is a very rare disease that affects several organ system, leading to severe osteoporosis and other abnormalities. We describe clinical and genetic findings of nine patients with this disease.
The Hajdu-Cheney syndrome (HCS) is a rare autosomal dominant disorder characterized by severe osteoporosis, acroosteolysis of the distal phalanges, renal cysts, and other abnormalities. Recently, heterozygous mutations in NOTCH2 were identified as the cause of HCS.
Nine patients with typical presentations of HCS took part in this study: five affected patients from two small families and four sporadic cases. Peripheral blood DNA was obtained and exome sequencing performed in one affected individual per family and in all four sporadic cases. Sanger sequencing confirmed mutations in all patients.
One of the identified mutations was introduced in a plasmid encoding NOTCH2. Wild-type and mutant NOTCH2 were transiently expressed in HEK293 cells to assess intracellular localization after ligand activation. Deleterious heterozygous mutations in the last NOTCH2 exon were identified in all patients; five of the six mutations were novel.
Consistent with previous reports, all mutations are predicted to result in a loss of the proline/glutamic acid/serine/threonine sequence, which harbors signals for degradation, therefore suggesting activating mutations. One of the six mutations furthermore predicted disruption of the second nuclear localization signal of NOTCH2, but the mutant revealed normal nuclear localization after transfection, which is consistent with the proposed gain-of-function mechanism as the cause of this autosomal dominant disease. Our findings confirm that heterozygous NOTCH2 mutations are the cause of HCS and expand the mutational spectrum of this disorder.
C1 [Zhao, W.; Petit, E.; Mannstadt, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Seton, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
[Gafni, R. I.; Collins, M. T.; Robey, P. G.] NIDCR, CSDB, NIH, Bethesda, MD USA.
[Miller, K. K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
RP Mannstadt, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Thier 10,55 Fruit St, Boston, MA 02114 USA.
EM mmannstadt@partners.org
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
FU NHGRI [U54 HG003067]; National Institute of Diabetes and Digestive and
Kidney Disease [K08-DK081669-01]; Division of Intramural Research,
NIDCR, a part of the Intramural Research Program of the NIH, DHHS
FX We like to thank all patients and family members who participated in
this study. We thank the Broad Institute for generating high-quality
sequence data supported by NHGRI funds (U54 HG003067, PI Eric Lander),
Harald Juppner for support and Spyros Artavanis-Tsakonas for the Notch2
cDNA plasmid. This research was supported, in part, by grants from the
National Institute of Diabetes and Digestive and Kidney Disease
(K08-DK081669-01 to M. M.) and by the Division of Intramural Research,
NIDCR, a part of the Intramural Research Program of the NIH, DHHS.
NR 25
TC 8
Z9 8
U1 0
U2 5
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
EI 1433-2965
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD AUG
PY 2013
VL 24
IS 8
BP 2275
EP 2281
DI 10.1007/s00198-013-2298-5
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 181GH
UT WOS:000321655500015
PM 23389697
ER
PT J
AU Kim, J
Loggia, ML
Edwards, RR
Wasan, AD
Gollub, RL
Napadow, V
AF Kim, Jieun
Loggia, Marco L.
Edwards, Robert R.
Wasan, Ajay D.
Gollub, Randy L.
Napadow, Vitaly
TI Sustained deep-tissue pain alters functional brain connectivity
SO PAIN
LA English
DT Article
DE Somatosensory; Sensorimotor network; Salience network; Dorsal attention
network; Frontoparietal control network; Functional connectivity
ID DIABETIC NEUROPATHIC PAIN; INDEPENDENT COMPONENT ANALYSIS; BLOOD-FLOW
CHANGES; RESTING-STATE; SOMATOSENSORY CORTEX; INSULAR CORTEX; STRUCTURAL
CONNECTIVITY; INDIVIDUAL-DIFFERENCES; SUBJECTIVE EXPERIENCE; SELECTIVE
ATTENTION
AB Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, frontoparietal control, and default mode networks: SMN, SLN, DAN, FCN, and DMN) was evaluated with functional-connectivity magnetic resonance imaging, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable, with no significant changes of subjects' pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula, and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to interindividual differences in pain sensitivity. (C) 2013 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
C1 [Kim, Jieun; Loggia, Marco L.; Gollub, Randy L.; Napadow, Vitaly] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA.
[Loggia, Marco L.; Edwards, Robert R.; Wasan, Ajay D.; Napadow, Vitaly] Harvard Univ, Brigham & Womens Hosp, Med Sch HMS, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
[Loggia, Marco L.; Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, HMS, Boston, MA 02114 USA.
[Edwards, Robert R.; Wasan, Ajay D.] Brigham & Womens Hosp, Dept Psychiat, HMS, Boston, MA 02115 USA.
RP Kim, J (reprint author), Massachusetts Gen Hosp, 2301,149 13th St, Charlestown, MA 02129 USA.
EM seesaw@nmr.mgh.harvard.edu
OI Gollub, Randy L./0000-0002-9434-4044
FU National Institutes of Health [R01-AT004714, P01-AT002048,
1K23DA020681-01A1]; NCRR [P41RR14075, CRC 1 UL1 RR025758]; American
College of Rheumatology; Arthritis Foundation
FX We would like to thank the National Institutes of Health for funding
support (VN: R01-AT004714, P01-AT002048; AW: 1K23DA020681-01A1), the
NCRR (P41RR14075; CRC 1 UL1 RR025758, Harvard Clinical and Translational
Science Center). Dr. Edwards received support for this study from the
American College of Rheumatology and the Arthritis Foundation. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of our sponsors.
NR 82
TC 12
Z9 12
U1 0
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD AUG
PY 2013
VL 154
IS 8
BP 1343
EP 1351
DI 10.1016/j.pain.2013.04.016
PG 9
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 176XF
UT WOS:000321339400024
PM 23718988
ER
PT J
AU Bortsov, AV
Smith, JE
Diatchenko, L
Soward, AC
Ulirsch, JC
Rossi, C
Swor, RA
Hauda, WE
Peak, DA
Jones, JS
Holbrook, D
Rathlev, NK
Foley, KA
Lee, DC
Collette, R
Domeier, RM
Hendry, PL
McLean, SA
AF Bortsov, Andrey V.
Smith, Jennifer E.
Diatchenko, Luda
Soward, April C.
Ulirsch, Jacob C.
Rossi, Catherine
Swor, Robert A.
Hauda, William E.
Peak, David A.
Jones, Jeffrey S.
Holbrook, Debra
Rathlev, Niels K.
Foley, Kelly A.
Lee, David C.
Collette, Renee
Domeier, Robert M.
Hendry, Phyllis L.
McLean, Samuel A.
TI Polymorphisms in the glucocorticoid receptor co-chaperone FKBP5 predict
persistent musculoskeletal pain after traumatic stress exposure
SO PAIN
LA English
DT Article
DE Motor vehicle collision; Rape; Musculoskeletal pain; Single nucleotide
polymorphism; Glucocorticoid receptor
ID WHIPLASH-ASSOCIATED DISORDERS; SEXUAL ASSAULT HISTORY; REPEATED SOUND
STRESS; EMERGENCY-DEPARTMENT; ASSOCIATION; POPULATION; AXIS;
HYPERALGESIA; SYMPTOMS; RISK
AB Individual vulnerability factors influencing the function of the hypothalamic-pituitary-adrenal axis may contribute to the risk of the development of persistent musculoskeletal pain after traumatic stress exposure. The objective of the study was to evaluate the association between polymorphisms in the gene encoding FK506 binding protein 51, FKBP5, a glucocorticoid receptor co-chaperone, and musculoskeletal pain severity 6 weeks after 2 common trauma exposures. The study included data from 2 prospective emergency department-based cohorts: a discovery cohort (n = 949) of European Americans experiencing motor vehicle collision and a replication cohort of adult European American women experiencing sexual assault (n = 53). DNA was collected from trauma survivors at the time of initial assessment. Overall pain and neck pain 6 weeks after trauma exposure were assessed using a 0-10 numeric rating scale. After adjustment for multiple comparisons, 6 FKBP5 polymorphisms showed significant association (minimum P < 0.0001) with both overall and neck pain in the discovery cohort. The association of rs3800373, rs9380526, rs9394314, rs2817032, and rs2817040 with neck pain and/or overall pain 6 weeks after trauma was replicated in the sexual assault cohort, showing the same direction of the effect in each case. The results of this study indicate that genetic variants in FKBP5 influence the severity of musculoskeletal pain symptoms experienced during the weeks after motor vehicle collision and sexual assault. These results suggest that glucocorticoid pathways influence the development of persistent posttraumatic pain, and that such pathways may be a target of pharmacologic interventions aimed at improving recovery after trauma. (C) 2013 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
C1 [Bortsov, Andrey V.; Smith, Jennifer E.; Soward, April C.; Ulirsch, Jacob C.; McLean, Samuel A.] Univ N Carolina, TRYUMPH Res Program, Chapel Hill, NC 27599 USA.
[Bortsov, Andrey V.; Smith, Jennifer E.; Soward, April C.; Ulirsch, Jacob C.; McLean, Samuel A.] Univ N Carolina, Dept Anesthesiol, Chapel Hill, NC 27599 USA.
[Diatchenko, Luda] Univ N Carolina, Reg Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA.
[Rossi, Catherine] Cone Hlth Syst, Dept Med, Forens Nursing Program, Greensboro, NC USA.
[Swor, Robert A.] William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48072 USA.
[Hauda, William E.] Inova Fairfax Hosp, Forens Assessment & Consultat Teams, Falls Church, VA USA.
[Peak, David A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Jones, Jeffrey S.] Spectrum Hlth Syst, Dept Emergency Med, Grand Rapids, MI USA.
[Holbrook, Debra] Mercy Med Ctr, SANE Sexual Assault Nurse Examiner Program, Baltimore, MD USA.
[Rathlev, Niels K.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA.
[Foley, Kelly A.] Sentara Norfolk Hosp, Dept Emergency Med, Norfolk, VA USA.
[Lee, David C.] N Shore Univ Hosp, Dept Emergency Med, Manhasset, NY USA.
[Collette, Renee] Mission Hlth Syst, SANE Program, Asheville, NC USA.
[Domeier, Robert M.] St Joseph Mercy Hlth Syst, Dept Emergency Med, Ypsilanti, MI USA.
[Hendry, Phyllis L.] Univ Florida, Dept Emergency Med, Jacksonville, FL USA.
[McLean, Samuel A.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC 27599 USA.
RP McLean, SA (reprint author), Univ N Carolina, Sch Med, Wing C CB 7010, Chapel Hill, NC 27599 USA.
EM smclean@aims.unc.edu
OI McLean, Samuel/0000-0001-9482-3582
FU National Institute of Arthritis, Musculoskeletal, and Skin Diseases [R01
AR056328]; National Center for Research Resources [UL1RR025747]
FX Funding for this study was provided by the National Institute of
Arthritis, Musculoskeletal, and Skin Diseases (R01 AR056328: Samuel A.
McLean) and by the National Center for Research Resources (UL1RR025747:
Samuel A. McLean). None of the above funding agencies had any role in
the design and conduct of the study, in the collection, management,
analysis and interpretation of the data, or in the preparation, review,
or approval of the manuscript.
NR 56
TC 20
Z9 20
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD AUG
PY 2013
VL 154
IS 8
BP 1419
EP 1426
DI 10.1016/j.pain.2013.04.037
PG 8
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 176XF
UT WOS:000321339400033
PM 23707272
ER
PT J
AU Medoff, BD
AF Medoff, Benjamin D.
TI Fat, fire and muscle - The role of adiponectin in pulmonary vascular
inflammation and remodeling
SO PULMONARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
DE Pulmonary hypertension; Obesity; Adiponectin; Pulmonary vascular disease
ID SERUM RESPONSE FACTOR; ACTIVATED PROTEIN-KINASE; ADIPOSE-SPECIFIC
PROTEIN; CORONARY-ARTERY-DISEASE; SMOOTH-MUSCLE; GROWTH-FACTOR;
MYOCARDIAL-INFARCTION; PLASMA-CONCENTRATIONS; CELL DIFFERENTIATION;
MOUSE MODEL
AB Pulmonary hypertension is a life-threatening condition that results from a heterogeneous group of diseases, many of which demonstrate characteristic pathologic changes of pulmonary vascular inflammation and remodeling. Recent clinical studies indicate obesity to be a risk factor for the development of pulmonary hypertension; however, the mechanisms leading to this association are unknown. Adipocytes secrete multiple bioactive mediators that can influence inflammation and tissue remodeling, suggesting that adipose tissue may directly influence the pathogenesis of pulmonary hypertension. One of these mediators is adiponectin, a protein with a wide range of metabolic, anti-inflammatory, and antiproliferative activities. Paradoxically, adiponectin is present in high concentration in the serum of lean healthy individuals, but decreases in obesity. Studies suggest that relative adiponectin-deficiency may contribute to the development of inflammatory diseases in obesity, and recent animal studies implicate adiponectin in the pathogenesis of pulmonary hypertension. Most notably, experimental studies show that adiponectin can reduce lung vascular remodeling in response to inflammation and hypoxia. Moreover, mice deficient in adiponectin develop a spontaneous lung vascular phenotype characterized by age-dependent increases in pen-vascular inflammatory cells and elevated pulmonary artery pressures. Emerging evidence indicates adiponectin's effects are mediated through anti-inflammatory and anti-proliferative actions on cells in the lung. This review aims to synthesize the existing data related to adiponectin's effects on the pulmonary vasculature and to discuss how changes in adiponectin levels might contribute to the development of pulmonary hypertension. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Medoff, Benjamin D.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Medoff, Benjamin D.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
[Medoff, Benjamin D.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Medoff, BD (reprint author), Massachusetts Gen Hosp, Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA.
EM bmedoff@partners.org
NR 112
TC 1
Z9 1
U1 1
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1094-5539
J9 PULM PHARMACOL THER
JI Pulm. Pharmacol. Ther.
PD AUG
PY 2013
VL 26
IS 4
BP 420
EP 426
DI 10.1016/j.pupt.2012.06.006
PG 7
WC Pharmacology & Pharmacy; Respiratory System
SC Pharmacology & Pharmacy; Respiratory System
GA 177WT
UT WOS:000321406800004
PM 22750271
ER
PT J
AU Dougan, SK
Dougan, M
Kim, J
Turner, JA
Ogata, S
Cho, HI
Jaenisch, R
Celis, E
Ploegh, HL
AF Dougan, Stephanie K.
Dougan, Michael
Kim, Jun
Turner, Jacob A.
Ogata, Souichi
Cho, Hyun-Il
Jaenisch, Rudolf
Celis, Esteban
Ploegh, Hidde L.
TI Transnuclear TRP1-Specific CD8 T Cells with High or Low Affinity TCRs
Show Equivalent Antitumor Activity
SO CANCER IMMUNOLOGY RESEARCH
LA English
DT Article
ID CANCER-IMMUNOTHERAPY; METASTATIC MELANOMA; BINDING-PROPERTIES;
VIRAL-INFECTION; TUMOR VACCINES; REGULATORY T; MICE; BLOCKADE; PEPTIDE;
ACTIVATION
AB We have generated, via somatic cell nuclear transfer, two independent lines of transnuclear mice, using as nuclear donors CD8 T cells, sorted by tetramer staining, that recognize the endogenous melanoma antigen tyrosinase related protein 1 (TRP1). These two lines of nominally identical specificity differ greatly in their affinity for antigen (TRP1(high) or TRP1(low)) as inferred from tetramer dissociation and peptide responsiveness. Ex vivo-activated CD8 T cells from either TRP1(high) or TRP1(low) mice show cytolytic activity in three-dimensional tissue culture and in vivo, and slow the progression of subcutaneous B16 melanoma. Although naive TRP1(low) CD8 T cells do not affect tumor growth, upon activation these cells function indistinguishably from TRP1(high) cells in vivo, limiting tumor cell growth and increasing mouse survival. The antitumor effect of both TRP1(high) and TRP1(low) CD8 T cells is enhanced in RAG-deficient hosts. However, tumor outgrowth eventually occurs, likely due to T cell exhaustion. The TRP1 transnuclear mice are an excellent model for examining the functional attributes of T cells conferred by T cell receptor (TCR) affinity, and they may serve as a platform for screening immunomodulatory cancer therapies. (C) 2013 AACR.
C1 [Dougan, Stephanie K.; Dougan, Michael; Kim, Jun; Turner, Jacob A.; Ogata, Souichi; Jaenisch, Rudolf; Ploegh, Hidde L.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Kim, Jun] MIT, Cambridge, MA 02139 USA.
[Dougan, Michael] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Turner, Jacob A.] Univ Cincinnati, Cincinnati, OH USA.
[Ogata, Souichi] Janssen Res & Dev, Div Janssen Pharmaceut NV, Beerse, Belgium.
[Cho, Hyun-Il; Celis, Esteban] H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL USA.
RP Ploegh, HL (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr,Rm 361, Cambridge, MA 02142 USA.
EM ploegh@wi.mit.edu
FU Cancer Research Institute; Bushrod H. Campbell and Adah F. Hall Charity
Fund; Harold Whitworth Pierce Charitable Trust; Janssen Pharmaceutica
NV; NIH; Janssen Pharmaceuticals, Inc; AACR-Pancreatic Cancer Action
Network
FX S.K. Dougan was funded by the Cancer Research Institute and by the
Bushrod H. Campbell and Adah F. Hall Charity Fund and Harold Whitworth
Pierce Charitable Trust. S. Ogata was funded by Janssen Pharmaceutica
NV.E. Celis, H.L. Ploegh, and R. Jaenisch are funded by grants from the
NIH. S.K. Dougan and H.L. Ploegh are funded by Janssen Pharmaceuticals,
Inc. and by the AACR-Pancreatic Cancer Action Network.
NR 56
TC 9
Z9 9
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2326-6066
EI 2326-6074
J9 CANCER IMMUNOL RES
JI Cancer Immunol. Res.
PD AUG
PY 2013
VL 1
IS 2
BP 99
EP 111
DI 10.1158/2326-6066.CIR-13-0047
PG 13
WC Oncology; Immunology
SC Oncology; Immunology
GA AM7FG
UT WOS:000340029500004
PM 24459675
ER
PT J
AU Dolmatova, E
Mahida, S
Ellinor, PT
Lubitz, SA
AF Dolmatova, Elena
Mahida, Saagar
Ellinor, Patrick T.
Lubitz, Steven A.
TI Genetic Etiology and Evaluation of Sudden Cardiac Death
SO CURRENT CARDIOLOGY REPORTS
LA English
DT Article
DE Sudden cardiac death; Ventricular tachycardia and fibrillation;
Genetics; Inherited arrhythmia
ID LONG-QT SYNDROME; POLYMORPHIC VENTRICULAR-TACHYCARDIA;
ST-SEGMENT-ELEVATION; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR;
TERM-FOLLOW-UP; GENOTYPE-PHENOTYPE CORRELATION;
AMERICAN-HEART-ASSOCIATION; GENOME-WIDE ASSOCIATION; BUNDLE-BRANCH
BLOCK; HYPERTROPHIC CARDIOMYOPATHY
AB A wide range of inherited syndromes can result in ventricular arrhythmias and sudden cardiac death (SCD). The natural histories of inherited arrhythmia syndromes are highly variable and current risk stratification techniques are limited. Thus, the management of these conditions can be difficult and often involves a combination of risk assessment, lifestyle modification, cardiac interventions, counselling, and family screening. Recent advances in high throughput sequencing have enabled routine testing in patients with a high clinical index of suspicion for an inherited arrhythmia condition, and cascade screening in relatives of mutation carriers. Given the complexity in screening and data interpretation that has been introduced by recent genomic advances, individuals with inherited arrhythmia syndromes are encouraged to seek care at specialized centers with cardiovascular genetics expertise. In this review, we discuss the etiologies of SCD syndromes and discuss strategies for the evaluation of patients at risk for SCD with a focus on the role of genetic testing and family screening.
C1 [Dolmatova, Elena; Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Mahida, Saagar] Leeds Gen Infirm, Leeds LS1 3EX, W Yorkshire, England.
[Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
RP Lubitz, SA (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA.
EM slubitz@partners.org
NR 130
TC 4
Z9 4
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3782
EI 1534-3170
J9 CURR CARDIOL REP
JI Curr. Cardiol. Rep.
PD AUG
PY 2013
VL 15
IS 8
AR 389
DI 10.1007/s11886-013-0389-8
PG 14
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AT6YO
UT WOS:000345083200008
PM 23812838
ER
PT J
AU Sanchez-Tejada, L
Sanchez-Ortiga, R
Moreno-Perez, O
Montanana, CF
Niveiro, M
Tritos, NA
Alfonso, AMP
AF Sanchez-Tejada, Laura
Sanchez-Ortiga, Ruth
Moreno-Perez, Oscar
Fajardo Montanana, Carmen
Niveiro, Maria
Tritos, Nicholas A.
Pico Alfonso, Antonio M.
TI Pituitary tumor transforming gene and insulin-like growth factor 1
receptor expression and immunohistochemical measurement of Ki-67 as
potential prognostic markers of pituitary tumors aggressiveness
SO ENDOCRINOLOGIA Y NUTRICION
LA English
DT Article
DE Pituitary adenoma; Pituitary tumor transforming gene protein; Humans;
Ki-67 antigen; Insulin-like growth factor 1 receptor
AB Introduction and objective: The ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGFIR), and Ki-67.
Materials and methods: In this retrospective study, the normalized copy number (NCN) of PTIG and IGFIR mRNA was measured using RT-PCR, and the Ki-67 index was measured by immunohistochemistry in 46 PA samples. Clinical data, histological subtype, and radiographic characteristics were collected to assess associations between variables and tumor behavior. Progression of tumor remnants and its association to markers was also studied in 14 patients with no adjuvant treatment after surgery followed up for 46 +/- 36 months.
Results: Extrasellar tumors had a lower PUG expression as compared to sellar tumors (0.065 [1st-3rd quartile: 0.000-0.089] NCN vs. 0.135 [0.105-0.159] NCN, p= 0.04). IGFIR expression changed depending on histological subtype (p= 0.014), and was greater in tumor with remnant growth greater than 20% during follow-up (10.69 +/- 3.84 NCN vs. 5.44 +/- 3.55 NCN, p= 0.014).
Conclusions: Our results suggest that the IGFIR is a more helpful molecular marker than PUG in PA management. Ki-67 showed no association to tumor behavior. However, the potential of these markers should be established in future studies with standardized methods and on larger samples. (C) 2012 SEEN. Published by Elsevier Espana, S.L. All rights reserved.
C1 [Sanchez-Tejada, Laura; Sanchez-Ortiga, Ruth; Moreno-Perez, Oscar; Pico Alfonso, Antonio M.] Hosp Gen Univ Alicante, Res Unit, Dept Endocrinol, Alicante, Spain.
[Fajardo Montanana, Carmen] Hosp Univ La Ribera, Dept Endocrinol, La Ribera, Spain.
[Niveiro, Maria] Hosp Gen Univ Alicante, Dept Pathol, Alicante, Spain.
[Tritos, Nicholas A.] Massachusetts Gen Hosp, Neuroendocrin Unit, Boston, MA 02114 USA.
[Tritos, Nicholas A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Alfonso, AMP (reprint author), Hosp Gen Univ Alicante, Res Unit, Dept Endocrinol, Alicante, Spain.
EM antonio.pico@umh.es
RI Moreno-Perez, Oscar/F-4556-2016
OI Moreno-Perez, Oscar/0000-0002-8670-6404
FU Pfizer Grant
FX This work was supported by Pfizer Grant.
NR 30
TC 11
Z9 16
U1 0
U2 2
PU ELSEVIER DOYMA SL
PI BARCELONA
PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN
SN 1575-0922
EI 1579-2021
J9 ENDOCRINOL NUTR
JI Endocrinol. Nutr.
PD AUG-SEP
PY 2013
VL 60
IS 7
BP 358
EP 367
DI 10.1016/j.endoen.2013.10.001
PG 10
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA V43XT
UT WOS:000209714800003
PM 23416216
ER
PT J
AU Krim, SR
Vivo, RP
Krim, NR
Qian, F
Cox, M
Ventura, H
Hernandez, AF
Bhatt, DL
Fonarow, GC
AF Krim, Selim R.
Vivo, Rey P.
Krim, Nassim R.
Qian, Feng
Cox, Margueritte
Ventura, Hector
Hernandez, Adrian F.
Bhatt, Deepak L.
Fonarow, Gregg C.
TI Racial/Ethnic Differences in B-Type Natriuretic Peptide Levels and Their
Association With Care and Outcomes Among Patients Hospitalized With
Heart Failure Findings From Get With The Guidelines-Heart Failure
SO JACC-HEART FAILURE
LA English
DT Article
DE BNP; heart failure; outcome; quality of care; race
AB Objectives This study sought to determine if there were differences in B-type natriuretic peptide (BNP) levels across racial/ethnic groups and in their association with quality of care and in-hospital outcomes among patients with heart failure (HF).
Background It remains unclear whether BNP levels and their associations with quality of care and prognosis vary by race/ethnicity among patients hospitalized with HF.
Methods Using Get With The Guidelines-Heart Failure (GWTG-HF), patient characteristics and BNP levels at admission were compared among 4 racial/ethnic populations: white, black, Hispanic, and Asian. The associations between BNP, quality of care, in-hospital mortality, and length of stay (LOS) across these groups were analyzed.
Results A total of 92,072 patients (65,037 white, 19,092 black, 6,747 Hispanic, and 1,196 Asian) from 264 hospitals were included. Median BNP levels were higher in Asian (1,066 pg/ml) and black (866 pg/ml) patients than in white (776 pg/ml) and Hispanic (737 pg/ml) patients, and race/ethnicity was independently associated with BNP levels (p < 0.0001). Irrespective of race/ethnicity, patients in higher BNP quartiles (Q3, Q4) were more likely to be older and male and have lower body mass index, reduced ejection fraction, and renal insufficiency, whereas those in the lowest quartile (Q1) were more likely to have diabetes. With some exceptions, there were no significant racial/ethnic differences in the association of BNP levels with performance measure adherence. In multivariate analysis, elevated BNP levels remained associated with longer LOS and increased mortality in all racial/ethnic groups.
Conclusions Asian and black patients with HF had higher BNP levels at admission compared with white and Hispanic patients. BNP levels at admission provided prognostic value for in-hospital mortality and hospital LOS irrespective of race/ethnicity. (C) 2013 by the American College of Cardiology Foundation
C1 [Krim, Selim R.; Ventura, Hector] Ochsner Clin Fdn, John Ochsner Heart & Vasc Inst, New Orleans, LA 70121 USA.
[Vivo, Rey P.] Univ Texas Med Branch, Galveston, TX 77555 USA.
[Vivo, Rey P.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA.
[Krim, Nassim R.] Bronx Lebanon Hosp Ctr, Bronx, NY USA.
[Qian, Feng] SUNY Albany, Rensselaer, NY USA.
[Cox, Margueritte; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA.
[Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA.
[Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA.
RP Krim, SR (reprint author), Ochsner Clin Fdn, John Ochsner Heart & Vasc Inst, Div Cardiol, 1514 Jefferson Highway, New Orleans, LA 70121 USA.
EM krimselim@hotmail.com
RI Ventura, Hector/A-7691-2011; Hernandez, Adrian F./A-7818-2016
OI Hernandez, Adrian F./0000-0003-3387-9616
NR 20
TC 9
Z9 9
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1779
EI 2213-1787
J9 JACC-HEART FAIL
JI JACC-Heart Fail.
PD AUG
PY 2013
VL 1
IS 4
BP 345
EP 352
DI 10.1016/j.jchf.2013.04.008
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V41GX
UT WOS:000209535800011
PM 24621938
ER
PT J
AU Vaduganathan, M
Fonarow, GC
Gheorghiade, M
AF Vaduganathan, Muthiah
Fonarow, Gregg C.
Gheorghiade, Mihai
TI Drug Therapy to Reduce Early Readmission Risk in Heart Failure Ready for
Prime Time?
SO JACC-HEART FAILURE
LA English
DT Editorial Material
DE acute heart failure; digoxin; mineralocorticoid receptor antagonists;
readmissions
AB Readmission for heart failure remains a major focus of policymakers, clinicians, and patients. Despite meeting key national performance measures and frequent use of evidence-based therapies, rates of 30-day post-discharge rehospitalization may be as high as 25%. Digoxin and mineralocorticoid antagonists are known to reduce admissions for heart failure, but are significantly underused in current clinical practice despite their proven benefits. (C) 2013 by the American College of Cardiology Foundation
C1 [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA.
[Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA.
[Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA.
RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 645 North Michigan Ave,Suite 1006, Chicago, IL 60611 USA.
EM m-gheorghiade@northwestern.edu
NR 25
TC 7
Z9 7
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1779
EI 2213-1787
J9 JACC-HEART FAIL
JI JACC-Heart Fail.
PD AUG
PY 2013
VL 1
IS 4
BP 361
EP 364
DI 10.1016/j.jchf.2013.04.010
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V41GX
UT WOS:000209535800013
PM 24621940
ER
PT J
AU Morris, ED
Kim, SJ
Sullivan, JM
Wang, S
Normandin, MD
Constantinescu, CC
Cosgrove, KP
AF Morris, Evan D.
Kim, Su Jin
Sullivan, Jenna M.
Wang, Shuo
Normandin, Marc D.
Constantinescu, Cristian C.
Cosgrove, Kelly P.
TI Creating Dynamic Images of Short-lived Dopamine Fluctuations with
lp-ntPET: Dopamine Movies of Cigarette Smoking
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Behavior; Issue 78; Neuroscience; Neurobiology; Molecular Biology;
Biomedical Engineering; Medicine; Anatomy; Physiology; Image Processing;
Computer-Assisted; Receptors; Dopamine; Dopamine; Functional
Neuroimaging; Binding; Competitive; mathematical modeling (systems
analysis); Neurotransmission; transient; dopamine release; PET;
modeling; linear; time-invariant; smoking; F-test; ventral-striatum;
clinical techniques
AB We describe experimental and statistical steps for creating dopamine movies of the brain from dynamic PET data. The movies represent minute-to-minute fluctuations of dopamine induced by smoking a cigarette. The smoker is imaged during a natural smoking experience while other possible confounding effects (such as head motion, expectation, novelty, or aversion to smoking repeatedly) are minimized.
We present the details of our unique analysis. Conventional methods for PET analysis estimate time-invariant kinetic model parameters which cannot capture short-term fluctuations in neurotransmitter release. Our analysis - yielding a dopamine movie - is based on our work with kinetic models and other decomposition techniques that allow for time-varying parameters(1-7). This aspect of the analysis - temporal-variation - is key to our work. Because our model is also linear in parameters, it is practical, computationally, to apply at the voxel level. The analysis technique is comprised of five main steps: pre-processing, modeling, statistical comparison, masking and visualization. Preprocessing is applied to the PET data with a unique 'HYPR' spatial filter(8) that reduces spatial noise but preserves critical temporal information. Modeling identifies the time-varying function that best describes the dopamine effect on C-11-raclopride uptake. The statistical step compares the fit of our (lp-ntPET) model (7) to a conventional model(9). Masking restricts treatment to those voxels best described by the new model. Visualization maps the dopamine function at each voxel to a color scale and produces a dopamine movie. Interim results and sample dopamine movies of cigarette smoking are presented.
C1 [Morris, Evan D.; Kim, Su Jin; Sullivan, Jenna M.; Wang, Shuo; Cosgrove, Kelly P.] Yale Univ, New Haven, CT 06520 USA.
[Morris, Evan D.; Kim, Su Jin; Sullivan, Jenna M.; Wang, Shuo; Cosgrove, Kelly P.] Yale Univ, Yale PET Ctr, New Haven, CT 06520 USA.
[Normandin, Marc D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Constantinescu, Cristian C.] Univ Calif Irvine, Irvine, CA USA.
RP Morris, ED (reprint author), Yale Univ, New Haven, CT 06520 USA.
EM evan.morris@yale.edu
RI Normandin, Marc/C-6728-2015
OI Normandin, Marc/0000-0003-1645-523X
FU [R21 AA15077]; [K02 DA031750]
FX Much of the development of the ntPET techniques was supported by R21
AA15077 to E. Morris. K. Cosgrove is supported by K02 DA031750.
NR 39
TC 2
Z9 2
U1 1
U2 6
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD AUG
PY 2013
IS 78
AR UNSP e50358
DI 10.3791/50358
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36RH
UT WOS:000209228000015
ER
PT J
AU Tseng, JC
Kung, AL
AF Tseng, Jen-Chieh
Kung, Andrew L.
TI In vivo Imaging Method to Distinguish Acute and Chronic Inflammation
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Immunology; Issue 78; Infection; Medicine; Cellular Biology; Molecular
Biology; Biomedical Engineering; Anatomy; Physiology; Cancer Biology;
Stem Cell Biology; Inflammation; Phagocytes; Phagocyte; Superoxides;
Molecular Imaging; chemiluminescence; in vivo imaging; superoxide;
bioluminescence; chronic inflammation; acute inflammation; phagocytes;
cells; imaging; animal model
AB Inflammation is a fundamental aspect of many human diseases. In this video report, we demonstrate non-invasive bioluminescence imaging techniques that distinguish acute and chronic inflammation in mouse models. With tissue damage or pathogen invasion, neutrophils are the first line of defense, playing a major role in mediating the acute inflammatory response. As the inflammatory reaction progresses, circulating monocytes gradually migrate into the site of injury and differentiate into mature macrophages, which mediate chronic inflammation and promote tissue repair by removing tissue debris and producing anti-inflammatory cytokines. Intraperitoneal injection of luminol (5-amino-2,3-dihydro-1,4-phthalazinedione, sodium salt) enables detection of acute inflammation largely mediated by tissue-infiltrating neutrophils. Luminol specifically reacts with the superoxide generated within the phagosomes of neutrophils since bioluminescence results from a myeloperoxidase (MPO) mediated reaction. Lucigenin (bis-N-methylacridinium nitrate) also reacts with superoxide in order to generate bioluminescence. However, lucigenin bioluminescence is independent of MPO and it solely relies on phagocyte NADPH oxidase (Phox) in macrophages during chronic inflammation. Together, luminol and lucigenin allow non-invasive visualization and longitudinal assessment of different phagocyte populations across both acute and chronic inflammatory phases. Given the important role of inflammation in a variety of human diseases, we believe this non-invasive imaging method can help investigate the differential roles of neutrophils and macrophages in a variety of pathological conditions.
C1 [Tseng, Jen-Chieh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lurie Family Imaging Ctr, Cambridge, MA 02138 USA.
[Kung, Andrew L.] Columbia Univ, Med Ctr, Div Pediat Hematol Oncol Stem Cell Transplant, New York, NY 10027 USA.
RP Tseng, JC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lurie Family Imaging Ctr, Cambridge, MA 02138 USA.
EM jen-chieh_tseng@dfci.harvard.edu
OI Kung, Andrew/0000-0002-9091-488X
FU Nancy Lurie Marks Foundation
FX This work was supported by the Nancy Lurie Marks Foundation. We thank
Dr. Nancy E. Kohl for critical reading of the manuscript. We thank Kin
K. Wong for his assistance in preparing this video report.
NR 31
TC 0
Z9 0
U1 1
U2 5
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD AUG
PY 2013
IS 78
AR UNSP e50690
DI 10.3791/50690
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36RH
UT WOS:000209228000050
ER
PT J
AU Kumar, R
Korideck, H
Ngwa, W
Berbeco, RI
Makrigiorgos, GM
Sridhar, S
AF Kumar, Rajiv
Korideck, Houari
Ngwa, Wilfred
Berbeco, Ross I.
Makrigiorgos, G. Mike
Sridhar, Srinivas
TI Third generation gold nanoplatform optimized for radiation therapy
SO TRANSLATIONAL CANCER RESEARCH
LA English
DT Article
DE Gold nanoparticles; PEGylation; multifunctional nanoparticles;
clonogenic assay; radiation therapy
AB We report the design and fabrication of third generation ultrasmall PEGylated gold nanoparticles based platform (AuRadTM) optimized for applications in radiation therapy. The AuRadTM nanoplatform has the following key features: (I) surface coating of hetero-bifunctional-PEG with amine, carboxyl, methoxy functional groups, which make this a versatile nanoplatform to conjugate various moieties like fluorophores, peptides, drugs, radiolabels; (II) size that is optimized for longer circulation, higher tumor uptake and modulated clearance; (III) high radiation enhancement. We have synthesized ultrasmall 2-3 nm gold nanoparticles, followed by attachment of hetero-bifunctional PEG and further conjugation of fluorophore AlexaFlour 647 for optical imaging, with a stability of more than 6 months. Confocal bioimaging with HeLa cells showed robust uptake of biocompatible nanoparticles in cells. Irradiation experiments X-rays showed greater than 2.8-fold cell kill enhancement as demonstrated by clonogenic survival assays. The results indicate that AuRad nanoplatform can act as potential theranostic agent in radiation therapy.
C1 [Kumar, Rajiv; Sridhar, Srinivas] Northeastern Univ, Elect Mat Res Inst, 110 Forsyth St 111 Dana, Boston, MA 02115 USA.
[Kumar, Rajiv; Sridhar, Srinivas] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
[Kumar, Rajiv; Korideck, Houari; Ngwa, Wilfred; Berbeco, Ross I.; Makrigiorgos, G. Mike; Sridhar, Srinivas] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA USA.
RP Sridhar, S (reprint author), Northeastern Univ, Elect Mat Res Inst, 110 Forsyth St 111 Dana, Boston, MA 02115 USA.
EM s.sridhar@neu.edu
FU BWH Biomedical Research Institute; [NSF-DGE-0965843];
[HHS/1U54CA151881 CORE1]; [1R03 CA164645-01]
FX This work was supported partially by NSF-DGE-0965843, HHS/1U54CA151881
CORE1, 1R03 CA164645-01 and a seed grant from the BWH Biomedical
Research Institute.
NR 50
TC 7
Z9 8
U1 2
U2 6
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2218-676X
EI 2219-6803
J9 TRANSL CANCER RES
JI Transl. Cancer Res.
PD AUG
PY 2013
VL 2
IS 4
BP 228
EP +
DI 10.3978/j.issn.2218-676X.2013.07.02
PG 13
WC Oncology
SC Oncology
GA V42WF
UT WOS:000209643200002
ER
PT J
AU Haymond, M
Kappelgaard, AM
Czernichow, P
Biller, BMK
Takano, K
Kiess, W
AF Haymond, Morey
Kappelgaard, Anne-Marie
Czernichow, Paul
Biller, Beverly M. K.
Takano, Koji
Kiess, Wieland
CA Global Advisory Panel Meeting
TI Early recognition of growth abnormalities permitting early intervention
SO ACTA PAEDIATRICA
LA English
DT Review
DE Growth failure; Growth hormone; Short stature
ID IDIOPATHIC SHORT STATURE; HORMONE DEFICIENCY; WESSEX GROWTH; POOR
GROWTH; WORK-UP; CHILDREN; HEIGHT; POPULATION; RELIABILITY; PREVALENCE
AB Normal growth is a sign of good health. Monitoring for growth disturbances is fundamental to children's health care. Early detection and diagnosis of the causes of short stature allows management of underlying medical conditions, optimizing attainment of good health and normal adult height. Conclusion This review summarizes currently available information on monitoring for short stature in children and conditions usually associated with short stature and summarizes the authors' conclusions on the early recognition of growth disorders.
C1 [Haymond, Morey] Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA.
[Kappelgaard, Anne-Marie] Novo Nordisk AS, DK-2880 Bagsvaerd, Denmark.
[Czernichow, Paul] Hop Necker Enfants Malad, Paris, France.
[Biller, Beverly M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Takano, Koji] Univ Tokyo, Tokyo, Japan.
[Kiess, Wieland] Univ Leipzig, Hosp Children & Adolescents, D-04109 Leipzig, Germany.
RP Kappelgaard, AM (reprint author), Novo Nordisk AS, Vandtarnsvej 108-110, DK-2860 Soborg, Denmark.
EM amk@novonordisk.com
NR 52
TC 9
Z9 9
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0803-5253
J9 ACTA PAEDIATR
JI Acta Paediatr.
PD AUG
PY 2013
VL 102
IS 8
BP 787
EP 796
DI 10.1111/apa.12266
PG 10
WC Pediatrics
SC Pediatrics
GA 169KA
UT WOS:000320777700017
PM 23586744
ER
PT J
AU Vaz-Luis, I
Seah, D
Olson, EM
Wagle, N
Metzger-Filho, O
Sohl, J
Litsas, G
Burstein, HJ
Krop, IE
Winer, EP
Lin, NU
AF Vaz-Luis, Ines
Seah, Davinia
Olson, Erin M.
Wagle, Nikhil
Metzger-Filho, Otto
Sohl, Jessica
Litsas, Georgia
Burstein, Harold J.
Krop, Ian E.
Winer, Eric P.
Lin, Nancy U.
TI Clinicopathological Features Among Patients With Advanced Human
Epidermal Growth Factore-2-Positive Breast Cancer With Prolonged
Clinical Benefit to First-Line Trastuzumab-Based Therapy: A
Retrospective Cohort Study
SO CLINICAL BREAST CANCER
LA English
DT Article
DE HER2-positive; Outcomes; Treatment Duration
ID PHASE-II TRIAL; MOLECULAR PORTRAITS; MONOCLONAL-ANTIBODY; RECEPTOR
STATUS; HER2 THERAPY; CHEMOTHERAPY; EFFICACY; SAFETY; TUMORS;
VINORELBINE
AB The relationship between clinicopathological features and long-term benefit to trastuzumab-based therapy was evaluated in 164 HER2-positive metastatic breast cancer patients. Treatment duration was associated with hormone receptor status and use of adjuvant trastuzumab; however, with low predictive value. With growing availability of targeted treatments for HER2-positive disease, a major clinical priority is identifying molecular predictors of benefit of anti-HER2 therapies.
Background: The magnitude of benefit of trastuzumab for the treatment of advanced HER2-positive breast cancer varies widely. In this retrospective study, we investigated the clinicopathological features associated with prolonged first-line trastuzumab-based treatment duration. Patients and Methods: A total of 164 patients diagnosed with advanced HER2-positive breast cancer and treated with first-line trastuzumab-based therapy from 1999 to 2009 were identified. Duration of treatment was classified according to tertiles. Different logistic regression models including age, disease-free interval, number of metastatic sites, visceral disease, hormone receptor, and adjuvant trastuzumab were fitted to investigate associations with benefit of prolonged trastuzumab-based therapies. The predictive value of each model was assessed using C-statistics. Results: At a median follow-up of 5.8 years (range, 0.7-22.1 years), patients in the short-, intermediate-, and long-term treatment duration groups were given first-line trastuzumab-based therapy for < 7.2 months, 7.2 to 14 months, and > 14 months, respectively. In the multivariate analysis, patients with long-term clinical benefit had a higher likelihood of having hormone receptor-positive tumors (odds ratio [OR] positive vs. negative 2.39 [95% confidence interval (CI), 1.08-5.31]; P = .032); and a lower likelihood of having received adjuvant trastuzumab (ORadjuvant trastuzumab vs. no adjuvant trastuzumab 0.30 [95% CI, 0.10-0.96]; P = .043]. C-statistics varied between 0.634 and 0.699. Conclusion: Long-term benefit of trastuzumab-based therapy is associated with hormone receptor positivity and the absence of previous adjuvant trastuzumab. Nevertheless, clinicopathological features had a low predictive value for prolonged treatment duration. The validation of the current findings and the identification of molecular features associated the magnitude of trastuzumab benefit should be encouraged.
C1 [Vaz-Luis, Ines; Seah, Davinia; Wagle, Nikhil; Metzger-Filho, Otto; Sohl, Jessica; Litsas, Georgia; Burstein, Harold J.; Krop, Ian E.; Winer, Eric P.; Lin, Nancy U.] Dana Farber Canc Inst, Dept Med Oncol, Breast Oncol Ctr, Boston, MA 02215 USA.
[Vaz-Luis, Ines] Inst Mol Med, Clin & Translat Oncol Res Unit, Lisbon, Portugal.
[Olson, Erin M.] Ohio State Univ, Dept Med Oncol, Columbus, OH 43210 USA.
RP Lin, NU (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM Nancy_Lin@dfci.harvard.edu
FU Scholars in Clinical Science Program of Harvard Catalyst; Harvard
Clinical and Translational Science Center [UL1 RR025758]; National
Cancer Institute Specialized Program of Research Excellence in Breast
Cancer [NIH P50 CA089393]; National Comprehensive Cancer Network, Breast
Cancer Research Foundation; Nancy and Randy Berry Junior Faculty Award;
Karen Webster and David Evans Research Fund; Fundacao para a Ciencia e
Tecnologia [HMSP-ICS/0004/2011]
FX I. Vaz-Luis is supported by the Scholars in Clinical Science Program of
Harvard Catalyst, The Harvard Clinical and Translational Science Center
(Award No. UL1 RR025758) and contributions from Harvard University and
its affiliated academic health care centers.; The study was supported by
the National Cancer Institute Specialized Program of Research Excellence
in Breast Cancer (NIH P50 CA089393), the National Comprehensive Cancer
Network, Breast Cancer Research Foundation (to N.U. Lin), Nancy and
Randy Berry Junior Faculty Award (to N.U. Lin), the Karen Webster and
David Evans Research Fund, and Fundacao para a Ciencia e Tecnologia
(HMSP-ICS/0004/2011, Career development award to I. Vaz-Luis).
NR 31
TC 10
Z9 10
U1 0
U2 5
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1526-8209
J9 CLIN BREAST CANCER
JI Clin. Breast Cancer
PD AUG
PY 2013
VL 13
IS 4
BP 254
EP 263
DI 10.1016/j.clbc.2013.02.010
PG 10
WC Oncology
SC Oncology
GA 175OI
UT WOS:000321239600005
PM 23829891
ER
PT J
AU Yang, L
Lawson, KA
Teteak, CJ
Zou, JH
Hacquebord, J
Patterson, D
Ghatan, AC
Mei, Q
Zielinska-Kwiatkowska, A
Bain, SD
Fernandes, RJ
Chansky, HA
AF Yang, Liu
Lawson, Kevin A.
Teteak, Colin J.
Zou, Junhui
Hacquebord, Jacques
Patterson, David
Ghatan, Andrew C.
Mei, Qi
Zielinska-Kwiatkowska, Anna
Bain, Steven D.
Fernandes, Russell J.
Chansky, Howard A.
TI ESET histone methyltransferase is essential to hypertrophic
differentiation of growth plate chondrocytes and formation of epiphyseal
plates
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Epigenetics; Chondrogenesis; Chondrocyte hypertrophy; Chondrocyte
differentiation; Epiphyseal plate; Long bone formation; Endochondral
ossification; Trabecular bone; Histone deacetylase; Indian hedgehog gene
Hh
ID EMBRYONIC STEM-CELLS; OSTEOBLAST DIFFERENTIATION; BONE-FORMATION;
CANCER-CELLS; SET DOMAIN; INTERACTS; LINEAGE; CBFA1; RUNX2; G9A
AB The ESET (also called SETDB1) protein contains an N-terminal tudor domain that mediates protein-protein interactions and a C-terminal SET domain that catalyzes methylation of histone H3 at lysine 9. We report here that ESET protein is transiently upregulated in prehypertrophic chondrocytes in newborn mice. To investigate the in vivo effects of ESET on chondrocyte differentiation, we generated conditional knockout mice to specifically eliminate the catalytic SET domain of ESET protein only in mesenchymal cells. Such deletion of the ESET gene caused acceleration of chondrocyte hypertrophy in both embryos and young animals, depleting chondrocytes that are otherwise available to form epiphyseal plates for endochondral bone growth. ESET-deficient mice are thus characterized by defective long bone growth and trabecular bone formation. To understand the underlying mechanism for ESET regulation of chondrocytes, we carried out co-expression experiments and found that ESET associates with histone deacetylase 4 to bind and inhibit the activity of Runx2, a hypertrophy-promoting transcription factor. Repression of Runx2-mediated gene transactivation by ESET is dependent on its H3-K9 methyltransferase activity as well as its associated histone deacetylase activity. In addition, knockout of ESET is associated with repression of Indian hedgehog gene in pre- and early hypertrophic chondrocytes. Together, these results provide clear evidence that ESET controls hypertrophic differentiation of growth plate chondrocytes and endochondral ossification during embryogenesis and postnatal development. Published by Elsevier Inc.
C1 [Yang, Liu; Lawson, Kevin A.; Teteak, Colin J.; Zou, Junhui; Hacquebord, Jacques; Patterson, David; Ghatan, Andrew C.; Zielinska-Kwiatkowska, Anna; Bain, Steven D.; Fernandes, Russell J.; Chansky, Howard A.] Univ Washington, Dept Orthoped & Sports Med, Seattle, WA 98108 USA.
[Yang, Liu; Mei, Qi; Chansky, Howard A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Yang, L (reprint author), Univ Washington, Dept Orthoped & Sports Med, 1660 S Columbian Way,GMR 151, Seattle, WA 98108 USA.
EM lyang@u.washington.edu
OI Lawson, Kevin/0000-0002-2931-5263
FU NIH grant [RO1 AR051455, RO1 AR057025]; VA Merit Review Award
FX We thank Dr. Y. Shinkai for frozen mouse embryos harboring the foxed
ESET allele, Dr. J. J. Westendorf for pOG2-Luc reporter, Dr. G. Karsenty
for pCMV-HA-Runx2 plasmid, and S. L. Carey for assistance in mouse
breeding. This work is supported in part by NIH grant RO1 AR051455 (to
L.Y.), RO1 AR057025 (to R.J.F), and by VA Merit Review Award (to
H.A.C.).
NR 28
TC 16
Z9 17
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2013
VL 380
IS 1
BP 99
EP 110
DI 10.1016/j.ydbio.2013.04.031
PG 12
WC Developmental Biology
SC Developmental Biology
GA 170DC
UT WOS:000320829100009
PM 23652029
ER
PT J
AU Socransky, SS
Haffajee, AD
Teles, R
Wennstrom, JL
Lindhe, J
Bogren, A
Hasturk, H
van Dyke, T
Wang, XS
Goodson, JM
AF Socransky, Sigmund S.
Haffajee, Anne D.
Teles, Ricardo
Wennstrom, Jan L.
Lindhe, Jan
Bogren, Anna
Hasturk, Hatice
van Dyke, Thomas
Wang, Xiaoshan
Goodson, Jo Max
TI Effect of periodontal therapy on the subgingival microbiota over a
2-year monitoring period. I. Overall effect and kinetics of change
SO JOURNAL OF CLINICAL PERIODONTOLOGY
LA English
DT Article
DE chronic periodontitis; kinetics; microbiology; therapy
ID CONTROLLED CLINICAL-TRIAL; GENERALIZED AGGRESSIVE PERIODONTITIS;
ACTINOMYCETEMCOMITANS-ASSOCIATED PERIODONTITIS; DNA-DNA HYBRIDIZATION;
ADULT PERIODONTITIS; NONSURGICAL TREATMENT; DOUBLE-BLIND; METRONIDAZOLE;
AMOXICILLIN; DISEASE
AB Aim To examine the 2-year post-therapy kinetics of change in the composition of subgingival biofilms.
Material and Methods In this study, 178 chronic periodontitis subjects were recruited and clinically monitored at baseline, 3, 6, 12, 18 and 24months after therapy. All subjects received scaling and root planing and 156 one or more of periodontal surgery, systemically administered amoxicillin+metronidazole or local tetracycline at pockets 5mm. Subgingival biofilm samples taken from each subject at each time point were analysed for their content of 40 bacterial species using checkerboard DNA-DNA hybridization. The significance of changes in median species counts over time was sought using the Wilcoxon or Friedman tests and adjusted for multiple comparisons.
Results Mean counts were significantly reduced from baseline to 2years for 30 of the 40 taxa. Marked reductions were observed for periodontal pathogens including Tannerella forsythia, Treponema denticola and Eubacterium nodatum. The kinetics of change differed from species to species. When data were subset according to baseline PD, patterns of change in the microbial profiles were generally similar.
Conclusion Periodontal therapy leads to a rapid reduction in periodontal pathogens, followed by a slower reduction in other taxa that can be sustained for at least 2years.
C1 [Socransky, Sigmund S.; Haffajee, Anne D.; Teles, Ricardo; Hasturk, Hatice; van Dyke, Thomas; Goodson, Jo Max] Forsyth Inst, Ctr Periodontol, Dept Appl Oral Sci, Cambridge, MA 02142 USA.
[Wennstrom, Jan L.; Lindhe, Jan; Bogren, Anna] Univ Gothenburg, Sahlgrenska Acad, Inst Odontol, Dept Periodontol, Gothenburg, Sweden.
[Wang, Xiaoshan] Forsyth Inst, Ctr Clin & Translat Res, Dept Appl Oral Sci Epidemiol & Biostat Core, Cambridge, MA 02142 USA.
RP Teles, R (reprint author), Forsyth Inst, Ctr Periodontol, Dept Appl Oral Sci, 245 1st St, Cambridge, MA 02142 USA.
EM rteles@forsyth.org
RI Wang, Xiaoshan/D-6292-2014
OI Wang, Xiaoshan/0000-0002-6760-5456
FU National Institute of Dental and Craniofacial [DE12861, RR025771]; GCRC
[RR00533, RR01032]
FX This study was supported by the National Institute of Dental and
Craniofacial Research grants DE12861 and RR025771 and GCRC funding from
RR00533 and RR01032. There are no conflicts of interest to report.
NR 39
TC 12
Z9 12
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0303-6979
J9 J CLIN PERIODONTOL
JI J. Clin. Periodontol.
PD AUG
PY 2013
VL 40
IS 8
BP 771
EP 780
DI 10.1111/jcpe.12117
PG 10
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 178GK
UT WOS:000321433300006
PM 23710672
ER
PT J
AU Haslinger, R
Pipa, G
Lewis, LD
Nikolic, D
Williams, Z
Brown, E
AF Haslinger, Robert
Pipa, Gordon
Lewis, Laura D.
Nikolic, Danko
Williams, Ziv
Brown, Emery
TI Encoding Through Patterns: Regression Tree-Based Neuronal Population
Models
SO NEURAL COMPUTATION
LA English
DT Article
ID NEURAL SPIKING ACTIVITY; RESPONSE VARIABILITY; CORTICAL NETWORKS; TRAIN
DATA; INFORMATION; MONKEY; RELIABILITY; SYNCHRONY; DIRECTION; ENSEMBLE
AB Although the existence of correlated spiking between neurons in a population is well known, the role such correlations play in encoding stimuli is not. We address this question by constructing pattern-based encoding models that describe how time-varying stimulus drive modulates the expression probabilities of population-wide spike patterns. The challenge is that large populations may express an astronomical number of unique patterns, and so fitting a unique encoding model for each individual pattern is not feasible. We avoid this combinatorial problem using a dimensionality-reduction approach based on regression trees. Using the insight that some patterns may, from the perspective of encoding, be statistically indistinguishable, the tree divisively clusters the observed patterns into groups whose member patterns possess similar encoding properties. These groups, corresponding to the leaves of the tree, are much smaller in number than the original patterns, and the tree itself constitutes a tractable encoding model for each pattern. Our formalism can detect an extremely weak stimulus-driven pattern structure and is based on maximizing the data likelihood, not making a priori assumptions as to how patterns should be grouped. Most important, by comparing pattern encodings with independent neuron encodings, one can determine if neurons in the population are driven independently or collectively. We demonstrate this method using multiple unit recordings from area 17 of anesthetized cat in response to a sinusoidal grating and show that pattern-based encodings are superior to those of independent neuron models. The agnostic nature of our clustering approach allows us to investigate encoding by the collective statistics that are actually present rather than those (such as pairwise) that might be presumed.
C1 [Haslinger, Robert] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Haslinger, Robert; Lewis, Laura D.; Brown, Emery] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Pipa, Gordon] Univ Osnabruck, Dept Neuroinformat, D-49069 Osnabruck, Germany.
[Nikolic, Danko] Max Planck Inst Brain Res, Dept Neurophysiol, Frankfurt, Germany.
[Nikolic, Danko] Goethe Univ Frankfurt, Frankfurt Inst Adv Studies, D-60528 Frankfurt, Germany.
[Nikolic, Danko] Max Planck Gesell, Ernst Strungman Inst Neurosci, Frankfurt, Germany.
[Williams, Ziv] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Brown, Emery] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
RP Haslinger, R (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM rob.haslinger@gmail.com; gpipa@uos.de; ldlewis@mit.edu;
danko.nikolic@googlemail.com; ZWILLIAMS1@partners.org;
enb@neurostat.mit.edu
RI Pipa, Gordon/M-1813-2014
OI Pipa, Gordon/0000-0002-3416-2652
FU NIH [K25 NS052422-02, DP1 OD003646-0, MH59733-07]; Hertie Foundation;
Deutsche Forschungsgemeinschaft [NI 708/2-1]; Hertie Stiftung;
Max-Planck Society; Frankfurt Institute for Advanced Studies
FX We thank Demba Ba, Zhe Chen, and Cosma Shalizi for helpful conversations
regarding the research presented in this article. This work was
supported by NIH grants K25 NS052422-02 (R.H.), DP1 OD003646-0,
MH59733-07 (E.N.), and the Hertie Foundation (G.P.). Experiments with
cat recordings (D.N.) were supported by a Deutsche
Forschungsgemeinschaft Grant NI 708/2-1, Hertie Stiftung, Max-Planck
Society, and the Frankfurt Institute for Advanced Studies.
NR 54
TC 6
Z9 6
U1 0
U2 8
PU MIT PRESS
PI CAMBRIDGE
PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA
SN 0899-7667
J9 NEURAL COMPUT
JI Neural Comput.
PD AUG
PY 2013
VL 25
IS 8
BP 1953
EP 1993
DI 10.1162/NECO_a_00464
PG 41
WC Computer Science, Artificial Intelligence; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA 166XG
UT WOS:000320592700001
PM 23607564
ER
PT J
AU Chase, MH
AF Chase, Michael H.
TI Motor control during sleep and wakefulness: Clarifying controversies and
resolving paradoxes
SO SLEEP MEDICINE REVIEWS
LA English
DT Review
DE Motor control; Postsynaptic inhibition; REM sleep; Wakefulness;
Reticular response-reversal; Hypocretin cataplexy
ID EYE-MOVEMENT SLEEP; MUSCLE EMG AMPLITUDE; MEDULLARY RETICULAR NEURONS;
NUCLEUS PONTIS ORALIS; IN-VIVO MICRODIALYSIS; REM-SLEEP; ACTIVE SLEEP;
LUMBAR MOTONEURONS; BEHAVIOR DISORDER; POSTSYNAPTIC POTENTIALS
AB Data accumulated during the last 40 years, since the discovery that there is a loss of muscle tone during REM sleep, have delineated many of the neurotransmitter systems, synaptic mechanisms and neuronal circuitries involved in the control of somatic motoneurons during sleep and waking states. Nevertheless, there are still a number of extant controversies as well as paradoxical and conflicting data. For example, the paradoxical modulation of motor activity that occurs in individuals with cataplexy during wakefulness compared to REM sleep is unresolved as are the mechanisms that are responsible for the control of hypoglossal motoneurons during normal states and those that are operative during sleep disorders such as obstructive sleep apnea. In addition, the circuitry whereby the hypocretinergic system promotes motor activation during wakefulness, and motor inhibition during REM sleep, has yet to be clarified. The use of new techniques, such those involving optogenetics and nanoparticles, will help to clarify the preceding issues and provide as a foundation for addressing a number of current critical unanswered questions such as those dealing with the differential control of motor activity in newborns and the aged. The resulting data will strengthen the foundation for the development of efficacious therapeutics to treat disorders of motor control that occur during sleep as well as wakefulness. (C) 2012 Published by Elsevier Ltd.
C1 Univ Calif Los Angeles, Sch Med, VA Greater Angeles Healthcare Syst, WebSci Int, Los Angeles, CA 90095 USA.
RP Chase, MH (reprint author), Univ Calif Los Angeles, Sch Med, VA Greater Angeles Healthcare Syst, WebSci Int, 1251 Westwood Blvd, Los Angeles, CA 90095 USA.
EM mchase@websciences.org
NR 116
TC 13
Z9 13
U1 1
U2 26
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1087-0792
J9 SLEEP MED REV
JI Sleep Med. Rev.
PD AUG
PY 2013
VL 17
IS 4
BP 299
EP 312
DI 10.1016/j.smrv.2012.09.003
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 173QQ
UT WOS:000321094400008
PM 23499211
ER
PT J
AU Zhang, XY
Tang, W
Xiu, MH
Chen, DC
Yang, FD
Tan, YL
Wang, ZR
Zhang, FX
Liu, JH
Liu, LJ
Chen, YL
Wen, N
Kosten, TR
AF Zhang, Xiang Yang
Tang, Wei
Xiu, Mei Hong
Chen, Da Chun
Yang, Fu De
Tan, Yun Long
Wang, Zhi Ren
Zhang, Feixue
Liu, Jiahong
Liu, Linjing
Chen, Yuanling
Wen, Na
Kosten, Thomas R.
TI Interleukin 18 and cognitive impairment in first episode and drug naive
schizophrenia versus healthy controls
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Schizophrenia; Cognition; Interleukin-18; Immune function;
Psychopathology
ID NEUROPSYCHOLOGICAL STATUS; INFLAMMATORY CYTOKINES; REPEATABLE BATTERY;
PRENATAL INFECTION; ALZHEIMERS-DISEASE; SIGNALING PATHWAYS; GLIAL-CELLS;
BRAIN; IL-18; EXPRESSION
AB Alterations in the inflammatory and immune systems have been documented to occur from the earliest stages of schizophrenia, and have been associated with neurodevelopmental changes. Cognitive impairment is a core feature in the pathology of schizophrenia, and recent studies showed a significant increase in serum IL-18 in schizophrenia, and a putative role of IL-18 in neuroprogression and thus neurocognitive defects. The purpose of this study was to examine the association of IL-18 with cognitive deficits in schizophrenia. We recruited 77 first episode and drug naive schizophrenic patients and 75 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-18 in both groups. Schizophrenic symptoms were assessed using the positive and negative syndrome scale (PANSS). We found that IL-18 levels were non-significantly higher in patients than controls (206.0 +/- 92.9 pg/ml vs 193.2 +/- 41.8 pg/ml, p = 0.28). Cognitive scores on the RBANS and nearly all of its five subscales (all p < 0.05) except for the Visuospatial/Constructional index (p > 0.05) were significantly lower in schizophrenic patients than normal controls. For the patients, IL-18 was positively associated with the Visuospatial/Constructional domain of cognitive deficits in schizophrenia. Our findings suggest that cognitive deficits occur during the acute stage of a schizophrenic episode, and IL-18 may be involved in Visuospatial/Constructional deficits of these patients. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Zhang, Xiang Yang; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Zhang, Xiang Yang; Kosten, Thomas R.] Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA.
[Zhang, Xiang Yang; Xiu, Mei Hong; Chen, Da Chun; Yang, Fu De; Tan, Yun Long; Wang, Zhi Ren; Kosten, Thomas R.] Peking Univ, Beijing HuiLongGuan Hosp, Ctr Biol Psychiat, Beijing 100096, Peoples R China.
[Tang, Wei; Zhang, Feixue; Liu, Jiahong; Liu, Linjing; Chen, Yuanling; Wen, Na] Kangning Hosp, Wenzhou 325000, Peoples R China.
RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM xyzhang@bcm.edu; kosten@bcm.edu
FU Wenzhou Science and Technology Bureau [Y20100324]; National Natural
Science Foundation of China [81000509]; Beijing Municipal Excellent
Talents Foundation [2010D003034000032]; Stanley Medical Research
Institute [03T-459, 05T-726]; United States National Institute of Health
[K05-DA0454, P50-DA18827, U01-MH79639]
FX This study was funded by the Wenzhou Science and Technology Bureau
(Y20100324), the National Natural Science Foundation of China
(81000509), the Beijing Municipal Excellent Talents Foundation
(2010D003034000032), the Stanley Medical Research Institute (03T-459 and
05T-726), and the United States National Institute of Health K05-DA0454,
P50-DA18827 and U01-MH79639.
NR 76
TC 11
Z9 11
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 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD AUG
PY 2013
VL 32
BP 105
EP 111
DI 10.1016/j.bbi.2013.03.001
PG 7
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 168YG
UT WOS:000320743300013
PM 23499732
ER
PT J
AU Hoge, EA
Chen, MM
Orr, E
Metcalf, CA
Fischer, LE
Pollack, MH
DeVivo, I
Simon, NM
AF Hoge, Elizabeth A.
Chen, Maxine M.
Orr, Esther
Metcalf, Christina A.
Fischer, Laura E.
Pollack, Mark H.
DeVivo, Immaculata
Simon, Naomi M.
TI Loving-Kindness Meditation practice associated with longer telomeres in
women
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Telomere length; Aging; Mortality; Meditation; Loving-Kindness; Metta
ID CIGARETTE-SMOKING; STRESS-REDUCTION; LENGTH; MINDFULNESS; DISEASE; RISK;
NEUROENDOCRINE; INTERVENTION; MORTALITY; HEALTH
AB Relatively short telomere length may serve as a marker of accelerated aging, and shorter telomeres have been linked to chronic stress. Specific lifestyle behaviors that can mitigate the effects of stress might be associated with longer telomere lengths. Previous research suggests a link between behaviors that focus on the well-being of others, such as volunteering and caregiving, and overall health and longevity. We examined relative telomere length in a group of individuals experienced in Loving-Kindness Meditation (LKM), a practice derived from the Buddhist tradition which utilizes a focus on unselfish kindness and warmth towards all people, and control participants who had done no meditation. Blood was collected by venipuncture, and Genomic DNA was extracted from peripheral blood leukocytes. Quantitative real time PCR was used to measure relative telomere length (RTL) (Cawthon, 2002) in fifteen LKM practitioners and 22 control participants. There were no significant differences in age, gender, race, education, or exposure to trauma, but the control group had a higher mean body mass index (BMI) and lower rates of past depression. The LKM practitioners had longer RTL than controls at the trend level (p = .083); among women, the LKM practitioners had significantly longer RTL than controls, (p = .007), which remained significant even after controlling for BMI and past depression. Although limited by small sample size, these results offer the intriguing possibility that LKM practice, especially in women, might alter RTL, a biomarker associated with longevity. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Hoge, Elizabeth A.; Metcalf, Christina A.; Fischer, Laura E.; DeVivo, Immaculata; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Hoge, Elizabeth A.; Metcalf, Christina A.; Fischer, Laura E.; DeVivo, Immaculata; Simon, Naomi M.] Harvard Univ, Sch Med, Boston, MA USA.
[Chen, Maxine M.; Orr, Esther] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[DeVivo, Immaculata] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Pollack, Mark H.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA.
RP Hoge, EA (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, 1 Bowdoin Sq,6th Flr, Boston, MA 02114 USA.
EM ehoge@partners.org
RI Hoge, Elizabeth/H-5879-2012;
OI Hoge, Elizabeth/0000-0002-5513-2292; Chen, Maxine/0000-0001-7138-6228
FU Mind and Life Institute; Highland Foundation; National Center for
Advancing Translational Sciences, National Institutes of Health
[8UL1TR000170-05]; Harvard University
FX we would like to thank the study participants, and also Pati Soule for
their help in this project. This project was supported in part by the
Mind and Life Institute and by the Highland Foundation (EH, NS, MP, LF,
CM). This work was also conducted with nursing support from Harvard
Clinical and Translational Science Center (National Center for Research
Resources and the National Center for Advancing Translational Sciences,
National Institutes of Health Award 8UL1TR000170-05 and financial
contributions from Harvard University and its affiliated academic health
care centers). The content is solely the responsibility of the authors
and does not necessarily represent the official views of Harvard
Catalyst, Harvard University and its affiliated academic health care
centers, or the National Institutes of Health.
NR 47
TC 22
Z9 22
U1 8
U2 57
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD AUG
PY 2013
VL 32
BP 159
EP 163
DI 10.1016/j.bbi.2013.04.005
PG 5
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 168YG
UT WOS:000320743300019
PM 23602876
ER
PT J
AU Jacob, MC
Harley, R
Sprich, S
Prairie, EM
AF Jacob, Michelle C.
Harley, Rebecca
Sprich, Susan
Prairie, Ellen M.
TI "Stay in the Game": Collecting Data on Symptom Improvement in
Naturalistic Settings in Order to Increase Reimbursement Rates
SO COGNITIVE AND BEHAVIORAL PRACTICE
LA English
DT Editorial Material
DE Dialectical Behavior Therapy; reimbursement rates; naturalistic settings
AB An industrious approach to increasing reimbursement rates from third-party payers is reviewed. Balancing fidelity to treatment with real-world demands at a local hospital is discussed, as well as ways we were able to increase reimbursement within our own department. Data in naturalistic settings, though not always able to adhere to randomized controlled trials, offers evidence of improvement in symptoms. This reaction paper encourages other clinical programs to "stay in the game" of data collection while balancing treatment fidelity.
C1 [Jacob, Michelle C.; Harley, Rebecca; Sprich, Susan; Prairie, Ellen M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA.
RP Jacob, MC (reprint author), Massachusetts Gen Hosp, 15 Parkman St,ACC 812, Boston, MA 02114 USA.
EM mjacobo@partners.org
NR 4
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 1077-7229
J9 COGN BEHAV PRACT
JI Cogn. Behav. Pract.
PD AUG
PY 2013
VL 20
IS 3
BP 331
EP 333
PG 3
WC Psychology, Clinical
SC Psychology
GA 170FB
UT WOS:000320834700009
ER
PT J
AU Hammad, MA
Abdel-Bakky, MS
Walker, LA
Ashfaq, MK
AF Hammad, Mohamed A.
Abdel-Bakky, Mohamed Sadek
Walker, Larry A.
Ashfaq, Mohammad K.
TI Tissue factor antisense deoxyoligonucleotide prevents monocrotaline/LPS
hepatotoxicity in mice
SO JOURNAL OF APPLIED TOXICOLOGY
LA English
DT Article
DE tissue factor; fibrinogen; oxidized low-density lipoprotein;
keratinocyte-derived chemokine; tissue factor antisense
oligodeoxynucleotides
ID RESPIRATORY-DISTRESS-SYNDROME; FACTOR-DEPENDENT COAGULATION; CHOLESTATIC
LIVER-INJURY; ESCHERICHIA-COLI SEPSIS; REPERFUSION INJURY;
BLOOD-COAGULATION; OXIDIZED LDL; RAT-LIVER; IN-VIVO; OLIGONUCLEOTIDES
AB Tissue factor (TF) is a membranous glycoprotein that functions as a receptor for coagulation factor VII/VIIa and activates the coagulation system when blood vessels or tissues are damaged. TF was upregulated in our monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity model. We tested the hypothesis that TF-dependent fibrin deposition and lipid peroxidation in the form of oxidized low-density-lipoprotein (ox-LDL) accumulation contribute to liver inflammation induced by MCT/LPS in mice. In the present study, we blocked TF using antisense oligodeoxynucleotides against mouse TF (TF-ASO). TF-ASO (5.6mgkg-1) was given i.v. to ND4 male mice 30min after administration of MCT (200mgkg-1) p.o. followed after 3.5h by LPS i.p. (6mgkg-1). Blood alanine aminotransferase (ALT), TF, ox-LDL, platelets, hematocrit and keratinocyte-derived chemokine (KC) levels were evaluated in different treatment groups. Fibrin deposition and ox-LDL accumulation were also analyzed in the liver sections using immunofluorescent staining. The results showed that TF-ASO significantly restored blood ALT, hematocrit and KC levels, distorted after MCT/LPS co-treatment, as well as preventing the accumulation of ox-LDL and the deposition of fibrin in the liver tissues, and thereby inhibited liver injury caused by MCT/LPS. In a separate experiment, TF-ASO administration significantly prolonged animal survival. The current study demonstrates that TF is associated with MCT/LPS-induced liver injury. Administration of TF-ASO successfully prevented this type of liver injury. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Hammad, Mohamed A.; Abdel-Bakky, Mohamed Sadek; Walker, Larry A.; Ashfaq, Mohammad K.] Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA.
[Hammad, Mohamed A.; Walker, Larry A.] Univ Mississippi, Sch Pharm, Dept Pharmacol, University, MS 38677 USA.
[Hammad, Mohamed A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA.
[Abdel-Bakky, Mohamed Sadek] Al Azhar Univ, Fac Pharm, Cairo, Egypt.
RP Ashfaq, MK (reprint author), Univ Mississippi, Sch Pharm, Thad Cochran Res Ctr, Room 2047, University, MS 38677 USA.
EM MKASHFAQ@OLEMISS.EDU
OI HAMMAD, MOHAMED/0000-0002-9684-2506
FU NSF [MRI 619774]; United States Department of Agriculture, Agricultural
Research Service [58-6408-2-0009]; US Food and Drug Administration
[5U01FD002071-09, 1U01FD003871-011]
FX The authors acknowledge the Light Microscopy Core Facility members, Dr
Zia Shariat-Madar and Mr Noah Osman (School of Pharmacy, University of
Mississippi) for their assistance. The Zeiss 510-META confocal
microscope service is supported through NSF grant no. MRI 619774 (ZSM).
We thank Mrs. Lavanya Madgula, Mrs. Mona Haron and all the vivarium
staff at the University of Mississippi for their help in completing the
experiments. This work was supported in part by grants from the United
States Department of Agriculture, Agricultural Research Service,
Specific Cooperative agreement (58-6408-2-0009) and the US Food and Drug
Administration (5U01FD002071-09 and 1U01FD003871-011).
NR 45
TC 3
Z9 3
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0260-437X
J9 J APPL TOXICOL
JI J. Appl. Toxicol.
PD AUG
PY 2013
VL 33
IS 8
BP 774
EP 783
DI 10.1002/jat.2728
PG 10
WC Toxicology
SC Toxicology
GA 169KH
UT WOS:000320778400008
PM 22407844
ER
PT J
AU Rapuano, BE
Singh, H
Boskey, AL
Doty, SB
MacDonald, DE
AF Rapuano, Bruce E.
Singh, Herman
Boskey, Adele L.
Doty, Stephen B.
MacDonald, Daniel E.
TI Heat and radiofrequency plasma glow discharge pretreatment of a titanium
alloy: Eveidence for enhanced osteoinductive properties
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE DENTAL IMPLANT; FIBRONECTIN; OSTEOBLAST; CELL DIFFERENTIATION; BONE
MINERALIZATION; HYDROXYAPATITE
ID OXIDE NET CHARGE; BONE SIALOPROTEIN; IN-VITRO; OSTEOBLAST ADHESION;
DENTAL IMPLANTS; CELL-LINE; FIBRONECTIN; DIFFERENTIATION;
MINERALIZATION; TISSUE
AB It is believed that orthopedic and implant longevity can be improved by optimizing fixation, or direct bone-implant contact, through the stimulation of new bone formation around the implant. The purpose of this study was to determine whether heat (600 degrees C) or radiofrequency plasma glow discharge (RFGD) pretreatment of Ti6Al4V stimulated calcium-phosphate mineral formation in cultures of attached MC3T3 osteoprogenitor cells with or without a fibronectin coating. Calcium-phosphate mineral was analyzed by flame atomic absorption spectrophotometry, scanning electron microscopy (SEM)/electron dispersive X-ray microanalysis (EDAX) and Fourier transformed infrared spectroscopy (FTIR). RFGD and heat pretreatments produced a general pattern of increased total soluble calcium levels, although the effect of heat pretreatment was greater than that of RFGD. SEM/EDAX showed the presence of calcium-and phosphorus-containing particles on untreated and treated disks that were more numerous on fibronectin-coated disks. These particles were observed earliest (1 week) on RFGD-pretreated surfaces. FTIR analyses showed that the heat pretreatment produced a general pattern of increased levels of apatite mineral at 2-4 weeks; a greater effect was observed for fibronectin-coated disks compared to uncoated disks. The observed findings suggest that heat pretreatment of Ti6Al4V increased the total mass of the mineral formed in MC3T3 osteoprogenitor cell cultures more than RFGD while the latter pretreatment hastened the early deposition of mineral. These findings help to support the hypothesis that the pretreatments enhance the osteoinductive properties of the alloy. J. Cell. Biochem. 114: 1917-1927, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Rapuano, Bruce E.; Singh, Herman; Boskey, Adele L.; Doty, Stephen B.; MacDonald, Daniel E.] Cornell Univ, Hosp Special Surg, Weill Med Coll, New York, NY 10021 USA.
[MacDonald, Daniel E.] James J Peters VA Med Ctr, Bronx, NY 10468 USA.
[MacDonald, Daniel E.] Columbia Univ, Langmuir Ctr Colloids & Interfaces, New York, NY 10027 USA.
RP MacDonald, DE (reprint author), Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA.
EM dem14@columbia.edu
OI Boskey, Adele/0000-0002-6181-2219
FU National Center for Research Resources, NIH [C06-RR12538-01]; [NIH R01
DE017695]
FX The project described was supported by Grant Number NIH R01 DE017695
(Awarded to DEM). The sponsor did not have any role in the study design;
the collection, analysis and interpretation of data; the writing of the
report; or the decision to submit the article for publication. This
material is also the result of work supported with resources and the use
of facilities at the James J. Peters VA Medical Center, Bronx, New York.
This investigation was also conducted at the HSS research facility
constructed with support of Grant C06-RR12538-01 from the National
Center for Research Resources, NIH. We would like to acknowledge Tony
Labissiere for technical assistance with the SEM/EDAX analyses. We would
also like to acknowledge Hayat Taleb, Kyle Hackshaw, and Carrie Guan for
assistance with FTIR and atomic absorption spectroscopy. Special thanks
goes to Kevin Pun for the preparation and treatment of titanium alloy
disks.
NR 50
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U1 2
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD AUG
PY 2013
VL 114
IS 8
BP 1917
EP 1927
DI 10.1002/jcb.24536
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 162OZ
UT WOS:000320276000023
PM 23494951
ER
PT J
AU Kim, SH
Lu, HF
Alano, C
AF Kim, Sun Hee
Lu, Huafei
Alano, Conrad
TI The mitochondrial sirtuin Sirt3 protects neurons from oxidative injury
SO JOURNAL OF NEUROSCIENCE RESEARCH
LA English
DT Meeting Abstract
CT 10th International Conference on Brain Energy Metabolism - Bioenergetics
of Neurological Disease and Aging
CY APR 17-20, 2012
CL Pacific Grove, CA
SP NINDS, NIA, Int Soc Neurochemistry (ISN) Conf Comm, NCIRE, Vet Hlth Res Inst, Wiley Blackwell, Seahorse Bioscience
C1 [Kim, Sun Hee; Lu, Huafei; Alano, Conrad] UCSF, San Francisco VA Med Ctr, Dept Neurol, San Francisco, CA 94121 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0360-4012
J9 J NEUROSCI RES
JI J. Neurosci. Res.
PD AUG
PY 2013
VL 91
IS 8
SI SI
BP 1096
EP 1096
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 171MO
UT WOS:000320933700037
ER
PT J
AU Carroll, JB
Fossale, E
Weston, R
Deik, A
Guide, J
Wheeler, VC
Seong, IS
Lee, JM
Clish, CB
MacDonald, ME
AF Carroll, Jeffrey B.
Fossale, Elisa
Weston, Rory
Deik, Amy
Guide, Jolene
Wheeler, Vanessa C.
Seong, Ihn Sik
Lee, Jong-Min
Clish, Clary B.
MacDonald, Marcy E.
TI Objective metabolic phenotyping of knock-in mice reveals novel
dysfunctional pathways in Huntington's disease
SO JOURNAL OF NEUROSCIENCE RESEARCH
LA English
DT Meeting Abstract
CT 10th International Conference on Brain Energy Metabolism - Bioenergetics
of Neurological Disease and Aging
CY APR 17-20, 2012
CL Pacific Grove, CA
SP NINDS, NIA, Int Soc Neurochemistry (ISN) Conf Comm, NCIRE, Vet Hlth Res Inst, Wiley Blackwell, Seahorse Bioscience
C1 [Carroll, Jeffrey B.; Fossale, Elisa; Guide, Jolene; Wheeler, Vanessa C.; Seong, Ihn Sik; Lee, Jong-Min; MacDonald, Marcy E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Deik, Amy; Clish, Clary B.; MacDonald, Marcy E.] MIT, Broad Inst, Cambridge, MA 02142 USA.
[Deik, Amy; Clish, Clary B.; MacDonald, Marcy E.] Harvard Univ, Cambridge, MA 02142 USA.
[Carroll, Jeffrey B.; Weston, Rory] Western Washington Univ, Dept Psychol, Behav Neurosci Program, Bellingham, WA 98225 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0360-4012
J9 J NEUROSCI RES
JI J. Neurosci. Res.
PD AUG
PY 2013
VL 91
IS 8
SI SI
BP 1099
EP 1099
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 171MO
UT WOS:000320933700045
ER
PT J
AU Reyes, R
Kim, JE
Brennan, AM
Swanson, RA
AF Reyes, Reno
Kim, Ji-Eun
Brennan, Angela M.
Swanson, Raymond A.
TI Malic enzyme can support neuronal superoxide production by providing
NADPH
SO JOURNAL OF NEUROSCIENCE RESEARCH
LA English
DT Meeting Abstract
CT 10th International Conference on Brain Energy Metabolism - Bioenergetics
of Neurological Disease and Aging
CY APR 17-20, 2012
CL Pacific Grove, CA
SP NINDS, NIA, Int Soc Neurochemistry (ISN) Conf Comm, NCIRE, Vet Hlth Res Inst, Wiley Blackwell, Seahorse Bioscience
C1 [Reyes, Reno; Kim, Ji-Eun; Brennan, Angela M.; Swanson, Raymond A.] San Francisco VA Med Ctr, Dept Neurol, San Francisco, CA USA.
[Reyes, Reno; Kim, Ji-Eun; Brennan, Angela M.; Swanson, Raymond A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0360-4012
J9 J NEUROSCI RES
JI J. Neurosci. Res.
PD AUG
PY 2013
VL 91
IS 8
SI SI
BP 1110
EP 1110
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 171MO
UT WOS:000320933700069
ER
PT J
AU Elborai, Y
Blanchette, A
Maher, O
Lehmann, L
Lee, M
AF Elborai, Yasser
Blanchette, Andrew
Maher, Ossama
Lehmann, Leslie
Lee, Michelle
TI RENAL AND BONE MARROW TOXICITY IN PEDIATRIC HSCT PATIENTS ON ACYCLOVIR
PROPHYLAXIS
SO PEDIATRIC TRANSPLANTATION
LA English
DT Meeting Abstract
C1 [Elborai, Yasser; Maher, Ossama] Cairo Univ, Natl Canc Inst, Ped Onc, Cairo, Egypt.
[Elborai, Yasser; Blanchette, Andrew; Lehmann, Leslie; Lee, Michelle] Harvard Univ, Dana Farber Canc Inst, Ped HSCT, Boston, MA 02115 USA.
[Maher, Ossama] Brooklyn Hosp Ctr, Brooklyn, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1397-3142
J9 PEDIATR TRANSPLANT
JI Pediatr. Transplant.
PD AUG
PY 2013
VL 17
SU 1
MA 133
BP 75
EP 75
PG 1
WC Pediatrics; Transplantation
SC Pediatrics; Transplantation
GA 178IC
UT WOS:000321439600133
ER
PT J
AU Nagy, AY
Lehmann, LE
AF Nagy, Ahmed Y.
Lehmann, Leslie E.
TI THE ASSOCIATION OF STEROID INDUCED CARDIAC VENTRICULAR HYPERTROPHY AND
TRANSPLANT-RELATED MORTALITY IN CHILDREN WITH HEMOPHAGOCYTIC
LYMPHOHISTIOCYTOSIS
SO PEDIATRIC TRANSPLANTATION
LA English
DT Meeting Abstract
C1 [Nagy, Ahmed Y.] Ain Shams Univ, Fac Med, Cairo, Egypt.
[Lehmann, Leslie E.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1397-3142
J9 PEDIATR TRANSPLANT
JI Pediatr. Transplant.
PD AUG
PY 2013
VL 17
SU 1
MA 134
BP 75
EP 75
PG 1
WC Pediatrics; Transplantation
SC Pediatrics; Transplantation
GA 178IC
UT WOS:000321439600134
ER
PT J
AU Shulman, DS
Lehmann, LE
AF Shulman, David S.
Lehmann, Leslie E.
TI INCIDENCE AND CAUSES OF HOSPITAL READMISSION FOR PEDIATRIC PATIENTS
UNDERGOING HEMATOIETIC CELL TRANSPLANT
SO PEDIATRIC TRANSPLANTATION
LA English
DT Meeting Abstract
C1 [Shulman, David S.] Harvard Univ, Sch Med, Boston, MA USA.
[Lehmann, Leslie E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1397-3142
J9 PEDIATR TRANSPLANT
JI Pediatr. Transplant.
PD AUG
PY 2013
VL 17
SU 1
MA 135
BP 75
EP 76
PG 2
WC Pediatrics; Transplantation
SC Pediatrics; Transplantation
GA 178IC
UT WOS:000321439600135
ER
PT J
AU Kuter, DJ
Mehta, A
Hollak, CEM
Giraldo, P
Hughes, D
Belmatoug, N
Brand, M
Muller, A
Schaaf, B
Giorgino, R
Zimran, A
AF Kuter, David J.
Mehta, Atul
Hollak, Carla E. M.
Giraldo, Pilar
Hughes, Derralynn
Belmatoug, Nadia
Brand, Monika
Muller, Audrey
Schaaf, Berthold
Giorgino, Ruben
Zimran, Ari
TI Miglustat therapy in type 1 Gaucher disease: Clinical and safety
outcomes in a multicenter retrospective cohort study
SO BLOOD CELLS MOLECULES AND DISEASES
LA English
DT Article
DE Gaucher disease; Miglustat; Outcomes; Safety; Tolerability
ID N-BUTYLDEOXYNOJIRIMYCIN; OPEN-LABEL; PERIPHERAL NEUROPATHY; MAINTENANCE
THERAPY; ENZYME REPLACEMENT; TREATED PATIENTS; OGT-918; ADULTS; 2-YEAR
AB We evaluated clinical and safety outcomes in adult patients with type 1 Gaucher disease receiving miglustat in clinical practice settings. An observational, retrospective cohort study was conducted in centers across the EU and the USA. Medical chart data were collected from consecutive patients between the 20th November 2002 and 31st December 2008. A total of 115 patients were included; 34 (30%) were enzyme replacement therapy-naive ('naive') and 81(70%) were enzyme pretreated ('pretreated'). Median (range) miglustat exposures in these groups were 15.1(0.6-52.9) months and 15.2 (0.3-62.1) months, respectively. Low numbers of patients were anemic (10/101) or thrombocytopenic (21/101) at initiation of miglustat therapy. The median (range) hemoglobin concentration at miglustat initiation was 12.8 (10.2-16.4) g/dl in naive patients and 13.6(7.3-17.4) g/dl in pretreated patients; median (range) changes in hemoglobin were 0.3 (-2.5-3.6) and -0.3 (-4-4.6) g/dl, respectively. The median (range) platelet counts at miglustat initiation were 101 (37-730) x 10(9)/l in naive patients and 173 (43-382) x 10(9)/l in pretreated patients; median (range) changes in platelet count were 8 (-77-145) x 10(9)/l and -10 (-144-434) x 10(9)/l, respectively. Plasma chitotriosidase was substantially reduced in naive but not in pretreated patients. Organ volumes were not routinely monitored. Forty-nine (43%) patients discontinued miglustat; most due to gastrointestinal manifestations and some due to tremor. Overall, hemoglobin and platelet counts tended to increase in naive patients treated with miglustat and to remain stable or decrease slightly in pretreated patients. The profile of safety and tolerability observed with miglustat in the current study is similar to previous studies. (c) 2013 Elsevier Inc. All rights reserved.
C1 [Kuter, David J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mehta, Atul; Hughes, Derralynn] Royal Free Hosp, London NW3 2QG, England.
[Hollak, Carla E. M.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
[Giraldo, Pilar] Hosp Univ Miguel Servet, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Zaragoza, Spain.
[Hughes, Derralynn] UCL, Sch Med, London W1N 8AA, England.
[Belmatoug, Nadia] Hop Beaujon, Clichy, France.
[Brand, Monika; Muller, Audrey; Giorgino, Ruben] Actel Pharmaceut Ltd, Allschwil, Switzerland.
[Schaaf, Berthold] Factum GmbH, Offenbach, Germany.
[Zimran, Ari] Shaare Zedek Med Ctr, Jerusalem, Israel.
RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Div Hematol, 55 Fruit St, Boston, MA 02114 USA.
EM DKUTER@PARTNERS.ORG
FU Actelion Pharmaceuticals Ltd
FX The authors would like to thank all participating physicians for their
valuable contributions to these data, and Harbajan Chadha-Boreham PhD,
Senior Statistician at Actelion for providing support on the Statistical
Analysis Plan. We would also like to thank Matthew Reilly PhD,
associated with InTouch Medical Ltd., for medical writing assistance in
the preparation of this manuscript. This study was funded by the
Actelion Pharmaceuticals Ltd.
NR 26
TC 21
Z9 23
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 1079-9796
J9 BLOOD CELL MOL DIS
JI Blood Cells Mol. Dis.
PD AUG
PY 2013
VL 51
IS 2
BP 116
EP 124
DI 10.1016/j.bcmd.2013.04.005
PG 9
WC Hematology
SC Hematology
GA 164LP
UT WOS:000320411900011
PM 23683771
ER
PT J
AU Nivison-Smith, L
Sun, D
Fletcher, EL
Marc, RE
Kalloniatis, M
AF Nivison-Smith, Lisa
Sun, Daniel
Fletcher, Erica L.
Marc, Robert E.
Kalloniatis, Michael
TI Mapping kainate activation of inner neurons in the rat retina
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE kainate; kainate receptors; agmatine; AGB; rat retina; glutamate; GABA;
glycine; immunocytochemistry
ID CONE BIPOLAR CELLS; NITRIC-OXIDE SYNTHASE; AMINO-ACID RECEPTORS;
IONOTROPIC GLUTAMATE RECEPTORS; CENTRAL-NERVOUS-SYSTEM; ZEBRAFISH
OLFACTORY-BULB; NK3 NEUROKININ RECEPTORS; DEVELOPING RABBIT RETINA;
AII-AMACRINE CELLS; PROTEIN KINASE-C
AB Kainate receptors mediate fast, excitatory synaptic transmission for a range of inner neurons in the mammalian retina. However, allocation of functional kainate receptors to known cell types and their sensitivity remains unresolved. Using the cation channel probe 1-amino-4-guanidobutane agmatine (AGB), we investigated kainate sensitivity of neurochemically identified cell populations within the structurally intact rat retina. Most inner retinal neuron populations responded to kainate in a concentration-dependent manner. OFF cone bipolar cells demonstrated the highest sensitivity of all inner neurons to kainate. Immunocytochemical localization of AGB and macromolecular markers confirmed that type 2 bipolar cells were part of this kainate-sensitive population. The majority of amacrine (ACs) and ganglion cells (GCs) showed kainate responses with different sensitivities between major neurochemical classes (-aminobutyric acid [GABA]/glycine ACs > glycine ACs > GABA ACs; glutamate [Glu]/weakly GABA GCs > Glu GCs). Conventional and displaced cholinergic ACs were highly responsive to kainate, whereas dopaminergic ACs do not appear to express functional kainate receptors. These findings further contribute to our understanding of neuronal networks in complex multicellular tissues. J. Comp. Neurol. 521:2416-2438, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Nivison-Smith, Lisa; Kalloniatis, Michael] Univ New S Wales, Sch Optometry & Vis Sci, Sydney, NSW 2052, Australia.
[Sun, Daniel; Kalloniatis, Michael] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Sun, Daniel] Univ Auckland, Dept Optometry & Vis Sci, Auckland 1142, New Zealand.
[Fletcher, Erica L.; Kalloniatis, Michael] Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic 3010, Australia.
[Marc, Robert E.] Univ Utah, Sch Med, Dept Ophthalmol, Salt Lake City, UT 84113 USA.
[Kalloniatis, Michael] Ctr Eye Hlth, Sydney, NSW 2052, Australia.
RP Kalloniatis, M (reprint author), Univ New S Wales, Ctr Eye Hlth, Sydney, NSW 2052, Australia.
EM m.kalloniatis@unsw.edu.au
RI Fletcher, Erica/E-6364-2012;
OI Fletcher, Erica/0000-0001-9412-9523; Nivison-Smith,
Lisa/0000-0001-6677-1949
FU National Health and Medical Research Council of Australia [1009342,
1021042]; National Institutes of Health [EY02576, EY014800]
FX Grant sponsor: the National Health and Medical Research Council of
Australia; Grant numbers: 1009342 (to M. K. and E. L. F.) and 1021042
(to E. L. F. and M. K.); Grant sponsor: the National Institutes of
Health; Grant numbers: EY02576 and EY014800 (to R.E.M.).
NR 119
TC 10
Z9 10
U1 1
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9967
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD AUG 1
PY 2013
VL 521
IS 11
BP 2416
EP 2438
DI 10.1002/cne.23305
PG 23
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA 158KU
UT WOS:000319970100002
PM 23348566
ER
PT J
AU Muller, LPD
Liu, J
Solomon, A
Rodriguez, A
Brecha, NC
AF Mueller, Luis Perez De Sevilla
Liu, Janelle
Solomon, Alexander
Rodriguez, Allen
Brecha, Nicholas C.
TI Expression of voltage-gated calcium channel 24 subunits in the mouse and
rat retina
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE calcium channel; 24 subunit; Muller cell; photoreceptor; retina; mouse;
rat
ID PHOTORECEPTOR RIBBON SYNAPSE; ACID TRANSPORTER EXPRESSION;
TISSUE-SPECIFIC EXPRESSION; PIG HORIZONTAL CELLS; PROTEIN KINASE-C;
MAMMALIAN RETINA; FUNCTIONAL ABNORMALITIES; BIPOLAR CELLS; ALPHA(2)DELTA
SUBUNIT; CELLULAR-DISTRIBUTION
AB High-voltage activated Ca channels participate in multiple cellular functions, including transmitter release, excitation, and gene transcription. Ca channels are heteromeric proteins consisting of a pore-forming 1 subunit and auxiliary 2 and subunits. Although there are reports of 24 subunit mRNA in the mouse retina and localization of the 24 subunit immunoreactivity to salamander photoreceptor terminals, there is a limited overall understanding of its expression and localization in the retina. 24 subunit expression and distribution in the mouse and rat retina were evaluated by using reverse transcriptase polymerase chain reaction, western blot, and immunohistochemistry with specific primers and a well-characterized antibody to the 24 subunit. 24 subunit mRNA and protein are present in mouse and rat retina, brain, and liver homogenates. Immunostaining for the 24 subunit is mainly localized to Muller cell processes and endfeet, photoreceptor terminals, and photoreceptor outer segments. This subunit is also expressed in a few displaced ganglion cells and bipolar cell dendrites. These findings suggest that the 24 subunit participates in the modulation of L-type Ca2+ current regulating neurotransmitter release from photoreceptor terminals and Ca2+-dependent signaling pathways in bipolar and Muller cells. J. Comp. Neurol. 521:2486-2501, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Mueller, Luis Perez De Sevilla; Liu, Janelle; Solomon, Alexander; Rodriguez, Allen; Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
RP Muller, LPD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med Los Angeles, Dept Neurobiol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA.
EM luisperez@mednet.ucla.edu
FU U.S. Army Medical Research & Materiel Command (USAMRMC); Telemedicine &
Advanced Technology Research Center (TATRC), at Fort Detrick, MD
[W81XWH-10-2-0077]; National Institutes of Health [EY04067]; Veterans
Administration Merit Review
FX Grant sponsor: the U.S. Army Medical Research & Materiel Command
(USAMRMC) and the Telemedicine & Advanced Technology Research Center
(TATRC), at Fort Detrick, MD; Grant number: W81XWH-10-2-0077; Grant
sponsor: National Institutes of Health; Grant number: EY04067; Grant
sponsor: Veterans Administration Merit Review (to N.C.B., who is also a
Veterans Administration Career Research Scientist) J.L. and A. S.
contributed equally to this work.
NR 95
TC 4
Z9 4
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9967
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD AUG 1
PY 2013
VL 521
IS 11
BP 2486
EP 2501
DI 10.1002/cne.23294
PG 16
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA 158KU
UT WOS:000319970100005
ER
PT J
AU Knowles, JK
Simmons, DA
Nguyen, TVV
Vander Griend, L
Xie, YM
Zhang, H
Yang, T
Pollak, J
Chang, T
Arancio, O
Buckwalter, MS
Wyss-Coray, T
Massa, SM
Longo, FM
AF Knowles, Juliet K.
Simmons, Danielle A.
Nguyen, Thuy-Vi V.
Vander Griend, Lilith
Xie, Youmei
Zhang, Hong
Yang, Tao
Pollak, Julia
Chang, Timothy
Arancio, Ottavio
Buckwalter, Marion S.
Wyss-Coray, Tony
Massa, Stephen M.
Longo, Frank M.
TI A small molecule p75(NTR) ligand prevents cognitive deficits and neurite
degeneration in an Alzheimer's mouse model
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Alzheimers' disease; p75 neurotrophin receptor; Neuritic dystrophy;
LM11A-31
ID NERVE GROWTH-FACTOR; P75 NEUROTROPHIN RECEPTOR; BASAL FOREBRAIN NEURONS;
LONG-TERM DEPRESSION; FACTOR GENE-THERAPY; TRANSGENIC MICE;
INTRACEREBROVENTRICULAR INFUSION; ADULT-RAT; DISEASE; EXPRESSION
AB The p75 neurotrophin receptor (p75(NTR)) is associated with multiple mechanisms linked to Alzheimer's disease (AD); hence, modulating its function might confer therapeutic effects. In previous in vitro work, we developed small molecule p75(NTR) ligands that inhibited amyloid-beta-induced degenerative signaling and prevented neurite degeneration. In the present study, a prototype p75(NTR) ligand, LM11A-31, was administered orally to the Thy-1 hAPP(Lond/Swe) (APP(L/S)) AD mouse model. LM11A-31 reached brain concentrations known to inhibit degenerative signaling without toxicity or induction of hyperalgesia. It prevented deficits in novel object recognition after 2.5 months and, in a separate cohort, deficits in Y-maze performance after 3 months of treatment. Stereology studies found that the number and size of basal forebrain cholinergic neurons, which are normal in APP(L/S) mice, were unaffected. Neuritic dystrophy, however, was readily apparent in the basal forebrain, hippocampus and cortex, and was significantly reduced by LM11A-31, with no effect on amyloid levels. These studies reveal that p75(NTR) is an important and tractable in vivo drug target for AD, with LM11A-31 representing a novel class of therapeutic candidates. (c) 2013 Elsevier Inc. All rights reserved.
C1 [Knowles, Juliet K.; Simmons, Danielle A.; Nguyen, Thuy-Vi V.; Vander Griend, Lilith; Yang, Tao; Pollak, Julia; Chang, Timothy; Buckwalter, Marion S.; Wyss-Coray, Tony; Longo, Frank M.] Stanford Univ, Dept Neurol & Neurol Sci, Palo Alto, CA 94304 USA.
[Knowles, Juliet K.; Xie, Youmei] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA.
[Zhang, Hong; Arancio, Ottavio] Columbia Univ, Dept Pathol, New York, NY USA.
[Zhang, Hong; Arancio, Ottavio] Columbia Univ, Taub Inst, New York, NY USA.
[Wyss-Coray, Tony] Palo Alto Vet Affairs Hlth Care Syst, Palo Alto, CA USA.
[Massa, Stephen M.] San Francisco VA Med Ctr, Dept Neurol, San Francisco, CA USA.
[Massa, Stephen M.] San Francisco VA Med Ctr, Lab Computat Neurochem & Drug Discovery, San Francisco, CA USA.
[Massa, Stephen M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
RP Longo, FM (reprint author), Stanford Univ, Dept Neurol & Neurol Sci, Palo Alto, CA 94304 USA.
EM longo@stanford.edu
FU NINDS [F30 NA051971, NIA UO1 AG032225, NS049442]; Alzheimer's Drug
Discovery Foundation; Alzheimer's Association; Eastern Chapter of the
North Carolina Alzheimer's Association; Jean Perkins Foundation;
Horngren Family Alzheimer's Research Fund; Richard M. Lucas Foundation;
Veterans Administration
FX This project was supported by funding from NINDS F30 NA051971 (J.K.K.),
NIA UO1 AG032225 (F.M.L.), NS049442 (O.A.), the Alzheimer's Drug
Discovery Foundation (F.M.L.), Alzheimer's Association (F.M.L.), the
Eastern Chapter of the North Carolina Alzheimer's Association (F.M.L.),
the Jean Perkins Foundation (F.M.L.), and the Horngren Family
Alzheimer's Research Fund (F.M.L.), the Richard M. Lucas Foundation
(F.M.L.) and the Veterans Administration (S.M.M. and T.W.C.). The
authors thank Chihiro Ishikawa and Mary Wilson for their assistance in
the execution of this work.
NR 65
TC 33
Z9 35
U1 0
U2 22
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD AUG
PY 2013
VL 34
IS 8
BP 2052
EP 2063
DI 10.1016/j.neurobiolaging.2013.02.015
PG 12
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 156ED
UT WOS:000319803100013
PM 23545424
ER
PT J
AU Yue, XM
Nasr, S
Devaney, KJ
Holt, DJ
Tootell, RBH
AF Yue, Xiaomin
Nasr, Shahin
Devaney, Kathryn J.
Holt, Daphne J.
Tootell, Roger B. H.
TI FMRI analysis of contrast polarity in face-selective cortex in humans
and monkeys
SO NEUROIMAGE
LA English
DT Article
DE Face recognition; FFA; Contrast polarity; Face inversion; Monkey fMRI;
Face patches
ID PRIMARY VISUAL-CORTEX; LATERAL OCCIPITAL COMPLEX; TEMPORAL CORTEX;
FUNCTIONAL-ANALYSIS; RECOGNITION MEMORY; COORDINATE SYSTEM;
CEREBRAL-CORTEX; FUSIFORM GYRUS; CORTICAL AREAS; MACAQUE
AB Recognition is strongly impaired when the normal contrast polarity of faces is reversed. For instance, otherwise-familiar faces become very difficult to recognize when viewed as photographic negatives. Here, we used fMRI to demonstrate related properties in visual cortex: 1) fMRI responses in the human Fusiform Face Area (FFA) decreased strongly (26%) to contrast-reversed faces across a wide range of contrast levels (5.3-100% RMS contrast), in all subjects tested. In a whole brain analysis, this contrast polarity bias was largely confined to the Fusiform Face Area (FFA; p < 0.0001), with possible involvement of a left occipital face-selective region. 2) It is known that reversing facial contrast affects three image properties in parallel (absorbance, shading, and specular reflection). Here, comparison of FFA responses to those in V1 suggests that the contrast polarity bias is produced in FFA only when all three component properties were reversed simultaneously, which suggests a prominent non-linearity in FFA processing. 3) Across a wide range (180 degrees) of illumination source angles, 3D face shapes without texture produced response constancy in FFA, without a contrast polarity bias. 4) Consistent with psychophysics, analogous fMRI biases for normal contrast polarity were not produced by non-face objects, with image statistics similar to the face stimuli. 5) Using fMRI, we also demonstrated a contrast polarity bias in awake behaving macaque monkeys, in the cortical region considered homologous to human FFA. Thus common cortical mechanisms may underlie facial contrast processing across similar to 25 million years of primate evolution. (c) 2013 Elsevier Inc. All rights reserved.
C1 [Yue, Xiaomin; Nasr, Shahin; Devaney, Kathryn J.; Holt, Daphne J.; Tootell, Roger B. H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Yue, XM (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA.
EM xiaomin@nmr.mgh.harvard.edu
FU National Institute of Health [EY017081, EY022096, MH076054]; National
Alliance for Research on Schizophrenia and Depression (NARSAD); Sidney
J. Bear Trust; Martinos Center for Biomedical Imaging, NCRR [P41RR14075]
FX This study was supported by the National Institute of Health (EY017081
and EY022096 to RBHT, MH076054 to DJH) and the National Alliance for
Research on Schizophrenia and Depression (NARSAD) (RBT, DJH), with the
Sidney J. Bear Trust (DJH). Additional support came from the Martinos
Center for Biomedical Imaging, NCRR (P41RR14075).
NR 70
TC 7
Z9 7
U1 1
U2 20
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 AUG 1
PY 2013
VL 76
IS 1
BP 57
EP 69
DI 10.1016/j.neuroimage.2013.02.068
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 146KP
UT WOS:000319090300006
PM 23518007
ER
PT J
AU Lew, S
Sliva, DD
Choe, MS
Grant, PE
Okada, Y
Wolters, CH
Hamalainen, MS
AF Lew, Seok
Sliva, Danielle D.
Choe, Myong-sun
Grant, P. Ellen
Okada, Yoshio
Wolters, Carsten H.
Haemaelaeinen, Matti S.
TI Effects of sutures and fontanels on MEG and EEG source analysis in a
realistic infant head model
SO NEUROIMAGE
LA English
DT Article
DE MEG; EEG; FEM; Source analysis; Suture; Fontanel
ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; FINITE-ELEMENT-METHOD;
CORTICAL SURFACE; SOURCE LOCALIZATION; ELECTRICAL-CONDUCTIVITY;
COORDINATE SYSTEM; INVERSE PROBLEM; TERM INFANTS; HUMAN BRAIN
AB In infants, the fontanels and sutures as well as conductivity of the skull influence the volume currents accompanying primary currents generated by active neurons and thus the associated electroencephalography (EEG) and magnetoencephalography (MEG) signals. We used a finite element method (FEM) to construct a realistic model of the head of an infant based on MRI images. Using this model, we investigated the effects of the fontanels, sutures and skull conductivity on forward and inverse EEG and MEG source analysis. Simulation results show that MEG is better suited than EEG to study early brain development because it is much less sensitive than EEG to distortions of the volume current caused by the fontanels and sutures and to inaccurate estimates of skull conductivity. Best results will be achieved when MEG and EEG are used in combination. (C) 2013 Elsevier Inc All rights reserved.
C1 [Lew, Seok; Choe, Myong-sun; Grant, P. Ellen; Haemaelaeinen, Matti S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Sliva, Danielle D.; Choe, Myong-sun; Grant, P. Ellen; Okada, Yoshio] Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA 02115 USA.
[Okada, Yoshio] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Wolters, Carsten H.] Univ Munster, Inst Biomagnetism & Biosignalanal, D-48149 Munster, Germany.
RP Lew, S (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA.
EM slew@nmr.mgh.harvard.edu
RI Hamalainen, Matti/C-8507-2013; Wolters, Carsten/R-4234-2016
OI Wolters, Carsten/0000-0001-6233-424X
FU NIH [R01EB0009048, R21EB008547, P41RR14075]; NSF [0958669]; German DFG
[WO1425/3-1]
FX We would like to thank Ruopeng Wang for his support in using Freeview,
Benjamin Lanfer for his support in implementing infant magnetometer
coils, and Moritz Dannhauer for providing the NeuroFEM FIFF file reader.
This study was supported by NIH grants R01EB0009048, R21EB008547, and
P41RR14075, NSF grant 0958669, and German DFG-project WO1425/3-1.
NR 73
TC 24
Z9 24
U1 0
U2 18
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD AUG 1
PY 2013
VL 76
IS 1
BP 282
EP 293
DI 10.1016/j.neuroimage.2013.03.017
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 146KP
UT WOS:000319090300027
PM 23531680
ER
PT J
AU Bakkour, A
Morris, JC
Wolk, DA
Dickerson, BC
AF Bakkour, Akram
Morris, John C.
Wolk, David A.
Dickerson, Bradford C.
TI The effects of aging and Alzheimer's disease on cerebral cortical
anatomy: Specificity and differential relationships with cognition
SO NEUROIMAGE
LA English
DT Article
DE Magnetic resonance imaging; Cerebral cortex; Aging; Alzheimer' disease;
Parietal lobe; Frontal lobe; Temporal lobe
ID VOXEL-BASED MORPHOMETRY; NORMAL NEUROANATOMICAL VARIATION; SURFACE-BASED
ANALYSIS; PITTSBURGH COMPOUND-B; MEDIAL TEMPORAL-LOBE; MILD AD DEMENTIA;
HUMAN BRAIN; FUNCTIONAL CONNECTIVITY; AMYLOID DEPOSITION; ELDERLY
SUBJECTS
AB Although both normal aging and Alzheimer's disease (AD) are associated with regional cortical atrophy, few studies have directly compared the spatial patterns and magnitude of effects of these two processes. The extant literature has not addressed two important questions: 1) Is the pattern of age-related cortical atrophy different if cognitively intact elderly individuals with silent AD pathology are excluded?.and 2) Does the age- or AD-related atrophy relate to cognitive function? Here we studied 142 young controls, 87 older controls, and 28 mild AD patients. In addition, we studied 35 older controls with neuroimaging data indicating the absence of brain amyloid. Whole-cortex analyses identified regions of interest (ROIs) of cortical atrophy in aging and in AD. Results showed that some regions are predominantly affected by age with relatively little additional atrophy in patients with AD, e.g., calcarine cortex; other regions are predominantly affected by AD with much less of an effect of age, e.g., medial temporal cortex. Finally, other regions are affected by both aging and AD, e.g., dorsolateral prefrontal cortex and inferior parietal lobule. Thus, the processes of aging and AD have both differential and partially overlapping effects on specific regions of the cerebral cortex. In particular, some frontoparietal regions are affected by both processes, most temporal lobe regions are affected much more prominently by AD than aging, while sensorimotor and some prefrontal regions are affected specifically by aging and minimally more by AD. Within normal older adults, atrophy in aging-specific cortical regions relates to cognitive performance, while in AD patients atrophy in AD-specific regions relates to cognitive performance. Further work is warranted to investigate the behavioral and clinical relevance of these findings in additional detail, as well as their histological basis; ROIs generated from the present study could be used strategically in such investigations. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Bakkour, Akram; Dickerson, Bradford C.] Massachusetts Gen Hosp, Frontotemporal Dementia Unit, Boston, MA 02114 USA.
[Bakkour, Akram; Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA.
[Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Bakkour, Akram; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Dickerson, Bradford C.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA.
[Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Morris, John C.] Washington Univ, Sch Med, Alzheimers Dis Res Ctr, St Louis, MO USA.
[Wolk, David A.] Univ Penn, Dept Neurol, Alzheimers Dis Core Ctr, Penn Memory Ctr, Philadelphia, PA 19104 USA.
RP Dickerson, BC (reprint author), MGH Frontotemporal Dementia Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA.
EM bradd@nmr.mgh.harvard.edu
OI Bakkour, Akram/0000-0002-6070-4945
FU NIA [R01-AG29411, R21-AG29840, P50-AG05134, P50-AG05681, P01-AG03991];
NCRR [P41-RR14075, U24-RR021382]; Alzheimer's Association; Mental
Illness and Neuroscience Discovery (MIND) Institute
FX This study was supported by grants from the NIA R01-AG29411,
R21-AG29840, P50-AG05134, P50-AG05681, and P01-AG03991, the NCRR
P41-RR14075 and U24-RR021382, the Alzheimer's Association, and the
Mental Illness and Neuroscience Discovery (MIND) Institute.
NR 95
TC 20
Z9 20
U1 0
U2 34
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 AUG 1
PY 2013
VL 76
IS 1
BP 332
EP 344
DI 10.1016/j.neuroimage.2013.02.059
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 146KP
UT WOS:000319090300032
PM 23507382
ER
PT J
AU Cassetta, L
Kajaste-Rudnitski, A
Coradin, T
Saba, E
Della Chiara, G
Barbagallo, M
Graziano, F
Alfano, M
Cassol, E
Vicenzi, E
Poli, G
AF Cassetta, Luca
Kajaste-Rudnitski, Anna
Coradin, Tiziana
Saba, Elisa
Della Chiara, Giulia
Barbagallo, Marialuisa
Graziano, Francesca
Alfano, Massimo
Cassol, Edana
Vicenzi, Elisa
Poli, Guido
TI M1 polarization of human monocyte-derived macrophages restricts pre and
postintegration steps of HIV-1 replication
SO AIDS
LA English
DT Article
DE APOBEC3A; APOBEC3G; cytokines; HIV-1; integration; M1 polarization;
macrophage; transcription
ID DEAMINASE ACTIVITY; APOBEC3 PROTEINS; GENE-EXPRESSION; HUMAN-CELLS;
T-CELLS; IN-VIVO; VIRUS; ACTIVATION; INFECTION; DNA
AB Objective: Functional polarization of human monocyte-derived macrophages (MDMs) into M1 cells leads to inhibition of R5 HIV-1 replication and viral DNA synthesis in comparison to control, unpolarized cells together with CD4 downregulation from the cell surface and upregulation of CCR5-binding chemokine secretion. We here investigated whether a postentry restriction of virus replication is also induced by M1 polarization of MDM.
Design: MDM were first polarized to M1 cells by 18 h stimulation with interferon-g and tumor necrosis factor-alpha; the cytokines were then removed and the cells were infected with vesicular stomatitis virus G-protein pseudotyped enhanced green fluorescence protein HIV-1 (HIV-GFP) generating a single-round infection cycle.
Methods: HIV-1 expression was monitored in terms of eGFP expression by fluorescence activated cell sorter (FACS) analysis and real-time PCR analysis of total HIV-1 gag DNA, 2-long terminal repeat DNA, proviral DNA, and multiply spliced RNA transcripts. Expression of apolipopoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G (APOBEC3G), and APOBEC3A was tested by western blotting and FACS analysis.
Results: Inhibition of HIV-GFP expression was observed in M1-MDM along with impaired viral DNA synthesis, delayed proviral integration, and reduced proviral transcription. Although APOBEC3G levels were similar in M1 and unpolarized MDM, APOBEC 3A was selectively expressed only by M1 cells.
Conclusion: M1 polarization of in-vitro differentiated primary MDM determines a transient, but profound restriction of HIV-1 replication affecting multiple (entry and postentry) steps in the virus life cycle likely involving the upregulated expression of APOBEC3A. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Cassetta, Luca; Saba, Elisa; Della Chiara, Giulia; Barbagallo, Marialuisa; Graziano, Francesca; Alfano, Massimo; Cassol, Edana; Poli, Guido] Ist Sci San Raffaele, AIDS Immunopathogenesis Unit, I-20132 Milan, Italy.
[Kajaste-Rudnitski, Anna; Coradin, Tiziana; Vicenzi, Elisa] Ist Sci San Raffaele, Viral Pathogens & Biosafety Unit, Div Immunol Transplantat & Infect Dis, I-20132 Milan, Italy.
[Graziano, Francesca; Poli, Guido] Univ Vita Salute Salute San Raffaele, Sch Med, Milan, Italy.
[Cassetta, Luca] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10467 USA.
[Coradin, Tiziana] Univ Trento, Ctr Integrat Biol, Mattarello, Trento, Italy.
[Kajaste-Rudnitski, Anna] Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy.
[Della Chiara, Giulia] European Inst Oncol, Dept Expt Oncol, Milan, Italy.
[Cassol, Edana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
RP Poli, G (reprint author), P2-P3 Labs,DIBIT 1,Via Olgettina 58, I-20132 Milan, Italy.
EM poli.guido@hsr.it
OI Kajaste-Rudnitski, Anna/0000-0003-1549-2426; Vicenzi,
Elisa/0000-0003-0051-3968
FU CARIPLO [2008-2230]; Ministry of Health, Italy [40H76, 40H18, 40H11]
FX This study was supported by the CARIPLO grant 2008-2230 (to G. P.) and
by the grants n. 40H76, 40H18, and 40H11 (to G. P., E. V., and M. A.,
respectively) of the Program of AIDS research 2009-2010 of the Ministry
of Health, Italy.
NR 40
TC 18
Z9 18
U1 1
U2 3
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 JUL 31
PY 2013
VL 27
IS 12
BP 1847
EP 1856
DI 10.1097/QAD.0b013e328361d059
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 301IK
UT WOS:000330525800002
PM 23612004
ER
PT J
AU Smurzynski, M
Wu, KL
Schouten, JT
Lok, JJ
Bosch, RJ
Taiwo, B
Johnson, VA
Collier, AC
AF Smurzynski, Marlene
Wu, Kunling
Schouten, Jeffrey T.
Lok, Judith J.
Bosch, Ronald J.
Taiwo, Babafemi
Johnson, Victoria Anne
Collier, Ann C.
TI Factors associated with remaining on initial randomized
efavirenz-containing regimens
SO AIDS
LA English
DT Article
DE clinical trials; cohort study; efavirenz; HAART; HIV
ID COMBINATION ANTIRETROVIRAL THERAPY; HIV-INFECTED INDIVIDUALS;
INJECTION-DRUG USERS; VIROLOGICAL FAILURE; TRIALS ALLRT; ADHERENCE;
COHORT; PHARMACOGENETICS; DISCONTINUATION; RECOMMENDATIONS
AB Objective: Efavirenz (EFV) along with two nucleoside reverse transcriptase inhibitors (NRTIs) is a recommended initial antiretroviral regimen. Understanding characteristics related to EFV success is clinically useful.
Design: Data from 2220 antiretroviral-naive participants randomized to EFV and two to three NRTIs in four ACTG trials as well as a long-term cohort were analysed.
Methods: Logistic regression, using inverse probability of censoring weighting to address selective-follow-up bias, was used to identify factors associated with EFV success (no treatment interruptions of >30 days, HIV RNA<200 copies/ml) 1 year post initiation and at years 2-5 if successful at year 1.
Results: Pretreatment characteristics were median age 38 years, 82% male, 40% white, 10% history of IDU (HxIDU), median CD4(+) T-lymphocyte 227 cells/mu l and 33% HIV RNA more than 100 000 copies/ml. In a multivariable model, factors associated with year 1 EFV success were race [white odds ratio (OR) 1.5; P<0.001; Hispanic OR 1.5; P=0.003 vs. black], no pretreatment sign/symptom grade 3 or higher (OR 1.7; P=0.008) and no HxIDU (OR 1.7; P=0.001). Predictors of EFV success at years 2-5 were no HxIDU (years 2-5; ORs 1.9-2.2); self-reported complete (4 days prior to study visit) adherence during year 1 (years 2-4; ORs 1.6-1.9); fewer missed visits during year 1 (years 2, 4, 5; ORs 0.92-0.98/1% increase); HIV RNA less than 50 copies/ml at year 1 (years 2, 3; ORs 1.9-2.2); and older age (>50 vs. <= 30 years) (years 2-4: ORs 2.3-3.7).
Conclusion: Characteristics predictive of EFV success in the short-term and longer term differed except for HxIDU. Behaviours occurring during year 1 were associated with EFV success over 5 years. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Smurzynski, Marlene; Wu, Kunling; Lok, Judith J.; Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Schouten, Jeffrey T.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Schouten, Jeffrey T.; Collier, Ann C.] Univ Washington, Seattle, WA 98195 USA.
[Taiwo, Babafemi] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA.
[Johnson, Victoria Anne] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
[Johnson, Victoria Anne] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA.
RP Smurzynski, M (reprint author), George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, 2100-W Penn Ave NW,8th Floor, Washington, DC 20037 USA.
EM msmurzyn@e-mail.gwu.edu
FU Statistical and Data Management Center of the AIDS Clinical Trials
Group, under the National Institute of Allergy and Infectious Diseases
[1 UM1 AI068634, 1 UM1 AI068636]; National Institute of Allergy and
Infectious Diseases grant: UAB Center for AIDS Research [P30AI27767];
National Institute of Allergy and Infectious Diseases grant: Alabama
Clinical Trials Unit [UM1AI069452]; National Institute of Allergy and
Infectious Diseases grant: UW Clinical HIV Integrated Research Program
[5 UM1 AI 69434-06, R01AI100762]
FX This work was supported by the Statistical and Data Management Center of
the AIDS Clinical Trials Group, under the National Institute of Allergy
and Infectious Diseases grant [1 UM1 AI068634] and the Leadership grant
[1 UM1 AI068636]. Members of the team were also supported under the
following National Institute of Allergy and Infectious Diseases grants:
UAB Center for AIDS Research [P30AI27767], Alabama Clinical Trials Unit
[UM1AI069452], UW Clinical HIV Integrated Research Program [5 UM1 AI
69434-06] and [R01AI100762].
NR 41
TC 1
Z9 1
U1 1
U2 5
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 JUL 31
PY 2013
VL 27
IS 12
BP 1887
EP 1897
DI 10.1097/QAD.0b013e328361645f
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 301IK
UT WOS:000330525800006
PM 23925417
ER
PT J
AU Shapiro, RL
Kitch, D
Ogwu, A
Hughes, MD
Lockman, S
Powis, K
Souda, S
Moffat, C
Moyo, S
McIntosh, K
van Widenfelt, E
Zwerski, S
Mazhani, L
Makhema, J
Essex, M
AF Shapiro, Roger L.
Kitch, Douglas
Ogwu, Anthony
Hughes, Michael D.
Lockman, Shahin
Powis, Kathleen
Souda, Sajini
Moffat, Claire
Moyo, Sikhulile
McIntosh, Kenneth
van Widenfelt, Erik
Zwerski, Sheryl
Mazhani, Loeto
Makhema, Joseph
Essex, Max
TI HIV transmission and 24-month survival in a randomized trial of HAART to
prevent MTCT during pregnancy and breastfeeding in Botswana
SO AIDS
LA English
DT Article
DE Africa; antiretrovirals; Botswana; HIV; infant survival; maternal
health; mother-to-child HIV transmission
ID TO-CHILD TRANSMISSION; ANTIRETROVIRAL THERAPY; INFECTED WOMEN; INFANTS;
MALAWI; PROPHYLAXIS; MORTALITY; MOTHERS; BORN; ZIDOVUDINE
AB Objectives: HAART for prevention of mother-to-child HIV transmission (MTCT) may impact long-term survival of women and children.
Design: Randomized clinical trial.
Methods: HIV-infected pregnant women with CD4(+) cell count at least 200 cells/mu l were randomly assigned to abacavir, zidovudine, lamivudine (arm A) or lopinavir-ritonavir, zidovudine-lamivudine (arm B) from week 26 to 34 gestation through planned weaning by 6 months postpartum. Women with baseline CD4(+) cell count less than 200 cells/mu l received nevirapine-zidovudine-lamivudine indefinitely (Obs arm), as did randomized women later qualifying for treatment.
Results: Among 560 randomized and 170 observational women enrolled, there were 14 deaths (1.9%) - one antenatally (Obs), three from delivery to 6 months postpartum (1 arm A, 2 Obs), and 10 from 6 to 24 months postpartum (5 arm A, 3 arm B, 2 Obs). Time to death or CD4(+) cell count below 200 cells/mu l was shorter in arm A vs. B (P=0.03). Of the 709 live-born children, 97% breastfed for a median of 5.8 months. Of 37 (5.2%) deaths by 24 months, nine were before breastfeeding initiated (3 arm A, 2 arm B, 4 Obs); six while breastfeeding (1 arm A, 2 arm B, 3 Obs); and 22 after weaning (9 arm A, 11 arm B, 2 Obs). Only eight children (1.1%) were HIV-infected at 24 months (6 arm A, 1 arm B, 1 Obs), all before 6 months.
Conclusion: Low MTCT was maintained through extended follow-up in all arms. Disease progression appeared slower after discontinuing protease inhibitor-based HAART, but a concerning number of maternal deaths occurred after stopping either regimen. Strategies to improve maternal and child survival in the postintervention period are required. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
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.; Ogwu, Anthony; Lockman, Shahin; Powis, Kathleen; Souda, Sajini; Moffat, Claire; Moyo, Sikhulile; van Widenfelt, Erik; Makhema, Joseph; Essex, Max] Botswana Harvard AIDS Inst Partnership HIV Res &, Gaborone, Botswana.
[Kitch, Douglas; Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Lockman, Shahin] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA.
[Powis, Kathleen] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Powis, Kathleen] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[McIntosh, Kenneth] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Zwerski, Sheryl] NIAID, NIH, Bethesda, MD 20892 USA.
[Mazhani, Loeto] Univ Botswana, Sch Med, Gaborone, Botswana.
RP Shapiro, RL (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 110 Francis St,Suite GB, Boston, MA 02215 USA.
EM rshapiro@hsph.harvard.edu
RI Moyo, Sikhulile/E-1464-2015
OI Moyo, Sikhulile/0000-0003-3821-4592
FU National Institute of Allergy and Infectious Diseases [U01-AI066454]
FX National Institute of Allergy and Infectious Diseases (U01-AI066454) /
clinicaltrials.-gov Identifier: NCT00270296.
NR 29
TC 11
Z9 11
U1 0
U2 7
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 JUL 31
PY 2013
VL 27
IS 12
BP 1911
EP 1920
DI 10.1097/QAD.0b013e32836158b0
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 301IK
UT WOS:000330525800008
PM 24180000
ER
PT J
AU Sever, S
Trachtman, H
Wei, CL
Reiser, J
AF Sever, Sanja
Trachtman, Howard
Wei, Changli
Reiser, Jochen
TI Is There Clinical Value in Measuring suPAR Levels in FSGS?
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; UROKINASE RECEPTOR
C1 [Sever, Sanja] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA USA.
[Trachtman, Howard] NYU, Dept Pediat, New York, NY 10016 USA.
[Wei, Changli; Reiser, Jochen] Rush Univ, Dept Med, Chicago, IL 60612 USA.
RP Reiser, J (reprint author), Rush Univ, Med Ctr, Dept Med, Cohn Biomed Res Bldg,Suite 724, Chicago, IL 60612 USA.
EM jochen_reiser@rush.edu
OI Trachtman, Howard/0000-0001-7447-9489
NR 13
TC 13
Z9 13
U1 0
U2 5
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD JUL 31
PY 2013
VL 8
IS 8
BP 1273
EP 1275
DI 10.2215/CJN.06170613
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 201EC
UT WOS:000323122500001
PM 23886567
ER
PT J
AU O'Hare, AM
AF O'Hare, Ann M.
TI Vascular Access for Hemodialysis in Older Adults: A "Patient First"
Approach
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID CHRONIC KIDNEY-DISEASE; DECISION-MAKING; FISTULA 1ST;
ARTERIOVENOUS-FISTULA; ELDERLY-PATIENT; REFER PATIENTS; DIALYSIS; CARE;
GUIDELINE; OUTCOMES
C1 Univ Washington, Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 98108 USA.
RP O'Hare, AM (reprint author), Univ Washington, Vet Affairs Puget Sound Healthcare Syst, 1160 South Columbian Way, Seattle, WA 98108 USA.
EM ann.ohare@va.gov
NR 29
TC 8
Z9 8
U1 0
U2 5
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUL 31
PY 2013
VL 24
IS 8
BP 1187
EP 1190
DI 10.1681/ASN.2013050507
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 198GD
UT WOS:000322909400004
PM 23813217
ER
PT J
AU Rhee, EP
Clish, CB
Ghorbani, A
Larson, MG
Elmariah, S
McCabe, E
Yang, Q
Cheng, S
Pierce, K
Deik, A
Souza, AL
Farrell, L
Domos, C
Yeh, RW
Palacios, I
Rosenfield, K
Vasan, RS
Florez, JC
Wang, TJ
Fox, CS
Gerszten, RE
AF Rhee, Eugene P.
Clish, Clary B.
Ghorbani, Anahita
Larson, Martin G.
Elmariah, Sammy
McCabe, Elizabeth
Yang, Qiong
Cheng, Susan
Pierce, Kerry
Deik, Amy
Souza, Amanda L.
Farrell, Laurie
Domos, Carly
Yeh, Robert W.
Palacios, Igor
Rosenfield, Kenneth
Vasan, Ramachandran S.
Florez, Jose C.
Wang, Thomas J.
Fox, Caroline S.
Gerszten, Robert E.
TI A Combined Epidemiologic and Metabolomic Approach Improves CKD
Prediction
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; GENERAL-POPULATION;
ARGININE SYNTHESIS; RENAL METABOLISM; KYNURENIC ACID; AMINO-ACIDS; RAT
NEPHRON; DISEASE; PHOSPHATIDYLCHOLINE
AB Metabolomic approaches have begun to catalog the metabolic disturbances that accompany CKD, but whether metabolite alterations can predict future CKD is unknown. We performed liquid chromatography/mass spectrometry-based metabolite profiling on plasma from 1434 participants in the Framingham Heart Study (FHS) who did not have CKD at baseline. During the following 8 years, 123 individuals developed CKD, defined by an estimated GFR of <60 ml/min per 1.73 m(2). Numerous metabolites were associated with incident CKD, including 16 that achieved the Bonferroni-adjusted significance threshold of P0.00023. To explore how the human kidney modulates these metabolites, we profiled arterial and renal venous plasma from nine individuals. Nine metabolites that predicted CKD in the FHS cohort decreased more than creatinine across the renal circulation, suggesting that they may reflect non-GFR-dependent functions, such as renal metabolism and secretion. Urine isotope dilution studies identified citrulline and choline as markers of renal metabolism and kynurenic acid as a marker of renal secretion. In turn, these analytes remained associated with incident CKD in the FHS cohort, even after adjustment for eGFR, age, sex, diabetes, hypertension, and proteinuria at baseline. Addition of a multimarker metabolite panel to clinical variables significantly increased the c-statistic (0.77-0.83, P<0.0001); net reclassification improvement was 0.78 (95% confidence interval, 0.60 to 0.95; P<0.0001). Thus, the addition of metabolite profiling to clinical data may significantly improve the ability to predict whether an individual will develop CKD by identifying predictors of renal risk that are independent of estimated GFR.
C1 [Rhee, Eugene P.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA.
[Ghorbani, Anahita; Elmariah, Sammy; Cheng, Susan; Farrell, Laurie; Domos, Carly; Yeh, Robert W.; Palacios, Igor; Rosenfield, Kenneth; Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Charlestown, MA 02129 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Charlestown, MA 02129 USA.
[Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
[Rhee, Eugene P.; Clish, Clary B.; Pierce, Kerry; Deik, Amy; Souza, Amanda L.; Gerszten, Robert E.] Broad Inst, Cambridge, MA USA.
[Ghorbani, Anahita; Larson, Martin G.; Cheng, Susan; Vasan, Ramachandran S.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Ghorbani, Anahita; Larson, Martin G.; Cheng, Susan; Vasan, Ramachandran S.; Fox, Caroline S.] Boston Univ, Sch Med, Framingham, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[McCabe, Elizabeth; Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Cheng, Susan] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston Med Ctr, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA.
[Wang, Thomas J.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN USA.
[Wang, Thomas J.] Vanderbilt Heart & Vasc Inst, Nashville, TN USA.
[Fox, Caroline S.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
RP Rhee, EP (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, 149 13th St,8th Floor,8401, Charlestown, MA 02129 USA.
EM eprhee@partners.org; rgerszten@partners.org
RI Yang, Qiong/G-5438-2014;
OI Larson, Martin/0000-0002-9631-1254; Ramachandran,
Vasan/0000-0001-7357-5970
FU National Institutes of Health (NIH) [N01-HC-25195, R01-DK-HL081572];
Leducq Foundation; American Heart Association; NIH [K08-DK-090142]
FX This work was supported by National Institutes of Health (NIH) contract
N01-HC-25195 to the Framingham Heart Study, R01-DK-HL081572 (R. E. G.
and T.J.W.), the Leducq Foundation (R. E. G.), and an Established
Investigator Award from the American Heart Association (R. E. G.). E. P.
R. received support from NIH award K08-DK-090142.
NR 35
TC 47
Z9 47
U1 4
U2 19
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 JUL 31
PY 2013
VL 24
IS 8
BP 1330
EP 1338
DI 10.1681/ASN.2012101006
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 198GD
UT WOS:000322909400021
PM 23687356
ER
PT J
AU Bandyopadhyay, S
Cahill, C
Balleidier, A
Huang, CN
Lahiri, DK
Huang, XD
Rogers, JT
AF Bandyopadhyay, Sanghamitra
Cahill, Catherine
Balleidier, Amelie
Huang, Conan
Lahiri, Debomoy K.
Huang, Xudong
Rogers, Jack T.
TI Novel 5 ' Untranslated Region Directed Blockers of Iron-Regulatory
Protein-1 Dependent Amyloid Precursor Protein Translation: Implications
for Down Syndrome and Alzheimer's Disease
SO PLOS ONE
LA English
DT Article
ID APP-MESSENGER-RNA; 5'-UNTRANSLATED REGION; RESPONSIVE ELEMENT; BETA
PEPTIDE; EXPRESSION; MICE; IDENTIFICATION; DEGENERATION; DYSFUNCTION;
INHIBITORS
AB We reported that iron influx drives the translational expression of the neuronal amyloid precursor protein (APP), which has a role in iron efflux. This is via a classic release of repressor interaction of APP mRNA with iron-regulatory protein-1 (IRP1) whereas IRP2 controls the mRNAs encoding the L-and H-subunits of the iron storage protein, ferritin. Here, we identified thirteen potent APP translation blockers that acted selectively towards the uniquely configured iron-responsive element (IRE) RNA stem loop in the 5' untranslated region (UTR) of APP mRNA. These agents were 10-fold less inhibitory of 5 ' UTR sequences of the related prion protein (PrP) mRNA. Western blotting confirmed that the 'ninth' small molecule in the series selectively reduced neural APP production in SH-SY5Y cells at picomolar concentrations without affecting viability or the expression of a-synuclein and ferritin. APP blocker-9 (JTR-009), a benzimidazole, reduced the production of toxic Ab in SH-SY5Y neuronal cells to a greater extent than other well tolerated APP 5'UTR-directed translation blockers, including posiphen, that were shown to limit amyloid burden in mouse models of Alzheimer's disease (AD). RNA binding assays demonstrated that JTR-009 operated by preventing IRP1 from binding to the IRE in APP mRNA, while maintaining IRP1 interaction with the H-ferritin IRE RNA stem loop. Thus, JTR-009 constitutively repressed translation driven by APP 5'UTR sequences. Calcein staining showed that JTR-009 did not indirectly change iron uptake in neuronal cells suggesting a direct interaction with the APP 5'UTR. These studies provide key data to develop small molecules that selectively reduce neural APP and Ab production at 10-fold lower concentrations than related previously characterized translation blockers. Our data evidenced a novel therapeutic strategy of potential impact for people with trisomy of the APP gene on chromosome 21, which is a phenotype long associated with Down syndrome (DS) that can also cause familial Alzheimer's disease.
C1 [Bandyopadhyay, Sanghamitra; Cahill, Catherine; Balleidier, Amelie; Huang, Conan; Huang, Xudong; Rogers, Jack T.] Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Charlestown, MA USA.
[Bandyopadhyay, Sanghamitra; Cahill, Catherine; Balleidier, Amelie; Huang, Conan; Huang, Xudong; Rogers, Jack T.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Cahill, Catherine] Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA USA.
[Lahiri, Debomoy K.] Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, Mol Neurogenet Lab, Indianapolis, IN 46202 USA.
RP Rogers, JT (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Charlestown, MA USA.
EM jrogers@partners.org
OI Bandyopadhyay, Sanghamitra /0000-0002-1490-3599
FU Alzheimer's Association Zenith Award; Michael JFOX NADD grant; NICH;
[R21 NS077079-01A1]
FX JR was funded from an R21 NS077079-01A1 (Post Transcriptional Control of
hemorrhagic iron damage). JR is a recipient of the Alzheimer's
Association Zenith Award, and of a Michael JFOX NADD grant. CC was
supported by an R01 Supplement from the NICH. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 49
TC 17
Z9 17
U1 0
U2 15
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 JUL 31
PY 2013
VL 8
IS 7
AR e65978
DI 10.1371/journal.pone.0065978
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 194LB
UT WOS:000322633700001
PM 23935819
ER
PT J
AU Kong, J
Spaeth, R
Cook, A
Kirsch, I
Claggett, B
Vangel, M
Gollub, RL
Smoller, JW
Kaptchuk, TJ
AF Kong, Jian
Spaeth, Rosa
Cook, Amanda
Kirsch, Irving
Claggett, Brian
Vangel, Mark
Gollub, Randy L.
Smoller, Jordan W.
Kaptchuk, Ted J.
TI Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue
Conditioning and Their Association
SO PLOS ONE
LA English
DT Article
ID DISPOSITIONAL OPTIMISM; EXPERIMENTAL PAIN; ANALGESIA; EXPECTANCY;
TRIALS; NEEDLE; DISSOCIATION; MECHANISMS; NETWORK; BLIND
AB Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol), sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for "placebo responders." However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non-specific effects of acupuncture may contribute to the analgesic effect observed in genuine acupuncture analgesia.
C1 [Kong, Jian; Spaeth, Rosa; Cook, Amanda; Gollub, Randy L.; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA.
[Kong, Jian; Spaeth, Rosa; Cook, Amanda; Gollub, Randy L.; Smoller, Jordan W.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Kirsch, Irving; Kaptchuk, Ted J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Program Placebo Studies, Boston, MA 02215 USA.
[Kirsch, Irving] Univ Plymouth, Sch Psychol, Plymouth PL4 8AA, Devon, England.
[Claggett, Brian] Harvard Univ, Sch Med, Div Cardiovasc Med, Boston, MA USA.
[Claggett, Brian] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Vangel, Mark] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA.
RP Kong, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA.
EM kongj@nmr.mgh.harvard.edu
OI Gollub, Randy L./0000-0002-9434-4044
FU NCCAM [KO1AT003883, R21AT004497, R01AT006364, R01AT005280, K24AT004095,
P01 AT006663]; NIDA [R03AT218317]; NIMH [K24MH094614]
FX This work was supported by KO1AT003883 (NCCAM), R21AT004497 (NCCAM),
R03AT218317 (NIDA), and R01AT006364 (NCCAM) to Jian Kong; R01AT005280
(NCCAM) to Randy Gollub; K24AT004095 (NCCAM) to Ted Kaptchuk;
K24MH094614 (NIMH) to Jordan W. Smoller, and P01 AT006663 (NCCAM) to
Bruce Rosen. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 50
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U1 5
U2 36
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 JUL 31
PY 2013
VL 8
IS 7
AR e67485
DI 10.1371/journal.pone.0067485
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 194LB
UT WOS:000322633700004
PM 23935833
ER
PT J
AU Bornigen, D
Morgan, XC
Franzosa, EA
Ren, BY
Xavier, RJ
Garrett, WS
Huttenhower, C
AF Boernigen, Daniela
Morgan, Xochitl C.
Franzosa, Eric A.
Ren, Boyu
Xavier, Ramnik J.
Garrett, Wendy S.
Huttenhower, Curtis
TI Functional profiling of the gut microbiome in disease-associated
inflammation
SO GENOME MEDICINE
LA English
DT Review
ID RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; BOWEL-DISEASE; VITAMIN-D;
ATOPIC-DERMATITIS; ANTIBIOTIC-RESISTANCE; ALLERGIC DISEASES; WIDE
ASSOCIATION; PROTEIN FAMILIES; INNATE IMMUNITY
AB The microbial residents of the human gut are a major factor in the development and lifelong maintenance of health. The gut microbiota differs to a large degree from person to person and has an important influence on health and disease due to its interaction with the human immune system. Its overall composition and microbial ecology have been implicated in many autoimmune diseases, and it represents a particularly important area for translational research as a new target for diagnostics and therapeutics in complex inflammatory conditions. Determining the biomolecular mechanisms by which altered microbial communities contribute to human disease will be an important outcome of current functional studies of the human microbiome. In this review, we discuss functional profiling of the human microbiome using metagenomic and metatranscriptomic approaches, focusing on the implications for inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis. Common themes in gut microbial ecology have emerged among these diverse diseases, but they have not yet been linked to targetable mechanisms such as microbial gene and genome composition, pathway and transcript activity, and metabolism. Combining these microbial activities with host gene, transcript and metabolic information will be necessary to understand how and why these complex interacting systems are altered in disease-associated inflammation.
C1 [Boernigen, Daniela; Morgan, Xochitl C.; Franzosa, Eric A.; Ren, Boyu; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Boernigen, Daniela; Morgan, Xochitl C.; Franzosa, Eric A.; Xavier, Ramnik J.; Garrett, Wendy S.; Huttenhower, Curtis] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA.
[Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Garrett, Wendy S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Garrett, Wendy S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Huttenhower, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
EM chuttenh@hsph.harvard.edu
OI Morgan, Xochitl/0000-0002-6264-6961; Huttenhower,
Curtis/0000-0002-1110-0096
FU National Science Foundation [DBI-1053486]; Danone research grant
[PLF-5972-GD]; National Institutes of Health (NIH) [1R01HG005969]; NIH
[R01CA154426, K08AI078942, R01GM099531]; Burroughs Wellcome Career in
Medical Sciences Award; Searle Scholars Award; NIH/NIDDK [R01DK092405];
Crohn's and Colitis Foundation of America; Juvenile Diabetes Research
Foundation
FX The authors would like to thank Timothy Tickle and Levi Waldron for
assistance with figures, Carolyn Ingalls and Nicole Levesque for their
editorial assistance, and the members of the Huttenhower laboratory for
their input and thoughtful discussions. This work was supported by
National Science Foundation grant DBI-1053486 (CH), Danone research
grant PLF-5972-GD (WSG), National Institutes of Health (NIH) grant
1R01HG005969 (CH), NIH R01CA154426 (WSG), K08AI078942 (WSG), R01GM099531
(WSG), a Burroughs Wellcome Career in Medical Sciences Award (WSG), a
Searle Scholars Award (WSG), Cancer Research Institute Investigator,
NIH/NIDDK R01DK092405 (RJX), the Crohn's and Colitis Foundation of
America (CH and RJX), and the Juvenile Diabetes Research Foundation
(RJX).
NR 127
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U1 2
U2 102
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-994X
J9 GENOME MED
JI Genome Med.
PD JUL 31
PY 2013
VL 5
AR 65
DI 10.1186/gm469
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 193FJ
UT WOS:000322543400001
PM 23906180
ER
PT J
AU Corcoran, RB
Rothenberg, SM
Hata, AN
Faber, AC
Piris, A
Nazarian, RM
Brown, RD
Godfrey, JT
Winokur, D
Walsh, J
Mino-Kenudson, M
Maheswaran, S
Settleman, J
Wargo, JA
Flaherty, KT
Haber, DA
Engelman, JA
AF Corcoran, Ryan B.
Rothenberg, Stephen Michael
Hata, Aaron N.
Faber, Anthony C.
Piris, Adriano
Nazarian, Rosalynn M.
Brown, Ronald D.
Godfrey, Jason T.
Winokur, Daniel
Walsh, John
Mino-Kenudson, Mari
Maheswaran, Shyamala
Settleman, Jeffrey
Wargo, Jennifer A.
Flaherty, Keith T.
Haber, Daniel A.
Engelman, Jeffrey A.
TI TORC1 Suppression Predicts Responsiveness to RAF and MEK Inhibition in
BRAF-Mutant Melanoma
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID VIVO ANTITUMOR-ACTIVITY; METASTATIC MELANOMA; ACQUIRED-RESISTANCE;
TUBEROUS SCLEROSIS; CUTANEOUS MELANOMA; KINASE INHIBITORS; IMPROVED
SURVIVAL; V600E MUTATION; HUMAN CANCER; S6 KINASE
AB RAF and MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase) inhibitors are effective in treating patients with BRAF-mutant melanoma. However, most responses are partial and short-lived, and many patients fail to respond at all. We found that suppression of TORC1 activity in response to RAF or MEK inhibitors, as measured by decreased phosphorylation of ribosomal protein S6 (P-S6), effectively predicted induction of cell death by the inhibitor in BRAF-mutant melanoma cell lines. In resistant melanomas, TORC1 activity was maintained after treatment with RAF or MEK inhibitors, in some cases despite robust suppression of mitogen-activated protein kinase (MAPK) signaling. In in vivo mouse models, suppression of TORC1 after MAPK inhibition was necessary for induction of apoptosis and tumor response. Finally, in paired biopsies obtained from patients with BRAF-mutant melanoma before treatment and after initiation of RAF inhibitor therapy, P-S6 suppression predicted significantly improved progression-free survival. Such a change in P-S6 could be readily monitored in real time by serial fine-needle aspiration biopsies, making quantitation of P-S6 a valuable biomarker to guide treatment in BRAF-mutant melanoma.
C1 [Corcoran, Ryan B.; Rothenberg, Stephen Michael; Hata, Aaron N.; Faber, Anthony C.; Brown, Ronald D.; Godfrey, Jason T.; Winokur, Daniel; Walsh, John; Maheswaran, Shyamala; Wargo, Jennifer A.; Flaherty, Keith T.; Haber, Daniel A.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA.
[Corcoran, Ryan B.; Rothenberg, Stephen Michael; Hata, Aaron N.; Flaherty, Keith T.; Haber, Daniel A.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Piris, Adriano; Nazarian, Rosalynn M.; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA.
[Piris, Adriano; Nazarian, Rosalynn M.; Mino-Kenudson, Mari; Wargo, Jennifer A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Settleman, Jeffrey] Genentech Inc, San Francisco, CA 94080 USA.
[Wargo, Jennifer A.] Massachusetts Gen Hosp, Dept Surg, Boston, 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, Boston, MA 02129 USA.
EM dhaber@partners.org; jengelman@partners.org
OI Nazarian, Rosalynn/0000-0003-4003-7193
FU Damon Runyon Clinical Investigator Award; NIH/National Institute of
Dental and Craniofacial Research [1K08DE020139]; NIH [R01CA137008];
National Cancer Institute [CA129933]
FX This work was funded by a Damon Runyon Clinical Investigator Award (to
R.B.C.), NIH/National Institute of Dental and Craniofacial Research
grant 1K08DE020139 (to S.M.R.), NIH grant R01CA137008 (to J.A.E.),
National Cancer Institute grant CA129933 (to D.A.H.).
NR 46
TC 15
Z9 16
U1 1
U2 2
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 JUL 31
PY 2013
VL 5
IS 196
AR 196ra98
DI 10.1126/scitranslmed.3005753
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 193WG
UT WOS:000322591600002
PM 23903755
ER
PT J
AU Elkabets, M
Vora, S
Juric, D
Morse, N
Mino-Kenudson, M
Muranen, T
Tao, J
Campos, AB
Rodon, J
Ibrahim, YH
Serra, V
Rodrik-Outmezguine, V
Hazra, S
Singh, S
Kim, P
Quadt, C
Liu, M
Huang, A
Rosen, N
Engelman, JA
Scaltriti, M
Baselga, J
AF Elkabets, Moshe
Vora, Sadhna
Juric, Dejan
Morse, Natasha
Mino-Kenudson, Mari
Muranen, Taru
Tao, Jessica
Campos, Ana Bosch
Rodon, Jordi
Ibrahim, Yasir H.
Serra, Violeta
Rodrik-Outmezguine, Vanessa
Hazra, Saswati
Singh, Sharat
Kim, Phillip
Quadt, Cornelia
Liu, Manway
Huang, Alan
Rosen, Neal
Engelman, Jeffrey A.
Scaltriti, Maurizio
Baselga, Jose
TI mTORC1 Inhibition Is Required for Sensitivity to PI3K p110 alpha
Inhibitors in PIK3CA-Mutant Breast Cancer
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID ADVANCED SOLID TUMORS; ANTITUMOR-ACTIVITY; PIK3CA MUTATIONS; 3-KINASE
PATHWAY; PHASE-I; KINASE; GROWTH; RESISTANCE; CELLS; GENE
AB Activating mutations of the PIK3CA gene occur frequently in breast cancer, and inhibitors that are specific for phosphatidylinositol 3-kinase (PI3K) p110 alpha, such as BYL719, are being investigated in clinical trials. In a search for correlates of sensitivity to p110 alpha inhibition among PIK3CA-mutant breast cancer cell lines, we observed that sensitivity to BYL719 (as assessed by cell proliferation) was associated with full inhibition of signaling through the TORC1 pathway. Conversely, cancer cells that were resistant to BYL719 had persistently active mTORC1 signaling, although Akt phosphorylation was inhibited. Similarly, in patients, pS6 (residues 240/4) expression (a marker of mTORC1 signaling) was associated with tumor response to BYL719, and mTORC1 was found to be reactivated in tumors from patients whose disease progressed after treatment. In PIK3CA-mutant cancer cell lines with persistent mTORC1 signaling despite PI3K p110 alpha blockade (that is, resistance), the addition of the allosteric mTORC1 inhibitor RAD001 to the cells along with BYL719 resulted in reversal of resistance in vitro and in vivo. Finally, we found that growth factors such as insulin-like growth factor 1 and neuregulin 1 can activate mammalian target of rapamycin (mTOR) and mediate resistance to BYL719. Our findings suggest that simultaneous administration of mTORC1 inhibitors may enhance the clinical activity of p110 alpha-targeted drugs and delay the appearance of resistance.
C1 [Elkabets, Moshe; Morse, Natasha; Campos, Ana Bosch; Scaltriti, Maurizio; Baselga, Jose] Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Elkabets, Moshe; Morse, Natasha; Campos, Ana Bosch; Scaltriti, Maurizio; Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Elkabets, Moshe; Vora, Sadhna; Juric, Dejan; Tao, Jessica; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, CNY 149, Charlestown, MA 02129 USA.
[Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Muranen, Taru] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Rodon, Jordi; Ibrahim, Yasir H.; Serra, Violeta] Vall Hebron Inst Oncol, Expt Therapeut Grp, Barcelona 08035, Spain.
[Rodrik-Outmezguine, Vanessa; Rosen, Neal] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA.
[Hazra, Saswati; Singh, Sharat; Kim, Phillip] Prometheus Therapeut & Diagnost, San Diego, CA 92121 USA.
[Quadt, Cornelia] Novartis Pharma AG, CH-4056 Basel, Switzerland.
[Liu, Manway; Huang, Alan] Novartis Inst BioMed Res, Cambridge, MA 02139 USA.
RP Scaltriti, M (reprint author), Human Oncol & Pathogenesis Program, 1275 York Ave,Box 20, New York, NY 10065 USA.
EM scaltrim@mskcc.org; baselgaj@mskcc.org
OI Rodrik - Outmezguine, Vanessa/0000-0002-3024-4490
FU Stand Up To Cancer Dream Team Translational Cancer Research Grant, a
program of the Entertainment Industry Foundation [SU2C-AACR-DT0209];
Breast Cancer Research Foundation; European Research Council
[AdG09250244]; Instituto de Salud Carlos III [Intrasalud PSO9/00623];
Spanish Society of Medical Oncology (SEOM); ASCO YIA; American
Association for Cancer Research-Genentech BioOncology Fellowship; Terri
Brodeur Breast Cancer Foundation; [RO1CA137008]
FX This work was funded by a Stand Up To Cancer Dream Team Translational
Cancer Research Grant, a program of the Entertainment Industry
Foundation (SU2C-AACR-DT0209 to J.B.), the Breast Cancer Research
Foundation (to J.B.), the European Research Council (AdG09250244 to
J.B.), the Instituto de Salud Carlos III (Intrasalud PSO9/00623 to
J.B.), and RO1CA137008 (to J.A.E.). M.E. is an International Sephardic
Education Foundation postdoctoral fellow. A.B.C. holds a Translational
Research Fellowship from the Spanish Society of Medical Oncology (SEOM).
S.V. is supported by an ASCO YIA, American Association for Cancer
Research-Genentech BioOncology Fellowship, and Terri Brodeur Breast
Cancer Foundation research grant.
NR 49
TC 51
Z9 52
U1 4
U2 7
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 JUL 31
PY 2013
VL 5
IS 196
AR 196ra99
DI 10.1126/scitranslmed.3005747
PG 14
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 193WG
UT WOS:000322591600004
PM 23903756
ER
PT J
AU Bonderman, D
Ghio, S
Felix, SB
Ghofrani, HA
Michelakis, E
Mitrovic, V
Oudiz, RJ
Boateng, F
Scalise, AV
Roessig, L
Semigran, MJ
AF Bonderman, Diana
Ghio, Stefano
Felix, Stephan B.
Ghofrani, Hossein-Ardeschir
Michelakis, Evangelos
Mitrovic, Veselin
Oudiz, Ronald J.
Boateng, Francis
Scalise, Andrea-Viviana
Roessig, Lothar
Semigran, Marc J.
CA Left Ventricular Systolic Dysfunct
TI Riociguat for Patients With Pulmonary Hypertension Caused by Systolic
Left Ventricular Dysfunction A Phase IIb Double-Blind, Randomized,
Placebo-Controlled, Dose-Ranging Hemodynamic Study
SO CIRCULATION
LA English
DT Article
DE clinical trial; heart failure, systolic; hypertension, pulmonary;
riociguat; soluble guanylate cyclase
ID CHRONIC HEART-FAILURE; SOLUBLE GUANYLATE-CYCLASE; INHALED NITRIC-OXIDE;
ENDOTHELIAL DYSFUNCTION; DILATED CARDIOMYOPATHY; PROGNOSTIC VALUE;
ANTAGONIST; SILDENAFIL; MORTALITY; SECONDARY
AB Background-Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality; however, no treatment is approved for this indication. We hypothesized that riociguat, a novel soluble guanylate cyclase stimulator, would have beneficial hemodynamic effects in patients with pulmonary hypertension caused by systolic left ventricular dysfunction.
Methods and Results-Overall, 201 patients with heart failure resulting from pulmonary hypertension caused by systolic left ventricular dysfunction were randomized to double-blind treatment with oral placebo or riociguat (0.5, 1, or 2 mg 3 times daily) for 16 weeks in 4 parallel arms. The primary outcome was the placebo-corrected change from baseline at week 16 in mean pulmonary artery pressure. Although the decrease in mean pulmonary artery pressure in the riociguat 2 mg group (-6.1+/-1.3 mm Hg; P<0.0001 versus baseline) was not significantly different from placebo (P=0.10), cardiac index (0.4 L.min(-1).m(-2); 95% confidence interval, 0.2-0.5; P=0.0001) and stroke volume index (5.2 mL.m(-2);95% confidence interval, 2.0-8.4; P=0.0018) were significantly increased without changes in heart rate or systemic blood pressure compared with placebo. Both pulmonary (-46.6 dynes.s(-1).cm(-5); 95% confidence interval, -89.4 to -3.8; P=0.03) and systemic vascular resistance (-239.3 dynes.s(-1).cm(-5); 95% confidence interval, -363.4 to -115.3; P=0.0002) were significantly reduced with riociguat 2 mg. Riociguat reduced the Minnesota Living With Heart Failure score (P=0.0002). Discontinuation of treatment was similar between treatment groups.
Conclusions-Although the primary end point of the study was not met, riociguat was well tolerated in patients with pulmonary hypertension caused by systolic left ventricular dysfunction and improved cardiac index and pulmonary and systemic vascular resistance.
C1 [Bonderman, Diana] Med Univ Vienna, Dept Internal Med 2, Vienna, Austria.
[Ghio, Stefano] Univ Hosp, Fdn IRCCS Policlin San Matteo, Dept Cardiol, Pavia, Italy.
[Felix, Stephan B.] Univ Med Greifswald, Dept Cardiol & Internal Med B, Greifswald, Germany.
[Felix, Stephan B.] DZHK German Ctr Cardiovasc Res, Greifswald, Germany.
[Ghofrani, Hossein-Ardeschir] Univ Giessen, D-35390 Giessen, Germany.
[Ghofrani, Hossein-Ardeschir] Marburg Lung Ctr, Giessen, Germany.
[Ghofrani, Hossein-Ardeschir] German Ctr Lung Res, Giessen, Germany.
[Michelakis, Evangelos] Univ Alberta, Dept Med, Edmonton, AB, Canada.
[Mitrovic, Veselin] Forschungsgesell GmbH, Kerckhoff Klin, Bad Nauheim, Germany.
[Oudiz, Ronald J.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.
[Boateng, Francis] Bayer HealthCare Pharmaceut, New York, NY USA.
[Scalise, Andrea-Viviana] Bayer Hispania, Barcelona, Spain.
[Roessig, Lothar] Bayer Pharma AG, Berlin, Germany.
[Semigran, Marc J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Fruit St, Boston, MA 02114 USA.
EM msemigran@partners.org
FU Bayer HealthCare Pharmaceuticals (Berlin, Germany)
FX This study was supported by Bayer HealthCare Pharmaceuticals (Berlin,
Germany).
NR 30
TC 83
Z9 85
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUL 30
PY 2013
VL 128
IS 5
BP 502
EP U95
DI 10.1161/CIRCULATIONAHA.113.001458
PG 27
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 301LE
UT WOS:000330533000010
PM 23775260
ER
PT J
AU Weiner, RB
Wang, F
Isaacs, SK
Malhotra, R
Berkstresser, B
Kim, JH
Hutter, AM
Picard, MH
Wang, TJ
Baggish, AL
AF Weiner, Rory B.
Wang, Francis
Isaacs, Stephanie K.
Malhotra, Rajeev
Berkstresser, Brant
Kim, Jonathan H.
Hutter, Adolph M., Jr.
Picard, Michael H.
Wang, Thomas J.
Baggish, Aaron L.
TI Blood Pressure and Left Ventricular Hypertrophy During American-Style
Football Participation
SO CIRCULATION
LA English
DT Article
DE blood pressure; cardiomegaly, exercise-induced; exercise; hypertension;
hypertrophy, left ventricular
ID CARDIOVASCULAR-DISEASE MORTALITY; RISK-FACTORS; EXERCISE; HYPERTENSION;
IMPACT; ENDURANCE; RECOMMENDATIONS; METAANALYSIS; PREVALENCE; DIMENSIONS
AB Background-Hypertension, a strong determinant of cardiovascular disease risk, has been documented among elite, professional American-style football (ASF) players. The risk of increased blood pressure (BP) and early adulthood hypertension among the substantially larger population of collegiate ASF athletes is not known. Methods and Results-We conducted a prospective, longitudinal study to examine BP, the incidence of hypertension, and left ventricular remodeling among collegiate ASF athletes. Resting BP and left ventricular structure were assessed before and after a single season of competitive ASF participation in 6 consecutive groups of first-year university athletes (n=113). ASF participation was associated with significant increases in systolic BP (116+/-8 versus 125+/-13 mm Hg; P<0.001) and diastolic BP (64+/-8 mm Hg versus 66+/-10 mm Hg; P<0.001). At the postseason assessment, the majority of athletes met criteria for Joint National Commission (seventh report) prehypertension (53 of 113, 47%) or stage 1 hypertension (16 of 113, 14%). Among measured characteristics, lineman field position, intraseason weight gain, and family history of hypertension were the strongest independent predictors of postseason BP. Among linemen, there was a significant increase in the prevalence of concentric left ventricular hypertrophy (2 of 64 [3%] versus 20 of 64 [31%]; P<0.001) and change in left ventricular mass correlated with intraseason change in systolic BP (R=0.46, P<0.001). Conclusions-Collegiate ASF athletes may be at risk for clinically relevant increases in BP and the development of hypertension. Enhanced surveillance and carefully selected interventions may represent important opportunities to improve later-life cardiovascular health outcomes in this population.
C1 [Weiner, Rory B.; Hutter, Adolph M., Jr.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA.
[Weiner, Rory B.; Isaacs, Stephanie K.; Malhotra, Rajeev; Kim, Jonathan H.; Hutter, Adolph M., Jr.; Picard, Michael H.; Wang, Thomas J.; Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Wang, Francis; Berkstresser, Brant; Baggish, Aaron L.] Harvard Univ, Univ Hlth Serv, Cambridge, MA 02138 USA.
RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Yawkey Ste 5B,55 Fruit St, Boston, MA 02114 USA.
EM abaggish@partners.org
OI Picard, Michael/0000-0002-9264-3243; Malhotra,
Rajeev/0000-0003-0120-4630
FU American Heart Association [09FTF2220328]
FX This work was supported by the American Heart Association (09FTF2220328
to Dr Baggish).
NR 30
TC 20
Z9 21
U1 1
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUL 30
PY 2013
VL 128
IS 5
BP 524
EP 531
DI 10.1161/CIRCULATIONAHA.113.003522
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 301LE
UT WOS:000330533000012
PM 23897848
ER
PT J
AU Ullrich, NJ
Kieran, MW
Miller, DT
Gordon, LB
Cho, YJ
Silvera, VM
Giobbie-Hurder, A
Neuberg, D
Kleinman, ME
AF Ullrich, Nicole J.
Kieran, Mark W.
Miller, David T.
Gordon, Leslie B.
Cho, Yoon-Jae
Silvera, V. Michelle
Giobbie-Hurder, Anita
Neuberg, Donna
Kleinman, Monica E.
TI Neurologic features of Hutchinson-Gilford progeria syndrome after
lonafarnib treatment
SO NEUROLOGY
LA English
DT Article
ID FARNESYLTRANSFERASE INHIBITOR; PHENOTYPE; DISEASE
AB Objectives: The objective of this study was to retrospectively evaluate neurologic status pre-and posttreatment with the oral farnesyltransferase inhibitor lonafarnib in children with Hutchinson-Gilford progeria syndrome (HGPS), a rare, fatal disorder of segmental premature aging that results in early death by myocardial infarction or stroke.
Methods: The primary outcome measure for intervention with lonafarnib was to assess increase over pretherapy in estimated annual rate of weight gain. In this study, neurologic signs and symptoms were compared pre-and posttreatment with lonafarnib.
Results: Twenty-six participants were treated for a minimum of 2 years. Frequency of clinical strokes, headaches, and seizures was reduced from pretrial rates. Three patients with a history of frequent TIAs and average clinical stroke frequency of 1.75/year during the year before treatment experienced no new events during treatment. One patient with a history of stroke died due to large-vessel hemispheric stroke after 5 months on treatment. Headache prevalence and frequency were reduced. Four patients exhibited pretherapy seizures and no patients experienced recurrent or new-onset seizures
Conclusions: This study provides preliminary evidence that lonafarnib therapy may improve neurologic status of children with HGPS. To address this question, we have incorporated prospective neuroimaging and neurologic assessments as measures in subsequent studies involving children with HGPS.
Classification of evidence: This study provides Class IV evidence that lonafarnib 115-150 mg/m(2) for 24 to 29 months reduces the prevalence of stroke and TIA and the prevalence and frequency of headache over the treatment period.
C1 [Ullrich, Nicole J.; Cho, Yoon-Jae] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Kieran, Mark W.] Boston Childrens Hosp, Dept Hematol Oncol, Boston, MA USA.
[Gordon, Leslie B.; Kleinman, Monica E.] Boston Childrens Hosp, Dept Anesthesia, Boston, MA USA.
[Miller, David T.] Boston Childrens Hosp, Dept Genet, Boston, MA USA.
[Silvera, V. Michelle] Boston Childrens Hosp, Dept Radiol, Boston, MA USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Gordon, Leslie B.] Hasbro Childrens Hosp, Dept Pediat, Providence, RI USA.
Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Giobbie-Hurder, Anita; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Ullrich, NJ (reprint author), Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
EM nicole.ullrich@childrens.harvard.edu
OI Kieran, Mark/0000-0003-2184-7692
FU Progeria Research Foundation [PRFCLIN2007-01]; Dana-Farber Cancer
Institute Stop & Shop Pediatric Brain Tumor Program; C.J. Buckley Fund;
Kyle Johnson Fund; National Center for Research Resources, NIH
[MO1-RR02172, UL1 RR025758-01]
FX This project was funded by The Progeria Research Foundation
(PRFCLIN2007-01), the Dana-Farber Cancer Institute Stop & Shop Pediatric
Brain Tumor Program, the C.J. Buckley Fund, the Kyle Johnson Fund, by a
National Center for Research Resources, NIH grant to the Children's
Hospital Boston General Clinical Research Center (MO1-RR02172), and a
grant from the National Center for Research Resources, NIH, to the
Harvard Catalyst Clinical & Translational Science Center (Harvard
Catalyst) (UL1 RR025758-01).
NR 10
TC 8
Z9 9
U1 1
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 30
PY 2013
VL 81
IS 5
BP 427
EP 430
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 304JB
UT WOS:000330741800010
PM 23897869
ER
PT J
AU Frisoni, GB
Bocchetta, M
Chetelat, G
Rabinovici, GD
de Leon, MJ
Kaye, J
Reiman, EM
Scheltens, P
Barkhof, F
Black, SE
Brooks, DJ
Carrillo, MC
Fox, NC
Herholz, K
Nordberg, A
Jack, CR
Jagust, WJ
Johnson, KA
Rowe, CC
Sperling, RA
Thies, W
Wahlund, LO
Weiner, MW
Pasqualetti, P
DeCarli, C
AF Frisoni, Giovanni B.
Bocchetta, Martina
Chetelat, Gael
Rabinovici, Gil D.
de Leon, Mony J.
Kaye, Jeffrey
Reiman, Eric M.
Scheltens, Philip
Barkhof, Frederik
Black, Sandra E.
Brooks, David J.
Carrillo, Maria C.
Fox, Nick C.
Herholz, Karl
Nordberg, Agneta
Jack, Clifford R., Jr.
Jagust, William J.
Johnson, Keith A.
Rowe, Christopher C.
Sperling, Reisa A.
Thies, William
Wahlund, Lars-Olof
Weiner, Michael W.
Pasqualetti, Patrizio
DeCarli, Charles
CA ISTAART
TI Imaging markers for Alzheimer disease Which vs how
SO NEUROLOGY
LA English
DT Review
ID MILD COGNITIVE IMPAIRMENT; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE;
ASSOCIATION WORKGROUPS; FDG-PET; DIFFERENTIAL-DIAGNOSIS; REVISED
CRITERIA; DEMENTIA; RECOMMENDATIONS; BIOMARKERS
AB Revised diagnostic criteria for Alzheimer disease (AD) acknowledge a key role of imaging biomarkers for early diagnosis. Diagnostic accuracy depends on which marker (i.e., amyloid imaging, F-18-fluorodeoxyglucose [FDG]-PET, SPECT, MRI) as well as how it is measured ("metric": visual, manual, semiautomated, or automated segmentation/computation). We evaluated diagnostic accuracy of marker vs metric in separating AD from healthy and prognostic accuracy to predict progression in mild cognitive impairment. The outcome measure was positive (negative) likelihood ratio, LR+ (LR-), defined as the ratio between the probability of positive (negative) test outcome in patients and the probability of positive (negative) test outcome in healthy controls. Diagnostic LR+ of markers was between 4.4 and 9.4 and LR- between 0.25 and 0.08, whereas prognostic LR+ and LR- were between 1.7 and 7.5, and 0.50 and 0.11, respectively. Within metrics, LRs varied up to 100-fold: LR+ from approximately 1 to 100; LR- from approximately 1.00 to 0.01. Markers accounted for 11% and 18% of diagnostic and prognostic variance of LR1 and 16% and 24% of LR-. Across all markers, metrics accounted for an equal or larger amount of variance than markers: 13% and 62% of diagnostic and prognostic variance of LR+, and 29% and 18% of LR-. Within markers, the largest proportion of diagnostic LR+ and LR- variability was within F-18-FDG-PET and MRI metrics, respectively. Diagnostic and prognostic accuracy of imaging AD biomarkers is at least as dependent on how the biomarker is measured as on the biomarker itself. Standard operating procedures are key to biomarker use in the clinical routine and drug trials.
C1 [Frisoni, Giovanni B.; Bocchetta, Martina] IRCCS, LENITEM Lab Epidemiol Neuroimaging & Telemed, Brescia, Italy.
[Chetelat, Gael] INSERM, U1077, Caen, France.
[Chetelat, Gael] Univ Caen Basse Normandie, UMR S1077, Caen, France.
[Chetelat, Gael] Ecole Prat Hautes Etud, UMR S1077, Caen, France.
[Chetelat, Gael] CHU Caen, U1077, F-14000 Caen, France.
[Rabinovici, Gil D.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA.
[Weiner, Michael W.; DeCarli, Charles] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[de Leon, Mony J.] NYU, Sch Med, Ctr Brain Hlth, New York, NY USA.
[Kaye, Jeffrey] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Kaye, Jeffrey] Portland VA Med Ctr, Phoenix, AZ USA.
[Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ USA.
[Scheltens, Philip] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands.
[Scheltens, Philip] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands.
[Barkhof, Frederik] Vrije Univ Amsterdam, Med Ctr, Dept Radiol, Amsterdam, Netherlands.
[Barkhof, Frederik] Vrije Univ Amsterdam, Med Ctr, Dept Nucl Med, Amsterdam, Netherlands.
[Black, Sandra E.] Univ Toronto, Sunnybrook Res Inst, Dept Med Neurol, Toronto, ON, Canada.
[Brooks, David J.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Brain Sci, London, England.
[Brooks, David J.] Aarhus Univ, DK-8000 Aarhus C, Denmark.
[Carrillo, Maria C.; Thies, William] Alzheimers Assoc, Med & Sci Relat, Chicago, IL USA.
[Fox, Nick C.] UCL, Inst Neurol, London, England.
[Herholz, Karl] Univ Manchester, Inst Brain Behav & Mental Hlth, Wolfson Mol Imaging Ctr, Manchester M13 9PL, Lancs, England.
[Nordberg, Agneta] Karolinska Inst, Karolinska Univ Hosp Huddinge, Stockholm, Sweden.
[Nordberg, Agneta] Karolinska Inst, Alzheimer Neurobiol Ctr, Stockholm, Sweden.
[Jack, Clifford R., Jr.] Mayo Clin & Mayo Fdn, Dept Diagnost Radiol, Rochester, MN USA.
[Jagust, William J.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Jagust, William J.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
[Johnson, Keith A.; Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
[Rowe, Christopher C.] Austin Hlth, Ctr PET, Dept Nucl Med, Melbourne, Vic, Australia.
[Wahlund, Lars-Olof] Karolinska Inst, Div Clin Geriatr, NVS Dept, Stockholm, Sweden.
[Weiner, Michael W.] San Francisco VA Med Ctr, Rome, Italy.
[Pasqualetti, Patrizio] Fatebenefratelli Hosp, SeSMIT Serv Med Stat & Informat Technol, AFaR Fatebenefratelli Assoc Res, Rome, Italy.
[Pasqualetti, Patrizio] IRCCS San Raffaele Pisana, Unit Clin & Mol Epidemiol, Rome, Italy.
RP Frisoni, GB (reprint author), IRCCS, LENITEM Lab Epidemiol Neuroimaging & Telemed, Brescia, Italy.
EM gfrisoni@fatebenefratelli.it
RI Bocchetta, Martina/B-6331-2013; Fox, Nick/B-1319-2009; Jack,
Clifford/F-2508-2010; Frisoni, Giovanni B/K-1360-2016; Chetelat,
Gael/G-2316-2015;
OI Bocchetta, Martina/0000-0003-1814-5024; Fox, Nick/0000-0002-6660-657X;
Jack, Clifford/0000-0001-7916-622X; Frisoni, Giovanni
B/0000-0002-6419-1753; Pasqualetti, Patrizio/0000-0001-5560-1979; Black,
Sandra/0000-0001-7093-8289; Kaye, Jeffrey/0000-0002-9971-3478; Brooks,
David/0000-0003-2602-2518
FU Alzheimer's Association [IIRG-10-174022]
FX This study was partially funded by the Alzheimer's Association grant
IIRG-10-174022, "A Harmonized Protocol for Hippocampal Volumetry: An
EADC-ADNI Effort."
NR 46
TC 68
Z9 69
U1 3
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 30
PY 2013
VL 81
IS 5
BP 487
EP 500
PG 14
WC Clinical Neurology
SC Neurosciences & Neurology
GA 304JB
UT WOS:000330741800019
PM 23897875
ER
PT J
AU Samuel, R
Daheron, L
Liao, S
Vardam, T
Kamoun, WS
Batista, A
Buecker, C
Schafer, R
Han, XX
Au, P
Scadden, DT
Duda, DG
Fukumura, D
Jain, RK
AF Samuel, Rekha
Daheron, Laurence
Liao, Shan
Vardam, Trupti
Kamoun, Walid S.
Batista, Ana
Buecker, Christa
Schaefer, Richard
Han, Xiaoxing
Au, Patrick
Scadden, David T.
Duda, Dan G.
Fukumura, Dai
Jain, Rakesh K.
TI Generation of functionally competent and durable engineered blood
vessels from human induced pluripotent stem cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE diabetes; vascular endothelial cells; reprogramming
ID ENDOTHELIAL-CELLS; MYOCARDIAL-INFARCTION; REGENERATIVE MEDICINE;
VASCULAR-PERMEABILITY; PERIPHERAL-BLOOD; IN-VIVO; EXPRESSION; DISEASE;
DIFFERENTIATION; ANGIOGENESIS
AB Efficient generation of competent vasculogenic cells is a critical challenge of human induced pluripotent stem (hiPS) cell-based regenerative medicine. Biologically relevant systems to assess functionality of the engineered vessels in vivo are equally important for such development. Here, we report a unique approach for the derivation of endothelial precursor cells from hiPS cells using a triple combination of selection markers-CD34, neuropilin 1, and human kinase insert domain-containing receptor-and an efficient 2D culture system for hiPS cell-derived endothelial precursor cell expansion. With these methods, we successfully generated endothelial cells (ECs) from hiPS cells obtained from healthy donors and formed stable functional blood vessels in vivo, lasting for 280 d in mice. In addition, we developed an approach to generate mesenchymal precursor cells (MPCs) from hiPS cells in parallel. Moreover, we successfully generated functional blood vessels in vivo using these ECs and MPCs derived from the same hiPS cell line. These data provide proof of the principle that autologous hiPS cell-derived vascular precursors can be used for in vivo applications, once safety and immunological issues of hiPS-based cellular therapy have been resolved. Additionally, the durability of hiPS-derived blood vessels in vivo demonstrates a potential translation of this approach in long-term vascularization for tissue engineering and treatment of vascular diseases. Of note, we have also successfully generated ECs and MPCs from type 1 diabetic patient-derived hiPS cell lines and use them to generate blood vessels in vivo, which is an important milestone toward clinical translation of this approach.
C1 [Samuel, Rekha; Liao, Shan; Vardam, Trupti; Kamoun, Walid S.; Batista, Ana; Han, Xiaoxing; Au, Patrick; Duda, Dan G.; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA.
[Daheron, Laurence; Buecker, Christa; Schaefer, Richard] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Richard B Simches Res Ctr, Boston, MA 02114 USA.
RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA.
EM dai@steele.mgh.harvard.edu; jain@steele.mgh.harvard.edu
OI Schafer, Richard/0000-0003-1530-7980; Buecker,
Christa/0000-0003-3055-2642
FU Department of Biotechnology, Ministry of Science and Technology,
Government of India; Tosteson Postdoctoral Fellowship; Charles A. King
Trust Fellowship [K99HL111343-01A1]; Harvard Stem Cell Institute;
National Institutes of Health [P01-CA080124]; Federal Share/National
Cancer Institute Proton Beam Program Income Grants [R01-CA115767,
R01-CA085140, R01-CA126642, R01CA159258, R01-CA096915]; American Cancer
Society [120733-RSG-11-073-01-TBG]
FX We thank Sylvie Roberge, Peigen Huang, Christina Koppel, Phyllis
McNally, and Julia Kahn for outstanding technical assistance and Drs.
Vikash Pal Singh Chauhan, Ravi Mylvaganam, and Matija Snuderl for help
with the experiments. We also thank Dr. Douglas Melton for his generous
gift of T1D-iPS cell lines and helpful scientific input on our
manuscript. This work was supported by a fellowship from the Department
of Biotechnology, Ministry of Science and Technology, Government of
India (to R. Samuel); a Tosteson Postdoctoral Fellowship, Charles A.
King Trust Fellowship, and Grant K99HL111343-01A1 (to S. L.); funds from
the Harvard Stem Cell Institute; National Institutes of Health Grant
P01-CA080124; Federal Share/National Cancer Institute Proton Beam
Program Income Grants R01-CA115767, R01-CA085140, and R01-CA126642 (to
R. K. J.), R01CA159258 (to D. G. D.), and R01-CA096915 (to D. F.); and
American Cancer Society Grant 120733-RSG-11-073-01-TBG (to D.G.D.).
NR 45
TC 48
Z9 53
U1 4
U2 37
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 30
PY 2013
VL 110
IS 31
BP 12774
EP 12779
DI 10.1073/pnas.1310675110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 191VH
UT WOS:000322441500064
PM 23861493
ER
PT J
AU Donaldson, GC
Mullerova, H
Locantore, N
Hurst, JR
Calverley, PMA
Vestbo, J
Anzueto, A
Wedzicha, JA
AF Donaldson, Gavin C.
Muellerova, Hanna
Locantore, Nicholas
Hurst, John R.
Calverley, Peter M. A.
Vestbo, Jorgen
Anzueto, Antonio
Wedzicha, Jadwiga A.
TI Factors associated with change in exacerbation frequency in COPD
SO RESPIRATORY RESEARCH
LA English
DT Article
DE COPD; Exacerbations; Exacerbation frequency; Exacerbation phenotype
ID OBSTRUCTIVE PULMONARY-DISEASE; LUNG-FUNCTION DECLINE; QUALITY-OF-LIFE;
ECLIPSE COHORT; INFLAMMATORY MARKERS; TIME; POPULATION; SEVERITY;
SYMPTOMS; DISTANCE
AB Background: Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year. Although most patients do not change category from year to year, some will, and the factors associated with this behaviour have not been examined.
Methods: 1832 patients completing two year follow-up in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study were examined at baseline and then yearly. Exacerbations were defined by health care utilisation. Patient characteristics compared between those patients who did or did not change exacerbation category from year 1 to year 2.
Findings: Between years 1 and 2, 221 patients (17%) changed from IE to FE and 210 patients (39%) from FE to IE. More severe disease was associated with changing from IE to FE and less severe disease from FE to IE. Over the preceding year, small falls in FEV1 and 6-minute walking distance were associated with changing from IE to FE, and small falls in platelet count associated with changing from FE to IE.
Conclusion: No parameter clearly predicts an imminent change in exacerbation frequency category.
C1 [Donaldson, Gavin C.; Wedzicha, Jadwiga A.] UCL Med Sch, Ctr Resp Med, London NW3 2PF, England.
[Muellerova, Hanna] GlaxoSmithKline R&D, Uxbridge UB11 1BT, Middx, England.
[Locantore, Nicholas] GlaxoSmithKline, Res Triangle Pk, NC USA.
[Hurst, John R.] UCL, Ctr Inflammat & Tissue Repair, London, England.
[Calverley, Peter M. A.] Aintree Univ Hosp NHS Fdn Trust, Sch Ageing & Chron Dis, Liverpool L9 7AL, Merseyside, England.
[Vestbo, Jorgen] Odense Univ Hosp, Dept Resp Med, DK-5000 Odense, Denmark.
[Vestbo, Jorgen] Univ Southern Denmark, Odense, Denmark.
[Vestbo, Jorgen] Univ Manchester, Resp Res Grp, Sch Translat Med, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Anzueto, Antonio] Univ Texas Hlth Sci Ctr, Pulm Sect, San Antonio, TX USA.
[Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Donaldson, GC (reprint author), UCL Med Sch, Ctr Resp Med, Royal Free Campus,Rowland Hill St Hampstead, London NW3 2PF, England.
EM g.donaldson@ucl.ac.uk
OI Vestbo, Jorgen/0000-0001-6355-6362; Mullerova, Hana/0000-0002-0949-0101
FU GlaxoSmithKline
FX This work was funded by GlaxoSmithKline. The authors acknowledge the
principle investigators, steering and scientific committee of the
ECLIPSE study. The authors would also like to thank the patients
participating in the ECLIPSE study.
NR 39
TC 21
Z9 21
U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-993X
J9 RESP RES
JI Respir. Res.
PD JUL 30
PY 2013
VL 14
AR 79
DI 10.1186/1465-9921-14-79
PG 9
WC Respiratory System
SC Respiratory System
GA 193ZX
UT WOS:000322601100001
PM 23899210
ER
PT J
AU Pinto, DS
Pride, YB
AF Pinto, Duane S.
Pride, Yuri B.
TI Paved With Good Intentions and Marred by Half-Truths
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE cause of death; coronary intervention; mortality; public reporting; risk
avoidance
ID PERCUTANEOUS CORONARY INTERVENTION; OUTCOMES
C1 [Pinto, Duane S.; Pride, Yuri B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Sch Med,Dept Med, Boston, MA 02215 USA.
RP Pinto, DS (reprint author), Beth Israel Deaconess Med Ctr, 185 Pilgrim Rd,W Baker 4, Boston, MA 02215 USA.
EM dpinto@bidmc.harvard.edu
NR 7
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUL 30
PY 2013
VL 62
IS 5
BP 416
EP 417
DI 10.1016/j.jacc.2013.04.026
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 186SL
UT WOS:000322064900004
PM 23665366
ER
PT J
AU Hanlon, CA
Hartwell, KJ
Canterberry, M
Li, XB
Owens, M
LeMatty, T
Prisciandaro, JJ
Borckardt, J
Brady, KT
George, MS
AF Hanlon, Colleen A.
Hartwell, Karen J.
Canterberry, Melanie
Li, Xingbao
Owens, Max
LeMatty, Todd
Prisciandaro, James J.
Borckardt, Jeffrey
Brady, Kathleen T.
George, Mark S.
TI Reduction of cue-induced craving through realtime neurofeedback in
nicotine users: The role of region of interest selection and multiple
visits
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Addiction; Prefrontal cortex; Cingulate
ID SELF-CONTROL; SMOKING; ADDICTION; ACTIVATION; CESSATION; SMOKERS; LOCUS
AB This multi-visit, real-time functional magnetic resonance imaging feedback study demonstrates that treatment-seeking smokers can effectively modulate their behavioral and brain responses to smoking cues. They are more effective at decreasing activity in functionally defined regions involved in "craving" (e.g. ventral anterior cingulate cortex (vACC)) rather than increasing activity in regions involved in "resisting" (e.g. dorsal medial prefrontal cortex (dmPFC)). (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Hanlon, Colleen A.; Hartwell, Karen J.; Canterberry, Melanie; Li, Xingbao; Owens, Max; LeMatty, Todd; Prisciandaro, James J.; Borckardt, Jeffrey; Brady, Kathleen T.; George, Mark S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
[Brady, Kathleen T.; George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA.
RP Hanlon, CA (reprint author), Med Univ S Carolina, Dept Psychiat, Ctr Biomed Imaging, 67 President St, Charleston, SC 29425 USA.
EM hanlon@musc.edu
FU National Institutes of Health [K01DA027756, GA30523K, UL1 RR029882];
[R33DA026085]
FX Funding was provided by R33DA026085 (Brady) with additional support from
K01DA027756 (Hanlon), GA30523K and UL1 RR029882 (CSTA) from the National
Institutes of Health. The authors received no compensation from other
external organizations related to this manuscript.
NR 16
TC 24
Z9 24
U1 1
U2 22
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD JUL 30
PY 2013
VL 213
IS 1
BP 79
EP 81
DI 10.1016/j.pscychresns.2013.03.003
PG 3
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 169DF
UT WOS:000320756700011
PM 23683344
ER
PT J
AU Dai, J
Brooks, Y
Lefort, K
Getsios, S
Dotto, GP
AF Dai, Jun
Brooks, Yang
Lefort, Karine
Getsios, Spiro
Dotto, G. Paolo
TI The Retinoid-Related Orphan Receptor ROR alpha Promotes Keratinocyte
Differentiation via FOXN1
SO PLOS ONE
LA English
DT Article
ID LIGAND-BINDING DOMAIN; TERMINAL DIFFERENTIATION; NUCLEAR RECEPTOR;
CHOLESTEROL SULFATE; HUMAN EPIDERMIS; STEM-CELLS; SKIN; NOTCH; GENE;
EXPRESSION
AB ROR alpha is a retinoid-related orphan nuclear receptor that regulates inflammation, lipid metabolism, and cellular differentiation of several non-epithelial tissues. In spite of its high expression in skin epithelium, its functions in this tissue remain unclear. Using gain- and loss-of-function approaches to alter ROR alpha gene expression in human keratinocytes (HKCs), we have found that this transcription factor functions as a regulator of epidermal differentiation. Among the 4 ROR alpha isoforms, ROR alpha 4 is prominently expressed by keratinocytes in a manner that increases with differentiation. In contrast, ROR alpha levels are significantly lower in skin squamous cell carcinoma tumors (SCCs) and cell lines. Increasing the levels of ROR alpha 4 in HKCs enhanced the expression of structural proteins associated with early and late differentiation, as well as genes involved in lipid barrier formation. Gene silencing of ROR alpha impaired the ability of keratinocytes to differentiate in an in vivo epidermal cyst model. The pro-differentiation function of ROR alpha is mediated at least in part by FOXN1, a well-known pro-differentiation transcription factor that we establish as a novel direct target of ROR alpha in keratinocytes. Our results point to ROR alpha as a novel node in the keratinocyte differentiation network and further suggest that the identification of ROR alpha ligands may prove useful for treating skin disorders that are associated with abnormal keratinocyte differentiation, including cancer.
C1 [Dai, Jun; Brooks, Yang; Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA.
[Lefort, Karine] Univ Lausanne Hosp, Dept Dermatol, Epalinges, Switzerland.
[Getsios, Spiro] Northwestern Univ, Dept Dermatol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland.
RP Dotto, GP (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA.
EM Paolo.Dotto@unil.ch
RI Dai, Jun/J-9718-2015
FU National Institutes of Health/National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIH/NIAMS) [K01 AR062132, R01
AR039190, AR054856]; Swiss National Science Foundation [3100A0-122281/1,
CRSI33-130576/1]
FX This work was supported by grants from National Institutes of
Health/National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIH/NIAMS) (K01 AR062132 to J.D. and R01 AR039190 and AR054856
to G. P. D.) and by the Swiss National Science Foundation (Grant
3100A0-122281/1; CRSI33-130576/1) to G. P. D. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 59
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Z9 7
U1 0
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 JUL 29
PY 2013
VL 8
IS 7
AR e70392
DI 10.1371/journal.pone.0070392
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 204MP
UT WOS:000323369700181
PM 23922987
ER
PT J
AU Kaczmarek, E
Bakker, JP
Clarke, DN
Csizmadia, E
Kocher, O
Veves, A
Tecilazich, F
O'Donnell, CP
Ferran, C
Malhotra, A
AF Kaczmarek, Elzbieta
Bakker, Jessie P.
Clarke, Douglas N.
Csizmadia, Eva
Kocher, Olivier
Veves, Aristidis
Tecilazich, Francesco
O'Donnell, Christopher P.
Ferran, Christiane
Malhotra, Atul
TI Molecular Biomarkers of Vascular Dysfunction in Obstructive Sleep Apnea
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; FACTOR-KAPPA-B;
CELLULAR ADHESION MOLECULES; HYPOXIA-INDUCIBLE FACTOR-1; INTERMITTENT
HYPOXIA; OXIDATIVE STRESS; GENE-EXPRESSION; IN-VIVO; DEPENDENT MECHANISM
AB Untreated and long-lasting obstructive sleep apnea (OSA) may lead to important vascular abnormalities, including endothelial cell (EC) dysfunction, hypertension, and atherosclerosis. We observed a correlation between microcirculatory reactivity and endothelium-dependent release of nitric oxide in OSA patients. Therefore, we hypothesized that OSA affects (micro) vasculature and we aimed to identify vascular gene targets of OSA that could possibly serve as reliable biomarkers of severity of the disease and possibly of vascular risk. Using quantitative RT-PCR, we evaluated gene expression in skin biopsies of OSA patients, mouse aortas from animals exposed to 4-week intermittent hypoxia (IH; rapid oscillations in oxygen desaturation and reoxygenation), and human dermal microvascular (HMVEC) and coronary artery endothelial cells (HCAEC) cultured under IH. We demonstrate a significant upregulation of endothelial nitric oxide synthase (eNOS), tumor necrosis factor-alpha-induced protein 3 (TNFAIP3; A20), hypoxia-inducible factor 1 alpha (HIF-1 alpha?? and vascular endothelial growth factor (VEGF) expression in skin biopsies obtained from OSA patients with severe nocturnal hypoxemia (nadir saturated oxygen levels [SaO(2)]<75%) compared to mildly hypoxemic OSA patients (SaO(2) 75%-90%) and a significant upregulation of vascular cell adhesion molecule 1 (VCAM-1) expression compared to control subjects. Gene expression profile in aortas of mice exposed to IH demonstrated a significant upregulation of eNOS and VEGF. In an in vitro model of OSA, IH increased expression of A20 and decreased eNOS and HIF-1 alpha expression in HMVEC, while increased A20, VCAM-1 and HIF-1 alpha expression in HCAEC, indicating that EC in culture originating from distinct vascular beds respond differently to IH stress. We conclude that gene expression profiles in skin of OSA patients may correlate with disease severity and, if validated by further studies, could possibly predict vascular risk in OSA patients.
C1 [Kaczmarek, Elzbieta; Clarke, Douglas N.; Csizmadia, Eva; Ferran, Christiane] Harvard Univ, Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Div Vasc & Endovasc Surg,Dept Surg,Med Sch, Boston, MA 02215 USA.
[Bakker, Jessie P.; Malhotra, Atul] Harvard Univ, Brigham & Womens Hosp, Div Sleep Med, Sch Med, Boston, MA 02115 USA.
[Kocher, Olivier] Harvard Univ, Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Dept Pathol,Med Sch, Boston, MA 02215 USA.
[Veves, Aristidis; Tecilazich, Francesco] Harvard Univ, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Sch Med, Boston, MA 02215 USA.
[Veves, Aristidis; Tecilazich, Francesco] Harvard Univ, Beth Israel Deaconess Med Ctr, Joslin Beth Israel Deaconess Foot Ctr, Dept Surg,Med Sch, Boston, MA 02215 USA.
[O'Donnell, Christopher P.] Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
[Malhotra, Atul] Univ Calif San Diego, Div Pulm & Crit Care Med, La Jolla, CA 92093 USA.
RP Kaczmarek, E (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Div Vasc & Endovasc Surg,Dept Surg,Med Sch, Boston, MA 02215 USA.
EM ekaczmar@bidmc.harvard.edu
FU National Institutes of Health (NIH) [HL106227, HL077785, HL080130,
HL090897, HL093218, HL095491, HL110350, HL085188]; AHA [0840159N];
Harvard Catalyst [RR025758]
FX This study was supported by grants from National Institutes of Health
(NIH) (EK - HL106227; CPO - HL077785; CF - HL080130; AM - HL090897,
HL093218, HL095491, HL110350, HL085188), AHA (AM - 0840159N), and
Harvard Catalyst (AM - RR025758). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 68
TC 21
Z9 21
U1 0
U2 10
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 JUL 29
PY 2013
VL 8
IS 7
AR e70559
DI 10.1371/journal.pone.0070559
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 204MP
UT WOS:000323369700194
PM 23923005
ER
PT J
AU Zhao, ZM
Webb, BT
Jia, PL
Bigdeli, TB
Maher, BS
van den Oord, E
Bergen, SE
Amdur, RL
O'Neill, FA
Walsh, D
Thiselton, DL
Chen, XN
Pato, CN
Riley, BP
Kendler, KS
Fanous, AH
AF Zhao, Zhongming
Webb, Bradley T.
Jia, Peilin
Bigdeli, T. Bernard
Maher, Brion S.
van den Oord, Edwin
Bergen, Sarah E.
Amdur, Richard L.
O'Neill, Francis A.
Walsh, Dermot
Thiselton, Dawn L.
Chen, Xiangning
Pato, Carlos N.
Riley, Brien P.
Kendler, Kenneth S.
Fanous, Ayman H.
CA Int Schizophrenia Consortium
TI Association Study of 167 Candidate Genes for Schizophrenia Selected by a
Multi-Domain Evidence-Based Prioritization Algorithm and
Neurodevelopmental Hypothesis
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CONVERGENT FUNCTIONAL GENOMICS; COMMON
VARIANTS; BETA-CATENIN; NRG1 GENE; LINKAGE; METAANALYSIS; EXPRESSION;
IMPUTATION; FAMILIES
AB Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n = 3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene Ontology terms related to neurodevelopment. Subsequently, genotypes of 3725 SNPs in 167 genes from a custom Illumina iSelect array were used to evaluate the top ranked vs. hypothesis selected genes. Seventy-three genes were both highly ranked and involved in neurodevelopment (category 1) while 42 and 52 genes were exclusive to neurodevelopment (category 2) or highly ranked (category 3), respectively. The most significant associations were observed in genes PRKG1, PRKCE, and CNTN4 but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of schizophrenia showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted.
C1 [Zhao, Zhongming; Jia, Peilin] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA.
[Zhao, Zhongming] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA.
[Webb, Bradley T.; Bigdeli, T. Bernard; van den Oord, Edwin; Thiselton, Dawn L.; Chen, Xiangning; Riley, Brien P.; Kendler, Kenneth S.; Fanous, Ayman H.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA.
[Webb, Bradley T.; van den Oord, Edwin] Virginia Commonwealth Univ, Ctr Biomarker Res & Personalized Med, Richmond, VA USA.
[Maher, Brion S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
[Bergen, Sarah E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Bergen, Sarah E.] MIT, Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA.
[Bergen, Sarah E.] Harvard, Cambridge, MA USA.
[Amdur, Richard L.; Fanous, Ayman H.] Washington VA Med Ctr, Washington, DC USA.
[O'Neill, Francis A.] Queens Univ, Dept Psychiat, Belfast, Antrim, North Ireland.
[Walsh, Dermot] Hlth Res Board, Dublin, Ireland.
[Chen, Xiangning; Riley, Brien P.; Kendler, Kenneth S.; Fanous, Ayman H.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA.
[Chen, Xiangning; Riley, Brien P.; Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA.
[Fanous, Ayman H.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA.
[Pato, Carlos N.; Fanous, Ayman H.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA.
RP Fanous, AH (reprint author), Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA.
EM ayman.fanous@va.gov
RI Webb, Bradley/B-1459-2009;
OI Webb, Bradley/0000-0002-0576-5366; Bergen, Sarah/0000-0002-5888-0034;
O'Neill, Francis Anthony/0000-0002-7531-7657
FU National Institute of Mental Health [N01 MH900001, MH074027]; Eli Lilly
and Company; Department of Veterans Affairs Merit Review Program
[1I01CX000278]; NARSAD Maltz Investigator Award; NARSAD Young
Investigator Award
FX Two dataset(s) used in the analyses described in this manuscript were
obtained from the database of Genotype and Phenotype (dbGaP) found at
http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number [GAIN:
phs000021.v2.p1, nonGAIN: phs00167.v1.p1]. For the GAIN dataset, the
genotyping of samples was provided through the Genetic Association
Information Network (GAIN). The CATIE trial was funded by a grant from
the National Institute of Mental Health (N01 MH900001) along with
MH074027 (PI PF Sullivan). Genotyping was funded by Eli Lilly and
Company. The CATIE dataset was approved to use in this analysis through
the authors' application. This work was supported by Department of
Veterans Affairs Merit Review Program (1I01CX000278, to AHF), 2009
NARSAD Maltz Investigator Award (to ZZ) and 2010 NARSAD Young
Investigator Award (to PJ). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 51
TC 3
Z9 3
U1 1
U2 5
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 JUL 29
PY 2013
VL 8
IS 7
AR e67776
DI 10.1371/journal.pone.0067776
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 204MP
UT WOS:000323369700002
PM 23922650
ER
PT J
AU Sung, YJ
Sheppard, CJR
Barbastathis, G
Ando, M
Gupta, R
AF Sung, Yongjin
Sheppard, Colin J. R.
Barbastathis, George
Ando, Masami
Gupta, Rajiv
TI Full-wave approach for x-ray phase imaging
SO OPTICS EXPRESS
LA English
DT Article
ID DARK-FIELD; CONTRAST MICROTOMOGRAPHY; RYTOV APPROXIMATION;
ARTICULAR-CARTILAGE; TOMOGRAPHY; DIFFRACTION; SCATTERING; RESOLUTION;
ANALYZER
AB We present a rigorous forward model for phase imaging of a 3-D object illuminated by a cone-shaped x-ray beam. Our model is based on a full-wave approach valid under the first Rytov approximation, and thus can be used with large and thick objects, e. g., luggage and human patients. We unify light-matter interaction and free-space propagation into an integrated wave optics framework. Therefore, our model can accurately calculate x-ray phase images formed with sources of arbitrary shape, and it can be effectively incorporated into x-ray phase tomography as a forward model. Within the best of our knowledge, this is the first non-paraxial, full-wave model for X-ray phase imaging. (C) 2013 Optical Society of America
C1 [Sung, Yongjin; Barbastathis, George] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
[Sung, Yongjin; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Sung, Yongjin; Gupta, Rajiv] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Sheppard, Colin J. R.] Ist Italiano Tecnol, I-16163 Genoa, Italy.
[Ando, Masami] Tokyo Univ Sci, Res Inst Sci & Technol, Noda, Chiba 2788510, Japan.
RP Sung, YJ (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM yongjin.sung@gmail.com
FU Department of Homeland Security's Science and Technology Directorate
[HSHQDC-11-C-0083]; National Research Foundation of Singapore through
the Singapore-MIT Alliance for Research and Technology Centre; DARPA
AXiS program [N66001-11-4204, 1300217190]
FX This work was supported by the Department of Homeland Security's Science
and Technology Directorate through contract HSHQDC-11-C-0083, the
National Research Foundation of Singapore through the Singapore-MIT
Alliance for Research and Technology Centre, and the DARPA AXiS program
(Grant No. N66001-11-4204, P.R. No. 1300217190). The experiment was
performed under the approval of the PF User Association (PF-UA) at KEK
under No. 2008S2-002, 2011G-672 for use of the Photon Factory. The
authors thank Dr. Synho Do and Dr. Omid Khalilzadeh for helpful
discussion.
NR 37
TC 5
Z9 5
U1 1
U2 14
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1094-4087
J9 OPT EXPRESS
JI Opt. Express
PD JUL 29
PY 2013
VL 21
IS 15
BP 17547
EP 17557
DI 10.1364/OE.21.017547
PG 11
WC Optics
SC Optics
GA 190UJ
UT WOS:000322366300015
PM 23938626
ER
PT J
AU Mansour, MR
Sanda, T
Lawton, LN
Li, XY
Kreslavsky, T
Novina, CD
Brand, M
Gutierrez, A
Kelliher, MA
Jamieson, CHM
von Boehmer, H
Young, RA
Look, AT
AF Mansour, Marc R.
Sanda, Takaomi
Lawton, Lee N.
Li, Xiaoyu
Kreslavsky, Taras
Novina, Carl D.
Brand, Marjorie
Gutierrez, Alejandro
Kelliher, Michelle A.
Jamieson, Catriona H. M.
von Boehmer, Harald
Young, Richard A.
Look, A. Thomas
TI The TAL1 complex targets the FBXW7 tumor suppressor by activating
miR-223 in human T cell acute lymphoblastic leukemia
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; GENE-EXPRESSION; TRANSCRIPTIONAL CONTROL;
HUMAN GRANULOPOIESIS; UBIQUITIN LIGASE; HUMAN CANCERS; DIFFERENTIATION;
SCL; MICRORNA-223; ONCOPROTEIN
AB The oncogenic transcription factor TAL1/SCL is aberrantly expressed in 60% of cases of human T cell acute lymphoblastic leukemia (T-ALL) and initiates T-ALL in mouse models. By performing global microRNA (miRNA) expression profiling after depletion of TAL1, together with genome-wide analysis of TAL1 occupancy by chromatin immunoprecipitation coupled to massively parallel DNA sequencing, we identified the miRNA genes directly controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3, and RUNX1. The most dynamically regulated miRNA was miR-223, which is bound at its promoter and up-regulated by the TAL1 complex. miR-223 expression mirrors TAL1 levels during thymic development, with high expression in early thymocytes and marked down-regulation after the double-negative-2 stage of maturation. We demonstrate that aberrant miR-223 up-regulation by TAL1 is important for optimal growth of TAL1-positive T-ALL cells and that sustained expression of miR-223 partially rescues T-ALL cells after TAL1 knockdown. Overexpression of miR-223 also leads to marked down-regulation of FBXW7 protein expression, whereas knockdown of TAL1 leads to up-regulation of FBXW7 protein levels, with a marked reduction of its substrates MYC, MYB, NOTCH1, and CYCLIN E. We conclude that TAL1-mediated up-regulation of miR-223 promotes the malignant phenotype in T-ALL through repression of the FBXW7 tumor suppressor.
C1 [Mansour, Marc R.; Sanda, Takaomi; Gutierrez, Alejandro; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02216 USA.
[Li, Xiaoyu; Kreslavsky, Taras; Novina, Carl D.; von Boehmer, Harald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02216 USA.
[Mansour, Marc R.] UCL, Univ Coll London Canc Inst, Dept Haematol, London WC1E 6BT, England.
[Sanda, Takaomi] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117599, Singapore.
[Lawton, Lee N.; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Novina, Carl D.] Broad Inst Harvard, Cambridge, MA 02142 USA.
[Novina, Carl D.] MIT, Cambridge, MA 02142 USA.
[Brand, Marjorie] Ottawa Hosp Res Inst, Sprott Ctr Stem Cell Res, Dept Regenerat Med, Ottawa, ON K1Y 4E9, Canada.
[Brand, Marjorie] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada.
[Gutierrez, Alejandro; Look, A. Thomas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Kelliher, Michelle A.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA.
[Jamieson, Catriona H. M.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Jamieson, Catriona H. M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02142 USA.
RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02216 USA.
EM thomas_look@dfci.harvard.edu
RI Young, Richard/F-6495-2012;
OI Young, Richard/0000-0001-8855-8647; Gutierrez,
Alejandro/0000-0002-0249-9007
FU Kay Kendall Leukaemia Fund of the UK; Team Path To the Cure grant;
National Cancer Institute [5P01CA109901, 5P01CA68484, 1K99CA157951];
National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research; William Lawrence and Blanche Hughes Foundation;
Children's Leukemia Research Association; Japan Society for the
Promotion of Science; NIH [1K08CA133103]
FX This research was supported by the Kay Kendall Leukaemia Fund of the UK
(M. R. Mansour), Team Path To the Cure grant (M. R. Mansour and A. T.
Look), grants from the National Cancer Institute (5P01CA109901,
5P01CA68484, and 1K99CA157951), and by the Intramural Research Program
of the National Institutes of Health (NIH), National Cancer Institute,
Center for Cancer Research. T. Sanda is supported by grants from the
William Lawrence and Blanche Hughes Foundation, the Children's Leukemia
Research Association and the Japan Society for the Promotion of Science.
A. Gutierrez is supported by NIH grant 1K08CA133103 and is a Scholar of
the American Society of Hematology-Amos Faculty Development Program.
NR 52
TC 41
Z9 43
U1 0
U2 5
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 JUL 29
PY 2013
VL 210
IS 8
BP 1545
EP 1557
DI 10.1084/jem.20122516
PG 13
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 190WG
UT WOS:000322372800005
PM 23857984
ER
PT J
AU Jones, V
Katiyar, SK
AF Jones, Virginia
Katiyar, Santosh K.
TI Emerging phytochemicals for prevention of melanoma invasion
SO CANCER LETTERS
LA English
DT Review
DE Cyclooxygenase-2; Melanoma; Phytochemicals; Prostaglandins; beta-Catenin
ID E-CADHERIN EXPRESSION; EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN
BREAST-CANCER; NF-KAPPA-B; BETA-CATENIN; MALIGNANT-MELANOMA; CUTANEOUS
MELANOMA; CELL-LINES; GREEN TEA; PANCREATIC-CARCINOMA
AB Cutaneous malignant melanoma is the leading cause of death from skin diseases due to its propensity to metastasize. Once diagnosed with metastatic melanoma, most patients will die of their disease within 2 years. As suppression of metastases requires long-term interventions, potential anti-metastatic agents must not only be efficacious but also have low toxicity. Many phytochemicals used in traditional medicine have low toxicity and recent studies suggest that some are promising candidates for the prevention or treatment of metastatic melanoma. Here, we review the recent literature regarding phytochemicals that have shown inhibitory effects on melanoma cell migration or invasion. (c) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Jones, Virginia; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA.
[Katiyar, Santosh K.] Univ Alabama Birmingham, Skin Dis Res Ctr, Birmingham, AL 35294 USA.
[Katiyar, Santosh K.] Univ Alabama Birmingham, Nutr Obes Res Ctr, Birmingham, AL 35294 USA.
[Katiyar, Santosh K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
[Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA.
RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, 1670,Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA.
EM skatiyar@uab.edu
FU Veterans Administration Merit Review Award [1I01BX001410]; National
Institutes of Health/NCI [CA166883]
FX The work reported from Dr. Katiyar's laboratory was supported by
Veterans Administration Merit Review Award (1I01BX001410) and National
Institutes of Health/NCI (CA166883). The content of this article does
not necessarily reflect the views or policies of the funding sources. We
thank Dr. Fiona Hunter for her assistance in editing the manuscript.
NR 77
TC 9
Z9 9
U1 2
U2 10
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD JUL 28
PY 2013
VL 335
IS 2
BP 251
EP 258
DI 10.1016/j.canlet.2013.02.056
PG 8
WC Oncology
SC Oncology
GA 168CE
UT WOS:000320682500001
PM 23474498
ER
PT J
AU Briant, JA
Kotton, CN
AF Briant, Judith A.
Kotton, Camille N.
TI Two "Lost Boys of Sudan" Undergo Liver Transplantation: Infectious
Disease Issues
SO TRANSPLANTATION
LA English
DT Letter
ID PRESUMPTIVE TREATMENT; SCHISTOSOMIASIS
C1 [Briant, Judith A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kotton, Camille N.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Briant, JA (reprint author), 15 Parkman St,Wang 625, Boston, MA 02114 USA.
EM jbriant@partners.org
NR 7
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD JUL 27
PY 2013
VL 96
IS 2
BP E7
EP E9
DI 10.1097/TP.0b013e318297ae0e
PG 4
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 299EO
UT WOS:000330378600004
PM 23857005
ER
PT J
AU Kang, SA
Pacold, ME
Cervantes, CL
Lim, D
Lou, HJ
Ottina, K
Gray, NS
Turk, BE
Yaffe, MB
Sabatini, DM
AF Kang, Seong A.
Pacold, Michael E.
Cervantes, Christopher L.
Lim, Daniel
Lou, Hua Jane
Ottina, Kathleen
Gray, Nathanael S.
Turk, Benjamin E.
Yaffe, Michael B.
Sabatini, David M.
TI mTORC1 Phosphorylation Sites Encode Their Sensitivity to Starvation and
Rapamycin
SO SCIENCE
LA English
DT Article
ID GENETICALLY HETEROGENEOUS MICE; MESSENGER-RNA TRANSLATION; EXTENDS
LIFE-SPAN; MAMMALIAN TARGET; PROTEIN-KINASE; S6 KINASE; FKBP12-RAPAMYCIN
COMPLEX; INHIBITION; AUTOPHAGY; PATHWAY
AB The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) protein kinase promotes growth and is the target of rapamycin, a clinically useful drug that also prolongs life span in model organisms. A persistent mystery is why the phosphorylation of many bona fide mTORC1 substrates is resistant to rapamycin. We find that the in vitro kinase activity of mTORC1 toward peptides encompassing established phosphorylation sites varies widely and correlates strongly with the resistance of the sites to rapamycin, as well as to nutrient and growth factor starvation within cells. Slight modifications of the sites were sufficient to alter mTORC1 activity toward them in vitro and to cause concomitant changes within cells in their sensitivity to rapamycin and starvation. Thus, the intrinsic capacity of a phosphorylation site to serve as an mTORC1 substrate, a property we call substrate quality, is a major determinant of its sensitivity to modulators of the pathway. Our results reveal a mechanism through which mTORC1 effectors can respond differentially to the same signals.
C1 [Kang, Seong A.; Pacold, Michael E.; Cervantes, Christopher L.; Ottina, Kathleen; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Kang, Seong A.; Pacold, Michael E.; Cervantes, Christopher L.; Ottina, Kathleen; Yaffe, Michael B.; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Pacold, Michael E.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Pacold, Michael E.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA.
[Lim, Daniel; Yaffe, Michael B.; Sabatini, David M.] MIT, David H Koch Ctr Integrat Canc Res, Cambridge, MA 02139 USA.
[Lou, Hua Jane; Turk, Benjamin E.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA.
[Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Yaffe, Michael B.] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Dept Surg, Boston, MA 02215 USA.
RP Sabatini, DM (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM sabatini@wi.mit.edu
FU NIH [CA103866, AI047389, ES015339, GM59281, CA112967]; Department of
Defense [W81XWH-07-0448]; W.M. Keck Foundation; LAM
(lymphangioleiomyomatosis) Foundation; American Cancer Society; LAM
Foundation; Damon Runyon Cancer Research Foundation; Department of
Defense Breast Cancer Research Program
FX We thank members of the Sabatini laboratory for helpful discussions,
especially S. Wang, D. Kim, C. Thoreen, T. Wang, and J. Cantor and E.
Spooner for the mass spectrometric analysis of samples. We also thank M.
Pende for the S6K1/2 null cells and R. Shaw and C. Thompson for the
ULK1/2 null cells. This work was supported by grants from the NIH
(CA103866 and AI047389 to D. M. S.; ES015339, GM59281, and CA112967 to
M.B.Y.) and Department of Defense (W81XWH-07-0448 to D. M. S.); awards
from the W.M. Keck Foundation and the LAM (lymphangioleiomyomatosis)
Foundation to D. M. S.; fellowships from the American Cancer Society and
the LAM Foundation to S. A. K. and the Damon Runyon Cancer Research
Foundation and the Department of Defense Breast Cancer Research Program
to M. E. P. D. M. S. is an investigator of the Howard Hughes Medical
Institute. Torin1, the inhibitor used here, is part of a
Whitehead-Dana-Farber Cancer Institute patent application on which S. A.
K., N.S.G., and D. M. S. are inventors. Shared reagents are subject to a
materials transfer agreement.
NR 49
TC 115
Z9 118
U1 6
U2 31
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JUL 26
PY 2013
VL 341
IS 6144
BP 364
EP +
AR 1236566
DI 10.1126/science.1236566
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 189HX
UT WOS:000322259200040
PM 23888043
ER
PT J
AU Galaleldeen, A
Taylor, AB
Chen, D
Schuermann, JP
Holloway, SP
Hou, SP
Gong, SQ
Zhong, GM
Hart, PJ
AF Galaleldeen, Ahmad
Taylor, Alexander B.
Chen, Ding
Schuermann, Jonathan P.
Holloway, Stephen P.
Hou, Shuping
Gong, Siqi
Zhong, Guangming
Hart, P. John
TI Structure of the Chlamydia trachomatis Immunodominant Antigen Pgp3
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Bacterial Pathogenesis; Chlamydia; Immunology; Tumor Necrosis Factor
(TNF); X-ray Crystallography; Beta-Helix; Beta-Propeller; Helical
Coiled-coil; Pgp3; Sexually Transmitted Disease
ID SEGMENTED COILED-COIL; TUMOR-NECROSIS-FACTOR; C-TERMINAL DOMAIN;
CRYSTAL-STRUCTURE; BACTERIOPHAGE-T4 FIBRITIN; BACILLUS-ANTHRACIS;
TRANSCRIPTIONAL REGULATOR; VIRULENCE FACTOR; PROTEIN; PLASMID
AB Chlamydia trachomatis infection is the most common sexually transmitted bacterial disease. Left untreated, it can lead to ectopic pregnancy, pelvic inflammatory disease, and infertility. Here we present the structure of the secreted C. trachomatis protein Pgp3, an immunodominant antigen and putative virulence factor. The approximate to 84-kDa Pgp3 homotrimer, encoded on a cryptic plasmid, consists of globular N- and C-terminal assemblies connected by a triple-helical coiled-coil. The C-terminal domains possess folds similar to members of the TNF family of cytokines. The closest Pgp3 C-terminal domain structural homologs include a lectin from Burkholderia cenocepacia, the C1q component of complement, and a portion of the Bacillus anthracis spore surface protein BclA, all of which play roles in bioadhesion. The N-terminal domain consists of a concatenation of structural motifs typically found in trimeric viral proteins. The central parallel triple-helical coiled-coil contains an unusual alternating pattern of apolar and polar residue pairs that generate a rare right-handed superhelical twist. The unique architecture of Pgp3 provides the basis for understanding its role in chlamydial pathogenesis and serves as the platform for its optimization as a potential vaccine antigen candidate.
C1 [Galaleldeen, Ahmad; Taylor, Alexander B.; Holloway, Stephen P.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
[Chen, Ding; Hou, Shuping; Gong, Siqi; Zhong, Guangming] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA.
[Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78229 USA.
[Galaleldeen, Ahmad] St Marys Univ, Dept Biol Sci, San Antonio, TX 78228 USA.
[Schuermann, Jonathan P.] Cornell Univ, Dept Chem & Chem Biol, Northeastern Collaborat Access Team, Ithaca, NY 14853 USA.
[Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA.
RP Zhong, GM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol, San Antonio, TX 78229 USA.
EM zhongg@uthscsa.edu; pjhart@biochem.uthscsa.edu
FU National Institutes of Health [AI47997, AI64537]; Robert A. Welch
Foundation [AQ-1399]; National Center for Research Resources at the
National Institute of Health [RR-15301]; U.S. Department of Energy,
Office of Basic Energy Sciences [W-31-109-ENG-38]; Cancer Therapy &
Research Center Cancer Center [NCI P30CA054174]; United States
Department of Defense to the UTSA/UTHSCSA Center for Excellence in
Genomics Research [W911NF-11-1-0136]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants AI47997 and AI64537 (to G.Z.). This work was also
supported by Robert A. Welch Foundation Grant AQ-1399 (to P.J.H.). This
work is partially the result of research conducted at the Northeastern
Collaborative Access Team beamlines of the Advanced Photon Source,
supported by Award RR-15301 from the National Center for Research
Resources at the National Institute of Health. Use of the Advanced
Photon Source is supported by the U.S. Department of Energy, Office of
Basic Energy Sciences under Contract W-31-109-ENG-38. This work was also
supported in part by Cancer Therapy & Research Center Cancer Center
Support Grant NCI P30CA054174 and Contract Number W911NF-11-1-0136 from
the United States Department of Defense to the UTSA/UTHSCSA Center for
Excellence in Genomics Research.
NR 76
TC 6
Z9 8
U1 1
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 26
PY 2013
VL 288
IS 30
BP 22068
EP 22079
DI 10.1074/jbc.M113.475012
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 277TJ
UT WOS:000328841900052
PM 23703617
ER
PT J
AU Fernandez, TF
Samal, AB
Bedwell, GJ
Chen, YB
Saad, JS
AF Fernandez, Timothy F.
Samal, Alexandra B.
Bedwell, Gregory J.
Chen, Yabing
Saad, Jamil S.
TI Structural and Biophysical Characterization of the Interactions between
the Death Domain of Fas Receptor and Calmodulin
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Apoptosis; Calmodulin; Fas; NMR; Surface Plasmon Resonance (SPR);
Cholangiocarcinoma
ID SIZE-DISTRIBUTION ANALYSIS; HIV-1 MATRIX PROTEIN; CHOLANGIOCARCINOMA
CELLS; ANALYTICAL ULTRACENTRIFUGATION; TARGET RECOGNITION; BINDING
DOMAIN; PEPTIDE INTERACTION; MEDIATED APOPTOSIS; INHIBITORY PROTEIN;
NMR-SPECTROSCOPY
AB The extrinsic apoptotic pathway is initiated by cell surface death receptors such as Fas. Engagement of Fas by Fas ligand triggers a conformational change that allows Fas to interact with adaptor protein Fas-associated death domain (FADD) via the death domain, which recruits downstream signaling proteins to form the death-inducing signaling complex (DISC). Previous studies have shown that calmodulin (CaM) is recruited into the DISC in cholangiocarcinoma cells, suggesting a novel role of CaM in Fas-mediated signaling. CaM antagonists induce apoptosis through a Fas-related mechanism in cholangiocarcinoma and other cancer cell lines possibly by inhibiting Fas-CaM interactions. The structural determinants of Fas-CaM interaction and the underlying molecular mechanisms of inhibition, however, are unknown. Here we employed NMR and biophysical techniques to elucidate these mechanisms. Our data show that CaM binds to the death domain of Fas (FasDD) with an apparent dissociation constant (K-d) of approximate to 2 m and 2:1 CaM:FasDD stoichiometry. The interactions between FasDD and CaM are endothermic and entropically driven, suggesting that hydrophobic contacts are critical for binding. We also show that both the N- and C-terminal lobes of CaM are important for binding. NMR and surface plasmon resonance data show that three CaM antagonists (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide, tamoxifen, and trifluoperazine) greatly inhibit Fas-CaM interactions by blocking the Fas-binding site on CaM. Our findings provide the first structural evidence for Fas-CaM interactions and mechanism of inhibition and provide new insight into the molecular basis for a novel role of CaM in regulating Fas-mediated apoptosis.
C1 [Fernandez, Timothy F.; Samal, Alexandra B.; Bedwell, Gregory J.; Saad, Jamil S.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Chen, Yabing] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Chen, Yabing] Birmingham Vet Affairs Med Ctr, Res Dept, Birmingham, AL 35294 USA.
RP Saad, JS (reprint author), 845 19th St S, Birmingham, AL 35294 USA.
EM saad@uab.edu
FU NCI, National Institutes of Health (NIH) [P30CA13148]; NIH
[1S10RR026478]
FX We thank members of our laboratories and Dr. Jay McDonald (University of
Alabama at Birmingham) for helpful discussions. We thank Diego Esposito
and Paul Driscoll (Medical Research Council National Institute for
Medical Research, United Kingdom) for providing NMR signal assignments
of FasDD. We thank the University of Alabama Comprehensive Cancer Center
X-ray core facility, funded by NCI, National Institutes of Health (NIH)
Grant P30CA13148, which houses the Auto-ITC200, acquired
through NIH Grant 1S10RR026478.
NR 68
TC 11
Z9 11
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 26
PY 2013
VL 288
IS 30
AR 21898
DI 10.1074/jbc.M113.471821
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 277TJ
UT WOS:000328841900038
PM 23760276
ER
PT J
AU Izamis, ML
Tolboom, H
Uygun, B
Berthiaume, F
Yarmush, ML
Uygun, K
AF Izamis, Maria-Louisa
Tolboom, Herman
Uygun, Basak
Berthiaume, Francois
Yarmush, Martin L.
Uygun, Korkut
TI Resuscitation of Ischemic Donor Livers with Normothermic Machine
Perfusion: A Metabolic Flux Analysis of Treatment in Rats
SO PLOS ONE
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; CYTOCHROME-C-OXIDASE; FATTY-ACID OXIDATION;
NITRIC-OXIDE; REPERFUSION INJURY; CULTURED-HEPATOCYTES; MITOCHONDRIAL
RESPIRATION; EXTRACORPOREAL PERFUSION; COLD-STORAGE; TRANSPLANTATION
AB Normothermic machine perfusion has previously been demonstrated to restore damaged warm ischemic livers to transplantable condition in animal models. However, the mechanisms of recovery are unclear, preventing rational optimization of perfusion systems and slowing clinical translation of machine perfusion. In this study, organ recovery time and major perfusate shortcomings were evaluated using a comprehensive metabolic analysis of organ function in perfusion prior to successful transplantation. Two groups, Fresh livers and livers subjected to 1 hr of warm ischemia (WI) received perfusion for a total preservation time of 6 hrs, followed by successful transplantation. 24 metabolic fluxes were directly measured and 38 stoichiometrically-related fluxes were estimated via a mass balance model of the major pathways of energy metabolism. This analysis revealed stable metabolism in Fresh livers throughout perfusion while identifying two distinct metabolic states in WI livers, separated at t = 2 hrs, coinciding with recovery of oxygen uptake rates to Fresh liver values. This finding strongly suggests successful organ resuscitation within 2 hrs of perfusion. Overall perfused livers regulated metabolism of perfusate substrates according to their metabolic needs, despite supraphysiological levels of some metabolites. This study establishes the first integrative metabolic basis for the dynamics of recovery during perfusion treatment of marginal livers. Our initial findings support enhanced oxygen delivery for both timely recovery and long-term sustenance. These results are expected to lead the optimization of the treatment protocols and perfusion media from a metabolic perspective, facilitating translation to clinical use.
C1 [Izamis, Maria-Louisa; Uygun, Basak; Yarmush, Martin L.; Uygun, Korkut] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA.
[Izamis, Maria-Louisa; Uygun, Basak; Yarmush, Martin L.; Uygun, Korkut] Shriners Hosp Children, Boston, MA USA.
[Tolboom, Herman] Univ Zurich Hosp, Div Cardiac & Vasc Surg, CH-8091 Zurich, Switzerland.
[Berthiaume, Francois; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA.
RP Uygun, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA.
EM uygun.korkut@mgh.harvard.edu
RI Uygun, Basak/I-1792-2012
OI Uygun, Basak/0000-0002-2600-7900
FU National Institutes of Health [R01DK096075, R01EB008678, R00DK080942,
K99DK088962]; Shriners Hospitals for Children
FX This work was supported by grants from the National Institutes of Health
(R01DK096075, R01EB008678, R00DK080942, K99DK088962), and the Shriners
Hospitals for Children. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 62
TC 11
Z9 13
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 26
PY 2013
VL 8
IS 7
AR e69758
DI 10.1371/journal.pone.0069758
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197GU
UT WOS:000322838900078
PM 23922793
ER
PT J
AU Saeidi, N
Meoli, L
Nestoridi, E
Gupta, NK
Kvas, S
Kucharczyk, J
Bonab, AA
Fischman, AJ
Yarmush, ML
Stylopoulos, N
AF Saeidi, Nima
Meoli, Luca
Nestoridi, Eirini
Gupta, Nitin K.
Kvas, Stephanie
Kucharczyk, John
Bonab, Ali A.
Fischman, Alan J.
Yarmush, Martin L.
Stylopoulos, Nicholas
TI Reprogramming of Intestinal Glucose Metabolism and Glycemic Control in
Rats After Gastric Bypass
SO SCIENCE
LA English
DT Article
ID BARIATRIC SURGERY; INSULIN SENSITIVITY; CELL-PROLIFERATION; MEDICAL
THERAPY; TRANSPORT; MODEL; MICE
AB The resolution of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) attests to the important role of the gastrointestinal tract in glucose homeostasis. Previous studies in RYGB-treated rats have shown that the Roux limb displays hyperplasia and hypertrophy. Here, we report that the Roux limb of RYGB-treated rats exhibits reprogramming of intestinal glucose metabolism to meet its increased bioenergetic demands; glucose transporter-1 is up-regulated, basolateral glucose uptake is enhanced, aerobic glycolysis is augmented, and glucose is directed toward metabolic pathways that support tissue growth. We show that reprogramming of intestinal glucose metabolism is triggered by the exposure of the Roux limb to undigested nutrients. We demonstrate by positron emission tomography-computed tomography scanning and biodistribution analysis using 2-deoxy-2-[18F]fluoro-D-glucose that reprogramming of intestinal glucose metabolism renders the intestine a major tissue for glucose disposal, contributing to the improvement in glycemic control after RYGB.
C1 [Saeidi, Nima; Meoli, Luca; Nestoridi, Eirini; Gupta, Nitin K.; Kvas, Stephanie; Kucharczyk, John; Stylopoulos, Nicholas] Harvard Univ, Sch Med, Ctr Basic & Translat Obes Res, Div Endocrinol,Boston Childrens Hosp, Boston, MA 02115 USA.
[Saeidi, Nima; Bonab, Ali A.; Fischman, Alan J.; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA 02114 USA.
[Saeidi, Nima; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA.
RP Stylopoulos, N (reprint author), Harvard Univ, Sch Med, Ctr Basic & Translat Obes Res, Div Endocrinol,Boston Childrens Hosp, Boston, MA 02115 USA.
EM Nicholas.Stylopoulos@childrens.harvard.edu
RI Gupta, Nitin/A-1076-2016
OI Gupta, Nitin/0000-0002-4471-2363
FU Department of Medicine; Clinical and Translational Executive Committee
at Boston Children's Hospital; National Institutes of Health (NIH)
[T32DK007191, F32DK095558]; NIH [DK089503]
FX We thank N. Li for help with tissue sectioning, G. Gorski for help with
electron microscopy, M. Markle and M. Luitje for help with
biodistribution analysis, and A. Moses for help with lipid analysis.
This research was supported by funds from the Department of Medicine and
the Clinical and Translational Executive Committee at Boston Children's
Hospital (N. Stylopoulos) and grants T32DK007191 (N. K. G.) and
F32DK095558 (N. Saeidi) from the National Institutes of Health (NIH). We
used the core services of the Lipidomics Lab at the Nutrition Obesity
Research Center of the University of Michigan (Ann Arbor, MI), which is
supported by grant DK089503 from NIH.
NR 31
TC 112
Z9 116
U1 1
U2 54
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUL 26
PY 2013
VL 341
IS 6144
BP 406
EP 410
DI 10.1126/science.1235103
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 189HX
UT WOS:000322259200052
PM 23888041
ER
PT J
AU Edwards, AL
Gavathiotis, E
LaBelle, JL
Braun, CR
Opoku-Nsiah, KA
Bird, GH
Walensky, LD
AF Edwards, Amanda L.
Gavathiotis, Evripidis
LaBelle, James L.
Braun, Craig R.
Opoku-Nsiah, Kwadwo A.
Bird, Gregory H.
Walensky, Loren D.
TI Multimodal Interaction with BCL-2 Family Proteins Underlies the
Proapoptotic Activity of PUMA BH3
SO CHEMISTRY & BIOLOGY
LA English
DT Article
ID STABILIZED ALPHA-HELICES; BH3-ONLY PROTEINS; INDUCED APOPTOSIS;
CELL-DEATH; BAX ACTIVATION; MITOCHONDRIAL APOPTOSIS;
CONFORMATIONAL-CHANGE; NEURONAL APOPTOSIS; PROMOTE APOPTOSIS; IN-VIVO
AB PUMA is a proapoptotic BCL-2 family member that drives the apoptotic response to a diversity of cellular insults. Deciphering the spectrum of PUMA interactions that confer its context-dependent proapoptotic properties remains a high priority goal. Here, we report the synthesis of PUMA SAHBs, structurally stabilized PUMA BH3 helices that, in addition to broadly targeting antiapoptotic proteins, directly bind to proapoptotic BAX. NMR, photocrosslinking, and biochemical analyses revealed that PUMA SAHBs engage an alpha 1/alpha 6 trigger site on BAX to initiate its functional activation. We further demonstrated that a cell-permeable PUMA SAHB analog induces apoptosis in neuroblastoma cells and, like expressed PUMA protein, engages BCL-2, MCL-1, and BAX. Thus, we find that PUMA BH3 is a dual antiapoptotic inhibitor and proapoptotic direct activator, and its mimetics may serve as effective pharmacologic triggers of apoptosis in resistant human cancers.
C1 [Edwards, Amanda L.; Gavathiotis, Evripidis; LaBelle, James L.; Braun, Craig R.; Opoku-Nsiah, Kwadwo A.; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Linde Program Canc Chem Biol, Dept Pediat Oncol, Boston, MA 02215 USA.
RP Walensky, LD (reprint author), Dana Farber Canc Inst, Linde Program Canc Chem Biol, Dept Pediat Oncol, Boston, MA 02215 USA.
EM loren_walensky@dfci.harvard.edu
FU National Institutes of Health [5R01CA050239, 5R01GM090299]; Stand Up to
Cancer Innovative Research Grant; National Science Foundation Graduate
Research Fellowship
FX We thank E. Smith for editorial and graphics assistance, R. George and
T. Look for neuroblastoma cell lines, and D. Andrews for guidance on the
liposomal assay system. This work was supported by grants from the
National Institutes of Health (5R01CA050239 and 5R01GM090299), a Stand
Up to Cancer Innovative Research Grant (to L.D.W.), and a National
Science Foundation Graduate Research Fellowship (to A.L.E.). L.D.W. is a
scientific advisory board member and consultant for Aileron
Therapeutics.
NR 66
TC 29
Z9 30
U1 0
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
J9 CHEM BIOL
JI Chem. Biol.
PD JUL 25
PY 2013
VL 20
IS 7
BP 888
EP 902
DI 10.1016/j.chembiol.2013.06.007
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 195FL
UT WOS:000322687600006
PM 23890007
ER
PT J
AU Ballen, KK
Gluckman, E
Broxmeyer, HE
AF Ballen, Karen K.
Gluckman, Eliane
Broxmeyer, Hal E.
TI Umbilical cord blood transplantation: the first 25 years and beyond
SO BLOOD
LA English
DT Review
ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; MYELOABLATIVE
CONDITIONING REGIMEN; MULTIPOTENTIAL PROGENITOR CELLS;
VERSUS-HOST-DISEASE; ANTI-HLA ANTIBODIES; HEMATOPOIETIC STEM; UNRELATED
DONOR; ACUTE-LEUKEMIA; FANCONI-ANEMIA
AB Umbilical cord blood is an alternative hematopoietic stem cell source for patients with hematologic diseases who can be cured by allogeneic hematopoietic cell transplantation. Initially, umbilical cord blood transplantation was limited to children, given the low cell dose infused. Both related and unrelated cord blood transplants have been performed with high rates of success for a variety of hematologic disorders and metabolic storage diseases in the pediatric setting. The results for adult umbilical cord blood transplantation have improved, with greater emphasis on cord blood units of sufficient cell dose and human leukocyte antigen match and with the use of double umbilical cord blood units and improved supportive care techniques. Cord blood expansion trials have recently shown improvement in time to engraftment. Umbilical cord blood is being compared with other graft sources in both retrospective and prospective trials. The growth of the field over the last 25 years and the plans for future exploration are discussed.
C1 [Ballen, Karen K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Gluckman, Eliane] Univ Paris Diderot, Eurocord Hosp St Louis, APHP, Paris, France.
[Broxmeyer, Hal E.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Suite 118, Boston, MA 02114 USA.
EM kballen@partners.org
FU NHLBI NIH HHS [R01 HL067384, R01 HL112669]
NR 97
TC 163
Z9 168
U1 5
U2 29
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUL 25
PY 2013
VL 122
IS 4
BP 491
EP 498
DI 10.1182/blood-2013-02-453175
PG 8
WC Hematology
SC Hematology
GA 196RD
UT WOS:000322792300009
PM 23673863
ER
PT J
AU Salzer, WL
Asselin, B
Supko, JG
Devidas, M
Kaiser, NA
Plourde, P
Winick, NJ
Reaman, GH
Raetz, E
Carroll, WL
Hunger, SP
AF Salzer, Wanda L.
Asselin, Barbara
Supko, Jeffrey G.
Devidas, Meenakshi
Kaiser, Nicole A.
Plourde, Paul
Winick, Naomi J.
Reaman, Gregory H.
Raetz, Elizabeth
Carroll, William L.
Hunger, Stephen P.
TI Erwinia asparaginase achieves therapeutic activity after pegaspargase
allergy: a report from the Children's Oncology Group
SO BLOOD
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ESCHERICHIA-COLI-ASPARAGINASE; ACUTE
LYMPHOCYTIC-LEUKEMIA; CANCER-STUDY-GROUP; CEREBROSPINAL-FLUID; E. COLI;
INTENSIVE ASPARAGINASE; PEG-ASPARAGINASE; SINGLE-AGENT; PHARMACOKINETICS
AB AALL07P2 evaluated whether substitution of Erwinia asparaginase 25 000 IU/m(2) for 6 doses given intramuscularly Monday/Wednesday/Friday (M/W/F) to children and young adults with acute lymphoblastic leukemia and clinical allergy to pegaspargase would provide a 48-hour nadir serum asparaginase activity (NSAA) >= 0.10 IU/mL. AALL07P2 enrolled 55 eligible/evaluable patients. NSAA >= 0.1 IU/mL was achieved in 38 of 41 patients (92.7%) with acceptable samples 48 hours and in 38 of 43 patients (88.4%) 72 hours after dosing during course 1. Among samples obtained during all courses, 95.8% (252 of 263) of 48-hour samples and 84.5% (125 of 148) of 72-hour samples had NSAA >= 0.10-IU/mL. Pharmacokinetic parameters were estimated by fitting the serum asparaginase activity-time course for all 6 doses given during course 1 to a 1-compartment open model with first order absorption. Erwinia asparaginase administered with this schedule achieved therapeutic NSAA at both 48 and 72 hours and was well tolerated with no reports of hemorrhage, thrombosis, or death, and few cases of grade 2 to 3 allergic reaction (n = 6), grade 1 to 3 hyperglycemia (n = 6), or grade 1 pancreatitis (n = 1). Following allergy to pegaspargase, Erwinia asparaginase 25 000 IU/m(2) x 6 intramuscularly M/W/F can be substituted for a single dose of pegaspargase.
C1 [Salzer, Wanda L.] US Army Med Res & Mat Command, Ft Detrick, MD 21702 USA.
[Asselin, Barbara] Univ Rochester, Sch Med, Dept Pediat, Golisano Childrens Hosp,Med Ctr, Rochester, NY 14642 USA.
[Supko, Jeffrey G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Devidas, Meenakshi] Univ Florida, Dept Biostat, Coll Med, Coll Publ Hlth & Hlth Profess, Gainesville, FL USA.
[Kaiser, Nicole A.; Hunger, Stephen P.] Childrens Hosp Colorado, Aurora, CO USA.
[Plourde, Paul] EUSA Pharma, Langhorne, PA USA.
[Winick, Naomi J.] Univ Texas SW Med Ctr Dallas, Div Pediat Hematol Oncol, Dallas, TX 75390 USA.
[Reaman, Gregory H.] Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA.
[Raetz, Elizabeth] NYU, Langone Med Ctr, New York, NY USA.
[Carroll, William L.] NYU, Inst Canc, New York, NY USA.
[Hunger, Stephen P.] Univ Colorado, Dept Pediat, Sch Med, Aurora, CO USA.
[Hunger, Stephen P.] Childrens Hosp Colorado, Aurora, CO USA.
RP Salzer, WL (reprint author), US Army Med Res & Mat Command, Combat Casualty Care Res Program, 504 Scott St, Ft Detrick, MD 21702 USA.
EM wanda.l.salzer.mil@mail.mil
FU National Institutes of Health [CA13539, CA98543]
FX This work was supported by grants CA13539 and CA98543 from the National
Institutes of Health and a research agreement with Jazz Pharma, Inc
(Langhorne, PA), formerly EUSA Pharma, Inc. S. P. H. is the Ergen Family
Chair in Pediatric Cancer.
NR 50
TC 19
Z9 19
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUL 25
PY 2013
VL 122
IS 4
BP 507
EP 514
DI 10.1182/blood-2013-01-480822
PG 8
WC Hematology
SC Hematology
GA 196RD
UT WOS:000322792300011
PM 23741010
ER
PT J
AU Huik, K
Avi, R
Carrillo, A
Harper, N
Pauskar, M
Sadam, M
Karki, T
Krispin, T
Kongo, UK
Jermilova, T
Ruutel, K
Talu, A
Abel-Ollo, K
Uuskula, A
Ahuja, SK
He, WJ
Lutsar, I
AF Huik, Kristi
Avi, Radko
Carrillo, Andrew
Harper, Nathan
Pauskar, Merit
Sadam, Maarja
Karki, Tonis
Krispin, Tonu
Kongo, Ulvi-Kaire
Jermilova, Tatiana
Rueuetel, Kristi
Talu, Ave
Abel-Ollo, Katri
Uuskuela, Anneli
Ahuja, Sunil K.
He, Weijing
Lutsar, Irja
TI CCR5 Haplotypes Influence HCV Serostatus in Caucasian Intravenous Drug
Users
SO PLOS ONE
LA English
DT Article
ID CHRONIC HEPATITIS-C; HUMAN-IMMUNODEFICIENCY-VIRUS; DISEASE PROGRESSION;
HIV-1 INFECTION; INJECT DRUGS; CHEMOKINE; EXPRESSION; CCR5-DELTA-32;
ASSOCIATION; FREQUENCY
AB Background: Up to 90% HIV-1 positive intravenous drug users (IDUs) are co-infected with HCV. Although best recognized for its function as a major co-receptor for cell entry of HIV, CC chemokine receptor 5 (CCR5) has also been implicated in the pathogenesis of HCV infection. Here, we investigated whether CCR5 haplotypes influence HIV-1 and HCV seropositivity among 373 Caucasian IDUs from Estonia.
Methods: Of these IDUs, 56% and 44% were HIV and HCV seropositive, respectively, and 47% were coinfected. 500 blood donors seronegative for HIV and HCV were also evaluated. CCR5 haplotypes (HHA to HHG*2) were derived after genotyping nine CCR2-CCR5 polymorphisms. The association between CCR5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis. Co-variates included in the models were length of intravenous drug use, HBV serostatus and copy number of CCL3L1, the gene encoding the most potent HIV-suppressive chemokine and ligand for CCR5.
Results: Compared to IDUs seronegative for both HCV and HIV (HCV2/HIV-), IDUs who were HCV+/HIV- and HCV+/HIV+ were 92% and 82%, respectively, less likely to possess the CCR5-HHG*1 haplotype, after controlling for co-variates (P-adjusted = 1.89x10(-4) and 0.003, respectively). This association was mostly due to subjects bearing the CCR5 HHE and HHG*1 haplotype pairs. Approximately 25% and < 10% of HCV-/HIV- IDUs and HCV2/HIV- blood donors, respectively, possessed the HHE/HHG*1 genotype.
Conclusions: Our findings suggest that HHG*1-bearing CCR5 genotypes influence HCV seropositivity in a group of Caucasian IDUs.
C1 [Huik, Kristi; Avi, Radko; Pauskar, Merit; Sadam, Maarja; Karki, Tonis; Krispin, Tonu; Lutsar, Irja] Univ Tartu, Fac Med, Dept Microbiol, EE-50090 Tartu, Estonia.
[Carrillo, Andrew; Harper, Nathan; Ahuja, Sunil K.; He, Weijing] South Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV 1 Infect, San Antonio, TX USA.
[Carrillo, Andrew; Harper, Nathan; Ahuja, Sunil K.; He, Weijing] South Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX USA.
[Carrillo, Andrew; Harper, Nathan; Ahuja, Sunil K.; He, Weijing] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Kongo, Ulvi-Kaire] North Estonia Med Ctr Fdn, Immunoheamatol Reference Lab, Tallinn, Estonia.
[Jermilova, Tatiana] Blood Ctr Kohtla Jarve, Kohtla Jarve, Estonia.
[Rueuetel, Kristi; Talu, Ave; Abel-Ollo, Katri] Natl Inst Hlth Dev, Tallinn, Estonia.
[Uuskuela, Anneli] Univ Tartu, Fac Med, Dept Publ Hlth, EE-50090 Tartu, Estonia.
RP He, WJ (reprint author), South Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV 1 Infect, San Antonio, TX USA.
EM hew@uthscsa.edu; Irja.Lutsar@ut.ee
RI lutsar, irja/H-3177-2015; Uuskula, Anneli/H-3303-2015
FU Veterans Affairs (VA) Center for AIDS and HIV Infection; VA Center for
Personalized Medicine of the South Texas Veterans Health Care System;
National Institutes of Health (NIH) [R37AI046326]; Doris Duke
Distinguished Clinical Scientist Award; VA MERIT award; Elizabeth Glaser
Pediatric AIDS Foundation; Max and Minnie Tomerlin Voelcker Fund;
European Union through the European Regional Development Fund; Estonian
Science Foundation [8004, 8415, 8856]; Basic Financing and the Target
Financing of Estonian Ministry of Education and Research [SF0180004s12];
European Commission funded project Expanding Network for Comprehensive;
Coordinated Action on HIV/AIDS prevention among IDUs and Bridging
Population [2005305]; Global Fund; National HIV/AIDS Strategy; US
Civilian Research Development Foundation [ESX0-2722-TA06]; US National
Institutes of Health, National Institute on Drug Abuse [R01DA03574];
Archimedes Foundation and Norwegian Financial Mechanism/ EEA [EE0016]
FX The work at San Antonio was supported by the Veterans Affairs (VA)
Center for AIDS and HIV Infection and VA Center for Personalized
Medicine of the South Texas Veterans Health Care System, a National
Institutes of Health (NIH) MERIT grant (R37AI046326), and the Doris Duke
Distinguished Clinical Scientist Award to S.K.A. S.K.A. is also
supported by a VA MERIT award, the Elizabeth Glaser Pediatric AIDS
Foundation, the Burroughs Welcome Clinical Scientist Award in
Translational Research and the Senior Scholar Award from the Max and
Minnie Tomerlin Voelcker Fund. The work at Estonia was supported by
European Union through the European Regional Development Fund; Estonian
Science Foundation (grants 8004, 8415 and 8856); Basic Financing and the
Target Financing of Estonian Ministry of Education and Research
(SF0180004s12); European Commission funded project Expanding Network for
Comprehensive and Coordinated Action on HIV/AIDS prevention among IDUs
and Bridging Population Nr. 2005305 (ENCAP); Global Fund to Fight HIV,
Tuberculosis and Malaria Program "Scaling up the response to HIV in
Estonia'' for 2003-2007; National HIV/AIDS Strategy for 2006-2015; US
Civilian Research Development Foundation (grant ESX0-2722-TA06); US
National Institutes of Health, National Institute on Drug Abuse (grant
R01DA03574); the Archimedes Foundation and Norwegian Financial
Mechanism/EEA(grant EE0016). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 42
TC 1
Z9 1
U1 0
U2 5
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 JUL 25
PY 2013
VL 8
IS 7
AR e70561
DI 10.1371/journal.pone.0070561
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 191SQ
UT WOS:000322433300109
PM 23936229
ER
PT J
AU Schulze, MSED
Anders, AK
Sethi, DK
Call, MJ
AF Schulze, Monika-Sarah E. D.
Anders, Anne-Kathrin
Sethi, Dhruv K.
Call, Melissa J.
TI Disruption of Hydrogen Bonds between Major Histocompatibility Complex
Class II and the Peptide N-Terminus Is Not Sufficient to Form a Human
Leukocyte Antigen-DM Receptive State of Major Histocompatibility Complex
Class II
SO PLOS ONE
LA English
DT Article
ID HLA-DR MOLECULES; HIGH-AFFINITY BINDING; CRYSTAL-STRUCTURE; PROTEIN
HLA-DR1; BOUND PEPTIDES; MHC; CHAIN; DISSOCIATION; EXCHANGE;
SUSCEPTIBILITY
AB Peptide presentation by MHC class II is of critical importance to the function of CD4+ T cells. HLA-DM resides in the endosomal pathway and edits the peptide repertoire of newly synthesized MHC class II molecules before they are exported to the cell surface. HLA-DM ensures MHC class II molecules bind high affinity peptides by targeting unstable MHC class II: peptide complexes for peptide exchange. Research over the past decade has implicated the peptide N-terminus in modulating the ability of HLA-DM to target a given MHC class II: peptide combination. In particular, attention has been focused on both the hydrogen bonds between MHC class II and peptide, and the occupancy of the P1 anchor pocket. We sought to solve the crystal structure of a HLA-DR1 molecule containing a truncated hemagglutinin peptide missing three N-terminal residues compared to the full-length sequence (residues 306-318) to determine the nature of the MHC class II: peptide species that binds HLA-DM. Here we present structural evidence that HLA-DR1 that is loaded with a peptide truncated to the P1 anchor residue such that it cannot make select hydrogen bonds with the peptide N-terminus, adopts the same conformation as molecules loaded with full-length peptide. HLA-DR1: peptide combinations that were unable to engage up to four key hydrogen bonds were also unable to bind HLA-DM, while those truncated to the P2 residue bound well. These results indicate that the conformational changes in MHC class II molecules that are recognized by HLA-DM occur after disengagement of the P1 anchor residue.
C1 [Schulze, Monika-Sarah E. D.; Anders, Anne-Kathrin; Sethi, Dhruv K.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Anders, Anne-Kathrin] Harvard Univ, Sch Med, Program Immunol, Boston, MA USA.
[Call, Melissa J.] Univ Melbourne, Struct Biol Div, Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
RP Call, MJ (reprint author), Univ Melbourne, Struct Biol Div, Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
EM call@wehi.edu.au
FU Australian Research Council Future Fellowship [FT120100145]; National
Multiple Sclerosis Society; National Institutes of Health
[5R01NS044914]; National Cancer Institute [Y1-CO-1020]; National
Institute of General Medical Sciences [Y1-GM-1104]; U.S. DOE
[DE-AC02-06CH11357]
FX MJC is supported by an Australian Research Council Future Fellowship
(FT120100145) and DKS is supported by a Postdoctoral Fellowship from The
National Multiple Sclerosis Society. This work was supported by the
National Institutes of Health (5R01NS044914). Diffraction data were
collected at the Advanced Photon Source using beamline 23-ID-D of the
General Medicine and Cancer Institutes Collaborative Access Team, which
is supported by grants from the National Cancer Institute (Y1-CO-1020)
and the National Institute of General Medical Sciences (Y1-GM-1104). Use
of the Advanced Photon Source, an Office of Science User Facility
operated for the U.S. Department of Energy (DOE) Office of Science by
Argonne National Laboratory, was supported by the U.S. DOE under
Contract No. DE-AC02-06CH11357. We thank the Dana-Farber Molecular
Biology Core Facility for Mass Spectrometry measurements. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 46
TC 5
Z9 6
U1 0
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 JUL 25
PY 2013
VL 8
IS 7
AR e69228
DI 10.1371/journal.pone.0069228
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 191SQ
UT WOS:000322433300028
PM 23976922
ER
PT J
AU Kalantar-Zadeh, K
Uppot, RN
Lewandrowski, KB
AF Kalantar-Zadeh, Kamyar
Uppot, Raul N.
Lewandrowski, Kent B.
TI Case 23-2013: A 54-Year-Old Woman with Abdominal Pain, Vomiting, and
Confusion
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID LACTIC-ACIDOSIS; RENAL-FAILURE; PANCREATITIS; INTOXICATION; DIALYSIS
C1 [Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Dept Med, Orange, CA 92717 USA.
[Uppot, Raul N.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Lewandrowski, Kent B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Uppot, Raul N.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA.
[Lewandrowski, Kent B.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA.
RP Kalantar-Zadeh, K (reprint author), Univ Calif Irvine, Dept Med, Orange, CA 92717 USA.
NR 19
TC 14
Z9 14
U1 0
U2 5
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 25
PY 2013
VL 369
IS 4
BP 374
EP 382
DI 10.1056/NEJMcpc1208154
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 188VJ
UT WOS:000322223900013
PM 23841704
ER
PT J
AU Ackerman, M
Alter, G
AF Ackerman, Margaret
Alter, Galit
TI Mapping the Journey to an HIV Vaccine
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID BROAD
C1 [Ackerman, Margaret] Dartmouth Coll, Sch Engn, Hanover, NH 03755 USA.
[Alter, Galit] MIT, Ragon Inst, Massachusetts Gen Hosp, Cambridge, MA 02139 USA.
[Alter, Galit] Harvard Univ, Cambridge, MA 02138 USA.
RP Ackerman, M (reprint author), Dartmouth Coll, Sch Engn, Hanover, NH 03755 USA.
NR 5
TC 9
Z9 9
U1 0
U2 8
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 25
PY 2013
VL 369
IS 4
BP 389
EP 391
DI 10.1056/NEJMcibr1304437
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 188VJ
UT WOS:000322223900016
PM 23883384
ER
PT J
AU McEvoy, J
Baillie, RA
Zhu, HJ
Buckley, P
Keshavan, MS
Nasrallah, HA
Dougherty, GG
Yao, JK
Kaddurah-Daouk, R
AF McEvoy, Joseph
Baillie, Rebecca A.
Zhu, Hongjie
Buckley, Peter
Keshavan, Matcheri S.
Nasrallah, Henry A.
Dougherty, George G.
Yao, Jeffrey K.
Kaddurah-Daouk, Rima
TI Lipidomics Reveals Early Metabolic Changes in Subjects with
Schizophrenia: Effects of Atypical Antipsychotics
SO PLOS ONE
LA English
DT Article
ID FATTY-ACIDS; SEROTONIN
AB There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naive patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease.
C1 [McEvoy, Joseph; Zhu, Hongjie; Kaddurah-Daouk, Rima] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27708 USA.
[Baillie, Rebecca A.] Rosa & Co LLC, San Carlos, CA USA.
[Buckley, Peter] Med Coll Georgia, Augusta, GA 30912 USA.
[Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Keshavan, Matcheri S.] Harvard Univ, Sch Med, Boston, MA USA.
[Nasrallah, Henry A.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Dougherty, George G.; Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
RP Kaddurah-Daouk, R (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27708 USA.
EM kaddu001@mc.duke.edu
FU National Institute of Mental Health (NIMH) [1R01MH084941-01A2];
Department of Veterans Affairs Senior Research Career Scientist Award
FX Funding for this study was provided by National Institute of Mental
Health (NIMH) Grant # 1R01MH084941-01A2 (RKD) and the Department of
Veterans Affairs Senior Research Career Scientist Award (JKY). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 17
TC 24
Z9 25
U1 1
U2 23
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 JUL 24
PY 2013
VL 8
IS 7
AR e68717
DI 10.1371/journal.pone.0068717
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 188BY
UT WOS:000322167900022
PM 23894336
ER
PT J
AU Haslinger, R
Ba, D
Galuske, R
Williams, Z
Pipa, G
AF Haslinger, Robert
Ba, Demba
Galuske, Ralf
Williams, Ziv
Pipa, Gordon
TI Missing mass approximations for the partition function of stimulus
driven lsing models
SO FRONTIERS IN COMPUTATIONAL NEUROSCIENCE
LA English
DT Article
DE lsing model; stimulus coding; population codes; partition function;
multiple unit recordings; network function
ID NEURAL SPIKING ACTIVITY; NEURONAL POPULATION; ENSEMBLE; PATTERNS;
HISTORY; CODES
AB lsing models are routinely used to quantify the second order, functional structure of neural populations. With some recent exceptions, they generally do not include the influence of time varying stimulus drive. Yet if the dynamics of network function are to be understood, time varying stimuli must be taken into account. Inclusion of stimulus drive carries a heavy computational burden because the partition function becomes stimulus dependent and must be separately calculated for all unique stimuli observed. This potentially increases computation time by the length of the data set. Here we present an extremely fast, yet simply implemented, method for approximating the stimulus dependent partition function in minutes or seconds. Noting that the most probable spike patterns (which are few) occur in the training data, we sum partition function terms corresponding to those patterns explicitly. We then approximate the sum over the remaining patterns (which are improbable, but many) by casting it in terms of the stimulus modulated missing mass (total stimulus dependent probability of all patterns not observed in the training data). We use a product of conditioned logistic regression models to approximate the stimulus modulated missing mass. This method has complexity of roughly O(LNNpat) where is L the data length, N the number of neurons and N-pat the number of unique patterns in the data, contrasting with the O(L2(N)) complexity of alternate methods. Using multiple unit recordings from rat hippocampus, macaque DLPFC and cat Area 18 we demonstrate our method requires orders of magnitude less computation time than Monte Carlo methods and can approximate the stimulus driven partition function more accurately than either Monte Carlo methods or deterministic approximations. This advance allows stimuli to be easily included in lsing models making them suitable for studying population based stimulus encoding.
C1 [Haslinger, Robert] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Haslinger, Robert; Ba, Demba] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Galuske, Ralf] Tech Univ Darmstadt, Dept Biol, Darmstadt, Germany.
[Williams, Ziv] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Pipa, Gordon] Univ Osnabruck, Inst Cognit Sci, Dept Neuroinformat, Osnabruck, Germany.
RP Haslinger, R (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA.
EM rob.haslinger@gmail.com
RI Pipa, Gordon/M-1813-2014
OI Pipa, Gordon/0000-0002-3416-2652
FU NIH [K25 N5052422-02, 5R01-HD059852]; PECASE; Whitehall Foundation
FX The authors would like to thank Emery Brown for helpful conversations
regarding the research presented in this paper and also the use of his
rat hippocampal data. This work was supported by NIH grant K25
N5052422-02 (Robert Haslinger), the Max Planck-Gesellschaft (Ralf
Galuske), and NIH grant 5R01-HD059852, PECASE and the Whitehall
Foundation (Ziv Williams).
NR 71
TC 1
Z9 1
U1 0
U2 2
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5188
J9 FRONT COMPUT NEUROSC
JI Front. Comput. Neurosci.
PD JUL 24
PY 2013
VL 7
AR UNSP 96
DI 10.3389/fncom.2013.00096
PG 21
WC Mathematical & Computational Biology; Neurosciences
SC Mathematical & Computational Biology; Neurosciences & Neurology
GA 192TW
UT WOS:000322509300001
PM 23898262
ER
PT J
AU Zhang, XL
Poschel, B
Faul, C
Upreti, C
Stanton, PK
Mundel, P
AF Zhang, Xiao-lei
Poeschel, Beatrice
Faul, Christian
Upreti, Chirag
Stanton, Patric K.
Mundel, Peter
TI Essential Role for Synaptopodin in Dendritic Spine Plasticity of the
Developing Hippocampus
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID LONG-TERM POTENTIATION; SCHAFFER COLLATERAL-CA1 SYNAPSES;
ACTIN-ASSOCIATED PROTEIN; SYNAPTIC PLASTICITY; PRESYNAPTIC RELEASE;
KIDNEY PODOCYTES; AMPA RECEPTORS; NITRIC-OXIDE; VESICLE POOL; LATE-PHASE
AB Dendritic spines are a major substrate of brain plasticity. Although many studies have focused on Ca2+/calmodulin-dependent protein kinase II (CaMKII)-mediated regulation of spine dynamics and synaptic function in adult brain, much less is know about protein kinase A (PKA)-dependent regulation of spine shape dynamics during postnatal brain development. Synaptopodin is a dendritic spine associated modulator of actin dynamics and a substrate of PKA. Here we show that NMDA and cAMP-induced dendritic spine expansion is impaired in hippocampal slices from 15- and 21-d-old synaptopodin-deficient mice. We further show that synaptopodin is required for full expression of PKA-dependent hippocampal long-term potentiation in 15- and 21-d-old, but not adult, mice. PKA-induced cAMP response element-binding phosphorylation is normal in the hippocampus of synaptopodin-deficient mice, suggesting that synaptopodin functions independently of cAMP response element-binding. Our results identify synaptopodin as a substrate of PKA in hippocampal neurons and point to an essential role for synaptopodin in activity-dependent regulation of dendritic spine dynamics and synaptic plasticity in postnatal brain development.
C1 [Zhang, Xiao-lei; Poeschel, Beatrice; Upreti, Chirag; Stanton, Patric K.] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA.
[Upreti, Chirag; Stanton, Patric K.] New York Med Coll, Dept Neurol, Valhalla, NY 10595 USA.
[Poeschel, Beatrice] Univ Med Ctr Hamburg Eppendorf, Ctr Mol Neurobiol, D-20251 Hamburg, Germany.
[Faul, Christian] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA.
[Mundel, Peter] Harvard Univ, Sch Med, Boston, MA 02129 USA.
[Mundel, Peter] Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA.
RP Mundel, P (reprint author), Massachusetts Gen Hosp, Div Nephrol, 149 13th St, Charlestown, MA 02129 USA.
EM patric_stanton@nymc.edu; mundel.peter@mgh.harvard.edu
FU US National Institutes of Health [DA18886, DK57683, NS044421]
FX This work was supported by US National Institutes of Health Grants
DA18886, DK57683 (to P. M.), and NS044421 (to P.S.). We thank Anna
Greka, Boston, MA, for helpful discussions.
NR 36
TC 19
Z9 19
U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 24
PY 2013
VL 33
IS 30
BP 12510
EP 12518
DI 10.1523/JNEUROSCI.2983-12.2013
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 188CF
UT WOS:000322168600033
PM 23884954
ER
PT J
AU Ferraro, PM
Taylor, EN
Eisner, BH
Gambaro, G
Rimm, EB
Mukamal, KJ
Curhan, GC
AF Ferraro, Pietro Manuel
Taylor, Eric N.
Eisner, Brian H.
Gambaro, Giovanni
Rimm, Eric B.
Mukamal, Kenneth J.
Curhan, Gary C.
TI History of Kidney Stones and the Risk of Coronary Heart Disease
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRE; METABOLIC SYNDROME;
CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; DIETARY CALCIUM;
BLOOD-PRESSURE; UNITED-STATES; NEPHROLITHIASIS; POPULATION; HYPERTENSION
AB IMPORTANCE Kidney stone disease is common and may be associated with an increased risk of coronary heart disease (CHD). Previous studies of the association between kidney stones and CHD have often not controlled for important risk factors, and the results have been inconsistent.
OBJECTIVE To examine the association between a history of kidney stones and the risk of CHD in 3 large prospective cohorts.
DESIGN, SETTING, AND PARTICIPANTS A prospective study of 45 748 men and 196 357 women in the United States without a history of CHD at baseline who were participants in the Health Professionals Follow-up Study (HPFS) (45 748 men aged 40-75 years; follow-up from 1986 to 2010), Nurses' Health Study I (NHS I) (90 235 women aged 30-55 years; follow-up from 1992 to 2010), and Nurses' Health Study II (NHS II) (106 122 women aged 25-42 years; follow-up from 1991 to 2009). The diagnoses of kidney stones and CHD were updated biennially during follow-up.
MAIN OUTCOMES AND MEASURES Coronary heart disease was defined as fatal or nonfatal myocardial infarction (MI) or coronary revascularization. The outcome was identified by biennial questionnaires and confirmed through review of medical records.
RESULTS Of a total of 242 105 participants, 19 678 reported a history of kidney stones. After up to 24 years of follow-up in men and 18 years in women, 16 838 incident cases of CHD occurred. After adjusting for potential confounders, among women, those with a reported history of kidney stones had an increased risk of CHD than those without a history of kidney stones in NHS I (incidence rate [IR], 754 vs 514 per 100 000 person-years; multivariable hazard ratio [HR], 1.18 [95% CI, 1.08-1.28]) and NHS II (IR, 144 vs 55 per 100 000 person-years; multivariable HR, 1.48 [95% CI, 1.23-1.78]). There was no significant association in men (IR, 1355 vs 1022 per 100 000 person-years; multivariable HR, 1.06 [95% CI, 0.99-1.13]). Similar results were found when analyzing the individual end points (fatal and nonfatal MI and revascularization).
CONCLUSIONS AND RELEVANCE Among the 2 cohorts of women, a history of kidney stones was associated with a modest but statistically significantly increased risk of CHD; there was no significant association in a separate cohort of men. Further research is needed to determine whether the association is sex-specific.
C1 [Ferraro, Pietro Manuel; Gambaro, Giovanni] Columbus Gemelli Hosp, Dept Internal Med & Med Specialties, Div Nephrol, Renal Program, Rome, Italy.
[Ferraro, Pietro Manuel; Taylor, Eric N.; Rimm, Eric B.; Curhan, Gary C.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Eisner, Brian H.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Curhan, Gary C.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA.
RP Ferraro, PM (reprint author), Univ Cattolica Sacro Cuore, Dept Internal Med & Med Specialties, Via G Moscati 31, I-00168 Rome, Italy.
EM manuel.ferraro@channing.harvard.edu
RI Ferraro, Pietro Manuel/H-1517-2012
OI Ferraro, Pietro Manuel/0000-0002-1379-022X
FU National Institutes of Health [DK91417, DK70756, CA087969, CA50385,
CA055075, HL034594, HL35464]
FX This work was supported by grants DK91417, DK70756, CA087969, CA50385,
CA055075, HL034594, and HL35464 from the National Institutes of Health.
NR 42
TC 40
Z9 40
U1 1
U2 9
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 JUL 24
PY 2013
VL 310
IS 4
BP 408
EP 415
DI 10.1001/jama.2013.8780
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 187LV
UT WOS:000322121500018
PM 23917291
ER
PT J
AU Simon, NM
AF Simon, Naomi M.
TI Treating Complicated Grief
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID COGNITIVE-BEHAVIORAL THERAPY; BEREAVEMENT-RELATED DEPRESSION; RANDOMIZED
CONTROLLED-TRIAL; DUAL PROCESS MODEL; QUALITY-OF-LIFE; PROLONGED GRIEF;
TRAUMATIC GRIEF; DIAGNOSTIC-CRITERIA; POSTTRAUMATIC STRESS; OLDER-ADULTS
AB IMPORTANCE The death of a loved one is one of life's greatest, universal stressors to which most bereaved individuals successfully adapt without clinical intervention. For a minority of bereaved individuals, grief is complicated by superimposed problems and healing does not occur. The resulting syndrome of complicated grief causes substantial distress and functional impairment even years after a loss, yet knowing when and how to intervene can be a challenge.
OBJECTIVE To discuss the differential diagnosis, risk factors for and management of complicated grief based on available evidence and clinical observations.
EVIDENCE REVIEW MEDLINE was searched from January 1990 to October 2012. Additional citations were procured from references of select research and review articles. Available treatment studies targeting complicated grief were included.
RESULTS A strong research literature led to inclusion of complicated grief in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (termed persistent complex bereavement disorder as a subtype of other specified trauma and stressor-related disorders), although it is a condition for which more research is formally recommended, and there is still ongoing discussion about the optimal name and diagnostic criteria for the disorder. Reliable screening instruments are available, and the estimated prevalence rate is 7% of bereaved people. Randomized controlled data support the efficacy of a targeted psychotherapy including elements that foster resolution of complicating problems and facilitate the natural healing process. Preliminary studies suggest antidepressant medications may be helpful.
CONCLUSION AND RELEVANCE Individuals with complicated grief have greater risk of adverse health outcomes, should be diagnosed and assessed for suicide risk and comorbid conditions such as depression and posttraumatic stress disorder, and should be considered for treatment.
C1 [Simon, Naomi M.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA.
[Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Complicated Grief Program, Boston, MA 02114 USA.
[Simon, Naomi M.] Red Sox Fdn MGH Home Base Program, Boston, MA USA.
RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA.
EM nsimon@partners.org
FU National Institute for Mental Health [5R01MH085308]
FX Clinical Crossroads receives no external support. Dr Simon's work was
supported in part by grant 5R01MH085308 from the National Institute for
Mental Health.
NR 66
TC 25
Z9 25
U1 5
U2 57
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 JUL 24
PY 2013
VL 310
IS 4
BP 416
EP 423
DI 10.1001/jama.2013.8614
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 187LV
UT WOS:000322121500019
PM 23917292
ER
PT J
AU Vemuri, P
Mormino, EC
AF Vemuri, Prashanthi
Mormino, Elizabeth C.
TI Cognitively stimulating activities to keep dementia at bay
SO NEUROLOGY
LA English
DT Editorial Material
ID DISEASE BIOMARKERS; ALZHEIMERS-DISEASE; RESERVE; RISK
C1 [Vemuri, Prashanthi] Mayo Clin, Dept Radiol, Rochester, MN 55902 USA.
[Mormino, Elizabeth C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
RP Vemuri, P (reprint author), Mayo Clin, Dept Radiol, Rochester, MN 55902 USA.
EM vemuri.prashanthi@mayo.edu
NR 10
TC 4
Z9 5
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 23
PY 2013
VL 81
IS 4
BP 308
EP 309
DI 10.1212/WNL.0b013e31829c5f05
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 304JX
UT WOS:000330744000004
PM 23825176
ER
PT J
AU Bohl, C
Bowder, D
Thompson, J
Abrahamyan, L
Gonzalez-Ramirez, S
Mao, YD
Sodroski, J
Wood, C
Xiang, SH
AF Bohl, Christopher
Bowder, Dane
Thompson, Jesse
Abrahamyan, Levon
Gonzalez-Ramirez, Sandra
Mao, Youdong
Sodroski, Joseph
Wood, Charles
Xiang, Shi-hua
TI A Twin-Cysteine Motif in the V2 Region of gp120 Is Associated with SIV
Envelope Trimer Stabilization
SO PLOS ONE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; NEUTRALIZING ANTIBODY PG9; HIV-1 GP120;
MONOCLONAL-ANTIBODIES; VARIABLE LOOPS; V1/V2 DOMAIN; AIDS; INFECTION;
PATHOGENESIS; GLYCOPROTEIN
AB The V1 and V2 variable regions of the primate immunodeficiency viruses contribute to the trimer association domain of the gp120 exterior envelope glycoprotein. A pair of V2 cysteine residues at 183 and 191 ("twin cysteines") is present in several simian immunodeficiency viruses, human immunodeficiency virus type 2 (HIV-2) and some SIVcpz lineages, but not in HIV-1. To examine the role of this potentially disulfide-bonded twin-cysteine motif, the cysteine residues in the SIVmac239 envelope glycoproteins were individually and pairwise substituted by alanine residues. All of the twin-cysteine mutants exhibited decreases in gp120 association with the Env trimer, membrane-fusing activity, and ability to support virus entry. Thus, the twin-cysteine motif plays a role in Env trimer stabilization in SIV and may do so in HIV-2 and some SIVcpz as well. This implies that HIV-1 lost the twin-cysteines, and may have relatively unstable Env trimers compared to SIV and HIV-2.
C1 [Bohl, Christopher; Bowder, Dane; Thompson, Jesse; Abrahamyan, Levon; Gonzalez-Ramirez, Sandra; Wood, Charles; Xiang, Shi-hua] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE USA.
[Thompson, Jesse; Xiang, Shi-hua] Univ Nebraska, Sch Vet Med & Biomed Sci, Lincoln, NE USA.
[Bohl, Christopher; Bowder, Dane; Abrahamyan, Levon; Gonzalez-Ramirez, Sandra; Wood, Charles; Xiang, Shi-hua] Univ Nebraska, Sch Biol Sci, Lincoln, NE USA.
[Mao, Youdong; Sodroski, Joseph] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Mao, Youdong; Sodroski, Joseph] Harvard Univ, Sch Med, Div Aids, Dept Microbiol & Immunol, Boston, MA USA.
[Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Sodroski, Joseph] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA.
RP Xiang, SH (reprint author), Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE USA.
EM sxiang2@unl.edu
RI Abrahamyan, Levon/E-1982-2013
OI Abrahamyan, Levon/0000-0002-0849-0134
FU Bill and Melinda Gates Foundation; National Institutes of Health (NIH)
[AI24755, AI67854]; National Institutes of Health (NIH) (Center for AIDS
Research) [AI060354]; International AIDS Vaccine Initiative; Public
Health Service grants NIGMS COBRE [P30 GM103509, D43 TW001492, T32
AI060547]
FX This work was supported by grants from the Bill and Melinda Gates
Foundation, and the National Institutes of Health (NIH) (AI24755,
AI67854 and Center for AIDS Research Award AI060354), the International
AIDS Vaccine Initiative and the late William F. McCarty-Cooper, and the
Public Health Service grants NIGMS COBRE grant P30 GM103509, D43
TW001492 and T32 AI060547; DB is an NIH Ruth L. Kirschstein Fellow. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 45
TC 7
Z9 7
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 JUL 23
PY 2013
VL 8
IS 7
AR e69406
DI 10.1371/journal.pone.0069406
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 228SX
UT WOS:000325211000114
PM 23936006
ER
PT J
AU Chanda, P
Huang, HL
Arking, DE
Bader, JS
AF Chanda, Pritam
Huang, Hailiang
Arking, Dan E.
Bader, Joel S.
TI Fast Association Tests for Genes with FAST
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; TRAITS; LOCI
AB Gene-based tests of association can increase the power of a genome-wide association study by aggregating multiple independent effects across a gene or locus into a single stronger signal. Recent gene-based tests have distinct approaches to selecting which variants to aggregate within a locus, modeling the effects of linkage disequilibrium, representing fractional allele counts from imputation, and managing permutation tests for p-values. Implementing these tests in a single, efficient framework has great practical value. Fast ASsociation Tests (FAST) addresses this need by implementing leading gene-based association tests together with conventional SNP-based univariate tests and providing a consolidated, easily interpreted report. Fast scales readily to genome-wide SNP data with millions of SNPs and tens of thousands of individuals, provides implementations that are orders of magnitude faster than original literature reports, and provides a unified framework for performing several gene based association tests concurrently and efficiently on the same data. Availability: https://bitbucket.org/baderlab/fast/downloads/FAST.tar.gz, with documentation at https://bitbucket.org/baderlab/fast/wiki/Home
C1 [Chanda, Pritam; Bader, Joel S.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA.
[Chanda, Pritam; Bader, Joel S.] Johns Hopkins Univ, Inst Med Genet, Baltimore, MD USA.
[Chanda, Pritam; Bader, Joel S.] Johns Hopkins Univ, Sch Med, High Throughput Biol Ctr, Baltimore, MD USA.
[Huang, Hailiang] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Huang, Hailiang] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
RP Bader, JS (reprint author), Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA.
EM joel.bader@jhu.edu
OI Huang, Hailiang/0000-0003-1461-5762
FU Robert J. Kleberg Jr. and Helen C. Kleberg Foundation; NSF
[DMS-1228248]; Simons Foundation [SFARI 137603]
FX JSB and PC acknowledge funding from the Robert J. Kleberg Jr. and Helen
C. Kleberg Foundation. JSB and DEA acknowledge funding from the NSF
(DMS-1228248). DEA, JSB, PC and HH acknowledge funding from the Simons
Foundation (SFARI 137603 to DEA). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 22
TC 6
Z9 6
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 JUL 23
PY 2013
VL 8
IS 7
AR e68585
DI 10.1371/journal.pone.0068585
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 228SX
UT WOS:000325211000031
PM 23935874
ER
PT J
AU Kucherlapati, MH
Esfahani, S
Habibollahi, P
Wang, JN
Still, ER
Bronson, RT
Mahmood, U
Kucherlapati, RS
AF Kucherlapati, Melanie H.
Esfahani, Shadi
Habibollahi, Peiman
Wang, Junning
Still, Eric R.
Bronson, Roderick T.
Mahmood, Umar
Kucherlapati, Raju S.
TI Genotype Directed Therapy in Murine Mismatch Repair Deficient Tumors
SO PLOS ONE
LA English
DT Article
ID DUAL PI3K/MTOR INHIBITOR; RENAL-CELL CARCINOMA; SERINE METABOLISM;
CANCER METABOLISM; NVP-BEZ235; PATHWAY; PI3K; IDENTIFICATION;
COMBINATION; ACTIVATION
AB The PI3K/AKT/mTOR pathway has frequently been found activated in human tumors. We show that in addition to Wnt signaling dysfunction, the PI3K/AKT/mTOR pathway is often upregulated in mouse Msh2(-/-) initiated intestinal tumors. NVP-BEZ235 is a dual PI3K/mTOR inhibitor toxic to many cancer cell lines and currently involved in clinical trials. We have treated two mouse models involving Msh2 that develop small intestinal and/or colonic tumors with NVP-BEZ235, and a subset of animals with NVP-BEZ235 and MEK inhibitor ADZ4266. The disease phenotype has been followed with pathology, F-18 FDG PET imaging, and endoscopy. Intestinal adenocarcinomas are significantly decreased in multiplicity by both drug regimens. The majority of tumors treated with combined therapy regress significantly, while a small number of highly progressed tumors persist. We have examined PTEN, AKT, MEK 1&2, MAPK, S6K, mTOR, PDPK1, and Cyclin D1 and find variable alterations that include downregulation of PTEN, upregulation of AKT and changes in its phosphorylated forms, upregulation of pMEK 1&2, p42p44MAPK, pS6K, and Cyclin D1. Apoptosis has been found intact in some tumors and not in others. Our data indicate that NVP-BEZ235 alone and in combination with ADZ4266 are effective in treating a proportion of colorectal cancers, but that highly progressed resistant tumors grow in the presence of the drugs. Pathways upregulated in some resistant tumors also include PDPK1, suggesting that metabolic inhibitors may also be useful in treating these tumors.
C1 [Kucherlapati, Melanie H.; Wang, Junning; Still, Eric R.; Kucherlapati, Raju S.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
[Kucherlapati, Melanie H.; Wang, Junning; Still, Eric R.; Kucherlapati, Raju S.] Brigham & Womens Hosp Boston, Dept Med, Div Genet, Boston, MA USA.
[Esfahani, Shadi; Habibollahi, Peiman; Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA.
[Bronson, Roderick T.] Harvard Univ, Sch Med, Rodent Histopathol Core, Boston, MA USA.
[Bronson, Roderick T.] Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA.
[Bronson, Roderick T.] Tufts Univ, Sch Vet Med, Dept Pathol, Boston, MA 02111 USA.
RP Kucherlapati, RS (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
EM mkucherlapati@partners.org
FU National Cancer Institute (NCI) [5U01CA084301-13]
FX The work in this study was supported by a grant from the National Cancer
Institute (NCI) to Raju S. Kucherlapati and Umar Mahmood, entitled:
Mouse Models for Human Cancer, 5U01CA084301-13. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 33
TC 4
Z9 4
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 23
PY 2013
VL 8
IS 7
AR e68817
DI 10.1371/journal.pone.0068817
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 228SX
UT WOS:000325211000039
PM 23935891
ER
PT J
AU Gibson, CM
Chakrabarti, AK
Mega, J
Bode, C
Bassand, JP
Verheugt, FWA
Bhatt, DL
Goto, S
Cohen, M
Mohanavelu, S
Burton, P
Stone, G
Braunwald, E
AF Gibson, C. Michael
Chakrabarti, Anjan K.
Mega, Jessica
Bode, Christophe
Bassand, Jean-Pierre
Verheugt, Freek W. A.
Bhatt, Deepak L.
Goto, Shinya
Cohen, Marc
Mohanavelu, Satishkumar
Burton, Paul
Stone, Gregg
Braunwald, Eugene
CA ATLAS-ACS 2 TIMI 51 Investigators
TI Reduction of Stent Thrombosis in Patients With Acute Coronary Syndromes
Treated With Rivaroxaban in ATLAS-ACS 2 TIMI 51
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE acute coronary syndrome(s); factor Xa inhibitor; rivaroxaban; stent
thrombosis
ID ANTIPLATELET THERAPY; TRIAL
AB Objectives The aim of this study was to determine if rivaroxaban is associated with a reduction in stent thrombosis among patients with acute coronary syndromes (ACS) in the ATLAS-ACS 2 TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51) trial.
Background Dual antiplatelet therapy (DAPT) has been the mainstay of efforts to prevent stent thrombosis. Because thrombin is a potent stimulant of platelet activation, we hypothesized that inhibition of thrombin generation via factor Xa inhibition may further reduce the risk of stent thrombosis.
Methods The ATLAS-ACS 2 TIMI 51 study was a placebo-controlled trial that randomly assigned 15,526 patients with recent ACS to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months.
Results Among patients who had a stent placed before or at the time of the index event, rivaroxaban significantly reduced independently adjudicated Academic Research Consortium definite and probable stent thrombosis in the pooled (1.9% vs. 1.5%; hazard ratio [HR]: 0.65; p = 0.017) and the 2.5 mg twice-daily (1.9% vs. 1.5%; HR: 0.61; p = 0.023) treatment groups when compared with placebo, with a trend toward a reduction in the 5 mg twice-daily treatment group (1.9% vs. 1.5%; HR: 0.70; p = 0.089). Among patients who received both aspirin and a thienopyridine (stratum 2), the benefit of rivaroxaban emerged during the period of active treatment with DAPT (HR: 0.68; 95% CI: 0.50 to 0.92, combined rivaroxaban group vs. placebo). Among stented patients who were treated with dual antiplatelet therapy, there was a mortality reduction among those treated with twice-daily rivaroxaban 2.5 mg (HR: 0.56; 95% CI: 0.35 to 0.89; p = 0.014).
Conclusions Among stented patients with ACS treated with DAPT, the administration of twice-daily rivaroxaban 2.5 mg was associated with a reduction in stent thrombosis and mortality. (An Efficacy and Safety Study for Rivaroxaban in Patients With Acute Coronary Syndrome; NCT00809965) (C) 2013 by the American College of Cardiology Foundation
C1 [Gibson, C. Michael; Chakrabarti, Anjan K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Cardiovasc Div, Boston, MA USA.
[Gibson, C. Michael; Mega, Jessica; Bhatt, Deepak L.; Mohanavelu, Satishkumar; Braunwald, Eugene] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div,TIMI Study Grp, Boston, MA USA.
[Bode, Christophe] Univ Freiburg, Dept Cardiol & Angiol, D-79106 Freiburg, Germany.
[Bassand, Jean-Pierre] Univ Hosp Jean Minjoz, Besancon, France.
[Verheugt, Freek W. A.] OnzeLieveVrouweGasthuis, Amsterdam, Netherlands.
[Bhatt, Deepak L.] VA Healthcare Syst, Boston, MA USA.
[Goto, Shinya] Tokai Univ, Sch Med, Dept Med Cardiol, Isehara, Kanagawa 25911, Japan.
[Cohen, Marc] Newark Beth Israel Med Ctr, Div Cardiol, Newark, NJ USA.
[Burton, Paul] Janssen Res & Dev, Titusville, NJ USA.
[Stone, Gregg] Columbia Univ, New York, NY 10027 USA.
RP Gibson, CM (reprint author), Beth Israel Deaconess Med Ctr, 185 Pilgrim Rd,Farr 319, Boston, MA 02215 USA.
EM mgibson@perfuse.org
RI Verheugt, F.W.A./H-8105-2014
NR 10
TC 34
Z9 35
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUL 23
PY 2013
VL 62
IS 4
BP 286
EP 290
DI 10.1016/j.jacc.2013.03.041
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 186SD
UT WOS:000322064100005
PM 23602776
ER
PT J
AU Mao, YD
Wang, LP
Gu, C
Herschhorn, A
Desormeaux, A
Finzi, A
Xiang, SH
Sodroski, JG
AF Mao, Youdong
Wang, Liping
Gu, Christopher
Herschhorn, Alon
Desormeaux, Anik
Finzi, Andres
Xiang, Shi-Hua
Sodroski, Joseph G.
TI Molecular architecture of the uncleaved HIV-1 envelope glycoprotein
trimer
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE vaccine immunogen; retrovirus; spike; cryo-EM; membrane protein
ID VIRUS TYPE-1 GP120; CONFORMATIONAL-CHANGES; NEUTRALIZING ANTIBODY;
ATOMIC-STRUCTURE; STRUCTURAL BASIS; RATIONAL DESIGN; AIDS PATIENTS;
INNER DOMAIN; CD4 BINDING; HTLV-III
AB The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, a membrane-fusing machine, mediates virus entry into host cells and is the sole virus-specific target for neutralizing antibodies. Binding the receptors, CD4 and CCR5/CXCR4, triggers Env conformational changes from the metastable unliganded state to the fusion-active state. We used cryo-electron microscopy to obtain a 6-angstrom structure of the membrane-bound, heavily glycosylated HIV-1 Env trimer in its uncleaved and unliganded state. The spatial organization of secondary structure elements reveals that the unliganded conformations of both glycoprotein (gp)120 and gp41 subunits differ from those induced by receptor binding. The gp120 trimer association domains, which contribute to interprotomer contacts in the unliganded Env trimer, undergo rearrangement upon CD4 binding. In the unliganded Env, intersubunit interactions maintain the gp41 ecto-domain helical bundles in a "spring-loaded" conformation distinct from the extended helical coils of the fusion-active state. Quaternary structure regulates the virus-neutralizing potency of antibodies targeting the conserved CD4-binding site on gp120. The Env trimer architecture provides mechanistic insights into the metastability of the unliganded state, receptor-induced conformational changes, and quaternary structure-based strategies for immune evasion.
C1 [Mao, Youdong; Wang, Liping; Gu, Christopher; Herschhorn, Alon; Sodroski, Joseph G.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
[Mao, Youdong; Wang, Liping; Gu, Christopher; Herschhorn, Alon; Sodroski, Joseph G.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
[Desormeaux, Anik; Finzi, Andres] Univ Montreal, Ctr Rech, Ctr Hosp Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada.
[Xiang, Shi-Hua] Univ Nebraska, Nebraska Ctr Virol, Sch Vet Med & Biomed Sci, Lincoln, NE 68583 USA.
[Sodroski, Joseph G.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA.
[Sodroski, Joseph G.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Mao, YD (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
EM youdong_mao@dfci.harvard.edu; joseph_sodroski@dfci.harvard.edu
FU National Science Foundation (NSF) under NSF Award [ECS-0335765];
National Institutes of Health [AI93256, AI67854, AI24755]; Ragon
Institute of Massachusetts General Hospital, Massachusetts Institute of
Technology, and Harvard; International AIDS Vaccine Initiative; Mathilde
Krim Fellowship in Basic Science from the American Foundation for AIDS
Research; Canada Foundation for Innovation Program Leader [29866];
Canadian Institutes of Health Research operating [257792]; Fonds de
Recherche en Sante du Quebec Chercheur Boursier Junior 1 fellowship
[24639]
FX We thank P. Kwong, J. Robinson, P. Poignard, S. Zolla-Pazner, H.
Katinger, M. Posner, and L. Cavacini for kindly providing antibodies; D.
R. Burton for helpful discussion and encouragement; A. Leschziner for
help in cryo-specimen preparation; D. Bell and E. Hodges for
coordination in data collection; J. Faltskog, S. Doktor, and B. Battle
for laboratory coordination; J. Jackson and B. Richter for assistance in
building and maintaining the high-performance computing system; and Y.
McLaughlin and E. Carpelan for assistance in manuscript preparation. The
experiments and data processing were performed in part at the Center for
Nanoscale Systems at Harvard University, a member of National
Nanotechnology Infrastructure Network, which is supported by the
National Science Foundation (NSF) under NSF Award ECS-0335765. This work
was funded by National Institutes of Health Grants AI93256, AI67854, and
AI24755, by an Innovation Award and a Fellowship Award from the Ragon
Institute of Massachusetts General Hospital, Massachusetts Institute of
Technology, and Harvard, by the International AIDS Vaccine Initiative,
and by gifts from Mr. and Mrs. Daniel J. Sullivan, Jr. and the late
William F. McCarty-Cooper. A.H. is the recipient of a Mathilde Krim
Fellowship in Basic Science from the American Foundation for AIDS
Research. A.F. is the recipient of a Canada Foundation for Innovation
Program Leader (#29866), a Canadian Institutes of Health Research
operating (#257792) and an Fonds de Recherche en Sante du Quebec
Chercheur Boursier Junior 1 fellowship (#24639).
NR 52
TC 52
Z9 52
U1 4
U2 53
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 23
PY 2013
VL 110
IS 30
BP 12438
EP 12443
DI 10.1073/pnas.1307382110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187JA
UT WOS:000322112300067
PM 23757493
ER
PT J
AU Ye, L
Wu, J
Cohen, P
Kazak, L
Khandekar, MJ
Jedrychowski, MP
Zeng, X
Gygi, SP
Spiegelman, BM
AF Ye, Li
Wu, Jun
Cohen, Paul
Kazak, Lawrence
Khandekar, Melin J.
Jedrychowski, Mark P.
Zeng, Xing
Gygi, Steven P.
Spiegelman, Bruce M.
TI Fat cells directly sense temperature to activate thermogenesis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Ucp1; cold sensing
ID BROWN ADIPOSE-TISSUE; DIET-INDUCED THERMOGENESIS; HEAT-EVOKED
ACTIVATION; CAPSAICIN-RECEPTOR; ADULT HUMANS; ION-CHANNEL; TRP CHANNEL;
WHITE FAT; ADIPOCYTES; OBESITY
AB Classic brown fat and inducible beige fat both dissipate chemical energy in the form of heat through the actions of mitochondrial uncoupling protein 1. This nonshivering thermogenesis is crucial for mammals as a defense against cold and obesity/diabetes. Cold is known to act indirectly through the sympathetic nervous systems and beta-adrenergic signaling, but here we report that cool temperature (27-33 degrees C) can directly activate a thermogenic gene program in adipocytes in a cell-autonomous manner. White and beige fat cells respond to cool temperatures, but classic brown fat cells do not. Importantly, this activation in isolated cells is independent of the canonical cAMP/Protein Kinase A/cAMP response element-binding protein pathway downstream of the beta-adrenergic receptors. These findings provide an unusual insight into the role of adipose tissues in thermoregulation, as well as an alternative way to target nonshivering thermogenesis for treatment of obesity and metabolic diseases.
C1 [Ye, Li; Wu, Jun; Cohen, Paul; Kazak, Lawrence; Khandekar, Melin J.; Zeng, Xing; Spiegelman, Bruce M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Ye, Li; Wu, Jun; Cohen, Paul; Kazak, Lawrence; Khandekar, Melin J.; Jedrychowski, Mark P.; Zeng, Xing; Gygi, Steven P.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
EM Bruce_Spiegelman@dfci.harvard.edu
FU National Institutes of Health Interdisciplinary Training Grant
[DK071507]; National Institutes of Health Grant [DK094824, DK31403,
DK080261]
FX We thank Dr. Brad Lowell for providing the beta-less mice, Dr. Wolfgang
Liedtke for providing Trpv4-/- mice, and Dr. Jeffery Gimble
for providing human adipose cells. We also thank Dr. Sandra Kleiner, Dr.
Rana Gupta, Dr. Jorge Ruas, Dr. Patrick Seale, Dr. Jennifer Estall, Dr.
Shingo Kajimura, and Dr. Rajan Sah for discussion. Support was provided
by National Institutes of Health Interdisciplinary Training Grant
DK071507 (to L.Y.) and National Institutes of Health Grant DK094824 (to
J.W.) DK31403, and DK080261 (to B.M.S.).
NR 37
TC 73
Z9 73
U1 13
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 JUL 23
PY 2013
VL 110
IS 30
BP 12480
EP 12485
DI 10.1073/pnas.1310261110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187JA
UT WOS:000322112300074
PM 23818608
ER
PT J
AU Podrid, PJ
AF Podrid, Philip J.
TI ECG Response: July 23, 2013
SO CIRCULATION
LA English
DT Editorial Material
C1 [Podrid, Philip J.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Podrid, Philip J.] Harvard Univ, Sch Med, Boston, MA USA.
[Podrid, Philip J.] VA Boston Healthcare Syst, Boston, MA USA.
RP Podrid, PJ (reprint author), West Roxbury VA Hosp, Cardiol Sect, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM ppodrid@circulationjournal.org
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 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 23
PY 2013
VL 128
IS 4
BP 414
EP 414
DI 10.1161/CIRCULATIONAHA.113.004371
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 187MP
UT WOS:000322123500025
PM 23877064
ER
PT J
AU Jackevicius, CA
Tu, JV
Ko, DT
de Leon, N
Krumholz, HM
AF Jackevicius, Cynthia A.
Tu, Jack V.
Ko, Dennis T.
de Leon, Noelle
Krumholz, Harlan M.
TI Use of Niacin in the United States and Canada
SO JAMA INTERNAL MEDICINE
LA English
DT Letter
ID THERAPY; DISEASE
C1 [Jackevicius, Cynthia A.; de Leon, Noelle] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA USA.
[Jackevicius, Cynthia A.; Tu, Jack V.; Ko, Dennis T.] Inst Clin Evaluat Sci, Toronto, ON, Canada.
[Jackevicius, Cynthia A.; Tu, Jack V.; Ko, Dennis T.] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada.
[Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada.
[Tu, Jack V.; Ko, Dennis T.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Schulich Heart Ctr, Div Cardiol, Toronto, ON, Canada.
[Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Med, Sect Cardiovascr Med Epidemiol & Publ Hlth & Hlth, New Haven, CT 06510 USA.
[Krumholz, Harlan M.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT USA.
[Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA.
RP Jackevicius, CA (reprint author), Western Univ Hlth Sci, Coll Pharm, 309 E 2nd St, Pomona, CA 91766 USA.
EM cjackevicius@westernu.edu
OI Ko, Dennis/0000-0001-6840-8051
FU Canadian Institutes of Health Research; NHLBI NIH HHS [U01-HL105270-03]
NR 9
TC 11
Z9 11
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD JUL 22
PY 2013
VL 173
IS 14
BP 1379
EP 1383
DI 10.1001/jamainternmed.2013.6489
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 214TX
UT WOS:000324160100027
PM 23753308
ER
PT J
AU Yaffe, K
Falvey, CM
Hamilton, N
Harris, TB
Simonsick, EM
Strotmeyer, ES
Shorr, RI
Metti, A
Schwartz, AV
AF Yaffe, Kristine
Falvey, Cherie M.
Hamilton, Nathan
Harris, Tamara B.
Simonsick, Eleanor M.
Strotmeyer, Elsa S.
Shorr, Ronald I.
Metti, Andrea
Schwartz, Ann V.
CA Hlth ABC Study
TI Association Between Hypoglycemia and Dementia in a Biracial Cohort of
Older Adults With Diabetes Mellitus
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID COGNITIVE FUNCTION; ALZHEIMERS-DISEASE; RISK; DYSFUNCTION; IMPAIRMENT;
VETERANS; TRIAL
AB IMPORTANCE Hypoglycemia commonly occurs in patients with diabetes mellitus (DM) and may negatively influence cognitive performance. Cognitive impairment in turn can compromise DM management and lead to hypoglycemia.
OBJECTIVE To prospectively evaluate the association between hypoglycemia and dementia in a biracial cohort of older adults with DM.
DESIGN AND SETTING Prospective population-based study.
PARTICIPANTS We studied 783 older adults with DM (mean age, 74.0 years; 47.0% of black race/ethnicity; and 47.6% female) who were participating in the prospective population-based Health, Aging, and Body Composition Study beginning in 1997 and who had baseline Modified Mini-Mental State Examination scores of 80 or higher.
MAIN OUTCOME MEASURES Dementia diagnosis was determined during the follow-up period from hospital records indicating an admission associated with dementia or the use of prescribed dementia medications. Hypoglycemic events were determined during the follow-up period by hospital records.
RESULTS During the 12-year follow-up period, 61 participants (7.8%) had a reported hypoglycemic event, and 148 (18.9%) developed dementia. Those who experienced a hypoglycemic event had a 2-fold increased risk for developing dementia compared with those who did not have a hypoglycemic event (34.4% vs 17.6%, P < .001; multivariate-adjusted hazard ratio, 2.1; 95% CI, 1.0-4.4). Similarly, older adults with DM who developed dementia had a greater risk for having a subsequent hypoglycemic event compared with participants who did not develop dementia (14.2% vs 6.3%, P < .001; multivariate-adjusted hazard ratio, 3.1; 95% CI, 1.5-6.6). Further adjustment for stroke, hypertension, myocardial infarction, and cognitive change scores produced similar results.
CONCLUSION AND RELEVANCE Among older adults with DM, there seems to be a bidirectional association between hypoglycemia and dementia.
C1 [Yaffe, Kristine; Falvey, Cherie M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA.
[Yaffe, Kristine; Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA.
[Yaffe, Kristine; Falvey, Cherie M.; Hamilton, Nathan] San Francisco VA Med Ctr, San Francisco, CA USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Baltimore, MD 21224 USA.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Strotmeyer, Elsa S.; Metti, Andrea] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Shorr, Ronald I.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA.
RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St,POB 181, San Francisco, CA 94121 USA.
EM kristine.yaffe@ucsf.edu
RI Strotmeyer, Elsa/F-3015-2014; Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036
FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, K24AG031155]; National Institute of Nursing Research
[R01-AG028050, R01-NR012459]; Intramural Research Program of the
National Institutes of Health; American Health Assistance Foundation
[A201-0029]
FX This study was supported by grants N01-AG-6-2101, N01-AG-6-2103, and
N01-AG-6-2106 from the National Institute on Aging and by grants
R01-AG028050 and R01-NR012459 from the National Institute of Nursing
Research. This research was supported in part by the Intramural Research
Program of the National Institutes of Health, by the National Institute
on Aging, and by grant A201-0029 from the American Health Assistance
Foundation. Dr Yaffe is supported in part by grant K24AG031155 from the
National Institute on Aging.
NR 33
TC 76
Z9 79
U1 5
U2 15
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD JUL 22
PY 2013
VL 173
IS 14
BP 1300
EP +
DI 10.1001/jamainternmed.2013.6176
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 214TX
UT WOS:000324160100007
PM 23753199
ER
PT J
AU McCrum, ML
Joynt, KE
Orav, EJ
Gawande, AA
Jha, AK
AF McCrum, Marta L.
Joynt, Karen E.
Orav, E. John
Gawande, Atul A.
Jha, Ashish K.
TI Mortality for Publicly Reported Conditions and Overall Hospital
Mortality Rates
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID QUALITY; CARE; SURGERY; VOLUME
AB IMPORTANCE Federal efforts about public reporting and quality improvement programs for hospitals have focused primarily on a small number of medical conditions. Whether performance on these conditions accurately predicts the quality of broader hospital care is unknown.
OBJECTIVE To determine whether mortality rates for publicly reported medical conditions are correlated with hospitals' overall performance.
METHODS Using national Medicare data, we compared hospital performance at 2322 US acute care hospitals on 30-day risk-adjusted mortality, aggregated across the 3 publicly reported conditions (acute myocardial infarction, congestive heart failure, and pneumonia), with performance on a composite risk-adjusted mortality rate across 9 other common medical conditions, a composite mortality rate across 10 surgical conditions, and both composites combined. We also examined the relationship between alternative surrogates of quality (hospital size and teaching status) and performance on these composite outcomes.
RESULTS Our sample included 6 670 859 hospitalizations for Medicare fee-for-service beneficiaries from 2008 through 2009. Hospitals in the top quartile of performance on publicly reported conditions had a 3.6% lower absolute risk-adjusted mortality rate on the combined medical-surgical composite than those in the bottom quartile (9.4% vs 13.0%; P < .001). These top performers on publicly reported conditions had 5 times greater odds of being in the top quartile on the overall combined composite risk-adjusted mortality rate (odds ratio [OR], 5.3; 95% CI, 4.3-6.5). Mortality rates for the index condition were predictive of medical (OR, 8.4; 95% CI, 6.8-10.3) and surgical (2.7; 2.2-3.3) performance when these groups were considered separately. In comparison, large size (OR, 1.9; 95% CI, 1.5-2.4) and teaching status (2.4; 1.8-3.2) showed weaker relationships with overall hospital mortality rates.
CONCLUSIONS AND RELEVANCE Hospital performance on publicly reported conditions can potentially be used as a signal of overall hospital mortality rates.
C1 [McCrum, Marta L.; Joynt, Karen E.; Gawande, Atul A.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Orav, E. John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[McCrum, Marta L.; Gawande, Atul A.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA USA.
[Orav, E. John; Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA.
[Joynt, Karen E.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
[Gawande, Atul A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Joynt, Karen E.; Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA.
RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA.
EM ajha@hsph.harvard.edu
OI Gawande, Atul/0000-0002-1824-9176
FU Center for Surgery and Public Health at Brigham and Women's Hospital;
National Heart, Lung, and Blood Institute [1K23HL109177-01]; Brigham and
Women's Hospital, Division of Cardiovascular Medicine; Harvard School of
Public Health
FX This study was supported by the Cabot Fellowship from the Center for
Surgery and Public Health at Brigham and Women's Hospital (Dr McCrum);
grant 1K23HL109177-01 from the National Heart, Lung, and Blood Institute
(Dr Joynt); and the Lerner Research Award from Brigham and Women's
Hospital, Division of Cardiovascular Medicine (Dr Joynt). Additional
support was provided from internal department funds from the Harvard
School of Public Health.
NR 13
TC 12
Z9 12
U1 1
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD JUL 22
PY 2013
VL 173
IS 14
BP 1351
EP 1357
DI 10.1001/jamainternmed.2013.7049
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 214TX
UT WOS:000324160100017
PM 23797306
ER
PT J
AU Chen, CM
Wonsey, DR
Lemieux, ME
Kung, AL
AF Chen, Changmin
Wonsey, Diane R.
Lemieux, Madeleine E.
Kung, Andrew L.
TI Differential Disruption of EWS-FLI1 Binding by DNA-Binding Agents
SO PLOS ONE
LA English
DT Article
ID MAGNETIC-RESONANCE INVESTIGATIONS; ACTINOMYCIN-D; EWINGS-SARCOMA;
AQUEOUS-SOLUTION; ONCOGENIC TRANSCRIPTION; COMPLEX-FORMATION;
GROWTH-FACTOR; GENE; FUSION; TUMOR
AB Fusion of the EWS gene to FLI1 produces a fusion oncoprotein that drives an aberrant gene expression program responsible for the development of Ewing sarcoma. We used a homogenous proximity assay to screen for compounds that disrupt the binding of EWS-FLI1 to its cognate DNA targets. A number of DNA-binding chemotherapeutic agents were found to non-specifically disrupt protein binding to DNA. In contrast, actinomycin D was found to preferentially disrupt EWS-FLI1 binding by comparison to p53 binding to their respective cognate DNA targets in vitro. In cell-based assays, low concentrations of actinomycin D preferentially blocked EWS-FLI1 binding to chromatin, and disrupted EWS-FLI1-mediated gene expression. Higher concentrations of actinomycin D globally repressed transcription. These results demonstrate that actinomycin D preferentially disrupts EWS-FLI1 binding to DNA at selected concentrations. Although the window between this preferential effect and global suppression is too narrow to exploit in a therapeutic manner, these results suggest that base-preferences may be exploited to find DNA-binding compounds that preferentially disrupt subclasses of transcription factors.
C1 [Chen, Changmin; Wonsey, Diane R.; Lemieux, Madeleine E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Chen, Changmin; Wonsey, Diane R.; Lemieux, Madeleine E.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA.
[Kung, Andrew L.] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10027 USA.
RP Kung, AL (reprint author), Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10027 USA.
EM akung@columbia.edu
OI Lemieux, Madeleine/0000-0001-6355-8691; Kung, Andrew/0000-0002-9091-488X
FU St. Baldrick's Foundation
FX Funding provided by St. Baldrick's Foundation (Kung). The funder had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 31
TC 4
Z9 5
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 22
PY 2013
VL 8
IS 7
AR e69714
DI 10.1371/journal.pone.0069714
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187PW
UT WOS:000322132100077
PM 23894528
ER
PT J
AU Pfitzner, E
Wachauf, C
Kilchherr, F
Pelz, B
Shih, WM
Rief, M
Dietz, H
AF Pfitzner, Emanuel
Wachauf, Christian
Kilchherr, Fabian
Pelz, Benjamin
Shih, William M.
Rief, Matthias
Dietz, Hendrik
TI Rigid DNA Beams for High-Resolution Single-Molecule Mechanics
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE biophysics; DNA nanotechnology; DNA structures; force spectroscopy;
single-molecule experiments
ID OPTICAL TWEEZERS; NANOSCALE SHAPES; NUCLEIC-ACID; FOLDING DNA; PROTEIN;
TRAJECTORIES; LANDSCAPES; ELASTICITY; RIBOSWITCH; ORIGAMI
C1 [Pfitzner, Emanuel; Wachauf, Christian; Kilchherr, Fabian; Dietz, Hendrik] Tech Univ Munich, Dept Phys, Walter Schottky Inst, D-85748 Garching, Germany.
[Pelz, Benjamin; Rief, Matthias] Tech Univ Munich, Dept Phys, Lehrstuhl Biophys, D-85748 Garching, Germany.
[Shih, William M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Dietz, H (reprint author), Tech Univ Munich, Dept Phys, Walter Schottky Inst, Coulombwall 4A, D-85748 Garching, Germany.
EM dietz@tum.de
FU European Research Council [256270]; Deutsche Forschungsgemeinschaft
(DFG) through the programs Collaborative Research Center [SFB 863];
Center for Integrated Protein Science Munich; Nanosystems Initiative
Munich; CompInt of Elitenetzwerk Bayern
FX E.P., C.W., F.K. performed experiments; H.D. and M.R. designed research;
E.P., C.W., F.K., H.D., M.R. analyzed data; B.P. built the experimental
setup; W.S. provided custom reagents; E.P., C.W., H.D. prepared figures,
H.D. wrote the paper; M.R. and W.S. edited the paper. This work was
supported by a European Research Council Starting Grant to H.D. (GA no
256270), the Deutsche Forschungsgemeinschaft (DFG) through the programs
Collaborative Research Center SFB 863, Center for Integrated Protein
Science Munich, and Nanosystems Initiative Munich. F.K. was supported by
a stipend from CompInt of Elitenetzwerk Bayern. We thank Florian
Praetorius and Johannes Stigler for technical support, and Michael
Woodside, Felix Ritort, Ciro Cecconi, Zev Bryant, Thorsten Hugel, and
Achillefs Kapanidis for discussions.
NR 39
TC 29
Z9 29
U1 5
U2 69
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1433-7851
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PD JUL 22
PY 2013
VL 52
IS 30
BP 7766
EP 7771
DI 10.1002/anie.201302727
PG 6
WC Chemistry, Multidisciplinary
SC Chemistry
GA 184NE
UT WOS:000321896800031
PM 23794413
ER
PT J
AU Atkins, BD
Yoshida, S
Saito, K
Wu, CF
Lew, DJ
Pellman, D
AF Atkins, Benjamin D.
Yoshida, Satoshi
Saito, Koji
Wu, Chi-Fang
Lew, Daniel J.
Pellman, David
TI Inhibition of Cdc42 during mitotic exit is required for cytokinesis
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID GTPASE-ACTIVATING PROTEIN; CELL POLARITY DETERMINANTS; BUDDING YEAST
CYTOKINESIS; SACCHAROMYCES-CEREVISIAE; ACTOMYOSIN-RING; BUD EMERGENCE;
SEPTIN RING; LOCAL ACTIVATION; CLEAVAGE FURROW; MYOSIN-II
AB The role of Cdc42 and its regulation during cytokinesis is not well understood. Using biochemical and imaging approaches in budding yeast, we demonstrate that Cdc42 activation peaks during the G(1)/S transition and during anaphase but drops during mitotic exit and cytokinesis. Cdc5/Polo kinase is an important upstream cell cycle regulator that suppresses Cdc42 activity. Failure to down-regulate Cdc42 during mitotic exit impairs the normal localization of key cytokinesis regulators-Iqg1 and Inn1-at the division site, and results in an abnormal septum. The effects of Cdc42 hyperactivation are largely mediated by the Cdc42 effector p21-activated kinase Ste20. Inhibition of Cdc42 and related Rho guanosine triphosphatases may be a general feature of cytokinesis in eukaryotes.
C1 [Atkins, Benjamin D.; Yoshida, Satoshi; Pellman, David] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Atkins, Benjamin D.; Yoshida, Satoshi; Pellman, David] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Yoshida, Satoshi] Brandeis Univ, Dept Biol, Waltham, MA 02454 USA.
[Yoshida, Satoshi] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA.
[Pellman, David] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Saito, Koji; Wu, Chi-Fang; Lew, Daniel J.] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
EM david_pellman@dfci.harvard.edu
FU National Institutes of Health [RO1 GM061345, R01 GM62300]
FX This work was supported by National Institutes of Health grants RO1
GM061345 and R01 GM62300.
NR 65
TC 19
Z9 19
U1 0
U2 8
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD JUL 22
PY 2013
VL 202
IS 2
BP 231
EP 240
DI 10.1083/jcb.201301090
PG 10
WC Cell Biology
SC Cell Biology
GA 186RR
UT WOS:000322062300008
PM 23878274
ER
PT J
AU Janssen, AM
Rampersad, SM
Lucka, F
Lanfer, B
Lew, S
Aydin, U
Wolters, CH
Stegeman, DF
Oostendorp, TF
AF Janssen, A. M.
Rampersad, S. M.
Lucka, F.
Lanfer, B.
Lew, S.
Aydin, Ue
Wolters, C. H.
Stegeman, D. F.
Oostendorp, T. F.
TI The influence of sulcus width on simulated electric fields induced by
transcranial magnetic stimulation
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID BRAIN-TISSUE; IMPEDANCE METHOD; ELEMENT-METHOD; MODEL; GEOMETRY; TMS;
COMPUTATION; MECHANISMS; ANISOTROPY; ACCURACY
AB Volume conduction models can help in acquiring knowledge about the distribution of the electric field induced by transcranial magnetic stimulation. One aspect of a detailed model is an accurate description of the cortical surface geometry. Since its estimation is difficult, it is important to know how accurate the geometry has to be represented. Previous studies only looked at the differences caused by neglecting the complete boundary between cerebrospinal fluid (CSF) and grey matter (Thielscher et al 2011 NeuroImage 54 234-43, Bijsterbosch et al 2012 Med. Biol. Eng. Comput. 50 671-81), or by resizing the whole brain (Wagner et al 2008 Exp. Brain Res. 186 539-50). However, due to the high conductive properties of the CSF, it can be expected that alterations in sulcus width can already have a significant effect on the distribution of the electric field. To answer this question, the sulcus width of a highly realistic head model, based on T1-, T2- and diffusion-weighted magnetic resonance images, was altered systematically. This study shows that alterations in the sulcus width do not cause large differences in the majority of the electric field values. However, considerable overestimation of sulcus width produces an overestimation of the calculated field strength, also at locations distant from the target location.
C1 [Janssen, A. M.; Rampersad, S. M.; Stegeman, D. F.; Oostendorp, T. F.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6525 CG Nijmegen, Netherlands.
[Lucka, F.] Univ Munster, Inst Computat & Appl Math, D-48149 Munster, Germany.
[Lucka, F.; Lanfer, B.; Aydin, Ue; Wolters, C. H.] Univ Munster, Inst Biomagnetism & Biosignalanal, D-48149 Munster, Germany.
[Lanfer, B.] BESA GmbH, D-82166 Grafelfing, Germany.
[Lew, S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Stegeman, D. F.] Vrije Univ Amsterdam, Fac Human Movement Sci, Res Inst MOVE, NL-1081 BT Amsterdam, Netherlands.
RP Janssen, AM (reprint author), Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Reinier Postlaan 4, NL-6525 CG Nijmegen, Netherlands.
EM A.Janssen@neuro.umcn.nl
RI Wolters, Carsten/R-4234-2016
OI Wolters, Carsten/0000-0001-6233-424X
FU German Research Foundation [DFG WO1425/2-1]; BESA GmbH, Grafelfing,
Germany; German National Academic Foundation ('Studienstiftung des
deutschen Volkes'); NIH [R01EB0009048]
FX This study was performed in the context of the BrainGain Smart Mix
program of the Dutch government. It was further supported by funding
awarded to CHW from the German Research Foundation (DFG WO1425/2-1) for
UA and from BESA GmbH, Grafelfing, Germany, for BL. FL was funded by the
German National Academic Foundation ('Studienstiftung des deutschen
Volkes'). SL was funded by NIH (NIH grant R01EB0009048). The study was
made possible in part by software from the NIH/NIGMS Center for
Integrative Biomedical Computing, 2P41 RR0112553-12.
NR 28
TC 7
Z9 7
U1 3
U2 6
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD JUL 21
PY 2013
VL 58
IS 14
BP 4881
EP 4896
DI 10.1088/0031-9155/58/14/4881
PG 16
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 175PR
UT WOS:000321243600013
PM 23787706
ER
PT J
AU Kiaii, S
Clear, AJ
Ramsay, AG
Davies, D
Sangaralingam, A
Lee, A
Calaminici, M
Neuberg, DS
Gribben, JG
AF Kiaii, Shahryar
Clear, Andrew J.
Ramsay, Alan G.
Davies, Derek
Sangaralingam, Ajanthah
Lee, Abigail
Calaminici, Maria
Neuberg, Donna S.
Gribben, John G.
TI Follicular Lymphoma Cells Induce Changes in T-Cell Gene Expression and
Function: Potential Impact on Survival and Risk of Transformation
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID MELANIN-CONCENTRATING HORMONE; CHRONIC LYMPHOCYTIC-LEUKEMIA;
TUMOR-ASSOCIATED MACROPHAGES; NF-KAPPA-B; IMMUNE CELLS;
MICROENVIRONMENT; RECEPTOR; CANCER; ETV1
AB Purpose
Previous studies have demonstrated the prognostic importance of the immune microenvironment in follicular lymphoma (FL). To investigate the molecular mechanisms during which tumor-infiltrating T cells (TILs) are altered in the FL microenvironment, we studied highly purified CD4 and CD8 TILs from lymph node biopsies at diagnosis in treatment-naive patients with FL compared with reactive tonsils and the peripheral blood of healthy donors.
Patients and Methods
Gene expression profiling of highly purified CD4 and CD8 TILs was performed on the Affymetrix platform. Diagnostic tissue microarrays from an independent patient set (n = 172) were used to verify protein expression and analyze any impact of TIL-expressed genes on outcome. Time-lapse imaging was used to assess T-cell motility.
Results
The most upregulated genes in both CD4 and CD8 TILs were PMCH, ETV1, and TNFRSF9. PMCH is not expressed in peripheral blood T cells, but expression is highly induced on culture with FL. Both CD4 and CD8 TILs from patients with FL have significantly impaired motility compared with those of healthy TILs from reactive tonsils and this can be induced on healthy T cells by FL cells. During multivariate analysis, a model incorporating the number and location of T cells expressing PMCH, NAMPT, and ETV1 showed prognostic significance for overall survival and for time to transformation.
Conclusion
We showed altered gene expression in TILs in FL and demonstrated that altering the immune microenvironment in FL affects overall survival and time to transformation in this disease. (C) 2013 by American Society of Clinical Oncology
C1 [Kiaii, Shahryar; Clear, Andrew J.; Ramsay, Alan G.; Sangaralingam, Ajanthah; Lee, Abigail; Gribben, John G.] Barts Canc Inst, London, England.
[Sangaralingam, Ajanthah] Univ London, London Sch Med, London, England.
[Davies, Derek] Canc Res UK, London Res Inst, FACS Lab, London, England.
[Lee, Abigail; Calaminici, Maria] Barts Hlth NHS Trust, London, England.
[Neuberg, Donna S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Gribben, JG (reprint author), Queen Mary Univ London, Barts & London Sch Med, Ctr Haematooncol, Barts Canc Ins, Charterhouse Sq, London EC1M 6BQ, England.
EM j.gribben@qmul.ac.uk
RI Ramsay, Alan/A-8374-2015
OI Ramsay, Alan/0000-0002-0452-0420
FU Cancer Research UK [C1574/A6806]; National Cancer Institute [P01
CA81538]
FX Supported by Grant No. C1574/A6806 from Cancer Research UK (J.G.G.) and
Grant No. P01 CA81538 from the National Cancer Institute.
NR 38
TC 29
Z9 29
U1 1
U2 5
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 20
PY 2013
VL 31
IS 21
BP 2654
EP +
DI 10.1200/JCO.2012.44.2137
PG 9
WC Oncology
SC Oncology
GA 301NJ
UT WOS:000330538700012
PM 23775959
ER
PT J
AU Koreth, J
Pidala, J
Perez, WS
Deeg, HJ
Garcia-Manero, G
Malcovati, L
Cazzola, M
Park, S
Itzykson, R
Ades, L
Fenaux, P
Jadersten, M
Hellstrom-Lindberg, E
Gale, RP
Beach, CL
Lee, SJ
Horowitz, MM
Greenberg, PL
Tallman, MS
DiPersio, JF
Bunjes, D
Weisdorf, DJ
Cutler, C
AF Koreth, John
Pidala, Joseph
Perez, Waleska S.
Deeg, H. Joachim
Garcia-Manero, Guillermo
Malcovati, Luca
Cazzola, Mario
Park, Sophie
Itzykson, Raphael
Ades, Lionel
Fenaux, Pierre
Jadersten, Martin
Hellstrom-Lindberg, Eva
Gale, Robert Peter
Beach, C. L.
Lee, Stephanie J.
Horowitz, Mary M.
Greenberg, Peter L.
Tallman, Martin S.
DiPersio, John F.
Bunjes, Donald
Weisdorf, Daniel J.
Cutler, Corey
TI Role of Reduced-Intensity Conditioning Allogeneic Hematopoietic
Stem-Cell Transplantation in Older Patients With De Novo Myelodysplastic
Syndromes: An International Collaborative Decision Analysis
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; PROGNOSTIC
SCORING SYSTEM; HLA-IDENTICAL SIBLINGS; ACUTE MYELOID-LEUKEMIA;
MYELOPROLIFERATIVE DISORDERS; PREDICTING SURVIVAL; HODGKINS-DISEASE;
LIFE EXPECTANCY; PHASE-III
AB Purpose
Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders that are more common in patients aged >= 60 years and are incurable with conventional therapies. Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem-cell transplantation is potentially curative but has additional mortality risk. We evaluated RIC transplantation versus nontransplantation therapies in older patients with MDS stratified by International Prognostic Scoring System (IPSS) risk.
Patients and Methods
A Markov decision model with quality-of-life utility estimates for different MDS and transplantation states was assessed. Outcomes were life expectancy (LE) and quality-adjusted life expectancy (QALE). A total of 514 patients with de novo MDS aged 60 to 70 years were evaluated. Chronic myelomonocytic leukemia, isolated 5q-syndrome, unclassifiable, and therapy-related MDS were excluded. Transplantation using T-cell depletion or HLA-mismatched or umbilical cord donors was also excluded. RIC transplantation (n = 132) stratified by IPSS risk was compared with best supportive care for patients with nonanemic low/intermediate-1 IPSS (n = 123), hematopoietic growth factors for patients with anemic low/intermediate-1 IPSS (n = 94), and hypomethylating agents for patients with intermediate-2/high IPSS (n = 165).
Results
For patients with low/intermediate-1 IPSS MDS, RIC transplantation LE was 38 months versus 77 months with nontransplantation approaches. QALE and sensitivity analysis did not favor RIC transplantation across plausible utility estimates. For intermediate-2/high IPSS MDS, RIC transplantation LE was 36 months versus 28 months for nontransplantation therapies. QALE and sensitivity analysis favored RIC transplantation across plausible utility estimates.
Conclusion
For patients with de novo MDS aged 60 to 70 years, favored treatments vary with IPSS risk. For low/intermediate-1 IPSS, nontransplantation approaches are preferred. For intermediate-2/high IPSS, RIC transplantation offers overall and quality-adjusted survival benefit. (C) 2013 by American Society of Clinical Oncology
C1 [Koreth, John; Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Pidala, Joseph] H Lee Moffitt Canc & Res Inst, Tampa, FL USA.
[Perez, Waleska S.; Horowitz, Mary M.] Ctr Int Blood & Marrow Transplant Res, Ctr Stat, Milwaukee, WI USA.
[Deeg, H. Joachim; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Malcovati, Luca; Cazzola, Mario] Univ Pavia, Sch Med, I-27100 Pavia, Italy.
[Park, Sophie] Univ Paris 05, F-75270 Paris 06, France.
[Itzykson, Raphael; Ades, Lionel; Fenaux, Pierre] Univ Paris 13, Paris, France.
[Jadersten, Martin; Hellstrom-Lindberg, Eva] Karolinska Inst, Stockholm, Sweden.
[Gale, Robert Peter; Beach, C. L.] Celgene, Summit, NJ USA.
[Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, London, England.
[Greenberg, Peter L.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[DiPersio, John F.] Washington Univ, Sch Med, St Louis, MO USA.
[Bunjes, Donald] Univ Hosp Ulm, Ulm, Germany.
[Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA.
RP Koreth, J (reprint author), Dana Farber Canc Inst, D1B05,450 Brookline Ave, Boston, MA 02215 USA.
EM jkoreth@partners.org
FU Stem Cell Cyclists of the Pan Mass Challenge
FX J.K. is a Leukemia and Lymphoma Society Scholar in Clinical Research. C.
C. is supported by the Stem Cell Cyclists of the Pan Mass Challenge.
NR 56
TC 84
Z9 86
U1 0
U2 4
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 20
PY 2013
VL 31
IS 21
BP 2662
EP +
DI 10.1200/JCO.2012.46.8652
PG 10
WC Oncology
SC Oncology
GA 301NJ
UT WOS:000330538700013
PM 23797000
ER
PT J
AU Moy, B
Bradbury, AR
Helft, PR
Egleston, BL
Sheikh-Salah, M
Peppercorn, J
AF Moy, Beverly
Bradbury, Angela R.
Helft, Paul R.
Egleston, Brian L.
Sheikh-Salah, Moktar
Peppercorn, Jeffrey
TI Correlation Between Financial Relationships With Commercial Interests
and Research Prominence at an Oncology Meeting
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CONFLICTS-OF-INTEREST; CLINICAL-TRIALS; CANCER-RESEARCH; INDUSTRY;
POLICIES; PUBLICATION; ASSOCIATION; FREQUENCY
AB Purpose
Little is known about the effects of financial relationships between biomedical researchers and industry (financial conflicts of interest [FCOIs]) on research prominence. We examined the prevalence of FCOIs in oncology and associations between FCOIs and research prominence among abstracts presented at American Society of Clinical Oncology (ASCO) annual meetings.
Methods
We analyzed 20,718 abstracts presented at ASCO meetings in 2006 and 2008 to 2011. Measures included the following: financial relationships, peer review score (PRS), and meeting placement prominence (descending order of prominence: plenary session, clinical science symposium, oral presentation, poster discussion, general posters, and publish only).
Results
Of 20,718 abstracts, 36% reported at least one author with an FCOI. The proportion of abstracts with any FCOI increased from 33% in 2006 to 38% in 2011 (P < .001). Abstracts with FCOIs had significantly higher meeting prominence compared with publish only and general poster abstracts. The odds ratios compared with general posters were 7.3 for plenary session, 2.2 for clinical science symposium, 1.9 for oral presentation, and 1.7 for poster discussion (P < .001). Abstracts with FCOIs had significantly better PRSs compared with those without FCOIs. For all abstracts, PRS was 2.76 (95% CI, 2.75 to 2.77) with FCOIs compared with 3.01 (95% CI, 3.001 to 3.02) without FCOIs (P < 001). Omitting publish-only abstracts, PRS was 2.62 (95% CI, 2.61 to 2.63) with FCOIs compared with 2.73 without FCOIs (95% CI, 2.71 to 2.73).
Conclusion
Abstracts with FCOIs had more prominent meeting placement and better PRSs. FCOIs were reported more frequently by year, suggesting an increasing influence of industry on cancer research, greater disclosure, or both. (C) 2013 by American Society of Clinical Oncology
C1 [Moy, Beverly] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Bradbury, Angela R.] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Egleston, Brian L.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Helft, Paul R.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA.
[Sheikh-Salah, Moktar] Amer Soc Clin Oncol, Alexandria, VA USA.
[Peppercorn, Jeffrey] Duke Univ, Med Ctr, Durham, NC USA.
RP Moy, B (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 9A, Boston, MA 02114 USA.
EM bmoy@partners.org
FU Novartis
FX Research Funding: Jeffrey Peppercorn, Novartis
NR 29
TC 6
Z9 6
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 JUL 20
PY 2013
VL 31
IS 21
BP 2678
EP +
DI 10.1200/JCO.2012.46.6375
PG 8
WC Oncology
SC Oncology
GA 301NJ
UT WOS:000330538700015
PM 23775973
ER
PT J
AU Partridge, AH
Gelber, S
Piccart-Gebhart, MJ
Focant, F
Scullion, M
Holmes, E
Winer, EP
Gelber, RD
AF Partridge, Ann H.
Gelber, Shari
Piccart-Gebhart, Martine J.
Focant, Florine
Scullion, Matthew
Holmes, Eileen
Winer, Eric P.
Gelber, Richard D.
TI Effect of Age on Breast Cancer Outcomes in Women With Human Epidermal
Growth Factor Receptor 2-Positive Breast Cancer: Results From a
Herceptin Adjuvant Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID YOUNG-WOMEN; PATHOLOGICAL FEATURES; LESS-THAN-35 YEARS; SURVIVAL-DATA;
DIAGNOSIS; CHEMOTHERAPY; DISEASE; TRASTUZUMAB; EXPRESSION; PROGNOSIS
AB Purpose
Previous research has suggested that young age at diagnosis is an independent risk factor for breast cancer recurrence and death. No prior studies have adequately controlled for human epidermal growth factor receptor 2 (HER2) status or anti-HER2 treatment. We sought to evaluate whether age was a prognostic or predictive factor in the HERA trial.
Patients and Methods
We used 2-year median follow-up data and dichotomized age at 40 years to evaluate its prognostic effect on outcomes for women assigned to trastuzumab for 1 year or observation.
Results
Of the 1,703 women randomly assigned to 1 year of trastuzumab and 1,698 to observation, 722 (21%) were age <= 40 years at study entry. In separate Cox models, controlling for relevant prognostic and predictive factors, disease-free (DFS) and overall survival (OS) hazard ratios (HRs) were consistent for women age <= 40 versus > 40 years, regardless of treatment assignment (observation group: DFS HR age <= 40 v > 40 years, 1.18; 95% CI, 0.90 to 1.54; OS HR age <= 40 v > 40 years, 1.01; 95% CI, 0.60 to 1.69; trastuzumab group: DFS HR age <= 40 v > 40 years, 1.11; 95% CI, 0.81 to 1.51; OS HR age <= 40 v > 40 years, 1.18; 95% CI, 0.66 to 2.09). Interaction between age group and treatment effect was not statistically significant (DFS P = .89; OS P = .55).
Conclusion
In a retrospective analysis of a large randomized controlled trial of women with early-stage HER2-positive breast cancer, age was not strongly associated with risk of early recurrence or prediction of benefit from trastuzumab therapy. Future research should investigate whether age is a predictor of later recurrence and evaluate the impact of age within groups with other tumor subtypes. (C) 2013 by American Society of Clinical Oncology
C1 [Partridge, Ann H.; Gelber, Shari; Winer, Eric P.; Gelber, Richard D.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Piccart-Gebhart, Martine J.; Focant, Florine] Univ Libre Brussels, Inst Jules Bordet, Brussels, Belgium.
[Scullion, Matthew] Roche Prod Ltd, Welwyn Garden City AL7 3AY, Herts, England.
[Holmes, Eileen] Frontier Sci Scotland, Kincraig, Scotland.
RP Partridge, AH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM ahpartridge@partners.org
FU Roche; Genentech
FX Research Funding: Shari Gelber, Roche; Eileen Holmes, Roche; Eric P.
Winer, Genentech; Richard D. Gelber, Roche
NR 33
TC 36
Z9 37
U1 1
U2 5
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 20
PY 2013
VL 31
IS 21
BP 2692
EP 2698
DI 10.1200/JCO.2012.44.1956
PG 7
WC Oncology
SC Oncology
GA 301NJ
UT WOS:000330538700017
PM 23752109
ER
PT J
AU Ryoo, JJ
Ordin, DL
Antonio, ALM
Oishi, SM
Gould, MK
Asch, SM
Malin, JL
AF Ryoo, Joan J.
Ordin, Diana L.
Antonio, Anna Liza M.
Oishi, Sabine M.
Gould, Michael K.
Asch, Steven M.
Malin, Jennifer L.
TI Patient Preference and Contraindications in Measuring Quality of Care:
What Do Administrative Data Miss?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CELL LUNG-CANCER; CORONARY-ARTERY-DISEASE; RACIAL-DIFFERENCES;
PERFORMANCE-MEASURES; INITIAL TREATMENT; MEDICARE PATIENTS;
PRIVATE-SECTOR; VETERANS; SURVIVAL; CHEMOTHERAPY
AB Purpose
Prior studies report that half of patients with lung cancer do not receive guideline-concordant care. With data from a national Veterans Health Administration (VHA) study on quality of care, we sought to determine what proportion of patients refused or had a contraindication to recommended lung cancer therapy.
Patients and Methods
Through medical record abstraction, we evaluated adherence to six quality indicators addressing lung cancer-directed therapy for patients diagnosed within the VHA during 2007 and calculated the proportion of patients receiving, refusing, or having contraindications to recommended treatment.
Results
Mean age of the predominantly male population was 67.7 years (standard deviation, 9.4 years), and 15% were black. Adherence to quality indicators ranged from 81% for adjuvant chemotherapy to 98% for curative resection; however, many patients met quality indicator criteria without actually receiving recommended therapy by having a refusal (0% to 14%) or contraindication (1% to 30%) documented. Less than 1% of patients refused palliative chemotherapy. Black patients were more likely to refuse or bear a contraindication to surgery even when controlling for comorbidity; race was not associated with refusals or contraindications to other treatments.
Conclusion
Refusals and contraindications are common and may account for previously demonstrated low rates of recommended lung cancer therapy performance at the VHA. Racial disparities in treatment may be explained, in part, by such factors. These results sound a cautionary note for quality measurement that depends on data that do not reflect patient preference or contraindications in conditions where such considerations are important. (C) 2013 by American Society of Clinical Oncology
C1 [Ryoo, Joan J.; Ordin, Diana L.; Antonio, Anna Liza M.; Malin, Jennifer L.] Vet Adm Greater Los Angeles Healthcare Syst, West Los Angeles, CA USA.
[Ryoo, Joan J.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
[Ryoo, Joan J.] Kaiser Permanente Los Angeles Med Ctr, Los Angeles, CA 90027 USA.
[Antonio, Anna Liza M.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Oishi, Sabine M.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Gould, Michael K.] Kaiser Permanente So Calif, Pasadena, CA 91101 USA.
[Asch, Steven M.] Vet Adm Palo Alto Healthcare Syst, Palo Alto, CA USA.
[Asch, Steven M.] Stanford Sch Med, Palo Alto, CA USA.
[Ordin, Diana L.] Vet Hlth Adm, Washington, DC USA.
[Malin, Jennifer L.] WellPoint, Indianapolis, IN USA.
RP Ryoo, JJ (reprint author), Kaiser Permanente Los Angeles Med Ctr, Dept Radiat Oncol, 4950 Sunset Blvd,Second Floor, Los Angeles, CA 90027 USA.
EM joan.j.ryoo@kp.org
FU Robert Wood Johnson Clinical Scholars Program; University of California,
Los Angeles Career Development Program in Cancer Prevention and Control
Research National Cancer Institute R25 Grant
FX Supported in part by the Robert Wood Johnson Clinical Scholars Program
(J.J.R.) and the University of California, Los Angeles Career
Development Program in Cancer Prevention and Control Research National
Cancer Institute R25 Grant (J.J.R.).
NR 58
TC 17
Z9 17
U1 2
U2 6
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 20
PY 2013
VL 31
IS 21
BP 2716
EP +
DI 10.1200/JCO.2012.45.7473
PG 9
WC Oncology
SC Oncology
GA 301NJ
UT WOS:000330538700020
PM 23752110
ER
PT J
AU Chen, AB
Cronin, A
Weeks, JC
Chrischilles, EA
Malin, J
Hayman, JA
Schrag, D
AF Chen, Aileen B.
Cronin, Angel
Weeks, Jane C.
Chrischilles, Elizabeth A.
Malin, Jennifer
Hayman, James A.
Schrag, Deborah
TI Expectations About the Effectiveness of Radiation Therapy Among Patients
With Incurable Lung Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CARE OUTCOMES RESEARCH; INTERNATIONAL CONSENSUS WORKSHOP; PALLIATIVE
RADIOTHERAPY; SURVEILLANCE CONSORTIUM; MULTIPLE IMPUTATION; SYMPTOM
CONTROL; PROGNOSIS; PERCEPTIONS; PREDICTIONS; METASTASES
AB Purpose
Although radiation therapy (RT) can palliate symptoms and may prolong life, it is not curative for patients with metastatic lung cancer. We investigated patient expectations about the goals of RT for incurable lung cancers.
Patients and Methods
The Cancer Care Outcomes Research and Surveillance Consortium enrolled a population-and health system-based cohort of patients diagnosed with lung cancer from 2003 to 2005. We identified patients with stage wet IIIB or IV lung cancer who received RT and answered questions on their expectations about RT. We assessed patient expectations about the goals of RT and identified factors associated with inaccurate beliefs about cure.
Results
In all, 384 patients completed surveys on their expectations about RT. Seventy-eight percent of patients believed that RT was very or somewhat likely to help them live longer, and 67% believed that RT was very or somewhat likely to help them with problems related to their cancer. However, 64% did not understand that RT was not at all likely to cure them. Older patients and nonwhites were more likely to have inaccurate beliefs, and patients whose surveys were completed by surrogates were less likely to have inaccurate beliefs. Ninety-two percent of patients with inaccurate beliefs about cure from RT also had inaccurate beliefs about chemotherapy.
Conclusion
Although patients receiving RT for incurable lung cancer believe it will help them, most do not understand that it is not at all likely to cure their disease. This indicates a need to improve communication regarding the goals and limitations of palliative RT. (C) 2013 by American Society of Clinical Oncology
C1 [Chen, Aileen B.; Cronin, Angel; Weeks, Jane C.; Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Chen, Aileen B.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Chrischilles, Elizabeth A.] Univ Iowa, Iowa City, IA USA.
[Malin, Jennifer] Univ Calif Los Angeles, Los Angeles, CA USA.
[Hayman, James A.] Univ Michigan Hlth Syst, Ann Arbor, MI USA.
RP Chen, AB (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D1111, Boston, MA 02215 USA.
EM achen@lroc.harvard.edu
OI Chen, Aileen/0000-0002-5385-3360
FU Mentored Research Scholar Grants from the American Cancer Society
[MRSG-10-170-01-PCSM]; National Cancer Institute [U01 CA093332]; Harvard
Medical School/Northern California Cancer Center [U01 CA093324];
RAND/University of California, Los Angeles [U01 CA093348]; University of
Alabama at Birmingham [U01 CA093329]; University of Iowa [U01 CA093339];
University of North Carolina [U01 CA093326]; Statistical Coordinating
Center [U01 CA093344]; Department of Veterans Affairs [CRS 02-164]
FX Supported by Mentored Research Scholar Grants No. MRSG-10-170-01-PCSM
(A. B. C.) from the American Cancer Society; No. U01 CA093332 from the
National Cancer Institute to the Dana-Farber Cancer Institute/Cancer
Research Network; No. U01 CA093324 from Harvard Medical School/Northern
California Cancer Center; No. U01 CA093348 from RAND/University of
California, Los Angeles; No. U01 CA093329 from the University of Alabama
at Birmingham; No. U01 CA093339 from the University of Iowa; No. U01
CA093326 from the University of North Carolina; and No. U01 CA093344
from the Statistical Coordinating Center and by Department of Veterans
Affairs Grant No. CRS 02-164 to the Durham VA Medical Center.
NR 29
TC 29
Z9 29
U1 1
U2 6
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 20
PY 2013
VL 31
IS 21
BP 2730
EP 2735
DI 10.1200/JCO.2012.48.5748
PG 6
WC Oncology
SC Oncology
GA 301NJ
UT WOS:000330538700022
PM 23775958
ER
PT J
AU Rae, JM
Regan, M
Leyland-Jones, B
Hayes, DF
Dowsett, M
AF Rae, James M.
Regan, Meredith
Leyland-Jones, Brian
Hayes, Daniel F.
Dowsett, Mitch
TI CYP2D6 Genotype Should Not Be Used for Deciding About Tamoxifen Therapy
in Postmenopausal Breast Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID WOMEN; RECURRENCE; OUTCOMES; TUMORS; 22Q13
C1 [Rae, James M.; Hayes, Daniel F.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Rae, James M.; Hayes, Daniel F.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Regan, Meredith] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Regan, Meredith] Harvard Univ, Sch Med, Boston, MA USA.
[Leyland-Jones, Brian] Sanford Hlth & Res, Sioux Falls, SD USA.
[Dowsett, Mitch] Marsden Hosp, London, England.
[Dowsett, Mitch] Breakthrough Breast Canc Res Ctr, London, England.
RP Rae, JM (reprint author), Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
NR 15
TC 5
Z9 5
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 JUL 20
PY 2013
VL 31
IS 21
BP 2753
EP 2755
DI 10.1200/JCO.2013.49.4278
PG 4
WC Oncology
SC Oncology
GA 301NJ
UT WOS:000330538700030
PM 23775974
ER
PT J
AU Chen, AB
Schrag, D
AF Chen, Aileen B.
Schrag, Deborah
TI Radiation Therapy for Metastatic Non-Small-Cell Lung Cancer: When to
Bring in Palliative Care? Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID PAINFUL BONE METASTASES; FRACTION RADIOTHERAPY; SINGLE; PROGNOSIS
C1 [Chen, Aileen B.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Chen, Aileen B.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Chen, Aileen B.; Schrag, Deborah] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
RP Chen, AB (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
FU NCI NIH HHS [U01 CA093339, U01 CA093329, U01 CA093344, U01 CA093326, U01
CA093348, U01 CA093332, U01 CA093324]
NR 12
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 JUL 20
PY 2013
VL 31
IS 21
BP 2759
EP 2760
DI 10.1200/JCO.2013.50.2088
PG 3
WC Oncology
SC Oncology
GA 301NJ
UT WOS:000330538700036
PM 24040666
ER
PT J
AU Kotloff, KL
Nataro, JP
Blackwelder, WC
Nasrin, D
Farag, TH
Panchalingam, S
Wu, Y
Sow, SO
Sur, D
Breiman, RF
Faruque, ASG
Zaidi, AKM
Saha, D
Alonso, PL
Tamboura, B
Sanogo, D
Onwuchekwa, U
Manna, B
Ramamurthy, T
Kanungo, S
Ochieng, JB
Omore, R
Oundo, JO
Hossain, A
Das, SK
Ahmed, S
Qureshi, S
Quadri, F
Adegbola, RA
Antonio, M
Hossain, MJ
Akinsola, A
Mandomando, I
Nhampossa, T
Acacio, S
Biswas, K
O'Reilly, CE
Mintz, ED
Berkeley, LY
Muhsen, K
Sommerfelt, H
Robins-Browne, RM
Levine, MM
AF Kotloff, Karen L.
Nataro, James P.
Blackwelder, William C.
Nasrin, Dilruba
Farag, Tamer H.
Panchalingam, Sandra
Wu, Yukun
Sow, Samba O.
Sur, Dipika
Breiman, Robert F.
Faruque, Abu S. G.
Zaidi, Anita K. M.
Saha, Debasish
Alonso, Pedro L.
Tamboura, Boubou
Sanogo, Doh
Onwuchekwa, Uma
Manna, Byomkesh
Ramamurthy, Thandavarayan
Kanungo, Suman
Ochieng, John B.
Omore, Richard
Oundo, Joseph O.
Hossain, Anowar
Das, Sumon K.
Ahmed, Shahnawaz
Qureshi, Shahida
Quadri, Farheen
Adegbola, Richard A.
Antonio, Martin
Hossain, M. Jahangir
Akinsola, Adebayo
Mandomando, Inacio
Nhampossa, Tacilta
Acacio, Sozinho
Biswas, Kousick
O'Reilly, Ciara E.
Mintz, Eric D.
Berkeley, Lynette Y.
Muhsen, Khitam
Sommerfelt, Halvor
Robins-Browne, Roy M.
Levine, Myron M.
TI Burden and aetiology of diarrhoeal disease in infants and young children
in developing countries (the Global Enteric Multicenter Study, GEMS): a
prospective, case-control study
SO LANCET
LA English
DT Article
ID ENTEROPATHOGENIC ESCHERICHIA-COLI; SUB-SAHARAN AFRICA; ROTAVIRUS
VACCINATION; CHILDHOOD MORTALITY; ATTRIBUTABLE RISK; EPIDEMIOLOGY;
CASE/CONTROL; CRYPTOSPORIDIOSIS; PERFORMANCE; POPULATION
AB Background Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia.
Methods The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0-59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measure ments, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth.
Findings We enrolled 9439 children with moderate-to-severe diarrhoea and 13 129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella. Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni). Odds of dying during follow-up were 8.5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8.5, 95% CI 5.8-12.5, p<0.0001); most deaths (167 [87.9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio [HR] 1.9; 0.99-3.5) and typical enteropathogenic E coli (HR 2.6; 1.6-4.1) in infants aged 0-11 months, and Cryptosporidium (HR 2.3; 1.3-4.3) in toddlers aged 12-23 months.
Interpretation Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes.
C1 [Kotloff, Karen L.; Nataro, James P.; Blackwelder, William C.; Nasrin, Dilruba; Farag, Tamer H.; Panchalingam, Sandra; Wu, Yukun; Berkeley, Lynette Y.; Muhsen, Khitam; Levine, Myron M.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
[Kotloff, Karen L.; Nataro, James P.; Levine, Myron M.] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA.
[Kotloff, Karen L.; Nataro, James P.; Blackwelder, William C.; Nasrin, Dilruba; Farag, Tamer H.; Panchalingam, Sandra; Wu, Yukun; Muhsen, Khitam; Levine, Myron M.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Nataro, James P.] Univ Virginia, Sch Med, Dept Pediat, Charlottesville, VA 22908 USA.
[Sow, Samba O.; Tamboura, Boubou; Sanogo, Doh; Onwuchekwa, Uma] Ctr Dev Vaccins, Bamako, Mali.
[Sur, Dipika; Manna, Byomkesh; Ramamurthy, Thandavarayan; Kanungo, Suman] Natl Inst Cholera & Enter Dis, Kolkata, India.
[Breiman, Robert F.] US Ctr Dis Control & Prevent, Kenya Off, Global Dis Detect Div, Nairobi, Kenya.
[Faruque, Abu S. G.; Hossain, Anowar; Das, Sumon K.; Ahmed, Shahnawaz] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh.
[Zaidi, Anita K. M.; Qureshi, Shahida; Quadri, Farheen] Aga Khan Univ, Dept Paediat & Child Hlth, Karachi, Pakistan.
[Saha, Debasish; Adegbola, Richard A.; Antonio, Martin; Hossain, M. Jahangir; Akinsola, Adebayo] Med Res Council UK Unit, Fajara, Gambia.
[Alonso, Pedro L.; Mandomando, Inacio; Nhampossa, Tacilta; Acacio, Sozinho] Ctr Invest Saude Manhica, Maputo, Mozambique.
[Alonso, Pedro L.] Hosp Clin Univ Barcelona, Barcelona Ctr Int Hlth Res CRESIB, Barcelona, Spain.
[Ochieng, John B.; Omore, Richard; Oundo, Joseph O.] Ctr Dis Control & Prevent KEMRI CDC, Kenya Med Res Inst, Kisumu, Kenya.
[Adegbola, Richard A.] GlaxoSmithKline Biol, Global Med Affairs, Wavre, Belgium.
[Akinsola, Adebayo] Daffodils Pediat & Family Med, Tucker, GA USA.
[Mandomando, Inacio; Nhampossa, Tacilta; Acacio, Sozinho] Minist Saude, Inst Nacl Saude, Maputo, Mozambique.
[Biswas, Kousick] US Dept Vet Affairs, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA.
[O'Reilly, Ciara E.; Mintz, Eric D.] US Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA USA.
[Berkeley, Lynette Y.] Ctr Drug Evaluat & Res, Off Antimicrobial Prod, Div Antiinfect Prod, Silver Spring, MD USA.
[Sommerfelt, Halvor] Univ Bergen, Ctr Int Hlth, Bergen, Norway.
[Sommerfelt, Halvor] Norwegian Inst Publ Hlth, Div Infect Dis Control, Oslo, Norway.
[Robins-Browne, Roy M.] Univ Melbourne, Royal Childrens Hosp, Murdoch Childrens Res Inst, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia.
RP Kotloff, KL (reprint author), Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
EM kkotloff@medicine.umaryland.edu
OI Robins-Browne, Roy/0000-0001-9179-7884
FU Bill & Melinda Gates Foundation
FX The Bill & Melinda Gates Foundation.
NR 36
TC 604
Z9 616
U1 15
U2 135
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD JUL 20
PY 2013
VL 382
IS 9888
BP 209
EP 222
DI 10.1016/S0140-6736(13)60844-2
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA 193FL
UT WOS:000322543700031
PM 23680352
ER
PT J
AU Doros, G
Pencina, M
Rybin, D
Meisner, A
Fava, M
AF Doros, Gheorghe
Pencina, Michael
Rybin, Denis
Meisner, Allison
Fava, Maurizio
TI A repeated measures model for analysis of continuous outcomes in
sequential parallel comparison design studies
SO STATISTICS IN MEDICINE
LA English
DT Article
DE SPCD; repeated measures; placebo effect
ID PSYCHIATRIC CLINICAL-TRIALS; PLACEBO-RESPONSE
AB Previous authors have proposed the sequential parallel comparison design (SPCD) to address the issue of high placebo response rate in clinical trials. The original use of SPCD focused on binary outcomes, but recent use has since been extended to continuous outcomes that arise more naturally in many fields, including psychiatry. Analytic methods proposed to date for analysis of SPCD trial continuous data included methods based on seemingly unrelated regression and ordinary least squares. Here, we propose a repeated measures linear model that uses all outcome data collected in the trial and accounts for data that are missing at random. An appropriate contrast formulated after the model has been fit can be used to test the primary hypothesis of no difference in treatment effects between study arms. Our extensive simulations show that when compared with the other methods, our approach preserves the type I error even for small sample sizes and offers adequate power and the smallest mean squared error under a wide variety of assumptions. We recommend consideration of our approach for analysis of data coming from SPCD trials. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Doros, Gheorghe; Pencina, Michael; Rybin, Denis; Meisner, Allison] Boston Univ, Dept Biostat, Boston, MA 02118 USA.
[Doros, Gheorghe; Pencina, Michael] HCRI, Boston, MA 02215 USA.
[Doros, Gheorghe] VA Boston Healthcare Syst, Massachusetts Epidemiol Res & Informat Ctr MAVERI, Boston, MA USA.
[Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Doros, G (reprint author), Boston Univ, Dept Biostat, 801 Massachusetts Ave, Boston, MA 02118 USA.
EM doros@bu.edu
OI Rybin, Denis/0000-0002-3657-4829
NR 17
TC 9
Z9 9
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD JUL 20
PY 2013
VL 32
IS 16
BP 2767
EP 2789
DI 10.1002/sim.5728
PG 23
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 164HW
UT WOS:000320400900005
PM 23355369
ER
PT J
AU Mendivil, CO
Robles-Osorio, L
Horton, ES
Hamdy, O
Caballero, AE
AF Mendivil, Carlos O.
Robles-Osorio, Ludivina
Horton, Edward S.
Hamdy, Osama
Caballero, Augusto Enrique
TI Young Hispanics at risk of type 2 diabetes display endothelial
activation, subclinical inflammation and alterations of coagulation and
fibrinolysis
SO DIABETOLOGY & METABOLIC SYNDROME
LA English
DT Article
DE Diabetes; Cardiovacular disease; Endothelial; ICAM-1; Hispanics;
Prevention
ID INTERCELLULAR-ADHESION MOLECULE-1; CORONARY-HEART-DISEASE;
INSULIN-RESISTANCE; ADIPOSE-TISSUE; BODY-FAT; ATHEROSCLEROSIS;
DYSFUNCTION; MARKERS; PROTEIN; WOMEN
AB Background: Hispanics have a high rate of diabetes that exposes them to an increased risk of cardiovascular disease. We hypothesized that many of the pathophysiological mechanisms that cause atherosclerotic disease may be present in young Hispanics who do not have clinical diabetes but are at increased risk of developing it.
Methods: We studied 36 young Hispanic adults without diabetes (ages 18-40). Seventeen participants were at increased risk of developing type 2 diabetes given by overweight and a family history of diabetes on one or both parents (at risk group). Nineteen participants with normal body-mass index and no parental history of diabetes constituted the control group. We measured and compared plasma markers of endothelial dysfunction, disturbed coagulation and fibrinolysis, subclinical inflammation and adipose tissue dysfunction in the at risk and control groups.
Results: Participants at risk of diabetes were more insulin-resistant according to different indicators, and had significantly higher levels of soluble intercellular adhesion molecule-1 (sICAM-1), tissue plasminogen activator (tPA), inhibitor of plasminogen activator-1 (PAi-1), high sensitivity C-reactive protein and free fatty acids, signaling the presence of multiple proatherogenic alterations despite the absence of overt diabetes. Levels of the prothrombotic molecule PAi-1 were most elevated in participants who were not only at risk of diabetes by the study definition, but also abdominally obese.
Conclusions: Young adult Hispanics at risk of type 2 diabetes but without overt disease already bear considerably high levels of markers reflecting processes that lead to the development of atherosclerotic cardiovascular disease.
C1 [Mendivil, Carlos O.] Univ Los Andes, Sch Med, Bogota, Colombia.
[Robles-Osorio, Ludivina; Horton, Edward S.; Hamdy, Osama; Caballero, Augusto Enrique] Harvard Univ, Sch Med, Clin Res Ctr, Joslin Diabet Ctr, Boston, MA 02115 USA.
RP Caballero, AE (reprint author), Harvard Univ, Sch Med, Clin Res Ctr, Joslin Diabet Ctr, Boston, MA 02115 USA.
EM enrique.caballero@joslin.harvard.edu
NR 35
TC 3
Z9 4
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-5996
J9 DIABETOL METAB SYNDR
JI Diabetol. Metab. Syndr.
PD JUL 19
PY 2013
VL 5
AR 37
DI 10.1186/1758-5996-5-37
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 196AH
UT WOS:000322744800001
PM 23870459
ER
PT J
AU Ruan, GX
Kazlauskas, A
AF Ruan, Guo-Xiang
Kazlauskas, Andrius
TI Lactate Engages Receptor Tyrosine Kinases Axl, Tie2, and Vascular
Endothelial Growth Factor Receptor 2 to Activate Phosphoinositide
3-Kinase/Akt and Promote Angiogenesis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PHOSPHATIDYLINOSITOL 3-KINASE; DEPENDENT ACTIVATION; TUMOR ANGIOGENESIS;
PROLONGS SURVIVAL; CELLS; VEGF; EXPRESSION; HYPOXIA; AKT; METABOLISM
AB Although a high level of lactate is quintessential to both tumors and wound healing, the manner by which lactate impacts endothelial cells to promote angiogenesis and thereby create or restore vascular perfusion to growing tissues has not been fully elucidated. Here we report that lactate activated the PI3K/Akt pathway in primary human endothelial cells. Furthermore, activating this signaling pathway was required for lactate-stimulated organization of endothelial cells into tubes and for sprouting of vessels from mouse aortic explants. Lactate engaged the PI3K/Akt pathway via ligand-mediated activation of the three receptor tyrosine kinases Axl, Tie2, and VEGF receptor 2. Neutralizing the ligands for these receptor tyrosine kinases, pharmacologically inhibiting their kinase activity or suppressing their expression largely eliminated the ability of cells and explants to respond to lactate. Elucidating the mechanism by which lactate communicates with endothelial cells presents a previously unappreciated opportunity to improve our understanding of the angiogenic program and to govern it.
C1 [Ruan, Guo-Xiang; Kazlauskas, Andrius] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA.
RP Kazlauskas, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM andrius_kazlauskas@meei.harvard.edu
FU National Institutes of Health [EY018344]; Juvenile Diabetes Research
Foundation Advanced Postdoctoral Fellowship [102011367]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant EY018344 (to A. K.). This work was also supported by
Juvenile Diabetes Research Foundation Advanced Postdoctoral Fellowship
102011367 (to G. X. R.).
NR 51
TC 35
Z9 36
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 19
PY 2013
VL 288
IS 29
BP 21161
EP 21172
DI 10.1074/jbc.M113.474619
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 186AU
UT WOS:000322014400036
PM 23754286
ER
PT J
AU Yang, XH
Meyer, K
Friedl, A
AF Yang, Xinhai
Meyer, Kristy
Friedl, Andreas
TI STAT5 and Prolactin Participate in a Positive Autocrine Feedback Loop
That Promotes Angiogenesis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; N-TERMINAL FRAGMENTS; ANTIANGIOGENIC FACTOR;
RECEPTOR ANTAGONISTS; MOLECULAR-MECHANISMS; GENE-TRANSCRIPTION; CELL
PROLIFERATION; PITUITARY-TUMORS; RETINOIC ACID; FACTOR VEGF
AB We have shown previously that the murine prolactin/growth hormone family member proliferin plays a pivotal role in angiogenesis induced by the FGF2/STAT5 signaling cascade. To delineate the signaling pathway downstream of STAT5 in the human system, where proliferin does not exist, we expressed constitutively active (CA) or dominant-negative (DN) mutant STAT5A in hCMEC/D3 human brain endothelial cells. We found that conditioned medium from CA-STAT5A- but not from DN-STAT5A-overexpressing endothelial cells (EC) is sufficient to induce EC migration and tube formation but not proliferation, indicating that STAT5A regulates the secretion of autocrine proangiogenic factors. We identified prolactin (PRL) as a candidate autocrine factor. CA-STAT5A expression stimulates PRL production at the RNA and protein level, and STAT5A binds to the PRL promoter region, suggesting direct transcriptional regulation. Medium conditioned by CA-STAT5A-over-expressing EC induces phosphorylation of the PRL receptor and activates MAPK. Knockdown of PRL expression by shRNA or blocking of PRL activity with neutralizing antibodies removed the CA-STAT5A-dependent proangiogenic activity from the conditioned medium of EC. The addition of recombinant PRL restores this activity. STAT5A-induced PRL in the conditioned medium can activate STAT5, STAT1, and to a lesser extent STAT3 in hCMEC/D3 cells, suggesting the existence of a positive feedback loop between STAT5 and PRL that promotes angiogenesis. Furthermore, we find that VEGF, a potent proangiogenic factor, is induced by activation of STAT5A, and VEGF induction depends on PRL expression. These observations demonstrate a STAT5/PRL/VEGF signaling cascade in human brain EC and implicate PRL and VEGF as autocrine regulators of EC migration, invasion, and tube formation.
C1 [Yang, Xinhai; 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.
[Friedl, Andreas] UW Carbone Canc Ctr, Madison, WI 53792 USA.
RP Friedl, A (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, 6051 WIMR,MC-2275,1111 Highland Ave, Madison, WI 53705 USA.
EM afriedl@wisc.edu
FU UW Department of Pathology and Laboratory Medicine; UW Carbone Cancer
Center [P30 CA014520]
FX We thank Dr. Charles Clevenger, Northwestern University, for
immunohistochemical labeling of the glioma samples and Dr. Babette
Weksler, Weill Cornell Medical College, for kindly providing hCMEC/D3
cells. Korise Rasmusson helped with manuscript preparation. We thank the
University of Wisconsin Translational Research Initiatives in Pathology
laboratory, in part supported by the UW Department of Pathology and
Laboratory Medicine and UW Carbone Cancer Center Grant P30 CA014520 for
use of its facilities and services.
NR 63
TC 15
Z9 15
U1 0
U2 20
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 19
PY 2013
VL 288
IS 29
BP 21184
EP 21196
DI 10.1074/jbc.M113.481119
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 186AU
UT WOS:000322014400038
PM 23729680
ER
PT J
AU Kembabazi, A
Bajunirwe, F
Hunt, PW
Martin, JN
Muzoora, C
Haberer, JE
Bangsberg, DR
Siedner, MJ
AF Kembabazi, Annet
Bajunirwe, Francis
Hunt, Peter W.
Martin, Jeffrey N.
Muzoora, Conrad
Haberer, Jessica E.
Bangsberg, David R.
Siedner, Mark J.
TI Disinhibition in Risky Sexual Behavior in Men, but Not Women, during
Four Years of Antiretroviral Therapy in Rural, Southwestern Uganda
SO PLOS ONE
LA English
DT Article
ID HIV-INFECTED PATIENTS; SOUTH-AFRICA; PROSPECTIVE COHORT; HOMOSEXUAL-MEN;
PREVENTION; TRANSMISSION; SEROCONVERSION; INTERVENTIONS; METAANALYSIS;
ESTIMATOR
AB Background: In resource-rich areas, risky sexual behavior (RSB) largely diminishes after initiation of anti-retroviral therapy, with notable exceptions among some populations who perceive a protected benefit from anti-retroviral therapy (ART). Yet, there is limited data about long-term trends in risky sexual behavior among HIV-infected people in sub-Saharan Africa after initiation of anti-retroviral therapy.
Methods: We administered questionnaires every three months to collect sexual behavior data among patients taking ART in southwestern Uganda over four years of follow-up time. We defined RSB as having unprotected sex with an HIV-negative or unknown status partner, or unprotected sex with a casual partner. We fit logistic regression models to estimate changes in RSB by time on ART, with and without adjustment for calendar year and CD4 count.
Results: 506 participants were enrolled between 2005 and 2011 and contributed a median of 13 visits and 3.5 years of observation time. The majority were female (70%) and median age was 34 years (interquartile range 29-39). There was a decrease in the proportion of men reporting RSB from the pre-ART visit to the first post-ART visit (16.2 to 4.3%, p < 0.01) but not women (14.1 to 13.3%, p = 0.80). With each year of ART, women reported decreasing RSB (OR 0.85 per year, 95% CI 0.74-0.98, p = 0.03). In contrast, men had increasing odds of reporting RSB with each year of ART to near pre-treatment rates (OR 1.41, 95% CI 1.14-1.74, p = 0.001), which was partially confounded by changes in calendar time and CD4 count (AOR = 1.24, 95% CI 0.92-1.67, p = 0.16).
Conclusions: Men in southwestern Uganda reported increasing RSB over four years on ART, to levels approaching pretreatment rates. Strategies to promote long-term safe sex practices targeted to HIV-infected men on ART might have a significant impact on preventing HIV transmission in this setting.
C1 [Kembabazi, Annet; Muzoora, Conrad] Mbarara Univ Sci & Technol, Dept Med, Mbarara, Uganda.
[Bajunirwe, Francis] Mbarara Univ Sci & Technol, Dept Community Hlth, Mbarara, Uganda.
[Hunt, Peter W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Haberer, Jessica E.; Bangsberg, David R.; Siedner, Mark J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Haberer, Jessica E.; Bangsberg, David R.; Siedner, Mark J.] Harvard Univ, Sch Med, Boston, MA USA.
[Bangsberg, David R.] Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Cambridge, MA USA.
[Bangsberg, David R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Kembabazi, A (reprint author), Mbarara Univ Sci & Technol, Dept Med, Mbarara, Uganda.
EM akembabazi2005@yahoo.com
FU U.S. National Institutes of Health (NIH) [R01 MH54907, P30 AI27763]; NIH
[K23 MH087228, K24 MH87227, T32 AI007433]; Harvard Institute for Global
Health; Mark and Lisa Schwartz Family Foundation; Sullivan Family
Foundation; Bacca Foundation
FX The Uganda AIDS Rural Treatment Outcomes Study is funded by U.S.
National Institutes of Health (NIH) R01 MH54907 and P30 AI27763. The
authors also acknowledge the following additional sources of salary
support: NIH K23 MH087228 (Haberer); NIH K24 MH87227 (Bangsberg); the
Harvard Institute for Global Health and NIH T32 AI007433 (Siedner).
Additional study funding was provided by the Mark and Lisa Schwartz
Family Foundation, the Sullivan Family Foundation, and the Bacca
Foundation. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 36
TC 9
Z9 9
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 19
PY 2013
VL 8
IS 7
AR e69634
DI 10.1371/journal.pone.0069634
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 191CY
UT WOS:000322391400063
PM 23894514
ER
PT J
AU Wojczynski, MK
Li, MY
Bielak, LF
Kerr, KF
Reiner, AP
Wong, ND
Yanek, LR
Qu, LM
White, CC
Lange, LA
Ferguson, JF
He, J
Young, T
Mosley, TH
Smith, JA
Kral, BG
Guo, XQ
Wong, Q
Ganesh, SK
Heckbert, SR
Griswold, ME
O'Leary, DH
Budoff, M
Carr, JJ
Taylor, HA
Bluemke, DA
Demissie, S
Hwang, SJ
Paltoo, DN
Polak, JF
Psaty, BM
Becker, DM
Province, MA
Post, WS
O'Donnell, CJ
Wilson, JG
Harris, TB
Kavousi, M
Cupples, LA
Rotter, JI
Fornage, M
Becker, LC
Peyser, PA
Borecki, IB
Reilly, MP
AF Wojczynski, Mary K.
Li, Mingyao
Bielak, Lawrence F.
Kerr, Kathleen F.
Reiner, Alex P.
Wong, Nathan D.
Yanek, Lisa R.
Qu, Liming
White, Charles C.
Lange, Leslie A.
Ferguson, Jane F.
He, Jing
Young, Taylor
Mosley, Thomas H.
Smith, Jennifer A.
Kral, Brian G.
Guo, Xiuqing
Wong, Quenna
Ganesh, Santhi K.
Heckbert, Susan R.
Griswold, Michael E.
O'Leary, Daniel H.
Budoff, Matthew
Carr, J. Jeffrey
Taylor, Herman A., Jr.
Bluemke, David A.
Demissie, Serkalem
Hwang, Shih-Jen
Paltoo, Dina N.
Polak, Joseph F.
Psaty, Bruce M.
Becker, Diane M.
Province, Michael A.
Post, Wendy S.
O'Donnell, Christopher J.
Wilson, James G.
Harris, Tamara B.
Kavousi, Maryam
Cupples, L. Adrienne
Rotter, Jerome I.
Fornage, Myriam
Becker, Lewis C.
Peyser, Patricia A.
Borecki, Ingrid B.
Reilly, Muredach P.
TI Genetics of coronary artery calcification among African Americans, a
meta-analysis
SO BMC MEDICAL GENETICS
LA English
DT Article
DE Atherosclerosis; Coronary artery calcium; Genetics; Meta-analysis;
African-American
ID GENOME-WIDE ASSOCIATION; BEAM COMPUTED-TOMOGRAPHY; SINGLE NUCLEOTIDE
POLYMORPHISMS; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS MESA;
ETHNIC-DIFFERENCES; RISK-FACTORS; CARDIOVASCULAR-DISEASE; ASYMPTOMATIC
ADULTS; QUANTITATIVE-TRAIT
AB Background: Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants.
Methods: We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with similar to 2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse-variance weighted meta-analysis on results for 5,823 AA from 8 studies. Heritability was calculated using family studies. The most significant SNPs among AAs were evaluated in European Ancestry (EA) CAC data; conversely, the significance of published SNPs for CAC/CHD in EA was queried within our AA meta-analysis.
Results: Heritability of CAC was lower in AA (similar to 30%) than previously reported for EA (similar to 50%). No SNP reached genome wide significance (p < 5E-08). Of 67 SNPs with p < 1E-05 in AA there was no evidence of association in EA CAC data. Four SNPs in regions previously implicated in CAC/CHD (at 9p21 and PHACTR1) in EA reached nominal significance for CAC in AA, with concordant direction. Among AA, rs16905644 (p = 4.08E-05) had the strongest association in the 9p21 region.
Conclusions: While we observed substantial heritability for CAC in AA, we failed to identify loci for CAC at genome-wide significant levels despite having adequate power to detect alleles with moderate to large effects. Although suggestive signals in AA were apparent at 9p21 and additional CAC and CAD EA loci, overall the data suggest that even larger samples and an ethnic specific focus will be required for GWAS discoveries for CAC in AA populations.
C1 [Wojczynski, Mary K.; Province, Michael A.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
[Li, Mingyao; Qu, Liming] Univ Penn, Philadelphia, PA 19104 USA.
[Bielak, Lawrence F.; Smith, Jennifer A.; Peyser, Patricia A.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Kerr, Kathleen F.; Wong, Quenna] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Reiner, Alex P.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Wong, Nathan D.] Univ Calif Irvine, Heart Dis Prevent Program, Irvine, CA USA.
[Yanek, Lisa R.; Kral, Brian G.; Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[White, Charles C.; Demissie, Serkalem] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Ferguson, Jane F.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Ferguson, Jane F.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Young, Taylor] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Guo, Xiuqing; Rotter, Jerome I.] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
[Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Griswold, Michael E.] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA.
[O'Leary, Daniel H.; Polak, Joseph F.] Tufts Univ, Sch Med, Dept Radiol, Boston, MA 02111 USA.
[Budoff, Matthew] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[Carr, J. Jeffrey] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC USA.
[Taylor, Herman A., Jr.] Jackson State Univ, Tougaloo Coll, Jackson, MS USA.
[Taylor, Herman A., Jr.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Hwang, Shih-Jen; O'Donnell, Christopher J.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Hwang, Shih-Jen] Ctr Populat Studies, Framingham, MA USA.
[Paltoo, Dina N.] NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.
[Post, Wendy S.] Johns Hopkins Sch Med & Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Post, Wendy S.] Johns Hopkins Sch Med & Publ Hlth, Dept Med, Baltimore, MD USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA.
[O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA.
[Wilson, James G.] Univ Mississippi, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Kavousi, Maryam] Netherlands Genom Initiat Sponsored Netherlands C, Rotterdam, Netherlands.
[Kavousi, Maryam] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Fornage, Myriam] Univ Texas Houston, Houston Inst Mol Med, Houston, TX USA.
RP Wojczynski, MK (reprint author), Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
EM mwojczynski@wustl.edu; iborecki@wustl.edu; Muredach@mail.med.upenn.edu
RI Ferguson, Jane/C-7154-2011; Carr, John/A-1938-2012; Kerr,
Kathleen/A-2893-2013;
OI Ferguson, Jane/0000-0001-6896-1025; Carr, John/0000-0002-4398-8237;
Cupples, L. Adrienne/0000-0003-0273-7965; Bluemke,
David/0000-0002-8323-8086; Smith, Jennifer/0000-0002-3575-5468
FU NIH from NHLBI [R01-HL-087700, R01-HL-088215]; NIH from NIDDK
[R01-DK-8925601, R01-DK-075681]; National Heart, Lung, and Blood
Institute; University of Alabama at Birmingham [N01-HC-48047,
N01-HC-95095]; University of Minnesota [N01-HC-48048, N01-HC-95163];
Northwestern University [N01-HC-48049, N01-HC-95164]; Kaiser Foundation
Research Institute [N01-HC-48050]; Tufts-New England Medical Center
[N01-HC-45204]; Wake Forest University [N01-HC-45205, N01-HC-95165];
Harbor-UCLA Research and Education Institute [N01-HC-05187,
N01-HC-95169]; University of California, Irvine [N01-HC-45134,
N01-HC-95100]; Jackson Heart Study (JHS): Jackson State University
[N01-HC-95170]; University of Mississippi [N01-HC-95171]; Tougaloo
College [N01-HC-95172]; Multi-Ethnic Study of Atherosclerosis (MESA):
University of Washington [N01-HC-95159]; Regents of the University of
California [N01-HC-95160]; Columbia University [N01-HC-95161]; Johns
Hopkins University [N01-HC-95162, N01-HC-95168]; University of Vermont
[N01-HC-95166]; New England Medical Center [N01-HC-95167]; Cedars-Sinai
Medical Center [R01-HL-071205]; University of Virginia [R01-HL-071205];
National Heart, Lung, and Blood Institute [N01-HC-48047, N01-HC-95095,
N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45204, N01-HC-45205,
N01-HC-05187, N01-HC-45134]; NHLBI's Candidate-gene Association REsource
(CARe) Study; National Heart, Lung, and Blood Institute (NHLBI); United
States Environmental Protection Agency (EPA); NHLBI [N02-HL-6-4278];
National Heart, Lung, and Blood Institute (NHLBI) through the STAMPEED
[R01 HL087698-01]; NIH/National Institute of Nursing Research
[NR008153-01]; NIH/National Center for Research Resources
[M01-RR000052]; National Institutes of Health from National Heart, Lung,
Blood Institute [HL085571, HL087660, HL100245]; AXA Research Fund;
[R01-HL084099]; [U01-HG004729]; [R01HL071051]; [R01HL071205];
[R01HL071250]; [R01HL071251]; [R01HL071252]; [R01HL071258];
[R01HL071259]; [RD83169701]; [HL58625-01A1]; [HL59684];
[HL071025-01A1]; [R01-DK071224]; [R01-DK-090505]; [U01-HL108636];
[K24-HL107643]; [R01-HL113147]
FX The National Heart, Lung, and Blood Institute's Family Heart Study
(FamHS) was supported by NIH grants R01-HL-087700 and R01-HL-088215
(Michael A. Province, PI) from NHLBI; and R01-DK-8925601 and
R01-DK-075681 (Ingrid B. Borecki, PI) from NIDDK.; The authors from the
CARe Consortium wish to acknowledge the support of the National Heart,
Lung, and Blood Institute and the contributions of the research
institutions, study investigators, field staff and study participants in
creating this resource for biomedical research. The following studies
have contributed parent study data, ancillary study data, and DNA
samples through the Broad Institute (N01-HC-65226).; Coronary Artery
Risk in Young Adults (CARDIA): University of Alabama at Birmingham
(N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern
University (N01-HC-48049), Kaiser Foundation Research Institute
(N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095),
Tufts-New England Medical Center (N01-HC-45204), Wake Forest University
(N01-HC-45205), Harbor-UCLA Research and Education Institute
(N01-HC-05187), University of California, Irvine (N01-HC-45134,
N01-HC-95100); Jackson Heart Study (JHS): Jackson State University
(N01-HC-95170), University of Mississippi (N01-HC-95171), Tougaloo
College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis (MESA):
University of Washington (N01-HC-95159), Regents of the University of
California (N01-HC-95160), Columbia University (N01-HC-95161), Johns
Hopkins University (N01-HC-95162, N01-HC-95168), University of Minnesota
(N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest
University (N01-HC-95165), University of Vermont (N01-HC-95166), New
England Medical Center (N01-HC-95167), Harbor-UCLA Research and
Education Institute (N01-HC-95169), Cedars-Sinai Medical Center
(R01-HL-071205), University of Virginia (subcontract to R01-HL-071205).;
The Coronary Artery Risk Development in Young Adults (CARDIA) study is
funded by contracts N01-HC-95095, N01-HC-48047, N01-HC-48048,
N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205,
and N01-HC-45204 from the National Heart, Lung, and Blood Institute to
the CARDIA investigators. GWAS genotyping and quality control for the
CARDIA African-Americans was supported by the NHLBI's Candidate-gene
Association REsource (CARe) Study. Statistical analysis of CARDIA data
was supported by grants R01-HL084099 and U01-HG004729 to MF. This
manuscript has been reviewed by CARDIA for scientific content and
consistency of data interpretation with previous CARDIA publications.;
The MESA Family/Air Studies were conducted and supported by the National
Heart, Lung, and Blood Institute (NHLBI) and the United States
Environmental Protection Agency (EPA) in collaboration with MESA Family
and MESA Air investigators, respectively. Support for MESA Family is
provided by grants and contracts R01HL071051, R01HL071205, R01HL071250,
R01HL071251, R01HL071252, R01HL071258, and R01HL071259. Support for MESA
Air is provided by grant RD83169701. Funding for genotyping was provided
by NHLBI Contract N02-HL-6-4278. Genotyping was performed at the Broad
Institute of Harvard and MIT (Boston, Massachusetts, USA) and at
Affymetrix (Santa Clara, California, USA) using the Affymetrix
Genome-Wide Human SNP Array 6.0.; The GeneSTAR Study was supported by
the National Heart, Lung, and Blood Institute (NHLBI) through the
STAMPEED (R01 HL087698-01) consortium as well as grants HL58625-01A1,
HL59684, and HL071025-01A1, and a grant from the NIH/National Institute
of Nursing Research (NR008153-01).; Additional support was provided by a
grant from the NIH/National Center for Research Resources (M01-RR000052)
to the Johns Hopkins General Clinical Research Center.; The Genetic
Epidemiology Network of Arteriopathy (GENOA) is supported by the
National Institutes of Health, grant numbers HL085571, HL087660, and
HL100245 from National Heart, Lung, Blood Institute. We thank Eric
Boerwinkle, PhD from the Human Genetics Center and Institute of
Molecular Medicine and Division of Epidemiology, University of Texas
Health Science Center, Houston, Texas, USA and Julie Cunningham, PhD
from the Department of Health Sciences Research, Mayo Clinic College of
Medicine, Rochester, MN, USA for their help with genotyping.; MPR is
supported by R01-DK071224, R01-DK-090505, U01-HL108636, K24-HL107643 and
R01-HL113147.; MK is supported by the AXA Research Fund.
NR 46
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PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD JUL 19
PY 2013
VL 14
AR 75
DI 10.1186/1471-2350-14-75
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 193ED
UT WOS:000322539700001
PM 23870195
ER
PT J
AU Santagata, S
Mendillo, ML
Tang, YC
Subramanian, A
Perley, CC
Roche, SP
Wong, B
Narayan, R
Kwon, H
Koeva, M
Amon, A
Golub, TR
Porco, JA
Whitesell, L
Lindquist, S
AF Santagata, Sandro
Mendillo, Marc L.
Tang, Yun-chi
Subramanian, Aravind
Perley, Casey C.
Roche, Stephane P.
Wong, Bang
Narayan, Rajiv
Kwon, Hyoungtae
Koeva, Martina
Amon, Angelika
Golub, Todd R.
Porco, John A., Jr.
Whitesell, Luke
Lindquist, Susan
TI Tight Coordination of Protein Translation and HSF1 Activation Supports
the Anabolic Malignant State
SO SCIENCE
LA English
DT Article
ID HEAT-SHOCK FACTOR-1; TRANSCRIPTION FACTOR HSF1; EUKARYOTIC TRANSLATION;
AMINO-ACID; IN-VITRO; CANCER; EXPRESSION; STRESS; SILVESTROL; INHIBITORS
AB The ribosome is centrally situated to sense metabolic states, but whether its activity, in turn, coherently rewires transcriptional responses is unknown. Here, through integrated chemical-genetic analyses, we found that a dominant transcriptional effect of blocking protein translation in cancer cells was inactivation of heat shock factor 1 (HSF1), a multifaceted transcriptional regulator of the heat-shock response and many other cellular processes essential for anabolic metabolism, cellular proliferation, and tumorigenesis. These analyses linked translational flux to the regulation of HSF1 transcriptional activity and to the modulation of energy metabolism. Targeting this link with translation initiation inhibitors such as rocaglates deprived cancer cells of their energy and chaperone armamentarium and selectively impaired the proliferation of both malignant and premalignant cells with early-stage oncogenic lesions.
C1 [Santagata, Sandro] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA.
[Santagata, Sandro] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Santagata, Sandro] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Santagata, Sandro; Mendillo, Marc L.; Perley, Casey C.; Kwon, Hyoungtae; Koeva, Martina; Whitesell, Luke; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Mendillo, Marc L.; Tang, Yun-chi; Perley, Casey C.; Kwon, Hyoungtae; Koeva, Martina; Amon, Angelika; Lindquist, Susan] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02142 USA.
[Tang, Yun-chi; Amon, Angelika] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA.
[Tang, Yun-chi; Amon, Angelika] MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA.
[Subramanian, Aravind; Wong, Bang; Narayan, Rajiv; Golub, Todd R.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Roche, Stephane P.; Porco, John A., Jr.] Boston Univ, Dept Chem, Ctr Chem Methodol & Lib Dev CMLD BU, Boston, MA 02215 USA.
RP Whitesell, L (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM whitesell@wi.mit.edu; lindquist_admin@wi.mit.edu
FU Johnson & Johnson's Corporate Office of Science and Technology; Marble
Fund; NIH [R01 CA175744-01, K08NS064168]; NIH Common Fund's LINCS
program [5U54HG006093]; American Cancer Society New England
Division-SpinOdyssey [PF-09-253-01-DMC]; Brain Science Foundation;
American Brain Tumor Association; Beez Foundation; V Foundation; Jared
Branfman Sunflowers for Life Fund; [R03 MH086465-01]; [R03
DA027713-01]; [R01 GM073855]
FX We thank T. Volkert, J. Love, S. Gupta, and the WIBR-Genome Technology
Core for sequencing support; S. Malstrom (Koch Institute for Integrative
Cancer Research) for assistance with in vivo imaging; G. Bell, P. Thiru,
and A. Lancaster for assistance with informatics analysis; the
Connectivity Map team at the Broad Institute for generation of the LINCS
data set and query tools; Joe Negri and the MLPCN team at the Broad
Institute for chemical screening; and M. Duquette for assistance with
animal experiments. We also thank C. Rodrigo (Boston University) for
compound synthesis. We thank the Lindquist laboratory for helpful
discussions and suggestions. The work was supported by the Johnson &
Johnson's Corporate Office of Science and Technology focused funding
program (L. W.), the Marble Fund (S. L.), and NIH R01 CA175744-01 (L.
W.). The MLPCN screen was supported by R03 MH086465-01 and R03
DA027713-01 to L. W. This work was supported by the NIH Common Fund's
LINCS program (5U54HG006093, "Large scale gene expression analysis of
cellular states") to T. R. G. J. A. P. Jr. is supported by R01 GM073855.
S. L. is an Investigator of the Howard Hughes Medical Institute. M. L.
M. was supported by American Cancer Society New England
Division-SpinOdyssey (PF-09-253-01-DMC). S. S. is supported by NIH
(K08NS064168), the Brain Science Foundation, the American Brain Tumor
Association, the Beez Foundation, the V Foundation, and the Jared
Branfman Sunflowers for Life Fund. The expression profiling and ChIP-Seq
data are deposited in GEO (GSE45853). The MLPCN chemical screening data
are deposited in Pubchem (AID: 2118).
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PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JUL 19
PY 2013
VL 341
IS 6143
BP 250
EP +
AR 1238303
DI 10.1126/science.1238303
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 185HV
UT WOS:000321959300034
PM 23869022
ER
PT J
AU Farkas, MH
Grant, GR
White, JA
Sousa, ME
Consugar, MB
Pierce, EA
AF Farkas, Michael H.
Grant, Gregory R.
White, Joseph A.
Sousa, Maria E.
Consugar, Mark B.
Pierce, Eric A.
TI Transcriptome analyses of the human retina identify unprecedented
transcript diversity and 3.5 Mb of novel transcribed sequence via
significant alternative splicing and novel genes
SO BMC GENOMICS
LA English
DT Article
DE RNA-Seq; Transcriptome; Inherited retinal degeneration; Retina; Novel
genes; Alternative splicing
ID LEBERS CONGENITAL AMAUROSIS; BARDET-BIEDL SYNDROME; LONG NONCODING RNAS;
GENOME ANNOTATION; MAMMALIAN TRANSCRIPTOMES; PIGMENT-EPITHELIUM; KABUKI
SYNDROME; DISEASE GENES; HUMAN TISSUES; EXPRESSION
AB Background: The retina is a complex tissue comprised of multiple cell types that is affected by a diverse set of diseases that are important causes of vision loss. Characterizing the transcripts, both annotated and novel, that are expressed in a given tissue has become vital for understanding the mechanisms underlying the pathology of disease.
Results: We sequenced RNA prepared from three normal human retinas and characterized the retinal transcriptome at an unprecedented level due to the increased depth of sampling provided by the RNA-seq approach. We used a non-redundant reference transcriptome from all of the empirically-determined human reference tracks to identify annotated and novel sequences expressed in the retina. We detected 79,915 novel alternative splicing events, including 29,887 novel exons, 21,757 3 ' and 5 ' alternate splice sites, and 28,271 exon skipping events. We also identified 116 potential novel genes. These data represent a significant addition to the annotated human transcriptome. For example, the novel exons detected increase the number of identified exons by 3%. Using a high-throughput RNA capture approach to validate 14,696 of these novel transcriptome features we found that 99% of the putative novel events can be reproducibly detected. Further, 15-36% of the novel splicing events maintain an open reading frame, suggesting they produce novel protein products.
Conclusions: To our knowledge, this is the first application of RNA capture to perform large-scale validation of novel transcriptome features. In total, these analyses provide extensive detail about a previously uncharacterized level of transcript diversity in the human retina.
C1 [Farkas, Michael H.; White, Joseph A.; Sousa, Maria E.; Consugar, Mark B.; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst,Dept Ophthalmol, Boston, MA 02114 USA.
[Farkas, Michael H.; White, Joseph A.; Sousa, Maria E.; Consugar, Mark B.; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Berman Gund Lab Study Retinal Deg, Boston, MA USA.
[Grant, Gregory R.] Univ Penn, Penn Ctr Bioinformat, Philadelphia, PA 19104 USA.
RP Pierce, EA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst,Dept Ophthalmol, Boston, MA 02114 USA.
EM eric_pierce@meei.harvard.edu
OI Pierce, Eric/0000-0002-2354-4102
FU National Institutes of Health [RO1-EY020902, RO1-EY012910,
F32-EY020747]; Foundation Fighting Blindness USA; Penn Genome Frontiers
Institute
FX We thank the Penn Genome Frontiers Institute at the University of
Pennsylvania for sequencing the retinal transcriptome samples. This work
was supported by grants from the National Institutes of Health
RO1-EY020902 (EAP), RO1-EY012910 (E. A. P.), F32-EY020747 (M. H. F.);
the Foundation Fighting Blindness USA; the Penn Genome Frontiers
Institute. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the funding
organizations or the National Institutes of Health.
NR 92
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PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUL 18
PY 2013
VL 14
AR 486
DI 10.1186/1471-2164-14-486
PG 14
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 274RW
UT WOS:000328624900001
PM 23865674
ER
PT J
AU Smith, BW
Rozelle, SS
Leung, A
Ubellacker, J
Parks, A
Nah, SK
French, D
Gadue, P
Monti, S
Chui, DHK
Steinberg, MH
Frelinger, AL
Michelson, AD
Theberge, R
McComb, ME
Costello, CE
Kotton, DN
Mostoslavsky, G
Sherr, DH
Murphy, GJ
AF Smith, Brenden W.
Rozelle, Sarah S.
Leung, Amy
Ubellacker, Jessalyn
Parks, Ashley
Nah, Shirley K.
French, Deborah
Gadue, Paul
Monti, Stefano
Chui, David H. K.
Steinberg, Martin H.
Frelinger, Andrew L.
Michelson, Alan D.
Theberge, Roger
McComb, Mark E.
Costello, Catherine E.
Kotton, Darrell N.
Mostoslavsky, Gustavo
Sherr, David H.
Murphy, George J.
TI The aryl hydrocarbon receptor directs hematopoietic progenitor cell
expansion and differentiation
SO BLOOD
LA English
DT Article
ID PLURIPOTENT STEM-CELLS; BREAST-CANCER CELLS; REGULATORY T-CELLS;
GENE-EXPRESSION; AHR REPRESSOR; GENERATION;
2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; ACTIVATION; PLATELETS; RESPONSES
AB The evolutionarily conserved aryl hydrocarbon receptor (AhR) has been studied for its role in environmental chemical-induced toxicity. However, recent studies have demonstrated that the AhR may regulate the hematopoietic and immune systems during development in a cell-specific manner. These results, together with the absence of an in vitro model system enabling production of large numbers of primary human hematopoietic progenitor cells (HPs) capable of differentiating into megakaryocyte- and erythroid-lineage cells, motivated us to determine if AhR modulation could facilitate both progenitor cell expansion and megakaryocyte and erythroid cell differentiation. Using a novel, pluripotent stem cell-based, chemically-defined, serum and feeder cell-free culture system, we show that the AhR is expressed in HPs and that, remarkably, AhR activation drives an unprecedented expansion of HPs, megakaryocyte-lineage cells, and erythroid-lineage cells. Further AhR modulation within rapidly expanding progenitor cell populations directs cell fate, with chronic AhR agonism permissive to erythroid differentiation and acute antagonism favoring megakaryocyte specification. These results highlight the development of a new Good Manufacturing Practice-compliant platform for generating virtually unlimited numbers of human HPs with which to scrutinize red blood cell and platelet development, including the assessment of the role of the AhR critical cell fate decisions during hematopoiesis.
C1 [Smith, Brenden W.; Rozelle, Sarah S.; Leung, Amy; Nah, Shirley K.; Chui, David H. K.; Steinberg, Martin H.; Murphy, George J.] Boston Univ, Dept Med, Sch Med, Sect Hematol & Oncol, Boston, MA 02118 USA.
[Smith, Brenden W.; Rozelle, Sarah S.; Leung, Amy; Nah, Shirley K.; Kotton, Darrell N.; Mostoslavsky, Gustavo; Murphy, George J.] Boston Univ, Ctr Regenerat Med, Boston, MA 02118 USA.
[Smith, Brenden W.; Rozelle, Sarah S.; Leung, Amy; Nah, Shirley K.; Kotton, Darrell N.; Mostoslavsky, Gustavo; Murphy, George J.] Boston Med Ctr, Boston, MA USA.
[Ubellacker, Jessalyn; Parks, Ashley; Sherr, David H.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02118 USA.
[French, Deborah; Gadue, Paul] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA.
[Monti, Stefano] Boston Univ, Sect Computat Biomed, Sch Med, Dept Med, Boston, MA 02118 USA.
[Frelinger, Andrew L.; Michelson, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Boston Childrens Hosp, Ctr Platelet Res Studies,Div Hematol Oncol, Boston, MA 02115 USA.
[Theberge, Roger; McComb, Mark E.; Costello, Catherine E.] Boston Univ, Ctr Biomed Mass Spectrometry, Sch Med, Boston, MA 02118 USA.
RP Murphy, GJ (reprint author), Boston Univ, Ctr Regenerat Med, Sch Med, 650 Albany St,Suite 444, Boston, MA 02118 USA.
EM gjmurphy@bu.edu
OI Costello, Catherine/0000-0003-1594-5122; Steinberg,
Martin/0000-0001-8800-8020; Monti, Stefano/0000-0002-9376-0660; McComb,
Mark/0000-0002-4249-485X; Sherr, David/0000-0003-3353-0553; Murphy,
George/0000-0003-3464-793X; Kotton, Darrell/0000-0002-9604-8476
FU National Institutes of Health (NIH) [U01 HL107443-01]; American Society
of Hematology Scholar Award; Affinity Research Collaborative award from
the Evans Center for Interdisciplinary Research at Boston University;
NIH [5T32HL007501-30, P01-ES11624, P42ES007381]; Art beCAUSE Breast
Cancer Foundation; NIH Mass Spectrometer Resource [P41 GM104603]; NIH
National Heart, Lung, and Blood Institute Proteomics contract
[HHSN268201000031C]; Shared Instrument grant: MALDI-TOF/TOF [S10
OD010724]
FX This work was supported by National Institutes of Health (NIH) U01
HL107443-01, an American Society of Hematology Scholar Award, and an
Affinity Research Collaborative award from the Evans Center for
Interdisciplinary Research at Boston University (G.J.M.); an NIH
training grant 5T32HL007501-30 (S. S. R.); NIH P01-ES11624, P42ES007381,
and the Art beCAUSE Breast Cancer Foundation (J.U., A. P., and D. H.
S.); and by NIH Mass Spectrometer Resource (P41 GM104603), an NIH
National Heart, Lung, and Blood Institute Proteomics contract
(HHSN268201000031C), and a Shared Instrument grant: MALDI-TOF/TOF
(matrix-assisted laser
desorption/ionization-time-of-flight/time-of-flight) Mass Spectrometer
(S10 OD010724) (C. E. C., M. E. M., and R.T.).
NR 49
TC 32
Z9 34
U1 4
U2 16
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUL 18
PY 2013
VL 122
IS 3
BP 376
EP 385
DI 10.1182/blood-2012-11-466722
PG 10
WC Hematology
SC Hematology
GA 196QM
UT WOS:000322790500014
PM 23723449
ER
PT J
AU Frakt, AB
Trafton, J
Wallace, A
Neuman, M
Pizer, S
AF Frakt, Austin B.
Trafton, Jodie
Wallace, Amy
Neuman, Matthew
Pizer, Steven
TI Directed funding to address under-provision of treatment for substance
use disorders: a quantitative study
SO IMPLEMENTATION SCIENCE
LA English
DT Article
DE Substance use disorder; Veterans; Veterans Health Administration;
Funding
ID HEALTH-CARE UTILIZATION; ABUSE TREATMENT; ALCOHOLISM-TREATMENT;
MENTAL-HEALTH; BLOCK GRANTS; DRUG-ABUSE; COSTS; STATE; INTERVENTIONS;
BENEFIT
AB Background: Substance use disorders (SUDs) are a substantial problem in the United States (U. S.), affecting far more people than receive treatment. This is true broadly and within the U. S. military veteran population, which is our focus. To increase funding for treatment, the Veterans Health Administration (VA) has implemented several initiatives over the past decade to direct funds toward SUD treatment, supplementing the unrestricted funds VA medical centers receive. We study the 'flypaper effect' or the extent to which these directed funds have actually increased SUD treatment spending.
Methods: The study sample included all VA facilities and used observational data spanning years 2002 to 2010. Data were analyzed with a fixed effects, ordinary least squares specification with monetized workload as the dependent variable and funding dedicated to SUD specialty clinics the key dependent variable, controlling for unrestricted funding.
Results: We observed different effects of dedicated SUD specialty clinic funding over the period 2002 to 2008 versus 2009 to 2010. In the earlier period, there is no evidence of a significant portion of the dedicated funding sticking to its target. In the later period, a substantial proportion-38% in 2009 and 61% in 2010-of funding dedicated to SUD specialty clinics did translate into increased medical center spending for SUD treatment. In comparison, only five cents of every dollar of unrestricted funding is spent on SUD treatment.
Conclusions: Relative to unrestricted funding, dedicated funding for SUD treatment was much more effective in increasing workload, but only in years 2009 and 2010. The differences in those years relative to prior ones may be due to the observed management focus on SUD and SUD-related treatment in the later years. If true, this suggests that in a centrally directed healthcare organization such as the VA, funding dedicated to a service is a necessary, but not sufficient condition for increasing resources expended for that service.
C1 [Frakt, Austin B.; Pizer, Steven] Boston Univ, VA Boston Healthcare Syst, Boston, MA 02215 USA.
[Frakt, Austin B.; Pizer, Steven] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Trafton, Jodie; Neuman, Matthew] VA Palo Alto Healthcare Syst, Program Evaluat & Resource Ctr, Menlo Pk, CA USA.
[Wallace, Amy] Vet Adm North Texas Hlth Care Syst, Dept Psychiat, Bonham, TX USA.
RP Frakt, AB (reprint author), Boston Univ, VA Boston Healthcare Syst, Boston, MA 02215 USA.
EM frakt@bu.edu
FU VA Program Evaluation and Resource Center as part of an evaluation of VA
SUD funding initiatives
FX This work was funded by the VA Program Evaluation and Resource Center as
part of an evaluation of VA SUD funding initiatives and was deemed to be
non-generalizable program evaluation and thus non-research. The views
expressed are those of the authors and do not necessarily reflect the
position or policy of the Department of Veterans Affairs or the United
States government.
NR 38
TC 4
Z9 4
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD JUL 18
PY 2013
VL 8
AR 79
DI 10.1186/1748-5908-8-79
PG 8
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 189GO
UT WOS:000322255600001
PM 23866119
ER
PT J
AU Baggett, TP
Tobey, ML
Rigotti, NA
AF Baggett, Travis P.
Tobey, Matthew L.
Rigotti, Nancy A.
TI Tobacco Use among Homeless People - Addressing the Neglected Addiction
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID SMOKING
C1 [Baggett, Travis P.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Div Gen Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
[Tobey, Matthew L.] Massachusetts Gen Hosp, Global Primary Care Program, Boston, MA 02114 USA.
[Baggett, Travis P.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Baggett, Travis P.] Boston Hlth Care Homeless Program, Boston, MA USA.
RP Baggett, TP (reprint author), Massachusetts Gen Hosp, Div Gen Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
NR 5
TC 20
Z9 20
U1 1
U2 10
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 18
PY 2013
VL 369
IS 3
BP 201
EP 204
DI 10.1056/NEJMp1301935
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 185DQ
UT WOS:000321945800002
PM 23863048
ER
PT J
AU Woo, SB
Stone, JH
Kraft, S
AF Woo, Sook-Bin
Stone, John H.
Kraft, Stefan
TI Case 22-2013: A 51-Year-Old Woman with Epistaxis and Oral Mucosal Ulcers
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ERYTHEMA MULTIFORME; WEGENERS-GRANULOMATOSIS; PEMPHIGUS-VULGARIS;
LONG-TERM; RITUXIMAB; MANIFESTATIONS; CRITERIA; DISEASE; PATHOGENESIS;
DIAGNOSIS
C1 [Woo, Sook-Bin] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Woo, Sook-Bin] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Stone, John H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kraft, Stefan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Woo, Sook-Bin] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
[Stone, John H.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Kraft, Stefan] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Woo, SB (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
FU Genentech and Roche
FX Dr. Stone reports receiving consulting fees from Genentech and Roche,
grant support through his institution from Genentech and Roche, and
travel support through his institution from Genentech, Biogen Idec, and
Genzyme. No other potential conflict of interest relevant to this
article was reported.
NR 26
TC 1
Z9 1
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 18
PY 2013
VL 369
IS 3
BP 265
EP 274
DI 10.1056/NEJMcpc1209275
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 185DQ
UT WOS:000321945800013
PM 23863054
ER
PT J
AU Song, SJ
Poliseno, L
Song, MS
Ala, U
Webster, K
Ng, C
Beringer, G
Brikbak, NJ
Yuan, X
Cantley, LC
Richardson, AL
Pandolfi, PP
AF Song, Su Jung
Poliseno, Laura
Song, Min Sup
Ala, Ugo
Webster, Kaitlyn
Ng, Christopher
Beringer, Gary
Brikbak, Nicolai J.
Yuan, Xin
Cantley, Lewis C.
Richardson, Andrea L.
Pandolfi, Pier Paolo
TI MicroRNA-Antagonism Regulates Breast Cancer Stemness and Metastasis via
TET-Family-Dependent Chromatin Remodeling
SO CELL
LA English
DT Article
ID ESTROGEN-RECEPTOR-ALPHA; MESENCHYMAL TRANSITION; 5-HYDROXYMETHYLCYTOSINE
CONTENT; EPITHELIAL PHENOTYPE; DOWN-REGULATION; MIR-200 FAMILY;
MESSENGER-RNA; HUMAN GENES; TGF-BETA; CELLS
AB Tumor cells metastasize to distant organs through genetic and epigenetic alterations, including changes in microRNA (miR) expression. Here we find miR-22 triggers epithelial-mesenchymal transition (EMT), enhances invasiveness and promotes metastasis in mouse xenografts. In a conditional mammary gland-specific transgenic (TG) mouse model, we show that miR-22 enhances mammary gland side-branching, expands the stem cell compartment, and promotes tumor development. Critically, miR-22 promotes aggressive metastatic disease in MMTV-miR-22 TG mice, as well as compound MMTV-neu or -PyVT-miR-22 TG mice. We demonstrate that miR-22 exerts its metastatic potential by silencing antimetastatic miR-200 through direct targeting of the TET (Ten eleven translocation) family of methylcytosine dioxygenases, thereby inhibiting demethylation of the mir-200 promoter. Finally, we show that miR-22 overexpression correlates with poor clinical outcomes and silencing of the TET-miR-200 axis in patients. Taken together, our findings implicate miR-22 as a crucial epigenetic modifier and promoter of EMT and breast cancer stemness toward metastasis.
C1 [Song, Su Jung; Poliseno, Laura; Song, Min Sup; Ala, Ugo; Webster, Kaitlyn; Ng, Christopher; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Canc Genet Program,Div Genet,Dept Med & Pathol, Boston, MA 02115 USA.
[Ng, Christopher; Cantley, Lewis C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct,Dept Med, Boston, MA 02115 USA.
[Yuan, Xin] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Hematol Oncol Div,Dept Med, Boston, MA 02115 USA.
[Beringer, Gary; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Brikbak, Nicolai J.; Richardson, Andrea L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Pandolfi, PP (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Canc Genet Program,Div Genet,Dept Med & Pathol, Boston, MA 02115 USA.
EM ppandolf@bidmc.harvard.edu
RI Cantley, Lewis/D-1800-2014; Poliseno, Laura/B-5711-2012; Ala,
Ugo/K-2029-2016
OI Cantley, Lewis/0000-0002-1298-7653; Poliseno, Laura/0000-0001-6557-955X;
Ala, Ugo/0000-0001-5408-6397
FU NIH [CA 082328-14]
FX We are grateful to all members of the Pandolfi lab and in particular to
Keisuke Ito and Leonardo Salmena for advice and discussion. We thank
Thomas Garvey for critical editing of the manuscript as well as Yvonne
Tay, Luo Man-Lee, April Greene-Colozzi, and Soon Jung Kim for
experimental and technical support. This work was supported by NIH grant
CA 082328-14 awarded to P.P.P.
NR 60
TC 161
Z9 163
U1 9
U2 74
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUL 18
PY 2013
VL 154
IS 2
BP 311
EP 324
DI 10.1016/j.cell.2013.06.026
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 185FF
UT WOS:000321950700009
PM 23830207
ER
PT J
AU Manoach, DS
Agam, Y
AF Manoach, Dara S.
Agam, Yigal
TI Neural markers of errors as endophenotypes in neuropsychiatric disorders
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Review
DE error-related negativity; anterior cingulate; error processing; response
monitoring; imaging genetics
ID ANTERIOR CINGULATE CORTEX; OBSESSIVE-COMPULSIVE DISORDER; AUTISM
SPECTRUM DISORDERS; EVENT-RELATED FMRI; MEDIAL FRONTAL-CORTEX; DOPAMINE
D2 RECEPTOR; HIGH-FUNCTIONING AUTISM; CATECHOL-O-METHYLTRANSFERASE;
MATTER DIFFUSION ANISOTROPY; DEFAULT MODE NETWORK
AB Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach.
C1 [Manoach, Dara S.; Agam, Yigal] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA.
[Manoach, Dara S.; Agam, Yigal] Harvard Univ, Sch Med, Boston, MA USA.
[Manoach, Dara S.; Agam, Yigal] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Manoach, DS (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 1-111, Charlestown, MA 02129 USA.
EM dara@nmr.mgh.harvard.edu
FU National Institute for Mental Health [R01 MH67720, F32 MH088081]
FX The authors are grateful to Jordan Smoller and Daniel Z. Press for
consultation. Support: National Institute for Mental Health: R01 MH67720
(Dara S. Manoach); F32 MH088081 (Yigal Agam).
NR 258
TC 24
Z9 25
U1 6
U2 33
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD JUL 18
PY 2013
VL 7
AR 350
DI 10.3389/fnhum.2013.00350
PG 19
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA 185CM
UT WOS:000321942800001
PM 23882201
ER
PT J
AU Ebert, DH
Gabel, HW
Robinson, ND
Kastan, NR
Hu, LS
Cohen, S
Navarro, AJ
Lyst, MJ
Ekiert, R
Bird, AP
Greenberg, ME
AF Ebert, Daniel H.
Gabel, Harrison W.
Robinson, Nathaniel D.
Kastan, Nathaniel R.
Hu, Linda S.
Cohen, Sonia
Navarro, Adrija J.
Lyst, Matthew J.
Ekiert, Robert
Bird, Adrian P.
Greenberg, Michael E.
TI Activity-dependent phosphorylation of MeCP2 threonine 308 regulates
interaction with NCoR
SO NATURE
LA English
DT Article
ID METHYL-CPG; BDNF TRANSCRIPTION; RETT-SYNDROME; BINDING; REPRESSION;
CHROMATIN; ASSOCIATION; INHIBITION; MUTATIONS; DISORDER
AB Rett syndrome (RTT) is an X-linked human neurodevelopmental disorder with features of autism and severe neurological dysfunction in females. RTT is caused by mutations in methyl-CpG-binding protein 2 (MeCP2), a nuclear protein that, in neurons, regulates transcription, is expressed at high levels similar to that of histones, and binds to methylated cytosines broadly across the genome(1-5). By phosphotryptic mapping, we identify three sites (S86, S274 and T308) of activity-dependent MeCP2 phosphorylation. Phosphorylation of these sites is differentially induced by neuronal activity, brain-derived neurotrophic factor, or agents that elevate the intracellular level of 3',5'-cyclic AMP (cAMP), indicating that MeCP2 may function as an epigenetic regulator of gene expression that integrates diverse signals from the environment. Here we show that the phosphorylation of T308 blocks the interaction of the repressor domain of MeCP2 with the nuclear receptor co-repressor (NCoR) complex and suppresses the ability of MeCP2 to repress transcription. In knock-in mice bearing the common human RTT missense mutation R306C, neuronal activity fails to induce MeCP2 T308 phosphorylation, suggesting that the loss of T308 phosphorylation might contribute to RTT. Consistent with this possibility, the mutation of MeCP2 T308A in mice leads to a decrease in the induction of a subset of activity-regulated genes and to RTT-like symptoms. These findings indicate that the activity-dependent phosphorylation of MeCP2 at T308 regulates the interaction of MeCP2 with the NCoR complex, and that RTT in humans may be due, in part, to the loss of activity-dependent MeCP2 T308 phosphorylation and a disruption of the phosphorylation-regulated interaction of MeCP2 with the NCoR complex.
C1 [Ebert, Daniel H.; Gabel, Harrison W.; Robinson, Nathaniel D.; Kastan, Nathaniel R.; Hu, Linda S.; Cohen, Sonia; Navarro, Adrija J.; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Ebert, Daniel H.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lyst, Matthew J.; Ekiert, Robert; Bird, Adrian P.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
RP Greenberg, ME (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
EM michael_greenberg@hms.harvard.edu
OI Ekiert, Robert/0000-0002-8879-0646; Lyst, Matthew/0000-0001-9018-4138
FU NIH [RO1NS048276, K08MH90306, P30-HD 18655]; Rett Syndrome Research
Trust; Dupont-Warren Fellowship in the Department of Psychiatry at
Harvard Medical School; Nancy Lurie Marks Fellowship in Autism at
Harvard Medical School; Damon Runyon Cancer Research Foundation
[DRG-2048-10]
FX This work was supported by NIH grant RO1NS048276 and the Rett Syndrome
Research Trust to M. E. G. D. H. E was supported by NIH grant
K08MH90306, the Dupont-Warren Fellowship in the Department of Psychiatry
at Harvard Medical School, and the Nancy Lurie Marks Fellowship in
Autism at Harvard Medical School. H. W. G. was supported by Damon Runyon
Cancer Research Foundation Grant DRG-2048-10. The Mouse Gene
Manipulation Facility of the Boston Children's Hospital Intellectual and
Developmental Disabilities Research Center (IDDRC), funded by NIH grant
P30-HD 18655, assisted in generation of the knock-in mice. We thank
members of the Greenberg laboratory, particularly C. Mandel-Brehm and E.
Griffith, and also G. Mandel and R. S. Greenberg for helpful
discussions.
NR 26
TC 74
Z9 78
U1 2
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 18
PY 2013
VL 499
IS 7458
BP 341
EP U116
DI 10.1038/nature12348
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700037
PM 23770587
ER
PT J
AU Linger, RMA
Cohen, RA
Cummings, CT
Sather, S
Migdall-Wilson, J
Middleton, DHG
Lu, X
Baron, AE
Franklin, WA
Merrick, DT
Jedlicka, P
DeRyckere, D
Heasley, LE
Graham, DK
AF Linger, R. M. A.
Cohen, R. A.
Cummings, C. T.
Sather, S.
Migdall-Wilson, J.
Middleton, D. H. G.
Lu, X.
Baron, A. E.
Franklin, W. A.
Merrick, D. T.
Jedlicka, P.
DeRyckere, D.
Heasley, L. E.
Graham, D. K.
TI Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis,
blocks growth and enhances chemosensitivity of human non-small cell lung
cancer
SO ONCOGENE
LA English
DT Article
DE targeted therapy; receptor tyrosine kinase; MerTK; signal transduction;
xenograft; chemosensitivity
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ELEMENT-BINDING PROTEIN; NF-KAPPA-B;
GENE-EXPRESSION; BREAST-CANCER; TUMOR-GROWTH; THERAPEUTIC TARGETS;
PROLONGS SURVIVAL; DISEASE-ACTIVITY; DRUG-RESISTANCE
AB Non-small cell lung cancer (NSCLC) is a prevalent and devastating disease that claims more lives than breast, prostate, colon and pancreatic cancers combined. Current research suggests that standard chemotherapy regimens have been optimized to maximal efficiency. Promising new treatment strategies involve novel agents targeting molecular aberrations present in subsets of NSCLC. We evaluated 88 human NSCLC tumors of diverse histology and identified Mer and Axl as receptor tyrosine kinases (RTKs) overexpressed in 69% and 93%, respectively, of tumors relative to surrounding normal lung tissue. Mer and Axl were also frequently overexpressed and activated in NSCLC cell lines. Ligand-dependent Mer or Axl activation stimulated MAPK, AKT and FAK signaling pathways indicating roles for these RTKs in multiple oncogenic processes. In addition, we identified a novel pro-survival pathway-involving AKT, CREB, Bcl-xL, survivin, and Bcl-2-downstream of Mer, which is differentially modulated by Axl signaling. We demonstrated that short hairpin RNA (shRNA) knockdown of Mer or Axl significantly reduced NSCLC colony formation and growth of subcutaneous xenografts in nude mice. Mer or Axl knockdown also improved in vitro NSCLC sensitivity to chemotherapeutic agents by promoting apoptosis. When comparing the effects of Mer and Axl knockdown, Mer inhibition exhibited more complete blockade of tumor growth while Axl knockdown more robustly improved chemosensitivity. These results indicate that Mer and Axl have complementary and overlapping roles in NSCLC and suggest that treatment strategies targeting both RTKs may be more effective than singly-targeted agents. Our findings validate Mer and Axl as potential therapeutic targets in NSCLC and provide justification for development of novel therapeutic compounds that selectively inhibit Mer and/or Axl.
C1 [Linger, R. M. A.; Cohen, R. A.; Cummings, C. T.; Sather, S.; Migdall-Wilson, J.; DeRyckere, D.; Graham, D. K.] Univ Colorado, Dept Pediat, Sect Hematol Oncol & Bone Marrow Transplantat, Aurora, CO 80045 USA.
[Middleton, D. H. G.] Univ Colorado, Program Canc Biol, Aurora, CO 80045 USA.
[Lu, X.; Baron, A. E.] Univ Colorado, Dept Biostat & Informat, Aurora, CO 80045 USA.
[Franklin, W. A.; Merrick, D. T.; Jedlicka, P.] Univ Colorado, Dept Pathol, Aurora, CO 80045 USA.
[Merrick, D. T.] Denver VA Med Ctr, Dept Pathol, Denver, CO USA.
[Heasley, L. E.] Denver VA Med Ctr, Dept Craniofacial Biol, Denver, CO USA.
RP Graham, DK (reprint author), Univ Colorado, Dept Pediat, Sect Hematol Oncol & Bone Marrow Transplantat, Anschutz Med Campus,Mail Stop 8302,12800 East 19t, Aurora, CO 80045 USA.
EM doug.graham@ucdenver.edu
FU Uniting Against Lung Cancer: Elliot's Legacy (RMAL); Lung Cancer
Research Foundation (RMAL); American Cancer Society [RSG-08-291-01-LIB];
National Institutes of Health [RO1CA137078]; University of Colorado
Cancer Center SPORE in Lung Cancer [NIH 5P50CA058187]; Damon Runyon
Cancer Research Foundation [CI-39-07]
FX This work was supported in part by grants from Uniting Against Lung
Cancer: Elliot's Legacy (RMAL), the Lung Cancer Research Foundation
(RMAL), the American Cancer Society (RSG-08-291-01-LIB, DKG) and the
National Institutes of Health (RO1CA137078, DKG). RMA Linger received a
Career Development Award from the University of Colorado Cancer Center
SPORE in Lung Cancer (NIH 5P50CA058187). DK Graham is the Damon
Runyon-Novartis Clinical Investigator supported (in part) by the Damon
Runyon Cancer Research Foundation (CI-39-07). The authors wish to thank
Karen Helm, Christine Childs and Lester Acosta in the University of
Colorado Cancer Center Flow Cytometry Core for their expert technical
assistance, Randall Wong in the University of Colorado Denver Diabetes
and Endocrinology Research Center Molecular Biology Core Facility (NIH
P30 DK57516) for cell line authentication services, Patricia Lenhart for
help optimizing Mer and Axl immunohistochemistry of human tissues, and
Storey Wilson and Andrea Abeyta for technical assistance with the Aperio
imaging system used to digitize stained tumor microarray slides.
NR 65
TC 45
Z9 45
U1 3
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUL 18
PY 2013
VL 32
IS 29
BP 3420
EP 3431
DI 10.1038/onc.2012.355
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 186AZ
UT WOS:000322014900003
PM 22890323
ER
PT J
AU Kloverpris, HN
Stryhn, A
Harndahl, M
Carlson, JM
Leslie, AJ
Chen, F
Riddell, L
Mulenga, J
Walker, BD
Ndung'u, T
Buus, S
Goulder, P
AF Kloverpris, Henrik N.
Stryhn, Anette
Harndahl, Mikkel
Carlson, Jonathan M.
Leslie, Alasdair J.
Chen, Fabian
Riddell, Lynn
Mulenga, Joseph
Walker, Bruce D.
Ndung'u, Thumbi
Buus, Soren
Goulder, Philip
TI HLA-AM*68:02-restricted Gag-specific cytotoxic T lymphocyte responses
can drive selection pressure on HIV but are subdominant and ineffective
SO AIDS
LA English
DT Article
DE CD8(+) T cells; HIV-1; HLA-peptide binding
ID HLA CLASS-I; IMMUNODEFICIENCY-VIRUS TYPE-1; IMMUNE CONTROL; ESCAPE
PATHWAYS; INFECTED-CELLS; CTL EPITOPES; VIRAL LOAD; TRANSMISSION;
ASSOCIATIONS; IMMUNOGENICITY
AB Background:Human leukocyte allele (HLA) class I polymorphism has the greatest impact of human genetic variation on viral load set point. A substantial part of this effect is due to the action of HLA-B and HLA-C alleles. With few exceptions the role of HLA-A molecules in immune control of HIV is unclear.Methods:We here study HLA-A68:02, one of the most highly prevalent HLA-A alleles in C-clade infected sub-Saharan African populations, and one that plays a prominent role in the HIV-specific CD8(+) T-cell responses made against the virus.Results:We define eight epitopes restricted by this allele and propose the peptide binding motif for HLA-A68:02. Although one of these epitopes almost exactly overlaps an HLA-B57-restricted epitope in Gag linked with immune control of HIV, this HLA-A68:02-restricted Gag-TA10 response imposed only weak selection pressure on the virus and was not associated with significantly lower viral setpoint. The only HLA-A68:02-restricted responses imposing strong selection pressure on HIV were in the flanking regions of Pol-EA8 and Pol-EA11 and within the Vpr-EV10 epitope (P=8x10(-8)). However, targeting of this latter epitope was associated with significantly higher viral loads (P=0.003), suggesting lack of efficacy.Conclusion:This study is consistent with previous data showing that HLA-A-restricted Gag-specific responses can impose selection pressure on HIV. In the case of HLA-A68:02 the Gag response is subdominant, and apparently has little impact in natural infection. However, these data suggest the potential for high frequency vaccine-induced Gag responses restricted by this allele to have significant antiviral efficacy in vaccine recipients.
C1 [Kloverpris, Henrik N.; Goulder, Philip] Univ Oxford, Dept Paediat, Oxford, England.
[Kloverpris, Henrik N.; Stryhn, Anette; Harndahl, Mikkel; Buus, Soren] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark.
[Walker, Bruce D.; Ndung'u, Thumbi; Goulder, Philip] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Program, Durban, South Africa.
[Walker, Bruce D.] Massachusetts Inst Technol & Harvard, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Chen, Fabian] Royal Berkshire Hosp Reading, Dept Sexual Hlth, Reading, Berks, England.
[Riddell, Lynn] Northamptonshire Healthcare Natl Hlth Serv Trust, Northampton Gen Hosp, Dept Genitourinary Med, Northampton, England.
[Carlson, Jonathan M.] eSci Grp, Microsoft Res, Los Angeles, CA USA.
[Kloverpris, Henrik N.; Leslie, Alasdair J.] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, Nelson R Mandela Sch Med, K RITH, Kwa Zulu, South Africa.
[Mulenga, Joseph] Zambia Emory HIV Res Project, Lusaka, Zambia.
RP Kloverpris, HN (reprint author), Univ Oxford, Oxford, England.
EM henrik.kloverpris@k-rith.org
RI Buus, Soren/F-5446-2010
FU Welcome Trust; National Institutes of Health [R01 AI46995]; Danish
Agency for Science, Technology and Innovation [12-132295]
FX This work was supported by the Welcome Trust (P.G.) and the National
Institutes of Health, grant R01 AI46995. H.N.K. holds a grant from the
Danish Agency for Science, Technology and Innovation #12-132295.
NR 37
TC 4
Z9 4
U1 0
U2 3
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 JUL 17
PY 2013
VL 27
IS 11
BP 1717
EP 1723
DI 10.1097/QAD.0b013e32836146cd
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 250HL
UT WOS:000326841200004
PM 23525031
ER
PT J
AU Dowling, NM
Gleason, CE
Manson, JE
Hodis, HN
Miller, VM
Brinton, EA
Neal-Perry, G
Santoro, MN
Cedars, M
Lobo, R
Merriam, GR
Wharton, W
Naftolin, F
Taylor, H
Harman, SM
Asthana, S
AF Dowling, N. Maritza
Gleason, Carey E.
Manson, JoAnn E.
Hodis, Howard N.
Miller, Virginia M.
Brinton, Eliot A.
Neal-Perry, Genevieve
Santoro, M. Nanette
Cedars, Marcelle
Lobo, Rogerio
Merriam, George R.
Wharton, Whitney
Naftolin, Frederick
Taylor, Hugh
Harman, S. Mitchell
Asthana, Sanjay
TI Characterization of Vascular Disease Risk in Postmenopausal Women and
Its Association with Cognitive Performance
SO PLOS ONE
LA English
DT Article
ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; EARLY ESTROGEN
PREVENTION; APOLIPOPROTEIN-E GENOTYPE; NON-HISPANIC WHITES; BODY-MASS
INDEX; CARDIOVASCULAR RISK; ALZHEIMERS-DISEASE; SOCIOECONOMIC-STATUS;
DENSITY-LIPOPROTEIN
AB Objectives: While global measures of cardiovascular (CV) risk are used to guide prevention and treatment decisions, these estimates fail to account for the considerable interindividual variability in pre-clinical risk status. This study investigated heterogeneity in CV risk factor profiles and its association with demographic, genetic, and cognitive variables.
Methods: A latent profile analysis was applied to data from 727 recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Women were cognitively healthy, within three years of their last menstrual period, and free of current or past CV disease. Education level, apolipoprotein E epsilon 4 allele (APOE4), ethnicity, and age were modeled as predictors of latent class membership. The association between class membership, characterizing CV risk profiles, and performance on five cognitive factors was examined. A supervised random forest algorithm with a 10-fold cross-validation estimator was used to test accuracy of CV risk classification.
Results: The best-fitting model generated two distinct phenotypic classes of CV risk 62% of women were "low-risk" and 38% "high-risk". Women classified as low-risk outperformed high-risk women on language and mental flexibility tasks (p = 0.008) and a global measure of cognition (p = 0.029). Women with a college degree or above were more likely to be in the low-risk class (OR = 1.595, p = 0.044). Older age and a Hispanic ethnicity increased the probability of being at high-risk (OR = 1.140, p = 0.002; OR = 2.622, p = 0.012; respectively). The prevalence rate of APOE-epsilon 4 was higher in the high-risk class compared with rates in the low-risk class.
Conclusion: Among recently menopausal women, significant heterogeneity in CV risk is associated with education level, age, ethnicity, and genetic indicators. The model-based latent classes were also associated with cognitive function. These differences may point to phenotypes for CV disease risk. Evaluating the evolution of phenotypes could in turn clarify preclinical disease, and screening and preventive strategies. ClinicalTrials.gov NCT00154180
C1 [Dowling, N. Maritza] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53706 USA.
[Dowling, N. Maritza; Gleason, Carey E.; Asthana, Sanjay] Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA.
[Gleason, Carey E.; Wharton, Whitney; Asthana, Sanjay] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA.
[Gleason, Carey E.; Wharton, Whitney; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA.
[Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Hodis, Howard N.] Univ So Calif, Atherosclerosis Res Unit, Los Angeles, CA USA.
[Miller, Virginia M.] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN USA.
[Miller, Virginia M.] Mayo Clin, Dept Surg, Rochester, MN USA.
[Brinton, Eliot A.] Univ Utah, Dept Cardiovasc Genet, Salt Lake City, UT USA.
[Neal-Perry, Genevieve] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA.
[Neal-Perry, Genevieve] Albert Einstein Coll Med, Dominick Purpura Dept Neurosci, Bronx, NY 10467 USA.
[Santoro, M. Nanette] Univ Colorado, Sch Med, Dept Obstet & Gynecol, Aurora, CO USA.
[Cedars, Marcelle] Univ Calif San Francisco, Dept Obstet & Gynecol, San Francisco, CA 94143 USA.
[Lobo, Rogerio] Columbia Univ Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA.
[Merriam, George R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Merriam, George R.] Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA.
[Naftolin, Frederick] NYU, Dept Obstet & Gynecol, New York, NY 10016 USA.
[Taylor, Hugh] Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06510 USA.
[Harman, S. Mitchell] Kronos Longev Res Inst, Phoenix, AZ USA.
[Harman, S. Mitchell] Phoenix VA Med Ctr, Phoenix, AZ USA.
RP Dowling, NM (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53706 USA.
EM nmdowlin@biostat.wisc.edu
FU National Institutes of Health (NIH) [R01 AG029624, P50AG033514,
R01AG031790]; Aurora Foundation; NIH [HL90639]; Mayo [CTSA1 UL1
RR024150]; Einstein College of Medicine CTSA [UL1 RR025750, KL2
RR025749, TL1 RR025748]; Mayo Foundation; United States Department of
Veterans Affairs Puget Sound Health Care System; Brigham and Women's
Hospital/Harvard Medical School CTSA; CTSA [UL1 RR024139]; UCSF CTSA
from the National Center for Advancing Translational Sciences (NCATS), a
component of the NIH [UL1 RR024131]; NIH Roadmap for Medical Research
FX The KEEPS-cog project was supported by grants from the National
Institutes of Health (NIH) R01 AG029624, P50AG033514, and R01AG031790.
The parent KEEPS trial is funded by grants from the Aurora Foundation to
the Kronos Longevity Research Institute, NIH HL90639 to VMM, Mayo CTSA1
UL1 RR024150, the Einstein College of Medicine CTSA UL1 RR025750, KL2
RR025749 and TL1 RR025748, the Mayo Foundation, the United States
Department of Veterans Affairs Puget Sound Health Care System, Brigham
and Women's Hospital/Harvard Medical School CTSA, CTSA UL1 RR024139 and
UCSF CTSA UL1 RR024131 from the National Center for Advancing
Translational Sciences (NCATS), a component of the NIH and NIH Roadmap
for Medical Research. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 79
TC 4
Z9 4
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 17
PY 2013
VL 8
IS 7
AR UNSP e68741
DI 10.1371/journal.pone.0068741
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 185WH
UT WOS:000322000600022
PM 23874743
ER
PT J
AU Zhu, HJ
Bogdanov, MB
Boyle, SH
Matson, W
Sharma, S
Matson, S
Churchill, E
Fiehn, O
Rush, JA
Krishnan, RR
Pickering, E
Delnomdedieu, M
Kaddurah-Daouk, R
AF Zhu, Hongjie
Bogdanov, Mikhail B.
Boyle, Stephen H.
Matson, Wayne
Sharma, Swati
Matson, Samantha
Churchill, Erik
Fiehn, Oliver
Rush, John A.
Krishnan, Ranga R.
Pickering, Eve
Delnomdedieu, Marielle
Kaddurah-Daouk, Rima
CA Pharmacometabolomics Res Network
TI Pharmacometabolomics of Response to Sertraline and to Placebo in Major
Depressive Disorder - Possible Role for Methoxyindole Pathway
SO PLOS ONE
LA English
DT Article
ID SEROTONIN REUPTAKE INHIBITORS; VENTRAL TEGMENTAL AREA; PREFRONTAL
CORTEX; EXTRACELLULAR LEVELS; METABOLOMIC ANALYSIS; GABA CONCENTRATIONS;
PARKINSONS-DISEASE; CIRCADIAN-RHYTHMS; GOLDEN-HAMSTER; PINEAL-GLAND
AB Therapeutic response to selective serotonin (5-HT) reuptake inhibitors in Major Depressive Disorder (MDD) varies considerably among patients, and the onset of antidepressant therapeutic action is delayed until after 2 to 4 weeks of treatment. The objective of this study was to analyze changes within methoxyindole and kynurenine (KYN) branches of tryptophan pathway to determine whether differential regulation within these branches may contribute to mechanism of variation in response to treatment. Metabolomics approach was used to characterize early biochemical changes in tryptophan pathway and correlated biochemical changes with treatment outcome. Outpatients with MDD were randomly assigned to sertraline (n = 35) or placebo (n = 40) in a double-blind 4-week trial; response to treatment was measured using the 17-item Hamilton Rating Scale for Depression (HAMD(17)). Targeted electrochemistry based metabolomic platform (LCECA) was used to profile serum samples from MDD patients. The response rate was slightly higher for sertraline than for placebo (21/35 [60%] vs. 20/40 [50%], respectively, chi(2) (1) = 0.75, p = 0.39). Patients showing a good response to sertraline had higher pretreatment levels of 5-methoxytryptamine (5-MTPM), greater reduction in 5-MTPM levels after treatment, an increase in 5-Methoxytryptophol (5-MTPOL) and Melatonin (MEL) levels, and decreases in the (KYN)/MEL and 3-Hydroxykynurenine (3-OHKY)/MEL ratios post-treatment compared to pretreatment. These changes were not seen in the patients showing poor response to sertraline. In the placebo group, more favorable treatment outcome was associated with increases in 5-MTPOL and MEL levels and significant decreases in the KYN/MEL and 3-OHKY/MEL; changes in 5-MTPM levels were not associated with the 4-week response. These results suggest that recovery from a depressed state due to treatment with drug or with placebo could be associated with preferential utilization of serotonin for production of melatonin and 5-MTPOL.
C1 [Zhu, Hongjie; Boyle, Stephen H.; Churchill, Erik; Krishnan, Ranga R.; Kaddurah-Daouk, Rima] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27706 USA.
[Bogdanov, Mikhail B.] Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY USA.
[Matson, Wayne; Sharma, Swati; Matson, Samantha] Bedford VA Med Ctr, Dept Syst Biochem, Bedford, MA USA.
[Matson, Samantha] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fiehn, Oliver] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA.
[Rush, John A.; Krishnan, Ranga R.] Duke NUS Grad Med Sch, Singapore, Singapore.
[Pickering, Eve] Pfizer Global R&D, Clin Res Stat, Groton, CT USA.
[Delnomdedieu, Marielle] Pfizer Global R&D, Neurosci Clin Res, Groton, CT USA.
RP Kaddurah-Daouk, R (reprint author), Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27706 USA.
OI Rush, Augustus/0000-0003-2004-2382
FU Pfizer Corporation; National Institute of General Medical Sciences
[GM078233]
FX This work was done with funding from Pfizer Corporation and from
National Institute of General Medical Sciences grant GM078233, "The
Metabolomics Research Network for Drug Response Phenotype." The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 58
TC 21
Z9 22
U1 2
U2 17
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 JUL 17
PY 2013
VL 8
IS 7
AR e68283
DI 10.1371/journal.pone.0068283
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 185WH
UT WOS:000322000600007
PM 23874572
ER
PT J
AU Singh, JA
Lewallen, DG
AF Singh, Jasvinder A.
Lewallen, David G.
TI Operative diagnosis for revision total hip arthroplasty is associated
with patient-reported outcomes (PROs)
SO BMC MUSCULOSKELETAL DISORDERS
LA English
DT Article
DE Total hip replacement; Arthroplasty; Joint replacement; Patient-reported
outcomes; Diagnosis
ID TOTAL KNEE ARTHROPLASTY; UNITED-STATES; PREDICTORS; PAIN;
RESPONSIVENESS; QUESTIONNAIRE; COMORBIDITY; REPLACEMENT; FRACTURES;
MORBIDITY
AB Background: Little is known about the impact of the reason for revision total hip arthroplasty (THA) on the outcomes following revision THA. In this study, our objective was to assess the association of operative diagnosis with patient-reported outcomes (PROs) after revision THA.
Methods: We used prospectively collected data from the Mayo Clinic Total Joint Registry that collects pre- and post-operative pain and function outcomes using a validated Hip questionnaire, on all revision THAs from 1993-2005. We used logistic regression to assess the odds of moderate-severe index hip pain and moderate-severe limitation in activities of daily living (ADLs) 2- and 5-years after revision THA. We calculated odds ratios (OR) and 95% confidence intervals (CIs).
Results: For the 2- and 5-year cohorts, the operative diagnosis was loosening/wear/osteolysis in 73% and 75%; dislocation/bone or prosthesis fracture/instability or non-union in 17% and 15%; and failed prior arthroplasty with components removed/infection in 11% and 11%, respectively. In multivariable-adjusted analyses that included preoperative ADL limitations, compared to patients with loosening/wear/osteolysis, patients with dislocation/fracture/instability/non-union had OR of 2.2 (95% CI, 1.3-3.5; p = 0.002) for overall moderate-severe ADL limitation and those with failed prior arthroplasty/infection had OR of 1.6 (95% CI, 1.0-2.8; p = 0.06). At 5-years, ORs were lower and differences were no longer significant. Moderate-severe pain did not differ significantly by diagnosis, at 2- or 5-years in multivariable adjusted analyses, with one exception, i.e. failed prior arthroplasty/infection had a trend towards significance with odds ratio of 1.9 (95% CI, 0.9-3.8; p = 0.07).
Conclusions: Operative diagnosis is independently associated with ADL limitations, but not pain, at 2-years after revision THA. Patients should be informed of the risk of poorer short-term outcomes based on their diagnosis.
C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA.
[Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute care Res & Transit C SMART, Birmingham, AL USA.
[Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA.
[Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthopaed Surg, Rochester, MN USA.
[Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA.
[Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA.
RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA.
EM Jasvinder.md@gmail.com
OI singh, jasvinder/0000-0003-3485-0006
FU Mayo Clinic Orthopedic Surgery research funds; Agency for Health Quality
and Research Center for Education and Research on Therapeutics (CERTs);
National Institute of Arthritis, Musculoskeletal and Skin Diseases
(NIAMS); National Institute of Aging (NIA); National Cancer Institute
(NCI)
FX This material is the result of work supported Mayo Clinic Orthopedic
Surgery research funds and the resources and use of facilities at the
Birmingham VA Medical Center, Alabama, USA. J.A.S. is also supported by
grants from the Agency for Health Quality and Research Center for
Education and Research on Therapeutics (CERTs), National Institute of
Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institute
of Aging (NIA) and National Cancer Institute (NCI).
NR 31
TC 3
Z9 3
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2474
J9 BMC MUSCULOSKEL DIS
JI BMC Musculoskelet. Disord.
PD JUL 17
PY 2013
VL 14
AR 210
DI 10.1186/1471-2474-14-210
PG 7
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 188KY
UT WOS:000322193100001
PM 23866848
ER
PT J
AU Niziolek, CA
Guenther, FH
AF Niziolek, Caroline A.
Guenther, Frank H.
TI Vowel Category Boundaries Enhance Cortical and Behavioral Responses to
Speech Feedback Alterations
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SURFACE-BASED ANALYSIS; NEURAL-NETWORK MODEL; AUDITORY-FEEDBACK; FMRI;
PITCH; COMPENSATION; TIME; DISCRIMINATION; MANIPULATIONS; ACQUISITION
AB Auditory feedback is instrumental in the online control of speech, allowing speakers to compare their self-produced speech signal with a desired auditory target and correct for errors. However, there is little account of the representation of "target" and "error": does error depend purely on acoustic distance from a target, or is error enhanced by phoneme category changes? Here, we show an effect of vowel boundaries on compensatory responses to a real-time auditory perturbation. While human subjects spoke monosyllabic words, event-triggered functional magnetic resonance imaging was used to characterize neural responses to unexpected changes in auditory feedback. Capitalizing on speakers' natural variability, we contrasted the responses to feedback perturbations applied to two classes of utterances: (1) those that fell nearer to the category boundary, for which perturbations were designed to change the phonemic identity of the heard speech; and (2) those that fell farther from the boundary, for which perturbations resulted in only sub-phonemic auditory differences. Subjects' behavioral compensation was more than three times greater when feedback shifts were applied nearer to a category boundary. Furthermore, a near-boundary shift resulted in stronger cortical responses, most notably in right posterior superior temporal gyrus, than an identical shift that occurred far from the boundary. Across participants, a correlation was found between the amount of compensation to the perturbation and the amount of activity in a network of superior temporal and inferior frontal brain regions. Together, these results demonstrate that auditory feedback control of speech is sensitive to linguistic categories learned through auditory experience.
C1 [Niziolek, Caroline A.] Univ Calif San Francisco, Dept Otolaryngol, San Francisco, CA 94143 USA.
[Guenther, Frank H.] Boston Univ, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA.
[Guenther, Frank H.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
[Guenther, Frank H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Neuroimaging, Charlestown, MA 02139 USA.
[Guenther, Frank H.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
RP Niziolek, CA (reprint author), 513 Parnassus Ave,Box 0628, San Francisco, CA 94143 USA.
EM carrien@mit.edu
OI Niziolek, Caroline/0000-0002-6085-1371
FU National Institutes of Health [R01 DC002852, F32 DC011249]
FX This research was supported in part by National Institutes of Health
Grants R01 DC002852 (F. H. G.) and F32 DC011249 (C.A.N.). We thank Kevin
Reilly for providing formant analysis code.
NR 49
TC 14
Z9 14
U1 0
U2 5
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 17
PY 2013
VL 33
IS 29
BP 12090
EP 12098
DI 10.1523/JNEUROSCI.1008-13.2013
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 184MG
UT WOS:000321893500033
PM 23864694
ER
PT J
AU Clair, C
Rigotti, NA
Meigs, JB
AF Clair, Carole
Rigotti, Nancy A.
Meigs, James B.
TI Smoking Cessation, Weight Change, and Risk of Cardiovascular Disease
Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Clair, Carole] Univ Lausanne, Dept Ambulatory Care & Community Med, Lausanne, Switzerland.
[Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
RP Clair, C (reprint author), Policlin Med Univ, 44 Rue Bugnon, CH-1011 Lausanne Vaud, Switzerland.
EM carole.willi@gmail.com
RI Clair, Carole/D-9786-2014
OI Clair, Carole/0000-0001-5281-0943
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 17
PY 2013
VL 310
IS 3
BP 323
EP 323
DI 10.1001/jama.2013.7945
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 183RU
UT WOS:000321835700025
PM 23860997
ER
PT J
AU Heinrichs, S
Conover, LF
Bueso-Ramos, CE
Kilpivaara, O
Stevenson, K
Neuberg, D
Loh, ML
Wu, WS
Rodig, SJ
Garcia-Manero, G
Kantarjian, HM
Look, AT
AF Heinrichs, Stefan
Conover, Lillian F.
Bueso-Ramos, Carlos E.
Kilpivaara, Outi
Stevenson, Kristen
Neuberg, Donna
Loh, Mignon L.
Wu, Wen-Shu
Rodig, Scott J.
Garcia-Manero, Guillermo
Kantarjian, Hagop M.
Look, A. Thomas
TI MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid
malignancy
SO ELIFE
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; ARRAY ANALYSIS; B-MYB; IDENTIFICATION;
EXPRESSION; TRANSCRIPTION; CANCER; 5Q-SYNDROME; REDUCTION; PHENOTYPE
AB A common deleted region (CDR) in both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) affects the long arm of chromosome 20 and has been predicted to harbor a tumor suppressor gene. Here we show that MYBL2, a gene within the 20q CDR, is expressed at sharply reduced levels in CD34+ cells from most MDS cases (65%; n = 26), whether or not they harbor 20q abnormalities. In a murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of normal levels in multipotent hematopoietic progenitors resulted in clonal dominance of these 'sub-haploinsufficient' cells, which was reflected in all blood cell lineages. By 6 months post-transplantation, the reconstituted mice had developed a clonal myeloproliferative/myelodysplastic disorder originating from the cells with aberrantly reduced Mybl2 expression. We conclude that downregulation of MYBL2 activity below levels predicted by classical haploinsufficiency underlies the clonal expansion of hematopoietic progenitors in a large fraction of human myeloid malignancies.
C1 [Heinrichs, Stefan] Univ Hosp Essen, Inst Transfus Med, Essen, Germany.
[Heinrichs, Stefan; Conover, Lillian F.; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA.
[Bueso-Ramos, Carlos E.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA.
[Kilpivaara, Outi] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Stevenson, Kristen; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Loh, Mignon L.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Wu, Wen-Shu] Childrens Hosp, Oakland Res Inst, Ctr Cell Therapies, Oakland, CA 94609 USA.
[Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Garcia-Manero, Guillermo; Kantarjian, Hagop M.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
RP Heinrichs, S (reprint author), Univ Hosp Essen, Inst Transfus Med, Essen, Germany.
EM stefan.heinrichs@uk-essen.de
RI Wu, Wen-Shu/I-1258-2014
OI Wu, Wen-Shu/0000-0002-0225-2522
FU National Institutes of Health [NIH P01 CA-108631]
FX National Institutes of Health NIH P01 CA-108631 Stefan Heinrichs,
Lillian F Conover, Carlos E Bueso-Ramos, Outi Kilpivaara, Kristen
Stevenson, Donna Neuberg, Mignon L Loh, Guillermo Garcia-Manero, Hagop M
Kantarjian
NR 31
TC 6
Z9 6
U1 0
U2 2
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD JUL 16
PY 2013
VL 2
AR e00825
DI 10.7554/eLife.00825
PG 20
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 274QM
UT WOS:000328621200005
PM 23878725
ER
PT J
AU Usta, OB
Kim, Y
Ozer, S
Bruinsma, BG
Lee, J
Demir, E
Berendsen, TA
Puts, CF
Izamis, ML
Uygun, K
Uygun, BE
Yarmush, ML
AF Usta, O. Berk
Kim, Yeonhee
Ozer, Sinan
Bruinsma, Bote G.
Lee, Jungwoo
Demir, Esin
Berendsen, Tim A.
Puts, Catheleyne F.
Izamis, Maria-Louisa
Uygun, Korkut
Uygun, Basak E.
Yarmush, Martin L.
TI Supercooling as a Viable Non-Freezing Cell Preservation Method of Rat
Hepatocytes
SO PLOS ONE
LA English
DT Article
ID UNIVERSITY-OF-WISCONSIN; SUBZERO NONFREEZING STORAGE; UREA CYCLE
ENZYMES; LIVER PRESERVATION; HYPOTHERMIC PRESERVATION; SANDWICH
CONFIGURATION; ANTIFREEZE PROTEIN; COLLAGEN SANDWICH; GENE-EXPRESSION;
COLD-STORAGE
AB Supercooling preservation holds the potential to drastically extend the preservation time of organs, tissues and engineered tissue products, and fragile cell types that do not lend themselves well to cryopreservation or vitrification. Here, we investigate the effects of supercooling preservation (SCP at -4 degrees C) on primary rat hepatocytes stored in cryovials and compare its success (high viability and good functional characteristics) to that of static cold storage (CS at +4 degrees C) and cryopreservation. We consider two prominent preservation solutions a) Hypothermosol (HTS-FRS) and b) University of Wisconsin solution (UW) and a range of preservation temperatures (-4 to -10 degrees C). We find that there exists an optimum temperature (-4 degrees C) for SCP of rat hepatocytes which yields the highest viability; at this temperature HTS-FRS significantly outperforms UW solution in terms of viability and functional characteristics (secretions and enzymatic activity in suspension and plate culture). With the HTS-FRS solution we show that the cells can be stored for up to a week with high viability (similar to 56%); moreover we also show that the preservation can be performed in large batches (50 million cells) with equal or better viability and no loss of functionality as compared to smaller batches (1.5 million cells) performed in cryovials.
C1 [Usta, O. Berk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02115 USA.
Shriners Hosp Children, Boston, MA USA.
RP Usta, OB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02115 USA.
EM berkusta@gmail.com
RI USTA, O. Berk/A-5818-2008; Uygun, Basak/I-1792-2012;
OI USTA, O. Berk/0000-0001-9328-568X; Uygun, Basak/0000-0002-2600-7900;
Bruinsma, Bote/0000-0003-1537-4948
FU NIH [R01DK096075, R01EB008678, R00DK080942, K99DK088962]; Shriners
Fellowship [84202]
FX NIH #R01DK096075, NIH #R01EB008678, NIH #R00DK080942, NIH #K99DK088962,
Shriners Fellowship #84202. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 48
TC 5
Z9 6
U1 1
U2 17
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 JUL 16
PY 2013
VL 8
IS 7
AR e69334
DI 10.1371/journal.pone.0069334
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 186SF
UT WOS:000322064300098
PM 23874947
ER
PT J
AU Gellad, WF
Donohue, JM
Zhao, XH
Mor, MK
Thorpe, CT
Smith, J
Good, CB
Fine, MJ
Morden, NE
AF Gellad, Walid F.
Donohue, Julie M.
Zhao, Xinhua
Mor, Maria K.
Thorpe, Carolyn T.
Smith, Jeremy
Good, Chester B.
Fine, Michael J.
Morden, Nancy E.
TI Brand-Name Prescription Drug Use Among Veterans Affairs and Medicare
Part D Patients With Diabetes A National Cohort Comparison
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID HEALTH-CARE-SYSTEM; QUALITY-OF-CARE; GEOGRAPHIC-VARIATION; OLDER-ADULTS;
COST; PRICES; IMPLEMENTATION; HYPERTENSION; MEDICATIONS; PHYSICIANS
AB Background: Medicare Part D and the U.S. Department of Veterans Affairs (VA) use different approaches to manage prescription drug benefits, with implications for spending. Medicare relies on private plans with distinct formularies, whereas the VA administers its own benefit using a national formulary.
Objective: To compare overall and regional rates of brand-name drug use among older adults with diabetes in Medicare and the VA.
Design: Retrospective cohort.
Setting: Medicare and the VA, 2008.
Patients: 1 061 095 Medicare Part D beneficiaries and 510 485 veterans aged 65 years or older with diabetes.
Measurements: Percentage of patients taking oral hypoglycemics, statins, and angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) who filled brand-name drug prescriptions and percentage of patients taking long-acting insulins who filled analogue prescriptions. Sociodemographic-and health status-adjusted hospital referral region (HRR) brand-name drug use was compared, and changes in spending were calculated if use of brand-name drugs in 1 system mirrored the other.
Results: Brand-name drug use in Medicare was 2 to 3 times that in the VA: 35.3% versus 12.7% for oral hypoglycemics, 50.7% versus 18.2% for statins, 42.5% versus 20.8% for ACE inhibitors or ARBs, and 75.1% versus 27.0% for insulin analogues. Adjusted HRR-level brand-name statin use ranged (from the 5th to 95th percentiles) from 41.0% to 58.3% in Medicare and 6.2% to 38.2% in the VA. For each drug group, the 95th-percentile HRR in the VA had lower brand-name drug use than the 5th-percentile HRR in Medicare. Medicare spending in this population would have been $1.4 billion less if brand-name drug use matched that of the VA.
Limitation: This analysis cannot fully describe the factors underlying differences in brand-name drug use.
Conclusion: Medicare beneficiaries with diabetes use 2 to 3 times more brand-name drugs than a comparable group within the VA, at substantial excess cost.
C1 Univ Pittsburgh, RAND Corp, Vet Affairs Pittsburgh Healthcare Syst, Grad Sch Publ Hlth,Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA.
[Smith, Jeremy; Morden, Nancy E.] Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH 03766 USA.
US Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA.
Geisel Sch Med Dartmouth, Hanover, NH USA.
RP Gellad, WF (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr, Pittsburgh, PA 15206 USA.
EM walid.gellad@va.gov
FU U.S. Department of Veterans Affairs; National Institutes of Health;
Robert Wood Johnson Foundation
FX Primary Funding Source: U.S. Department of Veterans Affairs, National
Institutes of Health, and Robert Wood Johnson Foundation.
NR 49
TC 17
Z9 17
U1 4
U2 15
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUL 16
PY 2013
VL 159
IS 2
BP 105
EP W39
DI 10.7326/0003-4819-159-2-201307160-00664
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 187IX
UT WOS:000322112000016
PM 23752663
ER
PT J
AU Conn, A
AF Conn, Alasdair
TI Marathon Day at Massachusetts General
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Conn, A (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Founders 114, Boston, MA 02114 USA.
EM aconn@partners.org
NR 0
TC 3
Z9 3
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUL 16
PY 2013
VL 159
IS 2
BP 143
EP 144
DI 10.7326/0003-4819-159-2-201307160-00648
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 187IX
UT WOS:000322112000021
PM 23698555
ER
PT J
AU Luc, S
Orkin, SH
AF Luc, Sidinh
Orkin, Stuart H.
TI Delineating the mixed lineage leukemia gene expression network in
hematopoietic stem cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID DROSOPHILA-TRITHORAX; MLL TRANSLOCATIONS; SELF-RENEWAL; TISSUES; UNIQUE
C1 [Orkin, Stuart H.] Harvard Univ, Sch Med, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA 02115 USA.
EM stuart_orkin@dfci.harvard.edu
FU Howard Hughes Medical Institute
NR 16
TC 0
Z9 0
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 16
PY 2013
VL 110
IS 29
BP 11670
EP 11671
DI 10.1073/pnas.1310349110
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187AB
UT WOS:000322086100017
PM 23824294
ER
PT J
AU Butler, TC
Kardar, M
Chakraborty, AK
AF Butler, Thomas Charles
Kardar, Mehran
Chakraborty, Arup K.
TI Quorum sensing allows T cells to discriminate between self and nonself
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE statistical mechanics; T-cell-mediated autoimmunity; self tolerance
ID RANDOM-ENERGY MODEL; REPERTOIRE DIVERSITY; NEGATIVE SELECTION; RESPONSE
MAGNITUDE; CENTRAL TOLERANCE; THYMIC SELECTION; DENDRITIC CELLS;
IMMUNE-RESPONSE; AFFINITY; RECRUITMENT
AB T cells orchestrate pathogen-specific adaptive immune responses by identifying peptides derived from pathogenic proteins that are displayed on the surface of infected cells. Host cells also display peptide fragments from the host's own proteins. Incorrectly identifying peptides derived from the body's own proteome as pathogenic can result in autoimmune disease. To minimize autoreactivity, immature T cells that respond to self-peptides are deleted in the thymus by a process called negative selection. However, negative selection is imperfect, and autoreactive T cells exist in healthy individuals. To understand how autoimmunity is yet avoided, without loss of responsiveness to pathogens, we have developed a model of T-cell training and response. Our model shows that T cells reliably respond to infection and avoid autoimmunity because collective decisions made by the T-cell population, rather than the responses of individual T cells, determine biological outcomes. The theory is qualitatively consistent with experimental data and yields a criterion for thymic selection to be adequate for suppressing autoimmunity.
C1 [Butler, Thomas Charles; Kardar, Mehran] MIT, Dept Phys, Cambridge, MA 02139 USA.
[Butler, Thomas Charles] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Chakraborty, Arup K.] MIT, Inst Med Engn & Sci, Dept Chem Engn, Cambridge, MA 02139 USA.
[Chakraborty, Arup K.] MIT, Inst Med Engn & Sci, Dept Chem, Cambridge, MA 02139 USA.
[Chakraborty, Arup K.] MIT, Inst Med Engn & Sci, Dept Biol Engn, Cambridge, MA 02139 USA.
[Chakraborty, Arup K.] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA.
[Chakraborty, Arup K.] Harvard Univ, Cambridge, MA 02138 USA.
RP Kardar, M (reprint author), MIT, Dept Phys, Cambridge, MA 02139 USA.
EM kardar@mit.edu; arupc@mit.edu
FU National Institutes of Health; National Science Foundation [12-06323]
FX This work was partially supported by a National Institutes of Health
Pioneer Award (to A.K.C.) and National Science Foundation Grant 12-06323
(to M.K.).
NR 42
TC 15
Z9 15
U1 0
U2 24
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 16
PY 2013
VL 110
IS 29
BP 11833
EP 11838
DI 10.1073/pnas.1222467110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187AB
UT WOS:000322086100047
PM 23818603
ER
PT J
AU Lee, JH
Yi, LN
Li, JX
Schweitzer, K
Borgmann, M
Naumann, M
Wu, H
AF Lee, Jung-Hoon
Yi, Lina
Li, Jixi
Schweitzer, Katrin
Borgmann, Marc
Naumann, Michael
Wu, Hao
TI Crystal structure and versatile functional roles of the COP9 signalosome
subunit 1
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID GENE-EXPRESSION; 26S PROTEASOME; PCI DOMAIN; REGULATORY PARTICLE;
FISSION YEAST; KAPPA-B; COMPLEX; ARABIDOPSIS; PROTEIN; COP9/SIGNALOSOME
AB The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) plays key roles in many biological processes, such as repression of photomorphogenesis in plants and protein subcellular localization, DNA-damage response, and NF-kappa B activation in mammals. It is an evolutionarily conserved eight-protein complex with subunits CSN1 to CSN8 named following the descending order of molecular weights. Here, we report the crystal structure of the largest CSN subunit, CSN1 from Arabidopsis thaliana (atCSN1), which belongs to the Proteasome, COP9 signalosome, Initiation factor 3 (PCI) domain containing CSN subunit family, at 2.7 angstrom resolution. In contrast to previous predictions and distinct from the PCI-containing 26S proteasome regulatory particle subunit Rpn6 structure, the atCSN1 structure reveals an overall globular fold, with four domains consisting of helical repeat-I, linker helix, helical repeat-II, and the C-terminal PCI domain. Our small-angle X-ray scattering envelope of the CSN1-CSN7 complex agrees with the EM structure of the CSN alone (apo-CSN) and suggests that the PCI end of each molecule may mediate the interaction. Fitting of the CSN1 structure into the CSN-Skp1-Cul1-Fbox (SCF) EM structure shows that the PCI domain of CSN1 situates at the hub of the CSN for interaction with several other subunits whereas the linker helix and helical repeat-II of CSN1 contacts SCF using a conserved surface patch. Furthermore, we show that, in human, the C-terminal tail of CSN1, a segment not included in our crystal structure, interacts with I kappa B alpha in the NF-kappa B pathway. Therefore, the CSN complex uses multiple mechanisms to hinder NF-kappa B activation, a principle likely to hold true for its regulation of many other targets and pathways.
C1 [Lee, Jung-Hoon; Yi, Lina; Li, Jixi; Wu, Hao] Weill Cornell Med Coll, Dept Biochem, New York, NY 10065 USA.
[Yi, Lina; Li, Jixi; Wu, Hao] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02114 USA.
[Yi, Lina; Li, Jixi; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02114 USA.
[Schweitzer, Katrin; Borgmann, Marc; Naumann, Michael] Univ Magdeburg, Inst Expt Internal Med, D-39120 Magdeburg, Germany.
RP Wu, H (reprint author), Weill Cornell Med Coll, Dept Biochem, New York, NY 10065 USA.
EM hao.wu@childrens.harvard.edu
RI Naumann, Michael/B-5285-2011
OI Naumann, Michael/0000-0002-8060-2313
NR 50
TC 4
Z9 7
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 JUL 16
PY 2013
VL 110
IS 29
BP 11845
EP 11850
DI 10.1073/pnas.1302418110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187AB
UT WOS:000322086100049
PM 23818606
ER
PT J
AU Cheema, TA
Wakimoto, H
Fecci, PE
Ning, JF
Kuroda, T
Jeyaretna, DS
Martuza, RL
Rabkin, SD
AF Cheema, Tooba A.
Wakimoto, Hiroaki
Fecci, Peter E.
Ning, Jianfang
Kuroda, Toshihiko
Jeyaretna, Deva S.
Martuza, Robert L.
Rabkin, Samuel D.
TI Multifaceted oncolytic virus therapy for glioblastoma in an
immunocompetent cancer stem cell model
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE antiangiogenesis; immunotherapy; virotherapy
ID HERPES-SIMPLEX-VIRUS; REGULATORY T-CELLS; MALIGNANT GLIOMA; TUMORS;
EXPRESSION; VECTORS; IL-12; INTERLEUKIN-12; LINES; VIROTHERAPY
AB Glioblastoma (World Health Organization grade IV) is an aggressive adult brain tumor that is inevitably fatal despite surgery, radiation, and chemotherapy. Treatment failures are attributed to combinations of cellular heterogeneity, including a subpopulation of often-resistant cancer stem cells, aberrant vasculature, and noteworthy immune suppression. Current preclinical models and treatment strategies do not incorporate or address all these features satisfactorily. Herein, we describe a murine glioblastoma stem cell (GSC) model that recapitulates tumor heterogeneity, invasiveness, vascularity, and immunosuppressive microenvironment in syngeneic immunocompetent mice and should prove useful for a range of therapeutic studies. Using this model, we tested a genetically engineered oncolytic herpes simplex virus that is armed with an immunomodulatory cytokine, interleukin 12 (G47 Delta-mIL12). G47 Delta-mIL12 infects and replicates similarly to its unarmed oncolytic herpes simplex virus counterpart in mouse 005 GSCs in vitro, whereas in vivo, it significantly enhances survival in syngeneic mice bearing intracerebral 005 tumors. Mechanistically, G47 Delta-mIL12 targets not only GSCs but also increases IFN-gamma release, inhibits angiogenesis, and reduces the number of regulatory T cells in the tumor. The increased efficacy is dependent upon T cells, but not natural killer cells. Taken together, our findings demonstrate that G47 Delta-mIL12 provides a multifaceted approach to targeting GSCs, tumor microenvironment, and the immune system, with resultant therapeutic benefit in a stringent glioblastoma model.
C1 [Rabkin, Samuel D.] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Neurosurg, Mol Neurosurg Lab, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Rabkin, SD (reprint author), Massachusetts Gen Hosp, Brain Tumor Res Ctr, Boston, MA 02114 USA.
EM rabkin@helix.mgh.harvard.edu
OI Kuroda, Toshihiko/0000-0001-6660-8930
FU National Institutes of Health [R01NS032677, R01CA160762, R25NS065743];
Joelle Syverson American Brain Tumor Association Research Fellowship;
Rendina Family Foundation
FX We thank Drs. Inder Verma and Yasushi Soda for the 005 GSC cells; David
Dombowski for sorting of GFP-positive cells; Kat Folz-Donahue and Laura
Prickett-Rice from the Harvard Stem Cell Institute Flow Cytometry Core
facility for assistance with flow cytometry analysis; John Chen and
Derrick Jeon at the Massachusetts General Hospital Center for Systems
Biology for assistance with the bioluminescence imaging; and members of
the Molecular Neurosurgery Laboratory, especially Cecile Zaupa, Anoop
Patel, Melissa Humphreys, and Howie Latimer for technical assistance and
support. These studies were supported in part by National Institutes of
Health Grants R01NS032677 (to R.L.M.), R01CA160762 (to S.D.R.), and
R25NS065743 (to P.E.F.); a Joelle Syverson American Brain Tumor
Association Research Fellowship (to T.A.C.); and the Rendina Family
Foundation.
NR 50
TC 35
Z9 36
U1 1
U2 28
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 16
PY 2013
VL 110
IS 29
BP 12006
EP 12011
DI 10.1073/pnas.1307935110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187AB
UT WOS:000322086100076
PM 23754388
ER
PT J
AU Lee, JK
Shin, JH
Hwang, SG
Gwag, BJ
Mckee, AC
Lee, J
Kowall, NW
Ryu, H
Lim, DS
Choi, EJ
AF Lee, Jae Keun
Shin, Jin Hee
Hwang, Sang Gil
Gwag, Byoung Joo
McKee, Ann C.
Lee, Junghee
Kowall, Neil W.
Ryu, Hoon
Lim, Dae-Sik
Choi, Eui-Ju
TI MST1 functions as a key modulator of neurodegeneration in a mouse model
of ALS
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE neurotoxicity; ROS
ID AMYOTROPHIC-LATERAL-SCLEROSIS; INCREASED OXIDATIVE DAMAGE; MOTOR-NEURON
DEATH; PROTEIN-KINASE; AUTOPHAGY; ACTIVATION; APOPTOSIS; CELLS; STE20;
MICE
AB Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by loss of motor neurons. Dominant mutations in the gene for superoxide dismutase 1 (SOD1) give rise to familial ALS by an unknown mechanism. Here we show that genetic deficiency of mammalian sterile 20-like kinase 1 (MST1) delays disease onset and extends survival in mice expressing the ALS-associated G93A mutant of human SOD1. SOD1(G93A) induces dissociation of MST1 from a redox protein thioredoxin-1 and promotes MST1 activation in spinal cord neurons in a reactive oxygen species-dependent manner. Moreover, MST1 was found to mediate SOD1(G93A)-induced activation of p38 mitogen-activated protein kinase and caspases as well as impairment of autophagy in spinal cord motoneurons of SOD1(G93A) mice. Our findings implicate MST1 as a key determinant of neurodegeneration in ALS.
C1 [Lee, Jae Keun; Shin, Jin Hee; Choi, Eui-Ju] Korea Univ, Sch Life Sci & Biotechnol, Lab Cell Death & Human Dis, Seoul 136701, South Korea.
[Shin, Jin Hee; Gwag, Byoung Joo] GNT Pharma, Suwon 446906, South Korea.
[McKee, Ann C.; Lee, Junghee; Kowall, Neil W.; Ryu, Hoon] Boston Univ, Sch Med, Dept Neurol & Pathol, Boston, MA 02130 USA.
[McKee, Ann C.; Lee, Junghee; Kowall, Neil W.; Ryu, Hoon] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Lim, Dae-Sik] Korea Adv Inst Sci & Technol, Biomed Res Ctr, Dept Biol Sci, Taejon 305701, South Korea.
[Choi, Eui-Ju] Korea Univ, Coll Pharm, Yeongi 339700, Chungnam, South Korea.
RP Choi, EJ (reprint author), Korea Univ, Sch Life Sci & Biotechnol, Lab Cell Death & Human Dis, Seoul 136701, South Korea.
EM ejchoi@korea.ac.kr
RI Kowall, Neil/G-6364-2012; Lim, Dae-Sik/C-1599-2011
OI Kowall, Neil/0000-0002-6624-0213; Lim, Dae-Sik/0000-0003-2356-7555
FU National Research Foundation [2006-0093855, 2011-0030141, 2009-0081488];
Ministry of Science, ICT & Future Planning of Korea; Korea University;
Veterans Affairs Merit Award; [351-2009-1-E00030]
FX We thank S. Kang (Korea University) for providing Flag-SOD1 and
Flag-SOD1(G93A) cDNAs. This work was supported by Grant
351-2009-1-E00030 (to J.K.L) and by National Research Foundation Grants
2006-0093855, and 2011-0030141, and 2009-0081488 funded by the Ministry
of Science, ICT & Future Planning of Korea (to E.-J.C.). J.K.L was
supported by a Korea University grant. J.L. and N.W.K. were supported by
Veterans Affairs Merit Award.
NR 31
TC 12
Z9 13
U1 0
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 16
PY 2013
VL 110
IS 29
BP 12066
EP 12071
DI 10.1073/pnas.1300894110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187AB
UT WOS:000322086100086
PM 23818595
ER
PT J
AU Podrid, PJ
AF Podrid, Philip J.
TI ECG Challenge: July 16, 2013
SO CIRCULATION
LA English
DT Editorial Material
C1 [Podrid, Philip J.] Harvard Univ, Sch Med, Boston Univ, Sch Med, Boston, MA USA.
[Podrid, Philip J.] VA Boston Healthcare Syst, Boston, MA USA.
RP Podrid, PJ (reprint author), West Roxbury VA Hosp, Cardiol Sect, 1400 VFW Pkwy, West Roxbury, MA 02132 USA.
EM ppodrid@circulationjournal.org
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUL 16
PY 2013
VL 128
IS 3
BP 278
EP 278
DI 10.1161/CIRCULATIONAHA.113.004369
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 184NJ
UT WOS:000321897400023
ER
PT J
AU van Erven, B
Gubbels, CS
van Golde, RJ
Dunselman, GA
Derhaag, JG
de Wert, G
Geraedts, JP
Bosch, AM
Treacy, EP
Welt, CK
Berry, GT
Rubio-Gozalbo, ME
AF van Erven, Britt
Gubbels, Cynthia S.
van Golde, Ron J.
Dunselman, Gerard A.
Derhaag, Josien G.
de Wert, Guido
Geraedts, Joep P.
Bosch, Annet M.
Treacy, Eileen P.
Welt, Corrine K.
Berry, Gerard T.
Rubio-Gozalbo, M. Estela
TI Fertility preservation in female classic galactosemia patients
SO ORPHANET JOURNAL OF RARE DISEASES
LA English
DT Review
DE Classic galactosemia; GALT deficiency; Primary ovarian insufficiency;
POI; Fertility preservation; Cryopreservation
ID OVARIAN TISSUE CRYOPRESERVATION; HYPERGONADOTROPIC HYPOGONADISM;
PRENATAL EXPOSURE; CANCER-PATIENTS; GERM-CELLS; FAILURE; OOCYTE;
INSUFFICIENCY; DYSFUNCTION; PREGNANCY
AB Almost every female classic galactosemia patient develops primary ovarian insufficiency (POI) as a diet-independent complication of the disease. This is a major concern for patients and their parents, and physicians are often asked about possible options to preserve fertility. Unfortunately, there are no recommendations on fertility preservation in this group. The unique pathophysiology of classic galactosemia with a severely reduced follicle pool at an early age requires an adjusted approach. In this article recommendations for physicians based on current knowledge concerning galactosemia and fertility preservation are made. Fertility preservation is only likely to be successful in very young prepubertal patients. In this group, cryopreservation of ovarian tissue is currently the only available technique. However, this technique is not ready for clinical application, it is considered experimental and reduces the ovarian reserve. Fertility preservation at an early age also raises ethical questions that should be taken into account. In addition, spontaneous conception despite POI is well described in classic galactosemia. The uncertainty surrounding fertility preservation and the significant chance of spontaneous pregnancy warrant counseling towards conservative application of these techniques. We propose that fertility preservation should only be offered with appropriate institutional research ethics approval to classic galactosemia girls at a young prepubertal age.
C1 [van Erven, Britt; Rubio-Gozalbo, M. Estela] Maastricht Univ, Med Ctr, Dept Pediat, Maastricht, Netherlands.
[van Erven, Britt; Rubio-Gozalbo, M. Estela] Maastricht Univ, Med Ctr, Dept Genet Metab Dis Lab, Maastricht, Netherlands.
[van Erven, Britt; van Golde, Ron J.; Dunselman, Gerard A.; Derhaag, Josien G.; de Wert, Guido; Geraedts, Joep P.; Rubio-Gozalbo, M. Estela] Maastricht Univ, GROW, Res Sch Oncol & Dev Biol, Maastricht, Netherlands.
[Gubbels, Cynthia S.; Geraedts, Joep P.] Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands.
[van Golde, Ron J.; Dunselman, Gerard A.; Derhaag, Josien G.] Maastricht Univ, Med Ctr, Dept Obstet & Gynecol, Maastricht, Netherlands.
[de Wert, Guido] Maastricht Univ, Dept Hlth Eth & Soc, Maastricht, Netherlands.
[Bosch, Annet M.] Univ Amsterdam, Acad Med Ctr, Dept Pediat, NL-1105 AZ Amsterdam, Netherlands.
[Treacy, Eileen P.] Childrens Univ Hosp, Trinity Coll, Natl Ctr Inherited Metab Disorders, Dublin, Ireland.
[Welt, Corrine K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA USA.
[Berry, Gerard T.] Harvard Univ, Sch Med, Boston Childrens Hosp, Manton Ctr Orphan Dis Res,Div Genet, Boston, MA USA.
RP Rubio-Gozalbo, ME (reprint author), Maastricht Univ, Med Ctr, Dept Pediat, Maastricht, Netherlands.
EM estela.rubio@mumc.nl
RI rubio, estela/H-1833-2011;
OI Berry, Gerard/0000-0001-5299-3313; Welt, Corrine/0000-0002-8219-5504
FU Dutch Revalidatie Fonds
FX This study was financially supported by a grant from the Dutch
Revalidatie Fonds to CG and ER.
NR 68
TC 4
Z9 4
U1 1
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1172
J9 ORPHANET J RARE DIS
JI Orphanet J. Rare Dis.
PD JUL 16
PY 2013
VL 8
AR 107
DI 10.1186/1750-1172-8-107
PG 8
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 186HO
UT WOS:000322033100001
PM 23866841
ER
PT J
AU Lebl, DR
Bono, CM
Velmahos, G
Metkar, U
Nguyen, J
Harris, MB
AF Lebl, Darren R.
Bono, Christopher M.
Velmahos, George
Metkar, Umesh
Nguyen, Joseph
Harris, Mitchel B.
TI Vertebral Artery Injury Associated With Blunt Cervical Spine Trauma A
Multivariate Regression Analysis
SO SPINE
LA English
DT Article
DE cervical trauma; vertebral artery; vascular injury; computed tomographic
angiography
ID COMPUTED TOMOGRAPHIC ANGIOGRAPHY; DELAYED CORTICAL BLINDNESS;
NONINVASIVE SCREENING-TEST; CEREBROVASCULAR INJURIES; VASCULAR INJURY;
FRACTURE; DIAGNOSIS; OCCLUSION; OUTCOMES; TIME
AB Study Design. Retrospective analysis of prospective registry data.
Objective. To determine the patient characteristics, risk factors, and fracture patterns associated with vertebral artery injury (VAI) in patients with blunt cervical spine injury.
Summary of Background Data. VAI associated with cervical spine trauma has the potential for catastrophical clinical sequelae. The patterns of cervical spine injury and patient characteristics associated with VAI remain to be determined.
Methods. A retrospective review of prospectively collected data from the American College of Surgeons trauma registries at 3 level-1 trauma centers identified all patients with a cervical spine injury on multidetector computed tomographic scan during a 3-year period (January 1, 2007, to January 1, 2010). Fracture pattern and patient characteristics were recorded. Logistic multivariate regression analysis of independent predictors for VAI and subgroup analysis of neurological events related to VAI was performed.
Results. Twenty-one percent of 1204 patients with cervical injuries (n = 253) underwent screening for VAI by multidetector computed tomography angiogram. VAI was diagnosed in 17% (42 of 253), unilateral in 15% (38 of 253), and bilateral in 1.6% (4 of 253) and was associated with a lower Glasgow coma scale (P < 0.001), a higher injury severity score (P < 0.01), and a higher mortality (P < 0.001). VAI was associated with ankylosing spondylitis/diffuse idiopathic skeletal hyperosteosis (crude odds ratio [OR] = 8.04; 95% confidence interval [CI], 1.30-49.68; P = 0.034), and occipitocervical dissociation (P < 0.001) by univariate analysis and fracture displacement into the transverse foramen 1 mm or more (adjusted OR = 3.29; 95% CI, 1.15-9.41; P = 0.026), and basilar skull fracture (adjusted OR = 4.25; 95% CI, 1.25-14.47; P = 0.021), by multivariate regression model. Subgroup analyses of neurological events secondary to VAI occurred in 14% (6 of 42) and the stroke-related mortality rate was 4.8% (2 of 42). Neurological events were associated with male sex (P = 0.024), facet subluxation/ dislocation (crude OR = 9.00; 95% CI, 1.51-53.74; P = 0.004) and the diagnosis of ankylosing spondylitis/diffuse idiopathic skeletal hyperosteosis (OR = 40.67; 95% CI, 5.27-313.96; P < 0.001).
Conclusion. VAI associated with blunt cervical spine injury is a marker for more severely injured patients. High-risk patients with basilar skull fractures, occipitocervical dissociation, fracture displacement into the transverse foramen more than 1 mm, ankylosing spondylitis/diffuse idiopathic skeletal hyperosteosis, and facet subluxation/dislocation deserve focused consideration for VAI screening.
C1 [Lebl, Darren R.] Hosp Special Surg, Spine Care Inst, New York, NY 10021 USA.
[Bono, Christopher M.; Harris, Mitchel B.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA.
[Velmahos, George] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Metkar, Umesh] Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, Boston, MA 02215 USA.
[Nguyen, Joseph] Hosp Special Surg, New York, NY 10021 USA.
RP Lebl, DR (reprint author), Hosp Special Surg, Spine Care Inst, 523 East 72nd St, New York, NY 10021 USA.
EM drlebl@stanfordalumni.org
NR 44
TC 5
Z9 6
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0362-2436
EI 1528-1159
J9 SPINE
JI SPINE
PD JUL 15
PY 2013
VL 38
IS 16
BP 1352
EP 1361
DI 10.1097/BRS.0b013e318294bacb
PG 10
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 298YS
UT WOS:000330361500012
PM 23574813
ER
PT J
AU Khera, N
Storer, B
Sandmaier, BM
Chapko, MK
Lee, SJ
AF Khera, Nandita
Storer, Barry
Sandmaier, Brenda M.
Chapko, Michael K.
Lee, Stephanie J.
TI Costs of Second Allogeneic Hematopoietic Cell Transplantation
SO TRANSPLANTATION
LA English
DT Article
DE Hematopoietic cell transplantation; Economics; Costs; Cost
effectiveness; Pharmacoeconomics
ID BONE-MARROW-TRANSPLANTATION; MULTIPLE-MYELOMA; ACUTE-LEUKEMIA; GRAFT
FAILURE; RELAPSE; CHEMOTHERAPY; LYMPHOMA; SURVIVAL; BLOOD; SCT
AB Background. A second allogeneic transplantation after a prior allogeneic (allo-allo) or autologous (auto-allo) hematopoietic cell transplantation (HCT) is usually performed for graft failure, disease recurrence, secondary malignancy, and, as planned, auto-allo transplantation for some diseases.
Methods. We sought to describe the costs of second allogeneic HCT and evaluate their relationship with patient characteristics and posttransplantation complications. Clinical information and medical costs for the first 100 days after transplantation of 245 patients (allo-allo, 55; auto-allo, 190) who underwent a second HCT between 2004 and 2010 were collected.
Results. Median costs of the second allogeneic HCT were U.S. $151,000 (range, U.S. $62,000-405,000) for the allo-allo group and U.S. $109,000 (range, U.S. $26,000-490,000) for the auto-allo group. Median length of hospital stay was 23 days (range, 0-76) for the allo-allo group and 9 days (range, 0-96) for the auto-allo group. Only the year of transplantation and posttransplantation complications were significantly associated with costs in both groups when both pre- and posttransplantation variables were considered. The overall costs of the second HCT were higher than the first in the allo-allo group. For the auto-allo group, there was no difference between the costs whether preformed as a planned tandem or as salvage for relapse.
Conclusions. Our results suggest that second allogeneic HCT is costly, particularly if it follows a prior allogeneic transplantation, and is driven by the costs of complications.
C1 [Khera, Nandita] Mayo Clin Arizona, Div Hematol Oncol, Phoenix, AZ USA.
[Storer, Barry; Sandmaier, Brenda M.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Chapko, Michael K.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA.
RP Khera, N (reprint author), 5777 East Mayo Blvd,C-211, Phoenix, AZ 85054 USA.
EM khera.nandita@mayo.edu
FU National Center for Advancing Translational Sciences of the National
Institutes of Health [UL1TR000423]; National Institutes of Health [CA
78902, HL36444, CA18029]
FX The study was supported by the National Center for Advancing
Translational Sciences of the National Institutes of Health under award
number UL1TR000423 and grants CA 78902, HL36444, and CA18029 from the
National Institutes of Health.
NR 25
TC 3
Z9 3
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD JUL 15
PY 2013
VL 96
IS 1
BP 108
EP 115
DI 10.1097/TP.0b013e318294caf1
PG 8
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 299EJ
UT WOS:000330378000018
PM 23694949
ER
PT J
AU Nimptsch, K
Bernstein, AM
Giovannucci, E
Fuchs, CS
Willett, WC
Wu, KN
AF Nimptsch, Katharina
Bernstein, Adam M.
Giovannucci, Edward
Fuchs, Charles S.
Willett, Walter C.
Wu, Kana
TI Dietary Intakes of Red Meat, Poultry, and Fish During High School and
Risk of Colorectal Adenomas in Women
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE adenomatous polyps; adolescent; fish; food intake; meat; poultry
ID CANCER-RISK; BREAST-CANCER; COLON-CANCER; PREMENOPAUSAL WOMEN;
ADOLESCENT DIET; CONSUMPTION; COHORT; CHILDHOOD; MEN; ASSOCIATION
AB Adolescent diet may be etiologically relevant for colorectal carcinogenesis. We examined the association between meat and fish intakes during adolescence and the risk of colorectal adenomas later in life among 19,771 women participating in the Nurses' Health Study II. Subjects had completed a validated food frequency questionnaire in 1998 (when aged 34-51 years) about their diets during high school and subsequently underwent at least 1 lower-bowel endoscopy during the study period (1998-2007). During this period, 1,494 subjects were diagnosed with colorectal adenomas. Intake of red meat during adolescence was not associated with colorectal adenoma risk when comparing those in the highest versus lowest category of intake (odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.81, 1.35). Similarly, intake of fish during adolescence was not associated with colorectal adenoma risk (OR = 0.96, 95% CI: 0.78, 1.17). Intake of poultry during adolescence was associated with a lower risk of total colorectal (OR = 0.80, 95% CI: 0.64, 0.99), distal (OR = 0.71, 95% CI: 0.51, 0.99), rectal (OR = 0.51, 95% CI: 0.29, 0.90), and advanced (OR = 0.60, 95% CI: 0.38, 0.93) adenomas. Replacement of 1 serving per day of red meat with 1 serving per day of poultry or fish was associated with 41% and 35% decreased risks for rectal adenomas and advanced adenomas, respectively. Our findings do not suggest an association between red meat intake during adolescence and colorectal adenomas later in life, but higher poultry intake during this time was associated with a lower risk of colorectal adenomas.
C1 [Nimptsch, Katharina; Bernstein, Adam M.; Giovannucci, Edward; Willett, Walter C.; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Nimptsch, Katharina] Max Delbruck Ctr Mol Med, Mol Epidemiol Res Grp, Berlin, Germany.
[Giovannucci, Edward; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward; Fuchs, Charles S.; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Giovannucci, Edward; Fuchs, Charles S.; Willett, Walter C.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Bernstein, Adam M.] Cleveland Clin, Wellness Inst, Lyndhurst, OH USA.
RP Nimptsch, K (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA.
EM knimptsc@hsph.harvard.edu
OI Nimptsch, Katharina/0000-0001-7877-205X
FU American Institute for Cancer Research; National Cancer Institute [R01
CA50385]; Entertainment Industry Foundation's National Colorectal Cancer
Research Alliance
FX The authors acknowledge funding from the American Institute for Cancer
Research (investigator-initiated grant to K. W.), the National Cancer
Institute (grant R01 CA50385 to W. C. W.), and the Entertainment
Industry Foundation's National Colorectal Cancer Research Alliance.
NR 47
TC 5
Z9 6
U1 0
U2 19
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUL 15
PY 2013
VL 178
IS 2
BP 172
EP 183
DI 10.1093/aje/kwt099
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 186DD
UT WOS:000322021300002
PM 23785116
ER
PT J
AU Rosner, B
Glynn, RJ
Tamimi, RM
Chen, WY
Colditz, GA
Willett, WC
Hankinson, SE
AF Rosner, Bernard
Glynn, Robert J.
Tamimi, Rulla M.
Chen, Wendy Y.
Colditz, Graham A.
Willett, Walter C.
Hankinson, Susan E.
TI Breast Cancer Risk Prediction with Heterogeneous Risk Profiles According
to Breast Cancer Tumor Markers
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE breast cancer; competing risks; proportional hazards model
ID PROGESTERONE-RECEPTOR STATUS; COMPETING RISKS; NURSES HEALTH; ESTROGEN;
SUBTYPES; DISEASE
AB Relationships between some risk factors and breast cancer incidence are known to vary by tumor subtype. However, breast tumors can be classified according to a number of markers, which may be correlated, making it difficult to identify heterogeneity of risk factors with specific tumor markers when using standard competing-risk survival analysis. In this paper, we propose a constrained competing-risk survival model that allows for assessment of heterogeneity of risk factor associations according to specific tumor markers while controlling for other markers. These methods are applied to Nurses' Health Study data from 1980-2006, during which 3,398 incident invasive breast cancers occurred over 1.4 million person-years of follow-up. Results suggested that when estrogen receptor (ER) and progesterone receptor (PR) status are mutually considered, some risk factors thought to be characteristic of "estrogen-positive tumors," such as high body mass index during postmenopause and increased height, are actually significantly associated with PR-positive tumors but not ER-positive tumors, while other risk factors thought to be characteristic of "estrogen-negative tumors," such as late age at first birth, are actually significantly associated with PR-negative rather than ER-negative breast cancer. This approach provides a strategy for evaluating heterogeneity of risk factor associations by tumor marker levels while controlling for additional tumor markers.
C1 [Rosner, Bernard; Glynn, Robert J.; Tamimi, Rulla M.; Chen, Wendy Y.; Willett, Walter C.; Hankinson, Susan E.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Rosner, Bernard; Glynn, Robert J.; Tamimi, Rulla M.; Chen, Wendy Y.; Willett, Walter C.; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Colditz, Graham A.] Washington Univ, Alvin J Siteman Canc Ctr, St Louis, MO USA.
[Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA.
[Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Rosner, Bernard; Glynn, Robert J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Glynn, Robert J.] Harvard Univ, Sch Med, Div Prevent Med, Boston, MA USA.
[Chen, Wendy Y.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Rosner, B (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA.
EM stbar@channing.harvard.edu
RI Colditz, Graham/A-3963-2009
OI Colditz, Graham/0000-0002-7307-0291
FU National Cancer Institute [PO1 CA87969]; American Cancer Society
Clinical Research Professorship
FX This work was supported by the National Cancer Institute (grant PO1
CA87969). G.A.C. was also supported by an American Cancer Society
Clinical Research Professorship.
NR 13
TC 26
Z9 26
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUL 15
PY 2013
VL 178
IS 2
BP 296
EP 308
DI 10.1093/aje/kws457
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 186DD
UT WOS:000322021300016
PM 23645624
ER
PT J
AU Vaturi, M
Vaduganathan, M
Bental, T
Solodky, A
Kornowski, R
Lev, EI
AF Vaturi, Mordehay
Vaduganathan, Muthiah
Bental, Tamir
Solodky, Alejandro
Kornowski, Ran
Lev, Eli I.
TI Relation of Aspirin Response to Age in Patients With Stable Coronary
Artery Disease
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID LOW-DOSE ASPIRIN; HEART-ASSOCIATION COUNCIL; HEALTH-CARE PROFESSIONALS;
CARDIOVASCULAR-DISEASE; PLATELET REACTIVITY; THROMBOXANE BIOSYNTHESIS;
MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; SCIENTIFIC STATEMENT;
GERIATRIC-CARDIOLOGY
AB Recent studies have suggested that clopidogrel response may vary significantly with age. Limited data are available exploring the age dependency of ex vivo aspirin response in young and old patients with stable coronary artery disease. Patients with stable coronary artery disease (n = 583) who had been treated with aspirin 75 to 325 mg/day for >= 1 week were recruited from a general cardiology practice. The study cohort was divided into 2 groups: patients aged <75 years (n = 438) and patients aged >= 75 years (n = 145). Aspirin response was determined using the Verify Now Aspirin Test, and resistance was defined as >= 500 or 550 aspirin reaction units (ARU). The independent predictive value of age on Verify Now score (as a continuous function) was determined using multivariate linear regression, adjusted for gender, body mass index, and diabetes mellitus. Younger and older patients had similar baseline clinical profiles, including relative doses of aspirin therapy. The mean Verify Now Aspirin Test score was significantly higher in patients aged >= 75 years: 450 +/- 54 versus 434 +/- 53 ARU (p = 0.0007). After accounting for the primary covariates, age remained a predictor of Verify Now score (p = 0.007). Aspirin resistance on the basis of the 500-ARU cutoff was higher in older patients (19% vs 11%, p = 0.009), but there was no difference when the 550-ARU cutoff was used (7% vs 5%, p = 0.40). In conclusion, aspirin response differs significantly by age in patients with stable CAD. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Vaturi, Mordehay; Bental, Tamir; Solodky, Alejandro; Kornowski, Ran; Lev, Eli I.] Rabin Med Ctr, Dept Cardiol, Petah Tiqwa, Israel.
[Vaturi, Mordehay; Bental, Tamir; Solodky, Alejandro; Kornowski, Ran; Lev, Eli I.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Vaduganathan, Muthiah] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA.
RP Lev, EI (reprint author), Rabin Med Ctr, Dept Cardiol, Petah Tiqwa, Israel.
EM elil@clalit.org.il
NR 27
TC 7
Z9 8
U1 1
U2 6
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 15
PY 2013
VL 112
IS 2
BP 212
EP 216
DI 10.1016/j.amjcard.2013.03.022
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 188PR
UT WOS:000322206500012
PM 23566542
ER
PT J
AU Kandala, J
Upadhyay, GA
Pokushalov, E
Wu, S
Drachman, DE
Singh, JP
AF Kandala, Jagdesh
Upadhyay, Gaurav A.
Pokushalov, Evgeny
Wu, Sean
Drachman, Douglas E.
Singh, Jagmeet P.
TI Meta-Analysis of Stem Cell Therapy in Chronic Ischemic Cardiomyopathy
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID MARROW MONONUCLEAR-CELLS; LEFT-VENTRICULAR FUNCTION; CHRONIC
HEART-FAILURE; MYOCARDIAL-INFARCTION; PROGENITOR CELLS; TRANSPLANTATION;
DELIVERY; TRIAL; NEOVASCULARIZATION; INJECTION
AB Studies investigating bone marrow stem cell therapy (BMSCT) in patients with chronic ischemic cardiomyopathy have yielded mixed results. A meta-analysis of randomized controlled trials of BMSCT in patients with chronic ischemic cardiomyopathy was undertaken to assess its efficacy and the best route of administration. The MEDLINE, Embase, Cumulative Index to Nursing & Allied Health Literature, and Cochrane Library databases were searched through April 2012 for randomized controlled trials that investigated the impact of BMSCT and its route of administration on left ventricular (LV) function in patients with chronic ischemic cardiomyopathy and systolic dysfunction. Of the 226 reports identified, 10 randomized controlled trials including 519 patients (average LV ejection fraction [LVEF] at baseline 32 +/- 7%) were included in the analysis. On the basis of a random-effects model, BMSCT improved the LVEF at 6 months by 4.48% (95% confidence interval [CI] 2.43% to 6.53%, p = 0.0001). A greater improvement in the LVEF was seen with intramyocardial injection compared with intracoronary infusion (5.13% [95% CI 3.17% to 7.10%], p <0.00001, vs 2.32% [95% CI -2.06% to 6.70%], p = 0.30). Overall, there were reductions in LV end-systolic volume of -20.64 ml (95% CI -33.21 to -8.07, p = 0.001) and LV end-diastolic volume of -16.71 ml (95% CI -31.36 to -2.06, p = 0.03). In conclusion, stem cell therapy may improve LVEF and favorably remodel the heart in patients with chronic ischemic cardiomyopathy. On the basis of current limited data, intramyocardial injection may be superior to intracoronary infusion in patients with LV systolic dysfunction. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Kandala, Jagdesh; Upadhyay, Gaurav A.; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02115 USA.
[Wu, Sean] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
[Drachman, Douglas E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Pokushalov, Evgeny] State Res Inst Circulat Pathol, Novosibirsk, Russia.
RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02115 USA.
EM jsingh@partners.org
RI Pokushalov, Evgeny/L-7993-2014
OI Pokushalov, Evgeny/0000-0002-2560-5167
NR 27
TC 36
Z9 36
U1 1
U2 14
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 15
PY 2013
VL 112
IS 2
BP 217
EP 225
DI 10.1016/j.amjcard.2013.03.021
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 188PR
UT WOS:000322206500013
PM 23623290
ER
PT J
AU Bethel, MA
Chacra, AR
Deedwania, P
Fulcher, GR
Holman, RR
Jenssen, T
Kahn, SE
Levitt, NS
McMurray, JJV
Califf, RM
Raptis, SA
Thomas, L
Sun, JL
Haffner, SM
AF Bethel, M. Angelyn
Chacra, Antonio R.
Deedwania, Prakash
Fulcher, Gregory R.
Holman, Rury R.
Jenssen, Trond
Kahn, Steven E.
Levitt, Naomi S.
McMurray, John J. V.
Califf, Robert M.
Raptis, Sotirios A.
Thomas, Laine
Sun, Jie-Lena
Haffner, Steven M.
TI A Novel Risk Classification Paradigm for Patients With Impaired Glucose
Tolerance and High Cardiovascular Risk
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS;
FASTING GLUCOSE; LIVER FIBROSIS; TASK-FORCE; HEART; TRIAL; NATEGLINIDE;
PREVENTION
AB We used baseline data from the NAVIGATOR trial to (1) identify risk factors for diabetes progression in those with impaired glucose tolerance and high cardiovascular risk, (2) create models predicting 5-year incident diabetes, and (3) provide risk classification tools to guide clinical interventions. Multivariate Cox proportional hazards models estimated 5-year incident diabetes risk and simplified models examined the relative importance of measures of glycemia in assessing diabetes risk. The C-statistic was used to compare models; reclassification analyses compare the models' ability to identify risk groups defined by potential therapies (routine or intensive lifestyle advice or pharmacologic therapy). Diabetes developed in 3,254 (35%) participants over 5 years median follow-up. The full prediction model included fasting and 2-hour glucose and hemoglobin A1c (HbA1c) values but demonstrated only moderate discrimination for diabetes (C = 0.70). Simplified models with only fasting glucose (C = 0.67) or oral glucose tolerance test values (C = 0.68) had higher C statistics than models with HbA1c alone (C = 0.63). The models were unlikely to inappropriately reclassify participants to risk groups that might receive pharmacologic therapy. Our results confirm that in a population with dysglycemia and high cardiovascular risk, traditional risk factors are appropriate predictors and glucose values are better predictors than HbA1c, but discrimination is moderate at best, illustrating the challenges of predicting diabetes in a high-risk population. In conclusion, our novel risk classification paradigm based on potential treatment could be used to guide clinical practice based on cost and availability of screening tests. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Bethel, M. Angelyn; Holman, Rury R.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Diabet Trials Unit, Oxford, England.
[Bethel, M. Angelyn] Duke Univ, Med Ctr, Dept Med, Div Metab Endocrinol & Nutr, Durham, NC 27710 USA.
[Chacra, Antonio R.] Univ Fed Sao Paulo, Sao Paulo, Brazil.
[Deedwania, Prakash] Univ Calif San Francisco Program Fresno, Fresno, CA USA.
[Deedwania, Prakash] Vet Adm Cent Calif Hlth Care Syst, Fresno, CA USA.
[Fulcher, Gregory R.] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia.
[Jenssen, Trond] Univ Tromso, Oslo Univ Hosp, Rigshosp, Inst Clin Med, Oslo, Norway.
[Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA.
[Levitt, Naomi S.] Univ Cape Town, Dept Med, Groote Schuur Hosp, Endocrine Unit, ZA-7925 Cape Town, South Africa.
[McMurray, John J. V.] Univ Glasgow, Glasgow Cardiovasc Res Ctr, British Heart Fdn, Glasgow, Lanark, Scotland.
[Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC USA.
[Raptis, Sotirios A.] Attikon Univ Hosp, Hellen Natl Diabet Ctr, Dept Internal Med Endocrinol & Diabetol 2, Athens, Greece.
[Thomas, Laine] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA.
[Thomas, Laine; Sun, Jie-Lena] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
RP Bethel, MA (reprint author), Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Diabet Trials Unit, Oxford, England.
EM angelyn.bethel@dtu.ox.ac.uk
OI Kahn, Steven/0000-0001-7307-9002; mcmurray, john/0000-0002-6317-3975
FU Novartis Pharmaceuticals
FX The NAVIGATOR trial was funded by Novartis Pharmaceuticals.
NR 21
TC 2
Z9 2
U1 0
U2 1
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 15
PY 2013
VL 112
IS 2
BP 231
EP 237
DI 10.1016/j.amjcard.2013.03.019
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 188PR
UT WOS:000322206500015
PM 23608615
ER
PT J
AU Villiger, M
Zhang, EZ
Nadkarni, SK
Oh, WY
Vakoc, BJ
Bouma, BE
AF Villiger, Martin
Zhang, Ellen Ziyi
Nadkarni, Seemantini K.
Oh, Wang-Yuhl
Vakoc, Benjamin J.
Bouma, Brett E.
TI Spectral binning for mitigation of polarization mode dispersion
artifacts in catheter-based optical frequency domain imaging
SO OPTICS EXPRESS
LA English
DT Article
ID COHERENCE TOMOGRAPHY; IN-VIVO; MAINTAINING FIBER; BIREFRINGENCE;
ORIENTATION; COLLAGEN; PMD
AB Polarization mode dispersion (PMD) has been recognized as a significant barrier to sensitive and reproducible birefringence measurements with fiber-based, polarization-sensitive optical coherence tomography systems. Here, we present a signal processing strategy that reconstructs the local retardation robustly in the presence of system PMD. The algorithm uses a spectral binning approach to limit the detrimental impact of system PMD and benefits from the final averaging of the PMD-corrected retardation vectors of the spectral bins. The algorithm was validated with numerical simulations and experimental measurements of a rubber phantom. When applied to the imaging of human cadaveric coronary arteries, the algorithm was found to yield a substantial improvement in the reconstructed birefringence maps. (C) 2013 Optical Society of America
C1 [Villiger, Martin; Zhang, Ellen Ziyi; Nadkarni, Seemantini K.; Vakoc, Benjamin J.; Bouma, Brett E.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Villiger, Martin; Zhang, Ellen Ziyi; Nadkarni, Seemantini K.; Vakoc, Benjamin J.; Bouma, Brett E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Oh, Wang-Yuhl] Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305701, South Korea.
[Vakoc, Benjamin J.; Bouma, Brett E.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02142 USA.
RP Villiger, M (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA.
EM mvilliger@partners.org
FU National Institutes of Health [P41 EB015903, R01 CA163528]; NRF of Korea
[2012-0005633]; Terumo Corporation; Swiss National Science Foundation
FX Research reported in this publication was supported in part by the
National Institutes of Health, grants P41 EB015903 and R01 CA163528, by
the NRF of Korea, grant 2012-0005633, and by Terumo Corporation. M.V.
was supported by a fellowship from the Swiss National Science
Foundation.
NR 31
TC 23
Z9 23
U1 2
U2 13
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1094-4087
J9 OPT EXPRESS
JI Opt. Express
PD JUL 15
PY 2013
VL 21
IS 14
BP 16353
EP 16369
DI 10.1364/OE.21.016353
PG 17
WC Optics
SC Optics
GA 183MK
UT WOS:000321819400015
PM 23938487
ER
PT J
AU Jubran, A
AF Jubran, Amal
TI Has the Twitching Hour Arrived for the Ventilated Patient?
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID MECHANICAL VENTILATION; RANDOMIZED-TRIAL; PRESSURE; DURATION; FAILURE;
SUPPORT; HUMANS; MUSCLE
C1 [Jubran, Amal] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA.
[Jubran, Amal] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA.
RP Jubran, A (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 12
TC 2
Z9 2
U1 0
U2 1
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 JUL 15
PY 2013
VL 188
IS 2
BP 126
EP 128
DI 10.1164/rccm.201305-0890ED
PG 4
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 183LV
UT WOS:000321817400004
PM 23855688
ER
PT J
AU Esteban, A
Frutos-Vivar, F
Muriel, A
Ferguson, ND
Penuelas, O
Abraira, V
Raymondos, K
Rios, F
Nin, N
Apezteguia, C
Violi, DA
Thille, AW
Brochard, L
Gonzalez, M
Villagomez, AJ
Hurtado, J
Davies, AR
Du, B
Maggiore, SM
Pelosi, P
Soto, L
Tomicic, V
D'Empaire, G
Matamis, D
Abroug, F
Moreno, RP
Soares, MA
Arabi, Y
Sandi, F
Jibaja, M
Amin, P
Koh, Y
Kuiper, MA
Bulow, HH
Zeggwagh, AA
Anzueto, A
AF Esteban, Andres
Frutos-Vivar, Fernando
Muriel, Alfonso
Ferguson, Niall D.
Penuelas, Oscar
Abraira, Victor
Raymondos, Konstantinos
Rios, Fernando
Nin, Nicolas
Apezteguia, Carlos
Violi, Damian A.
Thille, Arnaud W.
Brochard, Laurent
Gonzalez, Marco
Villagomez, Asisclo J.
Hurtado, Javier
Davies, Andrew R.
Du, Bin
Maggiore, Salvatore M.
Pelosi, Paolo
Soto, Luis
Tomicic, Vinko
D'Empaire, Gabriel
Matamis, Dimitrios
Abroug, Fekri
Moreno, Rui P.
Soares, Marco Antonio
Arabi, Yaseen
Sandi, Freddy
Jibaja, Manuel
Amin, Pravin
Koh, Younsuck
Kuiper, Michael A.
Bulow, Hans-Henrik
Zeggwagh, Amine Ali
Anzueto, Antonio
TI Evolution of Mortality over Time in Patients Receiving Mechanical
Ventilation
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE mechanical ventilation; mortality; epidemiology; cohort study
ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; RANDOMIZED
CONTROLLED-TRIAL; END-EXPIRATORY PRESSURE; LOWER TIDAL VOLUMES;
CRITICALLY-ILL PATIENTS; PROTECTIVE-VENTILATION; STRATEGY; METAANALYSIS;
SEDATION
AB Rationale: Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear.
Objectives: To estimate whether mortality in mechanically ventilated patients has changed over time.
Methods: Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models.
Measurements and Main Results: We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P, 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92).
Conclusions: Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials.gov (NCT01093482).
C1 [Esteban, Andres; Frutos-Vivar, Fernando; Penuelas, Oscar; Nin, Nicolas] Hosp Univ Getafe, Madrid 28905, Spain.
[Muriel, Alfonso; Abraira, Victor] Hosp Ramon & Cajal, Dept Clin Biostat, Inst Ramon y Cajal Invest Sanitaria, Madrid, Spain.
[Ferguson, Niall D.] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON M5S 1A1, Canada.
[Ferguson, Niall D.] Univ Toronto, Dept Med, Toronto, ON M5S 1A1, Canada.
[Ferguson, Niall D.] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A1, Canada.
[Raymondos, Konstantinos] Hannover Med Sch, Hannover, Germany.
[Rios, Fernando; Apezteguia, Carlos] Hosp Nacl Alejandro Posadas, Buenos Aires, DF, Argentina.
[Violi, Damian A.] Hosp Interzonal Gen Agudos Dr Luis Guemes, Haedo, Argentina.
[Thille, Arnaud W.] CHU Henri Mondor, F-94010 Creteil, France.
[Brochard, Laurent] Univ Hosp Geneva, Geneva, Switzerland.
[Gonzalez, Marco] Clin Medellin, Medellin, Colombia.
[Gonzalez, Marco] Univ Pontificia Bolivariana, Medellin, Colombia.
[Villagomez, Asisclo J.] Hosp Reg 1 Octubre, Inst Seguridad & Serv Sociales Trabajadores Estad, Mexico City, DF, Mexico.
[Hurtado, Javier] Hosp Clin Montevideo, Montevideo, Uruguay.
[Davies, Andrew R.] Alfred Hosp, Melbourne, Vic, Australia.
[Davies, Andrew R.] Monash Univ, Melbourne, Vic 3004, Australia.
[Du, Bin] Beijing Union Med Coll Hosp, Beijing, Peoples R China.
[Maggiore, Salvatore M.] Univ Cattolica Sacro Cuore, Policlin Agostino Gemelli, Rome, Italy.
[Pelosi, Paolo] Univ Genoa, Dipartimento Sci Chirurg & Diagnost Integrate, Genoa, Italy.
[Soto, Luis] Inst Nacl Torax Santiago, Santiago, Chile.
[Tomicic, Vinko] Clin Las Lilas Santiago, Santiago, Chile.
[D'Empaire, Gabriel] Hosp Clin Caracas, Caracas, Venezuela.
[Matamis, Dimitrios] Papageorgiou Hosp, Thessaloniki, Greece.
[Abroug, Fekri] Hosp Fattouma Bourguina, Monastir, Tunisia.
[Moreno, Rui P.] Ctr Hosp Lisboa Cent, Hosp Sao Jose, Unidade Cuidados Intens Neurocrit, Lisbon, Portugal.
[Soares, Marco Antonio] Hosp Univ Sao Jose, Belo Horizonte, MG, Brazil.
[Arabi, Yaseen] King Saud Bin Abdulaziz Univ Hlth Sci, Riyadh, Saudi Arabia.
[Sandi, Freddy] Hosp Obrero 1, La Paz, Bolivia.
[Jibaja, Manuel] Hosp Eugenio Espejo, Quito, Ecuador.
[Amin, Pravin] Bombay Hosp Inst Med Sci, Bombay, Maharashtra, India.
[Koh, Younsuck] Univ Ulsan, Asan Med Ctr, Seoul, South Korea.
[Kuiper, Michael A.] Med Ctr Leeuwarden, Leeuwarden, Netherlands.
[Bulow, Hans-Henrik] Reg Zealand Univ Copenhagen, Holbak Hosp, Copenhagen, Denmark.
[Zeggwagh, Amine Ali] Hop Ibn Sina, Rabat, Morocco.
[Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
RP Esteban, A (reprint author), Hosp Univ Getafe, Intens Care Unit, Carretera Toledo,Km 12,500, Madrid 28905, Spain.
EM aesteban@ucigetafe.com
OI Abraira, Victor/0000-0002-4615-8503; Frutos-Vivar,
Fernando/0000-0002-4648-9636; MAGGIORE, Salvatore
Maurizio/0000-0002-1828-9143; Ferguson, Niall/0000-0002-6213-5264;
Muriel, Alfonso /0000-0002-4805-4011
FU Centro de Investigacion Biomedica en red Enfermedades Respiratorias,
CIBER en Epidemiologia y Salud Publica; Instituto de Salud Carlos III,
Madrid, Spain; Instituto Ramon y Cajal de Investigacion Sanitaria,
Madrid, Spain; Canadian Institutes of Health Research (Ottawa, ON,
Canada)
FX Supported by Centro de Investigacion Biomedica en red Enfermedades
Respiratorias, CIBER en Epidemiologia y Salud Publica. Instituto de
Salud Carlos III, Madrid, Spain, Instituto Ramon y Cajal de
Investigacion Sanitaria, Madrid, Spain, and by a Canadian Institutes of
Health Research (Ottawa, ON, Canada) New Investigator Award (N.D.F.).
NR 43
TC 122
Z9 129
U1 2
U2 14
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 JUL 15
PY 2013
VL 188
IS 2
BP 220
EP 230
DI 10.1164/rccm.201212-2169OC
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 183LV
UT WOS:000321817400017
PM 23631814
ER
PT J
AU Schulz, TJ
Tseng, YH
AF Schulz, Tim J.
Tseng, Yu-Hua
TI Brown adipose tissue: development, metabolism and beyond
SO BIOCHEMICAL JOURNAL
LA English
DT Review
DE adipocyte; brown adipose tissue; obesity; thermogenesis; white adipose
tissue
ID BONE MORPHOGENETIC PROTEIN-7; DIET-INDUCED THERMOGENESIS; WHITE FAT;
TRANSCRIPTIONAL CONTROL; ENERGY-EXPENDITURE; SKELETAL-MUSCLE; INDUCED
OBESITY; ADULT HUMANS; STEM-CELLS; IN-VIVO
AB Obesity represents a major risk factor for the development of several of our most common medical conditions, including Type 2 diabetes, dyslipidaemia, non-alcoholic fatty liver, cardiovascular disease and even some cancers. Although increased fat mass is the main feature of obesity, not all fat depots are created equal. Adipocytes found in white adipose tissue contain a single large lipid droplet and play well-known roles in energy storage. By contrast, brown adipose tissue is specialized for thermogenic energy expenditure. Owing to its significant capacity to dissipate energy and regulate triacylglycerol (triglyceride) and glucose metabolism, and its demonstrated presence in adult humans, brown fat could be a potential target for the treatment of obesity and metabolic syndrome. Undoubtedly, fundamental knowledge about the formation of brown fat and regulation of its activity is imperatively needed to make such therapeutics possible. In the present review, we integrate the recent advancements on the regulation of brown fat formation and activity by developmental and hormonal signals in relation to its metabolic function.
C1 [Schulz, Tim J.] German Inst Human Nutr, Res Grp Adipocyte Dev, D-14558 Nuthetal, Germany.
[Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA.
[Tseng, Yu-Hua] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Tseng, YH (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA.
EM yu-hua.tseng@joslin.harvard.edu
RI Schulz, Tim/F-4842-2013
OI Schulz, Tim/0000-0002-8413-3972
FU National Institutes of Health [R01 DK077097]; Joslin Diabetes Center's
Diabetes Research Center (from the National Institute of Diabetes and
Digestive and Kidney Disease) [P30 DK036836]; American Diabetes
Association; Harvard Stem Cell Institute; Mary K. Iacocca Foundation;
German Research Foundation [SCHU 2445/1-1, SCHU 2445/2-1]; European
Research Council [ERC-StG-311082]
FX This work was supported, in part, by the National Institutes of Health
[grant number R01 DK077097 (to Y.-H.T.)], the Joslin Diabetes Center's
Diabetes Research Center [grant number P30 DK036836 (from the National
Institute of Diabetes and Digestive and Kidney Disease)], the American
Diabetes Association and the Harvard Stem Cell Institute (to Y.-H.T.).
T.J.S. was supported by the Mary K. Iacocca Foundation, the German
Research Foundation [grant numbers SCHU 2445/1-1 and SCHU 2445/2-1] and
the European Research Council [grant number ERC-StG-311082].
NR 149
TC 33
Z9 33
U1 4
U2 46
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0264-6021
J9 BIOCHEM J
JI Biochem. J.
PD JUL 15
PY 2013
VL 453
BP 167
EP 178
DI 10.1042/BJ20130457
PN 2
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 183IS
UT WOS:000321808800002
PM 23805974
ER
PT J
AU Fendt, SM
Bell, EL
Keibler, MA
Davidson, SM
Wirth, GJ
Fiske, B
Mayers, JR
Schwab, M
Bellinger, G
Csibi, A
Patnaik, A
Blouin, MJ
Cantley, LC
Guarente, L
Blenis, J
Pollak, MN
Olumi, AF
Vander Heiden, MG
Stephanopoulos, G
AF Fendt, Sarah-Maria
Bell, Eric L.
Keibler, Mark A.
Davidson, Shawn M.
Wirth, Gregory J.
Fiske, Brian
Mayers, Jared R.
Schwab, Matthias
Bellinger, Gary
Csibi, Alfredo
Patnaik, Akash
Blouin, Marie Jose
Cantley, Lewis C.
Guarente, Leonard
Blenis, John
Pollak, Michael N.
Olumi, Aria F.
Vander Heiden, Matthew G.
Stephanopoulos, Gregory
TI Metformin Decreases Glucose Oxidation and Increases the Dependency of
Prostate Cancer Cells on Reductive Glutamine Metabolism
SO CANCER RESEARCH
LA English
DT Article
ID PROLIFERATION; GROWTH; INHIBITION; RISK; FLUX; APOPTOSIS; THERAPY;
BIOLOGY; ARREST; EMU
AB Metformin inhibits cancer cell proliferation, and epidemiology studies suggest an association with increased survival in patients with cancer taking metformin; however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation, whereas increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer. (C) 2013 AACR.
C1 [Fendt, Sarah-Maria; Keibler, Mark A.; Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Bell, Eric L.; Davidson, Shawn M.; Fiske, Brian; Mayers, Jared R.; Guarente, Leonard; Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Davidson, Shawn M.; Fiske, Brian; Mayers, Jared R.; Vander Heiden, Matthew G.] MIT, Koch Inst Canc Res, Cambridge, MA 02139 USA.
[Wirth, Gregory J.; Olumi, Aria F.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[Bellinger, Gary; Cantley, Lewis C.] Beth Israel Deaconess Canc Ctr, Div Signal Transduct, Dept Med, Boston, MA USA.
[Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
[Csibi, Alfredo] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pollak, Michael N.] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
[Schwab, Matthias] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada.
[Schwab, Matthias] Doctor Margarete Fischer Bosch Inst Clin Pharmaco, Stuttgart, Germany.
[Schwab, Matthias] Univ Hosp, Inst Expt & Clin Pharmacol & Toxicol, Dept Clin Pharmacol, Tubingen, Germany.
RP Stephanopoulos, G (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM mvh@mit.edu; gregstep@mit.edu
RI Cantley, Lewis/D-1800-2014;
OI Cantley, Lewis/0000-0002-1298-7653; Wirth, Gregory
J./0000-0003-0636-3438; Mayers, Jared/0000-0002-8607-1787; Fendt,
Sarah-Maria/0000-0001-6018-9296
FU German Research Foundation (DFG) [FE1185]; NIH [5-P50-090381-09,
5-P30-CA14051-39, 1R01DK075850-01, 1R01CA160458-01A1]; Glenn Foundation
for Medical Research; LAM Foundation; Burrough's Wellcome Fund; Smith
Family; Damon Runyon Cancer Research Foundation
FX S.-M. Fendt is supported by the German Research Foundation (DFG), grant
FE1185. L. Guarente is supported by the NIH and the Glenn Foundation for
Medical Research. A. Csibi is supported by a fellowship from the LAM
Foundation. M.G. Vander Heiden acknowledges NIH grant support from
5-P50-090381-09 and 5-P30-CA14051-39 and support from the Burrough's
Wellcome Fund, the Smith Family, and the Damon Runyon Cancer Research
Foundation. The authors also received grants 1R01DK075850-01 and
1R01CA160458-01A1 from the NIH (G. Stephanopoulos).
NR 47
TC 64
Z9 65
U1 5
U2 28
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2013
VL 73
IS 14
BP 4429
EP 4438
DI 10.1158/0008-5472.CAN-13-0080
PG 10
WC Oncology
SC Oncology
GA 183NR
UT WOS:000321823600025
PM 23687346
ER
PT J
AU Wang, Q
Von, T
Bronson, R
Ruan, MZ
Mu, WX
Huang, A
Maira, SM
Zhao, JJ
AF Wang, Qi
Thanh Von
Bronson, Roderick
Ruan, Minzi
Mu, Wenxia
Huang, Alan
Maira, Sauveur-Michel
Zhao, Jean J.
TI Spatially distinct roles of class Ia PI3K isoforms in the development
and maintenance of PTEN hamartoma tumor syndrome
SO GENES & DEVELOPMENT
LA English
DT Article
DE genetic mouse models; PI3K inhibitors; PI3K isoforms; skin; PTEN
hamartoma tumor syndrome
ID PHOSPHOINOSITIDE 3-KINASE; P110-ALPHA ISOFORM; BREAST-CANCER; EPIDERMAL
HOMEOSTASIS; P110-BETA ISOFORMS; COWDEN-SYNDROME; MOUSE MODEL;
STEM-CELLS; SUPPRESSOR; SKIN
AB PTEN hamartoma tumor syndrome (PHTS) comprises a collection of genetic disorders associated with germline mutations in the tumor suppressor gene PTEN. Therapeutic options and preventative measures for PHTS are limited. Using both genetically engineered mouse models and pharmacological PI3K isoform-selective inhibitors, we found that the roles of PI3K isoforms are spatially distinct in the skin: While p110 alpha is responsible for the sustained survival of suprabasal cells of the epidermis in the absence of PTEN, p110 beta is important for the hyperproliferation of basal cells in PHTS. Furthermore, we identified a differential expression pattern of p110 alpha and p110 beta in basal and suprabasal keratinocytes as well as differential PI3K regulation by upstream signals in the basal and suprabasal compartments of the epidermis, providing a potential molecular mechanism underlying the specific roles of PI3K isoforms in the epidermis. Finally, we demonstrate that combined inhibition of both PI3K isoforms prevents the development of PHTS and also reverses skin hamartomas that have reached advanced stages in mice. Together, these results not only advance our overall understanding of the diverse roles of PI3K isoforms, but also have the potential for meaningful translation via the clinical utilization of PI3K inhibitors for both prevention and therapy in PHTS patients.
C1 [Wang, Qi; Thanh Von; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Wang, Qi; Thanh Von; Zhao, Jean J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA.
[Bronson, Roderick] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr Rodent Histopathol C, Boston, MA 02215 USA.
[Ruan, Minzi; Mu, Wenxia] VigeneTech Inc, Carlisle, MA 01741 USA.
[Huang, Alan] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
[Maira, Sauveur-Michel] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland.
RP Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
EM jean_zhao@dfci.harvard.edu
FU NIH [CA134502, CA172461-01]; Stand Up To Cancer [SU2C-AACR-DT0209];
Department of Defense [BC112689]
FX We thank T.M. Roberts, L.C. Cantley, P.P. Pandolfi, and D.M. Livingston
for scientific discussions, and L.K. Clayton for critical reading. We
thank A. Ang, P. Liu, and M. Pusung for technical assistance. K14Cre
mice were generously provided by J. Jonkers at the Netherlands Cancer
Institute, Netherlands. Floxed Pten mice were generously provided by H.
Wu at the University of California at Los Angeles School of Medicine.
This work was supported by NIH grants CA134502 (to J.J.Z.) and
CA172461-01 (to J.J.Z.), Stand Up To Cancer (SU2C-AACR-DT0209) (to
J.J.Z.), and the Department of Defense (BC112689 to J.J.Z.).
NR 46
TC 8
Z9 8
U1 0
U2 1
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD JUL 15
PY 2013
VL 27
IS 14
BP 1568
EP 1580
DI 10.1101/gad.216069.113
PG 13
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 185ZU
UT WOS:000322011500005
PM 23873941
ER
PT J
AU Sadovski, O
Hicks, JW
Parkes, J
Raymond, R
Nobrega, J
Houle, S
Cipriano, M
Fowler, CJ
Vasdev, N
Wilson, AA
AF Sadovski, Oleg
Hicks, Justin W.
Parkes, Jun
Raymond, Roger
Nobrega, Jose
Houle, Sylvain
Cipriano, Mariateresa
Fowler, Christopher J.
Vasdev, Neil
Wilson, Alan A.
TI Development and characterization of a promising fluorine-18 labelled
radiopharmaceutical for in vivo imaging of fatty acid amide hydrolase
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE PET; FAAH; Radiosynthesis; Fluorine-18; Rat; Endocannabinoid; Anandamide
ID POSITRON-EMISSION-TOMOGRAPHY; CANNABINOID CB1 RECEPTORS; ENDOCANNABINOID
SYSTEM; HUMAN BRAIN; FAAH; ANANDAMIDE; INHIBITORS; RAT; PET; EXPRESSION
AB Fatty acid amide hydrolase (FAAH), the enzyme responsible for terminating signaling by the endocannabinoid anandamide, plays an important role in the endocannabinoid system, and FAAH inhibitors are attractive drugs for pain, addiction, and neurological disorders. The synthesis, radiosynthesis, and evaluation, in vitro and ex vivo in rat, of an F-18-radiotracer designed to image FAAH using positron emission tomography (PET) is described.
Fluorine-18 labelled 3-(4,5-dihydrooxazol-2-yl)phenyl (5-fluoropentyl)carbamate, [F-18]5, was synthesized at high specific activity in a one-pot three step reaction using a commercial module with a radiochemical yield of 17-22% (from [F-18]fluoride). In vitro assay using rat brain homogenates showed that 5 inhibited FAAH in a time-dependent manner, with an IC50 value of 0.82 nM after a preincubation of 60 min. Ex vivo biodistribution studies and ex vivo autoradiography in rat brain demonstrated that [F-18]5 had high brain penetration with standard uptake values of up to 4.6 and had a regional distribution which correlated with reported regional FAAH enzyme activity. Specificity of binding to FAAH with [H-18]5 was high (>90%) as demonstrated by pharmacological challenges with potent and selective FAAH inhibitors and was irreversible as demonstrated by radioactivity measurements on homogenized brain tissue extracts.
We infer from these results that [F-18]5 is a highly promising candidate radiotracer with which to image FAAH in human subjects using PET and clinical studies are proceeding. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
C1 [Sadovski, Oleg; Hicks, Justin W.; Parkes, Jun; Raymond, Roger; Nobrega, Jose; Houle, Sylvain; Wilson, Alan A.] Ctr Addict & Mental Hlth, Res Imaging Ctr, Toronto, ON M5T 1R8, Canada.
[Nobrega, Jose; Houle, Sylvain; Wilson, Alan A.] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada.
[Cipriano, Mariateresa; Fowler, Christopher J.] Umea Univ, Dept Pharmacol & Clin Neurosci, SE-90187 Umea, Sweden.
[Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA.
[Vasdev, Neil] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Vasdev, Neil] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Wilson, AA (reprint author), Ctr Addict & Mental Hlth, Res Imaging Ctr, 250 Coll St, Toronto, ON M5T 1R8, Canada.
EM alan.wilson@camhpet.ca
RI Wilson, Alan/A-1788-2011;
OI Cipriano, Mariateresa/0000-0001-6644-7137
FU NIH [1R21MH094424]; University of Toronto Institute of Medical Science;
Swedish Research Council [12158]
FX This work was supported by NIH Grant # 1R21MH094424 to A.A.W., a
University of Toronto Institute of Medical Science Open Fellowship award
to J.W.H., and by a Grant from the Swedish Research Council (Grant no.
12158, medicine) to C.J.F. We would like to thank Armando Garcia,
Winston Stableford, Min Wong, and Alvina Ng for their assistance with
the radiochemistry and animal dissection experiments.
NR 51
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Z9 12
U1 3
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 15
PY 2013
VL 21
IS 14
BP 4351
EP 4357
DI 10.1016/j.bmc.2013.04.077
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 170GK
UT WOS:000320838200042
PM 23712084
ER
PT J
AU Guenova, E
Watanabe, R
Teague, JE
Desimone, JA
Jiang, Y
Dowlatshahi, M
Schlapbach, C
Schaekel, K
Rook, AH
Tawa, M
Fisher, DC
Kupper, TS
Clark, RA
AF Guenova, Emmanuella
Watanabe, Rei
Teague, Jessica E.
Desimone, Jennifer A.
Jiang, Ying
Dowlatshahi, Mitra
Schlapbach, Christoph
Schaekel, Knut
Rook, Alain H.
Tawa, Marianne
Fisher, David C.
Kupper, Thomas S.
Clark, Rachael A.
TI T(H)2 Cytokines from Malignant Cells Suppress T(H)1 Responses and
Enforce a Global T(H)2 Bias in Leukemic Cutaneous T-cell Lymphoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SEZARY-SYNDROME; MYCOSIS-FUNGOIDES; EORTC CLASSIFICATION; EXPRESS;
IMMUNOPATHOGENESIS; PROLIFERATION; SURVIVAL; SUBSETS; PATTERN; BLOOD
AB Purpose: In leukemic cutaneous T-cell lymphoma (L-CTCL), malignant T cells accumulate in the blood and give rise to widespread skin inflammation. Patients have intense pruritus, increased immunoglobulin E (IgE), and decreased T-helper (T-H)-1 responses, and most die from infection. Depleting malignant T cells while preserving normal immunity is a clinical challenge. L-CTCL has been variably described as a malignancy of regulatory, T(H)2 and T(H)17 cells.
Experimental Design: We analyzed phenotype and cytokine production in malignant and benign L-CTCL T cells, characterized the effects of malignant T cells on healthy T cells, and studied the immunomodulatory effects of treatment modalities in patients with L-CTCL.
Results: Twelve out of 12 patients with L-CTCL overproduced T(H)2 cytokines. Remaining benign T cells were also strongly T(H)2 biased, suggesting a global T(H)2 skewing of the T-cell repertoire. Culture of benign T cells away from the malignant clone reduced T(H)2 and enhanced T(H)1 responses, but separate culture had no effect on malignant T cells. Coculture of healthy T cells with L-CTCL T cells reduced IFN gamma production and neutralizing antibodies to interleukin (IL)-4 and IL-13 restored T(H)1 responses. In patients, enhanced T(H)1 responses were observed following a variety of treatment modalities that reduced malignant T-cell burden.
Conclusions: A global T(H)2 bias exists in both benign and malignant T cells in L-CTCL and may underlie the infectious susceptibility of patients. T(H)2 cytokines from malignant cells strongly inhibited T(H)1 responses. Our results suggest that therapies that inhibit T(H)2 cytokine activity, by virtue of their ability to improve T(H)1 responses, may have the potential to enhance both anticancer and antipathogen responses. (C) 2013 AACR.
C1 [Guenova, Emmanuella; Watanabe, Rei; Teague, Jessica E.; Desimone, Jennifer A.; Dowlatshahi, Mitra; Schlapbach, Christoph; Kupper, Thomas S.; Clark, Rachael A.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
[Guenova, Emmanuella; Watanabe, Rei; Teague, Jessica E.; Desimone, Jennifer A.; Dowlatshahi, Mitra; Schlapbach, Christoph; Kupper, Thomas S.; Clark, Rachael A.] Harvard Univ, Sch Med, Boston, MA USA.
[Tawa, Marianne; Fisher, David C.; Kupper, Thomas S.; Clark, Rachael A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
[Jiang, Ying] Temple Univ, Sch Med, Philadelphia, PA 19122 USA.
[Rook, Alain H.] Hosp Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA.
[Schaekel, Knut] Univ Heidelberg Hosp, Dept Dermatol, Heidelberg, Germany.
RP Clark, RA (reprint author), Brigham & Womens Hosp, Dept Dermatol, Room 505A,221 Longwood Ave, Boston, MA 02115 USA.
EM rclark1@partners.org
RI Guenova, Emmanuella/A-4656-2015; Schlapbach, Christoph/D-5832-2013
OI Schlapbach, Christoph/0000-0003-0258-1243
FU Damon Runyon Clinical Investigator Award [R01 AR056720, R03 MH095529];
SPORE in Skin Cancer [P50 CA9368305]; NIH/National Cancer Institute;
NIH/National Institute of Allergy and Infectious Diseases [R01
A1025082]; Leukemia & Lymphoma Society; German Research Foundation
(DFG); Swiss National Science Foundation; Fondation Rene Touraine; [R01
AI097128]; [R01 CA122569]; [GU1271/2-1]
FX This work was supported by a generous charitable contribution from
Edward P. Lawrence, Esq., a Damon Runyon Clinical Investigator Award (to
R.A. Clark) R01 AR056720 (to R.A. Clark) and R03 MH095529 (to R.A.
Clark), the SPORE in Skin Cancer P50 CA9368305 NIH/National Cancer
Institute (to T.S. Kupper), R01 A1025082 NIH/National Institute of
Allergy and Infectious Diseases (to T. S. Kupper), R01 AI097128 (to T.S.
Kupper and R.A. Clark), R01 CA122569 (to A.H. Rook), and by a Special
Fellow Award from the Leukemia & Lymphoma Society (to R. Watanabe).
Grant support GU1271/2-1 (to E. Guenova) was provided by the German
Research Foundation (DFG), and salary support for C. Schlapbach was
provided by the Swiss National Science Foundation and the Fondation Rene
Touraine.
NR 28
TC 31
Z9 32
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2013
VL 19
IS 14
BP 3755
EP 3763
DI 10.1158/1078-0432.CCR-12-3488
PG 9
WC Oncology
SC Oncology
GA 183NE
UT WOS:000321822000006
PM 23785046
ER
PT J
AU Zhang, YX
van Oosterwijk, JG
Sicinska, E
Moss, S
Remillard, SP
Van Wezel, T
Uhnemann, CB
Hassan, AB
Demetri, GD
Bovee, JVMG
Wagner, AJ
AF Zhang, Yi-Xiang
van Oosterwijk, Jolieke G.
Sicinska, Ewa
Moss, Samuel
Remillard, Stephen P.
Van Wezel, Tom
Uhnemann, Claudia B.
Hassan, Andrew B.
Demetri, George D.
Bovee, Judith V. M. G.
Wagner, Andrew J.
TI Functional Profiling of Receptor Tyrosine Kinases and Downstream
Signaling in Human Chondrosarcomas Identifies Pathways for Rational
Targeted Therapy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID IN-VITRO; ANTITUMOR-ACTIVITY; TUMOR-GROWTH; CELL-LINE; INHIBITOR;
CANCER; TRANSLATION; MUTATIONS; NVP-BEZ235; INSULIN
AB Purpose: Chondrosarcomas are notoriously resistant to cytotoxic chemotherapeutic agents. We sought to identify critical signaling pathways that contribute to their survival and proliferation, and which may provide potential targets for rational therapeutic interventions.
us were examined in chondrosarcoma primary tumor tissues. siRNA or small-molecule inhibitors against RTKs or downstream signaling proteins were applied to chondrosarcoma cells and changes in biochemical signaling, cell cycle, and cell viability were determined. In vivo antitumor activity of BEZ235, a phosphoinositide 3-kinase (PI3K)/mTOR inhibitor, was evaluated in a chondrosarcoma xenograft model.
Results: Several RTKs were identified as critical mediators of cell growth, but the RTK dependencies varied among cell lines. In exploration of downstream signaling pathways, strong S6 phosphorylation was found in 69% of conventional chondrosarcomas and 44% of dedifferentiated chondrosarcomas. Treatment with BEZ235 resulted in dramatic reduction in the growth of all chondrosarcoma cell lines. Tumor growth was similarly inhibited in a xenograft model of chondrosarcoma. In addition, chondrosarcoma cells with an NRAS mutation were sensitive to treatment with a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor. Functional NRAS mutations were found in 12% of conventional central chondrosarcomas.
Conclusions: RTKs are commonly activated in chondrosarcoma, but because of their considerable heterogeneity, targeted inhibition of the PI3K/mTOR pathway represents a rational therapeutic strategy. Chondrosarcomas with NRAS mutations may benefit from treatment with MEK inhibitors.
C1 [Zhang, Yi-Xiang; Remillard, Stephen P.; Demetri, George D.; Wagner, Andrew J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ludwig Ctr,Dana Farber Harvard, Boston, MA 02215 USA.
[Zhang, Yi-Xiang; Remillard, Stephen P.; Demetri, George D.; Wagner, Andrew J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol,Dept Med Oncol, Boston, MA 02215 USA.
[Sicinska, Ewa; Moss, Samuel] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Sicinska, Ewa; Moss, Samuel] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02215 USA.
[van Oosterwijk, Jolieke G.; Van Wezel, Tom; Bovee, Judith V. M. G.] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
[Uhnemann, Claudia B.; Hassan, Andrew B.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
RP Wagner, AJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM Andrew_Wagner@dfci.harvard.edu
RI van Wezel, Tom/A-9599-2008
OI Bovee, Judith/0000-0003-1155-0481; van Wezel, Tom/0000-0001-5773-7730
FU Dunkin Donuts Rising Star Award; Fund for Cancer Research supporting the
Dana-Farber/Harvard Ludwig Center; Netherlands Organization for
Scientific Research [91767-315]; Dutch Cancer Society [UL2010-4873]; EC
seventh framework programme [278742]
FX Dunkin Donuts Rising Star Award (to A.J. Wagner) and D.K. Ludwig Fund
for Cancer Research supporting the Dana-Farber/Harvard Ludwig Center (to
G.D. Demetri), the Netherlands Organization for Scientific Research
(91767-315; to J.G. van Oosterwijk and J.V.M.G. Bovee) and Dutch Cancer
Society (UL2010-4873; to J.G. van Oosterwijk and J.V.M.G. Bovee). Leiden
and Oxford are partners in the context of EuroSarc, an EC seventh
framework programme under grant agreement no 278742.
NR 46
TC 15
Z9 15
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2013
VL 19
IS 14
BP 3796
EP 3807
DI 10.1158/1078-0432.CCR-12-3647
PG 12
WC Oncology
SC Oncology
GA 183NE
UT WOS:000321822000010
PM 23714727
ER
PT J
AU Nishino, M
Giobbie-Hurder, A
Gargano, M
Suda, M
Ramaiya, NH
Hodi, FS
AF Nishino, Mizuki
Giobbie-Hurder, Anita
Gargano, Maria
Suda, Margaret
Ramaiya, Nikhil H.
Hodi, F. Stephen
TI Developing a Common Language for Tumor Response to Immunotherapy:
Immune-Related Response Criteria Using Unidimensional Measurements
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CELL LUNG-CANCER; GUIDELINE VERSION 1.1; SOLID TUMORS; PHASE-II;
DOUBLE-BLIND; RECIST; IPILIMUMAB; ANTIBODY; THERAPY; SAFETY
AB Purpose: Immune-related response criteria (irRC) was developed to adequately assess tumor response to immunotherapy. The irRC are based on bidimensional measurements, as opposed to unidimensional measurements defined by Response Evaluation Criteria in Solid Tumors, which has been widely used in solid tumors. We aimed to compare response assessment by bidimensional versus unidimensional irRC in patients with advanced melanoma treated with ipilimumab.
Experimental Design: Fifty-seven patients with advanced melanoma treated with ipilimumab in a phase II, expanded access trial were studied. Bidimensional tumor measurement records prospectively conducted during the trial were reviewed to generate a second set of measurements using unidimensional, longest diameter measurements. The percent changes of measurements at follow-up, best overall response, and time-to-progression (TTP) were compared between bidimensional and unidimensional irRC. Interobserver variability for bidimensional and unidimensional measurements was assessed in 25 randomly selected patients.
Results: The percent changes at follow-up scans were highly concordant between the 2 criteria (Spearman r: 0.953-0.965, first to fourth follow-up). The best immune-related response was highly concordant between the 2 criteria (kappa(w) = 0.881). TTP was similar between the bidimensional and unidimensional assessments (progression-free at 6 months: 70% vs. 81%, respectively). The unidimensional measurements were more reproducible than bidimensional measurements, with the 95% limits of agreement of (-16.1%, 5.8%) versus (-31.3%, 19.7%), respectively.
Conclusion: irRC using the unidimensional measurements provided highly concordant response assessment compared with the bidimensional irRC, with less measurement variability. The use of unidimensional irRC is proposed to assess response to immunotherapy in solid tumors, given its simplicity, higher reproducibility, and high concordance with the bidimensional irRC. (C) 2013 AACR.
C1 [Nishino, Mizuki; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA.
[Gargano, Maria; Suda, Margaret; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Gargano, Maria; Suda, Margaret; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
[Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Nishino, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 450 Brookline Ave, Boston, MA 02115 USA.
EM Mizuki_Nishino@dfci.harvard.edu
FU NCI [1K23CA157631]; Dana-Farber Cancer Institute
FX The investigator M. Nishino was supported by 1K23CA157631 (NCI) and
Dana-Farber Cancer Institute Fellowship for the Eleanor and Miles Shore
50th Anniversary Fellowship Program.
NR 20
TC 59
Z9 65
U1 0
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2013
VL 19
IS 14
BP 3936
EP 3943
DI 10.1158/1078-0432.CCR-13-0895
PG 8
WC Oncology
SC Oncology
GA 183NE
UT WOS:000321822000022
PM 23743568
ER
PT J
AU Ng, K
Tabernero, J
Hwang, J
Bajetta, E
Sharma, S
Del Prete, SA
Arrowsmith, ER
Ryan, DP
Sedova, M
Jin, J
Malek, K
Fuchs, CS
AF Ng, Kimmie
Tabernero, Josep
Hwang, Jimmy
Bajetta, Emilio
Sharma, Sunil
Del Prete, Salvatore A.
Arrowsmith, Edward R.
Ryan, David P.
Sedova, Michaela
Jin, Jin
Malek, Kamel
Fuchs, Charles S.
TI Phase II Study of Everolimus in Patients with Metastatic Colorectal
Adenocarcinoma Previously Treated with Bevacizumab-, Fluoropyrimidine-,
Oxaliplatin-, and Irinotecan-Based Regimens
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID KIRSTEN RAS MUTATIONS; ADVANCED SOLID TUMORS; MAMMALIAN TARGET;
NEUROENDOCRINE TUMORS; SIGNALING PATHWAYS; HUMAN CANCER; INHIBITION;
KINASE; MTOR; AKT
AB Purpose: Dysregulation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway is seen in 40% to 60% of patients with colorectal cancer. Everolimus, an oral inhibitor of mTOR, showed efficacy in patients with metastatic colorectal cancers in phase I studies.
Experimental Design: In sequential phase II studies assessing two dosing schedules, patients with metastatic colorectal cancers refractory to bevacizumab-, fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens received everolimus 70 mg/wk (n = 99) or 10 mg/d (n = 100). Primary endpoints were disease control rate (DCR) and objective response rate; secondary endpoints included progression-free survival (PFS), overall survival (OS), and duration of response or stable disease (SD). Tumor tissue was collected from all patients for predefined exploratory biomarker analyses.
Results: Seventy-one patients were included in the per-protocol set for each cohort. DCRs of 31.0% and 32.4% (all SD) were seen in the weekly and daily schedules, respectively. Median duration of SD was 3.9 months in each cohort. Median PFS and OS were 1.8 and 4.9 months and 1.8 and 5.9 months, respectively, for the weekly and daily schedules. Among patients receiving daily everolimus, those with a KRAS mutation experienced significantly shorter median OS (P = 0.008) and lower DCR (P = 0.035) compared with those with wild-type KRAS in exploratory biomarker analyses.
Conclusions: Everolimus 70 mg/wk or 10 mg/d was well tolerated but did not confer meaningful efficacy in heavily pretreated patients with metastatic colorectal cancers. Future studies may consider evaluating everolimus in combination with other agents or in patients with dysregulation of the PI3K/Akt/mTOR pathway. (C) 2013 AACR.
C1 [Ng, Kimmie; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Ryan, David P.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA.
[Tabernero, Josep] Univ Autonoma Barcelona, Dept Med Oncol, Vall dHebron Univ Hosp, E-08193 Barcelona, Spain.
[Hwang, Jimmy] Georgetown Univ, Lombardi Canc Ctr, Dept Hematol Oncol, Washington, DC USA.
[Bajetta, Emilio] Policlin Monza, Inst Oncol, Dept Med Oncol, Monza, Italy.
[Sharma, Sunil] Nevada Canc Inst, Las Vegas, NV USA.
[Del Prete, Salvatore A.] Hematol Oncol PC, Stamford, CT USA.
[Arrowsmith, Edward R.] Chattanooga Oncol Hematol Associates, Chattanooga, TN USA.
[Sedova, Michaela; Malek, Kamel] Novartis Pharma AG, Basel, Switzerland.
[Jin, Jin] Novartis Pharmaceut, E Hanover, NJ USA.
RP Ng, K (reprint author), Dana Farber Canc Inst, Ctr Gastrointestinal Oncol, Dept Med Oncol, 450 Brookline Ave,Dana 1220, Boston, MA 02215 USA.
EM Kimmie_Ng@dfci.harvard.edu
FU Novartis Pharmaceuticals Corporation
FX This work was supported by Novartis Pharmaceuticals Corporation.
NR 29
TC 17
Z9 17
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2013
VL 19
IS 14
BP 3987
EP 3995
DI 10.1158/1078-0432.CCR-13-0027
PG 9
WC Oncology
SC Oncology
GA 183NE
UT WOS:000321822000027
PM 23743569
ER
PT J
AU Stearns, V
Jacobs, LK
Fackler, M
Tsangaris, TN
Rudek, MA
Higgins, M
Lange, J
Cheng, Z
Slater, SA
Jeter, SC
Powers, P
Briest, S
Chao, C
Yoshizawa, C
Sugar, E
Espinoza-Delgado, I
Sukumar, S
Gabrielson, E
Davidson, NE
AF Stearns, Vered
Jacobs, Lisa K.
Fackler, MaryJo
Tsangaris, Theodore N.
Rudek, Michelle A.
Higgins, Michaela
Lange, Julie
Cheng, Zandra
Slater, Shannon A.
Jeter, Stacie C.
Powers, Penny
Briest, Susanne
Chao, Calvin
Yoshizawa, Carl
Sugar, Elizabeth
Espinoza-Delgado, Igor
Sukumar, Saraswati
Gabrielson, Edward
Davidson, Nancy E.
TI Biomarker Modulation following Short-Term Vorinostat in Women with Newly
Diagnosed Primary Breast Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR;
METHYLATION-SPECIFIC PCR; PROMOTER HYPERMETHYLATION; PHASE-II; CELLS;
TAMOXIFEN; ASSAY; THERAPY; TARGET
AB Purpose: Agents that target the epigenome show activity in breast cancer models. In preclinical studies, the histone deacetylase inhibitor vorinostat induces cell-cycle arrest, apoptosis, and differentiation. We evaluated biomarker modulation in breast cancer tissues obtained from women with newly diagnosed invasive disease who received vorinostat and those who did not.
Experimental Design: Tumor specimens were collected from 25 women who received up to 6 doses of oral vorinostat 300 mg twice daily and from 25 untreated controls in a nonrandomized study. Candidate gene expression was analyzed by reverse transcription PCR (RT-PCR) using the Oncotype DX 21-gene assay, and by immunohistochemistry for Ki-67 and cleaved caspase-3. Matched samples from treated women were analyzed for gene methylation by quantitative multiplex methylation-specific PCR (QM-MSP). Wilcoxon nonparametric tests were used to compare changes in quantitative gene expression levels pre- and post-vorinostat with changes in expression in untreated controls, and changes in gene methylation between pre- and post-vorinostat samples.
Results: Vorinostat was well tolerated and there were no study-related delays in treatment. Compared with untreated controls, there were statistically significant decreases in the expression of proliferation-associated genes Ki-67 (P = 0.003), STK15 (P = 0.005), and Cyclin B1 (P = 0.03) following vorinostat, but not in other genes by the Oncotype DX assay, or in expression of Ki-67 or cleaved caspase-3 by immunohistochemistry. Changes in methylation were not observed.
Conclusions: Short-term vorinostat administration is associated with a significant decrease in expression of proliferation-associated genes in untreated breast cancers. This demonstration of biologic activity supports investigation of vorinostat in combination with other agents for the management of breast cancer. (C) 2013 AACR.
C1 [Stearns, Vered; Fackler, MaryJo; Rudek, Michelle A.; Higgins, Michaela; Slater, Shannon A.; Jeter, Stacie C.; Powers, Penny; Briest, Susanne; Sugar, Elizabeth; Sukumar, Saraswati; Davidson, Nancy E.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Jacobs, Lisa K.; Tsangaris, Theodore N.; Lange, Julie] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
[Gabrielson, Edward] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Sugar, Elizabeth] Johns Hopkins Bloomberg, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Sugar, Elizabeth] Johns Hopkins Bloomberg, Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Cheng, Zandra] Anne Arundel Med Ctr, Annapolis, MD USA.
[Espinoza-Delgado, Igor] NCI, NIH, Bethesda, MD 20892 USA.
[Chao, Calvin; Yoshizawa, Carl] Genom Hlth Inc, Redwood City, CA USA.
RP Higgins, M (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM theodore.tsangaris@yale.edu; mjhiggins@partners.org
FU CTEP; NIH [U01 CA 70095]; SAIC [P6914, P30CA47904, U01-CA099168];
American Society of Clinical Oncology Advanced Clinical Research Award;
Young Investigator Award; Specialized Program of Research Excellence in
Breast Cancer [P50 CA88843]; Avon Foundation; Merck
FX This work was supported by the CTEP, NIH U01 CA 70095 (to V. Stearns VS
and M.A. Rudek) and SAIC (P6914 to V. Stearns), P30CA47904 (to M.
Egorin) and U01-CA099168 (to M. Egorin), American Society of Clinical
Oncology Advanced Clinical Research Award (to V. Stearns), Young
Investigator Award (to M.J. Higgins), Specialized Program of Research
Excellence in Breast Cancer (P50 CA88843 to S. Sukumar and N.E.
Davidson), and by the Avon Foundation. Vorinostat for the vorinostat and
tamoxifen study was supplied by Merck. The Oncotype DX 21-gene assays
were conducted by Genomic Health, Inc.
NR 23
TC 14
Z9 14
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2013
VL 19
IS 14
BP 4008
EP 4016
DI 10.1158/1078-0432.CCR-13-0033
PG 9
WC Oncology
SC Oncology
GA 183NE
UT WOS:000321822000029
PM 23719261
ER
PT J
AU Storer, NY
White, RM
Uong, A
Price, E
Nielsen, GP
Langenau, DM
Zon, LI
AF Storer, Narie Y.
White, Richard M.
Uong, Audrey
Price, Emily
Nielsen, G. Petur
Langenau, David M.
Zon, Leonard I.
TI Zebrafish rhabdomyosarcoma reflects the developmental stage of oncogene
expression during myogenesis
SO DEVELOPMENT
LA English
DT Article
DE Rhabdomyosarcoma; Zebrafish; Muscle
ID CHILDRENS-ONCOLOGY-GROUP; MOUSE SKELETAL-MUSCLE; EMBRYONAL
RHABDOMYOSARCOMA; ALVEOLAR RHABDOMYOSARCOMA; TRANSGENIC ZEBRAFISH;
GENE-EXPRESSION; M-CADHERIN; RAS GENES; CELLS; MUTATIONS
AB Rhabdomyosarcoma is a pediatric malignancy thought to arise from the uncontrolled proliferation of myogenic cells. Here, we have generated models of rhabdomyosarcoma in the zebrafish by inducing oncogenic KRAS(G12D) expression at different stages during muscle development. Several zebrafish promoters were used, including the cdh15 and rag2 promoters, which drive gene expression in early muscle progenitors, and the mylz2 promoter, which is expressed in differentiating myoblasts. The tumors that developed differed in their ability to recapitulate normal myogenesis. cdh15:KRAS(G12D) and rag2:KRAS(G12D) fish developed tumors that displayed an inability to complete muscle differentiation as determined by histological appearance and gene expression analyses. By contrast, mylz2: KRAS(G12D) tumors more closely resembled mature skeletal muscle and were most similar to well-differentiated human rhabdomyosarcoma in terms of gene expression. mylz2:KRAS(G12D) fish showed significantly improved survival compared with cdh15:KRAS(G12D) and rag2:KRAS(G12D) fish. Tumor-propagating activity was enriched in myf5-expressing cell populations within all of the tumor types. Our results demonstrate that oncogenic KRAS(G12D) expression at different stages during muscle development has profound effects on the ability of tumor cells to recapitulate normal myogenesis, altering the tumorigenic capability of these cells.
C1 [Storer, Narie Y.; Uong, Audrey; Price, Emily; Zon, Leonard I.] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
[Storer, Narie Y.; Uong, Audrey; Price, Emily; Zon, Leonard I.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Storer, Narie Y.; Uong, Audrey; Price, Emily; Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Storer, Narie Y.; Uong, Audrey; Price, Emily; Zon, Leonard I.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[White, Richard M.; Nielsen, G. Petur] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Langenau, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Zon, LI (reprint author), Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
FU National Institutes of Health [R01CA103846]; National Institute of
General Medical Sciences [T32GM007753]
FX This work was supported by the National Institutes of Health
[R01CA103846 to L.I.Z.] and the National Institute of General Medical
Sciences [T32GM007753 to N.Y.S.]. Deposited in PMC for release after 12
months.
NR 47
TC 11
Z9 13
U1 0
U2 2
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD JUL 15
PY 2013
VL 140
IS 14
BP 3040
EP 3050
DI 10.1242/dev.087858
PG 11
WC Developmental Biology
SC Developmental Biology
GA 176AQ
UT WOS:000321275700019
PM 23821038
ER
PT J
AU Youngblood, B
Noto, A
Porichis, F
Akondy, RS
Ndhlovu, ZM
Austin, JW
Bordi, R
Procopio, FA
Miura, T
Allen, TM
Sidney, J
Sette, A
Walker, BD
Ahmed, R
Boss, JM
Sekaly, RP
Kaufmann, DE
AF Youngblood, Ben
Noto, Alessandra
Porichis, Filippos
Akondy, Rama S.
Ndhlovu, Zaza M.
Austin, James W.
Bordi, Rebeka
Procopio, Francesco A.
Miura, Toshiyuki
Allen, Todd M.
Sidney, John
Sette, Alessandro
Walker, Bruce D.
Ahmed, Rafi
Boss, Jeremy M.
Sekaly, Rafick-Pierre
Kaufmann, Daniel E.
TI Cutting Edge: Prolonged Exposure to HIV Reinforces a Poised Epigenetic
Program for PD-1 Expression in Virus-Specific CD8 T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CHRONIC VIRAL-INFECTION; ANTIRETROVIRAL THERAPY; EXHAUSTION; MEMORY;
LIGANDS; DEMETHYLATION; REPLICATION; PERSISTENCE; COMMITMENT; TISSUE
AB Ag-specific CD8 T cells play a critical role in controlling HIV infection but eventually lose antiviral functions in part because of expression and signaling through the inhibitory programmed death-1 (PD-1) receptor. To better understand the impact of prolonged TCR ligation on regulation of PD-1 expression in HIV-specific CD8 T cells, we investigated the capacity of virus-specific CD8 T cells to modify the PD-1 epigenetic program after reduction in viral load. We observed that the transcriptional regulatory region was unmethylated in the PD-1 hi HIV-specific CD8 T cells, whereas it remained methylated in donor-matched naive cells at acute and chronic stages of infection. Surprisingly, the PD-1 promoter remained unmethylated in HIV-specific CD8 T cells from subjects with a viral load controlled by antiviral therapy for >2 y or from elite controllers. Together, these data demonstrate that the epigenetic program at the PD-1 locus becomes fixed after prolonged exposure to HIV virus.
C1 [Youngblood, Ben; Akondy, Rama S.; Austin, James W.; Ahmed, Rafi; Boss, Jeremy M.] Emory Univ, Emory Vaccine Ctr, Sch Med, Atlanta, GA 30322 USA.
[Youngblood, Ben; Akondy, Rama S.; Austin, James W.; Ahmed, Rafi; Boss, Jeremy M.] Emory Univ, Dept Microbiol & Immunol, Sch Med, Atlanta, GA 30322 USA.
[Noto, Alessandra; Bordi, Rebeka; Procopio, Francesco A.; Sekaly, Rafick-Pierre] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL 34987 USA.
[Porichis, Filippos; Ndhlovu, Zaza M.; Allen, Todd M.; Walker, Bruce D.; Kaufmann, Daniel E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA.
[Ndhlovu, Zaza M.] Univ KwaZulu Natal, Nelson Mandela Sch Med, HIV Pathogenesis Program, Durban, South Africa.
[Miura, Toshiyuki] ViiV Healthcare, Tokyo 1518566, Japan.
[Miura, Toshiyuki] Nagasaki Univ, Inst Trop Med, Nagasaki 8528521, Japan.
[Sidney, John; Sette, Alessandro] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Kaufmann, Daniel E.] Ctr Hosp Univ Montreal, Ctr Rech, Montreal, PQ H2X 1P1, Canada.
RP Sekaly, RP (reprint author), Vaccine & Gene Therapy Inst Florida, 9801 SW Discovery Way, Port St Lucie, FL 34987 USA.
EM rpsekaly@vgtifl.org; dkaufmann@partners.org
RI Allen, Todd/F-5473-2011;
OI Akondy, Rama/0000-0003-4737-5240
FU National Institutes of Health [P01 AI080192-04, R37 AI30048-17, R01
HL092565]; American Cancer Society Postdoctoral Fellowship
[PF-09-134-01-MPC]; Research Scholar Career Award of the Quebec Health
Research Fund (FRQS)
FX This work was supported by National Institutes of Health Grants P01
AI080192-04 (to R.A., J.M.B, R.-P.S., and D.E.K.), R37 AI30048-17 (to
R.A.), and R01 HL092565 (to D.E.K.), and American Cancer Society
Postdoctoral Fellowship PF-09-134-01-MPC (to B.Y.). D.E.K is supported
by a Research Scholar Career Award of the Quebec Health Research Fund
(FRQS).
NR 30
TC 47
Z9 48
U1 0
U2 11
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2013
VL 191
IS 2
BP 540
EP 544
DI 10.4049/jimmunol.1203161
PG 5
WC Immunology
SC Immunology
GA 175UW
UT WOS:000321260100005
PM 23772031
ER
PT J
AU Archambault, AS
Carrero, JA
Barnett, LG
McGee, NG
Sim, J
Wright, JO
Raabe, T
Chen, PQ
Ding, H
Allenspach, EJ
Dragatsis, I
Laufer, TM
Wu, GF
AF Archambault, Angela S.
Carrero, Javier A.
Barnett, Lisa G.
McGee, Nigel G.
Sim, Julia
Wright, Jonathan O.
Raabe, Tobias
Chen, Peiquin
Ding, Hua
Allenspach, Eric J.
Dragatsis, Ioannis
Laufer, Terri M.
Wu, Gregory F.
TI Cutting Edge: Conditional MHC Class II Expression Reveals a Limited Role
for B Cell Antigen Presentation in Primary and Secondary CD4 T Cell
Responses
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; DENDRITIC CELLS; IN-VIVO;
MICE; REQUIREMENT; PROGRESSION; MUTATIONS; IMMUNITY; DISEASE
AB The activation, differentiation, and subsequent effector functions of CD4 T cells depend on interactions with a multitude of MHC class II (MHCII)-expressing APCs. To evaluate the individual contribution of various APCs to CD4 T cell function, we have designed a new murine tool for selective in vivo expression of MHCII in subsets of APCs. Conditional expression of MHCII in B cells was achieved using a cre-loxP approach. After i.v. or s.c. priming, partial proliferation and activation of CD4 T cells was observed in mice expressing MHCII only by B cells. Restricting MHCII expression to B cells constrained secondary CD4 T cell responses in vivo, as demonstrated in a CD4 T cell-dependent model of autoimmunity, experimental autoimmune encephalomyelitis. These results highlight the limitations of B cell Ag presentation during initiation and propagation of CD4 T cell function in vivo using a novel system to study individual APCs by the conditional expression of MHCII.
C1 [Archambault, Angela S.; McGee, Nigel G.; Wright, Jonathan O.; Wu, Gregory F.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Carrero, Javier A.; Wu, Gregory F.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Barnett, Lisa G.; Allenspach, Eric J.; Laufer, Terri M.] Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19004 USA.
[Sim, Julia] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
[Raabe, Tobias; Chen, Peiquin] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19004 USA.
[Ding, Hua] Childrens Hosp Philadelphia, Joseph Stokes Jr Res Inst, Philadelphia, PA 19004 USA.
[Dragatsis, Ioannis] Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA.
[Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19004 USA.
RP Wu, GF (reprint author), Washington Univ, Sch Med, 660 South Euclid Ave,Box 8111, St Louis, MO 63110 USA.
EM wug@neuro.wustl.edu
OI Allenspach, Eric/0000-0001-7346-5835
FU National Cancer Institute Cancer Center Support Grant [P30 CA91842];
National Institute of Neurological Disorders and Stroke [5K08NS062138];
Barnes-Jewish Foundation
FX We thank the Alvin J. Siteman Cancer Center (supported in part by
National Cancer Institute Cancer Center Support Grant #P30 CA91842) and
the Barnes-Jewish Hospital for the use of the Embryonic Stem Cell Core,
which provided all ES cell services.; This work was supported by the
National Institute of Neurological Disorders and Stroke (Grant
5K08NS062138) and the Barnes-Jewish Foundation.
NR 25
TC 9
Z9 9
U1 0
U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2013
VL 191
IS 2
BP 545
EP 550
DI 10.4049/jimmunol.1201598
PG 6
WC Immunology
SC Immunology
GA 175UW
UT WOS:000321260100006
PM 23772037
ER
PT J
AU Liu, Z
Jiang, Y
Li, YH
Wang, J
Fan, LY
Scott, MJ
Xiao, GZ
Li, S
Billiar, TR
Wilson, MA
Fan, J
AF Liu, Zheng
Jiang, Yong
Li, Yuehua
Wang, Juan
Fan, Liyan
Scott, Melanie J.
Xiao, Guozhi
Li, Song
Billiar, Timothy R.
Wilson, Mark A.
Fan, Jie
TI TLR4 Signaling Augments Monocyte Chemotaxis by Regulating G
Protein-Coupled Receptor Kinase 2 Translocation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CHEMOKINE RECEPTORS; NEUTROPHIL MIGRATION; CELL RECRUITMENT; EXPRESSION;
GRK2; MICE; CHEMOATTRACTANT; DESENSITIZATION; INFLAMMATION; ACTIVATION
AB Monocytes are critical effector cells of the innate immune system that protect the host by migrating to inflammatory sites, differentiating to macrophages and dendritic cells, eliciting immune responses, and killing pathogenic microbes. MCP-1, also known as CCL2, plays an important role in monocyte activation and migration. The chemotactic function of MCP-1 is mediated by binding to the CCR2 receptor, a member of the G protein-coupled receptor (GPCR) family. Desensitization of GPCR chemokine receptors is an important regulator of the intensity and duration of chemokine stimulation. GPCR kinases (GRKs) induce GPCR phosphorylation, and this leads to GPCR desensitization. Regulation of subcellular localization of GRKs is considered an important early regulatory mechanism of GRK function and subsequent GPCR desensitization. Chemokines and LPS are both present during Gram-negative bacterial infection, and LPS often synergistically exaggerates leukocyte migration in response to chemokines. In this study, we investigated the role and mechanism of LPS-TLR4 signaling on the regulation of monocyte chemotaxis. We demonstrate that LPS augments MCP-1-induced monocyte migration. We also show that LPS, through p38 MAPK signaling, induces phosphorylation of GRK2 at serine 670, which, in turn, suppresses GRK2 translocation to the membrane, thereby preventing GRK2-initiated internalization and desensitization of CCR2 in response to MCP-1. This results in enhanced monocyte migration. These findings reveal a novel function for TLR4 signaling in promoting innate immune cell migration. The Journal of Immunology, 2013, 191: 857-864.
C1 [Liu, Zheng; Jiang, Yong; Wang, Juan] Southern Med Univ, Dept Pathophysiol, Guangzhou 510515, Guangdong, Peoples R China.
[Liu, Zheng; Li, Yuehua; Wang, Juan; Scott, Melanie J.; Billiar, Timothy R.; Wilson, Mark A.; Fan, Jie] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA.
[Fan, Liyan] Univ Pittsburgh, Sch Arts & Sci, Pittsburgh, PA 15213 USA.
[Xiao, Guozhi] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA.
[Li, Song] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA.
[Billiar, Timothy R.; Fan, Jie] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15219 USA.
[Wilson, Mark A.; Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Res & Dev, Pittsburgh, PA 15240 USA.
RP Fan, J (reprint author), Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA.
EM jiang48231@163.com; jif7@pitt.edu
FU National Institutes of Health [R01-HL-079669, R01-GM-50441]; National
Institutes of Health Center [P50-GM-53789]; Veterans Affairs Merit
Award; National Key Basic Research (973) Program of China
[2011CB510200]; National Natural Science Foundation of China [81030055];
Natural Science Foundation of China-Guangdong Joint Fund [U0632004];
Program for Changjiang Scholars and Innovative Research Team in
University [IRT0731]
FX This work was supported by National Institutes of Health Grant
R01-HL-079669 (to J.F. and M. A. W.), National Institutes of Health
Center Grant P50-GM-53789 (to T. R. B. and J.F.), National Institutes of
Health Grant R01-GM-50441 (to T. R. B.), a Veterans Affairs Merit Award
(to J.F.), National Key Basic Research (973) Program of China
2011CB510200 (to Y.J.), National Natural Science Foundation of China
81030055 (to Y.J.), Natural Science Foundation of China-Guangdong Joint
Fund U0632004 (to Y.J.), and Program for Changjiang Scholars and
Innovative Research Team in University IRT0731 (to Y.J.).
NR 45
TC 17
Z9 17
U1 0
U2 12
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2013
VL 191
IS 2
BP 857
EP 864
DI 10.4049/jimmunol.1300790
PG 8
WC Immunology
SC Immunology
GA 175UW
UT WOS:000321260100038
PM 23772028
ER
PT J
AU Spencer, TJ
Biederman, J
Faraone, SV
Madras, BK
Bonab, AA
Dougherty, DD
Batchelder, H
Clarke, A
Fischman, AJ
AF Spencer, Thomas J.
Biederman, Joseph
Faraone, Stephen V.
Madras, Bertha K.
Bonab, Ali A.
Dougherty, Darin D.
Batchelder, Holly
Clarke, Allison
Fischman, Alan J.
TI Functional Genomics of Attention-Deficit/Hyperactivity Disorder (ADHD)
Risk Alleles on Dopamine Transporter Binding in ADHD and Healthy Control
Subjects
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE ADHD; altropane; dopamine; dopamine transporter; genetics; PET imaging
ID DEFICIT HYPERACTIVITY DISORDER; REPORTER GENE-EXPRESSION; CANDIDATE
GENE; METHYLPHENIDATE; AVAILABILITY; POLYMORPHISMS; DENSITY; CHILDREN;
REGION; ADULTS
AB Background: The main aim of this study was to examine the relationship between dopamine transporter (DAT) binding in the striatum in individuals with and without attention-deficit/hyperactivity disorder (ADHD), attending to the 3'-untranslated region of the gene (3'-UTR) and intron8 variable number of tandem repeats (VNTR) polymorphisms of the DAT (SLC6A3) gene.
Methods: Subjects consisted of 68 psychotropic (including stimulant)-naive and smoking-naive volunteers between 18 and 55 years of age (ADHD n = 34; control subjects n = 34). Striatal DAT binding was measured with positron emission tomography with 11C altropane. Genotyping of the two DAT (SLC6A3) 3'-UTR and intron8 VNTRs used standard protocols.
Results: The gene frequencies of each of the gene polymorphisms assessed did not differ between the ADHD and control groups. The ADHD status (t = 2.99; p < .004) and 3'-UTR of SLC6A3 9 repeat carrier status (t = 2.74; p < .008) were independently and additively associated with increased DAT binding in the caudate. The ADHD status was associated with increased striatal (caudate) DAT binding regardless of 3'-UTR genotype, and 3'-UTR genotype was associated with increased striatal (caudate) DAT binding regardless of ADHD status. In contrast, there were no significant associations between polymorphisms of DAT intron8 or the 3'-UTR-intron8 haplotype with DAT binding.
Conclusions: The 3'-UTR but not intron8 VNTR genotypes were associated with increased DAT binding in both ADHD patients and healthy control subjects. Both ADHD status and the 3'-UTR polymorphism status had an additive effect on DAT binding. Our findings suggest that an ADHD risk polymorphism (3'-UTR) of SLC6A3 has functional consequences on central nervous system DAT binding in humans.
C1 [Spencer, Thomas J.; Biederman, Joseph; Batchelder, Holly; Clarke, Allison] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, Boston, MA 02114 USA.
[Spencer, Thomas J.; Biederman, Joseph; Dougherty, Darin D.; Batchelder, Holly; Clarke, Allison] Massachusetts Gen Hosp, Psychiat Serv, Dept Psychiat, Boston, MA 02114 USA.
[Bonab, Ali A.] Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA.
[Spencer, Thomas J.; Bonab, Ali A.; Fischman, Alan J.] Shriners Hosp Children, Boston, MA USA.
[Madras, Bertha K.] New England Primate Res Ctr, Div Neurosci, Boston, MA USA.
[Spencer, Thomas J.; Biederman, Joseph; Madras, Bertha K.; Bonab, Ali A.; Dougherty, Darin D.; Fischman, Alan J.] Harvard Univ, Sch Med, Boston, MA USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA.
RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit Yaw 6A, Fruit St, Boston, MA 02114 USA.
EM tspencer@partners.org
OI Faraone, Stephen/0000-0002-9217-3982
FU National Institute of Mental Health [RO1MH064019]; Shire Laboratories;
Cephalon; Eli Lilly and Company; Janssen; McNeil Pharmaceutical;
Novartis Pharmaceuticals; Department of Defense; GlaxoSmithKline;
Janssen Pharmaceutical; Pfizer; National Institute of Mental Health;
Massachusetts General Hospital (MGH) Corporate; Elminda; Shire; McNeil;
Alza; Abbott; AstraZeneca; Boston University; Bristol Myers Squibb;
Celltech; Esai; Fundacion Areces (Spain); Forest; Glaxo; Gliatech;
Hastings Center; Medice Pharmaceuticals (Germany); MMC Pediatric;
National Alliance for Research on Schizophrenia and Depression; National
Institute on Drug Abuse; New River; National Institute of Child Health
and Human Development; Noven; Neurosearch; Organon; Otsuka; Pharmacia;
Phase V Communications; Physicians Academy; The Prechter Foundation;
Quantia Communications; Reed Exhibitions; Spanish Child Psychiatry
Association; Stanley Foundation; UCB Pharma; Veritas; Wyeth; Alcobra;
National Institutes of Health; Medtronic; Cyberonics
FX Research support for this work was provided by National Institute of
Mental Health Grant RO1MH064019 (TJS).; In the last 2 years, TJS has
received research support from the following sources: Shire
Laboratories, Cephalon, Eli Lilly and Company, Janssen, McNeil
Pharmaceutical, Novartis Pharmaceuticals, and the Department of
Defense.; In previous years, TJS has received research support from,
been a speaker for, served on a Speakers' bureau, or has been an Advisor
or on an Advisory Board of the following sources: Shire Laboratories,
Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceutical, McNeil
Pharmaceutical, Novartis Pharmaceuticals, Cephalon, Pfizer, and the
National Institute of Mental Health.; TJS receives research support from
royalties and licensing fees on copyrighted
attention-deficit/hyperactivity disorder (ADHD) scales through
Massachusetts General Hospital (MGH) Corporate Sponsored Research and
Licensing.; JB is currently receiving research support from the
following sources: Elminda, Janssen, McNeil, and Shire.; In previous
years, JB received research support, consultation fees, or speaker's
fees for/from the following additional sources: Abbott, Alza,
AstraZeneca, Boston University, Bristol Myers Squibb, Celltech,
Cephalon, Eli Lilly and Company, Esai, Fundacion Areces (Spain), Forest,
Glaxo, Gliatech, Hastings Center, Janssen, McNeil, Medice
Pharmaceuticals (Germany), Merck, MMC Pediatric, National Alliance for
Research on Schizophrenia and Depression, National Institute on Drug
Abuse, New River, National Institute of Child Health and Human
Development, National Institute of Mental Health, Novartis, Noven,
Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications,
Physicians Academy, The Prechter Foundation, Quantia Communications,
Reed Exhibitions, Shire, the Spanish Child Psychiatry Association, The
Stanley Foundation, UCB Pharma, Veritas, and Wyeth.; In the past year,
SVF received consulting income and research support from Shire, Otsuka,
and Alcobra and research support from the National Institutes of Health.
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. SVF receives
royalties from books published by Guilford Press: Straight Talk about
Your Child's Mental Health; and Oxford University Press: Schizophrenia:
The Facts.; DDD has received honoraria from Medtronic and research
support from Medtronic, Cyberonics, and Eli Lilly.
NR 36
TC 20
Z9 20
U1 3
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUL 15
PY 2013
VL 74
IS 2
BP 84
EP 89
DI 10.1016/j.biopsych.2012.11.010
PG 6
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 173VF
UT WOS:000321108800004
PM 23273726
ER
PT J
AU Shenoy, ES
Kim, J
Rosenberg, ES
Cotter, JA
Lee, H
Walensky, RP
Hooper, DC
AF Shenoy, Erica S.
Kim, JiYeon
Rosenberg, Eric S.
Cotter, Jessica A.
Lee, Hang
Walensky, Rochelle P.
Hooper, David C.
TI Discontinuation of Contact Precautions for Methicillin-Resistant
Staphylococcus aureus: A Randomized Controlled Trial Comparing Passive
and Active Screening With Culture and Polymerase Chain Reaction
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE MRSA; infection control; contact precautions; isolation; clinical trial
ID HEALTH-CARE SETTINGS; XPERT MRSA ASSAY; RISK-FACTORS; HOSPITAL
DISCHARGE; INFECTION-CONTROL; CARRIAGE; ACQUISITION; DURATION;
COLONIZATION; TRANSMISSION
AB Background. There have been no randomized controlled trials comparing active and passive screening for documenting clearance of colonization with methicillin-resistant Staphylococcus aureus (MRSA). We compared the efficacy of active and passive screening using both culture and commercial polymerase chain reaction (PCR) for documentation of MRSA clearance and discontinuation of MRSA contact precautions (CPs).
Methods. Inpatients with a history of MRSA infection or colonization enrolled between December 2010 and September 2011 were randomized to either passive (nonintervention arm; n = 202; observation with local standard of care) or active screening (intervention arm; n = 405; study staff screened using culture and commercial PCR). The primary outcome was discontinuation of CPs by trial arm based on 3 negative cultures. In the intervention arm, sensitivity, specificity, and positive and negative predictive values of the first PCR were compared to cultures.
Results. CPs were discontinued significantly more often (rate ratio [RR], 4.1; 95% confidence interval [CI], 2.3%-7.1%) in the intervention arm, including in an intent-to-screen analysis (RR, 2.6; 95% CI, 1.5%-4.7%). The first PCR, compared to 3 cultures, detected MRSA with a sensitivity of 93.9% (95% CI, 85.4%-97.6%), a specificity of 92.0% (95% CI, 85.9%-95.6%), a positive predictive value of 86.1% (95% CI, 75.9%-93.1%), and a negative predictive value of 96.6% (95% CI, 91.6%-99.1%).
Conclusions. Compared to passive screening using culture methods, active screening resulted in discontinuation of MRSA CPs at a significantly higher frequency. Active screening with a single PCR would significantly increase the completion of the screening process.
C1 [Shenoy, Erica S.; Kim, JiYeon; Rosenberg, Eric S.; Walensky, Rochelle P.; Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA.
[Shenoy, Erica S.; Rosenberg, Eric S.; Walensky, Rochelle P.; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA.
[Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Walensky, Rochelle P.] Massachusetts Gen Hosp, Ctr AIDS Res, Boston, MA 02114 USA.
[Kim, JiYeon; Rosenberg, Eric S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Shenoy, Erica S.; Cotter, Jessica A.; Hooper, David C.] Massachusetts Gen Hosp, Infect Control Unit, Boston, MA 02114 USA.
RP Shenoy, ES (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Bulfinch 340, Boston, MA 02114 USA.
EM eshenoy@partners.org
OI Walensky, Rochelle P./0000-0002-8795-379X
FU Harvard Catalyst; National Center for Research Resources; National
Center for Advanced Translational Sciences; Harvard University; MGH
Clinical Innovation Award; National Institutes of Health [T32 A107061];
Harvard Clinical and Translational Science Center, National Institutes
of Health [8UL1TR000170-05, 1 UL1 RR025758]
FX This work was conducted with support from Harvard Catalyst, National
Center for Research Resources and the National Center for Advanced
Translational Sciences, and financial contributions from Harvard
University and its affiliated academic healthcare centers. This work was
supported by MGH 2010-2011 Clinical Innovation Award; National
Institutes of Health Training Grant (T32 A107061); and The Harvard
Clinical and Translational Science Center, National Institutes of Health
(8UL1TR000170-05, 1 UL1 RR025758). Reagents and PCR testing equipment
were provided without charge by Cepheid.
NR 30
TC 25
Z9 25
U1 1
U2 5
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 JUL 15
PY 2013
VL 57
IS 2
BP 176
EP 184
DI 10.1093/cid/cit206
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 173AY
UT WOS:000321051600003
PM 23572482
ER
PT J
AU D'Ascenzo, F
Biondi-Zoccai, G
Reed, MJ
Gabayan, GZ
Suzuki, M
Costantino, G
Furlan, R
Del Rosso, A
Sarasin, FP
Sun, BC
Modena, MG
Gaita, F
AF D'Ascenzo, Fabrizio
Biondi-Zoccai, Giuseppe
Reed, Matthew J.
Gabayan, Gelareh Z.
Suzuki, Masaru
Costantino, Giorgio
Furlan, Raffaello
Del Rosso, Andrea
Sarasin, Francois P.
Sun, Benjamin C.
Modena, Maria Grazia
Gaita, Fiorenzo
TI Incidence, etiology and predictors of adverse outcomes in 43,315
patients presenting to the Emergency Department with syncope: An
international meta-analysis
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Syncope; Meta-analysis; Prognosis; Prognosis; Multivariate predictors;
Emergency Department
ID RISK STRATIFICATION; SHORT-TERM; CLINICAL PREDICTORS; UNEXPLAINED
SYNCOPE; SCORE; MANAGEMENT; ARRHYTHMIAS; GUIDELINES; PROGNOSIS; QUALITY
AB Background: Syncope remains challenging for Emergency Department (ED) physicians due to difficulties in assessing the risk of future adverse outcomes. The aim of this meta-analysis is to establish the incidence and etiology of adverse outcomes as well as the predictors, in patients presenting with syncope to the ED.
Methods: A systematic electronic literature review was performed looking for eligible studies published between 1990 and 2010. Studies reporting multivariate predictors of adverse outcomes in patients presenting with syncope to the ED were included and pooled, when appropriate, using a random-effect method. Adverse events were defined as 'incidence of death, or of hospitalization and interventional procedures because of arrhythmias, ischemic heart disease or valvular heart disease'.
Results: 11 studies were included. Pooled analysis showed 42% (CI 95%; 32-52) of patients were admitted to hospital. Risk of death was 4.4% (CI 95%; 3.1-5.1) and 1.1% (CI 95%; 0.7-1.5) had a cardiovascular etiology. One third of patients were discharged without a diagnosis, while the most frequent diagnosis was 'situational, orthostatic or vasavagal syncope' in 29% (CI 95%; 12-47). 10.4% (CI 95%; 7.8-16) was diagnosed with heart disease, the most frequent type being bradyarrhythmia, 4.8% (CI 95%; 2.2-6.4) and tachyarrhythmia 2.6% (CI 95%; 1.1-3.1). Palpitations preceding syncope, exertional syncope, a history consistent of heart failure or ischemic heart disease, and evidence of bleeding were the most powerful predictors of an adverse outcome.
Conclusion: Syncope carries a high risk of death, mainly related to cardiovascular disease. This large study which has established the most powerful predictors of adverse outcomes, may enable care and resources to be better focused at high risk patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [D'Ascenzo, Fabrizio; Gaita, Fiorenzo] Univ Turin, Div Cardiol, I-10126 Turin, Italy.
[Biondi-Zoccai, Giuseppe; Modena, Maria Grazia] Univ Modena & Reggio Emilia, Div Cardiol, Modena, Italy.
[Gabayan, Gelareh Z.; Sun, Benjamin C.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Med, Los Angeles, CA USA.
[Reed, Matthew J.] Dept Emergency Med, Edinburgh, Midlothian, Scotland.
[Suzuki, Masaru] Keio Univ, Sch Med, Dept Emergency Med, Tokyo, Japan.
[Costantino, Giorgio; Furlan, Raffaello] Univ Milan, L Sacco Hosp, Syncope Unit, Milan, Italy.
[Del Rosso, Andrea] Azienda USL 11 Empoli, Dept Cardiol, Empoli, Italy.
[Sarasin, Francois P.] Univ Geneva, Hop Cantonal, Sch Med, Div Emergency Med, CH-1211 Geneva, Switzerland.
RP D'Ascenzo, F (reprint author), Univ Turin, S Giovanni Battista Molinette Hosp, Div Cardiol, Corso Bramante 88-90, I-10126 Turin, Italy.
EM fabrizio.dascenzo@gmail.com
RI modena, maria grazia/N-2442-2015;
OI modena, maria grazia/0000-0002-4704-4663; Furlan,
Raffaello/0000-0001-5209-6786; Reed, Matthew/0000-0003-1308-4824
FU Chief Scientist Office [CAF/06/01]
NR 38
TC 20
Z9 20
U1 1
U2 13
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD JUL 15
PY 2013
VL 167
IS 1
BP 57
EP 62
DI 10.1016/j.ijcard.2011.11.083
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 167AR
UT WOS:000320603100019
PM 22192287
ER
PT J
AU Zietman, A
AF Zietman, Anthony
TI Expanding the Number of Trainess in Radiation Oncology: Has the Pendulum
Swung Too Far?
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Zietman, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 4
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 15
PY 2013
VL 86
IS 4
BP 597
EP 597
DI 10.1016/j.ijrobp.2013.05.035
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 166WL
UT WOS:000320590200005
PM 23773385
ER
PT J
AU Terezakis, S
MacDonald, S
Nilsson, K
Villar, R
Dieckmann, K
Chen, M
Nechesnyuk, A
Ford, E
Ermoian, R
Winey, B
Malet, C
Claude, L
Tryggestad, E
AF Terezakis, S.
MacDonald, S.
Nilsson, K.
Villar, R.
Dieckmann, K.
Chen, M.
Nechesnyuk, A.
Ford, E.
Ermoian, R.
Winey, B.
Malet, C.
Claude, L.
Tryggestad, E.
TI Practice Patterns of Photon and Proton Pediatric Image Guided Radiation
Treatment: Results From an International Pediatric Research Consortium
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT Congress of the Pediatric-Radiation-Oncology-Society
CY MAY 08-11, 2013
CL Louisville, KY
SP Pediat Radiat Oncol Soc
C1 [Terezakis, S.; Ermoian, R.; Tryggestad, E.] Johns Hopkins Sch Med, Baltimore, MD USA.
[MacDonald, S.; Winey, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nilsson, K.] Akad Sjukhuset, Uppsala, Sweden.
[Villar, R.] Ctr Boldrini, Sao Paulo, Brazil.
[Dieckmann, K.] Univ Klin Strahlentherapie & Strahlenbiol, Vienna, Austria.
[Chen, M.] GRAACC Support Grp Adolescents & Children Canc, Sao Paulo, Brazil.
[Nechesnyuk, A.] Fed Sci Clin Ctr Pediat Hematol Oncol & Immunol, Moscow, Russia.
[Ford, E.] Univ Washington, Seattle, WA 98195 USA.
[Malet, C.; Claude, L.] Ctr Leon Berard, UNICANC, F-69373 Lyon, France.
NR 0
TC 0
Z9 0
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 JUL 15
PY 2013
VL 86
IS 4
MA OP9
BP 802
EP 803
PG 4
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 166WL
UT WOS:000320590200048
ER
PT J
AU Brunner, AM
Campigotto, F
Sadrzadeh, H
Drapkin, BJ
Chen, YB
Neuberg, DS
Fathi, AT
AF Brunner, Andrew M.
Campigotto, Federico
Sadrzadeh, Hossein
Drapkin, Benjamin J.
Chen, Yi-Bin
Neuberg, Donna S.
Fathi, Amir T.
TI Trends in all-cause mortality among patients with chronic myeloid
leukemia
SO CANCER
LA English
DT Article
DE chronic myeloid leukemia; population survival; tyrosine kinase
inhibitor; age groups; bcr-abl
ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; CML WORKING
PARTY; PHILADELPHIA-CHROMOSOME; TYROSINE KINASE; UNITED-STATES; BLAST
CRISIS; SURVIVAL; IMATINIB; THERAPY
AB BACKGROUND Outcomes for patients with chronic myeloid leukemia (CML) have improved after the advent of tyrosine kinase inhibitors (TKIs), which target the BCR/ABL fusion gene product. Nonetheless, differences in survival persist between age groups. The authors performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database to assess 5-year overall survival (OS) in various patient age groups. METHODS Patients who had a diagnosis of CML were identified using the SEER 19 registries database. Patients who were included had SEER diagnosis codes for CML not otherwise specified (code 9863) and BCR/ABL-positive CML (code 9875) diagnosed between January 2000 and December 2005. Patients were divided into cohorts based on age at diagnosis: ages 15 to 44 years, 45 to 64 years, 65 to 74 years, and 75 to 84 years. OS was estimated using the Kaplan-Meier method, and Cox regression was used to estimate predictors of patient survival. RESULTS In total, 5138 patients with a new CML diagnosis were identified. Five-year OS improved for all patients between the years 2000 and 2005. Compared with patients who were diagnosed in 2000, 5-year survival improved among patients ages 15 to 44 years (hazard ratio [HR] for mortality, 0.424; P<.0001), ages 45 to 64 years (HR, 0.716; P=.0315), and ages 65 to 74 years (HR, 0.692; P=.0126); and patients ages 75 to 84 years had an increased 5-year OS rate from 19.2% in 2000 to 36.4% in 2005 (HR, 0.568; P<.0001). CONCLUSIONS OS at 5 years improved among all patients, including those ages 75 to 84 years, a group with historically poor outcomes. However, older age retained an association with worse survival, suggesting opportunities for further progress. Cancer 2013;119:2620-2629. (c) 2013 American Cancer Society.
C1 [Brunner, Andrew M.; Sadrzadeh, Hossein; Drapkin, Benjamin J.; Chen, Yi-Bin; Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Campigotto, Federico; Neuberg, Donna S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Brunner, AM (reprint author), Massachusetts Gen Hosp, Hematol Oncol Associates, 100 Blossom St,COX 1, Boston, MA 02114 USA.
EM afathi@partners.org
NR 35
TC 14
Z9 14
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUL 15
PY 2013
VL 119
IS 14
BP 2620
EP 2629
DI 10.1002/cncr.28106
PG 10
WC Oncology
SC Oncology
GA 237JB
UT WOS:000325864500016
PM 23625575
ER
PT J
AU Mandeville, JB
Sander, CYM
Jenkins, BG
Hooker, JM
Catana, C
Vanduffel, W
Alpert, NM
Rosen, BR
Normandin, MD
AF Mandeville, Joseph B.
Sander, Christin Y. M.
Jenkins, Bruce G.
Hooker, Jacob M.
Catana, Ciprian
Vanduffel, Wim
Alpert, Nathaniel M.
Rosen, Bruce R.
Normandin, Marc D.
TI A receptor-based model for dopamine-induced fMRI signal
SO NEUROIMAGE
LA English
DT Article
DE fMRI; PET; Dopamine; Model; Striatum; NHP
ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL GLUCOSE-UTILIZATION; IN-VIVO
BINDING; HUMAN-BRAIN; ENDOGENOUS DOPAMINE; PHARMACOLOGICAL MRI;
BLOOD-VOLUME; D-2-DOPAMINE RECEPTORS; TEMPORAL RESPONSES;
NONHUMAN-PRIMATES
AB This report describes a multi-receptor physiological model of the fMRI temporal response and signal magnitude evoked by drugs that elevate synaptic dopamine in basal ganglia. The model is formulated as a summation of dopamine's effects at D1-like and D2-like receptor families, which produce functional excitation and inhibition, respectively, as measured by molecular indicators like adenylate cyclase or neuroimaging techniques like fMRI. Functional effects within the model are described in terms of relative changes in receptor occupancies scaled by receptor densities and neuro-vascular coupling constants. Using literature parameters, the model reconciles many discrepant observations and interpretations of pre-clinical data. Additionally, we present data showing that amphetamine stimulation produces fMRI inhibition at low doses and a biphasic response at higher doses in the basal ganglia of non-human primates (NHP), in agreement with model predictions based upon the respective levels of evoked dopamine. Because information about dopamine release is required to inform the fMRI model, we simultaneously acquired PET C-11-raclopride data in several studies to evaluate the relationship between raclopride displacement and assumptions about dopamine release. At high levels of dopamine release, results suggest that refinements of the model will be required to consistently describe the PET and fMRI data. Overall, the remarkable success of the model in describing a wide range of preclinical fMRI data indicate that this approach will be useful for guiding the design and analysis of basic science and clinical investigations and for interpreting the functional consequences of dopaminergic stimulation in normal subjects and in populations with dopaminergic neuroadaptations. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Mandeville, Joseph B.; Jenkins, Bruce G.; Hooker, Jacob M.; Catana, Ciprian; Vanduffel, Wim; Rosen, Bruce R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Sander, Christin Y. M.] MIT, Cambridge, MA 02139 USA.
[Alpert, Nathaniel M.; Normandin, Marc D.] Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA.
RP Mandeville, JB (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
EM jbm@nmr.mgh.harvard.edu
RI Normandin, Marc/C-6728-2015;
OI Normandin, Marc/0000-0003-1645-523X; Hooker, Jacob/0000-0002-9394-7708
FU NIH [R21NS072148, P41RR14075, P30DA28800, S10RR026666, S10RR017208,
S10RR022976, S10RR019933]
FX We thank Helen Deng, Steve Carlin, Chris Moseley, Grae Arabasz and
Shirley Hsu for their help with animal handling, radioligand synthesis,
and MR-PET imaging. This research was supported by NIH grants
R21NS072148, P41RR14075, P30DA28800, S10RR026666, S10RR017208,
S10RR022976, and S10RR019933.
NR 84
TC 14
Z9 14
U1 1
U2 33
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 JUL 15
PY 2013
VL 75
BP 46
EP 57
DI 10.1016/j.neuroimage.2013.02.036
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 134KB
UT WOS:000318208000006
PM 23466936
ER
PT J
AU Douw, L
de Groot, M
van Dellen, E
Aronica, E
Heimans, JJ
Klein, M
Stam, CJ
Reijneveld, JC
Hillebrand, A
AF Douw, L.
de Groot, M.
van Dellen, E.
Aronica, E.
Heimans, J. J.
Klein, M.
Stam, C. J.
Reijneveld, J. C.
Hillebrand, A.
TI Local MEG networks: The missing link between protein expression and
epilepsy in glioma patients?
SO NEUROIMAGE
LA English
DT Article
DE Functional connectivity; Graph theory; Neuro-oncology
ID TEMPORAL-LOBE EPILEPSY; FUNCTIONAL CONNECTIVITY; BRAIN ACTIVITY;
P-GLYCOPROTEIN; HUMAN CORTEX; EEG; MAGNETOENCEPHALOGRAPHY; LOCALIZATION;
ORGANIZATION; RESISTANCE
AB Connectivity and network analysis in neuroscience has been applied to multiple spatial scales, but the links between these different scales have rarely been investigated. In tumor-related epilepsy, altered network topology is related to behavior, but the molecular basis of these observations is unknown. We elucidate the associations between microscopic features of brain tumors, local network topology, and functional patient status. We hypothesize that expression of proteins related to tumor-related epilepsy is directly correlated with network characteristics of the tumor area. Glioma patients underwent magnetoencephalography, and functional network topology of the tumor area was used to predict tissue protein expression patterns of tumor tissue collected during neurosurgery. Protein expression and network topology were interdependent; in particular between-module connectivity was selectively associated with two epilepsy-related proteins. Total number of seizures was related to both the role of the tumor area in the functional network and to protein expression. Importantly, classification of protein expression was predicted by between-module connectivity with up to 100% accuracy. Thus, network topology may serve as an intermediate level between molecular features of tumor tissue and symptomatology in brain tumor patients, and can potentially be used as a non-invasive marker for microscopic tissue characteristics. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Douw, L.; de Groot, M.; van Dellen, E.; Heimans, J. J.; Reijneveld, J. C.] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, NL-1081 HV Amsterdam, Netherlands.
[Douw, L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02134 USA.
[Douw, L.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[de Groot, M.; Aronica, E.] Univ Amsterdam, Acad Med Ctr, Dept Neuro Pathol, NL-1105 AZ Amsterdam, Netherlands.
[Aronica, E.] Stichting Epilepie Instellingen Nederland, NL-2103 SW Heemstede, Netherlands.
[Klein, M.] Vrije Univ Amsterdam, Med Ctr, Dept Med Psychol, NL-1081 BT Amsterdam, Netherlands.
[Hillebrand, A.] Vrije Univ Amsterdam, Med Ctr, Dept Clin Neurophysiol, NL-1081 HZ Amsterdam, Netherlands.
[Hillebrand, A.] Vrije Univ Amsterdam, Med Ctr, MEG Ctr, NL-1081 HZ Amsterdam, Netherlands.
RP Douw, L (reprint author), MGH, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Room 2301,149 13th St, Charlestown, MA 02129 USA.
EM douw@nmr.mgh.harvard.edu
RI Klein, Martin/C-4192-2012
OI Klein, Martin/0000-0003-4160-5746
FU UCB Pharma; Dutch Epilepsy Foundation (NEF); Dutch Cancer Society (KWF
Kankerbestrijding); Foundation "NutsOhra"; Foundation
"STOPhersentumoren.nl"; UCB; Sanofi-Aventis; EU; National Brain Tumor
Foundation/Tug McGraw Foundation; Dutch Cancer Society; Royal Society;
Japan Society for the Promotion of Science; EPSRC; BBSRC; Dr. Hadwen
Trust
FX Dr. Douw and Mr. Van Dellen are sponsored by the Dutch Epilepsy
Foundation (NEF). Dr. De Groot is sponsored by UCB Pharma. Prof. Stam is
an unpaid advisor for Danone, associate editor of Clinical
Neurophysiology, and chair of the scientific board of the Dutch Epilepsy
Foundation (NEF). Prof. Heimans received research support from the Dutch
Epilepsy Foundation (NEF); the Dutch Cancer Society (KWF
Kankerbestrijding), Foundation "NutsOhra", and Foundation
"STOPhersentumoren.nl", and received unrestricted grants from UCB and
Sanofi-Aventis. Dr. Reijneveld received funding from EU Framework
Program 7, the Dutch Epilepsy Foundation (NEF), the Dutch Cancer Society
(KWF Kankerbestrijding), Foundation "NutsOhra", and Foundation
"STOPhersentumoren.nl", and the National Brain Tumor Foundation/Tug
McGraw Foundation, and received unrestricted grants from UCB and
Sanofi-Aventis. Dr. Aronica is supported by the Dutch Epilepsy
Foundation (NEF). Dr. Klein is consultant for Hoffmann-La Roche,
received funding from the Dutch Cancer Society, Foundation "NutsOhra",
and the National Brain Tumor Foundation/Tug McGraw Foundation. Dr.
Hillebrand received funding from The Royal Society, Japan Society for
the Promotion of Science, EPSRC, BBSRC, and the Dr. Hadwen Trust.
NR 64
TC 10
Z9 10
U1 2
U2 29
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JUL 15
PY 2013
VL 75
BP 195
EP 203
DI 10.1016/j.neuroimage.2013.02.067
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 134KB
UT WOS:000318208000021
PM 23507380
ER
PT J
AU Levitan, EB
Shikany, JM
Ahmed, A
Snetselaar, LG
Martin, LW
Curb, JD
Lewis, CE
AF Levitan, Emily B.
Shikany, James M.
Ahmed, Ali
Snetselaar, Linda G.
Martin, Lisa W.
Curb, J. David
Lewis, Cora E.
TI Calcium, magnesium and potassium intake and mortality in women with
heart failure: the Women's Health Initiative
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Heart failure; Mortality; Calcium; Magnesium; Potassium
ID QUALITY-OF-LIFE; PRIMARY HYPERTENSION; ENDOTHELIAL DYSFUNCTION;
SUPPLEMENTATION; MANAGEMENT; ADULTS; RISK; INFLAMMATION; ASSOCIATION;
DISEASE
AB Although diet is thought to affect the natural history of heart failure (HF), nutrient intake in HF patients has not been well studied. Based on prior research linking high intake of Ca, Mg and K to improved cardiovascular health, we hypothesised that these nutrients would be inversely associated with mortality in people with HF. Of the 161 808 participants in the Women's Health Initiative (WHI), we studied 3340 who experienced a HF hospitalisation. These participants were followed for post-hospitalisation all- cause mortality. Intake was assessed using questionnaires on food and supplement intake. Hazard ratios (HR) and 95% CI were calculated using Cox proportional hazards models adjusted for demographics, physical function, co-morbidities and dietary covariates. Over a median of 4.6 years of follow-up, 1433 (42.9%) of the women died. HR across quartiles of dietary Ca intake were 1.00 (referent), 0.86 (95% CI 0.73, 1.00), 0.88 (95% CI 0.75, 1.04) and 0.92 (95% CI 0.76, 1.11) (P for trend=0.63). Corresponding HR were 1.00 (referent), 0.86 (95% CI 0.71, 1.04), 0.88 (95% CI 0.69, 1.11) and 0.84 (95% CI 0.63, 1.12) (P for trend=0.29), across quartiles of dietary Mg intake, and 1.00 (referent), 1.20 (95% CI 1.01, 1.43), 1.06 (95% CI 0.86, 1.32) and 1.16 (95% CI 0.90, 1.51) (P for trend=0.35), across quartiles of dietary K intake. Results were similar when total (dietary plus supplemental) nutrient intakes were examined. In summary, among WHI participants with incident HF hospitalisation, intakes of Ca, Mg and K were not significantly associated with subsequent mortality.
C1 [Levitan, Emily B.; Shikany, James M.; Ahmed, Ali; Lewis, Cora E.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35924 USA.
[Ahmed, Ali] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA.
[Snetselaar, Linda G.] Univ Iowa, Iowa City, IA 52246 USA.
[Martin, Lisa W.] George Washington Univ, Washington, DC 20052 USA.
[Curb, J. David] Univ Hawaii Manoa, Honolulu, HI 96822 USA.
RP Levitan, EB (reprint author), Univ Alabama Birmingham, Dept Epidemiol, 1530 3rd Ave South,RPHB 230K, Birmingham, AL 35924 USA.
EM elevitan@uab.edu
OI Martin, Lisa Warsinger/0000-0003-4352-0914
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, US Department of Health and Human Services [N01WH 22110, 24152,
32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
42107-26, 42129-32, 44221]
FX All authors were involved in the design of the study. J. M. S., L. G.
S., L. W. M., J. D. C. and C. E. L. collected the data. E. B. L.
performed the statistical analysis and wrote the paper. All authors
revised the paper and are responsible for the final manuscript. The
authors declare no conflict of interest. The WHI program is funded by
the National Heart, Lung, and Blood Institute, National Institutes of
Health, US Department of Health and Human Services through contracts
N01WH 22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115,
32118-32119, 32122, 42107-26, 42129-32 and 44221. The authors thank the
WHI investigators and staff for their dedication, and the study
participants for making the program possible.
NR 35
TC 9
Z9 9
U1 1
U2 18
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
J9 BRIT J NUTR
JI Br. J. Nutr.
PD JUL 14
PY 2013
VL 110
IS 1
BP 179
EP 185
DI 10.1017/S0007114512004667
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 160MK
UT WOS:000320123500020
PM 23199414
ER
PT J
AU Hayes, SM
Hayes, JP
Cadden, M
Verfaellie, M
AF Hayes, Scott M.
Hayes, Jasmeet P.
Cadden, Margaret
Verfaellie, Mieke
TI A review of cardiorespiratory fitness-related neuroplasticity in the
aging brain
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Review
DE exercise; physical fitness; physical activity; fMRI; structural MRI;
diffusion tensor imaging; episodic memory; executive functions
ID MILD COGNITIVE IMPAIRMENT; WHITE-MATTER INTEGRITY; SEMANTIC MEMORY
ACTIVATION; PHYSICAL-ACTIVITY; ALZHEIMERS-DISEASE; AEROBIC FITNESS;
OLDER-ADULTS; DEFAULT NETWORK; CARDIOVASCULAR FITNESS; DENTATE GYRUS
AB The literature examining the relationship between cardiorespiratory fitness and the brain in older adults has increased rapidly, with 30 of 34 studies published since 2008. Here we review cross-sectional and exercise intervention studies in older adults examining the relationship between cardiorespiratory fitness and brain structure and function, typically assessed using Magnetic Resonance Imaging (MRI). Studies of patients with Alzheimer's disease are discussed when available. The structural MRI studies revealed a consistent positive relationship between cardiorespiratory fitness and brain volume in cortical regions including anterior cingulate, lateral prefrontal, and lateral parietal cortex. Support for a positive relationship between cardiorespiratory fitness and medial temporal lobe volume was less consistent, although evident when a region-of-interest approach was implemented. In fMRI studies, cardiorespiratory fitness in older adults was associated with activation in similar regions as those identified in the structural studies, including anterior cingulate, lateral prefrontal, and lateral parietal cortex, despite heterogeneity among the functional tasks implemented. This comprehensive review highlights the overlap in brain regions showing a positive relationship with cardiorespiratory fitness in both structural and functional imaging modalities. The findings suggest that aerobic exercise and cardiorespiratory fitness contribute to healthy brain aging, although additional studies in Alzheimer's disease are needed.
C1 [Hayes, Scott M.; Cadden, Margaret; Verfaellie, Mieke] Boston Univ, Sch Med, VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02118 USA.
[Hayes, Scott M.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA.
[Hayes, Scott M.; Hayes, Jasmeet P.; Verfaellie, Mieke] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Hayes, Jasmeet P.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA.
RP Hayes, SM (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr 151A, 150 South Huntington Ave, Boston, MA 02130 USA.
EM smhayes@bu.edu
OI Verfaellie, Mieke/0000-0001-5535-4584
FU Department of Veterans Affairs Rehabilitation Research & Development
Service [e7822w]; Department of Veterans Affairs Clinical Science
Research & Development Service; National Institutes of Health, National
Institutes of Mental Health [K23 MH084013]
FX This work was supported by the Department of Veterans Affairs
Rehabilitation Research & Development Service [Career Development Award
e7822w awarded to Scott M. Hayes], the Department of Veterans Affairs
Clinical Science Research & Development Service [Mieke Verfaellie], and
the National Institutes of Health, National Institutes of Mental Health
[grant number K23 MH084013 awarded to Jasmeet P. Hayes]. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the VA, NIH or NIMH. None of the authors
reported a conflict of interest.
NR 100
TC 39
Z9 39
U1 5
U2 55
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1663-4365
J9 FRONT AGING NEUROSCI
JI Front. Aging Neurosci.
PD JUL 12
PY 2013
VL 5
AR UNSP 31
DI 10.3389/fnagi.2013.00031
PG 16
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 205OO
UT WOS:000323454000001
PM 23874299
ER
PT J
AU Grove, ML
Yu, B
Cochran, BJ
Haritunians, T
Bis, JC
Taylor, KD
Hansen, M
Borecki, IB
Cupples, LA
Fornage, M
Gudnason, V
Harris, TB
Kathiresan, S
Kraaij, R
Launer, LJ
Levy, D
Liu, YM
Mosley, T
Peloso, GM
Psaty, BM
Rich, SS
Rivadeneira, F
Siscovick, DS
Smith, AV
Uitterlinden, A
van Duijn, CM
Wilson, JG
O'Donnell, CJ
Rotter, JI
Boerwinkle, E
AF Grove, Megan L.
Yu, Bing
Cochran, Barbara J.
Haritunians, Talin
Bis, Joshua C.
Taylor, Kent D.
Hansen, Mark
Borecki, Ingrid B.
Cupples, L. Adrienne
Fornage, Myriam
Gudnason, Vilmundur
Harris, Tamara B.
Kathiresan, Sekar
Kraaij, Robert
Launer, Lenore J.
Levy, Daniel
Liu, Yongmei
Mosley, Thomas
Peloso, Gina M.
Psaty, Bruce M.
Rich, Stephen S.
Rivadeneira, Fernando
Siscovick, David S.
Smith, Albert V.
Uitterlinden, Andre
van Duijn, Cornelia M.
Wilson, James G.
O'Donnell, Christopher J.
Rotter, Jerome I.
Boerwinkle, Eric
TI Best Practices and Joint Calling of the HumanExome BeadChip: The CHARGE
Consortium
SO PLOS ONE
LA English
DT Article
ID STUDY OBJECTIVES; DESIGN; ASSOCIATION; POPULATION; MUTATION; HEART
AB Genotyping arrays are a cost effective approach when typing previously-identified genetic polymorphisms in large numbers of samples. One limitation of genotyping arrays with rare variants (e.g., minor allele frequency [MAF] < 0.01) is the difficulty that automated clustering algorithms have to accurately detect and assign genotype calls. Combining intensity data from large numbers of samples may increase the ability to accurately call the genotypes of rare variants. Approximately 62,000 ethnically diverse samples from eleven Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium cohorts were genotyped with the Illumina HumanExome BeadChip across seven genotyping centers. The raw data files for the samples were assembled into a single project for joint calling. To assess the quality of the joint calling, concordance of genotypes in a subset of individuals having both exome chip and exome sequence data was analyzed. After exclusion of low performing SNPs on the exome chip and non-overlap of SNPs derived from sequence data, genotypes of 185,119 variants (11,356 were monomorphic) were compared in 530 individuals that had whole exome sequence data. A total of 98,113,070 pairs of genotypes were tested and 99.77% were concordant, 0.14% had missing data, and 0.09% were discordant. We report that joint calling allows the ability to accurately genotype rare variation using array technology when large sample sizes are available and best practices are followed. The cluster file from this experiment is available at www.chargeconsortium.com/main/exomechip.
C1 [Grove, Megan L.; Yu, Bing; Cochran, Barbara J.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA.
[Haritunians, Talin; Taylor, Kent D.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Bis, Joshua C.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Hansen, Mark] Illumina Inc, San Diego, CA USA.
[Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Gen, St Louis, MO USA.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Cupples, L. Adrienne; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Inst Mol Med, Houston, TX 77030 USA.
[Gudnason, Vilmundur; Smith, Albert V.] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland.
[Gudnason, Vilmundur; Smith, Albert V.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Populat Sci, Bethesda, MD 20892 USA.
[Peloso, Gina M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA USA.
[Kathiresan, Sekar] Broad Inst Harvard, Cambridge, MA USA.
[Kathiresan, Sekar] MIT, Cambridge, MA 02139 USA.
[Kraaij, Robert; Rivadeneira, Fernando] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Liu, Yongmei] Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA.
[Mosley, Thomas] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Seattle, WA USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA.
[Rivadeneira, Fernando; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, ErasmusAGE, Rotterdam, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre; van Duijn, Cornelia M.] Netherlands Genom Initiat, Netherlands Consortium Hlth Aging, Leiden, Netherlands.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
RP Grove, ML (reprint author), Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA.
EM Megan.L.Grove@uth.tmc.edu
RI Gudnason, Vilmundur/K-6885-2015; Rivadeneira, Fernando/O-5385-2015;
Smith, Albert/K-5150-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Rivadeneira,
Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845;
Cupples, L. Adrienne/0000-0003-0273-7965
FU Building on GWAS for NHLBI-diseases; U.S. CHARGE consortium through the
National Institutes of Health (NIH) American Recovery and Reinvestment
Act (ARRA) [5RC2HL102419]; NIH [N01-AG-12100]; NIA Intramural Research
Program; Icelandic Heart Association; Icelandic Parliament; National
Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN2682011000010C, HHSN2682011000011C,
HHSN2682011000012C]; National Heart, Lung, and Blood Institute [HL41993,
HL091244, N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049,
N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, N01-HC-45204,
U01 HL56563, U01 HL56564, U01 HL56565]; University of Washington
Clinical Nutrition Research Unit [DK-35816]; Medic One Foundation,
Seattle, WA; 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];
NIA [AG-023629, AG-15928, AG-20098, AG-027058, N01AG62101, N01AG62103,
N01AG62106, 1R01AG032098-01A1]; National Center of Advancing
Translational Technologies CTSI [UL1TR000124]; National Institute of
Diabetes and Digestive and Kidney Diseases [DK063491]; Cedars-Sinai
Board of Governors' Chair in Medical Genetics (JIR); Erasmus Medical
Center and Erasmus University, Rotterdam; Netherlands Organization for
the Health Research and Development (ZonMw); Research Institute for
Diseases in the Elderly (RIDE); Ministry of Education, Culture and
Science; Ministry for Health, Welfare and Sports; European Commission
(DG XII); Municipality of Rotterdam; Illumina, Inc.; Intramural Research
Program of the NIH, National Institute on Aging; National Center on
Minority Health and Health Disparities; [U01-HG-004729];
[R01-HL-084099]; [N01-HC-25195]; [N01-HC-95159]; [N01-HC-95160];
[N01-HC-95161]; [N01-HC-95162]; [N01-HC-95163]; [N01-HC-95164];
[N01-HC-95165]
FX Support for the centralized work was provided by Building on GWAS for
NHLBI-diseases: the U.S. CHARGE consortium through the National
Institutes of Health (NIH) American Recovery and Reinvestment Act of
2009 (ARRA) (5RC2HL102419) (PI: E. Boerwinkle). Funding support of the
individual cohorts is detailed below. The Age, Gene/Environment,
Susceptibility-Reykjavik (AGES) study is funded by NIH contract
N01-AG-12100, the NIA Intramural Research Program, the Icelandic Heart
Association, and the Icelandic Parliament. The Atherosclerosis Risk in
Communities (ARIC) Study is carried out as a collaborative study
supported by National Heart, Lung, and Blood Institute (NHLBI) contracts
(HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN2682011000010C,
HHSN2682011000011C, and HHSN2682011000012C). The authors thank the staff
and participants of the ARIC study for their important contributions.
The research reported in this manuscript on behalf of the Cardiac Arrest
Blood Study (CABS) was supported by grants from the National Heart,
Lung, and Blood Institute (HL41993 and HL091244); the University of
Washington Clinical Nutrition Research Unit (DK-35816); and the Medic
One Foundation, Seattle, WA. The authors gratefully acknowledge the
Coronary Artery Risk Development in Young Adults (CARDIA) study
participants and staff for their valuable contributions. The CARDIA
study is funded by contracts N01-HC-95095, N01-HC-48047, N01-HC-48048,
N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205,
and N01-HC-45204 from the National Heart, Lung, and Blood Institute to
the CARDIA investigators. Genotyping of the CARDIA participants was
supported by grants U01-HG-004729 and R01-HL-084099. This manuscript has
been reviewed by CARDIA for scientific content and consistency of data
interpretation with previous CARDIA publications. This CHS research was
supported by NHLBI 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, HHSN268201200036C and NHLBI grants HL080295, HL087652,
HL105756 with additional contribution from NINDS. Additional support was
provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the
NIA. See also http://www.chs-nhlbi.org/pi. DNA handling and genotyping
was supported in part by National Center of Advancing Translational
Technologies CTSI grant UL1TR000124, the National Institute of Diabetes
and Digestive and Kidney Diseases grant DK063491 to the Southern
California Diabetes Endocrinology Research Center, and Cedars-Sinai
Board of Governors' Chair in Medical Genetics (JIR). The Rotterdam Study
is supported by Erasmus Medical Center and Erasmus University,
Rotterdam, Netherlands Organization for the Health Research and
Development (ZonMw), the Research Institute for Diseases in the Elderly
(RIDE), the Ministry of Education, Culture and Science, the Ministry for
Health, Welfare and Sports, the European Commission (DG XII), and the
Municipality of Rotterdam. The authors are grateful to the study
participants, the staff from the Rotterdam Study and the participating
general practitioners and pharmacists. The NHLBI's Framingham Heart
Study is a joint project of the National Institutes of Health and Boston
University School of Medicine and was supported by contract N01-HC-25195
and its contract with Illumina, Inc. for genotyping services.; The
Family Heart Study (FamHS) was supported by grants from the National
Heart, Lung, & Blood Institute (U01 HL56563, U01 HL56564, U01 HL56565,
U01 HL56566, U01 HL56567, U01 HL56568, U01 HL56569, and K01-HL70444).
The Health, Aging, and Body Composition (HABC) Study is 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. This research was supported in part
by the Intramural Research Program of the NIH, National Institute on
Aging. The Jackson Heart Study (JHS) is supported by the National Heart,
Lung, and Blood Institute (N01 HC-95170, N01 HC-95171 and N01 HC-95172)
and the National Center on Minority Health and Health Disparities. The
authors thank the staff, interns and participants in JHS for their
long-term commitment and important contributions to the study. MESA is
supported by the National Heart, Lung, and Blood Institute (NHLBI) in
collaboration with MESA investigators. Support for MESA is provided by
contracts N01-HC-95159 through N01-HC-95169 and UL1-RR-024156. Funding
for MESA Family is provided by grants R01- HL-071051, R01-HL-071205,
R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258,
R01-HL-071259, UL1-RR-025005. The authors thank the other investigators,
the staff, and the participants of the MESA study for their valuable
contributions. A full list of participating MESA investigators and
institutions can be found at http://www.mesa-nhlbi.org. Gina Peloso was
supported by Award Number T32HL007208 from the National Heart, Lung, And
Blood Institute. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National
Heart, Lung, and Blood Institute or the National Institutes of Health.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 27
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U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 12
PY 2013
VL 8
IS 7
AR e68095
DI 10.1371/journal.pone.0068095
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 182CS
UT WOS:000321718700009
PM 23874508
ER
PT J
AU Jung, M
Arya, M
Viswanath, K
AF Jung, Minsoo
Arya, Monisha
Viswanath, Kasisomayajula
TI Effect of Media Use on HIV/AIDS-Related Knowledge and Condom Use in
Sub-Saharan Africa: A Cross-Sectional Study
SO PLOS ONE
LA English
DT Article
ID MASS-MEDIA; CAMPAIGNS; COUNTRIES; HEALTH
AB It is known that the level of HIV/AIDS-related knowledge and the degree of condom use varies by socioeconomic status (SES). However, there is limited research on the effect of mass media use on HIV/AIDS-related cognitive and behavioral outcomes in low-income countries and how it might influence the association between SES and HIV-related outcomes. We investigated the moderating effect of media use on the relationship between SES and HIV/AIDS-related knowledge and condom use in sub-Saharan Africa in terms of communication inequalities. Cross-sectional data from the Demographic Health Surveys from 13 sub-Saharan countries (2004-10) were pooled. Gender-stratified multivariable poisson regression of 151,209 women and 68,890 men were used to calculate adjusted relative ratios and 95% confidence intervals for the associations between SES, media use, HIV-related outcomes, and condom use. We found significant disparities in mass media use among people from different SES groups as well as among countries. Education and wealth are strongly and positively associated with awareness of HIV/AIDS and knowledge about transmission and prevention of HIV/AIDS and are significantly associated with condom use. These associations are attenuated when the use of various types of mass media is added to the models, with newspapers showing the strongest effect. The findings of this study suggest that media use has the potential to blunt the impact of socioeconomic status though not completely eliminate it. Thus, we need to pay attention to reducing communication inequalities among social groups and countries to moderate the effect of wealth and SES on HIV/AIDS.
C1 [Jung, Minsoo; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Jung, Minsoo] Dongduk Womens Univ, Dept Hlth Sci, Seoul, South Korea.
[Arya, Monisha] Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA.
[Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
RP Jung, M (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
EM minsoo_jung@dfci.harvard.edu
OI Jung, Minsoo/0000-0003-3317-6507
FU NIMH NIH HHS [K23 MH094235]
NR 29
TC 6
Z9 6
U1 0
U2 12
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 JUL 12
PY 2013
VL 8
IS 7
AR e68359
DI 10.1371/journal.pone.0068359
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 182CS
UT WOS:000321718700019
PM 23874598
ER
PT J
AU Saini, V
Marengi, DA
Barry, KJ
Fulzele, KS
Heiden, E
Liu, X
Dedic, C
Maeda, A
Lotinun, S
Baron, R
Pajevic, PD
AF Saini, Vaibhav
Marengi, Dean A.
Barry, Kevin J.
Fulzele, Keertik S.
Heiden, Erica
Liu, Xiaolong
Dedic, Christopher
Maeda, Akira
Lotinun, Sutada
Baron, Roland
Pajevic, Paola Divieti
TI Parathyroid Hormone (PTH)/PTH-related Peptide Type 1 Receptor (PPR)
Signaling in Osteocytes Regulates Anabolic and Catabolic Skeletal
Responses to PTH
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INCREASES BONE-FORMATION; LINING CELLS; EXPRESSION; SOST; MASS;
SCLEROSTIN; PROTEIN; OSTEOBLASTS; ACTIVATION; PREVENTION
AB Parathyroid hormone (PTH) is the only Food and Drug Administration-approved anabolic agent to treat osteoporosis; however, the cellular targets of PTH action in bone remain controversial. PTH modulates bone turnover by binding to the PTH/PTH-related peptide (PTHrP) type 1 receptor (PPR), a G-protein-coupled receptor highly expressed in bone and kidneys. Osteocytes, the most abundant cells in adult bone, also express PPR. However, the physiological relevance of PPR signaling in osteocytes remains to be elucidated. Toward this goal, we generated mice with PPR deletion in osteocytes (Ocy-PPRKO). Skeletal analysis of these mice revealed a significant increase in bone mineral density and trabecular and cortical bone parameters. Osteoblast activities were reduced in these animals, as demonstrated by decreased collagen type I alpha 1 mRNA and receptor activator of NF-kappa B ligand (RANKL) expression. Importantly, when subjected to an anabolic or catabolic PTH regimen, Ocy-PPRKO animals demonstrated blunted skeletal responses. PTH failed to suppress SOST/Sclerostin or induce RANKL expression in Ocy-PPRKO animals compared with controls. In vitro, osteoclastogenesis was significantly impaired in Ocy-PPRKO upon PTH administration, indicating that osteocytes control osteoclast formation through a PPR-mediated mechanism. Taken together, these data indicate that PPR signaling in osteocytes is required for bone remodeling, and receptor signaling in osteocytes is needed for anabolic and catabolic skeletal responses.
C1 [Saini, Vaibhav; Marengi, Dean A.; Barry, Kevin J.; Fulzele, Keertik S.; Heiden, Erica; Liu, Xiaolong; Dedic, Christopher; Maeda, Akira; Baron, Roland; Pajevic, Paola Divieti] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA.
[Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
RP Pajevic, PD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Thier 1101, Boston, MA 02114 USA.
EM divieti@helix.mgh.harvard.edu
FU National Institutes of Health from the NIDDK [DK079161]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant DK079161 from the NIDDK (to P.D.P.).
NR 31
TC 49
Z9 50
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 12
PY 2013
VL 288
IS 28
BP 20122
EP 20134
DI 10.1074/jbc.M112.441360
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 182BI
UT WOS:000321715100003
PM 23729679
ER
PT J
AU Takeuchi, K
Morizane, Y
Kamami-Levy, C
Suzuki, J
Kayama, M
Cai, WY
Miller, JW
Vavvas, DG
AF Takeuchi, Kimio
Morizane, Yuki
Kamami-Levy, Cynthia
Suzuki, Jun
Kayama, Maki
Cai, Wenyi
Miller, Joan W.
Vavvas, Demetrios G.
TI AMP-dependent Kinase Inhibits Oxidative Stress-induced Caveolin-1
Phosphorylation and Endocytosis by Suppressing the Dissociation between
c-Abl and Prdx1 Proteins in Endothelial Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CARBOXAMIDE RIBONUCLEOTIDE AICAR; PAG GENE-PRODUCT; TYROSINE KINASE;
GLUCOKINASE TRANSLOCATION; PHYSIOLOGICAL INHIBITOR; SRC KINASE;
ACTIVATION; MICE; PERMEABILITY; PATHWAY
AB Caveolin-1 is the primary structural component of endothelial caveolae that is essential for transcellular trafficking of albumin and is also a critical scaffolding protein that regulates the activity of signaling molecules in caveolae. Phosphorylation of caveolin-1 plays a fundamental role in the mechanism of oxidant-induced vascular hyper permeability. However, the regulatory mechanism of caveolin-1 phosphorylation remains unclear. Here we identify a previously unexpected role for AMPK in inhibition of caveolin-1 phosphorylation under oxidative stress. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR), inhibited oxidative stress-induced phosphorylation of both caveolin-1 and c-Abl, which is the major kinase of caveolin-1, and endocytosis of albumin in human umbilical vein endothelial cell. These effects were abolished by treatment with two specific inhibitors of AICAR, dipyridamole, and 5-iodotubericidin. Consistently, knockdown of the catalytic AMPK alpha subunit by siRNA abolished the inhibitory effect of AICAR on oxidant-induced phosphorylation of both caveolin-1 and c-Abl. Pretreatment with specific c-Abl inhibitor, imatinib mesylate, and knock down of c-Abl significantly decreased the caveolin-1 phosphorylation after H2O2 exposure and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Interestingly, knockdown of Prdx-1, an antioxidant enzyme associated with c-Abl, increased phosphorylation of both caveolin-1 and c-Abl and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Furthermore, co-immunoprecipitation experiment showed that AICAR suppressed the oxidant-induced dissociation between c-Abl and Prdx1. Overall, our results suggest that activation of AMPK inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis, and this effect is mediated in part by stabilizing the interaction between c-Abl and Prdx-1.
C1 [Takeuchi, Kimio; Morizane, Yuki; Kamami-Levy, Cynthia; Suzuki, Jun; Kayama, Maki; Cai, Wenyi; Miller, Joan W.; Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02114 USA.
[Morizane, Yuki] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Ophthalmol, Okayama 7008558, Japan.
RP Vavvas, DG (reprint author), 243 Charles St, Boston, MA 02114 USA.
EM Demetrios_Vavvas@meei.harvard.edu
OI Kamami-Levy, Cynthia/0000-0002-5770-5269; Vavvas,
Demetrios/0000-0002-8622-6478
FU National Institutes of Health [EY014104]; Research to Prevent Blindness
Foundation; Lions Eye Research Fund; Fight for Sight Grant in Aid;
Harvard Ophthalmology Department; Yeatts Family Fund; Bausch and Lomb
Japan Vitreoretinal fellowship
FX This work was supported, in whole or in part, by National Institutes of
Health Grant EY014104 (NEI). This work was also supported by an
unrestricted grant to Massachusetts Eye and Ear Infirmary from the
Research to Prevent Blindness Foundation (to D. G. V. and J. W. M.), the
Lions Eye Research Fund (to D. G. V. and J. W. M.), the Fight for Sight
Grant in Aid (to D. G. V.), the Harvard Ophthalmology Department (to D.
G. V.), Yeatts Family Fund (to D. G. V. and J. W. M.), and a Bausch and
Lomb Japan Vitreoretinal fellowship (to K. T., Y. M., J. S., and M. K.).
NR 52
TC 18
Z9 19
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 12
PY 2013
VL 288
IS 28
BP 20581
EP 20591
DI 10.1074/jbc.M113.460832
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 182BI
UT WOS:000321715100044
PM 23723070
ER
PT J
AU Pasquale, LR
Loomis, SJ
Weinreb, RN
Kang, JH
Yaspan, BL
Bailey, JC
Gaasterland, D
Gaasterland, T
Lee, RK
Scott, WK
Lichter, PR
Budenz, DL
Liu, YT
Realini, T
Friedman, DS
McCarty, CA
Moroi, SE
Olson, L
Schuman, JS
Singh, K
Vollrath, D
Wollstein, G
Zack, DJ
Brilliant, M
Sit, AJ
Christen, WG
Fingert, J
Kraft, P
Zhang, K
Allingham, RR
Pericak-Vance, MA
Richards, JE
Hauser, MA
Haines, JL
Wiggs, JL
AF Pasquale, Louis R.
Loomis, Stephanie J.
Weinreb, Robert N.
Kang, Jae H.
Yaspan, Brian L.
Bailey, Jessica Cooke
Gaasterland, Douglas
Gaasterland, Terry
Lee, Richard K.
Scott, William K.
Lichter, Paul R.
Budenz, Donald L.
Liu, Yutao
Realini, Tony
Friedman, David S.
McCarty, Catherine A.
Moroi, Sayoko E.
Olson, Lana
Schuman, Joel S.
Singh, Kuldev
Vollrath, Douglas
Wollstein, Gadi
Zack, Donald J.
Brilliant, Murray
Sit, Arthur J.
Christen, William G.
Fingert, John
Kraft, Peter
Zhang, Kang
Allingham, R. Rand
Pericak-Vance, Margaret A.
Richards, Julia E.
Hauser, Michael A.
Haines, Jonathan L.
Wiggs, Janey L.
TI Estrogen pathway polymorphisms in relation to primary open angle
glaucoma: An analysis accounting for gender from the United States
SO MOLECULAR VISION
LA English
DT Article
ID HORMONE REPLACEMENT THERAPY; CENTRAL CORNEAL THICKNESS;
INTRAOCULAR-PRESSURE; RECEPTOR-BETA; REPRODUCTIVE FACTORS;
MENSTRUAL-CYCLE; COMT VAL158MET; GENE VARIANTS; OPTIC-NERVE; ASSOCIATION
AB Purpose: Circulating estrogen levels are relevant in glaucoma phenotypic traits. We assessed the association between an estrogen metabolism single nucleotide polymorphism (SNP) panel in relation to primary open angle glaucoma (POAG), accounting for gender.
Methods: We included 3,108 POAG cases and 3,430 controls of both genders from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium genotyped on the Illumina 660W-Quad platform. We assessed the relation between the SNP panels representative of estrogen metabolism and POAG using pathway- and gene-based approaches with the Pathway Analysis by Randomization Incorporating Structure (PARIS) software. PARIS executes a permutation algorithm to assess statistical significance relative to the pathways and genes of comparable genetic architecture. These analyses were performed using the meta-analyzed results from the GLAUGEN and NEIGHBOR data sets. We evaluated POAG overall as well as two subtypes of POAG defined as intraocular pressure (IOP) >= 22 mmHg (high-pressure glaucoma [HPG]) or IOP <22 mmHg (normal pressure glaucoma [NPG]) at diagnosis. We conducted these analyses for each gender separately and then jointly in men and women.
Results: Among women, the estrogen SNP pathway was associated with POAG overall (permuted p=0.006) and HPG (permuted p<0.001) but not NPG (permuted p=0.09). Interestingly, there was no relation between the estrogen SNP pathway and POAG when men were considered alone (permuted p>0.99). Among women, gene-based analyses revealed that the catechol-O-methyltransferase gene showed strong associations with HTG (permuted gene p <= 0.001) and NPG (permuted gene p=0.01).
Conclusions: The estrogen SNP pathway was associated with POAG among women.
C1 [Pasquale, Louis R.; Loomis, Stephanie J.; Wiggs, Janey L.] Harvard Univ, Sch Med, Dept Ophthalmol, Mass Eye & Ear Infirm, Boston, MA USA.
[Pasquale, Louis R.; Kang, Jae H.] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA USA.
[Weinreb, Robert N.; Zhang, Kang] Univ Calif San Diego, Dept Ophthalmol, Sd, CA USA.
[Weinreb, Robert N.; Zhang, Kang] Univ Calif San Diego, Hamilton Glaucoma Ctr, Sd, CA USA.
[Yaspan, Brian L.] Genentech Inc, San Francisco, CA 94080 USA.
[Bailey, Jessica Cooke; Olson, Lana; Haines, Jonathan L.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA.
[Gaasterland, Douglas] Eye Doctors Washington, Chevy Chase, MD USA.
[Gaasterland, Terry] Univ Calif San Diego, Scripps Genome Ctr, San Diego, CA 92103 USA.
[Lee, Richard K.; Scott, William K.; Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
[Lee, Richard K.; Scott, William K.; Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Hussman Inst Human Gen, Miami, FL 33136 USA.
[Lichter, Paul R.; Moroi, Sayoko E.; Richards, Julia E.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[Budenz, Donald L.] Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC USA.
[Liu, Yutao; Allingham, R. Rand; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
[Liu, Yutao; Hauser, Michael A.] Duke Univ, Med Ctr, Durham, NC USA.
[Realini, Tony] W Virginia Univ, Inst Eye, Dept Ophthalmol, Morgantown, WV 26506 USA.
[Friedman, David S.; Zack, Donald J.] Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[McCarty, Catherine A.] Essentia Inst Rural Hlth, Duluth, MN USA.
[Schuman, Joel S.; Wollstein, Gadi] Univ Pittsburgh, Dept Ophthalmol, UPMC Eye Ctr, Pittsburgh, PA 15260 USA.
[Singh, Kuldev] Stanford Univ, Dept Ophthalmol, Palo Alto, CA 94304 USA.
[Vollrath, Douglas] Stanford Univ, Dept Genet, Palo Alto, CA 94304 USA.
[Brilliant, Murray] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA.
[Sit, Arthur J.] Mayo Clin, Dept Ophthalmol, Rochester, MN USA.
[Christen, William G.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Fingert, John] Univ Iowa, Coll Med, Dept Ophthalmol, Iowa City, IA USA.
[Fingert, John] Univ Iowa, Coll Med, Dept Anat Cell Biol, Iowa City, IA USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Pasquale, LR (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM Louis_Pasquale@meei.harvard.edu
RI Fingert, John/F-8787-2012; Schuman, Joel/K-7304-2012;
OI Fingert, John/0000-0002-0377-0479; Schuman, Joel/0000-0002-8885-3766;
Zack, Don/0000-0002-7966-1973; Sit, Arthur/0000-0002-3904-2625
FU Harvard Glaucoma Center of Excellence and Margolis fund (Boston, MA);
Prevent Blindness, Inc. (New York, NY); American Health Assistance
Foundation (Clarksburg, MD); Glaucoma Foundation (New York, NY);
National Institutes of Health [HHSN268200782096C]; National Human Genome
Research Institute (Bethesda, MD) [HG004728, HG004424, HG004446];
National Eye Institute [HG005259-01]; National Human Genome Research
Institute (Bethesda, MD); National Institutes of Health (Bethesda, MD)
[EY015543, EY006827, HL073389, EY13315, EY09611, EY009149, HG004608,
EY008208, EY015473, EY012118, EY015682, EY011671, EY09580, EY013178,
EY015872, EY010886, EY009847, EY011008, EY144428, EY144448, EY18660]
FX Funding/Support: A Horizon Grant to MEEI from Allergan (Irvine, CA)
supported the collection of some glaucoma feature data. The Harvard
Glaucoma Center of Excellence and Margolis fund (Boston, MA) support LRP
and JLW. LRP, JER and JLW are also supported by Research to Prevent
Blindness, Inc. (New York, NY). The Arthur Ashley Foundation also
supports Dr. Pasquale. The Glaucoma Research Foundation (San Francisco,
CA), American Health Assistance Foundation (Clarksburg, MD), and the
Glaucoma Foundation (New York, NY) support YL. The following National
Institutes of Health grants support the maintenance of the Nurses Health
Study and Health Professionals Follow-up, allowing these health
professionals to contribute to this analysis: CA87969, CA49449, UM1
CA167552, and HL35464. The following grants from the National Human
Genome Research Institute (Bethesda, MD) supported GLAUGEN: HG004728
(LRP), HG004424 (Broad Institute to support genotyping), HG004446 (C.
Laurie, U. Washington, to support genotype data cleaning and analysis).
Genotyping services for the NEIGHBOR study were provided by the Center
for Inherited Disease Research (CIDR) and were supported by the National
Eye Institute through grant HG005259-01 (JLW). Additionally CIDR is
funded through a federal contract from the National Institutes of Health
to The Johns Hopkins University, contract number HHSN268200782096C. The
National Eye Institute (Bethesda, MD) through ARRA grants EY015872 (JLW)
and EY019126 (MAH) supported the collection and processing of samples
for the NEIGHBOR dataset. Funding for the collection of cases and
controls was provided by National Institutes of Health (Bethesda, MD)
grants: EY015543 (RRA), EY006827 (DG), HL073389 (Hauser, E); EY13315
(MAH); EY09611 (Hankinson, S), and EY015473 (LRP). EY009149 (PRL),
HG004608 (CAM), EY008208 (Medeiros, P.), EY015473 (LRP), EY012118
(MAP-V), EY015682 (TR), EY011671 (JER), EY09580 (JER), EY013178 (JSS),
EY015872 (JLW), EY010886 (JLW), EY009847 (JLW), EY011008 (Zangwill, L),
EY144428 (KZ), EY144448 (KZ), EY18660 (KZ). None of the authors have any
commercial interests in the subject of the manuscript or in entities
discussed in the manuscript. This work was presented in part at the
American Society of Human Genetics Meeting, November 2012, San
Francisco, CA and at the ARVO Meeting May 2013, Seattle Washington.
NR 56
TC 17
Z9 17
U1 0
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JUL 12
PY 2013
VL 19
BP 1471
EP 1481
PG 11
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 183AT
UT WOS:000321786700003
PM 23869166
ER
PT J
AU Laviolette, LA
Wilson, J
Koller, J
Neil, C
Hulick, P
Rejtar, T
Karger, B
Teh, BT
Iliopoulos, O
AF Laviolette, Laura A.
Wilson, Jonas
Koller, Julia
Neil, Christopher
Hulick, Peter
Rejtar, Tomas
Karger, Barry
Teh, Bin Tean
Iliopoulos, Othon
TI Human Folliculin Delays Cell Cycle Progression through Late S and
G2/M-Phases: Effect of Phosphorylation and Tumor Associated Mutations
SO PLOS ONE
LA English
DT Article
ID BIRT-HOGG-DUBE; HEREDITARY MULTIPLE FIBROFOLLICULOMAS; GENE-PRODUCT;
SPONTANEOUS PNEUMOTHORAX; POLYCYSTIC KIDNEYS; SUPPRESSOR FLCN; MTOR
ACTIVATION; PROTEIN; NEOPLASIA; TRICHODISCOMAS
AB The Birt-Hogg-Dube disease occurs as a result of germline mutations in the human Folliculin gene (FLCN), and is characterized by clinical features including fibrofolliculomas, lung cysts and multifocal renal neoplasia. Clinical and genetic evidence suggest that FLCN acts as a tumor suppressor gene. The human cell line UOK257, derived from the renal cell carcinoma of a patient with a germline mutation in the FLCN gene, harbors a truncated version of the FLCN protein. Reconstitution of the wild type FLCN protein into UOK257 cells delays cell cycle progression, due to a slower progression through the late S and G2/M-phases. Similarly, Flcn(-/-) mouse embryonic fibroblasts progress more rapidly through the cell cycle than wild type controls (Flcn(flox/flox)). The reintroduction of tumor-associated FLCN mutants (FLCN Delta F157, FLCN 1-469 or FLCN K508R) fails to delay cell cycle progression in UOK257 cells. Additionally, FLCN phosphorylation (on Serines 62 and 73) fluctuates throughout the cell cycle and peaks during the G2/M phase in cells treated with nocodazole. In keeping with this observation, the reintroduction of a FLCN phosphomimetic mutant into the UOK257 cell line results in faster progression through the cell cycle compared to those expressing the wild type FLCN protein. These findings suggest that the tumor suppression function of FLCN may be linked to its impact on the cell cycle and that FLCN phosphorylation is important for this activity. Additionally, these observations describe a novel in vitro assay for testing the functional significance of FLCN mutations and/or genetic polymorphisms.
C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA 02129 USA.
Massachusetts Gen Hosp, Ctr Canc, Dept Med, Div Hematol Oncol, Boston, MA USA.
Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA.
Northeastern Univ, Barnett Inst, Boston, MA 02115 USA.
Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI USA.
[Teh, Bin Tean] Natl Canc Ctr Singapore, NCCS VARI Translat Res Lab, Singapore, Singapore.
RP Iliopoulos, O (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA 02129 USA.
EM oiliopoulos@partners.org
FU National Institutes of Health [RO1 CA-208647, RO1 GM15847];
Dana-Farber/Harvard Cancer Center Kidney Cancer SPORE Development Award
FX This work was supported by the National Institutes of Health [RO1
CA-208647 to OI, RO1 GM15847 to BK]; and by a Dana-Farber/Harvard Cancer
Center Kidney Cancer SPORE Development Award to OI. For the Barnett
Institute researchers [BK] this is manuscript contribution No 1022. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 34
TC 4
Z9 4
U1 0
U2 5
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 JUL 11
PY 2013
VL 8
IS 7
AR e66775
DI 10.1371/journal.pone.0066775
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 188UA
UT WOS:000322218800003
PM 23874397
ER
PT J
AU Fathi, AT
Le, L
Hasserjian, RP
Sadrzadeh, H
Levis, M
Chen, YB
AF Fathi, Amir T.
Le, Long
Hasserjian, Robert P.
Sadrzadeh, Hossein
Levis, Mark
Chen, Yi-Bin
TI FLT3 inhibitor-induced neutrophilic dermatosis
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; TYROSINE KINASE
INHIBITOR; C/EBP-ALPHA; ADULT PATIENTS; IN-VIVO; MUTATIONS;
DIFFERENTIATION; EXPRESSION; CELLS
AB The FLT3-ITD mutation is associated with poor outcomes in acute myeloid leukemia. Multiple FMS-like tyrosine kinase 3 (FLT3)-inhibitors have been studied in clinical trials. Recently, potent FLT3 inhibition was shown to induce terminal differentiation of FLT3-mutant myeloblasts. In 3 patients who developed characteristic skin nodules on initiation of FLT3-inhibition, we conducted dermatopathologic evaluation of skin samples, as well as FLT3 and NPM1 mutational analysis and fluorescence in situ hybridization. All 3 patients demonstrated characteristically deep dermal and subcutaneous neutrophilic infiltrates without evidence of myeloblasts. Discovery of FLT3-ITD and NPM1 mutations in 2 of the samples, as well as the presence of FLT3-ITD and deletion of 7q in the other, confirmed the ancestry of the differentiated neutrophils as that of the original FLT3-mutant myeloblasts. FLT3 inhibition can lead to clinically distinct dermatoses, which suggests the effect of FLT3 inhibition on myeloid differentiation and a manifestation of a broader "syndrome" associated with this therapy.
C1 [Fathi, Amir T.; Le, Long; Hasserjian, Robert P.; Sadrzadeh, Hossein; Chen, Yi-Bin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
[Levis, Mark] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
RP Fathi, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Zero Emerson Pl,Suite 118, Boston, MA 02114 USA.
EM afathi@partners.org
FU Bayer/Onyx
FX M.L. is on the clinical advisory board for Ambit Biosciences. Y.C.
receives grant support from Bayer/Onyx to conduct clinical trials. The
remaining authors declare no competing financial interests.
NR 27
TC 9
Z9 9
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUL 11
PY 2013
VL 122
IS 2
BP 239
EP 242
DI 10.1182/blood-2013-01-478172
PG 4
WC Hematology
SC Hematology
GA 184QY
UT WOS:000321909600013
PM 23687091
ER
PT J
AU Carss, KJ
Stevens, E
Foley, AR
Cirak, S
Riemersma, M
Torelli, S
Hoischen, A
Willer, T
van Scherpenzeel, M
Moore, SA
Messina, S
Bertini, E
Bonnemann, CG
Abdenur, JE
Grosmann, CM
Kesari, A
Punetha, J
Quinlivan, R
Waddell, LB
Young, HK
Wraige, E
Yau, S
Brodd, L
Feng, L
Sewry, C
MacArthur, DG
North, KN
Hoffinan, E
Stemple, DL
Hurles, ME
van Bokhoven, H
Campbell, KP
Lefeber, DJ
Lin, YY
Muntoni, F
AF Carss, Keren J.
Stevens, Elizabeth
Foley, A. Reghan
Cirak, Sebahattin
Riemersma, Moniek
Torelli, Silvia
Hoischen, Alexander
Willer, Tobias
van Scherpenzeel, Monique
Moore, Steven A.
Messina, Sonia
Bertini, Enrico
Boennemann, Carsten G.
Abdenur, Jose E.
Grosmann, Carla M.
Kesari, Akanchha
Punetha, Jaya
Quinlivan, Ros
Waddell, Leigh B.
Young, Helen K.
Wraige, Elizabeth
Yau, Shu
Brodd, Lina
Feng, Lucy
Sewry, Caroline
MacArthur, Daniel G.
North, Kathryn N.
Hoffinan, Eric
Stemple, Derek L.
Hurles, Matthew E.
van Bokhoven, Hans
Campbell, Kevin P.
Lefeber, Dirk J.
Lin, Yung-Yao
Muntoni, Francesco
CA UK10K consortium
TI Mutations in GDP-Mannose Pyrophosphorylase B Cause Congenital and
Limb-Girdle Muscular Dystrophies Associated with Hypoglycosylation of
alpha-Dystroglycan
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID WALKER-WARBURG-SYNDROME; CELL-WALL INTEGRITY; O-GLYCAN STRUCTURES;
DEFECTIVE GLYCOSYLATION; ABNORMAL GLYCOSYLATION; GLYCOPROTEIN COMPLEX;
SKELETAL-MUSCLE; GENE; ZEBRAFISH; LAMININ
AB Congenital muscular dystrophies with hypoglycosylation of alpha-dystroglycan (alpha-DG) are a heterogeneous group of disorders often associated with brain and eye defects in addition to muscular dystrophy. Causative variants in 14 genes thought to be involved in the glycosylation of alpha-DG have been identified thus far. Allelic mutations in these genes might also cause milder limb-girdle muscular dystrophy phenotypes. Using a combination of exome and Sanger sequencing in eight unrelated individuals, we present evidence that mutations in guanosine diphosphate mannose (GDP-mannose) pyrophosphorylase B (GMPPB) can result in muscular dystrophy variants with hypoglycosylated alpha-DG. GMPPB catalyzes the formation of GDP-mannose from GTP and mannose-l-phosphate. GDP-mannose is required for O-mannosylation of proteins, including alpha-DG, and it is the substrate of cytosolic mannosyltransferases. We found reduced alpha-DG glycosylation in the muscle biopsies of affected individuals and in available fibroblasts. Overexpression of wild-type GMPPB in fibroblasts from an affected individual partially restored glycosylation of alpha-DG. Whereas wild-type GMPPB localized to the cytoplasm, five of the identified missense mutations caused formation of aggregates in the cytoplasm or near membrane protrusions. Additionally, knockdown of the GMPPB ortholog in zebrafish caused structural muscle defects with decreased motility, eye abnormalities, and reduced glycosylation of alpha-DG. Together, these data indicate that GMPPB mutations are responsible for congenital and limb-girdle muscular dystrophies with hypoglycosylation of alpha-DG.
C1 [Carss, Keren J.; Stemple, Derek L.; Hurles, Matthew E.; Lin, Yung-Yao] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
[Stevens, Elizabeth; Foley, A. Reghan; Cirak, Sebahattin; Torelli, Silvia; Quinlivan, Ros; Feng, Lucy; Sewry, Caroline; Muntoni, Francesco] UCL Inst Child Hlth, Dubowitz Neuromuscular Ctr, London WC1N 1EH, England.
[Cirak, Sebahattin; Kesari, Akanchha; Punetha, Jaya; Hoffinan, Eric] Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA.
[Riemersma, Moniek; Lefeber, Dirk J.] Radboud Univ Nijmegen, Med Ctr, Inst Genet & Metab Dis, Dept Neurol, NL-6525 HB Nijmegen, Netherlands.
[Riemersma, Moniek; van Scherpenzeel, Monique; Lefeber, Dirk J.] Radboud Univ Nijmegen, Med Ctr, Inst Genet & Metab Dis, Dept Lab Med, NL-6525 HB Nijmegen, Netherlands.
[Riemersma, Moniek; Hoischen, Alexander] Radboud Univ Nijmegen, Med Ctr, Inst Genet & Metab Dis, Dept Human Genet,Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands.
[Willer, Tobias; Campbell, Kevin P.] Univ Iowa, Carver Coll Med, Howard Hughes Med Inst, Iowa City, IA 52242 USA.
[Willer, Tobias; Campbell, Kevin P.] Univ Iowa, Carver Coll Med, Dept Neurol, Iowa City, IA 52242 USA.
[Willer, Tobias; Campbell, Kevin P.] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA.
[Willer, Tobias; Campbell, Kevin P.] Univ Iowa, Carver Coll Med, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA.
[Moore, Steven A.] Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA 52242 USA.
[Messina, Sonia] Univ Messina, Azienda Osped Univ Policlin G Martino, Dept Neurosci, I-98125 Messina, Italy.
[Bertini, Enrico] Bambino Gesu Childrens Res Hosp, Mol Med Lab, I-00146 Rome, Italy.
[Boennemann, Carsten G.] NINDS, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Abdenur, Jose E.] Childrens Hosp Orange Cty, Div Metab Disorders, Orange, CA 92868 USA.
[Abdenur, Jose E.] Univ Calif Irvine, Sch Med, Dept Pediat, Irvine, CA 92697 USA.
[Grosmann, Carla M.] Univ Calif San Diego, Rady Childrens Hosp, Sch Med, Dept Neurosci, San Diego, CA 92123 USA.
[Grosmann, Carla M.] Univ Calif San Diego, Rady Childrens Hosp, Sch Med, Dept Pediat, San Diego, CA 92123 USA.
[Punetha, Jaya; Hoffinan, Eric] George Washington Univ, Sch Med & Hlth Sci, Dept Integrat Syst Biol, Washington, DC 20037 USA.
[Quinlivan, Ros] Natl Hosp Neurol & Neurosurg, MRC Ctr Neuromuscular Dis, London WC1N 3BG, England.
[Waddell, Leigh B.; North, Kathryn N.] Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Sydney, NSW 2145, Australia.
[Young, Helen K.] Childrens Hosp Westmead, Dept Neurogenet, Sydney, NSW 2145, Australia.
[Young, Helen K.] Univ Sydney, Royal N Shore Hosp, Northern Clin Sch, St Leonards, NSW 2065, Australia.
[Wraige, Elizabeth] Guys & St Thomas NHS Fdn Trust, Evelina Childrens Hosp, Dept Paediat Neurol, London SE1 7EH, England.
[Yau, Shu; Brodd, Lina] GSTS Pathol, DNA Lab, London SE1 9RT, England.
[Sewry, Caroline] Robert Jones & Agnes Hunt Orthopaed Hosp NHS Fdn, Wolfson Ctr Inherited Neuromuscular Dis, Oswestry SY10 7AG, Shrops, England.
[MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[MacArthur, Daniel G.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[North, Kathryn N.] Univ Sydney, Sydney Med Sch, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia.
[North, Kathryn N.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia.
[van Bokhoven, Hans] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands.
[van Bokhoven, Hans] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6500 HB Nijmegen, Netherlands.
[Lin, Yung-Yao] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England.
RP Muntoni, F (reprint author), UCL Inst Child Hlth, Dubowitz Neuromuscular Ctr, London WC1N 1EH, England.
EM f.muntoni@ucl.ac.uk
RI Schmidts, Miriam/A-3777-2012; van Scherpenzeel, Monique/N-7008-2015;
North, Kathryn/K-6476-2012; McQuillin, Andrew/C-1623-2008; Scambler,
Peter/C-4998-2008; Moayyeri, Alireza/N-3332-2014; Lefeber,
Dirk/A-2146-2014; Bolton, Patrick/E-8501-2010; Hoischen,
Alexander/D-1282-2013; Bokhoven, J.H.L.M./H-8015-2014
OI Messina, Sonia/0000-0001-7994-3391; Suvisaari,
Jaana/0000-0001-7167-0990; Schmidts, Miriam/0000-0002-1714-6749; van
Scherpenzeel, Monique/0000-0002-9696-4562; North,
Kathryn/0000-0003-0841-8009; McQuillin, Andrew/0000-0003-1567-2240;
Scambler, Peter/0000-0002-1487-4628; Ritchie,
Graham/0000-0002-6456-9736; Punetha, Jaya/0000-0002-6774-4464; Moayyeri,
Alireza/0000-0002-9143-2161; Bolton, Patrick/0000-0002-5270-6262;
Hoischen, Alexander/0000-0002-8072-4476;
FU Wellcome Trust [WT091310]
FX This study makes use of data generated by the UK10K Consortium. A full
list of the investigators who contributed to the generation of the data
is available at http://www.uk10k.org/publications_and_posters.html.
Funding for UK10K was provided by the Wellcome Trust under award
WT091310. We are grateful to the UK10K consortium for making this study
possible. Acknowledgments are continued in the Supplemental Data.
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 11
PY 2013
VL 93
IS 1
BP 29
EP 41
DI 10.1016/j.ajhg.2013.05.009
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 183HG
UT WOS:000321804500003
PM 23768512
ER
PT J
AU Chudasama, KK
Winnay, J
Johansson, S
Claudi, T
Konig, R
Haldorsen, I
Johansson, B
Woo, JR
Aarskog, D
Sagen, JV
Kahn, CR
Molven, A
Njolstad, PR
AF Chudasama, Kishan Kumar
Winnay, Jonathon
Johansson, Stefan
Claudi, Tor
Koenig, Rainer
Haldorsen, Ingfrid
Johansson, Bente
Woo, Ju Rang
Aarskog, Dagfinn
Sagen, Jorn V.
Kahn, C. Ronald
Molven, Anders
Njolstad, Pal Rasmus
TI SHORT Syndrome with Partial Lipodystrophy Due to Impaired
Phosphatidylinositol 3 Kinase Signaling
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID PHOSPHOINOSITIDE 3-KINASE; REGULATORY SUBUNIT; ADIPOCYTES; MUTATIONS;
P85-ALPHA; PATHWAYS; BINDING
AB The phosphatidylinositol 3 kinase (PI3K) pathway regulates fundamental cellular processes such as metabolism, proliferation, and survival. A central component in this pathway is the p85 alpha, regulatory subunit, encoded by PIK3R1. Using whole-exome sequencing, we identified a heterozygous PIK3R1 mutation (c.1945C>T [p.Arg649Trp]) in two unrelated families affected by partial lipodystrophy, low body mass index, short stature, progeroid face, and Rieger anomaly (SHORT syndrome). This mutation led to impaired interaction between p85 alpha and IRS-1 and reduced AKT-mediated insulin signaling in fibroblasts from affected subjects and in reconstituted Pik3r1-knockout preadipocytes. Normal PI3K activity is critical for adipose differentiation and insulin signaling; the mutated PIK3R1 therefore provides a unique link among lipodystrophy, growth, and insulin signaling.
C1 [Chudasama, Kishan Kumar; Johansson, Stefan; Johansson, Bente; Aarskog, Dagfinn; Sagen, Jorn V.; Molven, Anders; Njolstad, Pal Rasmus] Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, N-5020 Bergen, Norway.
[Chudasama, Kishan Kumar; Johansson, Stefan] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway.
[Winnay, Jonathon; Woo, Ju Rang; Kahn, C. Ronald; Molven, Anders] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA.
[Claudi, Tor] Nordlandssykehuset, Dept Med, N-8092 Bodo, Norway.
[Koenig, Rainer] Goethe Univ Frankfurt, Dept Human Genet, G-60325 Frankfurt, Germany.
[Haldorsen, Ingfrid; Molven, Anders] Univ Bergen, Dept Clin Med, N-5020 Bergen, Norway.
[Sagen, Jorn V.] Univ Bergen, Dept Clin Sci, N-5020 Bergen, Norway.
[Sagen, Jorn V.] Haukeland Hosp, Hormone Lab, N-5021 Bergen, Norway.
[Molven, Anders] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway.
[Njolstad, Pal Rasmus] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway.
[Njolstad, Pal Rasmus] Broad Inst Harvard & MIT, Med & Populat Genet Program, Cambridge, MA 02142 USA.
RP Njolstad, PR (reprint author), Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, N-5020 Bergen, Norway.
EM pal.njolstad@uib.no
RI Johansson, Stefan/C-4394-2011;
OI Johansson, Stefan/0000-0002-2298-7008; Haldorsen, Ingfrid
S./0000-0001-9313-7564; Johansson, Bente Berg/0000-0001-8893-1915
FU Research Council of Norway; University of Bergen; K.G. Jebsen
Foundation; Helse Vest; Innovest; European Research Council; Nils
Normans Foundation; National Institutes of Health [DK55545]
FX We thank the families for participation, as well as Stig A. Eide and
Louise Grevle for technical assistance, Francisco S. Roque and Inge
Jonassen for support with computational analysis, and the University of
Bergen Audiovisual Section for help with the photographs. The study was
supported by the Research Council of Norway, the University of Bergen,
the K.G. Jebsen Foundation, Helse Vest, Innovest, and the European
Research Council (to P.R.N.), the Nils Normans Foundation (to S.J.), and
National Institutes of Health grant DK55545 (to C.R.K.).
NR 26
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U2 3
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 11
PY 2013
VL 93
IS 1
BP 150
EP 157
DI 10.1016/j.ajhg.2013.05.023
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 183HG
UT WOS:000321804500015
PM 23810379
ER
PT J
AU Reece-Hoyes, JS
Pons, C
Diallo, A
Mori, A
Shrestha, S
Kadreppa, S
Nelson, J
DiPrima, S
Dricot, A
Lajoie, BR
Ribeiro, PSM
Weirauch, MT
Hill, DE
Hughes, TR
Myers, CL
Walhout, AJM
AF Reece-Hoyes, John S.
Pons, Carles
Diallo, Alos
Mori, Akihiro
Shrestha, Shaleen
Kadreppa, Sreenath
Nelson, Justin
DiPrima, Stephanie
Dricot, Amelie
Lajoie, Bryan R.
Ribeiro, Philippe Souza Moraes
Weirauch, Matthew T.
Hill, David E.
Hughes, Timothy R.
Myers, Chad L.
Walhout, Albertha J. M.
TI Extensive Rewiring and Complex Evolutionary Dynamics in a C. elegans
Multiparameter Transcription Factor Network
SO MOLECULAR CELL
LA English
DT Article
ID GENE REGULATORY NETWORK; DNA INTERACTION NETWORK; ONE-HYBRID ASSAYS;
DUPLICATE GENES; PROTEIN-DNA; DOSAGE SENSITIVITY; SYSTEMS-APPROACH;
YEAST; FAMILY; RECOGNITION
AB Gene duplication results in two identical paralogs that diverge through mutation, leading to loss or gain of interactions with other biomolecules. Here, we comprehensively characterize such network rewiring for C. elegans transcription factors (TFs) within and across four newly delineated molecular networks. Remarkably, we find that even highly similar TFs often have different interaction degrees and partners. In addition, we find that most TF families have a member that is highly connected in multiple networks. Further, different TF families have opposing correlations between network connectivity and phylogenetic age, suggesting that they are subject to different evolutionary pressures. Finally, TFs that have similar partners in one network generally do not in another, indicating a lack of pressure to retain cross-network similarity. Our multiparameter analyses provide unique insights into the evolutionary dynamics that shaped TF networks.
C1 [Reece-Hoyes, John S.; Diallo, Alos; Mori, Akihiro; Shrestha, Shaleen; Kadreppa, Sreenath; Lajoie, Bryan R.; Walhout, Albertha J. M.] Univ Massachusetts, Sch Med, Program Mol Med, Program Syst Biol, Worcester, MA 01605 USA.
[Pons, Carles; Nelson, Justin; DiPrima, Stephanie; Ribeiro, Philippe Souza Moraes; Myers, Chad L.] Univ Minnesota Twin Cities, Dept Comp Sci & Engn, Minneapolis, MN 55455 USA.
[Dricot, Amelie; Hill, David E.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA.
[Weirauch, Matthew T.; Hughes, Timothy R.] Univ Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Dept Mol Genet, Toronto, ON M5S 3E1, Canada.
[Weirauch, Matthew T.] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA.
[Weirauch, Matthew T.] Cincinnati Childrens Hosp Med Ctr, CAGE, Cincinnati, OH 45229 USA.
RP Myers, CL (reprint author), Univ Minnesota Twin Cities, Dept Comp Sci & Engn, Minneapolis, MN 55455 USA.
EM cmyers@cs.umn.edu; marian.walhout@umassmed.edu
RI Pons, Carles/B-6841-2016;
OI Walhout, Marian/0000-0001-5587-3608
FU National Institutes of Health (NIH) [GM082971, DK06429, HG005084-01A1,
HG005853-01]; CIHR [MOP-111007]; CIFAR; National Science Foundation [DBI
0953881]
FX We thank members of the Walhout and Myers laboratories, J. Dekker, and
N. Springer for discussions and critical reading of the manuscript. This
work was supported by National Institutes of Health (NIH) grant GM082971
to A.J.M.W. and D.E.H.; NIH grant DK06429 to A.J.M.W.; CIHR grant
MOP-111007 to T.R.H.; fellowships from CIHR and CIFAR to M.T.W.; and
C.L.M., C.P., J.N., and P.S.M.R. are partially supported by grants from
the NIH (HG005084-01A1, HG005853-01) and the National Science Foundation
(DBI 0953881).
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U2 10
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 JUL 11
PY 2013
VL 51
IS 1
BP 116
EP 127
DI 10.1016/j.molcel.2013.05.018
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 183DL
UT WOS:000321794100012
PM 23791784
ER
PT J
AU Lawrence, MS
Stojanov, P
Polak, P
Kryukov, GV
Cibulskis, K
Sivachenko, A
Carter, SL
Stewart, C
Mermel, CH
Roberts, SA
Kiezun, A
Hammerman, PS
McKenna, A
Drier, Y
Zou, LH
Ramos, AH
Pugh, TJ
Stransky, N
Helman, E
Kim, J
Sougnez, C
Ambrogio, L
Nickerson, E
Shefler, E
Cortes, ML
Auclair, D
Saksena, G
Voet, D
Noble, M
DiCara, D
Lin, P
Lichtenstein, L
Heiman, DI
Fennell, T
Imielinski, M
Hernandez, B
Hodis, E
Baca, S
Dulak, AM
Lohr, J
Landau, DA
Wu, CJ
Melendez-Zajgla, J
Hidalgo-Miranda, A
Koren, A
McCarroll, SA
Mora, J
Lee, RS
Crompton, B
Onofrio, R
Parkin, M
Winckler, W
Ardlie, K
Gabriel, SB
Roberts, CWM
Biegel, JA
Stegmaier, K
Bass, AJ
Garraway, LA
Meyerson, M
Golub, TR
Gordenin, DA
Sunyaev, S
Lander, ES
Getz, G
AF Lawrence, Michael S.
Stojanov, Petar
Polak, Paz
Kryukov, Gregory V.
Cibulskis, Kristian
Sivachenko, Andrey
Carter, Scott L.
Stewart, Chip
Mermel, Craig H.
Roberts, Steven A.
Kiezun, Adam
Hammerman, Peter S.
McKenna, Aaron
Drier, Yotam
Zou, Lihua
Ramos, Alex H.
Pugh, Trevor J.
Stransky, Nicolas
Helman, Elena
Kim, Jaegil
Sougnez, Carrie
Ambrogio, Lauren
Nickerson, Elizabeth
Shefler, Erica
Cortes, Maria L.
Auclair, Daniel
Saksena, Gordon
Voet, Douglas
Noble, Michael
DiCara, Daniel
Lin, Pei
Lichtenstein, Lee
Heiman, David I.
Fennell, Timothy
Imielinski, Marcin
Hernandez, Bryan
Hodis, Eran
Baca, Sylvan
Dulak, Austin M.
Lohr, Jens
Landau, Dan-Avi
Wu, Catherine J.
Melendez-Zajgla, Jorge
Hidalgo-Miranda, Alfredo
Koren, Amnon
McCarroll, Steven A.
Mora, Jaume
Lee, Ryan S.
Crompton, Brian
Onofrio, Robert
Parkin, Melissa
Winckler, Wendy
Ardlie, Kristin
Gabriel, Stacey B.
Roberts, Charles W. M.
Biegel, Jaclyn A.
Stegmaier, Kimberly
Bass, Adam J.
Garraway, Levi A.
Meyerson, Matthew
Golub, Todd R.
Gordenin, Dmitry A.
Sunyaev, Shamil
Lander, Eric S.
Getz, Gad
TI Mutational heterogeneity in cancer and the search for new
cancer-associated genes
SO NATURE
LA English
DT Article
ID COMPREHENSIVE GENOMIC CHARACTERIZATION; CHRONIC LYMPHOCYTIC-LEUKEMIA;
SOMATIC MUTATIONS; HUMAN-PAPILLOMAVIRUS; MAMMALIAN GENOMES; DNA;
LANDSCAPE; CARCINOMA; PATHWAYS; LYMPHOMA
AB Major international projects are underway that are aimed at creating a comprehensive catalogue of all the genes responsible for the initiation and progression of cancer(1-9). These studies involve the sequencing of matched tumour-normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false-positive findings that overshadow true driver events. We show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, MutSigCV, for resolving the problem. We apply MutSigCV to exome sequences from 3,083 tumour-normal pairs and discover extraordinary variation in mutation frequency and spectrum within cancer types, which sheds light on mutational processes and disease aetiology, and in mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and enable the identification of genes truly associated with cancer.
C1 [Lawrence, Michael S.; Stojanov, Petar; Polak, Paz; Kryukov, Gregory V.; Cibulskis, Kristian; Sivachenko, Andrey; Carter, Scott L.; Stewart, Chip; Mermel, Craig H.; Kiezun, Adam; Hammerman, Peter S.; McKenna, Aaron; Drier, Yotam; Zou, Lihua; Ramos, Alex H.; Pugh, Trevor J.; Stransky, Nicolas; Helman, Elena; Kim, Jaegil; Sougnez, Carrie; Ambrogio, Lauren; Nickerson, Elizabeth; Shefler, Erica; Cortes, Maria L.; Auclair, Daniel; Saksena, Gordon; Voet, Douglas; Noble, Michael; DiCara, Daniel; Lin, Pei; Lichtenstein, Lee; Heiman, David I.; Fennell, Timothy; Imielinski, Marcin; Hernandez, Bryan; Hodis, Eran; Baca, Sylvan; Dulak, Austin M.; Lohr, Jens; Landau, Dan-Avi; Koren, Amnon; McCarroll, Steven A.; Onofrio, Robert; Parkin, Melissa; Winckler, Wendy; Ardlie, Kristin; Gabriel, Stacey B.; Stegmaier, Kimberly; Bass, Adam J.; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd R.; Sunyaev, Shamil; Lander, Eric S.; Getz, Gad] Broad Inst MIT & Harvard, Cambridge, MA 02141 USA.
[Stojanov, Petar; Hammerman, Peter S.; Pugh, Trevor J.; Hodis, Eran; Baca, Sylvan; Dulak, Austin M.; Lohr, Jens; Landau, Dan-Avi; Wu, Catherine J.; Lee, Ryan S.; Crompton, Brian; Roberts, Charles W. M.; Stegmaier, Kimberly; Bass, Adam J.; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Polak, Paz; Kryukov, Gregory V.; Drier, Yotam; Pugh, Trevor J.; Wu, Catherine J.; Koren, Amnon; McCarroll, Steven A.; Lee, Ryan S.; Roberts, Charles W. M.; Bass, Adam J.; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd R.; Sunyaev, Shamil; Lander, Eric S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Polak, Paz; Kryukov, Gregory V.; Sunyaev, Shamil] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Mermel, Craig H.; Drier, Yotam; Imielinski, Marcin; Getz, Gad] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Roberts, Steven A.; Gordenin, Dmitry A.] NIEHS, Lab Mol Genet, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[McKenna, Aaron] Univ Washington, Seattle, WA 98195 USA.
[Drier, Yotam; Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Stransky, Nicolas] Blueprint Med, Cambridge, MA 02142 USA.
[Helman, Elena; Lander, Eric S.] MIT, Cambridge, MA 02139 USA.
[Landau, Dan-Avi] Yale Canc Ctr, Dept Hematol, New Haven, CT 06510 USA.
[Melendez-Zajgla, Jorge; Hidalgo-Miranda, Alfredo] Inst Nacl Med Genom, Mexico City 14610, DF, Mexico.
[Mora, Jaume] Hosp St Joan de Deu, Dept Pediat Oncol, Barcelona 08950, Spain.
[Lee, Ryan S.; Crompton, Brian; Roberts, Charles W. M.; Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA 02115 USA.
[Biegel, Jaclyn A.] Childrens Hosp, Philadelphia, PA 19104 USA.
RP Lander, ES (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02141 USA.
EM lander@broadinstitute.org; gadgetz@broadinstitute.org
RI Hidalgo-Miranda, Alfredo/B-2123-2010; Kryukov, Gregory/A-9592-2008;
Drier, Yotam/K-5208-2012;
OI Hidalgo-Miranda, Alfredo/0000-0003-2315-3977; Drier,
Yotam/0000-0003-1725-2995; Gordenin, Dmitry/0000-0002-8399-1836
FU Intramural Research Program of the National Institute of Environmental
Health Sciences (National Institutes of Health, United States Department
of Health and Human Services) [ES065073]
FX This work was conducted as part of TCGA, a project of the National
Cancer Institute and National Human Genome Research Institute. This work
was conducted as part of the Slim Initiative for Genomic Medicine, a
joint US-Mexico project founded by the Carlos Slim Health Institute.
Support to D. A. G. and S. A. R. was through the Intramural Research
Program of the National Institute of Environmental Health Sciences
(National Institutes of Health, United States Department of Health and
Human Services) project ES065073 (principal investigator M. Resnick).
NR 30
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U2 207
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 11
PY 2013
VL 499
IS 7457
BP 214
EP 218
DI 10.1038/nature12213
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600063
PM 23770567
ER
PT J
AU Sharma, S
Quintana, A
Findlay, GM
Mettlen, M
Baust, B
Jain, M
Nilsson, R
Rao, A
Hogan, PG
AF Sharma, Sonia
Quintana, Ariel
Findlay, Gregory M.
Mettlen, Marcel
Baust, Beate
Jain, Mohit
Nilsson, Roland
Rao, Anjana
Hogan, Patrick G.
TI An siRNA screen for NFAT activation identifies septins as coordinators
of store-operated Ca2+ entry
SO NATURE
LA English
DT Article
ID CHANNEL ACTIVATION; ORAI1; STIM1; CALCIUM; CYTOSKELETON; RELEASE; CRAC;
FORCHLORFENURON; ORGANIZATION; DOMAINS
AB The STIM1-ORAI1 pathway of store-operated Ca2+ entry is an essential component of cellular Ca2+ signalling(1). STIM1 senses depletion of intracellular Ca2+ stores in response to physiological stimuli, and relocalizes within the endoplasmic reticulum to plasma-membrane-apposed junctions, where it recruits and gates open plasma membrane ORAI1 Ca2+ channels. Here we use a genome-wide RNA interference screen in HeLa cells to identify filamentous septin proteins as crucial regulators of store-operated Ca2+ entry. Septin filaments and phosphatidylinositol-4,5-bisphosphate (also known as PtdIns(4,5)P-2) rearrange locally at endoplasmic reticulum-plasma membrane junctions before and during formation of STIM1-ORAI1 clusters, facilitating STIM1 targeting to these junctions and promoting the stable recruitment of ORAI1. Septin rearrangement at junctions is required for PtdIns(4,5) P2 reorganization and efficient STIM1-ORAI1 communication. Septins are known to demarcate specialized membrane regions such as dendritic spines, the yeast bud and the primary cilium, and to serve as membrane diffusion barriers and/or signalling hubs in cellular processes such as vesicle trafficking, cell polarity and cytokinesis2-4. Our data show that septins also organize the highly localized plasma membrane domains that are important in STIM1-ORAI1 signalling, and indicate that septins may organize membrane microdomains relevant to other signalling processes.
C1 [Sharma, Sonia; Quintana, Ariel; Rao, Anjana; Hogan, Patrick G.] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
[Sharma, Sonia; Quintana, Ariel; Findlay, Gregory M.; Baust, Beate; Rao, Anjana; Hogan, Patrick G.] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Mettlen, Marcel] Scripps Res Inst, La Jolla, CA 92037 USA.
[Jain, Mohit] Broad Inst, Cambridge, MA 02142 USA.
[Jain, Mohit] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
[Nilsson, Roland] Karolinska Inst, S-17176 Stockholm, Sweden.
RP Rao, A (reprint author), La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
EM arao@liai.org; phogan@liai.org
FU National Institutes of Health (NIH) [AI040127, AI084167]; NIH [AI092763,
K08 HL107451, R01GM73165]; Canadian Institutes for Health Research;
Leukemia & Lymphoma Society; Deutsche Forschungsgemeinschaft
[QU298/1-1]; Knut & Alice Wallenberg Foundation
FX We thank C. Shamu, S. Rudnicki, S. Johnston and D. Wrobel for screening
support; A. Carpenter and M. Bray for CellProfiler optimization; P.
Meraner and Y. Zhou for cell lines and constructs; S. Schmid, J.
Fitzpatrick and the Waitt Advanced Biophotonics Center at the Salk
Institute for access to TIRF microscopes; C. Junker for the RFP-ER
construct; S. Field for the PLC delta-PH-eGFP plasmid; and S. Schmid for
manuscript review. The work was supported by National Institutes of
Health (NIH) R01 grants AI040127 and AI084167(to A. R. and P. G. H.),
NIH RC4 grant AI092763 (to A. R. and S. S.); a Fellowship from the
Canadian Institutes for Health Research and a Special Fellowship from
The Leukemia & Lymphoma Society (to S. S.); postdoctoral fellowship
QU298/1-1 from the Deutsche Forschungsgemeinschaft (to A. Q.); NIH grant
K08 HL107451 (to M. J.); a postdoctoral scholarship from the Knut &
Alice Wallenberg Foundation (to R. N.); NIH R01 grant R01GM73165 (to S.
Schmid, which supports M.M.).
NR 30
TC 84
Z9 84
U1 1
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 11
PY 2013
VL 499
IS 7457
BP 238
EP +
DI 10.1038/nature12229
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600068
PM 23792561
ER
PT J
AU Hamid, O
Robert, C
Daud, A
Hodi, FS
Hwu, WJ
Kefford, R
Wolchok, JD
Hersey, P
Joseph, RW
Weber, JS
Dronca, R
Gangadhar, TC
Patnaik, A
Zarour, H
Joshua, AM
Gergich, K
Elassaiss-Schaap, J
Algazi, A
Mateus, C
Boasberg, P
Tumeh, PC
Chmielowski, B
Ebbinghaus, SW
Li, XN
Kang, SP
Ribas, A
AF Hamid, Omid
Robert, Caroline
Daud, Adil
Hodi, F. Stephen
Hwu, Wen-Jen
Kefford, Richard
Wolchok, Jedd D.
Hersey, Peter
Joseph, Richard W.
Weber, Jeffrey S.
Dronca, Roxana
Gangadhar, Tara C.
Patnaik, Amita
Zarour, Hassane
Joshua, Anthony M.
Gergich, Kevin
Elassaiss-Schaap, Jeroen
Algazi, Alain
Mateus, Christine
Boasberg, Peter
Tumeh, Paul C.
Chmielowski, Bartosz
Ebbinghaus, Scot W.
Li, Xiaoyun Nicole
Kang, S. Peter
Ribas, Antoni
TI Safety and Tumor Responses with Lambrolizumab (Anti-PD-1) in Melanoma
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID METASTATIC MELANOMA; CANCER; IMMUNOTHERAPY; PHASE; BLOCKADE; ANTIBODY;
CRITERIA; THERAPY; PD-1
AB BACKGROUND
The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti-PD-1 antibody lambrolizumab (previously known as MK-3475) in patients with advanced melanoma.
METHODS
We administered lambrolizumab intravenously at a dose of 10 mg per kilogram of body weight every 2 or 3 weeks or 2 mg per kilogram every 3 weeks in patients with advanced melanoma, both those who had received prior treatment with the immune checkpoint inhibitor ipilimumab and those who had not. Tumor responses were assessed every 12 weeks.
RESULTS
A total of 135 patients with advanced melanoma were treated. Common adverse events attributed to treatment were fatigue, rash, pruritus, and diarrhea; most of the adverse events were low grade. The confirmed response rate across all dose cohorts, evaluated by central radiologic review according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, was 38% (95% confidence interval [CI], 25 to 44), with the highest confirmed response rate observed in the cohort that received 10 mg per kilogram every 2 weeks (52%; 95% CI, 38 to 66). The response rate did not differ significantly between patients who had received prior ipilimumab treatment and those who had not (confirmed response rate, 38% [95% CI, 23 to 55] and 37% [95% CI, 26 to 49], respectively). Responses were durable in the majority of patients (median follow-up, 11 months among patients who had a response); 81% of the patients who had a response (42 of 52) were still receiving treatment at the time of analysis in March 2013. The overall median progression-free survival among the 135 patients was longer than 7 months.
CONCLUSIONS
In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects.
C1 [Hamid, Omid; Boasberg, Peter] Angeles Clin & Res Inst, Los Angeles, CA USA.
[Tumeh, Paul C.; Chmielowski, Bartosz; Ribas, Antoni] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
[Robert, Caroline; Mateus, Christine] Inst Gustave Roussy, Villejuif, France.
[Daud, Adil; Algazi, Alain] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hwu, Wen-Jen] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Kefford, Richard] Univ Sydney, Westmead Hosp, Sydney, NSW 2006, Australia.
[Kefford, Richard] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia.
[Hersey, Peter] Melanoma Inst Australia, Kolling Inst, Newcastle, NSW, Australia.
[Hersey, Peter] Newcastle Melanoma Unit, Newcastle, NSW, Australia.
[Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Joseph, Richard W.] Mayo Clin, Jacksonville, FL 32224 USA.
[Weber, Jeffrey S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Dronca, Roxana] Mayo Clin, Rochester, MN USA.
[Gangadhar, Tara C.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Patnaik, Amita] South Texas Accelerated Res Therapeut, San Antonio, TX USA.
[Zarour, Hassane] Univ Pittsburgh, Pittsburgh, PA USA.
[Joshua, Anthony M.] Princess Margaret Canc Ctr, Toronto, ON, Canada.
[Gergich, Kevin; Elassaiss-Schaap, Jeroen; Ebbinghaus, Scot W.; Li, Xiaoyun Nicole; Kang, S. Peter] Merck Sharp & Dohme Ltd, Whitehouse Stn, NJ USA.
RP Ribas, A (reprint author), Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Jonsson Comprehens Canc Ctr, 11-934 Factor Bldg,10833 Le Conte Ave, Los Angeles, CA 90095 USA.
EM aribas@mednet.ucla.edu
RI Li, Xiaoyun/P-8265-2014; Kanemura, Takashi/H-5717-2015; Elassaiss-Schaap
, Jeroen/Q-5451-2016;
OI Chmielowski, Bartosz/0000-0002-2374-3320
FU Merck Sharp; Dohme
FX Supported by Merck Sharp and Dohme.
NR 16
TC 1212
Z9 1256
U1 31
U2 168
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 11
PY 2013
VL 369
IS 2
BP 134
EP 144
DI 10.1056/NEJMoa1305133
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 180BH
UT WOS:000321567300009
PM 23724846
ER
PT J
AU Wing, R
Bolin, P
Brancati, FL
Bray, GA
Clark, JM
Coday, M
Crow, RS
Curtis, JM
Egan, CM
Espeland, MA
Evans, M
Foreyt, JP
Ghazarian, S
Gregg, EW
Harrison, B
Hazuda, HP
Hill, JO
Horton, ES
Hubbard, V
Jakicic, JM
Jeffery, RW
Johnson, KC
Kahn, SE
Kitabchi, AE
Knowler, WC
Lewis, CE
Maschak-Carey, BJ
Montez, MG
Murillo, A
Nathan, DM
Patricio, J
Peters, A
Pi-Sunyer, X
Pownall, H
Reboussin, D
Regensteiner, JG
Rickman, AD
Ryan, DH
Safford, M
Wadden, TA
Wagenknecht, LE
West, DS
Williamson, DF
Yanovski, SZ
AF Wing, Rena
Bolin, Paula
Brancati, Frederick L.
Bray, George A.
Clark, Jeanne M.
Coday, Mace
Crow, Richard S.
Curtis, Jeffrey M.
Egan, Caitlin M.
Espeland, Mark A.
Evans, Mary
Foreyt, John P.
Ghazarian, Siran
Gregg, Edward W.
Harrison, Barbara
Hazuda, Helen P.
Hill, James O.
Horton, Edward S.
Hubbard, Van S.
Jakicic, John M.
Jeffery, Robert W.
Johnson, Karen C.
Kahn, Steven E.
Kitabchi, Abbas E.
Knowler, William C.
Lewis, Cora E.
Maschak-Carey, Barbara J.
Montez, Maria G.
Murillo, Anne
Nathan, David M.
Patricio, Jennifer
Peters, Anne
Pi-Sunyer, Xavier
Pownall, Henry
Reboussin, David
Regensteiner, Judith G.
Rickman, Amy D.
Ryan, Donna H.
Safford, Monika
Wadden, Thomas A.
Wagenknecht, Lynne E.
West, Delia S.
Williamson, David F.
Yanovski, Susan Z.
CA Look AHEAD Res Grp
TI Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2
Diabetes
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID LOOK-AHEAD ACTION; WEIGHT-LOSS; CLINICAL-TRIAL; OBESE ADULTS;
PREVENTION; MORTALITY; HEALTH; INDIVIDUALS; MELLITUS; PROGRAM
AB Background
Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients.
Methods
In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years.
Results
The trial was stopped early on the basis of a futility analysis when the median follow- up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P = 0.51).
Conclusions
An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes.
C1 [Wing, Rena; Curtis, Jeffrey M.] Brown Univ, Warren Alpert Med Sch, Weight Control & Diabet Res Ctr, Providence, RI 02903 USA.
[Bolin, Paula; Evans, Mary; Harrison, Barbara; Hubbard, Van S.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Brancati, Frederick L.; Clark, Jeanne M.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Bray, George A.] Pennington Biomed Res Ctr, Baton Rouge, LA USA.
[Coday, Mace; Johnson, Karen C.; Kitabchi, Abbas E.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Crow, Richard S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Curtis, Jeffrey M.] NIDDK, NIH, Phoenix, AZ USA.
[Egan, Caitlin M.] Miriam Hosp, Providence, RI 02906 USA.
[Espeland, Mark A.] Wake Forest Univ, Dept Biostat Sci, Sch Med, Winston Salem, NC 27109 USA.
[Foreyt, John P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Ghazarian, Siran; Peters, Anne] Roybal Comprehens Hlth Ctr, Los Angeles, CA USA.
[Gregg, Edward W.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Hazuda, Helen P.; Montez, Maria G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Clin Epidemiol, San Antonio, TX 78229 USA.
[Hill, James O.] Univ Colorado, Hlth Sci Ctr, Ctr Human Nutr, Aurora, CO USA.
[Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Jakicic, John M.] Univ Pittsburgh, Dept Hlth & Phys Act, Pittsburgh, PA USA.
[Jeffery, Robert W.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Kahn, Steven E.; Murillo, Anne] Univ Washington, Dept Med, Seattle, WA USA.
[Knowler, William C.] NIDDK, NIH, Southwest Amer Indian Ctr, Phoenix, AZ USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA.
[Maschak-Carey, Barbara J.] Univ Penn, Weight & Eating Disorder Program, Philadelphia, PA 19104 USA.
[Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Patricio, Jennifer] St Lukes Roosevelt Hosp, Dept Med, New York, NY 10025 USA.
[Pi-Sunyer, Xavier] St Lukes Roosevelt Hosp, Dept Med, New York, NY 10025 USA.
[Pownall, Henry] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Reboussin, David] Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27109 USA.
[Regensteiner, Judith G.] Univ Colorado, Hlth Sci Ctr, Ctr Womens Hlth Res, Aurora, CO USA.
[Rickman, Amy D.] Univ Pittsburgh, Dept Hlth & Phys Act, Pittsburgh, PA USA.
[Ryan, Donna H.] Pennington Biomed Res Ctr, Baton Rouge, LA USA.
[Safford, Monika] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA.
[Wadden, Thomas A.] Univ Penn, Weight & Eating Disorder Program, Philadelphia, PA 19104 USA.
[Wagenknecht, Lynne E.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[West, Delia S.] Univ Arkansas Med Sci, Coll Publ Hlth, Dept Hlth Behav & Hlth Educ, Little Rock, AR 72205 USA.
[Williamson, David F.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Yanovski, Susan Z.] NIDDK, NIH, Bethesda, MD USA.
RP Wing, R (reprint author), Brown Univ, Warren Alpert Med Sch, Weight Control & Diabet Res Ctr, 196 Richmond St, Providence, RI 02903 USA.
EM rwing@lifespan.org
OI Kahn, Steven/0000-0001-7307-9002
FU National Institutes of Health (NIH); Department of Health and Human
Services agencies; National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) [DK57136, DK57149, DK56990, DK57177, DK57171,
DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219,
DK57008, DK57135, DK56992]; Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases; National Heart,
Lung, and Blood Institute; National Institute of Nursing Research;
National Center on Minority Health and Health Disparities; NIH Office of
Research on Women's Health; Centers for Disease Control and Prevention;
Johns Hopkins Medical Institutions Bayview General Clinical Research
Center [M01RR02719]; Massachusetts General Hospital Mallinckrodt General
Clinical Research Center; Massachusetts Institute of Technology General
Clinical Research Center [M01RR01066]; University of Colorado Health
Sciences Center General Clinical Research Center [M01RR00051]; Clinical
Nutrition Research Unit [P30 DK48520]; University of Tennessee at
Memphis General Clinical Research Center [M01RR0021140]; University of
Pittsburgh General Clinical Research Center [M01RR000056]; Clinical
Translational Research Center; Clinical and Translational Science Award
[UL1 RR 024153]; NIH [DK 046204]; VA Puget Sound Health Care System
Medical Research Service, Department of Veterans Affairs; Frederic C.
Bartter General Clinical Research Center [M01RR01346]; FedEx; Health
Management Resources; Johnson Johnson; Nestle HealthCare Nutrition;
Hoffmann-La Roche; Abbott Nutrition; Unilever North America
FX Supported by the National Institutes of Health (NIH) and other
Department of Health and Human Services agencies through cooperative
agreements with the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) (DK57136, DK57149, DK56990, DK57177, DK57171,
DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219,
DK57008, DK57135, and DK56992). Additional funding was provided by the
Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; the National Heart, Lung, and Blood
Institute; the National Institute of Nursing Research; the National
Center on Minority Health and Health Disparities; the NIH Office of
Research on Women's Health; and the Centers for Disease Control and
Prevention. The Indian Health Service (IHS) provided personnel, medical
oversight, and use of facilities. Additional support was provided by the
Johns Hopkins Medical Institutions Bayview General Clinical Research
Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt
General Clinical Research Center and the Massachusetts Institute of
Technology General Clinical Research Center (M01RR01066); the University
of Colorado Health Sciences Center General Clinical Research Center
(M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the
University of Tennessee at Memphis General Clinical Research Center
(M01RR0021140); the University of Pittsburgh General Clinical Research
Center(M01RR000056) and Clinical Translational Research Center (funded
by a Clinical and Translational Science Award [UL1 RR 024153] and an NIH
grant [DK 046204]); the VA Puget Sound Health Care System Medical
Research Service, Department of Veterans Affairs; and the Frederic C.
Bartter General Clinical Research Center (M01RR01346); and by FedEx,
Health Management Resources, Johnson & Johnson, Nestle HealthCare
Nutrition, Hoffmann-La Roche, Abbott Nutrition, and Unilever North
America.
NR 28
TC 578
Z9 589
U1 10
U2 102
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 11
PY 2013
VL 369
IS 2
BP 145
EP 154
DI 10.1056/NEJMoa1212914
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 180BH
UT WOS:000321567300010
ER
PT J
AU Sullivan, RJ
Lawrence, DP
Wargo, JA
Oh, KS
Gonzalez, RG
Piris, A
AF Sullivan, Ryan J.
Lawrence, Donald P.
Wargo, Jennifer A.
Oh, Kevin S.
Gonzalez, R. Gilberto
Piris, Adriano
TI Case 21-2013: A 68-Year-Old Man with Metastatic Melanoma
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; BRAIN METASTASES; OPEN-LABEL;
ANTITUMOR-ACTIVITY; IMPROVED SURVIVAL; MEK INHIBITION; PHASE-2 TRIAL;
T-CELLS; IPILIMUMAB; VEMURAFENIB
C1 [Sullivan, Ryan J.; Lawrence, Donald P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Wargo, Jennifer A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Oh, Kevin S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA.
[Piris, Adriano] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Sullivan, Ryan J.; Lawrence, Donald P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Wargo, Jennifer A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Oh, Kevin S.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA.
[Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Dept Neuroradiol, Boston, MA USA.
[Piris, Adriano] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Sullivan, RJ (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
NR 39
TC 21
Z9 22
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 11
PY 2013
VL 369
IS 2
BP 173
EP 183
DI 10.1056/NEJMcpc1302332
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 180BH
UT WOS:000321567300014
PM 23841733
ER
PT J
AU Eypper, EH
Johnson, PV
Purro, EI
Hohmann, EL
AF Eypper, Elizabeth H.
Johnson, Paul V.
Purro, Eva I.
Hohmann, Elizabeth L.
TI Transcutaneous immunization of healthy volunteers with an attenuated
Listeria monocytogenes vaccine strain and cholera toxin adjuvant
SO VACCINE
LA English
DT Article
DE Listeria monocytogenes; Transcutaneous; Vaccination; ELISpot; attenuated
vector; Clinical trial
ID SAFETY; IMMUNITY; CELLS
AB Background: Attenuated Listeria monocytogenes vaccine strains have been administered intravenously (Le et al. [1], Maciag et al. [21) and orally (Angelakopoulos et al. [3], Johnson et al. [4]) to humans. Here, one was given transcutaneously with cholera toxin adjuvant.
Methods: Eight healthy volunteers were studied (5 active, 3 placebo). Safety was assessed by physical exam and labs. Systemic immunological responses were measured by ELISA and IFN-gamma ELISpot.
Results: 4/5 active volunteers had cellular responses to listerial antigens. 5/5 active volunteers showed humoral responses to cholera toxin.
Conclusions: An attenuated L. monocytogenes vector was safely administered transcutaneously. Topical administration appeared at least as immunogenic as previously studied oral delivery. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
C1 [Eypper, Elizabeth H.; Johnson, Paul V.; Hohmann, Elizabeth L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Purro, Eva I.] List Biol Inc, Campbell, CA 95008 USA.
RP Hohmann, EL (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA.
EM ehohmann@partners.org
FU National Institute for Allergy and Infectious Diseases at the National
Institutes of Health [R01AI51206]
FX EIP is a full-time employee of List Biologicals. EHE, PVJ, ELH have no
conflicts of interest. Funding: This work was supported in part by
National Institute for Allergy and Infectious Diseases at the National
Institutes of Health [R01AI51206] to ELH. The funder had no role in the
design or execution of the study nor in the preparation or submission of
the article.
NR 12
TC 6
Z9 7
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUL 11
PY 2013
VL 31
IS 32
BP 3257
EP 3261
DI 10.1016/j.vaccine.2013.05.028
PG 5
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 179RE
UT WOS:000321538200008
PM 23707162
ER
PT J
AU Munshi, NC
Anderson, KC
AF Munshi, Nikhil C.
Anderson, Kenneth C.
TI Minimal Residual Disease in Multiple Myeloma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID STEM-CELL TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; FLOW-CYTOMETRY;
BONE-MARROW; AUTOLOGOUS TRANSPLANTATION; LENALIDOMIDE; MAINTENANCE;
REMISSION; THERAPY
C1 [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst,VA Boston Healthcare Syst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
[Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,VA Boston Healthcare Syst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA.
FU BLRD VA [I01 BX001584]; NCI NIH HHS [P50 CA100707, P01 CA078378, P01
CA155258]; PHS HHS [P01-155258, P01-78378, P50-100007, R01-124929,
R01-50947]
NR 27
TC 17
Z9 18
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 10
PY 2013
VL 31
IS 20
BP 2523
EP 2526
DI 10.1200/JCO.2013.49.2124
PG 4
WC Oncology
SC Oncology
GA 301NA
UT WOS:000330537800012
PM 23733782
ER
PT J
AU Mack, JW
Chen, K
Boscoe, FP
Gesten, FC
Roohan, PJ
Weeks, JC
Schymura, MJ
Schrag, D
AF Mack, Jennifer W.
Chen, Kun
Boscoe, Francis P.
Gesten, Foster C.
Roohan, Patrick J.
Weeks, Jane C.
Schymura, Maria J.
Schrag, Deborah
TI Underuse of Hospice Care by Medicaid-Insured Patients With Stage IV Lung
Cancer in New York and California
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; MENTAL-HEALTH; END; OUTCOMES; DEATH; CARCINOMA; PLACE
AB Purpose
Medicare patients with advanced cancer have low rates of hospice use. We sought to evaluate hospice use among patients in Medicaid, which insures younger and indigent patients, relative to those in Medicare.
Patients and Methods
Using linked patient-level data from California (CA) and New York (NY) state cancer registries, state Medicaid programs, NY Medicare, and CA Surveillance, Epidemiology, and End Results-Medicare data, we identified 4,797 CA Medicaid patients and 4,001 NY Medicaid patients ages 21 to 64 years, as well as 27,416 CA Medicare patients and 16,496 NY Medicare patients ages >= 65 years who were diagnosed with stage IV lung cancer between 2002 and 2006. We evaluated hospice use, timing of enrollment, and location of death (inpatient hospice; long-term care facility or skilled nursing facility; acute care facility; home with hospice; or home without hospice). We used multiple logistic regressions to evaluate clinical and sociodemographic factors associated with hospice use.
Results
Although 53% (CA) and 44% (NY) of Medicare patients ages >= 65 years used hospice, fewer than one third of Medicaid-insured patients ages 21 to 64 years enrolled in hospice after a diagnosis of stage IV lung cancer (CA, 32%; NY, 24%). A minority of Medicaid patient deaths (CA, 19%; NY, 14%) occurred at home with hospice. Most Medicaid patient deaths were either in acute-care facilities (CA, 28%; NY, 36%) or at home without hospice (CA, 39%; NY, 41%). Patient race/ethnicity was not associated with hospice use among Medicaid patients.
Conclusion
Given low rates of hospice use among Medicaid enrollees and considerable evidence of suffering at the end of life, opportunities to improve palliative care delivery should be prioritized. (C) 2013 by American Society of Clinical Oncology
C1 [Mack, Jennifer W.; Chen, Kun; Weeks, Jane C.; Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Mack, Jennifer W.] Childrens Hosp, Boston, MA 02115 USA.
[Boscoe, Francis P.; Schymura, Maria J.] New York State Dept Hlth, State Canc Registry, Albany, NY 12237 USA.
[Gesten, Foster C.; Roohan, Patrick J.] New York State Dept Hlth, Off Qual & Patient Safety, Albany, NY USA.
RP Mack, JW (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM Jennifer_mack@dfci.harvard.edu
FU National Cancer Institute [R01CA131847, RC2CA148185-01]; American Cancer
Society Mentored Research Scholar Grant from the American Cancer
Society; Association of Schools of Public Health/Centers for Disease
Control and Prevention Cooperative Agreement [S3888]
FX Supported by Grants No. R01CA131847 (D. S.; Medicaid patients) and
RC2CA148185-01 (J.C.W.) from the National Cancer Institute, an American
Cancer Society Mentored Research Scholar Grant (J.W.M.) from the
American Cancer Society, and the Association of Schools of Public
Health/Centers for Disease Control and Prevention Cooperative Agreement
No. S3888 (Augmenting New York Cancer Registry Data to Assess Breast and
Colorectal Cancer Care; M.J.S.).
NR 24
TC 21
Z9 21
U1 0
U2 7
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 10
PY 2013
VL 31
IS 20
BP 2569
EP +
DI 10.1200/JCO.2012.45.9271
PG 12
WC Oncology
SC Oncology
GA 301NA
UT WOS:000330537800026
PM 23733768
ER
PT J
AU Judson, TJ
Bennett, AV
Rogak, LJ
Sit, L
Barz, A
Kris, MG
Hudis, CA
Scher, HI
Sabattini, P
Schrag, D
Basch, E
AF Judson, Timothy J.
Bennett, Antonia V.
Rogak, Lauren J.
Sit, Laura
Barz, Allison
Kris, Mark G.
Hudis, Clifford A.
Scher, Howard I.
Sabattini, Paul
Schrag, Deborah
Basch, Ethan
TI Feasibility of Long-Term Patient Self-Reporting of Toxicities From Home
via the Internet During Routine Chemotherapy
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID NATIONAL-CANCER-INSTITUTE; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL;
MANAGEMENT-SYSTEM ASYMS(C); OUTCOMES ASSESSMENT; CLINICAL-TRIALS;
COMMUNICATION; CARE; MYELOFIBROSIS; RUXOLITINIB
AB Purpose
Patient-reported outcomes are increasingly used in routine outpatient cancer care to guide clinical decisions and enhance communication. Prior evidence suggests good patient compliance with reporting at scheduled clinic visits, but there is limited evidence about compliance with long-term longitudinal reporting between visits.
Patients and Methods
Patients receiving chemotherapy for lung, gynecologic, genitourinary, or breast cancer at a tertiary cancer center, with access to a home computer and prior e-mail experience, were asked to self-report seven symptomatic toxicities via the Web between visits. E-mail reminders were sent to participants weekly; patient-reported high-grade toxicities triggered e-mail alerts to nurses; printed reports were provided to oncologists at visits. A priori threshold criteria were set to determine if this data collection approach merited further development based on monthly (>= 75% participants reporting at least once per month on average) and weekly compliance rates (60% at least once per week).
Results
Between September 2006 and November 2010, 286 patients were enrolled (64% were women; 88% were white; median age, 58 years). Mean follow-up was 34 weeks (range, 2 to 214). On average, monthly compliance was 83%, and weekly compliance was 62%, without attrition until the month before death. Greater compliance was associated with older age and higher education but not with performance status. Compliance was greatest during the initial 12 weeks. Symptomatic illness and technical problems were rarely barriers to compliance.
Conclusion
Monthly compliance with home Web reporting was high, but weekly compliance was lower, warranting strategies to enhance compliance in routine care settings. (C) 2013 by American Society of Clinical Oncology
C1 [Judson, Timothy J.; Basch, Ethan] Weill Cornell Med Coll, New York, NY USA.
[Bennett, Antonia V.; Rogak, Lauren J.; Sit, Laura; Barz, Allison; Kris, Mark G.; Hudis, Clifford A.; Scher, Howard I.; Sabattini, Paul; Basch, Ethan] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Basch, Ethan] Univ N Carolina, Chapel Hill, NC USA.
RP Basch, E (reprint author), Univ N Carolina, Canc Outcomes Res Program, 170 Manning Dr CB 7305,Phys Off Bldg,Suite 3185, Chapel Hill, NC 27599 USA.
EM ebasch@med.unc.edu
OI Kris, Mark/0000-0002-7317-5341
FU National Cancer Institute [5K07CA124851]
FX Supported by National Cancer Institute Grant No. 5K07CA124851.
NR 38
TC 29
Z9 29
U1 0
U2 7
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 10
PY 2013
VL 31
IS 20
BP 2580
EP +
DI 10.1200/JCO.2012.47.6804
PG 7
WC Oncology
SC Oncology
GA 301NA
UT WOS:000330537800027
PM 23733753
ER
PT J
AU McCleary, NJ
Meyerhardt, JA
Green, E
Yothers, G
de Gramont, A
Van Cutsem, E
O'Connell, M
Twelves, CJ
Saltz, LB
Haller, DG
Sargent, DJ
AF McCleary, Nadine J.
Meyerhardt, Jeffrey A.
Green, Erin
Yothers, Greg
de Gramont, Aimery
Van Cutsem, Eric
O'Connell, Michael
Twelves, Christopher J.
Saltz, Leonard B.
Haller, Daniel G.
Sargent, Daniel J.
TI Impact of Age on the Efficacy of Newer Adjuvant Therapies in Patients
With Stage II/III Colon Cancer: Findings From the ACCENT Database
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2009
CL Orlando, FL
SP Amer Soc Clin Oncol
ID COMPREHENSIVE GERIATRIC ASSESSMENT; COLORECTAL-CANCER; INDEPENDENTLY
CONTRIBUTE; ELDERLY-PATIENTS; PLUS LEUCOVORIN; POOLED ANALYSIS; III
CARCINOMA; OLDER-ADULTS; FLUOROURACIL; CHEMOTHERAPY
AB Purpose
Prior studies have suggested that patients with stage II/III colon cancer receive similar benefit from intravenous (IV) fluoropyrimidine adjuvant therapy regardless of age. Combination regimens and oral fluorouracil (FU) therapy are now standard. We examined the impact of age on colon cancer recurrence and mortality after adjuvant therapy with these newer options.
Patients and Methods
We analyzed 11,953 patients age <70 and 2,575 age >70 years from seven adjuvant therapy trials comparing IV FU with oral fluoropyrimidines (capecitabine, uracil, or tegafur) or combinations of fluoropyrimidines with oxaliplatin or irinotecan in stage II/III colon cancer. End points were disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR).
Results
In three studies comparing oxaliplatin-based chemotherapy with IV FU, statistically significant interactions were not observed between treatment arm and age (P interaction = .09 for DFS, .05 for OS, and .36 for TTR), although the stratified point estimates suggested limited benefit from the addition of oxaliplatin in elderly patients (DFS hazard ratio [HR], 0.94; 95% CI, 0.78 to 1.13; OS HR, 1.04; 95% CI, 0.85 to 1.27). No significant interactions by age were detected with oral fluoropyrimidine therapy compared with IV FU; noninferiority was supported in both age populations.
Conclusion
Patients age >= 70 years seemed to experience reduced benefit from adding oxaliplatin to fluoropyrimidines in the adjuvant setting, although statistically, there was not a significant effect modification by age, whereas oral fluoropyrimidines retained their efficacy. (C) 2013 by American Society of Clinical Oncology
C1 [McCleary, Nadine J.; Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Green, Erin; O'Connell, Michael; Sargent, Daniel J.] Mayo Clin, Rochester, MN USA.
[Yothers, Greg] Univ Pittsburgh, Pittsburgh, PA USA.
[Haller, Daniel G.] Univ Penn, Philadelphia, PA 19104 USA.
[de Gramont, Aimery] Hop St Antoine, F-75571 Paris, France.
[Van Cutsem, Eric] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium.
[Twelves, Christopher J.] Univ Leeds, Leeds, W Yorkshire, England.
[Twelves, Christopher J.] St Jamess Inst Oncol, Leeds, W Yorkshire, England.
[Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP McCleary, NJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM nj_mccleary@dfci.harvard.edu
OI Sargent, Daniel/0000-0002-2684-4741; Yothers, Greg/0000-0002-7965-7333;
Saltz, Leonard/0000-0001-8353-4670
FU NCI NIH HHS [CA25224, P50 CA127003, R01 CA169141, U10 CA025224]
NR 31
TC 52
Z9 53
U1 0
U2 7
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 10
PY 2013
VL 31
IS 20
BP 2600
EP +
DI 10.1200/JCO.2013.49.6638
PG 8
WC Oncology
SC Oncology
GA 301NA
UT WOS:000330537800030
PM 23733765
ER
PT J
AU Johnstone, DB
Ikizler, O
Zhang, JD
Holzman, LB
AF Johnstone, Duncan B.
Ikizler, Omer
Zhang, Jidong
Holzman, Lawrence B.
TI Background Strain and the Differential Susceptibility of
Podocyte-Specific Deletion of Myh9 on Murine Models of Experimental
Glomerulosclerosis and HIV Nephropathy
SO PLOS ONE
LA English
DT Article
ID DECAY-ACCELERATING FACTOR; NEPHROTOXIC NEPHRITIS; AFRICAN-AMERICANS;
KIDNEY-DISEASE; MYH9-RELATED DISEASE; EUROPEAN-AMERICANS;
BASEMENT-MEMBRANE; LUPUS NEPHRITIS; II-A; MICE
AB We previously reported that podocyte-specific deletion of Myh9 (conventional myosin heavy chain 2A) in C57BL/6 mice does not cause spontaneous kidney disease but instead results in a predisposition to glomerulosclerosis in response to a second model of glomerular injury. In contrast, other investigators reported that podocyte-specific deletion of Myh9 (Pod Delta Myh9) resulted in spontaneous glomerulosclerosis in mice on a mixed background, suggesting that the glomerulosclerosis is dependent on background strain. In order to elucidate the cause of this strain dependent effect Podocin::Cre and Myh9(flox) alleles were backcrossed to mouse strain FVB/N, which is highly susceptible to glomerulosclerosis, with the aim of intercrossing susceptible FVB/N and resistant C57BL/6 mice in subsequent congenic analyses. However, after backcrossing mice to FVB/N and aging mice to 28 weeks, we found no evidence of glomerular disease in Pod Delta Myh9 mice vs control littermates (urine MAC ratio all p > 0.05). We also tested C57BL/6 Pod Delta Myh9 mice for a predisposition to injury from models other than Adriamycin including HIV nephropathy (HIVAN), puromycin nephropathy, and sheep nephrotoxic serum. In the Tg26 model of HIVAN, we found that podocyte-specific deletion of Myh9 resulted in a modest hypersensitivity in adults compared to Tg26+ control littermates (urine MAC ratio, p < 0.05 or less). In contrast, we found that Pod Delta Myh9 mice were not predisposed to injury in response to other injury models including puromycin nephropathy and sheep nephrotoxic serum. While the mechanism of injury in these models is not fully understood, we conclude that Pod Delta Myh9 results in a variable susceptibility to glomerulosclerosis in response to different models of glomerular injury. In addition, based on the lack of a spontaneous phenotype of glomerulosclerosis in both C57BL/6 and FVB/N mice, we propose that Myh9 is not absolutely required in adult podocytes.
C1 [Johnstone, Duncan B.] Temple Univ, Sch Med, Div Nephrol, Philadelphia, PA 19122 USA.
[Ikizler, Omer; Zhang, Jidong; Holzman, Lawrence B.] Univ Penn, Sch Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA.
[Holzman, Lawrence B.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
RP Johnstone, DB (reprint author), Temple Univ, Sch Med, Div Nephrol, Philadelphia, PA 19122 USA.
EM duncan.johnstone@tuhs.temple.edu
FU VA merit award; [K08DK082616]
FX Sources of funding for this study were K08DK082616 (to DBJ) and VA merit
award (to LBH). These funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 43
TC 11
Z9 11
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 JUL 10
PY 2013
VL 8
IS 7
AR e67839
DI 10.1371/journal.pone.0067839
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 182SU
UT WOS:000321765300014
PM 23874454
ER
PT J
AU Sahani, DV
Jiang, T
Hayano, K
Duda, DG
Catalano, OA
Ancukiewicz, M
Jain, RK
Zhu, AX
AF Sahani, Dushyant V.
Jiang, Tao
Hayano, Koichi
Duda, Dan G.
Catalano, Onofrio A.
Ancukiewicz, Marek
Jain, Rakesh K.
Zhu, Andrew X.
TI Magnetic resonance imaging biomarkers in hepatocellular carcinoma:
association with response and circulating biomarkers after sunitinib
therapy
SO JOURNAL OF HEMATOLOGY & ONCOLOGY
LA English
DT Article
DE Hepatocellular carcinoma; Antiangiogenic treatment; Image biomarker;
Dynamic contrast-enhanced MRI; Diffusion-weighted imaging; Circulating
biomarker
ID ENDOTHELIAL GROWTH-FACTOR; CONTRAST-ENHANCED MRI; PHASE-II;
PHARMACOKINETIC MODELS; COMPUTED-TOMOGRAPHY; SYSTEMIC THERAPY; FACTOR
RECEPTOR; PORTAL-VEIN; DCE-MRI; CANCER
AB Background: To investigate the hypothesis that MRI derived diffusion-weighted imaging (DWI) and perfusion (MRP) parameters are sensitive image biomarkers for monitoring early antiangiogenic effects and predicting progression free survival (PFS) in advanced hepatocellular carcinoma (HCC).
Methods: In this phase II clinical trial, 23 of 34 patients were included in the imaging and circulating biomarker study. DWI and MRP were performed at the baseline and at 2-weeks after initiation of sunitinib. The imaging protocol included an axial DWI sequence using b values of 50, 400 and 800 sec/mm(2), and MRP using a series of coronal 3D-VIBE following 20 ml of Gd-DTPA at 2 ml/sec. These parameters were compared with clinical outcome and PFS at 6-months. Correlation between changes in MRI parameters and plasma biomarkers was also evaluated.
Results: After 2-week of sunitinib, substantial Ktrans changes in HCC were observed from median baseline value 2.15 min(-1) to 0.94 min(-1) (P = 0.0001) with increases in median apparent diffusion coefficient (ADC) from 0.88 x 10(-3) mm(2)/s to 0.98 x 10(-3) mm(2)/s (P = 0.0001). Tumor size remained unchanged by RECIST and mRECIST (both P > 0.05). Patients who showed larger drop in Ktrans and Kep at 2 weeks correlated with favorable clinical outcome, and higher baseline Ktrans and larger drop in EVF correlated with longer PFS (all P < 0.05). There was a significant association between a decrease in sVEGFR2 and the drop in Ktrans and Kep (P = 0.044, P = 0.030), and a significant and borderline association between decrease in TNF-alpha and the drop in Ktrans and Kep, respectively (P = 0.051, P = 0.035).
Conclusion: In HCC, MRP may be a more sensitive biomarker in predicting early response and PFS following sunitinib than RECIST and mRECIST.
C1 [Sahani, Dushyant V.; Jiang, Tao; Hayano, Koichi; Catalano, Onofrio A.] Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
[Sahani, Dushyant V.; Jiang, Tao; Hayano, Koichi; Catalano, Onofrio A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jiang, Tao] Second Mil Med Univ, ChangZheng Hosp, Dept Radiol, Shanghai 200003, Peoples R China.
[Duda, Dan G.; Ancukiewicz, Marek; Jain, Rakesh K.] Massachusetts Gen Hosp, Steele Lab, Boston, MA 02114 USA.
[Catalano, Onofrio A.] IRCCS, Dept Radiol, SDN Fdn, I-80143 Naples, Italy.
[Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM dsahani@partners.org
FU National Natural Science Foundation of China [81101044]; NIH
[P01-CA080124]
FX Tao Jiang, M. D. received research support from the National Natural
Science Foundation of China (No. 81101044). The research of Drs. Jain
and Duda is in part supported through NIH grant P01-CA080124.
NR 43
TC 23
Z9 26
U1 0
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-8722
J9 J HEMATOL ONCOL
JI J. Hematol. Oncol.
PD JUL 10
PY 2013
VL 6
AR 51
DI 10.1186/1756-8722-6-51
PG 11
WC Oncology; Hematology
SC Oncology; Hematology
GA 188LX
UT WOS:000322195600001
PM 23842041
ER
PT J
AU Harvey, HB
Cohen, IG
AF Harvey, H. Benjamin
Cohen, I. Glenn
TI The Looming Threat of Liability for Accountable Care Organizations and
What to Do About It
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Harvey, H. Benjamin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Cohen, I. Glenn] Harvard Univ, Sch Law, Cambridge, MA 02138 USA.
RP Cohen, IG (reprint author), Harvard Univ, Sch Law, 1525 Massachusetts Ave,Griswold Hall,Room 503, Cambridge, MA 02138 USA.
EM igcohen@law.harvard.edu
NR 7
TC 5
Z9 5
U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 10
PY 2013
VL 310
IS 2
BP 141
EP 142
DI 10.1001/jama.2013.7339
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 179HU
UT WOS:000321511500008
PM 23775236
ER
PT J
AU Madison, K
Schmidt, H
Volpp, KG
AF Madison, Kristin
Schmidt, Harald
Volpp, Kevin G.
TI Smoking, Obesity, Health Insurance, and Health Incentives in the
Affordable Care Act
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Madison, Kristin] Northeastern Univ, Sch Law, Boston, MA 02115 USA.
[Madison, Kristin] Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA.
[Schmidt, Harald] Univ Penn, Dept Med Eth & Hlth Policy, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Volpp, Kevin G.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA.
RP Madison, K (reprint author), Northeastern Univ, Sch Law, 400 Huntington Ave, Boston, MA 02115 USA.
EM k.madison@neu.edu
NR 6
TC 17
Z9 17
U1 0
U2 15
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 JUL 10
PY 2013
VL 310
IS 2
BP 143
EP 144
DI 10.1001/jama.2013.7617
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 179HU
UT WOS:000321511500009
PM 23765171
ER
PT J
AU Matlock, DD
Groeneveld, PW
Sidney, S
Shetterly, S
Goodrich, G
Glenn, K
Xu, S
Yang, L
Farmer, SA
Reynolds, K
Cassidy-Bushrow, AE
Lieu, T
Boudreau, DM
Greenlee, RT
Tom, J
Vupputuri, S
Adams, KF
Smith, DH
Gunter, MJ
Go, AS
Magid, DJ
AF Matlock, Daniel D.
Groeneveld, Peter W.
Sidney, Steve
Shetterly, Susan
Goodrich, Glenn
Glenn, Karen
Xu, Stan
Yang, Lin
Farmer, Steven A.
Reynolds, Kristi
Cassidy-Bushrow, Andrea E.
Lieu, Tracy
Boudreau, Denise M.
Greenlee, Robert T.
Tom, Jeffrey
Vupputuri, Suma
Adams, Kenneth F.
Smith, David H.
Gunter, Margaret J.
Go, Alan S.
Magid, David J.
TI Geographic Variation in Cardiovascular Procedure Use Among Medicare
Fee-for-Service vs Medicare Advantage Beneficiaries
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID LIFE TREATMENT INTENSITY; REGIONAL-VARIATION; UNITED-STATES; RESOURCE
USE; HEALTH-CARE; QUALITY; PERCEPTIONS; OUTCOMES; POLICY; RISK
AB IMPORTANCE Little is known about how different financial incentives between Medicare Advantage and Medicare fee-for-service (FFS) reimbursement structures influence use of cardiovascular procedures.
OBJECTIVE To compare regional cardiovascular procedure rates between Medicare Advantage and Medicare FFS beneficiaries.
DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of Medicare beneficiaries older than 65 years between 2003-2007 comparing rates of coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery across 32 hospital referral regions in 12 states.
MAIN OUTCOMES AND MEASURES Rates of coronary angiography, PCI, and CABG surgery.
RESULTS We evaluated a total of 878 339 Medicare Advantage patients and 5 013 650 Medicare FFS patients. Compared with Medicare FFS patients, Medicare Advantage patients had lower age-, sex-, race-, and income-adjusted procedure rates per 1000 person-years for angiography (16.5 [95% CI, 14.8-18.2] vs 25.9 [95% CI, 24.0-27.9]; P < .001) and PCI (6.8 [95% CI, 6.0-7.6] vs 9.8 [95% CI, 9.0-10.6]; P < .001) but similar rates for CABG surgery (3.1 [95% CI, 2.8-3.5] vs 3.4 [95% CI, 3.1-3.7]; P = .33). There were no significant differences between Medicare Advantage and Medicare FFS patients in the rates per 1000 person-years of urgent angiography (3.9 [95% CI, 3.6-4.2] vs 4.3 [95% CI, 4.0-4.6]; P = .24) or PCI (2.4 [95% CI, 2.2-2.7] vs 2.7 [95% CI, 2.5-2.9]; P = .16). Procedure rates varied widely across hospital referral regions among Medicare Advantage and Medicare FFS patients. For angiography, the rates per 1000 person-years ranged from 9.8 to 40.6 for Medicare Advantage beneficiaries and from 15.7 to 44.3 for Medicare FFS beneficiaries. For PCI, the rates ranged from 3.5 to 16.8 for Medicare Advantage and from 4.7 to 16.1 for Medicare FFS. The rates for CABG surgery ranged from 1.5 to 6.1 for Medicare Advantage and from 2.5 to 6.0 for Medicare FFS. Across regions, we found no statistically significant correlation between Medicare Advantage and Medicare FFS beneficiary utilization for angiography (Spearman r = 0.19, P = .29) and modest correlations for PCI (Spearman r = 0.33, P = .06) and CABG surgery (Spearman r = 0.35, P = .05). Among Medicare Advantage beneficiaries, adjustment for additional cardiac risk factors had little influence on procedure rates.
CONCLUSIONS AND RELEVANCE Although Medicare beneficiaries enrolled in capitated Medicare Advantage programs had lower angiography and PCI procedure rates than those enrolled in Medicare FFS, the degree of geographic variation in procedure rates was substantial among Medicare Advantage beneficiaries and was similar in magnitude to that observed among Medicare FFS beneficiaries.
C1 [Matlock, Daniel D.] Univ Colorado, Sch Med, Aurora, CO USA.
[Matlock, Daniel D.; Shetterly, Susan; Xu, Stan; Magid, David J.] Colorado Cardiovasc Outcomes Res Grp, Denver, CO USA.
[Matlock, Daniel D.; Shetterly, Susan; Goodrich, Glenn; Glenn, Karen; Xu, Stan; Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA.
[Groeneveld, Peter W.; Yang, Lin] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Groeneveld, Peter W.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Sidney, Steve; Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Farmer, Steven A.] Northwestern Univ, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA.
[Farmer, Steven A.] Northwestern Univ, Kellogg Sch Management, Chicago, IL 60611 USA.
[Reynolds, Kristi] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA.
[Cassidy-Bushrow, Andrea E.] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA.
[Lieu, Tracy] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA.
[Lieu, Tracy] Harvard Univ, Sch Med, Boston, MA USA.
[Boudreau, Denise M.] Grp Hlth Res Inst, Seattle, WA USA.
[Greenlee, Robert T.] Marshfield Clin Res Fdn, Marshfield, WI USA.
[Tom, Jeffrey] Kaiser Permanente Ctr Hlth Res, Honolulu, HI USA.
[Vupputuri, Suma] Kaiser Permanente Ctr Hlth Res Southeast, Atlanta, GA USA.
[Adams, Kenneth F.] HealthPartners Res Fdn, Minneapolis, MN USA.
[Smith, David H.] Kaiser Permanente Northwest Ctr Hlth Res, Portland, OR USA.
[Gunter, Margaret J.] Lovelace Clin Fdn, Albuquerque, NM USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Go, Alan S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA.
RP Matlock, DD (reprint author), Univ Colorado Denver, Sch Med, Div Gen Internal Med, Acad Off 1, 12631 E 17th Ave,Campus Box B-180, Aurora, CO 80045 USA.
EM daniel.matlock@ucdenver.edu
OI Cassidy-Bushrow, Andrea/0000-0001-8272-4448
FU National Institute on Aging [1K23AG040696]; National Heart, Lung, and
Blood Institute; Cardiovascular Research Network [U19 HL91179-01,
1RC2HL101666-01, 1R01HL086919]; Agency for Healthcare Research and
Quality [1R01HS018403]
FX Dr Matlock was supported by a career development award from the National
Institute on Aging (1K23AG040696). The study was supported by the
National Heart, Lung, and Blood Institute and the Cardiovascular
Research Network (U19 HL91179-01, 1RC2HL101666-01, and 1R01HL086919).
Medicare data for the project were obtained under Agency for Healthcare
Research and Quality grant 1R01HS018403.
NR 30
TC 23
Z9 23
U1 0
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 10
PY 2013
VL 310
IS 2
BP 155
EP 162
DI 10.1001/jama.2013.7837
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 179HU
UT WOS:000321511500014
PM 23839749
ER
PT J
AU Heilig, EA
Gutti, U
Tai, T
Shen, J
Kelleher, RJ
AF Heilig, Elizabeth A.
Gutti, Usha
Tai, Tara
Shen, Jie
Kelleher, Raymond J., III
TI Trans-Dominant Negative Effects of Pathogenic PSEN1 Mutations on
gamma-Secretase Activity and A beta Production
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; PRESENILIN-1 PROTECTS;
ASPARTYL PROTEASE; TRANSGENIC MICE; NEURONAL LOSS; NICASTRIN; COMPLEX;
MUTANT; EXPRESSION
AB Mutations in the PSEN1 gene encoding Presenilin-1 (PS1) are the predominant cause of familial Alzheimer's disease (FAD), but the underlying mechanisms remain unresolved. To reconcile the dominant action of pathogenic PSEN1 mutations with evidence that they confer a loss of mutant protein function, we tested the hypothesis that PSEN1 mutations interfere with gamma-secretase activity in a dominant-negative manner. Here, we show that pathogenic PSEN1 mutations act in cis to impair mutant PS1 function and act in trans to inhibit wild-type PS1 function. Coexpression of mutant and wild-type PS1 at equal gene dosage in presenilin-deficient mouse embryo fibroblasts resulted in trans-dominant-negative inhibition of wild-type PS1 activity, suppressing gamma-secretase-dependent cleavage of APP and Notch. Surprisingly, mutant PS1 could stimulate production of A beta 42 by wild-type PS1 while decreasing its production of A beta 40. Mutant and wild-type PS1 efficiently coimmunoprecipitated, suggesting that mutant PS1 interferes with wild-type PS1 activity via physical interaction. These results support the conclusion that mutant PS1 causes wild-type PS1 to adopt an altered conformation with impaired catalytic activity and substrate specificity. Our findings reveal a novel mechanism of action for pathogenic PSEN1 mutations and suggest that dominant-negative inhibition of presenilin activity plays an important role in FAD pathogenesis.
C1 [Heilig, Elizabeth A.; Gutti, Usha; Tai, Tara; Kelleher, Raymond J., III] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Heilig, Elizabeth A.; Gutti, Usha; Tai, Tara; Kelleher, Raymond J., III] Harvard Univ, Sch Med, MGH Simches Res Ctr, Boston, MA 02114 USA.
[Shen, Jie] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
[Shen, Jie] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Shen, Jie; Kelleher, Raymond J., III] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Shen, Jie; Kelleher, Raymond J., III] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
RP Kelleher, RJ (reprint author), MGH Simches Res Ctr, CPZN 6234,185 Cambridge St, Boston, MA 02114 USA.
EM kelleher@helix.mgh.harvard.edu
OI Gutti, Usha/0000-0003-0927-0923
FU National Institute of Neurological Disorders and Stroke [R01NS041783,
R01NS075346]; Alzheimer's Association; National Institutes of Health
[T32 AG000222-18]; Pew Scholar award; John Merck Scholar award
FX This work was supported by the National Institute of Neurological
Disorders and Stroke Grant R01NS041783 to J.S., National Institute of
Neurological Disorders and Stroke Grant R01NS075346 to R.J.K., and the
Alzheimer's Association (to J.S. and R.J.K.). E. A. H. was supported by
National Institutes of Health Training Grant T32 AG000222-18. R.J.K. was
supported by Pew Scholar and John Merck Scholar awards. We thank Dr.
Alison Goate for the APP C99 construct, Dr. Raphael Kopan for the Notch
Delta E construct, and members of the J.S. and R.J.K. laboratories for
helpful discussions.
NR 39
TC 20
Z9 20
U1 1
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 10
PY 2013
VL 33
IS 28
BP 11606
EP 11617
DI 10.1523/JNEUROSCI.0954-13.2013
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 180TX
UT WOS:000321622600025
PM 23843529
ER
PT J
AU Hanlon, CA
Canterberry, M
Taylor, JJ
DeVries, W
Li, XB
Brown, TR
George, MS
AF Hanlon, Colleen A.
Canterberry, Melanie
Taylor, Joseph J.
DeVries, William
Li, Xingbao
Brown, Truman R.
George, Mark S.
TI Probing the Frontostriatal Loops Involved in Executive and Limbic
Processing via Interleaved TMS and Functional MRI at Two Prefrontal
Locations: A Pilot Study
SO PLOS ONE
LA English
DT Article
ID TRANSCRANIAL MAGNETIC STIMULATION; RHESUS-MONKEY; MOTOR CORTEX;
BOLD-FMRI; MEMORY FORMATION; WORKING-MEMORY; BASAL GANGLIA; REWARD
SYSTEM; ACTIVATION; ORGANIZATION
AB Background: The prefrontal cortex (PFC) is an anatomically and functionally heterogeneous area which influences cognitive and limbic processing through connectivity to subcortical targets. As proposed by Alexander et al. (1986) the lateral and medial aspects of the PFC project to distinct areas of the striatum in parallel but functionally distinct circuits. The purpose of this preliminary study was to determine if we could differentially and consistently activate these lateral and medial cortical-subcortical circuits involved in executive and limbic processing though interleaved transcranial magnetic stimulation (TMS) in the MR environment.
Methods: Seventeen healthy individuals received interleaved TMS-BOLD imaging with the coil positioned over the dorsolateral (EEG: F3) and ventromedial PFC (EEG: FP1). BOLD signal change was calculated in the areas directly stimulated by the coil and in subcortical regions with afferent and efferent connectivity to the TMS target areas. Additionally, five individuals were tested on two occasions to determine test-retest reliability.
Results: Region of interest analysis revealed that TMS at both prefrontal sites led to significant BOLD signal increases in the cortex under the coil, in the striatum, and the thalamus, but not in the visual cortex (negative control region). There was a significantly larger BOLD signal change in the caudate following medial PFC TMS, relative to lateral TMS. The hippocampus in contrast was significantly more activated by lateral TMS. Post-hoc voxel-based analysis revealed that within the caudate the location of peak activity was in the ventral caudate following medial TMS and the dorsal caudate following lateral TMS. Test-retest reliability data revealed consistent BOLD responses to TMS within each individual but a large variation between individuals.
Conclusion: These data demonstrate that, through an optimized TMS/BOLD sequence over two unique prefrontal targets, it is possible to selectively interrogate the patency of these established cortical-subcortical networks in healthy individuals, and potentially patient populations.
C1 [Hanlon, Colleen A.; Canterberry, Melanie; Taylor, Joseph J.; DeVries, William; Li, Xingbao; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA.
[Hanlon, Colleen A.; Brown, Truman R.; George, Mark S.] Med Univ S Carolina, Ctr Biomed Imaging, Charleston, SC 29425 USA.
[Brown, Truman R.] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA.
[George, Mark S.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA.
RP Hanlon, CA (reprint author), Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA.
EM hanlon@musc.edu
FU National Institutes of Health [K01DA027756, 1F30DA033748-01,
T32DA007288]
FX This work was supported by the National Institutes of Health (grant
numbers, K01DA027756 (CAH), 1F30DA033748-01 (JJT), T32DA007288). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 49
TC 10
Z9 10
U1 2
U2 16
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 JUL 9
PY 2013
VL 8
IS 7
AR e67917
DI 10.1371/journal.pone.0067917
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 182JD
UT WOS:000321736900036
PM 23874466
ER
PT J
AU Hwang, WY
Fu, YF
Reyon, D
Maeder, ML
Kaini, P
Sander, JD
Joung, JK
Peterson, RT
Yeh, JRJ
AF Hwang, Woong Y.
Fu, Yanfang
Reyon, Deepak
Maeder, Morgan L.
Kaini, Prakriti
Sander, Jeffry D.
Joung, J. Keith
Peterson, Randall T.
Yeh, Jing-Ruey Joanna
TI Heritable and Precise Zebrafish Genome Editing Using a CRISPR-Cas System
SO PLOS ONE
LA English
DT Article
ID ZINC-FINGER NUCLEASES; TARGETED GENE DISRUPTION; TALENS; ENDONUCLEASE;
MUTAGENESIS; BACTERIA; ARCHAEA; CELLS
AB We have previously reported a simple and customizable CRISPR (clustered regularly interspaced short palindromic repeats) RNA-guided Cas9 nuclease (RGN) system that can be used to efficiently and robustly introduce somatic indel mutations in endogenous zebrafish genes. Here we demonstrate that RGN-induced mutations are heritable, with efficiencies of germline transmission reaching as high as 100%. In addition, we extend the power of the RGN system by showing that these nucleases can be used with single-stranded oligodeoxynucleotides (ssODNs) to create precise intended sequence modifications, including single nucleotide substitutions. Finally, we describe and validate simple strategies that improve the targeting range of RGNs from 1 in every 128 basepairs (bps) of random DNA sequence to 1 in every 8 bps. Together, these advances expand the utility of the CRISPR-Cas system in the zebrafish beyond somatic indel formation to heritable and precise genome modifications.
C1 [Hwang, Woong Y.; Kaini, Prakriti; Peterson, Randall T.; Yeh, Jing-Ruey Joanna] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
[Hwang, Woong Y.; Kaini, Prakriti; Peterson, Randall T.; Yeh, Jing-Ruey Joanna] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Fu, Yanfang; Reyon, Deepak; Maeder, Morgan L.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA USA.
[Fu, Yanfang; Reyon, Deepak; Maeder, Morgan L.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA.
[Fu, Yanfang; Reyon, Deepak; Sander, Jeffry D.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Peterson, Randall T.] Broad Inst, Cambridge, MA USA.
RP Peterson, RT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
EM peterson@cvrc.mgh.harvard.edu; jyeh1@partners.org
FU National Institutes of Health [R01 GM088040]; NIH Director's Pioneer
Award [DP1 OD006862, K01 AG031300, R01 CA140188]; Defense Advanced
Research Projects Agency (DARPA) [W911NF-11-2-0056]; Jim and Ann Orr MGH
Research Scholar award; Charles and Ann Sanders MGH Research Scholar
award; MGH Claflin Distinguished Scholar Award
FX This work was supported by National Institutes of Health [R01 GM088040
to JKJ and RTP, NIH Director's Pioneer Award DP1 OD006862 to JKJ, K01
AG031300 to JRJY, R01 CA140188 to JRJY]; Defense Advanced Research
Projects Agency (DARPA) [W911NF-11-2-0056 to JKJ]; the Jim and Ann Orr
MGH Research Scholar award (JKJ); the Charles and Ann Sanders MGH
Research Scholar award (RTP); and the MGH Claflin Distinguished Scholar
Award (JRJY). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 35
TC 126
Z9 131
U1 9
U2 95
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 JUL 9
PY 2013
VL 8
IS 7
AR e68708
DI 10.1371/journal.pone.0068708
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 182JD
UT WOS:000321736900106
PM 23874735
ER
PT J
AU Bekelman, DB
Plomondon, ME
Sullivan, MD
Nelson, K
Hattler, B
McBryde, C
Lehmann, KG
Potfay, J
Heidenreich, P
Rumsfeld, JS
AF Bekelman, David B.
Plomondon, Mary E.
Sullivan, Mark D.
Nelson, Karin
Hattler, Brack
McBryde, Connor
Lehmann, Kenneth G.
Potfay, Jonathan
Heidenreich, Paul
Rumsfeld, John S.
TI Patient-centered disease management (PCDM) for heart failure: study
protocol for a randomised controlled trial
SO BMC CARDIOVASCULAR DISORDERS
LA English
DT Article
DE Heart failure; Clinical trial; Patient reported outcomes; Quality of
life; Health status
ID HEALTH-STATUS; RESOURCE UTILIZATION; CARE MANAGEMENT; HOSPITALIZATION;
DEPRESSION; POPULATION; OUTCOMES; TRENDS; DEATH; RISK
AB Background: Chronic heart failure (HF) disease management programs have reported inconsistent results and have not included comorbid depression management or specifically focused on improving patient-reported outcomes. The Patient Centered Disease Management (PCDM) trial was designed to test the effectiveness of collaborative care disease management in improving health status (symptoms, functioning, and quality of life) in patients with HF who reported poor HF-specific health status.
Methods/design: Patients with a HF diagnosis at four VA Medical Centers were identified through population-based sampling. Patients with a Kansas City Cardiomyopathy Questionnaire (KCCQ, a measure of HF-specific health status) score of < 60 (heavy symptom burden and impaired quality of life) were invited to enroll in the PCDM trial. Enrolled patients were randomized to receive usual care or the PCDM intervention, which included: (1) collaborative care management by VA clinicians including a nurse, cardiologist, internist, and psychiatrist, who worked with patients and their primary care providers to provide guideline-concordant care management, (2) home telemonitoring and guided patient self-management support, and (3) screening and treatment for comorbid depression. The primary study outcome is change in overall KCCQ score. Secondary outcomes include depression, medication adherence, guideline-based care, hospitalizations, and mortality.
Discussion: The PCDM trial builds on previous studies of HF disease management by prioritizing patient health status, implementing a collaborative care model of health care delivery, and addressing depression, a key barrier to optimal disease management. The study has been designed as an 'effectiveness trial' to support broader implementation in the healthcare system if it is successful.
C1 [Bekelman, David B.; McBryde, Connor] Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Denver, CO 80220 USA.
[Bekelman, David B.; Hattler, Brack; McBryde, Connor; Rumsfeld, John S.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA.
[Plomondon, Mary E.; Hattler, Brack; Rumsfeld, John S.] Eastern Colorado Hlth Care Syst Cardiol 111B, Dept Vet Affairs, Denver, CO 80220 USA.
[Sullivan, Mark D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Nelson, Karin; Lehmann, Kenneth G.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
[Nelson, Karin; McBryde, Connor] Northwest HSR&D Ctr Excellence, Seattle, WA USA.
[Nelson, Karin] Univ Washington, Dept Med, Seattle, WA USA.
[Potfay, Jonathan] Richmond VA Med Ctr, Richmond, VA 23249 USA.
[Heidenreich, Paul] VA Palo Alto Hlth Care Syst Cardiol 111C, Palo Alto, CA 94304 USA.
RP Bekelman, DB (reprint author), Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Res 151,1055 Clermont St, Denver, CO 80220 USA.
EM david.bekelman@va.gov
OI Heidenreich, Paul/0000-0001-7730-8490
FU Department of Veterans Affairs HSRD [IIR 06-068]; Department of Veterans
Affairs [HSRD CDA 08-022]
FX The PCDM trial is funded by the Department of Veterans Affairs HSR&D
grant IIR 06-068. Dr. Bekelman is funded by the Department of Veterans
Affairs (HSR&D CDA 08-022). After approval of funding, the funding
organizations did not participate in the study design or manuscript
preparation. We thank our nurse coordinators, Darcy Donaldson, Laura
Gaskin, Julie LaGuire, Susan Walker, and Barbara Watson for the care
they provided. The views in this article are those of the authors and do
not necessarily reflect the views of the Department of Veterans Affairs.
NR 27
TC 4
Z9 4
U1 2
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2261
J9 BMC CARDIOVASC DISOR
JI BMC Cardiovasc. Disord.
PD JUL 9
PY 2013
VL 13
AR 49
DI 10.1186/1471-2261-13-49
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 186IU
UT WOS:000322037600001
PM 23837415
ER
PT J
AU Bowman, SK
Simon, MD
Deaton, AM
Tolstorukov, M
Borowsky, ML
Kingston, RE
AF Bowman, Sarah K.
Simon, Matthew D.
Deaton, Aimee M.
Tolstorukov, Michael
Borowsky, Mark L.
Kingston, Robert E.
TI Multiplexed Illumina sequencing libraries from picogram quantities of
DNA
SO BMC GENOMICS
LA English
DT Article
DE Illumina; ChIP-seq; Multiplex; Barcoding; Library preparation
ID CHIP-SEQ; GENOME; AMPLIFICATION
AB Background: High throughput sequencing is frequently used to discover the location of regulatory interactions on chromatin. However, techniques that enrich DNA where regulatory activity takes place, such as chromatin immunoprecipitation (ChIP), often yield less DNA than optimal for sequencing library preparation. Existing protocols for picogram-scale libraries require concomitant fragmentation of DNA, pre-amplification, or long overnight steps.
Results: We report a simple and fast library construction method that produces libraries from sub-nanogram quantities of DNA. This protocol yields conventional libraries with barcodes suitable for multiplexed sample analysis on the Illumina platform. We demonstrate the utility of this method by constructing a ChIP-seq library from 100 pg of ChIP DNA that demonstrates equivalent genomic coverage of target regions to a library produced from a larger scale experiment.
Conclusions: Application of this method allows whole genome studies from samples where material or yields are limiting.
C1 [Bowman, Sarah K.; Simon, Matthew D.; Deaton, Aimee M.; Borowsky, Mark L.; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Bowman, Sarah K.; Simon, Matthew D.; Deaton, Aimee M.; Borowsky, Mark L.; Kingston, Robert E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
[Tolstorukov, Michael] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
[Tolstorukov, Michael] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
RP Bowman, SK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM bowman@molbio.mgh.harvard.edu
FU Damon Runyon Cancer Research Foundation [DRG-1995-08]; Helen Hay Whitney
Foundation
FX The authors would like to acknowledge Welcome Bender for supplying the
Drosophila strains used in the ChIP, Kaleena Shirley for assistance with
oligo design, and the MGH NextGen Sequencing Core as well as Kingston
lab members for helpful discussions. SKB was a Damon Runyon Fellow
supported by the Damon Runyon Cancer Research Foundation (DRG-1995-08)
and MDS was supported by a Helen Hay Whitney Foundation Postdoctoral
Fellowship.
NR 16
TC 28
Z9 30
U1 5
U2 36
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUL 9
PY 2013
VL 14
AR 466
DI 10.1186/1471-2164-14-466
PG 7
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 182XN
UT WOS:000321778200001
PM 23837789
ER
PT J
AU Maisel, A
Mueller, C
Neath, SX
Christenson, RH
Morgenthaler, NG
McCord, J
Nowak, RM
Vilke, G
Daniels, LB
Hollander, JE
Apple, FS
Cannon, C
Nagurney, JT
Schreiber, D
deFilippi, C
Hogan, C
Diercks, DB
Stein, JC
Headden, G
Limkakeng, AT
Anand, I
Wu, AHB
Papassotiriou, J
Hartmann, O
Ebmeyer, S
Clopton, P
Jaffe, AS
Peacock, WF
AF Maisel, Alan
Mueller, Christian
Neath, Sean-Xavier
Christenson, Robert H.
Morgenthaler, Nils G.
McCord, James
Nowak, Richard M.
Vilke, Gary
Daniels, Lori B.
Hollander, Judd E.
Apple, Fred S.
Cannon, Chad
Nagurney, John T.
Schreiber, Donald
deFilippi, Christopher
Hogan, Christopher
Diercks, Deborah B.
Stein, John C.
Headden, Gary
Limkakeng, Alexander T., Jr.
Anand, Inder
Wu, Alan H. B.
Papassotiriou, Jana
Hartmann, Oliver
Ebmeyer, Stefan
Clopton, Paul
Jaffe, Allan S.
Peacock, W. Frank
TI Copeptin Helps in the Early Detection of Patients With Acute Myocardial
Infarction Primary Results of the CHOPIN Trial (Copeptin Helps in the
early detection Of Patients with acute myocardial INfarction)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE copeptin; emergency department; myocardial infarction; quality
improvement; troponin
ID TERMINAL PROVASOPRESSIN COPEPTIN; HIGH-SENSITIVITY TROPONIN; CHRONIC
HEART-FAILURE; EMERGENCY-DEPARTMENT; PROGNOSTIC MARKER; CARDIAC
TROPONIN; RAPID RULE; VASOPRESSIN; PEPTIDE; RISK
AB Objectives The goal of this study was to demonstrate that copeptin levels <14 pmol/L allow ruling out acute myocardial infarction (AMI) when used in combination with cardiac troponin I (cTnI) <99th percentile and a nondiagnostic electrocardiogram at the time of presentation to the emergency department (ED).
Background Copeptin is secreted from the pituitary early in the course of AMI.
Methods This was a 16-site study in 1,967 patients with chest pain presenting to an ED within 6 hours of pain onset. Baseline demographic characteristics and clinical data were collected prospectively. Copeptin levels and a contemporary sensitive cTnI (99th percentile 40 ng/l; 10% coefficient of variation 0.03 mu g/l) were measured in a core laboratory. Patients were followed up for 180 days. The primary outcome was diagnosis of AMI. Final diagnoses were adjudicated by 2 independent cardiologists blinded to copeptin results.
Results AMI was the final diagnosis in 156 patients (7.9%). A negative copeptin and cTnI at baseline ruled out AMI for 58% of patients, with a negative predictive value of 99.2% (95% confidence interval: 98.5 to 99.6). AMIs not detected by the initial cTnI alone were picked up with copeptin >14 pmol/l in 23 (72%) of 32 patients. Non-ST-segment elevation myocardial infarctions undetected by cTnI at 0 h were detected with copeptin >14 pmol/l in 10 (53%) of 19 patients. Projected average time-to-decision could be reduced by 43% (from 3.0 h to 1.8 h) by the early rule out of 58% of patients. Both abnormal copeptin and cTnI were predictors of death at 180 days (p < 0.0001 for both; c index 0.784 and 0.800, respectively). Both were independent of age and each other and provided additional predictive value (all p < 0.0001).
Conclusions Adding copeptin to cTnI allowed safe rule out of AMI with a negative predictive value >99% in patients presenting with suspected acute coronary syndromes. This combination has the potential to rule out AMI in 58% of patients without serial blood draws. (Investigation of the Biomarker Copeptin in Patients With Acute Myocardial Infarction [NCT00952744]) (C) 2013 by the American College of Cardiology Foundation
C1 [Maisel, Alan; Clopton, Paul] VA San Diego Healthcare Syst, San Diego, CA USA.
[Maisel, Alan; Neath, Sean-Xavier; Vilke, Gary; Daniels, Lori B.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Mueller, Christian] Univ Basel Hosp, CH-4031 Basel, Switzerland.
[Christenson, Robert H.; deFilippi, Christopher] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Morgenthaler, Nils G.] Campus Virchow Klinikum, Charite, Berlin, Germany.
[McCord, James; Nowak, Richard M.] Henry Ford Hlth Syst, Detroit, MI USA.
[Hollander, Judd E.] Univ Penn, Philadelphia, PA 19104 USA.
[Apple, Fred S.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Cannon, Chad] Univ Kansas Hosp, Kansas City, KS USA.
[Nagurney, John T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Schreiber, Donald] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[Hogan, Christopher] Virginia Commonwealth Univ, Richmond, VA USA.
[Diercks, Deborah B.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA.
[Stein, John C.; Wu, Alan H. B.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Headden, Gary] Med Univ S Carolina, Charleston, SC 29425 USA.
[Limkakeng, Alexander T., Jr.] Duke Univ, Med Ctr, Durham, NC USA.
[Anand, Inder] VA Minneapolis, Minneapolis, MN USA.
[Papassotiriou, Jana; Hartmann, Oliver; Ebmeyer, Stefan] Thermo Fisher Sci BRAHMS GmbH, Thermo Sci Biomarkers, Hennigsdorf, Germany.
[Jaffe, Allan S.] Mayo Clin, Rochester, MN USA.
[Peacock, W. Frank] Baylor Coll Med, Houston, TX 77030 USA.
RP Maisel, A (reprint author), San Diego VA Healthcare, Cardiol, 3350 La Jolla Village Dr, San Diego, CA 92161 USA.
EM amaisel@ucsd.edu
OI Limkakeng, Alexander T./0000-0002-9822-5595; Hollander,
Judd/0000-0002-1318-2785
FU Thermo Fisher Scientific
FX The investigators thank BRAHMS AG (now part of Thermo Fisher Scientific)
for its generous and unrestricted support of this trial. We are grateful
for the work done by CLINDEVOR TriMed, Inc., for the organization,
management, and monitoring of this multinational trial.
NR 25
TC 61
Z9 68
U1 0
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUL 9
PY 2013
VL 62
IS 2
BP 150
EP 160
DI 10.1016/j.jacc.2013.04.011
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 176WY
UT WOS:000321338600012
PM 23643595
ER
PT J
AU Lee, KY
Yamamoto, Y
Boucher, J
Winnay, JN
Gesta, S
Cobb, J
Bluher, M
Kahn, CR
AF Lee, Kevin Y.
Yamamoto, Yuji
Boucher, Jeremie
Winnay, Jonathon N.
Gesta, Stephane
Cobb, John
Blueher, Matthias
Kahn, C. Ronald
TI Shox2 is a molecular determinant of depot-specific adipocyte function
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE developmental genes; adipose depots; lipid metabolism
ID BETA(3)-ADRENERGIC RECEPTOR GENE; BODY-FAT DISTRIBUTION; MOUSE
ADIPOSE-TISSUE; SHORT-STATURE; DIABETES-MELLITUS; TURNER-SYNDROME;
OBESITY; ALPHA; RISK; TRANSPLANTATION
AB Visceral and s.c. fat exhibit different intrinsic properties, including rates of lipolysis, and are associated with differential risk for the development of type 2 diabetes. These effects are in part related to cell autonomous differences in gene expression. In the present study, we show that expression of Shox2 (Short stature homeobox 2) is higher in s.c. than visceral fat in both rodents and humans and that levels are further increased in humans with visceral obesity. Fat-specific disruption of Shox2 in male mice results in protection from high fat diet-induced obesity, with a preferential loss of s.c. fat. The reduced adipocyte size is secondary to a twofold increase in the expression of beta 3 adrenergic receptor (Adrb3) at both the mRNA and protein level and a parallel increase in lipolytic rate. These effects are mimicked by knockdown of Shox2 in C3H10T1/2 cells. Conversely, overexpression of Shox2 leads to a repression of Adrb3 expression and decrease lipolytic rate. Shox2 does not affect differentiation but directly interacts with CCAAT/enhancer binding protein alpha and attenuates its transcriptional activity of the Adrb3 promoter. Thus, Shox2 can regulate the expression of Adrb3 and control the rate of lipolysis and, in this way, exerts control of the phenotypic differences between visceral and s.c. adipocytes.
C1 [Lee, Kevin Y.; Yamamoto, Yuji; Boucher, Jeremie; Winnay, Jonathon N.; Gesta, Stephane; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.
[Cobb, John] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada.
[Blueher, Matthias] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany.
RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.
EM c.ronald.kahn@joslin.harvard.edu
FU Joslin Training Grant [T32DK007260]; National Institutes of Health [DK
60837, DK 82655]; American Diabetes Association mentor-based award; Mary
K. Iacocca Professorship
FX We thank Dr. Denis Duboule (University of Geneva) for the Shox2 floxed
mice and Dr. Sheila Collins (Sanford-Burnham Medical Research Institute)
for the Adrb3-luciferase constructs. We are grateful to A. Clermont, M.
Poillucci [Diabetes Research Center (DRC) Physiology Core], and H. Li
(DRC Specialized Assay Core). This work was supported by Joslin Training
Grant T32DK007260, National Institutes of Health Grants DK 60837 and DK
82655, an American Diabetes Association mentor-based award, and the Mary
K. Iacocca Professorship (to C.R.K.).
NR 29
TC 17
Z9 18
U1 0
U2 15
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 9
PY 2013
VL 110
IS 28
BP 11409
EP 11414
DI 10.1073/pnas.1310331110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 183OT
UT WOS:000321827000054
PM 23798383
ER
PT J
AU Stanley, SA
Kawate, T
Iwase, N
Shimizu, M
Clatworthy, AE
Kazyanskaya, E
Sacchettini, JC
Ioerger, TR
Siddiqi, NA
Minami, S
Aquadro, JA
Grant, SS
Rubin, EJ
Hung, DT
AF Stanley, Sarah A.
Kawate, Tomohiko
Iwase, Noriaki
Shimizu, Motohisa
Clatworthy, Anne E.
Kazyanskaya, Edward
Sacchettini, James C.
Ioerger, Thomas R.
Siddiqi, Noman A.
Minami, Shoko
Aquadro, John A.
Grant, Sarah Schmidt
Rubin, Eric J.
Hung, Deborah T.
TI Diarylcoumarins inhibit mycolic acid biosynthesis and kill Mycobacterium
tuberculosis by targeting FadD32
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID INHA; ACTIVATION; INSIGHTS; GROWTH; DRUGS; IDENTIFICATION; ZEBRAFISH;
COUMARINS; INFECTION; DISCOVERY
AB Infection with the bacterial pathogen Mycobacterium tuberculosis imposes an enormous burden on global public health. New antibiotics are urgently needed to combat the global tuberculosis pandemic; however, the development of new small molecules is hindered by a lack of validated drug targets. Here, we describe the identification of a 4,6-diaryl-5,7-dimethyl coumarin series that kills M. tuberculosis by inhibiting fatty acid degradation